[ { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 1, "text": "", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_001.png", "summary": "No summary generated.", "questions": [] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 2, "text": "Illustrator:\nChristopher A. French, MD\nAssistant Professor of Pathology\nHarvard Medical School\nBrigham and Women\u2019s Hospital\nBoston, Massachusetts\nIllustrator:\nShogun G. Curtis, BA\nFounder and Head, Department of Art\nHumble School of Arts and Music\nBoston, Massachusetts", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_002.png", "summary": "The page lists the illustrators of the surgical pathology manual, including their names, titles, and affiliations.", "questions": [ "What is the significance of listing the illustrators in a surgical pathology manual?", "How are the illustrators chosen for such manuals?", "Do the illustrators play a role in the content creation or only in the visual representation?", "Are there specific qualifications or expertise required for someone to be an illustrator for a surgical pathology manual?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 3, "text": "Manual of\nSurgical\nPathology\nThird Edition \nSusan C. Lester, MD, PhD\nAssistant Professor of Pathology\nHarvard Medical School\nChief, Breast Pathology Services\nBrigham and Women\u2019s Hospital\nBoston, Massachusetts", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_003.png", "summary": "The manual of Surgical Pathology, Third Edition, authored by Susan C. Lester, MD, PhD, provides comprehensive information on breast pathology.", "questions": [ "What specific topics related to breast pathology are covered in this manual?", "How does the author's background and position contribute to the credibility of the information presented?", "Are there any notable updates or advancements in breast pathology included in this edition?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 4, "text": "1600 John F. Kennedy Blvd.\nSte 1800\nPhiladelphia, PA 19103-2899\nMANUAL OF SURGICAL PATHOLOGY\b\nISBN: 978-0-323-06516-0\nCopyright \u00a9 2010, 2006, 2000 by Saunders, an imprint of Elsevier Inc.\nAll rights reserved. No part of this publication may be reproduced or transmitted in any form or by \nany means, electronic or mechanical, including photocopying, recording, or any information storage and \nretrieval system, without permission in writing from the publisher. Details on how to seek permission, fur\u00ad\nther information about the Publisher\u2019s permissions policies and our arrangements with organizations such \nas the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: \nwww.elsevier.com/permissions.\nThis book and the individual contributions contained in it are protected under copyright by the Publisher \n(other than as may be noted herein).\nNotice\nKnowledge and best practice in this field are constantly changing. As new research and experience \nbroaden our understanding, changes in research methods, professional practices, or medical treatment \nmay become necessary. \nPractitioners and researchers must always rely on their own experience and knowledge in evaluat\u00ad\ning and using any information, methods, compounds, or experiments described herein. In using such \ninformation or methods they should be mindful of their own safety and the safety of others, including \nparties for whom they have a professional responsibility. \nWith respect to any drug or pharmaceutical products identified, readers are advised to check the \nmost current information provided (i) on procedures featured or (ii) by the manufacturer of each \nproduct to be administered, to verify the recommended dose or formula, the method and duration \nof administration, and contraindications. It is the responsibility of practitioners, relying on their own \nexperience and knowledge of their patients, to make diagnoses, to determine dosages and the best \ntreatment for each individual patient, and to take all appropriate safety precautions. \nTo the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, \nassume any liability for any injury and/or damage to persons or property as a matter of products liabil\u00ad\nity, negligence or otherwise, or from any use or operation of any methods, products, instructions, or \nideas contained in the material herein.\n\b\nThe Publisher\nPrevious editions copyrighted \nLibrary of Congress Cataloging-in-Publication Data\nManual of surgical pathology / [edited by] Susan C. Lester ; illustrators, Christopher A. French, Shogun \nG. Curtis. -- 3rd ed.\n p. ; cm.\n Other title: Surgical pathology\n Includes bibliographical references and index. \n ISBN 978-0-323-06516-0\n1. Pathology, Surgical--Handbooks, manuals, etc. I. Lester, Susan Carole. II. Title: Surgical pathology.\n [DNLM: 1. Pathology, Surgical. WO 142 M294 2010]\n RD57.M35 2010\n 617\u2019.07--dc22\b\n2010012832\nAcquisitions Editor: Bill Schmitt\nPublishing Services Manager: Deborah L. Vogel\nDevelopmental Editor: Andrea Vosburgh\nProject Manager: Annie Victor\nDesign Direction: Louis Forgione\nCover Designer: Christopher A. French, MD\nMarketing Manager: Brenna Christensen\nPrinted in the United States of America\nLast digit is the print number:\u2003 9\u2003 8\u2003 7\u2003 6\u2003 5\u2003 4\u2003 3\u2003 2\u2003 1", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_004.png", "summary": "The manual of surgical pathology provides important information on best practices and guidelines in the field, emphasizing the need for practitioners to stay updated with new research and changes in medical treatments.", "questions": [ "How often should practitioners in the field of surgical pathology update their knowledge and practices?", "What are the potential risks associated with not staying current with the latest research and best practices in surgical pathology?", "How can practitioners ensure they are following the most current guidelines and recommendations in surgical pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 5, "text": "", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_005.png", "summary": "No summary generated.", "questions": [] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 6, "text": "v\nWhen I was a pathology resident at Brigham and \nWomen\u2019s Hospital in Boston in the late 1980s, instruc\u00ad\ntion in the handling and processing of surgical pathol\u00ad\nogy specimens was passed on largely by oral tradition. \nOur surgical pathology manual contained few diagrams, \nand its written dissection instructions were often terse \nand cryptic. When faced with new or unusual surgical \nspecimens, I and other residents would search various \npathology and anatomy texts for pictures or diagrams \nthat would enable us to locate critical anatomic land\u00ad\nmarks needed for basic orientation (photocopies of the \nbest of these earned positions of honor, taped to the \ncabinets above the dissection bench). Actual instruction \nin how to dissect and sample new specimens, however, \nalmost invariably came verbally from more senior resi\u00ad\ndents, fellows, or attending pathologists. As might have \nbeen expected, these instructions varied widely in overall \napproach and meticulousness, and years of \u201cfine tuning\u201d \nwere required before I (and, I suspect, many patholo\u00ad\ngists) developed an effective and systematic approach to \nmany gross specimen types.\nEach year, the incoming surgical pathology fellows at \nthe Brigham were asked to review the surgical pathology \nmanual and offer suggestions for improvement. When my \nturn came, a quick read-through made clear to me the \nimmense magnitude of the effort that would be required \nto fix our manual\u2019s many problems. I therefore chose to \nfollow the longstanding tradition established by \u00adgenerations \nof fellows before me: I suggested a few cosmetic changes \nto a few sections before dumping the problem of our inad\u00ad\nequate manual onto the next year\u2019s fellows.\nThe following year, one of the new surgical pathology \nfellows, Dr. Susan Lester, apparently motivated by the \nselfless desire to finally bring order to the chaos that was \nour surgical pathology manual (possibly co-mingled with \nthe na\u00efve belief that process might not be that difficult), \nbegan the Herculean task of completely revising the \nentire volume. She succeeded in gathering perfect dia\u00ad\ngrams and pictures for each specimen type from various \nsources, and wrote explicit instructions for handling and \ndissecting each organ, with explanatory notes that made \nclear the reason for each step in the process. While she \nno doubt spent more time on this revision alone than we \nother fellows spent on all our fellowship duties combined, \nin the end she produced a spectacularly beautiful, surpris\u00ad\ningly elegant, and eminently practical surgical pathology \nmanual that served as the basis for first edition of this \nbook.\nEven in its first edition, however, this Manual was much \nmore than a simple dissection guide, including as it did \ndetailed instructions for handling intraoperative consul\u00ad\ntations, helpful insights into composing surgical pathol\u00ad\nogy reports, and comprehensive analyses of the utility of \nimmunophenotyping and other ancillary studies that pro\u00ad\nvide increasingly important contributions to pathologic \ndiagnosis, which are further expanded in this new edition. \nDr. Lester\u2019s thorough compilation of common immu\u00ad\nnohistochemical markers, to cite just one example, with \ndetailed notes on their diagnostic utility, sensitivity, and \nspecificity, perfectly demonstrates her ability to provide \nan elegant distillation and compilation of large amounts \nof extremely practical information \u2013 critically important \nto the practice of surgical pathology \u2013 that was previ\u00ad\nously impossible to find gathered in one place for quick \nreference.\nLearning diagnostic pathology is a long-term endeavor, \nwhich takes years to master. But with publication \nof the first edition of Manual of Surgical Pathology, \nDr. Lester proved that learning how to handle gross \npathology specimens and write surgical pathology \nreports need not be. Provided with such clear and \nexplicit descriptions of the goals of pathology specimen \nprocessing and step-by-step instructions on how to reach \nthem, even beginning residents could now quickly mas\u00ad\nter the process of identifying the pertinent gross lesions \nin surgical specimens, and insuring they are accurately \nrepresented in tissue sections submitted for microscopic \nexamination, thereby freeing pathologists-in-training \nto focus on learning the many subtleties and nuances \nof histopathologic interpretation. For many years at \nUCSF, we have provided a copy of Dr. Lester\u2019s Manual \nto each new resident, who have found it an extremely \nvaluable resource and introduction to the field. I like \nto tell our residents that it was clearly my influence on \nDr. Lester as a more senior resident and fellow during \nher surgical pathology rotations that made her so good \nat gross pathology (figuring she is too far away for them \nto attempt to verify that independently).\nForeword", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_006.png", "summary": "The surgical pathology manual at Brigham and Women's Hospital in the late 1980s was inadequate and relied heavily on oral tradition for instruction. Dr. Susan Lester took on the monumental task of completely revising the manual, resulting in a comprehensive and practical resource for surgical pathology.", "questions": [ "What challenges did the pathology residents face with the original surgical pathology manual?", "How did Dr. Susan Lester approach the task of revising the manual?", "What additional features were included in the revised surgical pathology manual?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 7, "text": "vi\n\ufeff\ufeffForeword\nIn the years since its first publication, Dr. Lester\u2019s \nManual of Surgical Pathology has been imitated but never \nequaled. It provides an invaluable resource to both begin\u00ad\nning residents and practicing pathologists alike, and \ndeserves its own position of honor on the bookshelf and in \nthe dissection room of everyone involved in the practice of \nsurgical pathology.\nPatrick Treseler, MD, PhD\nProfessor of Pathology\nDirector of Residency Training\nAssociate Director of Surgical Pathology\nUniversity of California, San Francisco", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_007.png", "summary": "Dr. Lester's Manual of Surgical Pathology is highly regarded and serves as a valuable resource for residents and practicing pathologists.", "questions": [ "What sets Dr. Lester's Manual of Surgical Pathology apart from other publications?", "How has the manual been received by residents and practicing pathologists?", "What specific information or resources does the manual offer to its readers?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 8, "text": "vii\nPreface to the First Edition\nI was \ufb01rst asked to edit the procedure manual for the \nBrigham and Women\u2019s Hospital Pathology Department \nin 1991. Over the years, the manual has been a col\u00ad\nlaborative effort, involving staff pathologists, residents, \nclinicians, pathology assistants, secretaries, and histotech\u00ad\nnologists. This is the manual\u2019s greatest strength. It reflects \nthe combined knowledge, experience, and opinions of \na multitude of people who produce and use pathologic \ninformation. It has been re\ufb01ned by almost a decade of use \nby staff, residents, and pathology assistants on the front \nlines of pathology.\nThis manual has grown over the years from instructors \nfor the gross examination of specimens to a comprehensive \nguide for the making of a pathologic diagnosis \u2013 from the \nsubmission of pathology specimens to the preparation of \nthe \ufb01nal surgical pathology report. Tables describing his\u00ad\ntochemical stains, immunoperoxidase studies, and electron \nmicroscopy \ufb01ndings can facilitate the interpretation of \nspecial studies. Checklists for diagnostic and prognostic \ninformation to be included for major tumor resections \nare provided, as well as information for standard tumor \nclassi\ufb01cation and staging. It is hoped that simplifying the \naccess to this information, currently only available from \nnumerous diverse sources, will enhance the provision of \nimportant pathologic information in pathology reports. \nComplementary recommendations have been published \nby the Association of Directors of Anatomic and Surgical \nPathology, the College of American Pathologists, and \nindividual institutions, and information from theses sourc\u00ad\nes has been incorporated when appropriate.\nThe Manual of Surgical Pathology is not intended to \nbe, and should not be misconstrued to be, a \u201cstandard \nof care.\u201d The \u201ccorrect\u201d method to process or report a \nspecimen can vary, depending on the speci\ufb01cs of a case, \ninstitutional policies, and the personal preferences of \nclinicians and pathologists, and will change over time. In \naddition, since unlimited budgets for specimen processing \nis an unobtainable goal, the cost of examining a specimen \nmust be balanced against the clinical signi\ufb01cance of the \ninformation obtained.\nFrom the surgical cutting room to the senior sign-out \narea, we keep this manual close at hand as a helpful refer\u00ad\nence. It is our sincere hope that others will \ufb01nd it equally \nas useful in their practice.\nSusan C. Lester", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_008.png", "summary": "The Manual of Surgical Pathology is a collaborative effort involving various individuals in the field of pathology, providing a comprehensive guide for making pathologic diagnoses.", "questions": [ "How has the manual evolved over the years?", "What are some of the key features included in the manual?", "How does the manual address the variability in processing and reporting specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 9, "text": "", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_009.png", "summary": "No summary generated.", "questions": [] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 10, "text": "ix\nPreface to the Second Edition\nA major advantage of pathology as a medical specialty is \nthat the biology of disease remains constant for the most \npart, resulting in a large body of knowledge that will never \nchange. On the other hand, our understanding of disease is \nexpanding rapidly. Pathologists are being asked to use new \ninformation to re-classify disease, provide better prognos\u00ad\ntic information, and to predict response to therapy. The \ngrowing amount of relevant data and the expanding role \nof pathologists has created the need for an updated version \nof this manual. In particular, every table in the manual has \nbeen revised and updated and many new tables added.\nNew antibodies with value for clinical diagnosis are \nintroduced almost monthly. Since the last edition, the \nnumber of antibodies used for diagnostic purposes has \nalmost doubled and is now approaching 200. To facilitate \nthe use of these markers, all of the immunohistochemistry \ntables have been updated, with many new tables for dif\u00ad\nferential diagnosis added.\nPathologists are also playing a larger role in determin\u00ad\ning tumor response to therapy. HER2/neu and breast \ncancer, CD117 (c-kit) and GIST, along with EGFR and \ncolon carcinoma, herald a new era of targeted therapy. \nInformation is provided about when these tests are appro\u00ad\npriate, and the reporting of results.\nCytogenetic studies are increasingly important in tumor \nclassification and prognosis. The recent discovery of a group \nof lung adenocarcinomas that are particularly susceptible to \ntreatment due to specific mutations in EFGR is only one \nexample. Expanded tables that list cytogenetic changes \nin solid tumors and hematological malignancies provide \nmany more examples of how this information is being used \nfor diagnosis, prognosis, and treatment. Pathologists can \nalso play an important role in suggesting which patients \nmay carry germline mutations that cause susceptibility to \ncancer. New tables provide the tumors and clinical settings \nin which a germline mutation is highly probable, and syn\u00ad\ndromes associated with pathologic findings.\nThe gross examination of specimens and histologic \nfeatures of carcinomas continue to be the most important \nfactors for predicting a patient\u2019s course. This information \nhas been critically evaluated and the College of American \nPathologists has issued new guidelines for the reporting \nof tumors. Information now considered to be required \nhas been highlighted in the \u201cPathologic Prognostic and \nDiagnostic Features Sign-out Checklists.\u201d In addition, \nspecific criteria have been provided for the grading or \nassessment of other relevant pathologic features.\nConcern about disease as a weapon of mass destruction \nis, unfortunately, also a new development since publication \nof the first edition. Pathologists may have the opportunity \nto be the first to recognize an agent of bioterrorism, but \nthese are not typically encountered in ordinary practice \nand may present a diagnostic challenge. A new table gives \ninformation on the most likely agents, their pathologic \nfeatures, and contact information for the CDC if such an \nagent is suspected.\nThe illustrations by Dr. Christopher French and Mr. \nGlenn Curtis are another very important addition to the \nsecond edition. Although some of the figures from the \nfirst edition have been maintained, all new illustrations are \ntheirs. As an experienced pathologist and an accomplished \nartist, Dr. French has been able to capture the essential \nmorphological differences among tumors that allow for \ngross diagnosis. Excellent examples include his illustra\u00ad\ntions of adrenal, kidney, liver, and pancreatic tumors.\nFinally, the manual has been refined through another \nfour years of exacting criticism by the residents of BWH. \nTheir constant vigilance keeps me on my toes and the \nmanual on the path to perfection. \nSusan C. Lester", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_010.png", "summary": "The field of pathology is rapidly evolving, with new information leading to re-classification of diseases, improved prognostic information, and the ability to predict response to therapy. The manual has been updated to reflect these changes, including new tables, antibodies, and guidelines.", "questions": [ "How are pathologists using new information to re-classify diseases?", "What role do antibodies play in clinical diagnosis and how has their usage changed?", "How are pathologists contributing to determining tumor response to therapy and what specific markers are being utilized?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 11, "text": "", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_011.png", "summary": "No summary generated.", "questions": [] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 12, "text": "xi\n\t\n\t\nxi\nPreface to the Third Edition\nEvery month there are new advances in our knowledge of \npathologic processes and the ability to use this information \nfor patient care. This edition of the Manual of Surgical \nPathology has been updated to include changes relevant \nfor surgical pathology.\nThe revisions for the 7th edition of the American Joint \nCommission on Cancer staging manual will take effect \nin 2010. The pathologic features of carcinomas and their \nregional lymph node involvement continue to be strong \nindicators of prognosis and the means by which patients \ncan be consistently divided into selected groups for com\u00ad\nparison in treatment trials. New types of tests, such as gene \nexpression profiling, use methodologies that analyze the \nbiologic make-up of cancer cells. The results of these stud\u00ad\nies reveal the potential ability of a cancer to metastasize, \nwhereas anatomic features establish the extent to which \nthe cancer has actually spread. The capacity to metastasize, \ncombined with the time and opportunity to do so, deter\u00ad\nmine the ultimate outcome. Both types of information will \nbe important for patient care and for the understanding of \ndisease. This third edition updates the recommendations \nfor AJCC classification and includes additional guidelines \nfor the assessment of critical pathologic features.\nThe number of antibodies commonly used in surgical \npathology continues to increase. The lengthy table of anti\u00ad\nbodies is now even lengthier. To assist in their use, new \ntables for central nervous system tumors, lung \u00adcarcinomas, \nfibroblastic/myofibroblastic lesions of the breast, signet \nring cell carcinomas, metastatic carcinomas to the abdo\u00ad\nmen, as well as others, have been added. Additional infor\u00ad\nmation is also included for the evaluation of microsatellite \ninstability in colon carcinomas using immunohistochemis\u00ad\ntry and other types of tests.\nThe role of viruses in certain types of tumors is becom\u00ad\ning more important for tumor classification as well as for \ntargeted treatment or prevention with vaccines. A new \ntable of virus types, associated neoplasms, and histologic \nfeatures has been created.\nFor aficionados of medical terminology, there is a new \nbrief guide to the plural forms of Latin and Greek words. \nThe bottom line \u2013 Greek and Latin grammer is not for \nneophytes (and that is neophytes \u2013 not neophytae or \n\u00adneophytodes!).\nThe illustrations of Dr. Christopher French and \nMr. Shogun G. Curtis convey what words cannot. Added \nin this edition are illustrations of viral inclusions, common \nfungi, and non-cellular material to aid in their recognition.\nThe manual has undergone yet another three years of \nevaluation, review, and criticism by the residents, fellows, \nand staff of our department. The users of the manual have \nalways been the key element in making this a working text \nof value to the person at the bench or at the microscope \nand I am, as always, grateful to all who have contributed \nto it.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_012.png", "summary": "The third edition of the Manual of Surgical Pathology has been updated to include changes relevant for surgical pathology, such as new advances in knowledge, revisions for the AJCC staging manual, increased use of antibodies, and the role of viruses in tumor classification.", "questions": [ "How do pathologic features of carcinomas and lymph node involvement affect prognosis?", "What new types of tests are being used in surgical pathology, and how do they analyze cancer cells?", "How are antibodies commonly used in surgical pathology, and what new tables have been added to assist in their use?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 13, "text": "", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_013.png", "summary": "No summary generated.", "questions": [] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 14, "text": "xiii\nThe requirement for a comprehensive detailed procedure \nmanual grew out of the needs of a large pathology depart\u00ad\nment handling numerous specimens using state-of-the-art \ntechniques. The Brigham and Women\u2019s Hospital Pathology \nDepartment will always be indebted to Dr. Ramzi Cotran \nas the department flourished under his outstanding leader\u00ad\nship and I am truly fortunate to have been both his trainee \nand, later, a member of his staff. Our current chairman, \nDr. Michael Gimbrone, has continued his legacy of \n\u00adexcellence in pathology service, teaching, and research.\nI also must thank Dr. Stan Robbins whose glimpses \nof gentle humor in The Pathologic Basis of Disease were \ntreasures for a medical student to find while studying late \nat night. He proved that a serious textbook need not be \ndevoid of humanity. \nThe original Brigham and Women\u2019s departmental man\u00ad\nual was edited by Dr. Joseph Corson and Dr. Geraldine \nPinkus for many years. Dr. Corson continued to co-edit \nthe current manual during his tenure as the Director of \nSurgical Pathology. His meticulous attention to detail, as \nwell as his enthusiastic love for pathology, are just two of \nthe many important things he taught me. As Dr. Corson\u2019s \nsuccessor, Dr. Christopher Fletcher has continued to set \nthe highest standards for the department.\nThe consulting authors have provided their expertise in \nall facets of pathology and I am grateful for their willing\u00ad\nness to lend their names and talents to the preparation of \nthe published manual. All credit should be given to them. \nAny deficiencies or errors are mine alone.\nMany other individuals have contributed over the years \nand their help is also gratefully acknowledged: Dr. Douglas \nAnthony, Dr. Kamran Badizadegan, Ms. Lynn Baldassano, \nDr. Raymond Barnhill, Dr. Michael Bennett, Dr. Frederick \nBieber, Dr. Ramon Blanco, Ms. Holly Bodman, Dr. Marcus \nBosenberg, Mr. David Bowman, Mr. Lynroy Brade, \nDr. Thomas Brenn, Dr. Felix Brown, Dr. Patty Brunker, \nDr. Elizabeth Bundock, Dr. Joseph Carlson, Dr. Diego \nCastrillon, Dr. Young Chang, Dr. Priscilla Chang, \nMs. Ghizlane Charki, Dr. Eleanor Chen, Dr. Gerald \nChu, Ms. Margaret Cialdea, Dr. James Connolly, \nDr. Christopher Corless, Dr. Milton Data, Dr. Johanna \nGibson, Dr. Umberto De Girolami, Dr. Briana Gleason, \nMs. Marilyn Donovan, Mr. Thomas Dunphy, Mr. Dan \nFaasse, Mr. John Fahey, Dr. Carol Farver, Ms. Delia \nFinne, Dr. Mark Fleming, Dr. Ann Folkins, Dr. Tim Foo, \nDr. Matthew Frosch, Dr. Eleanora Galvanek, Dr. David \nGenest, Ms. Kristi Gill, Dr. Jonathon Glickman, Dr. Meryl \nGoldstein, Dr. James Gulizia, Dr. Julie Gulizia, Dr. Susan \nHasegawa, Dr. Robert Hasserjian, Dr. Jonathan Hecht, \nDr. Jay Hess, Dr. Travis Hollman, Dr. David Kindelberger, \nMr. Mark Knowlton, Dr. Madeleine Kraus, Dr. Todd \nKroll, Dr. Frank Lee, Dr. Kenneth Lee, Dr. Kevin Long, \nMs. Danielle Long, Dr. Michelle Mantel, Dr. James \nMcGuire, Dr. Phillip McKee, Dr. Mairin McMenamin, \nMs. Lori Marini, Mr. Steve Mello, Ms. Kathleen Mitchell, \nDr. George Mutter, Dr. Alessandra Nascimento, Dr. Kirstine \nOh, Dr. Mana Parast, Ms. Lori Patruno, Mr. James Pepoon, \nDr. German Pihan, Mrs. Cathleen Quade, Ms. Catherine \nQuigley, Dr. Andrew Rosenberg, Dr. Mark S. Redston, \nDr. Andrew Renshaw, Ms. Chris Ridolphi, Dr. Brian \nRubin, Dr. Mark A. Rubin, Dr. Rachel Rucker-Schmidt, \nDr. Peter Sadow, Mr. Richard Sartorelli, Dr. Birgitta \nSchmidt, Dr. Jason Schmidt, Dr. Stuart Schnitt, Dr. Joseph \nSemple, Mr. Aliakbar Shahsafaer, Ms. Kathleen Sirois, \nDr. Jeffrey Sklar, Ms. Alyson Smeedy, Dr. Lincoln Stein, \nDr. Howard Stern, Dr. James Stone, Dr. Jerrold Turner, \nDr. Vijay Vanguri, Dr. Franz von Lichtenberg, Dr. Peter \nWang, Dr. David Weinberg, Dr. Michael Weinstein, \nDr. William Welch, Dr. Frances White, Dr. Greg Wolgamot, \nand Mr. Keith Yarid. \nThis list would not be complete without including \nDr. Patrick Treseler. As a fellow trainee he was a role \nmodel and a mentor. Pat is an excellent teacher and he \nproved during his residency and fellowship that pathol\u00ad\nogy lectures can be both enlightening and entertaining. \nIf the manual is entertaining at all, it is due to his influ\u00ad\nence. It is a true pleasure to have Pat as a friend and \na colleague.\nOur publisher, Elsevier (under the imprint of Saunders) \nmust be acknowledged, especially William Schmidt and \nAndrea Vosburgh (for this edition) and William Schmidt, \nRuth Swan, and Nora Naughton (for the previous edi\u00ad\ntions) whose immense patience and \u00adsupport made this \nproject possible.\nMy parents, Dr. Richard Lester and Mrs. Mary Lester, \nintroduced me to laboratories, microscopes, and the treat \nof drinking soda out of lab beakers - which is now, unfor\u00ad\ntunately, in violation of current regulations \u2013 however, \nI survived along with an appreciation for science and \n\u00adwriting, for which I will always be grateful to them. \nAcknowledgments", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_014.png", "summary": "The surgical pathology manual at Brigham and Women\u2019s Hospital acknowledges the contributions of various individuals over the years, highlighting the importance of attention to detail and dedication to the field.", "questions": [ "What role did Dr. Ramzi Cotran play in the development of the pathology department?", "How has Dr. Christopher Fletcher continued the legacy of excellence in the department?", "What is the significance of Dr. Joseph Corson's meticulous attention to detail in editing the manual?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 15, "text": "xiv\n\ufeff\ufeff Acknowledgments\nFinally, without support at home such a project would \nnever be possible. Tanya Badder, Heather McCartney, \nFritzi Rother, Sarah Schneemann, or Steffi Bauer were \nalways there when I couldn\u2019t be home. My husband, \nDr. Lloyd Klickstein, has been a steadfast supporter, \nhelpmate, computer crisis consultant, and best friend. My \nthree children, Isaac, Jacob, and Naomi have, hopefully, \nenjoyed their trips to the pathology department, peering \ndown microscopes, and drinking sodas (but not out of \nbeakers) as much as I have enjoyed showing them what \nI do. The last person in my family to write a book was \ntheir great great great grandfather John Regan, who trav\u00ad\neled to America from Scotland and published \u201cBackwoods \nand Prairies\u201d in 1850 to encourage other people to \nemigrate to the United States. I hope my children have \ninherited his spirit of adventure and love of writing, and \nthat it won\u2019t take our family another 151 years to produce \nanother book.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_015.png", "summary": "The author expresses gratitude towards their family for their support in completing the project of writing a book on surgical pathology.", "questions": [ "How did the author's family support them during the process of writing the book?", "What role did the author's husband play in supporting them?", "How does the author hope their children have been influenced by their ancestor who wrote a book in the past?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 16, "text": "xv\nConsultants\nJon Christopher Aster, MD, PhD\nProfessor of Pathology, Harvard Medical School; Associate \n\u00adPathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nLymph Nodes, Spleen, and Bone Marrow; Special Studies\nGilbert Brodsky, MD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Director, Surgical Pathology, Department of Pathology \nand Laboratory Medicine, Harvard Vanguard Medical Associates; \nConsultant Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nSpecimen Processing; Genitourinary Specimens; Head and Neck \nSpecimens\nLucian R. Chirieac, MD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nLung and Pleura Specimens\nEdmund S. Cibas, MD\nAssociate Professor of Pathology, Harvard Medical School; \n\u00adDirector, Cytology Division, Brigham and Women\u2019s Hospital, \nBoston, Massachusetts\nCytology Specimens\nJoseph M. Corson, MD\nProfessor of Pathology, Harvard Medical School; Director, \nSenior Pathologist, Brigham and Women\u2019s Hospital, Boston, \n\u00adMassachusetts\nLung and Pleura Specimens; Bone and Joint Specimens; Special \nStudies\nJames M. Crawford, MD, PhD\nSenior Vice President for Laboratory Services \nChairman of Pathology and Laboratory Medicine\nNorth Shore\u2013Long Island Jewish Health System\nNew Hyde Park, New York\nGastrointestinal Specimens\nChristopher P. Crum, MD\nProfessor of Pathology, Harvard Medical School; Director, \n\u00adWomen\u2019s and Perinatal Pathology Division, Brigham and \nWomen\u2019s Hospital, Boston, Massachusetts\nWomen\u2019s and Perinatal Specimens\nPaola Dal Cin, PhD\nAssociate Professor of Pathology, Harvard Medical School; \n\u00adAssociate Director, Cytogenetics, Brigham and Women\u2019s Hospi\u00ad\ntal, Boston, Massachusetts\nCytogenetics\nDeborah A.R. Dillon, MD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nBreast Specimens\nDavid M. Dorfman, MD, PhD\nAssociate Professor of Pathology, Harvard Medical School; \n\u00adMedical Director, Hematology Laboratory, Brigham and \nWomen\u2019s Hospital, Boston, Massachusetts\nThymus Specimens; Bone and Joint Specimens; Analytical Cytology \n(Flow Cytometry)\nChristopher D.M. Fletcher, MD, FRCPATH\nProfessor of Pathology, Harvard Medical School; Director, \n\u00adSurgical Pathology Division, Brigham and Women\u2019s Hospital, \nChief of Onco-Pathology, Dana Farber Cancer Institute, Boston, \nMassachusetts\nThe Surgical Pathology Report; Consultation Reports; Soft Tissue \nTumor (Sarcoma) Specimens; Special Studies\nJonathan A. Fletcher, MD\nAssociate Professor of Pathology and Pediatrics, Harvard \n\u00adMedical School; Cytogeneticist, Brigham and Women\u2019s Hospital, \nBoston, Massachusetts\nCytogenetics\nRebecca D. Folkerth, MD\nAssociate Professor of Pathology, Harvard Medical School; \nDirector of Neuropathology, Brigham and Women\u2019s Hospital; \nConsultant in Neuropathology, Children\u2019s Hospital, Boston, \n\u00adMassachusetts\nNeuropathology Specimens\nChristopher A. French, MD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nArtist; Cytology Specimens", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_016.png", "summary": "This page lists the consultants in various specialties at Brigham and Women's Hospital and their areas of expertise.", "questions": [ "What are the different specialties covered by the consultants listed?", "How are the consultants involved in the pathology department at Brigham and Women's Hospital?", "What role do these consultants play in the diagnosis and treatment of patients?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 17, "text": "xvi\nConsultants\nJohn J. Godleski, MD\nAssociate Professor of Pathology, Harvard Medical School; Chief, \nPulmonary Pathology Division, Brigham and Women\u2019s Hospital, \nBoston, Massachusetts\nLung and Pleura Specimens\nScott R. Granter, MD\nAssociate Professor of Pathology, Harvard Medical School; \nAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nDermatopathology Specimens; Special Studies\nMichelle S. Hirsch, MD, PhD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Brigham and Women\u2019s Hospital, \nBoston, Massachusetts\nGenitourinary Specimens; Women\u2019s and Perinatal Specimens; \nSpecial Studies\nJason L. Hornick, MD, PhD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist and Director of Surgical Pathology \n\u00adImmunohistochemistry Laboratory, Brigham and Women\u2019s \nHospital, Boston, Massachusetts\nGastrointestinal Specimens; Lymph Nodes, Spleen, and Bone \n\u00adMarrow Specimens; Soft Tissue (Sarcoma) Specimens; Special \nStudies\nLester Kobzik, MD\nProfessor of Pathology, Harvard Medical School; \u00adAssociate \nPathologist, Brigham and Women\u2019s Hospital, Boston, \n\u00adMassachusetts\nLung and Pleura Specimens\nJeffrey F. Krane, MD, PhD\nAssistant Professor of Pathology, Harvard Medical School; Chief, \nHead and Neck Pathology, Brigham and Women\u2019s Hospital, \nBoston, Massachusetts\nHead and Neck Specimens; Thyroid and Parathyroid Specimens\nFrank C. Kuo, MD, PhD\nAssistant Professor of Pathology, Harvard Medical School; Asso\u00ad\nciate Pathologist, Director of Pathology Information Technology, \nBrigham and Women\u2019s Hospital, Boston, Massachusetts\nThe Surgical Pathology Report; Lymph Nodes, Spleen, and Bone \nMarrow Specimens\nJeffery L. Kutok, MD, PhD\nAssociate Professor of Pathology, Harvard Medical School; \nAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nLymph Nodes, Spleen, and Bone Marrow Specimens; Special \n\u00adStudies\nKeith L. Ligon, MD, PhD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nNeuropathology Specimens\nMassimo F. Loda, MD\nProfessor of Pathology, Harvard Medical School; Associate \n\u00adPathologist, Chief, Genitourinary Pathology Service, Brigham \nand Women\u2019s Hospital, Boston, Massachusetts\nGenitourinary Specimens\nJanina A. Longtine, MD\nAssociate Professor of Pathology, Harvard Medical School; \nAssociate Pathologist, Co-Director of the Center for Advanced \nMolecular Diagnostics, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nMolecular Genetic Pathology; Lymph Nodes, Spleen, and Bone \n\u00adMarrow Specimens; Special Studies\nDanny A. Milner, Jr., MD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Assistant Medical Director of Microbiol\u00ad\nogy, Brigham and Women\u2019s Hospital, Boston, Massachusetts\nInfectious Disease and Microbiology\nRichard N. Mitchell, MD, PhD\nAssociate Professor of Pathology, Harvard Medical School; \nAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nCardiovascular Specimens\nV\u00e2nia Nos\u00e9, MD, PhD\nAssociate Professor of Pathology, Harvard Medical School; Asso\u00ad\nciate Director of Surgical Pathology, Chief, Endocrine Pathology \nService, Brigham and Women\u2019s Hospital, Boston, Massachusetts\nAdrenal Specimens; Thyroid and Parathyroid Specimens; Special \nStudies\nMarisa R. Nucci, MD, PhD\nAssociate Professor of Pathology, Harvard Medical School; \nAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nWomen\u2019s and Perinatal Specimens; Special Studies\nRobert D. Odze, MD\nAssociate Professor of Pathology, Harvard Medical School; Chief, \nGastrointestinal Pathology, Brigham and Women\u2019s Hospital, \nBoston, Massachusetts\nGastrointestinal Specimens\nRobert F. Padera, MD, PhD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nCardiovascular Specimens; Lung and Pleura Specimens\nGeraldine S. Pinkus, MD\nProfessor of Pathology, Harvard Medical School; Associate \nPathologist, Chief, Hematopathology Service, Brigham and \nWomen\u2019s Hospital, Boston, Massachusetts\nLymph Nodes, Spleen, and Bone Marrow Specimens; Special \n\u00adStudies", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_017.png", "summary": "This page lists the consultants and their specialties at Brigham and Women's Hospital for various types of surgical pathology specimens.", "questions": [ "What are the different specialties covered by the consultants listed?", "How are the consultants affiliated with Harvard Medical School and Brigham and Women's Hospital?", "What is the significance of having specialists for specific types of pathology specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 18, "text": "Consultants\nxvii\nBradley J. Quade, MD, PhD\nAssociate Professor of Pathology, Harvard Medical School; \nAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nWomen\u2019s and Perinatal Specimens\nHelmut G. Rennke, MD\nProfessor of Pathology, Harvard Medical School; Chief, Kidney \nPathology Service, Brigham and Women\u2019s Hospital, Boston, \n\u00adMassachusetts\nKidney Specimens; Special Studies\nAndrea L. Richardson, MD, PhD\nAssistant Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Brigham and Women\u2019s Hospital, \nBoston, Massachusetts\nBreast Specimens\nDrucilla J. Roberts, MD\nAssociate Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Massachusetts General Hospital, Boston, \nMassachusetts\nPerinatal Specimens\nFrederick J. Schoen, MD, PhD\nProfessor of Pathology and Health Sciences and Technology \n(HST), Harvard Medical School; Executive Vice-Chairman, Chief, \nCardiac Pathology, Brigham and Women\u2019s Hospital, Boston, \n\u00adMassachusetts\nCardiovascular Specimens\nSara O. Vargas, MD\nAssociate Professor of Pathology, Harvard Medical School; \n\u00adAssociate Pathologist, Brigham and Women\u2019s Hospital, \nChildren\u2019s Hospital, Boston, Massachusetts\nLung and Pleura Specimens\nWilliam R. Welch, MD\nAssociate Professor of Pathology, Harvard Medical School; \nAssociate Pathologist, Brigham and Women\u2019s Hospital, Boston, \nMassachusetts\nWomen\u2019s and Perinatal Specimens; Genitourinary Specimens\nTad J. Wieczorek, MD\nInstructor in Pathology, Harvard Medical School; Consultant \nin Cytopathology, Brigham and Women\u2019s Hospital; Staff \n\u00adPathologist, Faulkner Hospital, Boston, Massachusetts\nCytology Specimens\nGayle L. Winters, MD\nAssociate Professor of Pathology, Harvard Medical School; Direc\u00ad\ntor, Pathology Residency Training Program, Director, Autopsy \nDivision, Brigham and Women\u2019s Hospital, Boston, Massachusetts\nCardiovascular Specimens", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_018.png", "summary": "The page lists various pathology consultants specializing in different specimen types at Harvard Medical School and affiliated hospitals in Boston, Massachusetts.", "questions": [ "What are the different specimen types that each consultant specializes in?", "How do these consultants contribute to the pathology services at the hospitals?", "Are there any specific research interests or projects mentioned for these consultants?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 19, "text": "", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_019.png", "summary": "No summary generated.", "questions": [] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 20, "text": "2\n1\nRequests for Pathologic \nEvaluation\nThe pathologist has an essential role in patient care as \ndiagnostician, patient advocate, and clinical teacher. The \nsurgical pathologist examines tissues and foreign objects \nremoved from patients to identify disease processes, docu\u00ad\nment surgical procedures, and release tissue for research. \nSpecimens submitted for examination include:\n\t\u2022\t \u0007Fluids, cells, and tissues. Hair, fingernails, and toenails \nremoved for cosmetic reasons are not included, unless \nthere are specific indications for examination.\n\t\u2022\t \u0007Products of conception.\n\t\u2022\t \u0007Medical devices that have been implanted in the body. \nTemporary devices (such as IV catheters, endotracheal \ntubes, etc.) usually are not examined.\n\t\u2022\t \u0007Foreign objects removed from the body, including \nobjects introduced by trauma, such as bullets.\nA decision not to submit specific types of specimens \nfor pathologic examination should be made jointly by the \ndepartment of pathology, other involved departments, and \nthe institution\u2019s legal department to ensure that the best \ninterests of the patient, physicians, and hospital are being \nserved. Such decisions need to be documented as written \nhospital policy according to The Joint Commission (TJC) \nguidelines. Guidelines for determining the types of speci\u00ad\nmens that must be submitted for pathologic examination \nare discussed in Chapter 21.\nSUBMITTING PATHOLOGY SPECIMENS\nIt is the responsibility of all hospital personnel involved to \nensure that each patient\u2019s specimen is appropriately and \nsafely handled and processed for the maximum benefit \nto the patient and the physicians caring for him or her.1 \nTJC standards require that a request for pathologic exami\u00ad\nnation be made in writing or electronically and that the \nrequest be kept on file for two years. When a pathologic \nexamination is requested, the following information must \nbe provided:\nPatient Identification\nMisidentification of specimens can lead to serious errors \nin diagnosis or a failure to diagnose.2 The identification \nof specimens must include, as a minimum, the patient\u2019s \nfull name and date of birth. Preferably, a hospital or \nclinic identification number is also provided. This infor\u00ad\nmation must be attached firmly to the specimen con\u00ad\ntainer. Unattached paperwork is easily displaced from an \nunlabeled container and is not acceptable for definitive \nidentification.\nInappropriately identified specimens must be brought \nto the attention of the submitting clinician immediately. If \nthere is any uncertainty in determining the correct patient, \nthe clinician should come to the pathology department \nto identify the specimen. If the nature of the specimen is \nsuch that gross identification is not possible (e.g., a small \nbiopsy), and identification is uncertain, a repeat specimen \nshould be obtained if possible. There are tissue typing \nmethods that can match tissues from patients and speci\u00ad\nmens, but such techniques are time-consuming and costly \nand are best avoided by ensuring appropriate identifica\u00adtion \nat the time of performing the biopsy (see in Chapter 3, \n\u201cIdentification of Tissue\u201d).\nIdentification of the Individual(s) Requesting \nthe Examination\nThe names of all clinicians caring for the patient should \nbe provided in order for them to receive a copy of the final \nreport. This includes not only the physician sending the \nspecimen (e.g., a surgeon or gastroenterologist) but also \n\t\u2022\t \u0007Patient identification\n\t\u2022\t \u0007Identification of the individual(s) requesting the exam\u00ad\nination\n\t\u2022\t \u0007Procedure date. The time tissue specimens are removed \nfrom the patient is helpful to determine the length of \ntime prior to fixation and/or the time in fixation, when \nrelevant.\n\t\u2022\t \u0007Adequate clinical history\n\t\u2022\t \u0007Specimen identification, including tests requested and \nany special handling required\n\t\u2022\t \u0007Instructions for the disposition of gross specimens, if \nnot routine disposal (e.g., specimens to be returned to \nthe patient, products of conception requested for burial, \nmedical devices to be returned to the \u00admanufacturer).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_020.png", "summary": "Pathologists play a crucial role in patient care by examining tissues and foreign objects to identify disease processes, document surgical procedures, and release tissue for research. Specimens submitted for examination include fluids, cells, tissues, products of conception, medical devices, and foreign objects.", "questions": [ "What are the responsibilities of a pathologist in patient care?", "Why is it important to ensure proper identification of specimens?", "How are decisions made regarding which specimens to submit for pathologic examination?", "What information must be provided when requesting a pathologic examination?", "What are the consequences of misidentified specimens in pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 21, "text": "REQUESTS FOR PATHOLOGIC EVALUATION\u2003 Submitting Pathology Specimens\n3\nthe primary care physician and other involved specialists \n(e.g., an oncologist caring for a cancer patient). If a rush \nreading is requested, the name or names of physicians to be \ncontacted as well as a means to reach them (e.g., a beeper \nnumber or telephone number) must be provided.\nProcedure Date\nThe date of the procedure (day, month, and year) must be \ndocumented in order to:\n\t\u2022\t \u0007Correlate the biopsy findings with other clinical tests \n(e.g., radiologic examinations or serum chemistries).\n\t\u2022\t \u0007Determine whether there is a delay during transport to \nthe pathology department.\n\t\u2022\t \u0007Monitor turnaround time for pathology specimens.\n\t\u2022\t \u0007Fulfill requirements of Medicare/Medicaid and other \nthird party payers for billing purposes.\nThe time the specimen was removed from the patient \ncan be helpful to determine the length of time prior to \nfixation (which, if prolonged, can affect the results of some \nspecial studies). If the specimen is placed in a fixative for \nwhich the time of fixation is important (e.g., bone marrow \nbiopsies in Zenker\u2019s fixative, formalin fixation for breast \ncarcinoma specimens) the time of placing the specimen \ninto fixative should also be recorded.\nAdequate Clinical History\nAs for any medical consultation, the consultant can pro\u00ad\nvide the most helpful additional information when an \nadequate history is provided. Clinical history helps define \nthe need for, and the nature of, special studies that can be \nperformed. It has been shown that pathologists cannot \naccurately predict clinical information from the glass slides \nalone.3 Important elements of clinical history are listed at \nthe beginning of each chapter for each type of specimen.\nThe Joint Commission requires that \u201csurgical speci\u00ad\nmens are accompanied by pertinent clinical informa\u00ad\ntion and preoperative and postoperative diagnoses to the \ndegree known\u201d (Standard QC.2.30) and that \u201cadditional \ninformation required to select appropriate tests and to \nensure accurate test interpretation and reporting of results \n(for example, race/ethnicity, family history, pedigree)\u201d be \nprovided (Standard IM.6.190) (Comprehensive Accredita\u00ad\ntion Manual for Laboratory and Point-of-Care Testing, \n2009). Pertinent clinical history includes:\nPurpose of removal of the specimen and the type \nof specimen\n\t\u2022\t \u0007Diagnostic biopsy\n\t\u2022\t \u0007Resection of tumor or re-excision of tumor site\n\t\u2022\t \u0007Surgery for therapeutic purposes (e.g., a colostomy take\u00ad\ndown or joint replacement)\nNote: The purpose of the surgery often determines the \ntype of pathologic examination required (e.g., inking of \nmargins or tissue allocation for special studies). Inaccurate \nor insufficient labeling may lead to a suboptimal pathologic \nexamination. The type of specimen is also important for \naccurate billing.\nLocation and types of any lesions present\n\t\u2022\t \u0007Description by anatomic site (e.g., head of pancreas) or \nregion (e.g., upper outer quadrant)\n\t\u2022\t \u0007Identification by placement of a suture or staple\n\t\u2022\t \u0007Identification by radiologic imaging (e.g., radiography \nfor breast calcifications or clips; nuclear imaging for \noctreotide uptake)\n\t\u2022\t \u0007Number of lesions and distance between lesions\nSome lesions that are grossly evident in vivo may \nbecome less evident after excision and cessation of blood \nflow (e.g., vascular lesions, cystic lesions if incised). It may \nbe necessary to mark some cancers with clips prior to neo\u00ad\nadjuvant treatment as after treatment some cancers are no \nlonger grossly identifiable.\nPrior diagnoses\n\t\u2022\t \u0007History of prior known tumors (including type/site/date \nof removal/ stage of disease)\n\t\u2022\t \u0007Current or recent pregnancy. Pregnancy-related chan\u00ad\nges can mimic malignancies.\n\t\u2022\t \u0007Immune system status. It is important to know whether \nthe patient may be immunocompromised:\nHIV positive\nAssisted ventilation\nOrgan transplants\nExtensive burns\nChronic ambulatory-\n\u00adperitoneal dialysis\nChronic sinusitis\nDiabetes\nIndwelling catheters or \u00ad\nmonitoring devices\nThis information is important to help guide special stud\u00ad\nies (i.e., characteristic histologic responses to infectious \ndisease organisms may be absent), to interpret histologic \nfindings, and to aid in ensuring the safety of pathology per\u00ad\nsonnel handling specimens with infectious organisms.\nPrior or current treatment\n\t\u2022\t \u0007Radiation or chemotherapy. Treatment-related changes \ncan be mistaken for malignancy if this history is not \nprovided. Carcinomas can be difficult to find grossly \nafter treatment, although extensive disease may be pres\u00ad\nent microscopically. Identification of the tumor bed is \nimportant in order to assess response to treatment.\n\t\u2022\t \u0007Drug use that can alter the histologic appearance of tis\u00ad\nsues (especially important for the evaluation of liver and \nendometrial biopsies)\n\t\u2022\t \u0007Drug use that could make the patient susceptible to \nunusual infections (corticosteroid therapy, chemother\u00ad\napy, prophylactic antibacterial or antifungal therapy)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_021.png", "summary": "Pathology specimens must be accompanied by adequate clinical history to ensure accurate test interpretation and reporting of results. The purpose of the surgery and type of specimen are important factors in determining the type of pathologic examination required.", "questions": [ "Why is it important to provide adequate clinical history when submitting pathology specimens?", "How does the purpose of the surgery impact the type of pathologic examination required?", "What are the consequences of inaccurate or insufficient labeling of specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 22, "text": "REQUESTS FOR PATHOLOGIC EVALUATION\u2003 Submitting Pathology Specimens\n4\nSpecific purpose of consultation\nThe requisition should state whether special studies are \nneeded clinically, especially those studies requiring special \nhandling of the tissue (e.g., suspected lymphoma possibly \nrequiring marker studies, microbiologic culture of sus\u00ad\npected infection, crystal examination in joint tissues).\nRush diagnoses\nSpecimens from critically ill patients can be given prior\u00ad\nity over other specimens if this would lead to better clini\u00ad\ncal management. If a specimen requires a rapid diagnosis, \na means to reach the appropriate clinician (e.g., a beeper \nnumber) must be included. A rush diagnosis for one case \nTABLE 1\u20131.\u2003\nSPECIMENS REQUIRING SPECIAL PROCESSING\nTYPE OF SPECIMEN OR \nREQUESTED STUDY\nCONDITION OF \nSPECIMEN\nCOMMENTS\nBone marrow biopsy\nZenker\u2019s fixative\nProvides optimal cytologic detail and decalcifies the bone. If \u00admetastatic \ncarcinoma is suspected, soft tissue should be separated and, if \n\u00adpossible, fixed in formalin to optimize possible immunoperoxidase \nstudies.\nBullets or other potential \n\u00admedicolegal cases\nDirect transfer\nA direct chain of custody must be maintained.\nCytogenetics (e.g., some POCs, \nunusual tumors)\nUnfixed, viable\nCytogenetic studies require viable cells. Some genetic studies can be \nperformed on fixed tissue (e.g., FISH).\nFlow cytometric analysis\nUnfixed\nFlow cytometry is optimally performed on fresh tissue either for marker \nanalysis (e.g., lymphomas) or for ploidy and S-phase fraction (e.g., \n\u00adcarcinomas). Although flow can be performed on fixed tissue, S-phase \ndetermination is less accurate due to fragmentation of nuclei.\nFrozen section for rapid diagnosis\nUnfixed\nFixed tissues do not adhere well to slides.\nGout\nUnfixed\nUric acid crystals dissolve in formalin. Tissue should be fixed in 100% \nethanol for anaqueous processing.\nInfections\nUnfixed\nTissue should be taken for culture. In some cases, special procedures \nmay be required to protect pathology personnel (e.g., TB and \n\u00adCreutzfeldt-Jakob disease) and to decontaminate equipment.\nKidney biopsy\nUnfixed\nTissue also should be fixed for immunofluorescence and EM.\nLiver: acute fatty liver\nUnfixed\nLipids are dissolved during routine processing. Demonstration of \nmicrovesicular fat requires frozen section and special stains.\nLiver: copper\nSpecial\nThe specimen must not be touched with metal tools to avoid trace \n\u00adcontamination (see under \u201cLiver biopsies\u201d).\nLymphomas\nUnfixed\nSpecial studies including flow cytometry, DNA analysis, and some marker \nstudies are optimally performed on fresh or frozen tissue.\nMuscle biopsy\nUnfixed\nThe specimen should be well oriented and frozen for enzyme studies \nand fixed for EM.\nSkin biopsies for bullous disease or \nsystemic lupus erythematosus\nUnfixed or in IF \ntransport media\nTissue should be fixed for immunofluorescence.\nUnusual tumors: sarcomas, \nsmall round blue cell tumors, \n\u00admesotheliomas, metastatic \ntumor of unknown primary\nUnfixed\nSpecial studies may be helpful for classification and may require fresh \ntissue (cytogenetics) or special fixatives (EM).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_022.png", "summary": "The page provides guidelines for submitting pathology specimens, including the specific purpose of consultation and the importance of rush diagnoses. It also lists various types of specimens requiring special processing.", "questions": [ "What are some examples of special studies that may be needed clinically and require special handling of tissue?", "How are rush diagnoses prioritized for critically ill patients?", "Why is it important to maintain a direct chain of custody for bullets or other potential medicolegal cases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 23, "text": "REQUESTS FOR PATHOLOGIC EVALUATION\u2003 Submitting Pathology Specimens\n5\nresults in a delay for non-rush cases. Therefore, requests \nfor rush readings should only be made when required for \npatient care.\nRush cases must be seen by a staff pathologist the same \nday the slides are available. The requesting clinician must \nbe called and a diagnosis or informative hold note \u00adprovided.\nCritical values\nSome diagnoses require immediate notification of the sub\u00ad\nmitting physician (see in Chapter 4, \u201cGuidelines for Com\u00ad\nmunication of Urgent Results\u201d). In some cases, clinical \nhistory is necessary to determine whether or not a result \nwould be a \u201ccritical value.\u201d\nFor the majority of specimens, an adequate history \nprior to pathologic examination can be given in one or two \nsentences. For example:\nHistory of diverticulitis. Colostomy takedown.\nHistory of colon carcinoma with multiple positive nodes one \nyear ago. Now with ulcerated mass at colostomy site, biopsy \nshown to be carcinoma.\nWoman s/p invasive breast cancer (ER and PR positive) \nresected here in 1989 with 3 lymph nodes positive, s/p radi\u00ad\nation and chemotherapy, now with subcutaneous nodule in \nmastectomy scar. Please do ER, PR, and HER2 if tumor.\n52-year-old male s/p bone marrow transplant for large cell \nlymphoma, now with bilateral pulmonary infiltrates, sus\u00ad\npect opportunistic infection. Open lung biopsy for culture \nand histologic examination. R/o recurrent lymphoma.\nSpecimens Requiring Special Processing\nSpecimens requiring special studies or processing must be \nclearly identified. Most such specimens can be sent moist \non saline (Table 1-1).\nTimely and Appropriate Transport to the Laboratory\nAutolysis immediately begins after the surgical removal \nof tissues. Although it can be reduced by refrigeration, \nextended delays before fixation will adversely affect the \ndiagnostic quality of tissues. Immunoreactivity is dimin\u00ad\nished for some markers (e.g., for receptors in breast \u00adcancers).\nIn some cases, it is appropriate for clinicians to directly \nplace specimens into fixatives at 15 to 20 times the volume of \nthe tissue. The type of fixative must be identified on the con\u00ad\ntainer with a warning label identifying the fixative. The time of \nplacing the specimen in the fixative should be included when \nappropriate (e.g., for fixatives containing mercury such as \nZenker\u2019s, if rush processing is requested, or if time in fixation \naffects the results of requested immunohistochemical studies).\nAll tissues and objects removed from patients may be \nhazardous and must be transported in a safe fashion. The \ncontainer must be leakproof. Either plastic rigid containers \n(preferably with a screw cap lid) or bags (but not if there is \nliquid with the specimen) may be used. A leak-proof sec\u00ad\nondary container (usually a zip-lock plastic specimen bag) \nwith a clean outer surface is required.\nClinicians submitting specimens in inappropriate con\u00ad\ntainers, unlabeled containers, or containers with the outside \nsurface grossly contaminated must be contacted and advised \nof the hazards this poses to patients and hospital personnel.\nInstructions for the Disposition of Gross Specimens\nIf a patient wants to keep a specimen (e.g., a limb or prod\u00ad\nucts of conception for burial, a breast implant for legal \npurposes, or hardware from a joint prosthesis) this request \nmust be stated on the requisition form to avoid routine dis\u00ad\nposal of specimens after the final report is issued. Patients \nshould be informed that their specimens will be discarded \nto avoid later misunderstandings. Recommendations for \nretention times are presented in Table 1-2.\nState laws may also regulate retention times. Institu\u00ad\ntional practices vary and in some cases materials may be \nkept for longer periods of time. Ideally, paraffin blocks on \npatients with cancers would be kept for longer periods of \ntime as these blocks may be of value if the cancer recurs or \nthe patient is entered into an experimental protocol.\nThe disposal of human tissues may be governed by \nstate law (usually requiring incineration and/or inter\u00ad\nment). However, the wishes of patients should always be \nrespected. A legal opinion may be required if a patient \nrequest would interfere with optimal patient care or \ncould endanger him or her. There may be specific legal \nrequirements for informing parents of their rights and for \nappropriate disposition of products of conception (includ\u00ad\ning stillborn fetuses and fetal deaths).\nTABLE 1\u20132.\u2003\nRECOMMENDED RETENTION TIMES \nFOR PATHOLOGY RECORDS AND MATERIALS\nTJC*\nCAP**\nGross specimens\n7 days after final \nreport\n14 days after \nfinal report\nParaffin blocks\nAt least 2 years\n10 years\nSlides\n10 years\n10 years\nCytology slides\n5 years\n5 years\nFNA slides\n10 years\n10 years\nPathology report\n10 years\n10 years\n*The Joint Commission (TJC) Manual, Appendix E (www.jointcommission.org).\n**College of American Pathologists Laboratory Accreditation Program Inspection \nChecklists (www.cap.org).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_023.png", "summary": "The page discusses the importance of timely submission of pathology specimens, including rush cases and critical values, as well as the need for special processing and appropriate transport to the laboratory.", "questions": [ "What are the criteria for determining if a case should be considered a 'rush case'?", "What steps should be taken if a specimen requires special processing?", "Why is it important for clinicians to provide adequate clinical history along with the specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 24, "text": "REQUESTS FOR PATHOLOGIC EVALUATION\u2003 Submitting Pathology Specimens\n6\nLateral\nMedial\nLateral/\nSuperior\nInferior/anterior\nLateral\nToward nipple \nLateral\nSuperior\nSuperior\nMedial\nLateral\nPosterior\nInferior\nAnterior\nToo complex\nCannot determine superior/inferior\nMost specimens can be visualized \nas a box with six sides\nTwo orienting sutures must be at \nright angles, in the center of the\n\u201cside\u201d of the box, in order to identify\nthe remaining four margins\nIf the sutures are at the junction of\ntwo margins, it is difficult to identify\nthe boundaries of the other margins\nIf the sutures are not given standard\ndesignations, the other margins\ncannot be identified with respect\nto the patient\nA simple method uses two sutures:\nShort suture = Superior margin;\nLong suture = Lateral margin.\nCannot determine superior/inferior\n(e.g., is nipple inferior or superior?)\nPreferred\n(Short = Superior; Long = Lateral)\nFigure 1\u20131.\u2002 Orientation of specimens.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_024.png", "summary": "The page discusses the proper orientation of pathology specimens for evaluation, emphasizing the importance of using two orienting sutures to identify margins.", "questions": [ "How do the orienting sutures help in identifying the margins of the specimen?", "Why is it important to have the sutures at right angles in the center of the 'side' of the box?", "What challenges may arise if the sutures are not given standard designations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 25, "text": "REQUESTS FOR PATHOLOGIC EVALUATION\u2003 Orienting Pathology Specimens\n7\nPerson erect with head, eyes, and toes directed forward\nArms to the side with palms forward\nLegs straight and feet together\nPenis erect\nAll designations refer to the patient in the anatomic position.\nThe actual position of the patient at the time of removing the\nspecimen is irrelevant (e.g., supine, prone, sitting). Thus,\nsuperior is always cephalad, inferior caudad, etc.\nTerms for orientation\nAnterior (ventral): towards the front of the body. The volar\nsurface refers to the palm of the hand (also \u201cpalmar\u201d) or the\nsole of the foot.\nPosterior (dorsal): towards the back of the body. The upper\nsurface of the foot is termed the dorsal surface because this\nis the position of the foot during embryonic development.\nThe penis is in an erect position (the upper surface of the\npenis is the dorsal surface) for unknown reasons.\nSuperior (cephalic, cephalad): towards the head\nInferior (caudal, caudad): towards the feet. The inferior\nsurface of the foot is termed the plantar surface.\nMedial: median (midline) plane of the body\nLateral: away from the median plane of the body\nProximal: nearest the trunk or point of origin\nDistal: farthest from the trunk or point of origin\nSuperficial: nearest to the skin surface\nDeep: farthest from the skin surface\nTransverse section: a horizontal plane at right angles to the\nlongitudinal axis of the body or a body part with division into\nsuperior and inferior parts\nCoronal section: a vertical plane that divides the body or\nbody structure into anterior and posterior parts\nSagittal section: a vertical plane parallel to the median plane\nthat divides the body or body structure into medial and\nlateral parts (\u001f parasagittal)\nB\nC\nSuperior\nMedial\nLateral\nLateral\nPosterior\nInferior\nTransverse\nCoronal\nSagittal\nAnterior\nThe (almost) anatomic position\nA\nFigure 1\u20132.\u2002 The (almost) anatomic position.\nORIENTING PATHOLOGY SPECIMENS\nThe orientation of some specimens is evident from ana\u00ad\ntomical landmarks (e.g., a right colectomy). However, \nmany specimens are either difficult or impossible to ori\u00ad\nent once the specimen has been removed from the patient \n(Figs. 1-1 and 1-2).\nIf orientation is important for the evaluation of a speci\u00ad\nmen (e.g., excisions of malignant tumors), and orientation \nhas not been provided or is unclear, the pathologist should \ncontact the surgeon before processing the specimen. It \nis always preferable for the surgeon to personally discuss \ncomplicated specimens with the pathologist.\nFor most specimens, external markers must be used to \nprovide information about orientation for the pathologist. \nThe pathologist can then identify the site of the \u00adsections \ntaken and relate them to the anatomic location in the \npatient. Possible techniques include:\n\t\u2022\t \u0007Sutures of variable composition, length, or number to \nmark anatomical sites (e.g., \u201cdeep margin\u201d) or areas of \ngreatest concern (e.g., \u201cclosest margin\u201d): Two sutures", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_025.png", "summary": "The page discusses the importance of orienting pathology specimens for accurate evaluation, including the use of external markers and the need for communication between pathologists and surgeons.", "questions": [ "Why is it important to orient pathology specimens?", "What are some techniques used to provide orientation information for pathologists?", "Why is communication between pathologists and surgeons crucial for evaluating specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 26, "text": "REQUESTS FOR PATHOLOGIC EVALUATION\u2003 Orienting Pathology Specimens\n8\nat right angles are necessary to identify the remaining \nfour margins. Whip stitches can also be used to mark a \nregion of a specimen. Sutures of different colors may be \nproblematic, as the color may be obscured after inking \nmargins. A common, and easily remembered, system is \nto use a Long suture for the Lateral margin and a Short \nsuture for the Superior margin.\n\t\u2022\t \u0007Subdividing a specimen: Different areas may be submit\u00ad\nted as separate specimens (e.g., separating the levels of \nan axillary dissection for breast carcinoma or compart\u00ad\nments of a radical neck dissection).\n\t\u2022\t \u0007Suturing a specimen to a surgical drape: The surround\u00ad\ning cloth can be used to label areas or to draw the ana\u00ad\ntomic location.\n\t\u2022\t \u0007Drawing a diagram: Anatomic landmarks from the spec\u00ad\nimen or markers attached to the specimen (e.g., sutures) \ncan be used to correlate the diagram to the specimen.\n\t\u2022\t \u0007Small specimens: Orientation can be provided by plac\u00ad\ning the base of the biopsy on a plastic mesh (e.g., small \nbowel biopsies).\n\t\u2022\t \u0007Colored inks: Specific areas of the specimen can be iden\u00ad\ntified by using colored inks (e.g., margin locations).\nREFERENCES\n\t1.\t \u0007Nakhleh RE, Zarbo RJ. Surgical pathology specimen identifi\u00ad\ncation and accessioning. A College of American Pathologists \nQ-Probes study of 1,004,115 cases from 417 institutions. Arch \nPathol Lab Med 120:227-233, 1996.\n\t2.\t \u0007Makary MA, et al. Surgical specimen identification errors: \na\u00a0new measure of quality in surgical care. Surgery 141:450-455, \n2007.\n\t3.\t \u0007Bull AD, Cross SS, James DS, Silcocks PB. Do pathologists \nhave extrasensory perception?. BMJ 303:1604-1605, 1991.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_026.png", "summary": "The page discusses the importance of orienting pathology specimens correctly for identification purposes, including using sutures, colored inks, and diagrams.", "questions": [ "How do different methods of orienting pathology specimens help in identifying margins?", "What are some common techniques used to subdivide a specimen for evaluation?", "How do colored inks and diagrams assist in specimen orientation and identification?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 27, "text": "9\n2\nSpecimen Processing: \nFrom Gross Specimens to \nTissue Cassettes\nSurgical pathologists should deal with each specimen as if \nthey were the clinician \u2013 or, better yet, the patient \u2013 awaiting \nthe surgical pathology report. Questions such as whether to \nphotograph a gross specimen, how many sections to submit of \na particular lesion, how carefully to search for lymph nodes in \na radical procedure, whether to order recuts or special stains, \nwhether to write or dictate a microscopic description, and so \nforth all become answerable in terms of the single basic question, \n\u201cWere I either the clinician or the patient in this case, what \ninformation would I need about this specimen, and how can \nthat information best be supplied?\u201d\nSteven Silverberg\nPrinciples and Practice of Surgical Pathology and \nCytopathology, 1997\nThe gross evaluation and processing of specimens is the \ncornerstone upon which all other pathologic diagnoses \nrest.\nGENERAL PRINCIPLES OF PROCESSING SPECIMENS\nEach type of specimen will be described in detail in the \nspecific sections, along with any special procedures that \napply. The following discussion highlights principles com\u00ad\nmon to all specimens.\nSpecimen Identification\nMost pathology departments assign each case a unique iden\u00ad\ntification number that includes the year (e.g., S-10-M4382). \nThis number is used to identify all specimen containers, \nadditional materials (e.g., specimen radiographs), and \npaperwork. Each \u201ccase\u201d is usually defined as all specimens \nderived from the same surgical procedure. For example, \nfive skin biopsies from the same patient, performed on the \nsame day, would be given the same pathology number.\nThe first step in specimen processing is identification \nof all components of a specimen. The specimen container \nlabel must include the patient\u2019s name and date of birth or \nthe patient\u2019s assigned hospital or clinic number. The name \nor number is matched with any accompanying paperwork. \nThe number and types of specimens received are checked \nagainst the list given on a requisition form. Additional parts \nof the specimen generated by the pathology department \n(e.g., frozen section remnants or tissue taken for special \nstudies) are identified.\nAny inconsistencies in labeling or missing specimens \nmust be resolved the same day when memories are fresh \nand when it may be possible to recover a misplaced speci\u00ad\nmen or acquire a new specimen. The clinician submitting \nthe specimen is called as soon as a problem is found. If the \nclinician cannot be reached, the call and the time it was \nmade should be documented. The specimen should be kept \nintact (but fixed if possible) until any issues are resolved.\nGross Examination and Dissection\nEach specimen is approached with clear goals in mind based \non the type of specimen and the reason for the surgical \nprocedure. If it is unclear why a procedure was performed, \nit is always preferable to contact the clinician before pro\u00ad\nceeding. If it is a photogenic specimen or photography is \nrecommended (e.g., medicolegal cases), consider the best \nmethod to illustrate the pathology before inking or dissect\u00ad\ning (see Chapter 9).\nIdentify All Anatomic Structures Present.\u2002 This might \ninclude determining the parts of the bowel present, the \nlobe of lung, or muscle, bone, and nerve present in an \namputation for tumor. Diagrams in the sections on spe\u00ad\ncific specimens illustrate the anatomic components of large \nresections.\nOrientation Markers.\u2002 Anatomic (e.g., an axillary tail on a \nmastectomy) or surgically designated (e.g., a suture) orien\u00ad\ntation marks must be identified. These landmarks should \nnot be obscured or removed during dissection if they are \nnecessary for orientation. If a landmark must be removed, \nthe site can be identified by colored inks, sutures, or nicks \nin the attached skin.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_027.png", "summary": "The gross evaluation and processing of specimens is crucial for accurate pathologic diagnoses. Specimen identification and thorough gross examination are key principles in specimen processing.", "questions": [ "How important is specimen identification in the processing of specimens?", "What steps are involved in the gross examination and dissection of specimens?", "Why is it necessary to resolve any inconsistencies in labeling or missing specimens immediately?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 28, "text": "10\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Special Issues in Specimen Processing\nAt times, radiologic studies, operative notes, or addi\u00ad\ntional information from the surgeon can aid in under\u00ad\nstanding the orientation. If orientation is unclear (e.g., an \nunoriented simple mastectomy) from gross examination \nand the information available, the surgeon should be called \nto request additional information.\nMeasurements.\u2002 Dimensions (in metric units) and, for \nsome specimens, weights, should be taken on intact speci\u00ad\nmens prior to dissection and fixation.\nInking Margins.\u2002 Small biopsies for non-neoplastic dis\u00ad\nease (e.g., colon biopsies), incisional biopsies of tumors, or \nlarge specimens for non-neoplastic disease (e.g., diverticu\u00ad\nlitis) are not usually inked. Some departments find that ink\u00ad\ning small specimens (such as skin or core needle biopsies) is \nhelpful for embedding or sectioning such specimens.\nSmall simple specimens with known or potential neo\u00ad\nplasias are often best inked in their entirety before pro\u00ad\nceeding (e.g., primary breast biopsies or the margins of \nskin excisions for pigmented lesions). All margins with \nareas of gross tumor involvement in large resections are \ninked. However, for large complicated resections with \ngrossly negative margins, it may be better to delay inking \nuntil the closest area of the tumor to margin is identified \nafter sectioning. Globally inking large, complicated speci\u00ad\nmens may obscure anatomic landmarks and can increase \nthe likelihood of artifactually introducing ink into tissue \nthat is not present at the margin.\nCare must be taken to avoid smearing of ink by either \nblotting specimens dry or allowing the specimen to air \ndry before sectioning. Tissue blocks must be described \nadequately to avoid misinterpreting smeared ink as margin \ninvolvement.\nDissection.\u2002 No specimen is adequately examined until \nit has been completely dissected and serially sectioned. \nAlthough there are advantages to keeping specimens rela\u00ad\ntively intact, this is not an excuse for a limited and inadequate \nexamination. With experience, specimens can be thoroughly \nsectioned without rendering them unrecognizable.\nThe initial examination is simplified by opening all hol\u00ad\nlow structures (e.g., bowel sections for neoplasia; uteri) \nexcept in cases in which inflation provides better preserva\u00ad\ntion (e.g., bladders; colon resections for diverticular disease). \nFor cases with tumors, the examination is directed towards \ndetermining the site and size of the tumor, location and \nidentity of structures invaded by tumor, vascular invasion, \ndistance from resection margins, and the presence of lymph \nnodes in the specimen. For other specimens, identification \nof the suspected disease process (e.g., chronic cholecysti\u00ad\ntis and cholelithiasis), any incidental findings (e.g., serosal \ntumor implants on a cholecystectomy specimen), and the \nidentification of abnormal lymph nodes are important.\nIdentification of Pathologic Processes.\u2002 All pathologic \nlesions have characteristic gross appearances. Section \nTwo gives gross differential diagnoses of common lesions. \nIf a lesion reported to be present, or previously diagnosed \nby biopsy, cannot be found (e.g., a fistula tract or avascular \nnecrosis of the femoral head) or if the lesion is unusual \nin appearance, it is advisable to consult with the surgeon \nand/or the attending pathologist before further process\u00ad\ning of the specimen. It is important to document the \nabsence of a lesion if the surgical intent was to remove \nthe lesion (e.g., the absence of a biopsy cavity in a breast \nre-excision specimen or the absence of a large polyp in a \nbowel resection).\nHistologic \u2009Sections.\u2002 Sections are taken that best demon\u00ad\nstrate the features seen on gross examination, not simply \nrandom sections. For example, the best section demon\u00ad\nstrating penetration of the bowel wall by a colon carcinoma \nis the one showing the deepest extent of tumor. To find \nthis area, the entire carcinoma must be carefully sectioned. \nSimilarly, margins must be taken at the sites most likely to \nshow tumor at the margin.\nSPECIAL ISSUES IN SPECIMEN PROCESSING\nLymph Nodes\nLymph Nodes Are the Most Important Component of All \nTumor Resections!\u2002 Gross primary tumors tend to distract \nthe prosector, as the tumor is more interesting than lymph \nnodes (which may be small and difficult to find). However, \nfor a patient\u2019s prognosis, and thus for planning therapeu\u00ad\ntic options, the status of the lymph nodes is almost always \nmore important than documenting a known primary \ntumor. Lymph nodes free of tumor may indicate a surgical \ncure, whereas tumor metastatic to lymph nodes signifies \na worse prognosis and is often an indication for systemic \nchemotherapy or hormonal therapy. Fixing fatty tissue in \nBouin\u2019s fixative or clearing agents facilitates finding small \nnodes (see Chapter 27) but small nodes can also be found \nwith careful sectioning and palpation.\nEnlarged Lymph Nodes Must Be Searched for Diligently in \nAll Resections.\u2002 Occasionally an occult primary carcinoma \nor an unsuspected lymphoma is discovered by finding an \ninvolved lymph node in a resection for benign disease.\nIf fewer than expected lymph nodes are found, the pos\u00ad\nsible explanations include the following:\n\t\u2022\t \u0007Pathology factors: The prosector may not have found or \nsampled all of the lymph nodes in the specimen.\n\t\u2022\t \u0007Patient factors: Elderly patients tend to have fewer \nlymph nodes. Patients who have had prior surgery that \ntransects lymphatics may have fewer lymph nodes.\n\t\u2022\t \u0007Treatment factors: Radiation and/or chemotherapy can \nreduce the number of lymph nodes.\n\t\u2022\t \u0007Surgical factors: The specimen may be small in size and/\nor may not include the appropriate tissue containing \nlymph nodes.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_028.png", "summary": "Specimen processing involves taking measurements, inking margins, and thorough dissection to ensure accurate examination of tissues.", "questions": [ "How does inking margins help in specimen processing?", "What are the considerations for inking small specimens?", "Why is it important to completely dissect and serially section specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 29, "text": "11\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Special Issues in Specimen Processing\nThe pathologist should eliminate the first possibility in \nsuch cases. If only a few lymph nodes are found initially, \nit is usually of value to re-examine the specimen and to \nsubmit any additional tissue that may contain nodes for \nmicroscopic examination. A careful search should be docu\u00ad\nmented in the report (e.g., \u201cThe axillary tail is thinly sec\u00ad\ntioned and palpated and all firm tissue is submitted for \nhistologic examination.\u201d). See in Chapter 27, \u201cLymph \nNodes for Tumor Staging\u201d for additional information on \nprocessing and reporting lymph nodes.\nMargins\nMargins are taken on all resections to document the pres\u00ad\nence or absence of tumor and/or the viability of the resec\u00ad\ntion margin. Margin sections are taken in the area most \nlikely to show involvement by tumor (i.e., at the closest \napproach of the tumor).\nOrientation of margins for final diagnosis can be \nachieved by the following methods:\n\t\u2022\t \u0007Documentation of the site in the cassette key (e.g., \u201cCass \n3: Proximal ureteral margin, perpendicular\u201d).\n\t\u2022\t \u0007Colored inks used to mark specific designated \u00admargins. \nThe orientation should also be given in the \u00adcassette key \nto avoid mistaking artifactual ink for a true margin.\nThere are two types of margins: en face and perpen\u00ad\ndicular to the plane of resection. The type of margin must \nbe specified in the dictation, as this will determine whether \nor not a margin should be considered positive. For some \nspecimens (e.g., skin excisions) a combination of en face \nand perpendicular margins may be useful.\nEn face margins (shave, parallel, orange peel)\nThe margin is taken parallel to the plane of resection. This \nhas been likened to taking off an orange peel (Fig. 2-1, top).\nAdvantages\n\t\u2022\t \u000710 to 100 times more surface area can be examined than \nwhen sections are taken in a perpendicular plane.\n\t\u2022\t \u0007An entire anatomic structure can be evaluated (e.g., a \nbronchus or ureter).\nDisadvantages\n\t\u2022\t \u0007The exact distance of the tumor from the margin cannot be \nmeasured. Tumor can be reported to be within the width \nof the section to the margin (usually within 0.2 to 0.3 cm).\n\t\u2022\t \u0007This type of margin must be specified in the dictation as, \nunlike perpendicular margins, any tumor in the section \nis considered to be \u201cat the margin\u201d and ink will not be \npresent.\nLesion\nEn face margin\nAll tissue on the slide is at the margin.\nThe distance from the lesion cannot be measured.\nPerpendicular margin\nOnly the tissue at ink is at the margin.\nThe distance from the lesion can be measured.\nLesion\nFigure 2\u20131.\u2002 En face margin (above) and perpendicular margin (below).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_029.png", "summary": "This page discusses the importance of careful specimen processing, documentation of margins, and different types of margins (en face and perpendicular) in surgical pathology.", "questions": [ "What is the significance of re-examining specimens and submitting additional tissue for microscopic examination?", "How are margins documented and oriented for final diagnosis?", "What are the advantages and disadvantages of en face margins compared to perpendicular margins?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 30, "text": "12\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Special Issues in Specimen Processing\n\t\u2022\t \u0007Most pathologists are accustomed to evaluating perpen\u00ad\ndicular margins.\n\t\u2022\t \u0007Cautery artifact is often present and can make interpre\u00ad\ntation difficult.\nThe orientation of an en face margin as it is embedded for \nhistologic sections either for frozen sections or in a \u00adparaffin \nblock for permanent sections is important for tumors for \nwhich a narrow rim of normal tissue would be considered \nto be a negative margin. The tissue may be embedded so \nthat the first cut section is the true margin. If the opposite \nface is cut first, and tumor is present, then deeper sections \nmay be obtained, or the tissue re-embedded in the opposite \norientation, to evaluate the \u201ctrue\u201d margin. If specific orien\u00ad\ntation is important, one side of the tissue should be inked \nand a detailed note written on the log-in sheet (e.g., \u201cembed \nwith inked side down\u201d). It is also advisable to speak to some\u00ad\none in the histology laboratory about the case. It cannot be \nassumed that the orientation of the tissue in the cassette will \nbe the same as the orientation of the embedded tissue.\nPerpendicular margins\nThe margin is taken perpendicular to the plane of resec\u00ad\ntion (Fig. 2-1, bottom).\nAdvantages\n\t\u2022\t \u0007The exact distance of the tumor from the margin can be \ndetermined. Perpendicular margins are recommended \nwhen a small rim (e.g., less than 0.2 cm) of uninvolved \ntissue would be considered a negative margin.\n\t\u2022\t \u0007Most pathologists are familiar with interpreting this \ntype of margin.\nDisadvantages\n\t\u2022\t \u0007Very little tissue at the margin is actually sampled in \nlarge resections.\nMethod of inking margins\nThe outer surface of the specimen should be relatively \nclean and dry. Ink may be applied with a gauze pad, a cotton \nswab, or by immersing the entire specimen into a container \nof ink. After applying the ink, Bouin\u2019s solution, dilute ace\u00ad\ntic acid, or methanol is applied. These act as mordants and \nhelp both to fix the ink to the tissue and to prevent it from \ndissolving in formalin. Bouin\u2019s should not be used prior \nto frozen section because it may prevent good adherence \nof tissue to the slide. The inked surfaces are blotted dry \nbefore cutting the specimen to prevent artifactual ink on \ninterior surfaces. Multicolored inks are available for orien\u00ad\ntation of complicated specimens.\nMargins are sometimes stapled. The staples cannot be \nremoved without shredding the tissue. The staple line can \nbe carefully cut away as close as possible to the staples and \nthe next closest tissue taken as the margin. Sections that \ncontain staples should never be submitted for histologic \nprocessing as the staples will damage or destroy microtome \nblades and the tissue adjacent to the staple cannot be cut \nfor examination.\nMultiple Lesions\nOccasionally multiple gross neoplastic lesions will be \nfound in a specimen. It is important for both diagnosis and \nprognosis to determine whether these lesions \u00adrepresent \n(1) the same lesion with a microscopic interconnection \nbetween the two gross lesions; (2) a primary tumor and a \nmetastasis; or (3) two independent neoplasms. Each lesion \nis sampled separately and special studies taken as indi\u00ad\ncated. Always submit a section of tissue between two (or \nmore) lesions to evaluate whether they are truly separate \nor interconnected.\nMissing Specimens\nOn rare occasions, clinicians believe that a specimen should \nhave been received by the pathology department, but there \nis no record of the specimen. The most likely possibilities \nare the following:\n\t\u2022\t \u0007The specimen never arrived in pathology. The specimen \nmay have been left in a clinic or be in transit.\n\t\u2022\t \u0007The specimen is mislabeled. The patient name may be \nincorrect or may have been accessioned incorrectly (e.g., \nthe first name is used as the last name).\n\t\u2022\t \u0007The specimen may be included with another specimen \nfrom the same patient, possibly from a different day or \ndifferent procedure.\nRarely, a specimen container is received but appears \nto be empty. The container must be carefully \u00adexamined, \nincluding the lid, as small specimens may stick to the sides \nor top of the container. If there are multiple parts to the \nspecimen, the missing specimen may have been included \nin one of the other parts. If the specimen cannot be found, \nthe clinician submitting the specimen must be contacted \nthe same day. Document this contact in the report. The \ncontainer should be saved until the issue is resolved with \nthe clinician. It may be possible to recover specimens mis\u00ad\nlaid in the clinician\u2019s office or the clinician may decide to \nrebiopsy and submit additional tissue.\nSpecimens are rarely lost after they have been acces\u00ad\nsioned in a pathology department. Potential reasons \nfor a specimen not being in the usual location are the \n\u00adfollowing:\n\t\u2022\t \u0007The case was set aside because of infectious precautions.\n\t\u2022\t \u0007The specimen was inadvertently discarded. It may be \nuseful to save the waste containers from the gross proc\u00ad\nessing room for an extra day to allow for recovery of lost \nspecimens (or cassettes) if necessary.\nCassettes are also rarely lost before being received by \nthe histology laboratory. Usually the cassette failed to go \ninto the container for processing and was placed some\u00ad\nwhere else. The container for sharps, the original \u00adcontainer", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_030.png", "summary": "Specimen processing involves careful orientation of tissue margins to ensure accurate evaluation, with perpendicular margins being recommended for determining tumor distance.", "questions": [ "How does cautery artifact impact interpretation of specimens?", "Why is it important to ink margins and provide detailed orientation notes?", "What are the advantages and disadvantages of using perpendicular margins?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 31, "text": "13\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 General Principles of Gross Descriptions\n(if not all the tissue was submitted), sinks, and waste con\u00ad\ntainers are the most likely locations.\nOccasionally the cassette will be present but without tis\u00ad\nsue. Either the cassette was not properly closed and opened \nduring processing or the fragment was small enough to \nslip through the holes. The latter can be avoided by always \nwrapping small specimens in lens paper.\nGENERAL PRINCIPLES OF GROSS DESCRIPTIONS\nThe ability to accurately examine, describe, and process \ngross specimens is one of the most important skills of the \npathologist. Based on keen observation and detailed dis\u00ad\nsection, the precise microscopic sections are taken that \nyield important diagnostic and prognostic information for \npatients. Without these skills, many diagnoses will be left \nin the formalin jar. The most skilled microscopic examina\u00ad\ntion cannot overcome an inept gross one.\nOne study revealed that gross reexamination of mas\u00ad\ntectomies and sampling of additional tissue resulted in \n18% of the specimens having diagnostic discrepancies, as \ncompared to the original diagnosis.1 Almost half of the \ndiscrepancies were considered major (new diagnosis of \ncancer, different TNM stage, or new information lead\u00ad\ning to additional diagnostic or therapeutic procedures). \nIn contrast, a slide review only revealed major diagnostic \ndiscrepancies in 1% of cases. Many of the errors in gross\u00ad\ning occurred in the first few months of residency training. \nIn this study, careful gross examination was more impor\u00ad\ntant than the review of glass slides for the prevention of \nerrors.\nThe gross description provides a permanent record of \nall pertinent information regarding a specimen, includ\u00ad\ning the information provided by the submitting clinician, \nprocedures taking place during operating room consulta\u00ad\ntions, the description of the specimen as it was received \nand observations after dissection, disposition of all tissues \nsubmitted for special studies or for research, and a descrip\u00ad\ntion of the microscopic sections taken.\nIn some cases, for routine specimens, standard descrip\u00ad\ntive text can be used and specific descriptors added as \nappropriate. Standardization can reduce the number of \nerrors. However, the use of such forms should never sub\u00ad\nstitute for a careful gross examination or a specific descrip\u00ad\ntion of unusual specimens or unusual findings.\nAccurate and complete descriptions are very important \nfor the following reasons:\n\t\u2022\t \u0007Diagnosis: Gross descriptions provide important diag\u00ad\nnostic information that is used for staging and prog\u00ad\nnosis. Examination of glass slides alone cannot always \nprovide information about the size of tumors, multiple \ntumors, distance from margins, or number of lymph \nnodes examined.\n\t\u2022\t \u0007Correlation: Good gross descriptions allow the pathol\u00ad\nogist to correlate microscopic findings with the gross \nfindings. Artifacts (e.g., ink present on tissue not at a \nmargin) or errors (e.g., cassettes labeled with the wrong \nnumber) can be detected if there are discrepancies \nbetween the gross description and what is present on the \nglass slide.\n\t\u2022\t \u0007Documentation: Each specimen and the condition in \nwhich it arrived must be carefully documented for medi\u00ad\ncal and legal purposes. The gross description is the only \nrecord of what was received in the department.\n\t\u2022\t \u0007Training: Accurate gross descriptions reveal the \nstrengths and limitations of the gross examination as \ncompared to microscopic examination. For some speci\u00ad\nmens (e.g., colon carcinoma) almost the entire diagnosis \ncan be made grossly. This skill is especially important \nfor operating room consultations in which the patholo\u00ad\ngist must be able to rapidly select the tissue most likely \nto reveal important diagnostic information. In some \ncases a good gross examination can yield more informa\u00ad\ntion than a frozen section diagnosis.\nGross Descriptions\nA good gross description has the following qualities:\n\t\u2022\t \u0007Succinct and to the point. The important informa\u00ad\ntion can usually be captured in a few sentences. Long, \nrambling descriptions are often poor, because impor\u00ad\ntant information is buried in, or replaced by, irrelevant \ndetails.\n\t\u2022\t \u0007Good organization. Information is easily overlooked if \nit is not readily accessible and in the right anticipated \nlocation.\n\t\u2022\t \u0007Adequate dissection. A specimen cannot be described \naccurately until after it has been completely dissected \nand examined. Initial impressions often change after a \nthorough examination. Important findings and measure\u00ad\nments can be recorded in a notebook to aid in dictation \nafter the specimen has been dissected. This practice also \nprovides a backup gross description if a transcription is \nlost.\n\t\u2022\t \u0007Standardization. Standardization minimizes the risk of \nomission of important information. Creative dictations \nshould be reserved for the very unusual or complicated \nspecimen. Sample dictations for all large specimens are \nincluded in Section Two.\n\t\u2022\t \u0007Diagrams. Diagrams of complicated specimens are \nhelpful to show the site of tissue blocks. Some depart\u00ad\nments make use of photocopies of gross specimens for \nthis purpose.2 Photographs can also be used.3\nFormatting the Gross Description\nEven the most complex resections (e.g., extrapleural \npneumonectomies, complex hemipelvectomies with mul\u00ad\ntiple organs, Whipple pancreaticoduodenectomies, \u201cliving \nautopsies\u201d) can be clearly described and sampled, if the \nspecimen is approached systematically.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_031.png", "summary": "Accurate and complete gross descriptions are crucial for proper diagnosis and prognosis in pathology. Errors in gross examination can lead to major diagnostic discrepancies.", "questions": [ "Why is accurate gross description important for diagnosis and prognosis?", "What are some common errors that can occur during gross examination?", "How can standardization in gross descriptions help reduce errors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 32, "text": "14\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 General Principles of Gross Descriptions\nThere are six components to a gross description:\n\t1.\t \u0007The first part documents the patient\u2019s name, the speci\u00ad\nmen label, whether it was received fresh or in a type of \nfixative, and anatomic structures present in the speci\u00ad\nmen (with dimensions and weight as appropriate).\n\t2.\t \u0007The second part begins the description of the main \npathologic findings that caused the specimen to be \nresected (type of lesion, size, relationship to normal \nstructures and margins, etc.).\n\t3.\t \u0007The third part describes any secondary pathology not \ndescribed in the second part (e.g., incidental polyps, a \nsecond smaller lesion, diverticula, etc.).\n\t4.\t \u0007The fourth part describes any other normal structures \nnot conveniently fit into the first sentence (e.g., length \nand diameter of ureters from a bladder resection).\n\t5.\t \u0007The fifth part lists frozen sections, photographs, radio\u00ad\ngraphs, and any other special studies that were done. \nNote whether the margins were inked and if they are en \nface or perpendicular.\n\t6.\t \u0007The sixth part is a list of all the cassettes and the types \nof tissue sampled.\nThe first part: label, fixative, structures present\nThe gross description starts by documenting how the spec\u00ad\nimen was labeled and whether it was fresh or in fixative. \nSpecimens first seen as an operating room consultation are \ndictated as they were received there. For example:\n\u201cReceived fresh labeled with the patient\u2019s name and unit \nnumber and \u2018Ascending colon\u2019 is\u2026\u201d\nOr\n\u201cReceived in formalin labeled with the patient\u2019s name and \n\u2018PNBX\u2019 is.. .\u201d\nSpecial note should be taken of specimens that are iden\u00ad\ntified in unusual ways:\n\u201cReceived fresh in an unlabeled container hand-carried by Dr. \nG. Smith and identified as belonging to the patient, is . . .\u201d\nThe remainder of the first sentence documents all of the \ncomponents of the specimen. In order to keep the dicta\u00ad\ntion clear, measurements can be placed in parentheses. For \nexample:\n\u201cReceived fresh labeled with the patient\u2019s name and unit number \nand \u2018MRM\u2019 is a 563 gram left modified radical mastectomy \nspecimen (15 \u00d7 12 \u00d7 4.5 cm) with a white/tan skin ellipse \n(14 \u00d7 12 cm) and with attached axillary tail (6 \u00d7 5 \u00d7 4 cm).\u201d\nOr\n\u201cReceived fresh labeled with the patient\u2019s name and unit number \nand \u2018Colon\u2019 is a right colectomy specimen \u00adconsisting of terminal \nileum (5 cm in length \u00d7 3 cm in circumference), cecum and \nascending colon (30 cm in length \u00d7 6 cm in circumference), \nand appendix (7 cm in length \u00d7 0.8 cm in diameter).\u201d\nThe second part: principal pathologic finding\nThe second sentence starts the description of the main \npathological findings. For example:\n\u201cThere is an ulcerated tan/pink lesion (5 \u00d7 4 \u00d7 3 cm in depth) \nwith raised serpiginous borders 7 cm from the proximal \nmargin and 22 cm from the distal margin. The lesion \ngrossly extends through the muscularis propria and into \npericolonic soft tissue and is present at the serosal surface.\u201d\nOr\n\u201cThere is a 4 cm well healed surgical scar in the outer upper \nquadrant, 5 cm from the unremarkable nipple (1.0 \u00d7 0.9 \ncm). 2 cm deep to the scar there is a biopsy cavity (4 \u00d7 3 \u00d7 2 \ncm) filled with red/brown organizing thrombus. The cavity \nis surrounded by firm white tissue, 0.2 to 1.0 cm in thick\u00ad\nness, but no residual tumor is identified grossly. The cavity is \n1 cm from the deep margin which is a smooth fascial plane.\u201d\nDictate gross observations, not what was done with the \nspecimen.\nVerbose:\n\u201cUpon opening the colon longitudinally with a pair of scissors, \nit can be seen there is a 4 cm polypoid firm mass. On care\u00ad\nful serial sectioning it can be seen to ex\u00adtend through the \nmuscularis propria into pericolonic fat . . .\u201d\nBetter:\n\u201cThere is a 4 cm polypoid firm mass that extends through the \nmuscularis propria into pericolonic fat . . .\u201d\nA pathology report should not read like an operative \nnote. In the words of Jack Webb, \u201cthe facts, ma\u2019am, just \nthe facts.\u201d It can be assumed that the colon was opened, a \nlesion was observed, and it was carefully sectioned.\nHowever, there are specimens for which it will be nec\u00ad\nessary to stress an important negative finding in spite of \nmeticulous dissection:\n\u201cNo lymph nodes are found in the area designated by the sur\u00ad\ngeon as the axillary tail after careful palpation, overnight \nBouin\u2019s fixation, and 0.1 cm sectioning.\u201d\nThe third part: secondary pathologic findings\nAfter the main lesion has been dictated, all secondary \nlesions are dictated. This description always includes the \nrelationship of multiple lesions to each other.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_032.png", "summary": "The page discusses the six components of a gross description in surgical pathology, including documenting patient information, main pathologic findings, secondary pathology, normal structures, special studies, and tissue cassettes.", "questions": [ "How important is it to accurately document patient information and specimen details in a gross description?", "What are some challenges or considerations when describing secondary pathology in a specimen?", "Why is it necessary to list frozen sections, photographs, and other special studies in a gross description?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 33, "text": "15\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 General Principles of Gross Descriptions\n\u201c3 cm proximal to the ulcerated lesion is a tan/pink, soft, \nvillous polyp (3.0 \u00d7 2.0 \u00d7 2.0 cm) with a stalk (1.0 cm in \nlength \u00d7 0.4 cm in diameter).\u201d\nThe fourth part: lymph nodes, incidental findings, normal \nstructures\nNormal structures need not be dictated in detail. A pathol\u00ad\nogist or pathology assistant must be able to recognize what \nis normal and need not elaborate on these findings in the \ngross description. Summary statements are made such as \n\u201cthe remainder of the colonic mucosa is unremarkable\u201d or \u201cno \nother lesions are present.\u201d On the other hand, when there is \nan abnormality, this finding is described: \u201cthe colonic mucosa \nis dusky red\u201d or \u201cthe remainder of the breast parenchyma con\u00ad\nsists of firm white fibrous tissue with numerous blue dome cysts.\u201d \nThis section may also include additional measurements or \ndocumentary facts not comfortably fit into the first sen\u00ad\ntence:\n\u201cAlso received is a separate fragment of yellow/white adipose \ntissue (4.0 \u00d7 3.5 \u00d7 2.0 cm) without gross lesions.\u201d\nThe fifth part: special methods\nRoutine procedures (fixing the specimen overnight in for\u00ad\nmalin or serially sectioning the breast) do not need to be \nspecified. However, all procedures that are included in bill\u00ad\ning, in particular decalcification, must be specified. All non-\nroutine procedures and special fixatives must also be stated. \nThis will be the only record of what was done with the \ntissue and what is available for special studies. For example:\n\u201cA frozen section was performed on the tumor and the bron\u00ad\nchial resection margin.\u201d\n\u201cThe bone is fixed in formalin and then decalcified.\u201d\n\u201cPhotographs and radiographs are taken. Portions of the tumor \nare fixed in Zenker\u2019s, B Plus, and Bouin\u2019s solutions and are \nsnap-frozen. Samples are taken for cytogenetics, and elec\u00ad\ntron microscopy. Tumor (1 \u00d7 1 \u00d7 1 cm) and normal fat (1 \u00d7 \n1 \u00d7 1 cm) are given to Dr. Strangelove for special studies.\u201d\nIt is also helpful to state for some specimens (especially \ndiagnostic breast biopsies) whether or not all of the tissue \nhas been submitted. For example:\n\u201cAll of the tissue is submitted for histologic examination.\u201d\n\u201cSeventy percent of the tissue is submitted for histologic exam\u00ad\nination including all fibrous tissue.\u201d\n\u201cThe entire lesion and representative normal tissue are sub\u00ad\nmitted for histologic examination.\u201d\nThe sixth part: microscopic sections\nThe final section of the gross description is a list of each \ncassette and the tissue in the cassette, if cassettes contain \ndifferent types of tissue.\nNo new information should be included in the list that \nis not in the gross description (e.g., cassette number A23 \nshould not be \u201cnodule found upon further sectioning\u201d unless it \nhas been described previously). Also included is the num\u00ad\nber of fragments in the cassette (helpful for the person \nembedding the tissue and sometimes in identifying pos\u00ad\nsibly misidentified cassettes), the type of fixative (if not for\u00ad\nmalin), and whether all or only a portion of the tissue has \nbeen submitted. This can be denoted by:\nRSS: representative sections submitted. Additional tis\u00ad\nsue of this type could be submitted.\nESS: entire specimen (or designated portion of speci\u00ad\nmen) submitted. This indicates that no more tissue \nof this type can be submitted.\nGroups of cassettes can be dictated together if they all \ncontain the same category of tissue. For example:\nCassettes #A21-23, one lymph node per cassette, 6 frags, \nESS.\nThe following are examples of how cassettes from dif\u00ad\nferent cases might be dictated:\nPunch biopsy of skin:\nCassette A1: 1 fragment, ESS.\nBasal cell carcinoma, small skin ellipse:\nCassette A1: cross sections of lesion, 2 fragments, \nESS.\nCassette A2: ellipse tips, 2 fragments, ESS.\nProstate, TURP:\nCassettes A1 - 6: multiple fragments, ESS.\nEsophageal carcinoma resection:\nCassettes A1-3: Tumor including deepest extension and \ndeep margin, 3 fragments, RSS.\nCassette A4: Proximal margin, perpendicular, 1 frag\u00ad\nment, RSS.\nCassette A5: Distal margin, perpendicular, 2 fragments, \nRSS.\nCassette A6: Proximal granular pink mucosa, 2 frag\u00ad\nments, RSS.\nCassettes A7-11: Ten lymph nodes, two per cassette, 10 \nfrags, ESS.\nIf focal lesions are present, the cassettes containing the \nlesion must be specified, as the gross lesion may not be \napparent on microscopic examination or may not be pres\u00ad\nent on the initial slides prepared.\nThyroid resection:\nCassettes A1-4: well circumscribed nodule, 8 frags, \nESS.\nCassettes A5-6: representative sections of normal-\nappearing thyroid, 2 frags, RSS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_033.png", "summary": "The page discusses the general principles of gross descriptions in specimen processing, including the importance of recognizing normal structures, documenting abnormal findings, specifying special methods used, and detailing microscopic sections.", "questions": [ "How can a pathology assistant differentiate between normal and abnormal structures in a gross specimen?", "Why is it important to specify all procedures, including non-routine ones, used in specimen processing?", "What information should be included in the list of microscopic sections in the final part of the gross description?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 34, "text": "16\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 General Principles of Gross Descriptions\nAn Example of a Gross Description\nThe first part\nReceived fresh labeled with the patient\u2019s name and unit \nnumber and \u201cColon\u201d is a segment of colon (30 cm in length \n\u00d7 8 cm proximal circumference and 5 cm distal circumfer\u00ad\nence) with attached mesentery (30 cm \u00d7 5 cm) with a suture \nindicating the proximal margin.\nThe second part\nA centrally ulcerated, firm, tan/pink tumor (4.0 \u00d7 3.5 \u00d7 2.0 \ncm) with raised serpentine borders occupies approximately \n90% of the colon circumference. The residual lumen is \napproximately 0.5 cm in diameter and the proximal bowel \nis markedly dilated. The tumor grossly extends through \nthe muscularis propria into pericolonic fat and is 0.5 cm \nfrom the serosal surface, which is inked. The tumor is 5 \ncm from the distal margin and 19 cm from the proximal \nmargin.\nThe third part\nA sessile, firm, tan/pink smoothly lobulated polyp (1 \u00d7 1 \n\u00d7 0.8 cm), is located 2 cm distal to the tumor and 1 cm \nfrom the distal margin. The intervening mucosa is normal \nin appearance.\nThe fourth part\nApproximately 30 diverticula are noted in the remainder \nof the colon, which is otherwise unremarkable. There are \nfourteen fleshy, tan lymph nodes in the pericolonic fat, the \nlargest measuring 0.6 cm in greatest dimension.\nThe fifth part\nThe specimen is photographed. Tumor (1\u00d7 1\u00d7 1) is given \nto Dr. Brown for special studies.\nThe sixth part\nCassettes A1 and 2: Tumor and serosal surface, 2 frags, \nRSS.\nCassettes A3 and 4: Tumor and normal colon, 3 frags, \nRSS.\nCassette A5: Polyp, 2 frags, ESS.\nCassette A6: Distal margin, perpendicular, 1 frag, \nRSS.\nCassette A7: Diverticula, 2 frags, RSS.\nCassette A8-14: Lymph nodes, 2 per cassette, 14 frags, \nESS.\nComponents of the Gross Description\nSpecimens have dimensions of size and weight and fea\u00ad\ntures such as color, shape, smell, texture, and consistency. \nAll of these are used to paint a picture for readers of the \npathology report and to capture important gross features \nof pathologic processes.\nMeasurements\nMeasurements are in centimeters and fractions of centi\u00ad\nmeters and expressed as numbers (e.g., 3.5 cm, not \u201cthree \nand a half cm\u201d). They should be as accurate as they need \nto be. Tumor sizes are measured to the nearest millime\u00ad\nter (not rounded off) as these sizes will be used for staging \nand prognosis. On the other hand, the dimensions of tis\u00ad\nsues that contract (e.g., colon segments) or that are highly \ncompressible (e.g., lung) cannot be measured as precisely. \nInclude the dimension being measured when appropriate:\nImprecise: \u201cthe colon measures 5 cm \u00d7 2 cm.\u201d\nAccurate: \u201cthe colon measures 5 cm in circumference \u00d7 \n2 cm in length.\u201d\nOr\nImprecise: \u201creceived is a skin ellipse measuring 2.5 \u00d7 3.0 \n\u00d7 1.0 cm.\u201d\nAccurate: \u201creceived is a skin ellipse measuring 2.5 \u00d7 3.0 \u00d7 \n1.0 cm (depth).\u201d\nFragmented specimens can be measured in aggregate. In \nselected cases it is appropriate to indicate the size of the larg\u00ad\nest fragment (e.g., fragmented tumors) or a range of sizes.\nDo not over-measure normal structures (e.g., give seven \ndimensions of a normal cervix) or under-measure impor\u00ad\ntant ones (e.g., describe multiple tumors as \u201cseveral\u201d or \n\u201clarge\u201d).\nDo not use analogies for size (e.g., grapefruit size, the size \nof a child\u2019s fist, the size of a baseball). While picturesque, \nthey are imprecise and cannot be used for tumor staging.\nMeasurements can also change over time. Colon seg\u00ad\nments contract and need to be measured as soon as possible \nafter surgical removal.4 Lungs deflate. Tissues also shrink \nafter fixation and should be measured when unfixed.\nIt is preferable to always report sizes in centimeters in \nthe final report. It is easy for millimeters (\u201cmm\u201d) to mis\u00ad\ntaken for centimeters (\u201ccm\u201d) in typing and proofreading. If \ncentimeters are always used, one can immediately recog\u00ad\nnize any size in millimeters as an error.\nNumbers\nBe specific about numbers by giving an accurate count or \nat least an estimate.\nImprecise: \u201cThere are several gallstones.\u201d\nAccurate: \u201cThere are three gallstones\u201d or \u201cThere are \napproximately 30 gallstones.\u201d\nWeight\nWeight is expressed in grams. All solid organs (lungs, \nspleens, hearts, kidneys, adrenals, thyroids, prostates, \ntransurethral resections of the prostate), mastectomies,", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_034.png", "summary": "The page discusses the general principles of gross descriptions in surgical pathology, using an example of a colon specimen with a tumor and other findings.", "questions": [ "What are the key components of a gross description in surgical pathology?", "How are measurements of specimens and tumors typically expressed?", "Why is it important to accurately measure tumor sizes in pathology reports?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 35, "text": "17\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 General Principles of Gross Descriptions\nand reduction mammoplasties are weighed before fixation. \nParathyroid adenomas, adrenal tumors, and some sarco\u00ad\nmas are weighed, as this information may be useful for \neither diagnosis or prognosis.\nColors\nColor can be helpful in describing a specimen, especially if \nthe normal color of the tissue or organ has been altered.5 \nFew specimens have pure colors. However, instead of \nusing \u201cish\u201d words (e.g., reddish, brownish), combinations \nof colors can be used to express the fact that the specimen \nvaries slightly in color (e.g., red/brown, white/tan). Don\u2019t \nget carried away. Almost all specimens are \u201cgray/white to \npink/tan to yellow/orange to red/brown with focal lighter and \ndarker areas.\u201d\nColors are very important when describing small biop\u00ad\nsies. Blood is usually red/brown and tissues are usually \nwhite/tan. If one of three fragments grossly looks like \nblood clot this will correlate with only two tissue fragments \nalong with disaggregated blood cells on the slide. Colors \ndue to increased blood flow or congestion (e.g., in vascular \nlesions or inflammatory carcinoma of the breast) are often \nlost once the blood supply is terminated during excision.\nSome tumors, tissues, or pathologic processes have very \ncharacteristic colors (Table 2-1).\nConsistency\nThis can be a helpful descriptor in communicating \nwhether or not there is a malignant lesion present. Fortu\u00ad\nnately for pathologists, most tumors incite a desmoplastic \nresponse and are harder than the surrounding tissue. In \ncontrast, tissues that are soft or rubbery are less likely to \ncontain malignant tumors. However, tumors that occur in \ntissue that is normally firm, such as prostate, can be very \ndifficult to detect grossly. Other tumors, such as some \nlobular carcinomas of the breast, can be associated with a \nminimal desmoplastic response and may not form a pal\u00ad\npable mass.\nTumors after treatment often become softer and more \ndifficult to define grossly. It is often necessary to deter\u00ad\nmine the site of the tumor prior to treatment to guide tis\u00ad\nsue sampling.\nNecrotic areas are usually soft and friable. Papillary \ntumors are also often soft and can be mistaken for necrosis.\nShape and texture\nMalignant processes (but also many inflammatory pro\u00ad\ncesses) usually have infiltrative borders and irregular or \ndifficult to define shapes whereas lesions with well defined \nshapes and borders are less likely to be malignant. Tumors \nusually efface the underlying tissue planes and textures. \nUseful terms are listed in Table 2-2.\nPathologists have traditionally used food analogies to \ndescribe specimens.6 Gross descriptions can be embel\u00ad\nlished with the terms presented in Table 2-3. However, \n\u201cserially sectioned\u201d is preferred to \u201cbread-loafed.\u201d\nFluids can be described with the terms presented in \nTable 2-4.\nSmell\nFortunately, few surgical specimens have prominent odors. \nHowever, this is an important aspect to report because it \nusually indicates decomposition of the tissue. Sending \ntissue for cultures should be considered unless infection \nhas already been documented. A foul smell may indicate \nTABLE 2\u20131.\u2003\n\u0007CHARACTERISTIC COLORS \nOF PATHOLOGIC PROCESSES\nPATHOLOGIC PROCESS\nCOLOR\nRenal cell carcinoma (clear \ncell type)\nGolden yellow and hemor\u00ad\nrhagic\nNormal adrenal or adrenal \ncortical lesions\nOrange-yellow\nXanthogranulomatous \ninflammation (xanthos = \nyellow in Greek)\nYellow\nCirrhosis (kirrhos = orange-\nyellow in Greek)\nYellow\nSteroid-producing tumors\nOften pale or bright yellow\nChloroma or any purulent \nexudate (chloros = \ngreen in Greek)\nGreen\nPrior hemorrhage with \noxidation of blood\nGreen (e.g., in synovial tissue in \nhemochromatosis or PVNS)\nOchronosis (ochros = pale \nyellow in Greek)\nBlack or brown\nEndometriotic (chocolate) \ncyst\nBrown\nMelanoma (if pigmented) \n(melas = black in Greek)\nBlack\nMelanosis coli\nBlack mucosa\nAnthracotic pigment \n(anthrax = coal in Greek)\nBlack\nBlue dome cysts of the \nbreast\nDark blue or black\nGout or chondrocalcinosis\nChalky white\nPheochromocytoma \n(phaios = dusky + \nchromo = color in Greek)\nWhite to tan \u2013 chromaffin \nreaction changes color to \nmahogany brown to black or \npurple", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_035.png", "summary": "The text discusses the importance of colors, consistency, shape, texture, and smell in describing surgical specimens, as well as the significance of weight in certain cases.", "questions": [ "How can colors be used to describe a specimen effectively?", "What role does consistency play in determining the presence of malignant lesions?", "Why is it important to consider the weight of certain specimens like parathyroid adenomas and adrenal tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 36, "text": "18\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 General Principles of Gross Descriptions\nTABLE 2\u20132.\u2003\n\u0007USEFUL TERMS FOR DESCRIBING \nSHAPE AND TEXTURE\nSHAPE OR TEXTURE\nEXAMPLE(S)\nWell-circumscribed or push\u00ad\ning borders\nFibroadenoma, mixed tumor, \nhamartoma\nIrregular or spiculated \nborders\nInvasive carcinomas, surgical \nscars\nJagged or notched borders\nCutaneous melanoma\nSerpiginous borders (wind\u00ad\ning, snake-like)\nMucosal shape of colon \ncarcinoma\nSmoothly lobulated\nLipoma\nBosselated (rounded protu\u00ad\nberances)\nBone in degenerative joint \ndisease\nVerrucous (wart-like)\nCutaneous condyloma\nPapillary\nBladder tumors, papillary \nrenal cell carcinoma\nVillous (slender projections)\nVillous adenoma of the colon\nEburnated (like ivory)\nExposed polished bone \nsurface after loss of carti\u00ad\nlage in \u00addegenerative joint \ndisease\nVelvety\nNormal gallbladder mucosa\nPedunculated (with a stalk)\nSome colon polyps, achro\u00ad\ncordon\nSessile (broad-based)\nSome colon polyps\nMacule (flat lesion)\nLentigo, caf\u00e9-au-lait spot\nPapule (raised lesion)\nMole\nFriable (soft and falling apart \nor crumbly)\nPapillary renal cell carcinoma, \nnecrotic tumors\nExcrescence (an irregular \noutgrowth)\nCarcinoma invading through \nskin\nFimbriated (fringe-like)\nThe normal end of the fal\u00ad\nlopian tube\nExophytic (projecting out \nfrom a surface)\nA papilloma in a duct\nEndophytic (projecting \nwithin a space)\nInverted papilloma\nScabrous (covered with small \nprojections and rough to \nthe touch)\nPleural plaque\nPapyraceous (like parchment \nor paper)\nFetus papyraceous \u2013 a fetus \nfound within the placental \n\u00admembranes of a twin\nTABLE 2\u20133.\u2003\nFOOD-RELATED TERMS\nFOOD-RELATED TERM\nPATHOLOGIC PROCESS\nCurrant jelly\nPostmortem blood clot\nChicken fat\nPostmortem blood clot\nSugar-coated spleen\nPerisplenitis\nChocolate cyst\nEndometriotic cyst\nUnripe pear or \n\u00adwaterchestnut\nGritty consistency of breast \ncancer\nGrape vesicle\nThe villi of a hydatidiform mole\nSago spleen (sago is a pearly \nstarch [e.g., tapioca] made \nfrom the sago palm)\nMiliary nodules of amyloidosis\nStrawberry gallbladder\nCholesterolosis\nNutmeg liver\nChronic congestion\nApple-core lesion\nAn obstructing colonic \n\u00adadenocarcinoma (as seen \non x-ray)\nRice bodies\nLoose bodies in a joint\nLardaceous spleen\nAmyloidosis\nFish-mouth stenosis\nRheumatic heart valve\nVegetation\nThrombus on a heart valve\nCaseous necrosis\nCheese-like material (especially \nin tuberculous granulomas)\nTABLE 2\u20134.\u2003\nDESCRIPTIVE TERMS FOR FLUIDS\nDESCRIPTIVE TERMS \nFOR FLUIDS\nQUALITY OF FLUID\nViscous\nThick\nSerosanguinous\nSerum tinged with blood (also \nspelled serosanguineous)\nSerous\nLike serum \u2013 watery\nMucinous\nThick and sticky or gelatinous\nTacky\nSticky (e.g., silicone gel)\nSuppurative\nGreen thick exudate", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_036.png", "summary": "This page discusses useful terms for describing shape and texture of gross specimens, food-related terms related to pathologic processes, and descriptive terms for fluids.", "questions": [ "How can the terms for describing shape and texture of gross specimens aid in the diagnosis of different conditions?", "What role do food-related terms play in identifying specific pathologic processes?", "How do descriptive terms for fluids help in characterizing different types of fluid samples in pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 37, "text": "SPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 A Classical Interlude\n19\ndecomposition within the patient (e.g., a necrotic bowel) \nor inappropriate delayed handling of a specimen (e.g., a \nfresh specimen left overnight without refrigeration).\nBe Brief, But Be Precise!\nDescriptions should be simple and direct and use the mini\u00ad\nmum amount of words necessary to convey a clear idea of \nthe specimen.\nGrossly Recognizable.\u2002 If a structure can be identified \n(e.g., an appendix, gallbladder, lung), dictate it as such.\nVerbose: \u201cReceived is a grossly recognizable gallbladder . . .\u201d\nPrecise: \u201cReceived is a gallbladder . . .\u201d\nOn the other hand, if the specimen is a portion of a \nstructure that cannot be unequivocally identified, use \n\u201cgrossly consistent with.\u201d For example:\n\u201cReceived labeled \u2018gallbladder\u2019 is a 3 \u00d7 1 \u00d7 0.2 cm (wall thick\u00ad\nness) portion of velvety pink mucosa grossly consistent with \nthe wall of a gallbladder. . .\u201d\nSeen, Felt, Palpated, Found.\u2002 Just state the facts, not how \nthey were observed.\nVerbose: \u201cAfter sectioning the axillary fat, five lymph nodes \nare found which are firm upon palpation . . .\u201d\nPrecise: \u201cThere are five firm lymph nodes in the axillary \nfat . . .\u201d\nAvoid Chains of Single Fact Sentences When They Can Be \nCondensed into a Single Sentence.\u2002\nVerbose: \u201cThe specimen is received labeled with the \npatient\u2019s name. It is also labeled with the unit number. \nIt is received fresh. It is a right modified radical mastec\u00ad\ntomy. It measures 15 \u00d7 14 \u00d7 6 cm. There is an attached \naxillary tail. The axillary tail measures 6 \u00d7 4 \u00d7 2 cm. \nThe entire specimen weighs 182 gm. The white/tan skin \nellipse is 13 \u00d7 11 cm. The nipple is located in the center \nof the ellipse. There is a 3 cm well-healed surgical scar. \nIt is in the upper outer quadrant. It is 3 cm from the \nnipple. There is a fibrotic biopsy cavity measuring 3 \u00d7 3 \u00d7 \n2.5 cm. It is filled with red/brown friable material. The \nbiopsy cavity is 1 cm from the skin. The biopsy cavity is 2 \ncm from the deep margin. The deep margin is a smooth \nfascial plane.\u201d\nPrecise: \u201cReceived fresh labeled with the patient\u2019s name and \nunit number is a 182 gm right modified radical mastec\u00ad\ntomy specimen (15 \u00d7 14 \u00d7 6 cm) with a white/tan skin \nellipse (13 \u00d7 11 cm) and attached axillary tail (6 \u00d7 4 \u00d7 2 \ncm). There is a 3 cm well-healed surgical scar in the upper \nouter quadrant, 3 cm from the unremarkable nipple (0.7 \n\u00d7 0.6 cm). One cm deep to the scar is a fibrotic biopsy cavity \nfilled with red/brown friable material. The cavity is 2 cm \nfrom the deep margin, which is a smooth fascial plane . . .\u201d\nAvoid Making Uncertain Diagnoses.\u2002 Describe what is seen \nand do not make uncertain assumptions based on possible \ndiagnoses. Some gross diagnoses will later prove to be \nincorrect \u2013 although with experience this does not happen \nvery often. For example, it may turn out that the enlarged \nfirm lymph node was not \u201cgrossly involved by tumor\u201d \nbut actually was fibrotic or fatty. Recognize the differ\u00ad\nence between terms that are diagnostic and terms that are \ndescriptive (Table 2-5).\nIn the completed pathology report, the gross descrip\u00ad\ntion and the microscopic diagnosis should be in agree\u00ad\nment. Non-pathologists often do not realize that the gross \ndescription is not based on microscopic findings. If clini\u00ad\ncians read that there is an involved lymph node in the gross \ndescription, but there is no mention of it in the final diag\u00ad\nnosis, it will raise doubts about whether or not that node \nwas forgotten in the final report. These inconsistencies \nshould be corrected in the gross description or avoided ini\u00ad\ntially. For example, it is just as accurate to describe a \u201c2 cm \nfirm white lymph node\u201d and leave the diagnosis of tumor \nto the microscopic slides. Similarly, the final number of \nlymph nodes reported should ultimately correspond to the \nnumber of lymph nodes described grossly.\nA CLASSICAL INTERLUDE\nMany medical terms are derived from Latin or Greek and \nmay be used in their singular and plural forms. The follow\u00ad\ning are facts about forming plurals from Latin words:\n\t \u2022\t \u0007It is very complicated and requires detailed knowl\u00ad\nedge of the root word and its origin.\nTABLE 2\u20135.\u2003\n\u0007DIAGNOSTIC VERSUS DESCRIPTIVE \nTERMS\nDIAGNOSTIC/\nINTERPRETIVE TERMS\nDESCRIPTIVE TERMS\nCarcinoma\nMass\nHemorrhagic\nRed, brown\nNecrotic\nSoft, friable (papillary tumors \nare often mistakenly thought \nto be necrotic due to their \nsoft consistency)\nPurulent\nGreen, foul-smelling\nMalignant\nIrregular border, hard\nMucinous\nSticky, viscous\nInvasive\nIrregular\nFat necrosis\nYellow, chalky", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_037.png", "summary": "The text emphasizes the importance of concise and precise descriptions when processing gross specimens in pathology, providing examples and guidelines for accurate reporting.", "questions": [ "How can the use of concise and precise descriptions improve the accuracy of pathology reports?", "What are the potential consequences of inappropriate delayed handling of specimens?", "How can uncertain diagnoses impact the overall interpretation of pathology findings?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 38, "text": "20\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Selection of Tissue for Microscopic Exam\n\t \u2022\t \u0007It is better to look up a word than to guess the form \nof the plural as you will probably be wrong and may \nbe scorned by those who study ancient languages. \nFor example, Latin scholars cringe at \u201coctopi\u201d as the \ncorrect plural form is \u201coctopodes.\u201d Octopus is not a \nLatin word of the second declension, but a Latinized \nform of the Greek word oktopous (see how compli\u00ad\ncated it can get?). Since platypus is from the Greek \nword platypous (i.e., platys broad or flat + pous foot), \none could reason that the correct plural is platypo\u00ad\ndes and not platypi. Just to be safe, if you should \nbe so lucky as to have more than one, platypuses is \nacceptable.\n\t \u2022\t \u0007In some cases, more than one answer can be correct. \nFor many words, the English \u201cs\u201d ending is acceptable \nor preferred. For example, the correct plural form of \nspecimen is specimina \u2013 but \u201cspecimens\u201d is the com\u00ad\nmon usage.\n Table 2-6 presents the most common types of Latin \nplural endings and typical examples used in pathology.\nVirus has no plural form in Latin. Its original mean\u00ad\ning was a toxic agent that was an uncountable entity and, \ntherefore, did not require a plural form. The correct word \nfor more than one virus in its modern sense is viruses.\nCarcinoma, sarcoma, lymphoma, and stoma are Greek \nwords and the appropriate ending would be \u201cata.\u201d How\u00ad\never, the English \u201cs\u201d ending is commonly used.\nThe word epithelium is derived from the Greek epi \n(upon) and thele (nipple). It originally referred to the skin \ncovering the nipple. Therefore, related terms such as \nmesothelium and urothelium are technically misnomers. \nHowever, since only Greek scholars would likely find \nthis confusing, the terms will probably not be changed.\nSELECTION OF TISSUE FOR MICROSCOPIC EXAMINATION\nTissue is selected for microscopic examination to docu\u00ad\nment:\n\t\u2022\t \u0007All lesions. If multiple similar lesions are present, tissue \nbetween the lesions is submitted to determine whether \nthe lesions are separate or interconnected. The best \n\u00adsection to demonstrate pathologic features should be \ntaken, after complete dissection and examination of the \nspecimen.\n\t\u2022\t \u0007Lesional tissue placed in special fixatives for histologic \nexamination (e.g., B-plus).\n\t\u2022\t \u0007Representative sections of all normal structures not \nincluded in other sections. Random sections (equiva\u00ad\nlent to selecting tissue blindly) should not be taken. If a \n\u00adsection is to document a normal structure, the best rep\u00ad\nresentative tissue should be taken.\n\t\u2022\t \u0007Lymph nodes.\n\t\u2022\t \u0007All margins when appropriate.\n\t\u2022\t \u0007Frozen section remnants.\nMost specimens (including large complicated ones) can \nbe adequately sampled in no more than 20 cassettes.\nThe ideal number of tissue sections avoids both over- \nand undersampling:\nOversampling: Wasteful of resources and unnecessarily \nincreases costs.\nUndersampling: Important diagnostic or prognostic \ninformation may be lost, leading to suboptimal patho\u00ad\nlogic evaluation.\nFor some specimens (e.g., TURPs) studies have \nattempted to define the appropriate amount of sampling (see \nChapter 20). Decisions to limit or eliminate tissue sections \nshould be made in the context of such studies. The cost of \nexamining a few more slides may be significant for a pathol\u00ad\nogy department, but trivial in the overall cost of \u00adcaring for \na patient (with surgical costs running into the thousands of \ndollars) as well as personal costs in morbidity and mortality \nfor individual patients with suboptimal diagnoses.\nTABLE 2\u20136.\u2003\n\u0007LATIN SINGULAR AND PLURAL \nENDINGS\nSINGULAR \nENDING\nPLURAL \nENDING\nEXAMPLES\nSINGULAR\nPLURAL\na\nae\nTrabecula\nAmoeba\nFimbria\nTrabeculae\nAmoebae\nFimbriae\nius\nii\nRadius\nRadii\non\na\nGanglion\nGanglia\num\na\nBacterium\nDiverticulum\nAdnexum\nLabium\nAddendum\nCurriculum \nvitae\nBacteria\nDiverticula\nAdnexa\nLabia\nAddenda\nCurricula vitae\nis\nes\nPenis\nTestis\nPelvis\nPenes\nTestes\nPelves (or \npelvises)\nx\nces or ges\nPhalanx\nCervix\nFex\nAppendix\nPhalanges\nCervices (or \ncervixes)\nFeces\nAppendices\n2nd declension\nus\ni\nFungus\nNucleus\nFocus\nFungi\nNuclei\nFoci\n4th declension \nmasculine\nus\nEnglish \u201cs\u201d \npre\u00ad\nferred\nFetus\nFetuses", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_038.png", "summary": "The page discusses the selection of tissue for microscopic examination, emphasizing the importance of documenting all lesions, using special fixatives for lesional tissue, and ensuring representative sections of normal structures are included.", "questions": [ "Why is it important to document all lesions when selecting tissue for microscopic examination?", "What is the significance of using special fixatives for lesional tissue?", "Why should random sections not be taken when selecting tissue for examination?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 39, "text": "21\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Fixation\nFIXATION\nAfter the dissection and description of the gross speci\u00ad\nmen, tissues must be placed in a fixative. Ideally fixation \nserves to:\n\t\u2022\t \u0007Preserve tissue by preventing autolysis by cellular \nenzymes and prevent decomposition by the actions of \nbacteria and molds.\n\t\u2022\t \u0007Harden tissue to allow thin sectioning.\n\t\u2022\t \u0007Devitalize or inactivate infectious agents. However, \nCreutzfeldt-Jakob cases will remain infectious even in \ntissue on glass slides unless previously treated with for\u00ad\nmic acid.\n\t\u2022\t \u0007Stabilize tissue components.\n\t\u2022\t \u0007Enhance avidity for dyes.\nHowever, fixation also has undesirable effects on tissues:\n\t\u2022\t \u0007Alteration of protein structure: Proteins may be \ncross-linked, charges changed, and/or changes in ter\u00ad\ntiary structure may occur. This may result in loss of \nantigenicity that, to some extent, can be reversed by \nantigen retrieval methods. However, results of special \nstudies based on tissue fixed by one method cannot be \nextrapolated to tissue fixed by another method (e.g., \nmost immunohistochemical studies are performed on \nformalin-fixed tissue).\n\t\u2022\t \u0007Solubility of tissue components: Lipids and carbohy\u00ad\ndrates (e.g., glycogen) are often lost during processing \nunless special techniques are used.\n\t\u2022\t \u0007Shrinkage of tissue: Most fixatives cause shrinkage of \nthe tissue. If exact measurements are important (e.g., \ntumor size in breast carcinomas and sarcomas, distance \nto the distal margin in rectal resections), they should be \ntaken prior to fixation.\n\t\u2022\t \u0007DNA and RNA degradation: Some fixatives (especially \nthose containing picric acid) degrade nucleic acids and \nmust be avoided if studies of nucleic acids are \u00adanticipated.\nMost fixatives in use are combinations designed to max\u00ad\nimize the desirable properties of the fixatives and to mini\u00ad\nmize the undesirable properties.\nAdequate fixation depends upon:\nSufficient Volume.\u2002 An adequate amount of fixative is \nusually considered to be 15 to 20 times the volume of the \ntissue. If a specimen is received in saline, this should be \ndiscarded prior to adding fixative. Fixative contaminated \nwith blood or other fluids will be diluted and will not fix \ntissues well.\nAccess of Fixative to Tissue.\u2002 Fixatives penetrate slowly \n(approximately 0.1 cm per hour). Anatomic barriers (e.g., \nfascia, capsules) are barriers to fixative penetration and \nmust be incised to allow optimal fixation. Large specimens \nmust be thinly sectioned. Gauze pads can be used to wick \nfixative around each portion of the specimen and between \nthe specimen and the container. Large flat specimens (e.g., \ncolon segments, stomachs, large skin excisions) can be \npinned out on a paraffin block and floated upside down \nin a container containing fixative. A piece of gauze may be \nplaced between the specimen and the paraffin to wick fixa\u00ad\ntive around the tissue.\nIf adequate fixation of an entire specimen is difficult or \nmay be delayed, small thin sections of tumor should be \ntaken and fixed separately (\u201cquick fix formalin\u201d). These \nsections should be cut small enough to fit easily into a cas\u00ad\nsette to optimize fixation.\nTime.\u2002 Usually 6 to 8 hours is required for adequate fixa\u00ad\ntion in formalin. Other fixatives may penetrate more rap\u00ad\nidly or more slowly. Overfixation may result in hard brittle \ntissue in some fixatives or in loss of antigenicity.\nTemperature.\u2002 Increasing the temperature increases the \nrate of fixation but also increases the rate of autolysis and \nmust be carefully monitored. Most laboratories fix speci\u00ad\nmens at room temperature.\nPreservation of Biomolecules for \u201cCellular Chemistry\u201d\nPathology specimens contain DNA, mRNA, proteins, as \nwell as a multitude of other biomolecules that may be use\u00ad\nful for assays leading to disease classification, prognosis, \nand/or prediction of the response to treatments. The pres\u00ad\nervation of a biomolecule is dependent upon many factors:\n\t\u2022\t \u0007Patient factors: Disease state, drugs or other treat\u00ad\nments (e.g., radiation therapy), etc.\n\t\u2022\t \u0007Surgical factors: Time at which tissue is removed from \nblood flow (e.g., time of vascular ligation, time of needle \nbiopsy), time the specimen is removed from the patient, \nexposure to surgical instruments (e.g., cutting, cauteriz\u00ad\ning), length of time of surgery and time under anesthesia.\n\t\u2022\t \u0007Transport factors: Length of time of transport to the \npathology department, condition during transport (e.g., \nin fresh state, in fixative).\n\t\u2022\t \u0007Pathology factors: Length of time to fixation, thick\u00ad\nness of sections and adequacy of fixation, type of fixative, \nlength of time in fixation prior to processing of paraf\u00ad\nfin blocks, processing protocols (dehydration, clearing, \nimpregnation), type of paraffin, length of time in paraf\u00ad\nfin, conditions of block storage.\nIt is likely that different biomolecules will have different \nrequirements for optimal preservation. As assays are devel\u00ad\noped for patient care, it will be important to determine the \nimportant parameters for tissue handling for each specific \nassay. For example, recommendations have been made for \ntissues used for HER2/neu tests for breast carcinoma.7 It \nhas been recommended the following times be recorded:\n\t\u2022\t \u0007Ischemic time: The time from removal of the tissue \nfrom the body (recorded by the surgeon) to the time the \nspecimen (if large, the specimen must be sliced) is placed \nin fixative.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_039.png", "summary": "Fixation of tissues after dissection is crucial for preserving tissue integrity, allowing thin sectioning, and inactivating infectious agents, but it can also have undesirable effects such as altering protein structure and causing shrinkage.", "questions": [ "How does fixation prevent tissue autolysis and decomposition?", "What are the undesirable effects of fixation on tissues?", "Why is it important to take measurements prior to tissue fixation, especially in certain types of cancers?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 40, "text": "22\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Fixation\n\t\u2022\t \u0007Fixation time: The time the specimen is in fixative. \nBoth overfixation and underfixation can alter biomol\u00ad\necules.\nWhen these times are out of the range used for speci\u00ad\nmens to develop the assay in question, then the reliability \nof the assay results will be in doubt.\nUnfortunately, there are few studies that clearly mea\u00ad\nsure changes in specific analytes related to the numerous \nvariables in tissue handling. Such studies are necessary \nbefore instituting costly changes to the routine practice \nof pathology (especially in light of the fact that fewer \nthan 0.1% of all pathology specimens will likely undergo \nmolecular testing). Although standardization of all speci\u00ad\nmen processing is a laudable goal, it is unlikely to be \nachievable. For assays critical for patient care, it would be \nmore practical to devise ways to identify, remove, and pro\u00ad\ncess tissue specifically for the assay in designated patients. \nFinally, there is always a need to demonstrate that costly \nand difficult-to-perform assays are superior to standard \nmethods of pathologic analysis (sadly, something that is \ninfrequently done).8-11\nTypes of Fixatives\nChoice of fixative may limit the opportunities for other \nspecial studies. Before fixing tissue, consideration should \nbe given to cytogenetic (cell culture) studies and frozen tis\u00ad\nsue (RNA and DNA analysis), which require, or are best \nperformed on, unfixed tissue. Flow cytometry is optimally \nperformed using fresh tissue but can be performed on fixed \ntissue.\nSpecial gloves (e.g., nitrile gloves) should be worn when \nhandling fixatives or fixed tissues. Latex gloves offer pro\u00ad\ntection from biohazards when handling fresh tissues but do \nnot protect against absorption of chemicals.\nFormalin (Clear)\nComposition: 10% phosphate-buffered formalin (forma\u00ad\nlin is 40% formaldehyde in water, therefore 10% for\u00ad\nmalin is 4% formaldehyde). Formalin that is unbuffered \ndegrades rapidly and does not preserve nucleic acids \nwell.\nIndications: Formalin can be used for the routine fixation \nof all specimens.\nAdvantages: Formalin is the standard fixative of most \npathology departments and has been used in many stud\u00ad\nies of special stains and immunohistochemistry. It fixes \nmost tissues well and is compatible with most histologic \nstains. Tissue can be preserved in formalin for many \nmonths. Formalin is necessary to see the lacunar cells of \nthe nodular sclerosing variant of Hodgkin\u2019s disease and \nmay be used for a portion of the tissue if this diagnosis \nis suspected.\nDisadvantages: Fixation occurs due to cross-linking of \nproteins. Cross-linking occurs over time; therefore even \nsmall specimens (e.g., core needle biopsies) need to fix \nfor a minimum of 6 to 8 hours. Overfixation (over many \ndays to weeks) can diminish immunoreactivity. To some \nextent this is reversed by antigen retrieval methods. \nModifications adding zinc may also preserve antigenic\u00ad\nity. Because of the slower fixation time in comparison \nto other fixatives, fine bubbling of nuclei may occur due \nto chromatin coalescence. Formalin penetrates tissue at \nabout 0.4 cm each 24 hours. Formalin will dissolve uric \nacid crystals. Such specimens should be fixed in absolute \nalcohol. Calcifications in the breast can also dissolve if \nfixed over 24 hours.\nThe major toxic effects of acute exposure are eye, upper \nrespiratory tract, or dermal irritation. Very high levels can \ncause pulmonary edema, hemorrhage, and death in labora\u00ad\ntory animals. Formaldehyde has been classified as a human \ncarcinogen by the International Agency for Research \non Cancer (IARC). Epidemiologic studies have shown \nincreased rates of certain cancers in pathology workers, \nembalmers, and industrial workers exposed to formalde\u00ad\nhyde. However, it remains unclear whether formaldehyde \nis the causative agent in these cases.\nMost people can smell formaldehyde at levels of 0.1 to \n1.0 ppm. These are levels at which irritant effects occur \nand indicate that exposure should be reduced.12 However, \nsmell adapts quickly and is not a reliable method to deter\u00ad\nmine whether formaldehyde vapors are present.\nExposure to formaldehyde must be kept within federal \nand state limits (see www.osha.gov/ for federal regula\u00ad\ntions). Exposure to formaldehyde can be monitored using \nindividual badges and may be appropriate for individuals \nwith possible exposure to high formaldehyde levels.\nAlthough legal regulations only apply to workplaces, it \nis not advisable to release specimens to patients in formalin \n(see \u201cReturning Specimens to Patients\u201d).13-15\nNon-Formalin Fixatives\nComposition: Variable \u2013 many are alcohol based. \nThe ingredients of proprietary solutions may not be \navailable.\nIndications: May be used to avoid formaldehyde or to \nfix tissues for molecular protocols (see cgap-mf.nih.\ngov/ for the use of 70% ethanol fixation for molecular \nstudies).\nAdvantages: Most are not hazardous, do not require \nmonitoring, and can be disposed into the general sewer \nsystem. Although the purchase cost may be higher than \nformalin, this expense may be offset by cheaper disposal. \nSome types may be superior for immunoperoxidase \nstudies because proteins are not cross-linked.\nDisadvantages: Time of fixation may be critical with \nunder- and overfixation leading to suboptimal results. \nPenetration into larger or fatty specimens may be slow. \nNuclear and cytologic detail may not be as good as with \nformalin and other traditional fixatives. Some of these \nfixatives may not be optimal for estrogen and progester\u00ad\none immunoperoxidase studies.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_040.png", "summary": "Proper fixation of tissue specimens is crucial for accurate assay results in pathology. Standardization of specimen processing is challenging, but it is important to consider individualized processing for critical assays.", "questions": [ "How does fixation time affect the reliability of assay results?", "What are the considerations for choosing a fixative?", "Why is formalin commonly used as a fixative in pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 41, "text": "23\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Fixation \nBouin\u2019s solution (Yellow)\nComposition: Picric acid, formaldehyde, and acetic acid.\nIndications: Any tissue (but especially small biopsies).\nAdvantages: Fixation in Bouin\u2019s will result in sharp H&E \nstaining and is preferred by some pathologists. Bouin\u2019s \nfixation can facilitate finding small lymph nodes. The \nnodes will remain white and the fat is stained yellow. \nProlonged fixation can be used to decalcify tissue.\nDisadvantages: Tissues will become quite brittle and \nshould not be fixed for over 18 hours. Tissues can be \ntransferred to ethanol to avoid this. Large specimens \nshould not be fixed in Bouin\u2019s as it will color the entire \nspecimen yellow and it will be difficult to see details \ngrossly. Red cells will be lysed and iron and small cal\u00ad\ncium deposits dissolved. Immunoperoxidase studies per\u00ad\nformed on tissues fixed in Bouin\u2019s may be less sensitive. \nPicric acid can cause degradation of DNA and RNA and \nmay interfere with the use of tissues for special studies \nrequiring intact DNA, such as PCR (polymerase chain \nreaction).\nPicric acid is an explosive if dry and must be kept \nmoist!\nB-Plus (Clear)\nComposition: Buffered formalin with 0.5% zinc chloride.\nIndications: Used for the routine fixation of lymph nodes, \nspleens, and other tissues if a lymphoproliferative disor\u00ad\nder is suspected.\nAdvantages: B-Plus gives rapid fixation with excellent \ncytologic detail similar to that achieved with the mer\u00ad\ncury containing fixative, B-5. Antigen preservation for \nlymphoid markers is excellent. No special fixation times, \nwashing, or disposal procedures are required, other than \nthose used for formalin.\nDisadvantages: This fixative has the same disadvantages \nas other formalin-based fixatives.\nZenker\u2019s acetic fixative (Orange)\nComposition: Potassium dichromate, mercuric chloride, \nand acetic acid.\nIndications: May be used for bone marrow biopsies. \nRequires between 8 and 12 hours for decalcification \nand optimal cytologic preservation. Soft tissue tumors \nsuspected of having muscle differentiation (cross-stria\u00ad\ntions are especially well preserved) may be fixed for four \nhours.\nAdvantages: Rapidly fixes tissues with excellent histo\u00ad\nlogic detail. Zenker\u2019s will slowly decalcify tissues. Can \nbe used to demonstrate a chromaffin reaction in pheo\u00ad\nchromocytomas because of the potassium dichromate \nbut may be less sensitive than solutions not containing \nacetic acid (see Chapter 11). Sometimes preferred for \nbloody specimens, as red blood cells will be lysed.\nDisadvantages: Penetrates poorly. Fixation for lon\u00ad\nger than 24 hours may cause the tissue to become \nbrittle. The tissue can be transferred to formalin to \navoid this. Erythrocytes are lysed and iron may be dis\u00ad\nsolved. Tissues are rinsed in a water bath and then \nwashed for several hours in tap water (bone marrows \n\u22651 hour; soft tissue tumors \u22654 hours) after fixation \nto remove mercury precipitates before processing. \nTissues cannot be overwashed. There is poor antigen \npreservation for immunohistochemistry and Zenker\u2019s \ninterferes with chloroacetate esterase activity. Special \nprocedures for disposal are required due to the pres\u00ad\nence of mercury. Mercury containing fixative will cor\u00ad\nrode metal.\nCaution: Do not allow contact with skin \u2013 contains \nmercury!\nGlutaraldehyde (Clear)\nComposition: Glutaraldehyde, cacodylate buffer\nIndications: Tissues to be preserved for electron micros\u00ad\ncopy\nAdvantages: Excellent preservation of ultrastructural cel\u00ad\nlular detail\nDisadvantages: Penetrates slowly and poorly. Tissues \nmust be minced into small cubes and fixed rapidly. \nRefrigeration is required for storage. Can result in false \npositive PAS stains.\nAlcohol (Clear)\nComposition: Ethanol and methanol rapidly displace \nwater and denature protein.\nIndications: Synovial specimens if gout is suspected. Urate \ncrystals will be dissolved by water-containing fixatives \n(e.g., formalin). The tissue is fixed in 100% alcohol for \nnon-aqueous processing and H&E and Wright stains. \nSmears, touch preps, and frozen sections are fixed in \nmethanol before staining.\nAdvantages: Many antigens are preserved well. Most do \nnot require special disposal methods.\nDisadvantages: Alcohol dissolves lipids and penetrates \npoorly. Fixation times must be carefully monitored (for \nboth under- and overfixation). Ethanol and methanol \nwill shrink and harden tissue left in these fixatives over \ntime. This is not a problem with alcohol-based fixatives \nsuch as methacarn.\nDecalcification\nBone and other calcified tissues (blood vessels with calci\u00ad\nfied plaques, some teratomas, intervertebral discs, some \nmeningiomas, some ovarian tumors, calcified infarcted \nepiploic appendages, etc.) must have the calcium removed \nin order to allow the specimen to be sectioned. Some fixa\u00ad\ntives (e.g., Bouin\u2019s and Zenker\u2019s) will both fix and decal\u00ad\ncify tissues. Other decalcifying agents are not fixatives and \ntissues must be fixed first before using such agents. Small \nspecimens only require 1 to 2 hours whereas femoral heads", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_041.png", "summary": "The page discusses different fixation solutions used in specimen processing, including Bouin's solution, B-Plus, and Zenker's acetic fixative, highlighting their compositions, indications, advantages, and disadvantages.", "questions": [ "How does fixation in Bouin's solution differ from fixation in B-Plus or Zenker's acetic fixative?", "What are the specific indications for using each of the fixation solutions mentioned?", "What are the potential drawbacks or limitations of using these fixation solutions in specimen processing?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 42, "text": "24\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Returning Specimens to Patients\nmay require 1 to 2 days. Large calcified structures should \nbe sectioned with a bone saw prior to fixation and decal\u00ad\ncification.\nProlonged decalcification will adversely affect histologic \ndetail and preservation of some nuclear antigens, especially \nER, PR, p53, and Ki-67.16 Blood group H is also affected \n(see section under immunohistochemistry). Some antigens \nare relatively unaffected, but many have not been tested. \nIt may not be possible to perform FISH or other assays \nrequiring intact DNA on decalcified tissue. Specimens of \ndiagnostic importance (e.g., tumors) should be decalcified \nfor the least amount of time necessary by checking the tis\u00ad\nsue every few hours.\nUndecalcified sections are sometimes examined in the \nstudy for metabolic bone disease (see in Chapter 14, \u201cBiopsy, \nMetabolic Bone Disease\u201d). Special processing is required \nand sections must be embedded in plastic. Such studies are \nusually only performed by specialized laboratories.\nDISPOSAL OF FIXATIVES AND TISSUES\nTissue not submitted for histologic sections is generally \nheld for a period of time (CAP guidelines are 14 days; \nTJC guidelines are 7 days) after the final sign-out of the \ncase. This allows enough time for the clinician to receive \nthe report and ensures that additional tissue can be submit\u00ad\nted if any issues arise. Most departments do not have facili\u00ad\nties for long term storage of gross specimens. Clinicians \nshould inform their patients that specimens are discarded \n(especially in cases of possible medicolegal importance), to \navoid later misunderstanding should a patient want a speci\u00ad\nmen (see \u201cReturning Specimens to Patients\u201d).\nChemicals used in pathology can pose toxic, fire, explo\u00ad\nsive, and corrosive hazards. Tissues are potentially infec\u00ad\ntious. Care must be taken in how these materials are \nhandled and disposed for the safety of human beings (both \ninside and outside the hospital) and to meet current hos\u00ad\npital and state standards for waste disposal. Laboratories \nmust conform to federal standards regulated by OSHA (see \nwww.osha.gov/).\nFixatives and chemicals cannot be disposed into the \ngeneral waste water system (i.e., down sink drains). All \nfixatives must be placed into special designated containers \nfor disposal. Although adequate amounts of fixative should \nalways be used, unnecessary amounts of fixative must be \navoided. For example, the same fixative can be reused when \ntransferring a specimen into a new container. To remove \nexcess formalin from fixed specimens before handling, tis\u00ad\nsues may be rinsed in a water bath and the water disposed \nwith the formalin waste.\nMercury-containing fixatives (e.g., B-5 and Zenker\u2019s) \nmust be disposed according to institutional and legal stan\u00ad\ndards. B-Plus does not contain mercury.\nXylene and methanol must be disposed into special \nwaste containers. Xylene is a neurotoxin and short-term \nexposure can cause headaches, dizziness, lack of coordina\u00ad\ntion, confusion, and fatigue.\nClean ethanol can be disposed into sink drains. How\u00ad\never, ethanol that has been contaminated with any other \nsubstance (e.g., xylene during staining) must be placed in \nspecial waste containers.\nIf specimen containers are discarded that contain fixa\u00ad\ntive, the cap should be tightly screwed on. Otherwise the \nliquid fixative mixed with other garbage constitutes a haz\u00ad\nard and increases the amount of formalin in the air. Forma\u00ad\nlin containers for holding cassettes should have a lid.\nTissues and explanted synthetic materials are discarded \ninto biohazard bags in specifically marked boxes that are \nincinerated.\nDISPOSAL OF SHARPS\nAll tools used to process specimens (forceps, scissors, \nscalpel handles, probes) must be rinsed and carefully \nexamined between cases to prevent carrying tissue over to \nanother case. A small piece of malignant tissue transferred \nto the wrong cassette, barely visible to the eye, could \npotentially result in a diagnostic error or could require \nexpensive tests (typically costing thousands of dollars) for \ntissue typing.\nScalpel blades, glass slides, and needles must be dis\u00ad\ncarded into specific sharps containers. The person using \nthe sharp is responsible for its proper disposal. It is prefer\u00ad\nable to discard a sharp immediately after use, rather than \nto set it down on the working area. Before leaving a work \narea, always check for scalpels, blades, or syringe needles. \nSevere injuries have resulted from sharp blades and needles \nconcealed in surgical drapes or paper towels.\nRETURNING SPECIMENS TO PATIENTS\nPathology departments should have a formal policy for \nreturning specimens to patients.\nIssues to be addressed are:\nThe Rights of the Patient.\u2002 The legal ownership of tis\u00ad\nsues and materials removed from patients is not clear. In \npart, \u201cownership\u201d of a specimen may be affected by the \nexact wording in a consent form for surgery or admission \nto a hospital. Some specimens may be classified legally as \n\u201cmedical waste\u201d and may fall under state regulations for \ndisposal of hazardous waste. In general, when release of a \nspecimen does not involve the issues discussed below, the \npatient\u2019s wishes should be accommodated. However, in \nsome cases a legal opinion may be necessary.\nDiagnostic Issues.\u2002 It is rare for a patient to ask for \npossession of a specimen prior to diagnostic procedures \nbeing performed. However, should this happen, the \nrights of the patient would need to be balanced against \nthe duty of the hospital and physicians to do what is in \nthe best interest of the patient and to make sure that the \npatient is well informed of the possible consequences of \nthis action.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_042.png", "summary": "Proper specimen processing is crucial for maintaining histologic detail and preserving nuclear antigens. Disposal of fixatives and tissues must be done carefully to adhere to safety standards and regulations.", "questions": [ "How does prolonged decalcification affect histologic detail and preservation of nuclear antigens?", "What are the implications of not being able to perform FISH or other assays on decalcified tissue?", "What precautions should be taken when disposing of fixatives and tissues to ensure safety and compliance with regulations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 43, "text": "25\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Returning Specimens to Patients\nSafety of the Patient and Public.\u2002 Specimens that are \nclearly a hazard, in particular any tissue from a patient \nwith Creutzfeldt-Jacob disease, should definitely not be \nreleased. In general, foreign objects (e.g., hardware, pros\u00ad\ntheses, teeth) that are clean pose minimal if any hazard. \nActual tissue specimens may carry a risk of infection if not \nfixed, and fixatives are potentially hazardous. Such risk \ncan be minimized, but the patient should be informed of \npotential risks.\nIn general, fixatives should be removed and specimens \nwashed clean. It is preferable to place specimens in a heat-\nsealed plastic bag that can allow viewing of the specimen \nwithout opening the container. An informational release \nform may also be included (see below).\nMedicolegal Issues.\u2002 Some specimens may become evi\u00ad\ndence in lawsuits. In such cases it is useful to photograph a \nspecimen to retain a permanent visual record. For non-tissue \nspecimens (e.g., breast implants or bullets), it is preferable \nto not alter the specimen (e.g., by sterilization or cleaning) \nand to release it in the same condition as it was received.\nRecipient of Specimen.\u2002 In all cases (except bullets) it is \npreferable to release the specimen directly to the patient. \nThe patient may request that the specimen be released to a \nlegal representative or other party. In such cases, a signed \nrelease form from the patient must be obtained and medi\u00ad\ncal confidentiality must be maintained. Bullets, or other \nspecimens serving as evidence of a crime, should only be \nreleased to a police officer and the appropriate chain of \ncustody documentation maintained (see in Chapter 28, \n\u201cBullets\u201d).\nSpecimens requested for burial (usually limbs or prod\u00ad\nucts of conception) are generally released directly to a \nfuneral home.\nCommon specimens requested for return:\n\t \u2022\t \u0007Orthopedic hardware\n\t \u2022\t \u0007Foreign bodies\n\t \u2022\t \u0007Gallstones\n\t \u2022\t \u0007Teeth\nAs these specimens pose little threat to health if clean \nand placed in a clean container, return of such specimens \nis unlikely to cause harm. It has been questioned as to \nwhether gallstones placed in formalin are hazardous, as \nformalin is still detectable even after rinsing in water for \n30 minutes. Although patients and their families are not \nincluded under government regulations concerning for\u00ad\nmalin exposure, it would be inappropriate for physicians to \ngive a patient something that constitutes a health hazard as \nspecimens can fall into the wrong hands. There is a report \nof two children ingesting gallstones fixed in formalin.17 \nAlthough the children did not develop symptoms, the epi\u00ad\nsode did prompt a visit to an emergency room, x-rays, and \ntreatment with activated charcoal.\nGiven that the possibility of harm is low but possible, \nthe following procedures are suggested:\n\t\u2022\t \u0007If it is known that the patient wants the gallstones \nreturned, the stones can be washed clean, dried, and \nplaced in a sealed container.\n\t\u2022\t \u0007If the gallstones have been placed in formalin, they may \nbe rinsed in water and then dried. The stones can be \nplaced in a sealed container with a label indicating that \nthe stones had been fixed in formalin.\nIn either case, the patient should be informed that the \ngallstones are best left within the sealed container.\nIn June 2006, a placenta was found floating in a pond \nnear Wellesley College in Massachusetts. Concern for \nthe mother and infant led to the draining of the pond, a \nsearch of the campus, and intense media coverage. The \nplacenta had been saved frozen by a couple after a normal \ndelivery several months previously. For unknown reasons, \nthey decided to discard it in the pond. Although ultimately \nno one was harmed, the waste of police and community \nresources was considerable and could have been avoided if \nthe parents had been educated about the appropriate dis\u00ad\nposal of human tissues.\nSample Specimen Release Form\nFigure 2-2 is an example of a form that could be used \nto both inform patients of potential risks, appropriate \nprocedures for handling a specimen, and appropriate dis\u00ad\nposal, as well as to document the release of a specimen. \nIf the specimen is released to a person other than the \npatient, the patient must sign a separate form authoriz\u00ad\ning release of the specimen and the associated medical \ninformation.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_043.png", "summary": "The page discusses the safe handling and return of specimens to patients, including precautions for hazardous materials and medicolegal considerations.", "questions": [ "What are some examples of specimens that should not be released to patients?", "How should specimens be handled to minimize risks of infection or hazards?", "What are the guidelines for releasing specimens that may be used as evidence in lawsuits?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 44, "text": "26\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Returning Specimens to Patients\nDEPARTMENT OF PATHOLOGY\nREQUEST FOR RELEASE OF PATHOLOGY SPECIMENS\nPatient name: \n \n \n \n \n \n Date:\n \nSurgical Pathology Number:\n \nName of person requesting specimen:\n \nName of person authorizing the release of the specimen:\n \nType of specimen:\nSpecimens received by the pathology department are examined and sampled for diagnostic purposes. \nSpecimens are normally held for two weeks and then disposed of by incineration. Requests for return\nof specimens must be made at the time of surgery or within two weeks.\nRisks involved in handling pathology specimens\nPathology specimens consist of human tissues and/or prosthetic materials that have been in contact with \nhuman tissues. Although the specimen has been placed in an impermeable container, these tissues and \nmaterials may constitute a health hazard and must be handled and disposed of properly as described below. If \nyou wish to discard a specimen, you may return it to the department for disposal.\nUnfixed tissue (e.g., amputations, placentas): Unfixed human tissue potentially harbors infectious agents such \nas hepatitis B virus and the human immunodeficiency virus (HIV). Tissue must always be handled with \nprotective gloves and must not be allowed to contaminate surfaces. It is strongly recommended that such \nspecimens be handled directly and exclusively by a designated funeral home. Appropriate disposal is by burial \nor incineration only.\nFixed tissues (e.g., appendix, gallstones): Formalin is a fixative that will inactivate most infectious agents but will \nnot destroy the agent responsible for Creutzfeldt\u2013Jakob disease. Tissue must always be handled using \nprotective gloves and must not be allowed to contaminate other surfaces. Tissues must be disposed of by \nincineration.\nFormalin is a toxic respiratory irritant and potential carcinogen. It should never be inhaled, ingested, or allowed \nto come into contact with skin or mucosal surfaces. The container must be kept away from children and pets. \nContainers must only be opened in well-ventilated sites. The fixed specimen may have been washed, but small \namounts of formalin may remain in or on the specimen.\nSynthetic materials (e.g., orthopedic hardware, breast implants): This material may have been cleaned of all \ngross blood and tissue fragments but must be handled with caution. It is recommended that these materials be \nkept in a protective container and only handled using gloves. These materials should be disposed of by \nincineration.\nI have read and understand the information provided above and accept responsibility for handling and \ndisposing of the requested specimen appropriately.\nSignature \n \n \n \n \n \n Date \nRelationship to patient:\nFigure 2\u20132.\u2002 Informational request form for release of specimens.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_044.png", "summary": "The page provides information on the handling and disposal of pathology specimens, emphasizing the risks involved in handling human tissues and prosthetic materials.", "questions": [ "What are the risks associated with handling unfixed human tissue?", "How should fixed tissues be disposed of?", "What precautions should be taken when handling synthetic materials like orthopedic hardware?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 45, "text": "27\nSPECIMEN PROCESSING: FROM GROSS SPECIMENS TO TISSUE CASSETTES\u2003 Returning Specimens to Patients\nREFERENCES\n\t\u2002 1.\t \u0007Wiley EL, Keh P. Diagnostic discrepancies in breast speci\u00ad\nmens subjected to gross reexamination. Am J Surg Pathol \n23:876-879, 1999.\n\t\u2002 2.\t \u0007Olson DR. Specimen photocopying for surgical pathology \nreports. Am J Clin Pathol 70:94-95, 1978.\n\t\u2002 3.\t \u0007Walsh S, Mirza T, Smith G, Hyde N. Impact of colour \ndigital photography on pathologists\u2019 orientation of resected \nspecimens: a prospective pilot study. Br J Oral Maxillofac \nSurg, 2008:Epub.\n\t\u2002 4.\t \u0007Goldstein NS, Soman A, Sacksner J. Disparate surgical mar\u00ad\ngin lengths of colorectal resection specimens between in vivo \nand in vitro measurements. The effects of surgical resection \nand formalin fixation on organ shrinkage. Am J Clin Pathol \n111:349-351, 1999.\n\t\u2002 5.\t \u0007Dirckx JH. Chromatic fantasies. Color words in medicine. \nAm J Dermatopathol 7:157-161, 1985.\n\t\u2002 6.\t \u0007Bewtra C. Food in pathology. Am J Dermatopathol 18:555, \n1996.\n\t\u2002 7.\t \u0007Wolff AC, et al. American Society of Clinical Oncology/Col\u00ad\nlege of American Pathologists Guideline Recommendations \nfor Human Epidermal Growth Factor Receptor 2 Testing in \nBreast Cancer. Arch Pathol Lab Med 131:18-43, 2007.\n\t\u2002 8.\t \u0007Chung J-Y, Braunschweig T, Williams R, et al. Factors in tis\u00ad\nsue handling and processing that impact RNA obtained from \nformalin-fixed, paraffin embedded tissue. J Histochem &\n Cytochem 56:1033-1042, 2008.\n\t\u2002 9.\t \u0007Hewitt SM, Lewis FA, Cao Y, et al. Tissue handling and \nspecimen preparation in surgical pathology. Issues concern\u00ad\ning the recovery of nucleic acids from formalin-fixed, paraf\u00ad\nfin-embedded tissue. Arch Pathol Lab Med 132:1929-1935, \n2008.\n\t10.\t \u0007National Cancer Institute Office of Biorepositories and Bio\u00ad\nspecimen Research (http://biospecimens.cancer.gov).\n\t11.\t \u0007Van Maldegem F, de Wit M, Morsink F, et al. Effects of pro\u00ad\ncessing delay, formalin fixation, and immunohistochemistry \non RNA recovery from formalin-fixed paraffin-embedded \ntissue sections. Diagn Mol Pathol 17:51-58, 2008.\n\t12.\t \u0007Loomis TA. Formalin toxicity. Arch Pathol Lab Med \n103:321-324, 1979.\n\t13.\t \u0007Costa S, Coelho P, Costa C, et al. Genotoxic damage in \npathology anatomy laboratory workers exposed to formalde\u00ad\nhyde. Toxicology, 2008:Epub.\n\t14.\t \u0007Golden R, Pyatt D, Shields PG. Formaldehyde as a potential \nhuman leukemogen: an assessment of biological plausibility. \nCrit Rev Toxicol 36:135-153, 2006.\n\t15.\t \u0007IARC Monographs on the Evaluation of Carcinogenic Risks \nto Humans, Volume 88: Formaldehyde, 2-Butoxyethanol \nand 1-tert-Butoxy-2-propanol, World Health Organization, \nLyon, 2006.\n\t16.\t \u0007Arber JM, Arber DA, Jenkins KA, Battifora H. Effect of \ndecalcification and fixation in paraffin-section immunohisto\u00ad\nchemistry. Appl Immunohistochem 4:241-248, 1996.\n\t17.\t \u0007Dunn E, Nolte T. The potential toxicity of preserved gall\u00ad\nstones [letter], Vet Hum Toxicol 36:478, 1994.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_045.png", "summary": "This page discusses specimen processing from gross specimens to tissue cassettes and includes references on topics such as diagnostic discrepancies, specimen photocopying, impact of digital photography, surgical margin lengths, and tissue handling for RNA recovery.", "questions": [ "How do diagnostic discrepancies in breast specimens subjected to gross reexamination affect patient care?", "What is the significance of specimen photocopying for surgical pathology reports?", "How does the impact of color digital photography on pathologists' orientation of resected specimens influence the accuracy of diagnoses?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 46, "text": "28\n3\nThe Histology Laboratory: \nWhat the Pathologist Needs to \nKnow, from Tissue Cassettes \nto Glass Slides\nThe histotechnologist and the histology laboratory are \nessential for the accurate diagnosis of pathologic speci\u00ad\nmens. However, the process by which tissue in cassettes \nis converted into glass slides remains an enigma for many \npathologists. A basic knowledge about histologic labora\u00ad\ntory technique is necessary to facilitate communication \nbetween pathologists and histotechnologists. Poor com\u00ad\nmunication can lead to suboptimal evaluation and possibly \nerrors in diagnosis.\nHISTOLOGIC PROCESSING\nStandard tissue cassettes measure 3 \u00d7 2.5 \u00d7 0.4 cm. Tissue \nmust be cut to fit easily into the cassette and must be 0.3 \ncm or less in thickness (no more than the width of two \nnickels). Thin sections taken from such tissue will fit onto \nstandard microscope slides measuring 7.5 \u00d7 2.5 cm (Fig. \n3-1). Larger tissue sections can be produced using larger \ncassettes and glass slides, but require special equipment \nand training.\nTissue Processing\nThe tissue undergoes an automated processing step (usu\u00ad\nally requiring several hours) in which the tissue goes \nthrough three steps:\n 1.\t \u0007Dehydration: The water in the tissue is replaced by \nalcohol. Nonaqueous embedding media (such as paraf\u00ad\nfin) cannot penetrate tissues containing water.\n 2.\t \u0007Clearing: The alcohol is replaced by a clearing agent that \nmakes the tissue receptive to infiltration by the embed\u00ad\nding medium. The clearing agent must be miscible \nwith both alcohol and the embedding medium. Because \nxylene (a common clearing agent) has a high refractive \nindex, the tissue will also become transparent (\u201ccleared\u201d).\n 3.\t \u0007Infiltration: The xylene is replaced by paraffin or \nanother embedding medium. The paraffin stiffens the \ntissue, and this allows very thin sections (only a few \nmicrons in thickness) to be cut with a microtome.\nProblems with Submitted Tissue\nFatty Tissue.\u2002 Fixatives, and especially dehydrants, pene\u00ad\ntrate fatty tissues slowly. This type of tissue must be cut \nvery thin to fix and dehydrate well.\nTissue Too Thick or Large for the Cassette.\u2002 It is often \n\u00adtempting for pathologists to stuff cassettes with tissue \neither because it is easier than cutting thin sections or in \na (futile) attempt to have a larger area of tissue present on \nthe slide. Fixatives and processing solutions cannot gain \naccess to the tissue. The tissue will not process well and \nmay remain soft and it is often impossible to section such \ntissue. This outcome can have a significant adverse affect \non patient care if the tissue can never be examined (e.g., \nlymph nodes on a tumor resection). Tissue sections should \nbe no thicker than 0.2 to 0.3 cm.\nCalcified Substances.\u2002 As a general rule of thumb, any \ntissue submitted for processing should be easily sectioned \nwith a scalpel blade. Thick bone or calcified tissues cannot \nbe cut by a microtome and must be decalcified prior to \nprocessing.\nHair.\u2002 Hair can dull microtome blades and should be \ncarefully shaved off if abundant on a skin specimen or der\u00ad\nmoid cyst.\nHard Foreign Material.\u2002 Staples and clips must be removed \nfrom tissue. Metallic objects can be located by radiograph\u00ad\ning tissue, if necessary.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_046.png", "summary": "Histotechnologists and histology laboratories are crucial for accurate diagnosis of pathologic specimens. Pathologists need basic knowledge of histologic laboratory techniques to ensure effective communication and prevent errors in diagnosis.", "questions": [ "Why is it important for pathologists to have a basic understanding of histologic laboratory techniques?", "What are the three main steps involved in tissue processing?", "Why is it problematic to submit tissue that is too thick or large for the cassette?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 47, "text": "THE HISTOLOGY LABORATORY\u2003 Histologic Processing\n29\nB\nC\nA\nA specimen is cut into thin sections\nSections are placed into cassettes, \nfixed, and submitted for paraffin embedding\nIn this example, 2 paraffin blocks\nare produced\nA. Tissue is grossly serially sectioned (2 to\nseveral mm) to look for small lesions.\nB. Cassette: The tissue is placed in a plastic\ncassette for processing. The tissue slices\nshould be no thicker than 0.3 cm and should\nfit loosely in the cassette to allow access to all\nof the reagents.\nIn general, tissue processing (dehydration,\nclearing, and infiltration by paraffin) requires\nseveral hours and is usually performed\novernight.\nC. Block: Each block consists of the tissue in\nthe cassette embedded in paraffin and\nattached to the bottom of the same cassette\nfor identification.\nD. Slide: A microtome is used to generate a\nthin slice (less than the thickness of a cell \u2014\ntypically 4 microns) from each block for\nmounting on a glass slide for microscopic\nexamination.\nLevels: If 4-micron slices are cut, a 0.3-cm thick\ntissue section can yield up to 750 glass\nslides (levels). For special stains, \u201cno waste\u201d\nslices (i.e., consecutive slices) can be used. To\nevaluate more of the tissue in the block, sections\nfrom deeper levels within the tissue are\nprepared\u2014typically 20 microns apart. In order to\nevaluate all the tissue in a block (e.g., sentinel\nlymph nodes for breast cancer) levels may need\nto be prepared from sections several hundred\nmicrons apart.\nD\nGlass slides (three levels in this example)\nare produced for each block\nFigure 3\u20131.\u2002 From specimen to slide: tissue processing.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_047.png", "summary": "The histology laboratory processes tissue specimens by cutting them into thin sections, placing them in cassettes, fixing them, and embedding them in paraffin for microscopic examination.", "questions": [ "What is the purpose of grossly serially sectioning tissue?", "How many glass slides can be produced from a 0.3-cm thick tissue section?", "Why are levels prepared from sections several hundred microns apart for evaluating all the tissue in a block?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 48, "text": "30\nTHE HISTOLOGY LABORATORY\u2003 Information for the Histology Laboratory\nMultiple Small Tissue Fragments.\u2002 Fragments of tissue \nsmall enough to be lost through the holes in the cas\u00ad\nsette (0.1 to 0.2 cm) must be placed in a specimen bag or \nwrapped in lens paper. This also aids in identifying all tis\u00ad\nsue fragments for embedding.\nTissue Embedding\nAt the end of the processing step, the cassettes containing \ntissue are immersed in paraffin. The tissue is removed from \nthe cassette and placed in a metallic mold. The tissue is \noriented in an optimal fashion for sectioning in liquid par\u00ad\naffin. The paraffin is then solidified by cooling. The block \nof paraffin with the tissue within is attached to the bottom \nof the corresponding cassette for identification.\nSpecial instructions for embedding may be required for \nthe following:\nCross Sections of Tissues (e.g., Colon, Skin).\u2002 It is optimal to \nhave sections oriented to show the complete cross section \nperpendicular to the surface of the tissue. This orientation \nmay be obvious in large flat sections. Sponges placed in a \ncassette are sometimes helpful in holding tissue flat.\nSkin Shave Biopsies.\u2002 These biopsies often curl and are hard \nto orient. These specimens may be submitted intact and sec\u00ad\ntioned and oriented perpendicularly at the time of embedding.\nSmall (<0.4 cm) Punch Biopsies.\u2002 Small punch biopsies, \nespecially those with vesicular lesions, may be submitted \nintact and bisected and oriented at the time of embedding.\nSmall Lesions in Large Fragments of Tissue (e.g., a Hyper\u00ad\nplastic Polyp in the Colon).\u2002 Very small lesions may be seen \nonly on one face of a tissue section. In such cases, one side \nof the tissue can be inked and specific instructions provided \n(e.g., \u201cembed with inked tissue surface up\u201d). Avoid red ink, \nas it may be difficult to see. Black ink is preferred.\nTubular Structures (e.g., Temporal Arteries, Vas Deferens, Fal\u00ad\nlopian Tubes).\u2002 It is preferable to submit the entire tubular \nstructure in the cassette with instructions to cut into cross \nsections before embedding. It may be difficult, or impos\u00ad\nsible, to orient multiple small fragments after processing.\nMultiple Fragments.\u2002 The fragments should be embedded \nat the same level in the block in order to obtain a represen\u00ad\ntative section of each piece on the glass slide. It is preferable \nto limit the number of fragments per cassette if it is expected \nthat only some of the fragments may be diagnostic. In some \ncases, it may be helpful to separate fragments more likely \nto be diagnostic and to submit these in a separate cassette \n(e.g., breast cancer cores with radiologic calcifications may \nbe separated from those that do not have calcifications).\nSmall Intestine Biopsies.\u2002 These biopsies may be placed on \nmesh by the endoscopist to aid in orientation. The entire \nmesh and tissue can be wrapped in paper and submitted. \nEach specimen should be placed in a separate cassette. The \nspecimen can then be oriented for embedding.\nMaking Glass Slides\nThe \u201cblock\u201d (the tissue embedded in paraffin attached to \nthe bottom of the cassette) is mounted on a microtome and \na four micron section is cut from the surface of the block. \nThe cut tissue is floated in a water bath. In some cases \nthinner or thicker sections are appropriate. The tissue sec\u00ad\ntion is then placed on a glass slide. Plain glass slides are \nappropriate for most types of stains. Slides to be used for \nimmunohistochemistry require a special adhesive surface \non the glass to keep the tissue attached during the proce\u00ad\ndure. Commercial \u201cPlus\u201d (charged) slides are often used. \n\u201cDouble plus\u201d gold slides are more adhesive, but also more \nexpensive. They should be reserved for cases in which \n\u201cPlus\u201d slides have proved inadequate. This type of slide \nmust be specifically requested on the requisition form.\nThe slides are dried in an oven for variable periods of \ntime to remove any water present. The tissue can then be \nstained and a cover slip added. When properly prepared, \nsuch slides will be of good quality for many decades.\nProblems with tissue sections on glass slides (e.g., holes, \nmicroscopic chatter, scratches) are often due to problems \nwith tissue selection and fixation prior to arrival in the his\u00ad\ntology laboratory and can be minimized by careful gross \nprocessing by the pathologist.\nINFORMATION FOR THE HISTOLOGY LABORATORY\nThe histotechnologist often requires information about a \nspecimen to optimize the embedding and staining proce\u00ad\ndures. This is most easily accomplished by keeping a list of \ncassettes submitted on each case with room for notation of the \ninformation listed below. This list can also be used to ensure \nthat all cassettes are received by the histology laboratory.\nType of Tissue\nThe type of tissue can be important in deciding how a \nspeci\u00admen should be embedded. For example, needle biop\u00ad\nsies are ideally arranged in parallel rows perpendicular to \nthe long axis of the slide. It is also helpful to indicate speci\u00ad\nmens in which problems may be encountered (e.g., if it is \npossible that small bone chips or metallic fragments may \nbe present).\nType of Fixative\nThe type of fixative should be specified if not the usual \nfixative used by the laboratory. Some fixatives (e.g., those \ncontaining mercury) require special techniques for pro\u00ad\ncessing to remove precipitates and pigments. Anaqueous \nprocessing (e.g., to demonstrate uric acid crystals) is often \naccomplished by hand and not in tissue processors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_048.png", "summary": "The page discusses the process of tissue embedding in the histology laboratory, including special instructions for various types of tissue samples.", "questions": [ "What are some special instructions for embedding cross sections of tissues?", "How should skin shave biopsies be handled during embedding?", "Why is it important to limit the number of fragments per cassette during embedding?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 49, "text": "31\nTHE HISTOLOGY LABORATORY\u2003 Identification of Tissue\nNumber of Fragments\nThe number of tissue fragments present is important to \nensure that all the tissue in the cassette is processed. This \ninformation can also sometimes be helpful in detecting \nmislabeled cassettes.\nOrientation\nAfter processing, the tissue is removed from the cassette \nand re-embedded in a paraffin block. For most speci\u00ad\nmens, the orientation within the block is not important. \nHowever, special instructions for the orientation of cer\u00ad\ntain specimens for embedding should be provided when \nnecessary. For example, some small specimens are better \nprocessed intact and sectioned by the histotechnologist \nimmediately before embedding:\n\t \u2022\t \u0007Temporal arteries\n\t \u2022\t \u0007Vas deferens\n\t \u2022\t \u0007Small skin punch biopsies (< 0.4 cm)\n\t \u2022\t \u0007Skin punch biopsies with vesicular lesions\n\t \u2022\t \u0007Skin shave biopsies\nSome tissue slices should be embedded in a way such \nthat one side is face up and is sectioned first when prepar\u00ad\ning slides:\n\t \u2022\t \u0007Small lesions within a larger piece of tissue.\n\t \u2022\t \u0007En face margins for which specific orientation is \nimportant.\nThe tissue may be inked on one side and instructions \nprovided. For example, \u201cPlease embed with the inked side \nface up.\u201d\nSmall intestine biopsies submitted on mesh can be proc\u00ad\nessed attached to the mesh. The histotechnologist can use \nthe mesh as a guide to orientation.\nNumber of Levels per Paraffin Block\nThe tissue in a paraffin block is 0.1 to 0.3 cm in thick\u00ad\nness, if it has been appropriately sliced thinly. Tens to hun\u00ad\ndreds of glass slides can potentially be prepared from this \ntissue. The first slide made is a representative section of \nthis tissue. A \u201cribbon\u201d of tissue may be made from small \nspecimens and placed on the slide. This ribbon includes \nconsecutive tissue sections and rarely reveals new informa\u00ad\ntion unless the pathologic finding is very small (e.g., viral \ninclusions). For large lesions, one slide representative of \nthe tissue present is usually adequate.\nLevels refer to sections taken at different depths through \nthe block (typically 0.02 [20 microns] to 0.2 mm apart). \nMultiple levels can be helpful in the following circum\u00ad\nstances:\nSmall lesions (less than the thickness of the block, typ\u00ad\nically 1 to 2 mm) may be present on some levels but \nnot on others or better seen on some levels. Examples \ninclude small foci of prostatic carcinoma or breast duc\u00ad\ntal proliferations associated with calcifications.\nDemonstrating the relationship of a lesion to a margin \nover a small area (e.g., a close margin on a prostectomy).\nAdditional histochemical or immunoperoxidase stud\u00ad\nies: If it is anticipated that lesions may be small (e.g., \nprostate needle biopsies or sentinel lymph nodes for \nmelanoma), intervening unstained levels may be pre\u00ad\npared when the intial H&E slides are made. In the \nmajority of cases, however, enough lesional tissue is \npresent such that additional slides can be prepared later, \nif necessary.\nEvaluation of multiple fragments of tissue: Levels can \nensure that all fragments are well represented. Many \npathologists have experienced the \u201cAtlantis phenom\u00ad\nenon\u201d \u2013 when an entirely unexpected fragment of tis\u00ad\nsue appears on a deeper level because the fragment was \nlocated deeper in the block than the other fragments. \nAlthough it is optimal to have all fragments embed\u00ad\nded in the same plane, in practice this is difficult to \nachieve.\nThe number of routinely examined levels varies for dif\u00ad\nferent organ sites and pathology departments. A reasonable \napproach is to obtain two to three levels (the first superfi\u00ad\ncial and the last approximately halfway through the tissue) \nas standard processing for small biopsies. Good commu\u00ad\nnication between the clinician taking the biopsy and the \npathologist is very helpful to guide the need for additional \nlevels if the initial slides do not correlate with the lesion \nbiopsied.\nSpecial Stains\nFor some types of small biopsies, special stains are almost \nalways helpful and may be ordered on every case (liver, \ntransbronchial, kidney, transplant kidney, bone marrow, \ntesticular, and temporal artery biopsies; Table 3-1). The \ntypes of stains ordered will vary among institutions. For \nlarge specimens it is preferable to view the H&E sections \nfirst to decide whether special stains are needed and, if so, \nto choose the optimal blocks for the performance of the \nstudies.\nIDENTIFICATION OF TISSUE\nAll efforts must be made to ensure that tissues always cor\u00ad\nrespond to the correct patient:\n\t\u2022\t \u0007Always match the number on the cassette with the num\u00ad\nber on the specimen container and the specimen requisi\u00ad\ntion form before placing tissue in a cassette.\n\t\u2022\t \u0007Provide an accurate gross description of the tissue in \neach cassette (i.e., number of fragments, color if rel\u00ad\nevant).\n\t\u2022\t \u0007Avoid consecutive numbers for similar small specimens, \nif possible.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_049.png", "summary": "The histology laboratory focuses on the identification of tissue fragments, their orientation within paraffin blocks, and the number of levels per block for optimal processing and analysis.", "questions": [ "How does the orientation of tissue fragments within paraffin blocks impact the processing and analysis of specimens?", "What are some examples of specimens that require special orientation instructions for embedding?", "Why are multiple levels per paraffin block important in certain circumstances?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 50, "text": "32\nTHE HISTOLOGY LABORATORY\u2003 Identification of Tissue\nTABLE 3\u20131.\u2003\nROUTINE STAINS AND LEVELS AND INSTRUCTIONS FOR BIOPSIES\nTYPE OF BIOPSY\nROUTINE STAINS AND LEVELS\nCOMMENTS\nBladder\n2 H&E\nBone marrow\n2 Giemsa (1L, 3L), H&E (2L)\nBreast, needle\n3 H&E\nIndicate cassette with calcifications.\nCell block\n2 H&E\nSpecial stains, if needed\nColon\n2 H&E\nPolyp\n2 H&E\nSee Part 2 for instructions\nHeart\n3 H&E\nIf a specific diagnosis is suspected (e.g., \namyloid) additional studies may be \nrequired.\nKidney\n2\u2002 \u0007H&E (1L, 5L), 1 Jones Silver (3L)\n2\u2002 \u0007PAS (2L, 6L), 1 AFOG (4L)\nIf tumor is suspected, different studies may \nbe required.\nLarynx/oropharynx\n3 H&E\nLiver, needle for liver diseases\n2 H&E (1L, 5L), 1 TRI (2L), 1 IRON (3L), 1 RETIC \n(4L)\nIf tumor is known or suspected, see below.\nLiver, needle for masses\n3 H&E, unstained levels\nHistology stains are usually not helpful \nfor tumor cases. Often helpful to order \nunstained slides up front.\nLung\nEndobronchial\n3 H&E\nSpecial stains, if needed\nTransbronchial\n3 H&E (1L, 3L, 5L), 1 MSS (6L), Gram (2L), AFB \n(4L)\nDiffuse disease or transplant cases. If granu\u00ad\nlomatous disease is probable, also order \nAFB and Gram.\n3 H&E\nTumor cases\nProstate, needle\n3 H&E (1L, 3L, 5L), 2 unstained (2L, 4L)\nUnstained slides used for IHC, if necessary\nProstate, TURP\n1 H&E\nSubmit 12 cassettes. If 1 or 2, order 2L.\nSentinel lymph nodes\nBreast\n3 H&E\nEqually spaced levels (i.e., hundreds of \nmicrons apart)\nMelanoma\n3 H&E, intervening 5 unstained levels\nUnstained slides used for S100 and MART-1, \nif necessary\nSkin*\nPunch >0.3 cm\n3 H&E\nBisect or trisect\nPunch \u22640.3 cm\n3 H&E\nSubmit entire. Lab will bisect.\nPunch with vesicle\n3 H&E\nSubmit entire. Lab will bisect.\nShave\n2 H&E\nSubmit entire. Lab will section.\nEllipse\n3 H&E\nSmall bowel\n2 H&E\nStomach\n2 H&E, alcian yellow (3L)\ncontinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_050.png", "summary": "The page provides a list of routine stains and levels for various types of biopsies, along with specific instructions for each type of biopsy.", "questions": [ "What are the routine stains and levels for a bladder biopsy?", "Why are special stains needed for certain biopsies?", "What additional studies may be required if a specific diagnosis is suspected in a heart biopsy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 51, "text": "33\nTHE HISTOLOGY LABORATORY\u2003 Extraneous Tissue (\u201cFloaters\u201d)\nIf specimens are placed into the incorrect cassette, it \nmay be impossible to correctly identify the case histologi\u00ad\ncally if the types of tissue confused are similar (e.g., two \nskin punch biopsies). The gross description of the number \nand size of fragments may sometimes help in identifying \nthe correct case number.\nIn some cases it may be necessary to use special tech\u00ad\nniques to correctly match a specimen with a patient. How\u00ad\never, these methods are costly and time-consuming and \nshould be avoided if possible. In some cases, genetic insta\u00ad\nbility of a carcinoma may make matching a tumor with a \npatient difficult.\nMethods used to identify specimens have included the \nfollowing:\n\t\u2022\t \u0007Immunoperoxidase studies for ABH blood group anti\u00ad\ngens can be performed but they require a relatively large \npiece of tissue in order to have enough blood vessels (endo\u00ad\nthelial cells and red blood cells) to evaluate. This method is \nmost useful to identify a possible mix-up between two spe\u00ad\ncific specimens (e.g., two bone marrow biopsies) if the two \npatients are known to be of different blood types. Com\u00ad\nmon fixatives do not change antigenicity, but decalcifica\u00ad\ntion can diminish immunoreactivity for H antigen.\n\t\u2022\t \u0007HLA typing using PCR can be used to identify very \nsmall tissue fragments microdissected from glass slides.\n\t\u2022\t \u0007Polymorphic microsatellite markers can be analyzed \nusing PCR and can be used to provide a definite match \n(or mismatch) between a patient and a specimen.\nThe Armed Forces DNA Identification Laboratory \n(AFDIL) can identify fixed specimens using a variety of \ntechniques (see www.afip.org for details). The following \nlist of laboratories are all ASCLD-LAB (American Society \nof Crime Laboratory Directors-Laboratory Accreditation \nBoard) accredited and should be able to provide assistance \nfor DNA testing. The American Academy of Forensic \n\u00adSciences can provide additional sources (719-636-1100 \n).1-5\n \n1.\t \u0007ReliaGene Technologies, Inc.\nNew Orleans, LA \u2013 nucDNA/mtDNA/Ys\nSudhir K. Sinha \u2013 1-800-256-4106, \n \n2.\t \u0007Orchid Cellmark\nGermantown, MD \u2013 nucDNA/Ys Germantown, \nMD: 1-800-USA-LABS\nNashville, TN \u2013 nucDNA only Nashville, TN \n1-888-256-6383\nDallas, TX \u2013 nucDNA/mtDNA Dallas, TX: \n1-800-USA-LABS\n\n \n3.\t \u0007Mitotyping Technologies, LLC\nState College, PA \u2013 mtDNA typing only\nDr. Terry Melton \u2013 814-861-0676, \n \n4.\t \u0007The Bode Technology Group, Inc.\nSpringfield, VA \u2013 nucDNA/mtDNA\nRandy Nagy \u2013 703-644-1200, \n \n5.\t \u0007Serological Research Institute\nRichmond, CA \u2013 nucDNA/mtDNA/Ys\n510-223-SERI, \n \n6.\t \u0007National Medical Services\nWillow Grove, PA \u2013 nucDNA/Ys\n(800) 522-6671, \n \n7.\t \u0007Identigene\nHouston, TX \u2013 nucDNA/mtDNA/Ys\nVictor Alpizar \u2013 1-800-DNA-TYPE, http://www.id\nentigene.com.\n \n8.\t \u0007Laboratory Corporation of American (Labcorp)\nResearch Triangle Park, NC \u2013 nucDNA/mtDNA/\nYs\n1-800-533-0567 Department 6, \nEXTRANEOUS TISSUE (\u201cFLOATERS\u201d)\nExtraneous tissue consists of fragments of tissue that are \npresent on a slide but are derived from a different speci\u00ad\nmen. This becomes a significant problem if the extraneous \ntissue contains malignant cells, because it may be impossi\u00ad\nble to determine definitively that the tissue was not derived \nfrom the patient. Extraneous tissue may contaminate other \ntissue prior to the arrival in the pathology department, as it \nis being processed in the cutting room, from small pieces of \nTYPE OF BIOPSY\nROUTINE STAINS AND LEVELS\nCOMMENTS\nTemporal artery\n3 H&E (1L, 3L, 5L), 2 ET (2L, 4L)\nSubmit entire. Lab will cross section.\nTesticular\n2 H&E (1L, 5L), 1 PAS (2L), 1 ET (3L), 1 TRI (4L)\nVas deferens\n1 H&E\nSubmit entire. Lab will cross section.\n*Skin punches and shaves: If the clinical diagnosis is epidermal inclusion cyst, debridement, or necrotizing fasciitis, only one level is needed.\n1L, first level; 2L, second level, etc.\nNOTE: Small specimens not included in the table are not routine specimens and often do require additional levels and/or stains (e.g., needle biopsies of masses of unknown \norigin).\nTABLE 3\u20131.\u2003\nROUTINE STAINS AND LEVELS AND INSTRUCTIONS FOR BIOPSIES\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_051.png", "summary": "The page discusses the issue of extraneous tissue in the histology laboratory, potential mix-ups in specimen identification, and methods used to correctly match specimens with patients.", "questions": [ "What are some potential consequences of placing specimens into the incorrect cassette?", "How do immunoperoxidase studies for ABH blood group antigens help in identifying mix-ups between specimens?", "What are the advantages and disadvantages of using HLA typing and polymorphic microsatellite markers for specimen identification?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 52, "text": "34\nTHE HISTOLOGY LABORATORY\u2003 Extraneous Tissue (\u201cFloaters\u201d)\nloose tissue in a tissue processor (typically placental villi), \nor during slide preparation. Plasma may be added during \nthe preparation of cell blocks and may contain small frag\u00ad\nments of DNA.\nIn a large study, extraneous tissue was found on 0.6% \nof slides in a prospective study and 2.9% of slides in a ret\u00ad\nrospective study.6 Most of the extraneous tissue was intro\u00ad\nduced during preparation of the slide. In less than a third \nof the cases, the tissue was in the paraffin block. In 0.3% to \n3.1% of cases with extraneous tissue, the extraneous tissue \ncaused moderate to severe diagnostic difficulty.\nExtraneous tissue can also cause problems when micro\u00ad\ndissection and sensitive molecular techniques are used. \nSpecial microtomes, waterbaths, and cleaning procedures \nmay be required.\nExtraneous tissue should be diligently avoided by pay\u00ad\ning attention to the following:\nThe significance of extraneous tissue may range from \nthe trivial to the diagnostically dangerous. Strategies for \nidentifying tissue as extraneous include:\nThere is no standard procedure for documenting extra\u00ad\nneous tissue on a slide. Various methods used by patholo\u00ad\ngists include:\nIn exceptional cases in which it cannot be determined \nwhether important diagnostic tissue is intrinsic or extrinsic \nto a specimen, it may be necessary to type the tissue (see \n\u201cIdentification of Tissue\u201d earlier). If such methods fail to \nprovide a definitive answer, the case must be signed out \nwith extraneous tissue in the differential diagnosis. The \nclinician should be called and informed of the situation so \nthat he or she can decide whether additional biopsies are \nwarranted.\nREFERENCES\n\t1.\t \u0007Adegboyega PA, Gokhale S. Effect of decalcification on the \nimmunohistochemical expression of ABH blood group iso\u00ad\nantigens. Appl Immunohistochem Mol Morphol 11:194-197, \n2003.\n\t2.\t \u0007Bateman AC, Sage DA, Al-Talib RK, et al. Investigation of \nspecimen mislabelling in paraffin-embedded tissue using a \nrapid, allele-specific, PCR-based HLA class II typing method. \nHistopathol 28:169-174, 1996.\n\t3.\t \u0007Hunt JL. Identifying cross contaminants and specimen mix-\nups in surgical pathology. Adv Anatomic Pathol 15:211-217, \n2008.\n\t4.\t \u0007Hunt JL, Swalsky P, Sasatoni E, et al. A microdissection and \nmolecular genotyping assay to confirm the identity of tissue \nfloaters in paraffin-embedded tissue blocks. Am J Clin Pathol \n127:213-217, 2003.\n\t5.\t \u0007Ritter JH, Sutton TD, Wick MR. Use of immunostains to \nABH blood group antigens to resolve problems in identity of \ntissue specimens. Arch Pathol Lab Med 118:293-297, 1994.\n\t6.\t \u0007Gephardt GN, Zarbo RJ. Extraneous tissue in surgical \npathology. A College of American Pathologists Q-Probes \nstudy of 275 laboratories. Arch Pathol Lab Med 120:\n1009-1014, 1996.\n\t\u2022\t \u0007All dissecting tools (forceps, scissors, scalpel) should \nbe kept in a jar of water between uses. This will wash \noff small tissue fragments and avoid larger fragments \nadhering to dirty tools. Do not reuse scalpel blades \nbetween cases. Tissue often sticks to one side of a blade \n(inevitably the side one cannot see).\n\t\u2022\t \u0007The dissection area must be kept clean. After cutting \nin any case with known malignancy, one must be espe\u00ad\ncially fastidious in removing any soiled material on the \ncutting surface, gloves, or other surfaces.\n\t\u2022\t \u0007Small fragments and friable specimens should be \nwrapped in paper or placed in a bag to prevent tissue \nfragments escaping from a cassette.\n\t\u2022\t \u0007Solutions in tissue processors should be changed rou\u00ad\ntinely.\n\t\u2022\t \u0007During embedding, tools and equipment must be \ncleaned between cases.\n\t\u2022\t \u0007Water baths (used when making glass slides) should be \nkept free of extraneous tissue between specimens.\n\t\u2022\t \u0007Checking the block to see if the extra fragment is pres\u00ad\nent. If it is not, or additional recuts do not reveal the \nfragment, this is evidence that the fragment may have \nbeen introduced during slide preparation.\n\t\u2022\t \u0007Checking other cases processed the same day to deter\u00ad\nmine whether the tissue in the fragment resembles \nanother case.\n\t\u2022\t \u0007Checking for ink on the suspected extraneous tissue \nand comparing the results to the tissue from the cor\u00ad\nrect case. For example, if ink is present but the correct \nspecimen was not inked, this is evidence that the tissue \nis from a different case.\n\t\u2022\t \u0007Submitting additional tissue from the specimen to \ndetermine whether additional tissue fragments similar \nto the possible extraneous tissue are present.\n\t\u2022\t \u0007Circling the extraneous tissue and writing \u201cfloater\u201d or \nits equivalent on the glass slide.\n\t\u2022\t \u0007Making deeper levels that do not include the extrane\u00ad\nous tissue. The deeper levels become the permanent \nslides and the initial slide(s) are discarded.\n\t\u2022\t \u0007If the extraneous tissue is in the paraffin block, the tis\u00ad\nsue may be removed from the block and new slides pre\u00ad\npared. The initial slide(s) are discarded.\n\t\u2022\t \u0007Noting the presence of extraneous tissue in the pathol\u00ad\nogy report.\n\t\u2022\t \u0007Keeping a separate log book or computerized record of \nslides with extraneous tissue.\n\t\u2022\t \u0007Very obvious cases of no diagnostic importance may \nnot require documentation.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_052.png", "summary": "Extraneous tissue, also known as 'floaters,' can be found in tissue processors or during slide preparation, causing diagnostic difficulties and requiring special procedures for identification and avoidance.", "questions": [ "What are the potential consequences of extraneous tissue in pathology slides?", "What methods can be used to identify extraneous tissue?", "How can the presence of extraneous tissue impact the diagnostic process and patient care?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 53, "text": "35\n4\nThe Surgical Pathology Report: \nFrom the Glass Slide to the \nFinal Diagnosis\nAfter the specimen has been processed and the glass slides \nmade, the pathologist must render a diagnosis. Numer\u00ad\nous large, multi-volume, multi-authored pathology texts \nare available to aid in diagnosis. Once the interpretation \nhas been made, a surgical pathology report is issued and \nbecomes part of the patient\u2019s medical record. Pathology \nreports serve five main purposes:\n 1.\t \u0007Diagnostic and prognostic information for individ\u00ad\nual patients.\n 2.\t \u0007Information to guide treatment of individual patients.\n 3.\t \u0007Criteria for eligibility for clinical trials. Since the \nresults of these trials are used to determine the efficacy \nof treatments, the accuracy of information in the report \nwill affect not only the individual patient enrolled in a \ntrial, but many other patients as well.\n 4.\t \u0007Information for clinical databases to be used in both \nclinical and basic research. The content of pathology \nreports is important for the understanding of disease \nprocesses as well as new investigations into the treat\u00ad\nment and pathogenesis of disease.\n 5.\t \u0007Quality assurance. The contents of pathology reports \nmay be reviewed to evaluate various indicators of qual\u00ad\nity care for pathology departments and for the overall \ncare of patients.\nELEMENTS OF A SURGICAL PATHOLOGY REPORT\n\t\u2022\t \u0007Institution identifiers: Name, address, telephone num\u00ad\nber, fax number\n\t\u2022\t \u0007Patient identifiers: Name, date of birth, hospital identi\u00ad\nfication number, gender\n\t\u2022\t \u0007Name of the pathologist(s) responsible for signing the \nreport and/or responsible for other elements of the \nreport (e.g., OR consultation, gross examination)\n\t\u2022\t \u0007Name of the clinician(s) submitting the specimen as well \nas other clinicians caring for the patient\n\t\u2022\t \u0007Specimen number: A unique specimen identification \nnumber assigned by the pathology department. This \nnumber should be located prominently at the top por\u00ad\ntion of each page of the report for easy \u00adidentification.\n\t\u2022\t \u0007Date of procedure and date specimen was received\n\t\u2022\t \u0007Date the report was issued\n\t\u2022\t \u0007Clinical history\n\t\u2022\t \u0007Type of specimen submitted, including a list of all speci\u00ad\nmens submitted\n\t\u2022\t \u0007OR consultation reports: The specimen examined, type \nof examination (gross examination, frozen section, cyto\u00ad\nlogic preparations), and intraoperative diagnosis are \nincluded. The pathologist responsible for rendering the \ndiagnosis is identified.\n\t\u2022\t \u0007Gross description: Include the disposition of all \u00adtissue \n(e.g., saved for electron microscopy [EM], frozen, \nresearch, etc.) and any special techniques used (e.g., \ndecalcification, inking of margins). Specify whether all \nor only a part of the specimen has been submitted.\n\t\u2022\t \u0007Other materials received such as specimen radiographs \n(describe what they show) or peripheral blood smears\n\t\u2022\t \u0007Description of tissue submitted for microscopic \u00adsections: \nType of tissue, number of cassettes. It is preferable that \neach block of tissue has a unique identifier.\n\t\u2022\t \u0007Microscopic description: Provided when appropri\u00ad\nate (e.g., unusual tumors or diseases). A microscopic \ndescription is not necessary for every specimen if impor\u00ad\ntant information is provided in the diagnosis.\n\t\u2022\t \u0007Specimen heading: The organ, site, and type of pro\u00ad\ncedure are specified. In some cases, specific labeling \n\u00adprovided by the surgeon may be required to identify the \nspecimen (e.g., a specimen labeled \u201cclosest margin\u201d).\n\t\u2022\t \u0007Diagnosis: The type or types of pathologic pro\u00ad\ncesses present. Important information from the gross \n\u00adexamination (e.g., tumor size) is included. The results \nof special studies are discussed. Discrepancies between \nintraoperative diagnosis and the final diagnosis are \n\u00addiscussed.\n\t\u2022\t \u0007A statement that the pathologist has examined gross \nand/or microscopic tissues before rendering the diagno\u00ad\nsis may be required for billing purposes.\n\t\u2022\t \u0007Consultations: Intradepartmental consultations can be \ndocumented by including the names of the consult\u00ad\ning pathologists. External consultations initiated by", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_053.png", "summary": "The surgical pathology report is a crucial document that provides diagnostic and prognostic information for individual patients, guides treatment, determines eligibility for clinical trials, contributes to clinical databases for research, and ensures quality assurance.", "questions": [ "How are pathology reports used to guide treatment for individual patients?", "What role do pathology reports play in determining eligibility for clinical trials?", "How do pathology reports contribute to quality assurance in pathology departments?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 54, "text": "THE SURGICAL PATHOLOGY REPORT\u2003 Diagnostic Headings\n36\nthe pathologist can be documented by incorporating \nthe consultant\u2019s report. The incorporation of external \nconsultations not initiated by the pathologist may be \nincluded at his or her discretion.\n\t\u2022\t \u0007Checklists for malignant tumors: Includes all relevant \ninformation for prognosis and staging. Used in addition \nto, or sometimes in lieu of, a diagnosis in some insti\u00ad\ntutions. The CAP (see www.cap.org) and the ADASP \n(see www.adasp.org) have published suggested synoptic \nreporting forms (see Part 2).\n\t\u2022\t \u0007AJCC classification: For tumor resections, the patholo\u00ad\ngist should provide sufficient information for T and N \nclassifications to be made. The actual T and N catego\u00ad\nries should be provided, when possible. Staging is not \nrequired, as this often requires additional information \n(e.g., the results of the metastatic work-up) not available \nto the pathologist.\n\t\u2022\t \u0007Recommendations for further follow-up or treatment: \nThese are usually best discussed directly with the clini\u00ad\ncian. When incorporated into the report, they should, in \ngeneral, be phrased as suggestions.\n\t\u2022\t \u0007Clinically significant unsuspected findings: It is prefer\u00ad\nable that such findings be conveyed immediately to the \nclinician(s) with a phone call. The time and date of the \ncall should be documented in the report. (see \u201cGuide\u00ad\nlines for Communication of Urgent Results\u201d).\n\t\u2022\t \u0007Amended reports: An amended report should be clearly \nindicated, preferably on the first page of the report, and \nthe date of the amendment given. It should be stated \nwhether the new information is different from the origi\u00ad\nnal information. The information provided in previous \nreports should be included with an explanation for the \nchange in the report.\n\t\u2022\t \u0007A list of prior surgical and cytologic specimens from the \nsame institution is helpful to include. It is useful to have \navailable a list of all prior diagnoses pertaining on a patient \nat the time of final sign-out to aid in the interpretation of \nthe current specimen and to avoid possible errors.\nThis list incorporates the recommendations of the \nADASP.1\nDIAGNOSTIC HEADINGS\nHeadings need to be as accurate and as informative as \n\u00adpossible and should include:\nUsually the headings are based on the label used for the \nspecimen or the gross recognition of the type of specimen. \nIf the type of specimen or type of surgery cannot be \n\u00adrecognized, it is generally preferable to discuss the case with \nthe surgeon, as the type of specimen can affect the method \nof processing it as well as how the specimen should be billed.\nSpecimen headings using \u201cSpecimen labeled\u201d often do \nnot provide useful information on the type of specimen \nexamined. For example, [Specimen labeled \u201cRight Lung\u201d] \ncould be anything from a transbronchial biopsy to an \nextrapleural pneumonectomy. This type of heading forces \nthe reader to search for this important information in the \ngross description.\nExamples of appropriate headings are given in Table 4-1.\nNever use a label that may be misleading (e.g., one which \nmay imply an incorrect diagnosis) because someone \u00adreading \nthe report may easily mistake a heading for a \u00addiagnosis.\nWeights should be included when relevant for evalua\u00ad\ntion or for billing purposes (e.g., spleen, breast reduction \nmammoplasty, myomectomy).\nAll separately submitted specimens are given separate \ndiagnoses with separate headings. If multiple specimens \nhave the same name and it is appropriate to combine two \nor more separately submitted specimens (i.e., they all \nclearly represent the same type of tissue from the same site \nand separating the specimens does not provide additional \ninformation), this may be indicated in the heading: \u201cMes\u00ad\nenteric mass (two specimens).\u201d\nTABLE 4\u20131.\u2003\n\u0007EXAMPLES OF APPROPRIATE \nDIAGNOSTIC HEADINGS\nColon resections\nRight colectomy (ascending colon and \ncecum [44 cm], terminal ileum [4 cm], \nand appendix):\nSigmoid colon (30 cm), resection:\nAbdominoperineal resection (rectum \n[35 cm] and anus [15 cm]):\nBreast resections\nLeft breast, modified radical mastectomy \nand axillary dissection:\nRight breast, simple mastectomy:\nLeft breast, re-excision:\nRight breast excisional biopsy, wire \n\u00adlocalization for calcifications:\nLeft breast, stereotactic 14 gauge core \nneedle biopsies for an irregular mass:\nLung resections\nLeft lung, pneumonectomy:\nRight lower lobe of lung, lobectomy:\nRight upper lobe of lung, wedge \n\u00adresection:\nProstate\nProstate, radical prostatectomy (42 gms):\nProstate, suprapubic prostatectomy \n(150 gms):\nProstate, transurethral resection (33 gms):\nSkin\nSkin of chest, excision:\nSkin of right leg, 3 mm punch biopsy:\nSkin of face, shave biopsy:\n \t \u2022\t \u0007Organ or tissue\n\t\n\u2022\t \u0007Site\n\t\n\u2022\t \u0007Surgical procedure\n\t\n\u2022\t \u0007Relevant gross descriptors (e.g., length of colon, \nweight of the spleen)\n\t\n\u2022\t \u0007Specific designations given by the clinician (e.g., \n\u00ad\u201ctissue closest to the margin\u201d)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_054.png", "summary": "The surgical pathology report should include checklists for malignant tumors, AJCC classification for tumor resections, recommendations for further follow-up or treatment, clinically significant unsuspected findings, amended reports, and a list of prior surgical and cytologic specimens.", "questions": [ "How should recommendations for further follow-up or treatment be phrased in the report?", "What information should be included in an amended report?", "Why is it important to include a list of prior surgical and cytologic specimens from the same institution?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 55, "text": "37\nTHE SURGICAL PATHOLOGY REPORT\u2003 Modification of an Existing Report\nIf frozen sections were performed, they must be incor\u00ad\nporated into the heading for billing purposes: \u201cInguinal \nlymph node (including frozen section A and touch prepa\u00ad\nration A).\u201d\nSTANDARDIZED DIAGNOSIS FORMS\nCAP (www.cap.org) and ADASP (www.adasp.org) have \ndeveloped standardized reporting forms for most common \ntumors.\nAdvantages of a standardized synoptic (synoptic is \nGreek for an overall view of things, a summary or synop\u00ad\nsis) report include:\n\t\u2022\t \u0007Uniform diagnostic terms, criteria, and style are estab\u00ad\nlished for a department or group of pathologists. Addi\u00ad\ntional standard criteria can be included in each report \n(e.g., the basis of grading systems, definitions, etc.).\n\t\u2022\t \u0007Checklists ensure that important diagnostic/prognostic \nfeatures are always included. Some data elements are \nnow required for accreditation as a cancer center. Addi\u00ad\ntional information for AJCC classification and/or grad\u00ad\ning can be incorporated into a standard form for easy \naccess by the pathologist.\n\t\u2022\t \u0007Facilitates preparing the report by staff and residents.\n\t\u2022\t \u0007Facilitates typing of reports by secretaries as mnemon\u00ad\nics can be used for many sentences or phrases. This can \nshorten turnaround time by providing finished reports \nearlier.\n\t\u2022\t \u0007Important information is easily accessible for clinicians.\n\t\u2022\t \u0007Information is readily incorporated into computerized \ndatabases.\n\t\u2022\t \u0007Teaching tool \u2013 provides important diagnostic features \nof most common diagnoses for each organ system.\nHowever, unusual or complicated specimens should \nnot be squeezed into a standard format but must be \ngiven an appropriate individualized pathology report. \nAny type of standardized report needs to be flex\u00ad\nible enough to allow additional comments for unusual \n\u00adfindings.\nDisadvantages of synoptic reporting include -\n\t\u2022\t \u0007May adversely affect resident training by stifling inde\u00ad\npendent thinking. Residents may become dependent on \nchecklists and templates. Not all pathology findings can \nbe included in multiple-choice formats.\n\t\u2022\t \u0007Pathologists may not be able to reach a consensus on \nthe types of information to be provided or on specific \ndiagnostic criteria.\n\t\u2022\t \u0007Errors may be more difficult to detect with templates as \ncomplete sentences or parameters may be changed by \ntypographical errors.\nHowever, in most cases it should be possible to develop \na system with sufficient standardization to provide impor\u00ad\ntant information for clinical management but with enough \nflexibility to provide additional information for unusual \ncases. The use of checklists has been shown to significantly \nimprove the incorporation of important information into \npathology reports.2\nPart Two includes sign-out checklists for all major \ntumor types and resections that can be the basis for \nsynoptic reporting. The lists are based on published \nrecommendations, departmental recommendations by \nsubspecialists, and the local needs of surgeons and oncol\u00ad\nogists. The lists will need to be modified for the specific \nrequirements of each institution and will require modifi\u00ad\ncation over time.\nTURNAROUND TIME\nFor optimal patient care, surgical cases need to be signed \nout in a timely fashion and clinicians need to be kept \ninformed of the status of cases. Standards have been devel\u00ad\noped for different types of specimens.3\n\t\u2022\t \u0007Routine cases: two working days\n\t\u2022\t \u0007Complex cases: additional time allowed if special proce\u00ad\ndures are required\nTime is measured from the time of specimen accession \n(day 0) to the day the report is signed by the pathologist. In \nthe report cited above, 95% of routine biopsy cases and 91% \nof complex cases were signed out within two working days.\nMODIFICATION OF AN EXISTING REPORT\nAddendums\nOccasionally nondiagnostic errors or omissions are present \nin reports due to typographical mistakes, specimen mis\u00ad\nidentification, the absence of important clinical informa\u00ad\ntion, or additional studies that are to be performed. In the \nmajority of cases, changes and additional information can \nbe reported in an addendum. If the changes are significant, \nthe clinician must be notified. Pathologists must be aware \nthat because clinicians do not know that an addendum has \nbeen issued, many addenda are never seen or may be over\u00ad\nlooked by clinicians. If important information is pending, \nit is preferable in most instances to wait for the informa\u00ad\ntion to incorporate it into the main report (see below). If \nthat would create a substantial delay, it is helpful to indi\u00ad\ncate in the initial report that an addendum will be added \nin the future to alert clinicians to its existence. When an \naddendum is added, the original report is not unsigned and \nremains unchanged.\nAmended Reports \u2013 Revised Diagnosis\nIf there is a major error in a pathology report, it should be \nunsigned, corrected, and resigned. This is an \u201camended\u201d \nreport. The most common reasons for amending a report \nare the following:\n 1.\t \u0007Additional special stains or other studies are performed\n 2.\t \u0007An intradepartmental consultation occurs", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_055.png", "summary": "The page discusses the importance of standardized synoptic reporting in surgical pathology, highlighting its advantages and disadvantages.", "questions": [ "How can standardized synoptic reporting benefit pathologists and clinicians?", "What are some potential drawbacks of using standardized reporting forms?", "How can pathologists ensure that important information is still included in reports for unusual or complicated specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 56, "text": "38\nTHE SURGICAL PATHOLOGY REPORT\u2003 Guidelines for Communication of Urgent Results (\u201cCritical Values\u201d)\n 3.\t \u0007An extradepartmental review is requested by the \npathologist\n 4.\t \u0007Additional clinical information is provided\n 5.\t \u0007A review is requested by a clinician, often in the context \nof a tumor board\nAmending a report should be avoided due to the \npotential harm an erroneous diagnosis can cause. The \nfirst three reasons for amended reports can be avoided \nby delaying sign-out until all intra- and extradepart\u00ad\nmental consultations as well as special studies are \ncompleted.\nClinicians play an important role in detecting errors due \nto misidentification of patients or due to the failure to pro\u00ad\nvide sufficient clinical information for optimal interpreta\u00ad\ntion. Reviews at conferences are helpful in detecting errors \nin misinterpretation.\nUNSIGNING AND CHANGING A REPORT \nSHOULD ONLY BE USED IN VERY RARE CASES \nIN WHICH FAILURE TO CHANGE THE ORIGI\u00ad\nNAL REPORT COULD RESULT IN SIGNIFICANT \nHARM TO THE PATIENT. In general, fewer than \n1% of reports should require amending. The number of \namended/revised reports is used as a quality assurance \n(QA) measure and information on these reports is col\u00ad\nlected and reported by pathology departments. Therefore, \nthis option should only be used when absolutely neces\u00ad\nsary.4,5 The vast majority of corrections and additions are \nbest performed using an addendum.\nIf an original report is unsigned and resigned, the fol\u00ad\nlowing must happen because the original report is part of \nthe patient\u2019s medical record:\n\t\u2022\t \u0007The original report must be retained and/or all changes \nmust be carefully documented along with the date the \nchanges were made within the report. If the revised \n\u00addiagnosis replaces the original diagnosis in the main \nbody of the report, the original report should be retained \nbelow with a heading to the effect \u201cThe \u00adfollowing origi\u00ad\nnal diagnosis is retained for documentation purposes \nonly.\u201d\n\t\u2022\t \u0007The clinicians caring for the patient must be con\u00ad\ntacted directly by telephone and informed of the \nchanges. Any information important enough to war\u00ad\nrant unsigning a report would be considered a \u201ccritical \nvalue.\u201d\nChange in Patient Identification\nIn the survey sited above, in 0.39 per 1000 reports there \nwas a change in patient identification.4 Unfortunately, if \nthe specimen has been mislabeled, most such errors are \nundetectable by the pathology laboratory. Original reports \nshould be maintained for documentation purposes but \n\u00adcorrections must be made. In rare cases, it may be neces\u00ad\nsary to use tissue identification techniques to determine \nthe source of the specimen (see in Chapter 3, \u201cIdentifica\u00ad\ntion of Tissue\u201d).\nGUIDELINES FOR COMMUNICATION OF URGENT \nRESULTS (\u201cCRITICAL VALUES\u201d)\nAll pathology reports contain important information and \nit is expected that all routinely issued reports will be read \nin a timely fashion by physicians caring for a patient. In \ncertain urgent cases, it is necessary to communicate a \nresult directly to a licensed caregiver (MD, nurse practi\u00ad\ntioner, licensed nurse, or PA) as supported by guidelines \nfrom TJC and CAP. This should be by a telephone call \nfrom a staff pathologist or resident, or their designee, \nto the treating clinician (or other licensed designee who \ncan take action on the result). If the clinician cannot be \nreached by telephone or page, their office should be called \nwith a request that he or she contact the pathologist. If this \nis not possible, then an email may be sent with a request \nfor verification of receipt. If there is a covering physician \nfor the patient, this person should be contacted in the same \nmanner.\nThe communication must occur within six hours of the \ndiscovery of the result. All such communication is docu\u00ad\nmented in the pathology report.6\nExamples of critical values include:\n\t\u2022\t \u0007Unexpected or discrepant findings:\n\t \u2022\t \u0007Significant disagreement between frozen section and \nfinal diagnosis.\n\t \u2022\t \u0007Significant disagreement between immediate interpre\u00ad\ntation and final fine needle aspiration (FNA) diagnosis.\n\t \u2022\t \u0007Unexpected malignancy (as determined by the clinical \ninformation provided).\n\t \u2022\t \u0007Any other clinically significant and time-sensitive \nfinding that was unsuspected (as determined by the \nclinical information provided). This would include \nunsuspected infectious processes.\n\t \u2022\t \u0007Significant disagreement and/or change between \n\u00adprimary \npathologist \nand \noutside \npathologist \nconsultation (at either the original or consulting insti\u00ad\ntution).\n\t \u2022\t \u0007Significant information reported in an addendum \nnot expected by the clinician. Clinicians do not know \nwhen an addendum is issued so it is not uncommon \nfor this information to be overlooked unless it is \n\u00adspecifically brought to his or her attention.\n\t\u2022\t \u0007Cases that have immediate clinical consequences:\n\t \u2022\t \u0007Crescents in >50% of glomeruli in a kidney biopsy.\n\t \u2022\t \u0007Leukocytoclastic vasculitis.\n\t \u2022\t \u0007Uterine contents without villi or trophoblast in the \nsetting of suspected pregnancy.\n\t \u2022\t \u0007Fat in an endometrial curettage.\n\t \u2022\t \u0007Mesothelial cells in a heart biopsy.\n\t \u2022\t \u0007Fat in colonic endoscopic polypectomies.\n\t \u2022\t \u0007Transplant rejection.\n\t \u2022\t \u0007Malignancy in superior vena cava syndrome.\n\t \u2022\t \u0007Neoplasms causing paralysis.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_056.png", "summary": "The page discusses the importance of avoiding amending surgical pathology reports unless absolutely necessary, as errors can lead to harm. It also emphasizes the need for proper communication of critical values and guidelines for handling changes in patient identification.", "questions": [ "What are the potential consequences of amending a surgical pathology report?", "How are errors in patient identification typically addressed in the pathology laboratory?", "What are the guidelines for communicating urgent results or critical values in pathology reports?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 57, "text": "39\nTHE SURGICAL PATHOLOGY REPORT\u2003 Guidelines for Communication of Urgent Results (\u201cCritical Values\u201d)\n\t\u2022\t \u0007Infections:\n\t \u2022\t \u0007Bacteria or fungi in cerebrospinal fluid (CSF) cytology \nin all patients.\n\t \u2022\t \u0007Pneumocystis, fungi, or viral cytopathic changes in \nbronchoalveolar lavage, bronchial washings, or brush\u00ad\ning cytology specimens in all patients.\n\t \u2022\t \u0007Acid-fast bacilli in all patients.\n\t \u2022\t \u0007Fungi in FNA from immunocompromised patients.\n\t \u2022\t \u0007Bacteria in a heart valve or bone marrow.\n\t \u2022\t \u0007Herpes in PAP smears of near-term pregnant patients.\n\t \u2022\t \u0007Candida in placental membranes.\n\t \u2022\t \u0007Any invasive organism in any specimen from immu\u00ad\nnocompromised patients.\nREFERENCES\n\t1.\t \u0007ADASP. Standardization of the surgical pathology report. Am \nJ Surg Pathol 16:84-86, 1992.\n\t2.\t \u0007Zarbo RJ. Interinstitutional assessment of colorectal carci\u00ad\nnoma surgical pathology report adequacy. Arch Pathol Lab \nMed 116:1113-1119, 1992.\n\t3.\t \u0007Zarbo RJ, Gephardt GN, Howanitz PJ. Intralaboratory time\u00ad\nliness of surgical pathology reports. Arch Pathol Lab Med \n120:234-244, 1996.\n\t4.\t \u0007Nakhleh RE, Zarbo RJ. Amended reports in surgical pathol\u00ad\nogy and implications for diagnostic error detection and avoid\u00ad\nance. A College of American Pathologists Q-Probes Study of \n1,667,547 accessioned cases in 359 laboratories. Arch Pathol \nLab Med 122:303-309, 1998.\n\t5.\t \u0007Meier FA, Zarbo RJ, Varney RC, et al. Amended reports: \ndevelopment and validation of a taxonomy of defects. Am J \nClin Pathol 130:238-246, 2008.\n\t6.\t \u0007ADASP critical diagnoses (critical values) in anatomic pathol\u00ad\nogy. Hum Pathol 37:982-984, 2006 and Am J Surg Pathol \n30:897-899, 2006.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_057.png", "summary": "The surgical pathology report provides guidelines for communication of urgent results, known as 'Critical Values,' for various infections and organisms in different specimen types.", "questions": [ "What are some examples of Critical Values for infections in different specimen types?", "Why is it important to communicate urgent results for infections in immunocompromised patients?", "How do the references listed contribute to the guidelines for communication of Critical Values?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 58, "text": "40\n5\nConsultation Reports\nTYPES OF CONSULTATIONS\nPathology consultations occur when slides are shown to a \nsecond pathologist and a second interpretation of the slides \nis documented. There are many types of consultations and \neach has different features. Types of consultations include:\nThe Association of Directors of Anatomic and Surgical \nPathology has issued guidelines for consultations.1\nINTRA-INSTITUTIONAL (IN-HOUSE) CONSULTATIONS\nPathologists within an institution or group often show \nslides to each other if the case is difficult or unusual. Some \npathology groups have mandated review of certain types of \ncases, and such review can reduce errors.2 Daily or weekly \n\u201cdifficult case\u201d conferences are used for this purpose.\nThe typical legal standard of care for pathologists is \nthat the pathologist acted as another pathologist would \nin a similar situation. Thus, it is important to document \nthat the case was shown to another pathologist should a \nlegal issue arise. This can be accomplished by having two \npathologists sign the report, by a note in the report (e.g., \n\u201cThis case was shown to Dr. Smith who concurs with the \nabove diagnosis.\u201d) or as a record of departmental confer\u00ad\nences. If the second pathologist only reviewed selected \nslides, this should be noted.\nSPECIALIST CONSULTATIONS\nFor difficult and unusual cases, the opinion of a specialist \nmay be requested. A survey showed that 0.5% of cases, on \naverage, are sent for extradepartmental review.3 Usually, \nthis type of consultation is initiated by the original pathol\u00ad\nogist. The referring pathologist should provide:\n\t\u2022\t \u0007Selected representative slides. Recuts that the spe\u00ad\ncialist can keep for her or his files are often preferable. \nSpecial stains or immunoperoxidase studies should be \nincluded if they are important for diagnosis. Blocks or \nunstained (coated) slides should be included if it is antic\u00ad\nipated that additional studies will be needed.\n\t\u2022\t \u0007A letter explaining the reason for the consultation and \nthe difficulty as perceived by the referring pathologist. This \nletter should also contain any specific issues that need to be \naddressed. In turn, the consultant should directly address \nthese issues by direct communication with the referring \npathologist, in a letter, or in the consultation report.\n\t\u2022\t \u0007Clinical and demographic information on the patient. \nThis may include other reports as appropriate (e.g., \nradiologic reports of bone lesions) or operative notes.\n\t\u2022\t \u0007The pathology report including the gross descrip\u00ad\ntion and a description of the site of origin of each \nof the slides. The report need not be signed out if it is \nbeing held for the opinion of the consultant. Pathology \nreports on other specimens should be included if rel\u00ad\nevant to the consultation.\n\t\u2022\t \u0007The fax number, telephone number, and address of \nthe requesting pathologist in order for the consultant to \ncommunicate the results in a timely fashion.\n\t\u2022\t \u0007Reports of prior consultations on the same case. If \nsimultaneous consultations with other specialists have \nbeen requested it is helpful to include this information.\n\t\u2022\t \u0007Billing information. The cost of the consultation is \ngenerally borne by the referring pathologist or his or \nher pathology group.\nThe specialist will generate a report and communicate the \nfindings to the referring pathologist. Any irreplaceable mate\u00ad\nrials (blocks, cytology slides, slides of lesions that are not seen \non other levels) are returned to the original pathologist.\nThe results of the consultation should be incorporated \ninto the original pathology report and communicated to the \npatient\u2019s physicians, if the referring pathologist agrees with \nthe diagnosis. In unusual cases, if the referring pathologist \ndoes not agree with the diagnosis, it may be appropriate \nto seek consultation with other specialists. The referring \npathologist may be held legally liable for errors made by \nthe specialist and is responsible for the final diagnosis.\nIt is generally acknowledged that a specialist may use \nconsultation cases as part of a larger series of cases for pub\u00ad\nlication with acknowledgement of referring \u00adpathologists \nif possible. Specific case reports should be negotiated \nbetween the original pathologist and the specialist.\n\t\n\u2022\t \u0007Intra-institutional consultations\n\t\n\u2022\t \u0007Specialist consultations\n\t\n\u2022\t \u0007Consultations for special studies\n\t\n\u2022\t \u0007Institutional consultations\n\t\n\u2022\t \u0007Medicolegal consultations\n\t\n\u2022\t \u0007Review of pathology slides or blocks for treatment \nprotocols or research", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_058.png", "summary": "Pathology consultations involve showing slides to a second pathologist for a second interpretation. There are different types of consultations, including intra-institutional and specialist consultations.", "questions": [ "What are the guidelines issued by the Association of Directors of Anatomic and Surgical Pathology for consultations?", "How can pathologists within an institution or group reduce errors through consultations?", "What information should be provided when requesting a specialist consultation for a difficult case?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 59, "text": "CONSULTATION REPORTS\u2003 Institutional Consultations\n41\nInformation should not be withheld from the specialist. \nCases involved in legal actions should be treated as legal \nconsultations.\nIn some cases, a clinician or patient may initiate a sec\u00ad\nond review by a specialist. In such cases the results are, \nin general, conveyed by the specialist to the patient\u2019s \nphysician. In unusual cases, the patient may be contacted \ndirectly with the results. The results of the consultation \nshould always be sent to the original pathologist as well. \nThe cost is usually borne by the patient.\nCONSULTATIONS FOR SPECIAL STUDIES\nSpecial studies (most commonly immunoperoxidase \n\u00adstudies but also electron microscopy or DNA analy\u00ad\nsis) are sometimes required for the evaluation of certain \ncases. Appropriate materials may be sent either to other \n\u00adpathology departments or to commercial laboratories that \noffer these services. In order to obtain the maximum ben\u00ad\nefit from such consultations the following should be sent:\n\t \u2022\t \u0007Appropriate materials for the study requested (e.g., \nparaffin block[s] containing the lesion, fresh tissue, \ntissue fixed for EM).\n\t \u2022\t \u0007The diagnosis or differential diagnosis.\n\t \u2022\t \u0007The specific studies requested.\n\t \u2022\t \u0007Demographic information on the patient for identification.\n\t \u2022\t \u0007Billing information.\nA report giving the results of the special studies is gen\u00ad\nerated. The results should be incorporated into the origi\u00ad\nnal pathology report with an interpretation.\nIf an opinion on the diagnosis is also requested, the con\u00ad\nsultation is processed as for a specialist consultation.\nINSTITUTIONAL CONSULTATIONS\nInstitutions often require pathology review for all patients \nseeking a second opinion or treatment and this practice is \nrecommended by the ADASP. These consultations pro\u00ad\nvide the following:\n\t\u2022\t \u0007Confirmation of diagnoses prior to definitive treatment \n(e.g., chemotherapy or surgery).\n\t\u2022\t \u0007Provision of additional information that may be used at \nthe second institution, but not routinely provided in all \npathology reports (e.g., lymphovascular invasion associ\u00ad\nated with breast cancer).\n\t\u2022\t \u0007Correlation with subsequent pathologic lesions if the patient \nundergoes surgery at the second institution (e.g., evaluation \nof a re-excision for residual carcinoma after treatment).\nMany studies have analyzed the results of institutional \nconsultations with the following general conclusions:\n\t\u2022\t \u0007Pathology diagnosis is very accurate and in greater than \n90% of cases the original diagnosis is confirmed. These \nreports may be used as part of the Joint Commission-\nrequired quality assurance program.\n\t\u2022\t \u0007In approximately 5% of cases, a significant change in \ndiagnosis results in a change in patient treatment. The \nADASP has suggested that an acceptable threshold for \nsignificant disagreement is 2%.3\n\t\u2022\t \u0007In a greater number of cases, additional information is \nprovided by the second review and this information is \nuseful to help guide treatment at the second institution.\n\t\u2022\t \u0007When there is a disagreement, in most studies, the con\u00ad\nsultant\u2019s diagnosis is correct more often than the origi\u00ad\nnal diagnosis. In many cases, the discrepancy is due to \ndifferences in criteria or interpretive opinions for lesions \nwith known high degrees of interobserver disagreement. \nIn some cases, the original diagnosis will prove to be \ncorrect and the pathologist may choose to seek an opin\u00ad\nion from another consultant.\n\t\u2022\t \u0007The cost of reviewing pathology slides is minimal com\u00ad\npared to the cost of treatment or the potential morbidity \nof inappropriate treatment. Therefore, a second review \nis generally recommended to improve patient care and \nreduce medical costs.\nIf a consultation results in a significant change in inter\u00ad\npretation, it is recommended that the reviewing patholo\u00ad\ngist do the following:\n\t\u2022\t \u0007Contact the original pathologist to inform him or her in \nthe change in diagnosis. Both pathologists should try to \nresolve any differences that might be due to the review \nof different slides or levels, the performance of addi\u00ad\ntional special studies, or knowledge of additional clinical \ninformation. The second pathologist may choose to seek \nadditional opinions.\n\t\u2022\t \u0007Contact the treating physicians to ensure the patient \nreceives appropriate treatment.\n\t\u2022\t \u0007Provide a rationale for the change in diagnosis in the \nreport, when possible. For example, rather than report\u00ad\ning on lymph nodes previously diagnosed as free of \nmetastases as \u201cMetastatic carcinoma present in a lymph \nnode\u201d it is more helpful and informative to report the \nfindings as \u201cMetastatic carcinoma present in a lymph \nnode. The metastasis measures much less than 0.1 cm in \nsize and is seen only in the deeper level prepared for the \nconsultation; it is not seen in the original slide.\u201d If the \ndiscrepancy is in the interpretation of a difficult lesion, \nthis can also be explained (e.g., \u201cThe differential diagno\u00ad\nsis includes carcinoma in situ and high grade dysplasia, \nhowever the former diagnosis is favored due to the fol\u00ad\nlowing\u2026\u201d).\nThe following material should be sent for an interinsti\u00ad\ntutional consultation:\n\t\u2022\t \u0007Slides relevant to the consultation (see below). It is pref\u00ad\nerable that these slides be reviewed before being sent, \nparticularly if recuts are performed, to ensure that the \noriginal findings are present and that there are no new \nadditional findings.\n\t\u2022\t \u0007The original pathology report.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_059.png", "summary": "Consultation reports in pathology involve sharing information with specialists, legal considerations, and the need for special studies. Institutional consultations provide confirmation of diagnoses and additional information for patient treatment.", "questions": [ "What are the key considerations when initiating a second review by a specialist?", "How are the results of consultations typically conveyed to the patient's physician?", "What are the general conclusions drawn from studies analyzing institutional consultations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 60, "text": "CONSULTATION REPORTS\u2003 Legal Consultations\n42\n\t\u2022\t \u0007The reports of other consultations.\n\t\u2022\t \u0007A letter stating what materials are being sent and request\u00ad\ning return of the materials after consultation. This letter \nincludes the address and phone number of the institu\u00ad\ntion to facilitate the return of materials.\n\t\u2022\t \u0007Other reports, if relevant (e.g., hormone receptor stud\u00ad\nies for breast carcinomas if not included in the original \npathology report).\nBlocks need not be sent unless specifically requested. \nIn general, blocks and slides should not be sent together \nto avoid the possibility of loss of all of a patient\u2019s materi\u00ad\nals. If the second institution requests block(s) to perform \nspecial studies, only selected blocks should be sent or addi\u00ad\ntional glass slides can be prepared and sent. If the lesion is \nsmall (i.e., seen in only one block) it may be preferable to \nhave the original slides returned before the block is sent \nor to send unstained slides. In general, recuts and/or spe\u00ad\ncial studies performed by the consulting institution are not \nreturned to the original institution.\nIt is preferable that only slides relevant to the consulta\u00ad\ntion be sent. Due to the fact that second review is known \nto reveal errors in a small number of cases, it is impor\u00ad\ntant to focus such reviews on current medical treatment \nand not on potential medicolegal issues (see \u201cLegal Con\u00ad\nsultations\u201d). For example, review of prior prostate core \nneedle biopsies after a diagnosis of prostatic carcinoma has \nbeen rendered may reveal a small focus of atypical ducts or \ncarcinoma that had been missed. However, this is a legal \nand not a medical issue and would be better addressed as \na legal consultation. Slides that need not be sent would \ninclude:\n\t\u2022\t \u0007Prior benign biopsies (unless specifically requested).\n\t\u2022\t \u0007Prior FNAs or core needle biopsies if there has been a \nsubsequent excision with a concordant diagnosis. For \nexample, it would be appropriate to send an FNA with a \nsuspicious or malignant diagnosis if the subsequent exci\u00ad\nsion was diagnosed as benign, but not if it was diagnosed \nas malignant.\n\t\u2022\t \u0007Irrelevant specimens (e.g., a prior cholecystectomy in a \npatient with lung cancer).\n\t\u2022\t \u0007Irrelevant slides (e.g., slides that would not have findings \nthat would change current evaluation or treatment).\nThe choice to review or not review slides once they have \nbeen received by a second institution or pathologist is a \ncontroversial one and clear guidelines have not been devel\u00ad\noped. If the pathology is unrelated to the current disease or \ncurrently affected organ system, it is generally agreed that \nthese slides need not be reviewed at the discretion of the \npathologist, due to lack of medical necessity. Prior cyto\u00ad\nlogic diagnoses need not be reviewed if the diagnosis was \nsubsequently confirmed by a biopsy.\nSlides on specimens related to the patient\u2019s current dis\u00ad\nease should be reviewed. If certain types of specimens are \nnot reviewed, there should be a general policy that would \napply to all such cases (e.g., all prostate core needle \u00adbiopsies \nprior to a diagnosis of carcinoma or all lymph nodes from \nbreast cancer patients excised more than one year prior to \nconsultation).\nA report is generated by the second hospital. The cost \nof the consultation is usually borne by the patient or the \npatient\u2019s insurance company.\nAll original slides, blocks, and the consultation report \nare returned to the original institution. If the reviewing \npathologist wishes to keep original slides, the request must \nbe approved by the referring institution.\nLEGAL CONSULTATIONS\nRequests from lawyers for materials related to a legal \naction may be in the form of a subpoena and often include \na blanket request for all slides, reports, blocks, and wet \ntissue pertaining to the patient. The original slides are \nconsidered legal evidence. Provision of this material may \nbe difficult for pathologists, is often irrelevant to the case, \nand may also be requested by the opposing lawyers. Since \nthese materials constitute the patient\u2019s medical record, it \nis not in the patient\u2019s best interest that this entire record \nbecomes sequestered as legal evidence. Such materials \nmay not be returned after the legal action is finished. In \naddition, pathologists can be held liable for loss of such \nmaterials unless specifically ordered by a court to release \nthem.\nIt is preferable for the pathologist to discuss the case \nwith the lawyer to determine the actual material neces\u00ad\nsary for the legal evaluation of the case. In some cases, \nit may be arranged for the materials to be reviewed at \nthe original institution. This is recommended in cases \nin which the material is irreplaceable (e.g., cytology \nslides).\nReimbursement can be requested for the cost of review\u00ad\ning and retrieving slides and for making new slides if nec\u00ad\nessary. These requests may or may not be honored by the \nrequesting law firm.\nIt may be preferable to contact the insurer of the pathol\u00ad\nogist or institution before sending out materials. This is \nparticularly true if the institution or physicians associated \nwith the institution are named in the lawsuit.\nPathologists may be asked to be expert consultants for \nlegal cases. In general, a pathologist makes an agreement \nwith a law firm to review slides and possibly offer testi\u00ad\nmony in court or as a deposition. The pathologist may be \nasked to offer an expert opinion on issues not generally \naddressed medically. For example, a typical issue in failure \nto diagnose breast cancer is \u201cretrognosis\u201d (trying to deter\u00ad\nmine the probable size of the cancer in the past) as opposed \nto the typical medical issues of prognosis.\nIt is inappropriate for a patient, clinician, or pathologist \nto request review of a case for legal reasons as an insti\u00ad\ntutional consultation. Such consultations are intended \nfor review to guide patient care. Legal consultations are \n\u00adtypically handled as personal consultations to a specific \npathologist and billed to the legal firm.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_060.png", "summary": "The page discusses the process of sending consultation reports, including what materials to include, how to request return of materials, and which slides should be sent for review.", "questions": [ "What materials should be included in a consultation report?", "Why is it important to focus reviews on current medical treatment rather than potential medicolegal issues?", "What are some examples of slides that need not be sent for review?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 61, "text": "43\nCONSULTATION REPORTS\u2003 Sign-out of Consult Cases\nREVIEW FOR RESEARCH OR TREATMENT PROTOCOLS\nPathology materials are sometimes requested as part of a \nresearch project or a treatment protocol onto which the patient \nhas been enrolled. It is the pathologist\u2019s role to balance the best \ninterests of the patient with the need for medical research.\nBlanket requests for all slides and blocks to be stored \npermanently as part of a research protocol are generally \nnot in the best interest of the patient and may also inter\u00ad\nfere with other equally valid research projects. It is usually \nunknown how quickly such materials could be made avail\u00ad\nable for patient care. In addition, if the project is termi\u00ad\nnated there may not be funds to ensure the return of all the \nmaterials collected just as research projects rarely provide \nfunds for the collection and sending of such materials.\nThe following guidelines are suggested:\n\t\u2022\t \u0007Recut selected glass slides are preferable to releasing origi\u00ad\nnal material. Slides appropriate for the proposed study can \nbe sent (e.g., unstained tissue on coated slides for immuno\u00ad\nperoxidase studies). The researchers will need to address \nthe appropriateness of such materials for their studies (e.g., \npossible loss of antigenicity in cut slides over time).\n\t\u2022\t \u0007If blocks are released, a time limit should be imposed for \nreturn of the block. The researchers may make recuts \nbut should not exhaust the tissue in the block.\n\t\u2022\t \u0007Release of paraffin blocks for \u201cpermanent\u201d storage for \npossible future studies is, in general, discouraged, unless \nmultiple blocks demonstrating the pathologic lesion are \navailable. For example, new markers relevant to current \ntreatment of the patient (e.g., HER-2/neu immunohis\u00ad\ntochemistry for eligibility for Herceptin treatment) may \nrequire the ready accessibility of paraffin blocks.\n\t\u2022\t \u0007It may be possible to take cores of tissue from a block for \nthe preparation of tissue arrays, but to leave sufficient \ntumor tissue in the block should additional studies be \nrequired. The original pathology department should be \ncontacted before using blocks for such a purpose.\nThere are also evolving issues of patient confidentiality \nwith regard to their material being used in research pro\u00ad\ntocols. It is necessary for materials to be coded to prevent \nidentification of the patient unless the patient has given \ntheir informed consent. It is possible to remove patient \nidentifiers from pathology reports.4 In some cases, there \nmay be ethical issues as to revealing or not revealing new \ninformation discovered during examination of cases as part \nof a research protocol (e.g., gene carrier status, previously \nundetected lymph node metastases). These issues should \nbe addressed in conjunction with Human Studies Commit\u00ad\ntees prior to the start of a research project.\nRECEIVING CONSULTATION MATERIALS\nAll materials received for consultation must be docu\u00ad\nmented. This is important both for evaluating possible dis\u00ad\ncrepancies in diagnosis due to review of different materials \nand for appropriate return of the materials.\nThe materials received are checked against the letter \nstating the materials sent by the other institution. Any \ndiscrepancies should be resolved by calling the original \npathology department.\nAll slides and blocks must be accompanied by the cor\u00ad\nresponding pathology report to ensure that the slides cor\u00ad\nrespond to the correct patient. In unusual circumstances, \nif the original pathology report is unavailable (e.g., slides \nreceived from another country) the circumstances in how \nthe slides were received and the name of the person con\u00ad\nfirming the identification of the slides should be docu\u00ad\nmented.\nThe name and birthdate (or age) of the patient is \nchecked for each set of slides. Sometimes hospitals send \nall specimens from patients with the same name. Failure to \ndetect such errors can result in significant errors in diag\u00ad\nnosis and treatment.\nSENDING OUT SLIDES FOR CONSULTATION\nPathology departments frequently receive requests to send \nslides to other locations. The reason for the request must \nbe clearly stated, as this will determine the types of materi\u00ad\nals sent (see specific recommendations above).\nWhen slides are sent, they should always be accom\u00ad\npanied by the original pathology reports and other out\u00ad\nside consultation reports on the same material. This \nshould include information as to how the consultation \nshould be billed. In some cases it may be appropriate \nto send additional information such as operative notes, \nradiologic reports, electron micrographs, etc. If the \npatient is seeking a second opinion, it is often prefer\u00ad\nable to have the clinician request the slides so that the \nslides can be forwarded to the consulting pathologist \nwith the appropriate clinical history and the reason for \nconsultation.\nSlides must be sent in appropriate packaging, preferen\u00ad\ntially in a plastic slide holder (packed so that the slides do not \nrattle) placed within a cardboard box or tube with support\u00ad\ning packing to ensure their safe transfer to another institu\u00ad\ntion. Dr. P. P. Rosen has published useful suggestions.5\nSIGN-OUT OF CONSULT CASES\nThe headings give the name of the original hospital, the \ncity, and the state. The specimen headings, in general, \nshould be whatever the original hospital used. Include \nthe surgical number and the date. Specify that slides \nwere received and paraffin blocks if they were recut. For \n\u00adexample:\nConsult slides and paraffin blocks from Central Hospital, \nSomeplace, NJ:\nBezoarectomy and pyloroplasty (S04-1261; dated 3/10/04):\nIn addition to the diagnosis of the tissue on the slides, \nthe final report should also include the types of \u00adinformation", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_061.png", "summary": "Pathology materials are sometimes requested for research or treatment protocols, and it is important to balance the patient's best interests with the needs of medical research. Guidelines are suggested for the release of slides and blocks for such purposes.", "questions": [ "How can pathologists balance the best interests of the patient with the needs of medical research?", "What guidelines are suggested for the release of slides and blocks for research or treatment protocols?", "What are the evolving issues of patient confidentiality in research protocols, and how are they addressed?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 62, "text": "44\nCONSULTATION REPORTS\u2003 Sign-out of Consult Cases\nlisted below. Although the original surgical pathology \nreports should be kept on file they are often more diffi\u00ad\ncult to access than the consultation pathology report. In \naddition, the original report may not be readily available \nto clinicians or other pathologists later reviewing the \ncase. Therefore, all information of pathologic importance \nshould be abstracted from the original report and included \nin the consultation report (either in the gross description \nor final diagnosis).\n\t\u2022\t \u0007Prognostic information from the gross description \nshould be included (e.g., size of tumor, number of lymph \nnodes examined, etc.).\n\t\u2022\t \u0007If the slides are from a large resection, a brief description \nof the specimen (derived from the original gross descrip\u00ad\ntion) is helpful. For example:\n\u201cAccording to the original surgical pathology report, the speci\u00ad\nmen consisted of an \u2018ovoid tumor mass\u2019 (7 cm in greatest \ndimension) with focal areas of necrosis and hemorrhage \nwhich was covered by \u2018a few strands of connective tissue \nand muscle.\u2019\u201d\n\t\u2022\t \u0007Information included in the original report, but not \ndocumented by the slides received, should be mentioned \nbut with a disclaimer. For example:\n\u201cAccording to the original surgical pathology report, four of \nfive axillary lymph nodes were involved by metastatic car\u00ad\ncinoma (slides not received for review).\u201d\n\t\u2022\t \u0007Any additional information of pathologic importance \nprovided in the consultation material (e.g., results of \nelectron microscopy, immunoperoxidase studies, etc.) \nare included with a statement as to whether or not they \nwere reviewed here. For example:\n\u201cAccording to the original surgical pathology report the \ntumor cells were immunoreactive for S100 protein and \nmelanoma specific antigen (HMB-45) and negative for \nkeratin (CAM 5.2) (slides not received for review).\u201d\n\u201cAccording to the original surgical pathology report the \ntumor was sent for estrogen receptor analysis (positive at \n100 fm/mg) and flow cytometric analysis (DNA index \n1.9, S-phase fraction 22%).\u201d\n\t\u2022\t \u0007Review of special studies (e.g., histochemical stains and \nimmunoperoxidase studies) that are interpreted as part \nof the consultation must be documented. For example:\n\u201cImmunoperoxidase studies performed at the original insti\u00ad\ntution on formalin-fixed tissue and reviewed here reveal \nthat the malignant cells are immunoreactive for cytokera\u00ad\ntin (AE1/AE3) and not immunoreactive for S100 and \nleukocyte common antigen, supporting the diagnosis of \nmetastatic carcinoma.\u201d\n\t\u2022\t \u0007If there is a discrepancy with the original diagnosis, it is \nhelpful to provide information as to why this occurred \n(e.g., due to additional levels, special studies, or different \ndiagnostic criteria \u2013 see \u201cInstitutional Consults\u201d).\n\t\u2022\t \u0007If unstained slides and/or paraffin blocks are received \nand additional studies are performed, this is specifically \ndocumented:\n\u201cImmunoperoxidase studies on formalin-fixed tissue per\u00ad\nformed on recut sections reveal that the malignant cells \nare immunoreactive for S100 and HMB-45 and are not \nimmunoreactive for cytokeratin (AE1/AE3) or leukocyte \ncommon antigen, supporting the diagnosis of metastatic \nmelanoma.\u201d\nREFERENCES\n\t1.\t \u0007Consultations in surgical pathology. Am J Surg Pathol \n17:743-745, 1993 and Am J Clin Pathol 102:152-153. 1994 \nand Human Pathol 24:691-692, 1993.\n\t2.\t \u0007Renshaw AA, Pinnar NE, Jiroutek MR, Young ML. Quantify\u00ad\ning the value of in-house consultation in surgical pathology, \nAm J Clin Pathol 117:751-754\n\t3.\t \u0007Azam M, Nakhleh RE. Surgical pathology extradepartmental \nconsultation practices. A College of American Pathologists \nQ-probes study of 2746 consultations from 180 laboratories. \nArch Pathol Lab Med 126:405-412, 2002.\n\t4.\t \u0007Gupta D, Saul M, Gilbertson J. Evaluation of a deidentifi\u00ad\ncation (De-Id) software engine to share pathology reports \nand clinical documents for research. Am J Clin Pathol 121:\n169-171, 2004.\n\t5.\t \u0007Rosen PP. Special report: Perils, problems, and minimum \nrequirements in shipping pathology slides. Am J Clin Pathol \n91:348-354, 1989.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_062.png", "summary": "Consultation reports in surgical pathology should include all important pathologic information from the original report, as they are often easier to access than the original reports. Prognostic information, specimen descriptions, and additional pathologic findings should be included.", "questions": [ "Why is it important to include prognostic information in consultation reports?", "How should discrepancies with the original diagnosis be addressed in consultation reports?", "What steps should be taken if additional studies are performed on received slides and blocks?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 63, "text": "45\n6\nOperating Room Consultations\nPURPOSE OF OPERATING ROOM CONSULTATIONS\nI wish you pathologists would find a way to tell us surgeons \nwhether a growth is cancer or not while the patient is still on \nthe table.\nWilliam Mayo, 1905\nWhen cancer becomes a microscopic disease, there must be tissue \ndiagnosis in the operating room.\nJoseph Colt Bloodgood, 1927\nThere are three principal reasons for operating room \nconsultations:\n 1.\t \u0007To provide rapid gross or microscopic diagnoses to \nguide intra- or peri-operative patient management. The \nmost common diagnoses requested include:\n\t \u2022\t \u0007Identification of an unknown pathologic process\n\t \u2022\t \u0007Evaluation of margins\n\t \u2022\t \u0007Identification of lymph node metastases\n\t \u2022\t \u0007Identification of tissues\n 2.\t \u0007To optimally process tissue for special studies to be \nused for diagnosis, treatment, or research.\n 3.\t \u0007To confirm lesional tissue is present for diagnosis on \npermanent sections and/or after special studies.\nFROZEN SECTIONS ARE NOT PERMANENT SECTIONS\nThe diagnostic information provided by frozen section \nanalysis is limited compared to the information that can be \nprovided in the final sign-out of a case based on permanent \nsections:\n\t\u2022\t \u0007Sampling. Only minute portions of tissue can be frozen \nwell. Thus, the amount of tissue that can be evaluated \nmicroscopically is only a small proportion of the tissue \nthat is typically sampled for permanent sections.\n\t\u2022\t \u0007Ice crystal artifact. Freezing tissues can create artifacts \nthat make diagnosis difficult or sometimes impossible. \nThese tissues changes are permanent and small lesions \nof primary diagnostic importance should not be frozen \nin entirety. Other technical problems can also hinder \nintraoperative diagnoses.\n\t\u2022\t \u0007Lack of special studies. It is generally not possible to \nperform special histochemical or immunohistochemical \nstudies in the timeframe of a surgical operation. Final \ndiagnoses may require or be altered after information \ngleaned from such studies.\n\t\u2022\t \u0007Lack of consultation. For some difficult or unusual \nlesions, the opinions of additional pathologists may be \nrequired for a final diagnosis.\nFor these reasons, the goals of intraoperative consulta\u00ad\ntions must be limited to what is feasible and reliable under \nthese conditions. In most cases the pathologist is able to \nprovide the information needed by the surgeon to com\u00ad\nplete the operation.1\nINAPPROPRIATE FROZEN SECTIONS\nThe education of surgeons is the career-long task of the surgical \npathologist. It must be a collegial process, never confrontational \nand never attempted when a patient is under anesthesia.\nVirginia Li Volsi2\nPotentially inappropriate frozen sections include the \nfollowing: \n \n1.\t \u0007Unnecessary but not harmful to the patient. This \nwould include freezing a section of a large tumor for \nwhich further surgery or treatment is not antici\u00ad\npated prior to a permanent section diagnosis. Such \ncases may be avoided by discussion with the surgeon \neither during or after the procedure. Such practices \nwill result in increased charges without benefit to the \npatient.\n \n2.\t \u0007Unnecessary and potentially harmful to the \npatient. These cases are usually small primary \nlesions that would be frozen in entirety. Artifactual \ndistortion or loss of tissue could prevent diagnosis. \nAlthough true for any site, frozen sections should \nespecially be avoided for pigmented skin lesions \nand small breast lesions. In such cases the patholo\u00ad\ngist must be an advocate for the patient and clearly", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_063.png", "summary": "Operating room consultations are essential for providing rapid diagnoses to guide patient management, processing tissue for special studies, and confirming lesional tissue presence for permanent sections.", "questions": [ "What are the three principal reasons for operating room consultations?", "What are the limitations of frozen section analysis compared to permanent sections?", "Why is it important to avoid inappropriate frozen sections?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 64, "text": "OPERATING ROOM CONSULTATIONS\u2003 Preparing Frozen Sections\n46\nexplain that the patient\u2019s best interests (and ulti\u00ad\nmately the surgeon\u2019s) would be served by not per\u00ad\nforming a frozen section.\n \n3.\t \u0007Situations in which a frozen section has low \nsensitivity or specificity but in which a fro\u00ad\nzen section could rarely be useful. Examples \nof this type of case include frozen sections on a \nwell-\u00adcircumscribed follicular lesion of the thyroid \nto look for capsular invasion or examining breast \nre-excisions for ductal carcinoma in situ (DCIS) at \nthe margin. Pathologists, surgeons, and institutions \nusually have policies for examining such specimens. \nIf a frozen section is performed, the surgeon must \nbe aware of the possibility that there could be a \nchange in diagnosis on permanent sections. \nThe actual frequency of inappropriate frozen sections is \nreported to be less than 5% of all frozen sections.3 How\u00ad\never, frozen sections performed for apparently unnecessary \nreasons did result in a change in patient outcome in 9% of \ncases in another study.4 Thus, when confronted with what \nappears to be an inappropriate frozen section request, it \nwould be advisable to enter into a discussion with the sur\u00ad\ngeon to determine what information is required by the sur\u00ad\ngeon and how he or she intends to use this information. \nSuch a dialogue can be an ideal forum for optimizing the \nuse of intraoperative consultations.\nPERFORMING OPERATING ROOM CONSULTATIONS\n\t\u2022\t \u0007The specimen is transported to the OR consultation \nroom and must be accompanied by appropriate clinical \ninformation:\n\t \u2022\t \u0007Patient identifiers (preferably a hospital or clinic number)\n\t \u2022\t \u0007Relevant clinical history (e.g., results of a fine needle \naspiration of a thyroid nodule prior to resection or \nprior history of malignancy).\n\t \u2022\t \u0007The presence of infections posing risk to personnel \nperforming frozen sections (e.g., human immuno\u00ad\ndeficiency virus [HIV], hepatitis B, hepatitis C, and \ntuberculosis [TB]). In such cases, special protective \nequipment may be used and the cryostats will be \ndecontaminated if a frozen section (FS) is performed.\n\t \u2022\t \u0007Type of tissue or location of biopsy\n\t \u2022\t \u0007Purpose of the consultation\nIf the reason for examining the specimen is unclear, the \nsurgeon must be contacted to avoid inappropriate speci\u00ad\nmen processing.\n\t\u2022\t \u0007Examine the specimen and record a gross description \n(e.g., size and number of fragments, previously incised \ntumors, presence of localization wire). Information on \nwhat was done to the specimen (e.g., location of frozen \nsections, tissue removed for research, tissue taken for \nspecial studies) is recorded. A diagram can be invaluable \nto indicate the location of anatomic landmarks, lesions, \nmargins, sites sampled, etc. If the orientation is unclear, \ncall the surgeon to clarify.\n\t\u2022\t \u0007Prepare cytologic preparations and/or frozen section(s) \nas appropriate.\n\t\u2022\t \u0007An OR consultation diagnosis is rendered based on the \ngross and microscopic findings.\n\t\u2022\t \u0007The results are communicated to the surgeon. The OR \nshould be called first. If the surgeon is not present, page \nhim or her, call the surgeon\u2019s office, or leave an email \nmessage as necessary. If the surgeon cannot be con\u00ad\ntacted, this is documented in the report. If the patholo\u00ad\ngist is not speaking directly to the surgeon, the person \nreceiving the information should repeat it back to the \npathologist to ensure that it has been understood cor\u00ad\nrectly. The optimal turnaround time for frozen sections \nis 15 minutes or less. The time the specimen arrives in \nthe OR consultation room and the time the diagnosis \nis rendered are documented on the OR consultation \nform.\n\t\u2022\t \u0007Record any relevant clinical information received from \nthe surgeon or from the patient\u2019s chart, if it is provided. \nThis information is often critical for the evaluation \nof the specimen and should be communicated to the \npathologist responsible for the final diagnosis on perma\u00ad\nnent sections. This information can be recorded on the \nback of the OR consultation form.\n\t\u2022\t \u0007All frozen section remnants should be processed for per\u00ad\nmanent sections or saved frozen for special studies. The \ncomparison of frozen sections to the permanent sec\u00ad\ntions is an important quality control measure. Tissue for \nspecial studies is allocated and taken to the appropriate \nlaboratories.\nPREPARING FROZEN SECTIONS\nFreezing is an imperfect but rapid method for solidifying \nsmall pieces of tissue in order to make thin sections for \nhistologic examination. Ice crystals form within the tissue \nduring freezing and can cause significant permanent arti\u00ad\nfacts. The secret to good frozen sections is in the prepara\u00ad\ntion of the block.\nThere are many commercial types of cryostats and \nembedding techniques. However, the following general \nprinciples will apply to most.\nTips for Better Frozen Sections\nSelecting the Tissue.\u2002\n\t\u2022\t \u0007Small thin portions of tissue will freeze best (generally \nnot more than 0.5 \u00d7 0.5 \u00d7 0.3 cm). Never try to freeze \nfragments larger than the diameter of the chuck.\n\t\u2022\t \u0007Tissues with little water (e.g., fat) do not freeze well \nand are extremely difficult to section. Avoid including \nfat in the specimen (e.g., around lymph nodes or breast \nlesions).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_064.png", "summary": "The page discusses the importance of appropriate use of frozen sections in surgical pathology consultations, highlighting situations where a frozen section may have low sensitivity or specificity but could still be useful.", "questions": [ "What are examples of cases where a frozen section may have low sensitivity or specificity but could still be beneficial?", "What information should be included when transporting a specimen to the OR consultation room?", "How can a dialogue between pathologists and surgeons optimize the use of intraoperative consultations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 65, "text": "OPERATING ROOM CONSULTATIONS\u2003 Preparing Frozen Sections\n47\n\t\u2022\t \u0007Blot the outer surface of the specimen dry using a paper \ntowel or gauze pad.\n\t\u2022\t \u0007If orientation is important (e.g., with en face sections), \nrecord how the specimen is oriented in the block (i.e., if \nthe true margin is face up or face down). \nPreparing the Block (Embedding Medium Frozen on a \nMetal Chuck).\u2002\n\t\u2022\t \u0007Embedding medium is placed on a metal chuck that has \nbeen pre-cooled in a cryostat. When partially frozen, \nthe block can be inverted on the shelf to create a flat \nsurface.\n\t\u2022\t \u0007Blocks with frozen embedding medium should be pre\u00ad\npared prior to receipt of specimens to avoid wasting time \nwaiting for the medium to freeze.\n\t\u2022\t \u0007If multiple small fragments must be sectioned, a special \nblock may be prepared. After the embedding medium is \nfrozen, pre-cut the block on the cryostat to create a flat \nsurface in the plane of the blade. Tissue placed on this \nblock will all be in the same plane for cutting, which will \nmaximize the amount of tissue on each glass slide.\n\t\u2022\t \u0007Do not use old blocks (e.g., left overnight in a cryostat \nthat goes through a freeze-thaw cycle), as they will be \nsoft and crumbly.\n\t\u2022\t \u0007Embedding medium must be completely cleaned from \nthe chuck (a toothbrush works well) before reuse. Crys\u00ad\ntals can be removed by dipping the chuck in methanol.\nFreezing the Tissue.\u2002\n\t\u2022\t \u0007Place the tissue on the block making sure the tissue is \nnot folded. Cover the tissue rapidly with embedding \nmedium and activate a \u201cQuick Freeze\u201d option if avail\u00ad\nable, which cools the metal shelf holding the chucks.\n\t\u2022\t \u0007If positioning of a small fragment of tissue is important, \nadd a drop of embedding medium to the top of the frozen \nblock and place the tissue into this drop. The tissue can \nthen be oriented before the embedding medium freezes.\n\t\u2022\t \u0007Different tissues require different temperatures of freez\u00ad\ning to cut well. For example, breast, skin, and fatty tis\u00ad\nsues must be kept very cold (i.e., \u201320\u00b0C) or they will be \ntoo soft to cut. Lymph nodes, spleen, brain, and liver cut \nbetter if the temperature is higher (i.e., \u201310\u00b0C) and may \nshatter during sectioning if too cold.\n\t\u2022\t \u0007When the embedding medium is partially frozen (i.e., \nbegins to look opaque) the block may be rapidly cooled \nby turning the block upside down on the metal shelf. \nAlternatively, a \u201cheat extractor\u201d (a plunger-shaped metal \nbar) can be placed on top of the tissue. However, this \nmaneuver sometimes results in distortion of the tissue if \nit is performed before the embedding medium is suffi\u00ad\nciently frozen. Wait until the center, as well as the outer \nrim, has had time to cool.\nCommercially available aerosol sprays were used in \nthe past to rapidly cool the block or parts of the cryostat. \n\u00adHowever, they are not necessary for the preparation of good \nquality frozen sections and their use is not \u00adrecommended \nbecause of the danger of aerosolizing infectious agents. \nThree cases of conversions to positive tuberculin skin tests \nhave been linked to aerosols produced by spraying a tissue \nblock with a compressed gas coolant.5,6\nThe aerosol sprays also should not be inhaled! \nSymptoms of overexposure include lightheadedness and \nshortness of breath. It is a possible cause of cardiac arrhyth\u00ad\nmias. Direct exposure of skin may cause frostbite. And if \nthat isn\u2019t enough, the release of Freon contributes to the \ndestruction of the ozone layer!\nCutting Sections.\u2002\n\t\u2022\t \u0007After the block is well frozen, the chuck is positioned in \nthe cryostat for cutting. The block is manually moved \nforward until close to the blade.\n\t\u2022\t \u0007The blade and plate must be kept free of fragments of the \nembedding medium that can distort or wrinkle the fro\u00ad\nzen sections. Gauze firmly wrapped around a long swab \ncan be kept cooled in the cryostat to be used for clean\u00ad\ning unused sections from the blade or chuck and avoids \nchanging the temperature. This is also a much safer \nmethod of cleaning the blade. Avoid rubbing the gauze \nagainst the edge of the blade as this may dull the edge.\n\t\u2022\t \u0007As the blade cuts the tissue, the tissue must be gen\u00ad\ntly anchored to prevent folding or curling. This can \nbe accomplished with the anti-roll bar (a plastic plate \nattached to the cryostat) or by using a small pre-cooled \npaintbrush. After the section is cut, a glass slide is gently \nlaid on top of the section. The tissue section will melt \nonto the slide. The slide must be immediately placed \nin methanol. Any delay in this step will introduce sig\u00ad\nnificant drying artifacts.\n\t\u2022\t \u0007If the specimen is too cold and is shattering, the block \ncan be warmed slightly with a thumb.\n\t\u2022\t \u0007If true levels are desired (i.e., slides revealing deeper \nareas of the tissue), the block is moved forward manu\u00ad\nally, and another section taken at a deeper level. It would \ntake over 100 passes of the knife to cut through a 0.1 cm \nthick specimen if the block was not advanced manually. \nAdditional levels prepared without manual advancement \nrarely reveal additional histologic information.\n\t\u2022\t \u0007In general, two slides are sufficient for diagnosis and \ndocumentation. Additional slides may be made if the tis\u00ad\nsue is difficult to cut, true levels are made, or there are \nmultiple pieces of tissue on the block at different levels \nthat need to be evaluated. \nRemoving the Block from the Chuck.\u2002\n\t\u2022\t \u0007Never cut blocks off chucks with a razor blade. The \nhardness of the embedding medium is highly vari\u00ad\nable and it is very easy to lose control of the blade and \n\u00adaccidently cut the fingers holding the chuck. Warm the \nchuck slightly by holding the stem for about 30 seconds \nand the block can be removed with a finger. \u00adAlternatively \nthe chuck can be dipped briefly in formalin or left on the \ncounter for a minute or two.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_065.png", "summary": "The page provides detailed instructions on preparing frozen sections in the operating room, including blotting the specimen dry, embedding the tissue on a metal chuck, and freezing the tissue at specific temperatures.", "questions": [ "What are the key steps in preparing frozen sections in the operating room?", "Why is it important to avoid using old blocks that have gone through freeze-thaw cycles?", "How does the temperature of freezing impact the cutting of different types of tissues?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 66, "text": "OPERATING ROOM CONSULTATIONS\u2003 Preparing Frozen Sections\n48\n\t\u2022\t \u0007Excess embedding medium can be trimmed away from \nthe tissue. The remaining tissue is placed in formalin to \nbe submitted for permanent sections. Very small frag\u00ad\nments should be wrapped in paper or placed in a small \nspecimen bag.\n\t\u2022\t \u0007If tissue is to be saved frozen it should be transferred \nto another freezer. Most cryostats undergo freeze-thaw \ncycles, which will damage tissue.\n\t\u2022\t \u0007The most representative frozen section slide should be \nsaved for filing with the permanent sections. \nStaining Slides\nFixed sections are stained with hematoxylin and eosin. The \nfollowing procedure gives good results:\n 1.\t \u0007Stain in hematoxylin for a minimum of 90 seconds or 90 \ndips \u2013 agitation speeds staining process. Cytology speci\u00ad\nmens can be stained for a shorter period of time (e.g., \n30 seconds). Remove and blot excess dye on absorbant \nmaterial.\nStains nuclei blue.\n 2.\t \u0007Rinse slides in water with about 10 dips until gross \nstain is removed. Blot remaining water on a gauze pad. \nChange water frequently between cases.\nRemoves excess dye.\n 3.\t \u0007Dip three times or about 2 seconds in acid alcohol (1% \nHCl in distilled water). If nuclei are stained poorly it \ncould be due to too little hematoxylin staining or too \nlong in HCl.\nPreferentially removes hematoxylin from non-nuclear compo\u00ad\nnents - \u201cdifferentiation.\u201d\n 4.\t \u0007Dip three times or about 2 seconds in ammonia water \n(2% sodium borate).\nThis restores the basic pH to the dye and enhances the staining \n- \u201cblueing.\u201d\nThe color of the nuclei is changed from purple to blue. The \ntime spent in the ammonia water does not alter staining.\n 5.\t \u0007Stain in eosin for 20 to 30 seconds or dips. Blot excess \neosin on a gauze pad.\nStains cytoplasm and other constituents pink to red.\n 6.\t \u0007Dehydrate slide in successive increasing concentrations \nof alcohol dipping approximately ten times in each bea\u00ad\nker. Let all the fluid drain off the slide.\nRemoves excess eosin as well as water from the tissue.\nPoor staining can be due to prolonged time in alcohol.\n 7.\t \u0007Dip slides in xylene until the fluid runs clear on the \nslide (if there are streaks it means that there is water in \nthe tissue). Slides are left in xylene until coverslipped \nto avoid drying artifact that can make interpretation \n\u00addifficult or impossible. Any water present in the xylene \nwill result in cloudy sections.\nXylene has a high index of refraction and renders tissues trans\u00ad\nparent.\n 8.\t \u0007Remove excess xylene from the slide by blotting on \npaper towels. Add one to two drops of mounting \nmedium to the coverslip and gently place the slide on \nthe coverslip. Avoid introducing bubbles. If bubbles are \npresent, more xylene can be introduced under the edge \nof the coverslip to allow the slide to be read.\nSlide holders should be rinsed in a waste methanol con\u00ad\ntainer before replacing them in the methanol in the stain\u00ad\ning rack, to avoid carrying over xylene. Xylene in methanol \nwill produce almost unreadable cloudy slides with poor \nstaining and bubble artifacts. \nThe staining racks should be kept covered to avoid \nevaporation and changes in pH.\nSlides can be destained by going backwards through the \nsolutions but skipping the eosin.\nIf slides need to be left in a solution for a period of time, \nthe best choices are the ammonia water or the xylene. Pro\u00ad\nlonged time in HCl or alcohol will result in poor staining.\nPerforming Frozen Sections on Fixed Tissue\nFormalin fixation denatures proteins, which adversely \naffects the adherence of tissues to glass slides. Such tissues \ncan be extremely difficult to examine by frozen section, \nas the tissue tends to slide off the slide. If it is absolutely \nimperative to evaluate fixed tissue, the following modifica\u00ad\ntions may be helpful:\n\t\u2022\t \u0007If the tissue is relatively large, and has not been fixed for \na long time, tissue from the central portion of the speci\u00ad\nmen may have fewer changes due to fixation.\n\t\u2022\t \u0007Rinse the tissue in saline and blot dry prior to freezing. \nFormalin freezes at a lower temperature than water and \ncan produce large ice crystals.\n\t\u2022\t \u0007Use coated slides (e.g., the type of slides used for immu\u00ad\nnohistochemistry).\n\t\u2022\t \u0007Allow the tissue to dry on the slide prior to staining.\n\t\u2022\t \u0007The HCl and ammonia water steps may be omitted.\n\t\u2022\t \u0007Perform all staining steps very gently and keep the slide \nat an angle to prevent the tissue from sliding off.\nIntraoperative Cytology\nCytologic examination can be as accurate as frozen sections \nfor many specimens7 and has the following advantages:\n\t\u2022\t \u0007Rapid.\n\t\u2022\t \u0007No ice crystal artifact.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_066.png", "summary": "The page provides instructions on preparing frozen sections and staining slides in surgical pathology.", "questions": [ "What is the purpose of transferring tissue to another freezer if it is to be saved frozen?", "Why is it important to save the most representative frozen section slide for filing with the permanent sections?", "What are the potential consequences of not rinsing slides in water to remove excess dye?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 67, "text": "49\nOPERATING ROOM CONSULTATIONS\u2003 Reporting the Results of Operating Room Consultations\n\t\u2022\t \u0007Easy to perform.\n\t\u2022\t \u0007All tissue is preserved for permanent sections or special \nstudies.\n\t\u2022\t \u0007Can sample large areas of tissue.\n\t\u2022\t \u0007Cytologic information is provided:\n\t \u2022\t \u0007Cell-cell cohesiveness (e.g., carcinoma vs. lymphoma).\n\t \u2022\t \u0007Nuclear morphology (e.g., papillary thyroid carcinomas).\n\t\u2022\t \u0007Provides excellent teaching material with cytologic/\nhistologic correlation.\nCytologic preparations are especially useful in the fol\u00ad\nlowing situations:\n\t\u2022\t \u0007All suspected lymphoproliferative disorders.\n\t\u2022\t \u0007Most CNS lesions.\n\t\u2022\t \u0007Documentation of previously diagnosed malignancies \nbefore taking tissue for special studies or research.\n\t\u2022\t \u0007Thyroid nodules.\n\t\u2022\t \u0007Infectious cases (AIDS or hepatitis B) to avoid contami\u00ad\nnating the cryostats or aerosolizing infectious agents \n(see Chapter 8).\n\t\u2022\t \u0007Lung nodules with gross findings strongly suggesting \ninfectious granulomas.\n\t\u2022\t \u0007Minute specimens if additional material will not be \u00adavailable.\n\t\u2022\t \u0007To sample tissue that would be difficult to cut in the cryo\u00ad\nstat (e.g., fatty tissue, necrotic tissue, bone specimens). \nPreparation of cytology slides\u2002\n 1.\t \u0007Make a fresh cut through the tissue. The tissue should \nbe free of gross blood. Lungs and other bloody tissues \nmay require blotting of the surface with a paper towel.\n 2.\t \u0007Touch preparations are made by touching a glass slide \nto the tissue several times.\nSmears are made by scraping the tissue with the edge \nof a glass slide. The material removed is evenly smeared \nonto a second glass slide.\nFine needle aspirations may be performed using a 23 \nor 25 gauge needle attached to a 10 cc syringe and mak\u00ad\ning several passes through the lesion while pulling back \non the plunger to create a vacuum. A small drop (about \n0.2 to 0.3 cm in diameter) is expelled onto a glass slide \nand smeared with another glass slide.\n 3.\t \u0007Hematoxylin and eosin staining: The slides must \nbe fixed IMMEDIATELY in methanol (without hesi\u00ad\ntation) to avoid drying artifacts. The slides are stained \nusing the same protocol as for frozen sections. The \nappearance of the cells is similar to that seen on tissue \nsections and nuclear detail is well preserved.\nDiff-Quik or Giemsa staining: The slides are air-dried \nand then stained. The appearance of the cells is differ\u00ad\nent from that seen in non-air-dried slides. \u00adCytoplasmic \nfeatures are well seen but nuclear detail is less distinct. \nNon-cellular material is well seen (e.g., colloid, matrix \nin salivary gland lesions). This type of staining may be \npreferred for some specimens such as bone marrow \naspirates, parathyroid glands, and salivary glands.\nREPORTING THE RESULTS OF OPERATING ROOM \nCONSULTATIONS\nA verbal report directly to the surgeon and a correspond\u00ad\ning written report are generated.\nWritten Reports\nThe OR consultation report should include the following:\n\t\u2022\t \u0007Specimen heading (type and number of specimen).\n\t\u2022\t \u0007Type of examination (gross examination, frozen \nsection[s], cytologic examination).\n\t\u2022\t \u0007Diagnosis. The diagnosis should not include abbrevia\u00ad\ntions that may not be well understood by other health\u00ad\ncare workers reading the report in the patient\u2019s chart.\n\t\u2022\t \u0007Disposition of the tissue for special studies (e.g., \n\u201cTissue saved for EM and sent for flow cytometry.\u201d).\n\t\u2022\t \u0007The time the specimen was received and the time the \ndiagnosis was rendered.\nAn appropriate diagnosis can almost always be ren\u00ad\ndered by gross or microscopic examination. The annota\u00ad\ntion \u201cdiagnosis deferred\u201d is used only when a decision is \nmade not to provide a diagnosis (e.g., the tissue could not \nbe cut or the block was lost inside the cryostat). It is not \nused to indicate that the final diagnosis will be based on \npermanent sections as this should be understood to be \ntrue for all cases examined by frozen section. In general, \ndeferred diagnoses constitute less than 5% of all OR con\u00ad\nsultations.\nSample Operating Room Consultation Reports\nSUPRACLAVICULAR LYMPH NODE (FROZEN \nSECTION A1 AND TOUCH PREPARATION A2):\nLymph node with no tumor seen.\nLEFT BREAST BIOPSY, WIRE LOCALIZATION \nFOR A MASS (FROZEN SECTION A1):\nInvasive carcinoma (1.4 cm), present at the superior sur\u00ad\ngical resection margin.\nLEVEL 4 LYMPH NODES (FROZEN SECTIONS A1 \nAND A2):\nTwo lymph nodes with noncaseating granulomas.\nDifferential diagnosis includes sarcoidosis and infection.\nTissue is sent to microbiology for mycobacterial and \nfungal culture.\nLEFT \nEXTRAPLEURAL \nPNEUMONECTOMY \n(FROZEN SECTION B1):\nTumor present as multiple foci involving both pari\u00ad\netal and visceral pleura, grossly consistent with the", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_067.png", "summary": "Operating room consultations involve easy procedures that preserve tissue for further studies, provide cytologic information, and are especially useful in specific medical situations.", "questions": [ "What are the benefits of using cytologic preparations in operating room consultations?", "How are cytology slides prepared for analysis?", "What information should be included in a written report for an operating room consultation?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 68, "text": "50\nOPERATING ROOM CONSULTATIONS\u2003 Accuracy of Operating Room Consultations\npatient\u2019s prior diagnosis of MALIGNANT MESO\u00ad\nTHELIOMA.\nThe bronchial resection margin is free of tumor (frozen \nsection B1).\nTumor is fixed in formalin and taken for cytogenetics, \nelectron microscopy, and snap freezing.\nTumor (2 \u00d7 2 \u00d7 1 cm) and normal tissue (3 \u00d7 3 \u00d7 2 cm) \ntaken for the tissue bank.\nVerbal Reports\nThe results of all OR consultations are communicated \nto the surgeon as soon as possible. Failure to reach the \nsurgeon directly should be documented in the report \nand should include what was done to try to contact him \nor her.\nWhen calling back the results to the operating room, \nthe pathologist should identify him or herself (e.g., \u201cDr. \nSmith from Pathology\u201d), identify the patient, and identify \nthe specimen. The diagnosis should be clear and concise. \nIn general, surgeons are willing to speak directly to the \npathologist if requested. Physician-to-physician communi\u00ad\ncation is the most professional and enables him or her to \nask supplemental questions. It also minimizes the risk of \nmiscommunication through a third party.\nIf the surgeon cannot come to the phone, the diagnosis \nmust be relayed via a nurse in the OR. The nurse should \nwrite down the diagnosis and read the diagnosis back (this \nis a Joint Commission requirement). The pathologist must \nlisten to what the nurse tells the surgeon in order to make \ncorrections, if necessary. Avoid using the phrase \u201cno tumor \npresent,\u201d as this can be easily misinterpreted as \u201ctumor \npresent\u201d if not heard clearly. Alternative messages such as \n\u201cthe specimen is negative for tumor\u201d are less likely to cause \nconfusion.\nACCURACY OF OPERATING ROOM CONSULTATIONS\nThe accuracy of frozen section evaluation is reported to be \n94% to 97% when compared to permanent section evalu\u00ad\nation. CAP has suggested that an acceptable rate of major \ndiscrepancies is 3%.8 Discrepancies can be categorized for \nquality assurance analysis:\n\t\u2022\t \u0007Category A: Minor disagreement with no effect on \npatient care\n\t\u2022\t \u0007Category B: Disagreement with some, but not signifi\u00ad\ncant, consequence for patient care\n\t\u2022\t \u0007Category C: Major disagreement with serious impact \non patient care\nAccuracy will vary depending on the goal of the frozen \nsection. For example, when performed for the evaluation \nof margins, lymph node metastases, or for tissue identi\u00ad\nfication, accuracy can approach 100%. However, when \nperformed to evaluate an unknown pathologic process, \naccuracy is usually lower (e.g., 83.47%9).\nErrors can be classified into the following:\nMany of these errors can be avoided by using the proce\u00ad\ndures described below.\nSampling Error (Block or Specimen)\nSampling errors can include either errors in selecting the \nappropriate tissue after gross examination or failure to \ncompletely sample tissue in the frozen section block.\nSampling errors can be avoided or minimized: \n \n1.\t \u0007Thoroughly dissect large specimens. Gross sam\u00ad\npling errors can be minimized by processing spec\u00ad\nimens in the OR consultation room as one would \nduring final processing. This includes inking and \nserially \nsectioning/dissecting \nlarge \nspecimens. \nAlthough more time-consuming, this allows for \ncomplete examination of all tissue and the ability to \nselect the best tissue for frozen section.\n \n2.\t \u0007Freeze small specimens in entirety, when appro\u00ad\npriate. For example, if lymph nodes are being \nevaluated by frozen section to determine whether a \ndefinitive resection or complete lymph node dissec\u00ad\ntion should be performed subsequently, it is prefer\u00ad\nable to freeze the entire node when possible. Failure \nto find a metastasis in the nonfrozen tissue may lead \nto unecessary resections of stage IV tumors (e.g., for \nlung carcinoma) or subsequent additional surgery \n(e.g., a later axillary dissection for a missed positive \nsentinel node).\n \n3.\t \u0007Make sure all tissue frozen is represented on \nthe slide. Sampling error due to failure to examine \nall tissue frozen in the block can be minimized by \ncareful block preparation. If multiple fragments are \npresent, try to have all fragments at the same level \nin the block. Sections of all the fragments should be \nrepresented on the slides prepared. This may require \npreparing multiple slides and/or making true deeper \nlevels through the frozen tissue. \nInterpretive Error\nInterpretive errors can be avoided or minimized: \n \n1.\t \u0007Limit interpretations to what is necessary for \nthe surgeon to know at the time of surgery. In \nsome cases \u201clesional tissue\u201d is adequate. In others, \nbenign versus malignant will suffice. Rarely is a spe\u00ad\ncific histologic subtype or grade required at the time \nof frozen section and such information is likely to \nchange at final diagnosis.\n\t\u2022\t \u0007Sampling error (about 40%)\n\t\u2022\t \u0007Interpretative error (about 40%)\n\t\u2022\t \u0007Technical problems (about 10%)\n\t\u2022\t \u0007Incorrect/incomplete clinical history (about 10%)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_068.png", "summary": "Operating room consultations are crucial for communicating pathology results to surgeons, with a focus on accuracy and effective communication.", "questions": [ "How important is it for the pathologist to communicate results directly to the surgeon?", "What are the potential consequences of major discrepancies in frozen section evaluations?", "How can sampling errors in frozen section evaluations be minimized?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 69, "text": "51\nOPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n \n2.\t \u0007Review prior pathology slides, when relevant. If \nthe patient has had a prior diagnostic procedure, it \nis often helpful to review slides of prior resections, \nespecially in cases of unusual malignancies or tumors \ndifficult to diagnose by frozen section (e.g., signet \nring cell carcinomas, angiosarcomas, tumors after \ntreatment).\n \n3.\t \u0007Examine the tumor as well as margins by fro\u00ad\nzen section, when appropriate. In some cases it \nis extremely difficult to evaluate margins by frozen \nsection if the type of tumor is unknown or has been \npreviously treated. It is often very helpful to com\u00ad\npare changes at the margin with the tumor itself.\n \n4.\t \u0007Insist on well frozen and stained material. If the \ntechnical quality is poor (see below) and cannot be \nimproved, it may be preferable to defer a diagnosis.\n \n5.\t \u0007Insist on adequate relevant clinical history. An \naccurate evaluation of the findings often cannot be \nmade without knowledge of the clinical setting (e.g., \nprior diagnoses of malignancy, prior treatment, \nunusual gross appearance).\nIn some cases a definitive diagnosis cannot be made. In \nthese cases it is appropriate to defer the diagnosis until per\u00ad\nmanent sections can be examined. In most institutions, fewer \nthan 5% of intraoperative diagnoses need to be deferred.\nThere are well-known types of lesions that lend them\u00ad\nselves to interpretive error; these should be either com\u00ad\npletely avoided or only attempted when the surgeon \nis aware of the likelihood of a change in diagnosis. The \nmost common of these are the evaluation of malignancy \nin chronic pancreatitis, borderline lesions of the ovary, \nbreast lesions identified by mammography, and well-\u00ad\ncircumscribed follicular lesions of the thyroid.\nTechnical Problems\nThe interpretation of frozen sections can be made more \ndifficult due to poor technique in freezing tissue or pre\u00ad\nparing slides. Ice crystal artifact, thick sections, folded tis\u00ad\nsue, and xylene artifact can render the most obvious lesions \nuninterpretable. Careful attention to technique can mini\u00ad\nmize these problems.\nSome tissues are difficult to section and are best avoided. \nAdipose tissue freezes poorly due to the lower water con\u00ad\ntent and may not be evaluable. Large fragments of bone \ncannot be sectioned although cytologic preparations may \nbe attempted of marrow or intermingled soft tissue.\nIncorrect/Incomplete Clinical History\nThe reason for performing a frozen section should be clear \nto the pathologist before performing the frozen section. If \nnot, it is better to delay processing the tissue and obtain \nthe history rather than risk inappropriate tissue processing.\nThe pathologist must always have a high index of suspi\u00ad\ncion for prior procedures. If a prior biopsy site or \u00adatypical \ncells are present, then a history of possible radiation ther\u00ad\napy or chemotherapy should be queried.\nIt may be helpful to have the patient\u2019s chart brought to \nthe OR consultation room along with the tissue for exami\u00ad\nnation. The pathologist can then abstract the information \nrequired for pathologic evaluation and include this as clini\u00ad\ncal information on the pathology report.\nQUALITY CONTROL OF OPERATING ROOM \nCONSULTATIONS\nEach pathology department usually reviews the accuracy \nof operating room consultations. Tissue used for the fro\u00ad\nzen section is fixed and a permanent section prepared. The \nfinal diagnosis based on all tissue submitted is compared to \nthe intraoperative diagnosis. The original frozen section \nmust be reviewed if there is a discrepancy. In such cases \nthe reason for the discordance may be categorized as one \nof the following10: \n \n1.\t \u0007Interpretation\n \n2.\t \u0007Block sampling\n \n3.\t \u0007Specimen sampling\n \n4.\t \u0007Technical inadequacy\n \n5.\t \u0007Lack of essential clinical or pathologic data\n \n6.\t \u0007Other (indicate) \nWhen significant discrepancies occur between a frozen \nsection diagnosis and a final diagnosis, the reason for the \ndiscrepancy should be documented in the final report and \nthe surgeon notified of the change.\nCOMMON OPERATING ROOM CONSULTATIONS\nMost operating consultations fall into a few general cat\u00ad\negories and the objectives of the consultation are well \nknown to the pathologist and surgeon. If the reason for \nthe consultation is unclear, it is advisable to contact the \nsurgeon before processing the tissue.\nBone Biopsies\nBefore a bone lesion is approached surgically there will \nbe a presumptive diagnosis based on the radiographic \nappearance, the location, and the patient\u2019s age. Because \nthe approach to evaluation varies depending on the most \nlikely diagnosis and planned intraoperative treatment, the \nclinical/radiologic differential diagnosis must be provided \nbefore processing the specimen. Cancellous bone can be \ncut on a cryostat. Portions of cortical bone are thicker and \nshould not be cut.\nPresumptively Benign Lesions\nReason for Consultation.\u2002 To confirm a benign lesion before \ncontinuing with a procedure that could preclude limb preser\u00ad\nvation if malignancy is present (e.g., curettage and \u00adpacking).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_069.png", "summary": "Operating room consultations involve reviewing prior pathology slides, examining tumors and margins by frozen section, insisting on well frozen and stained material, and obtaining adequate relevant clinical history to ensure accurate evaluation of findings.", "questions": [ "What are some common technical problems that can affect the interpretation of frozen sections?", "Why is it important to have adequate relevant clinical history when evaluating intraoperative findings?", "What types of lesions are known to lend themselves to interpretive error during intraoperative consultations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 70, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n52\nChange in Surgery.\u2002 A definitive procedure will be com\u00ad\npleted if a malignancy is not present. If a benign diagnosis \nis confirmed on the small initial biopsy, the surgeon will \noften perform a curettage of the lesion which will provide \nabundant material for later permanent sections. If a malig\u00ad\nnancy is found, the surgeon will stop after the biopsy. If a \nmalignant tumor is missed on frozen section, the curet\u00ad\ntage will contaminate the entire bone and may result in the \nneed for an amputation.\nEvaluation.\u2002 In general, all the tissue initially provided \nshould be used for frozen section.\nPresumptively Malignant Lesions\nReason for Consultation.\u2002 To confirm that sufficient \ntissue is present for diagnosis.\nChange in Surgery.\u2002 Additional tissue may be taken if \nnecessary for diagnosis. Most patients will then undergo \nradiation and chemotherapy before a definitive resection.\nEvaluation.\u2002 A frozen section or cytologic preparation is \nperformed on only a small portion of the tissue to con\u00ad\nfirm that diagnostic tissue is present and to guide appor\u00ad\ntionment of tissue (e.g., consider cytogenetics if Ewing\u2019s/\nPNET is a possibility).\nMargins on Large Resections\nReason for Consultation.\u2002 To determine whether the mar\u00ad\ngins are free of a known malignant tumor.\nChange in Surgery.\u2002 Additional tissue may be resected to \nobtain clean margins.\nEvaluation.\u2002 In general, the resected bone must be \nbisected in order to identify the distance of the tumor \ngrossly from the margin. A frozen section can be taken of \nthe cancellous bone at the margin or a cytologic prepara\u00ad\ntion may be prepared from the marrow space.\nFrozen section of cancellous bone removed with a \ncurette from a mandibular margin has been reported to be \nan accurate determination of final margin status.11\nRevision Total Joint Arthroplasty\nReason for Consultation.\u2002 To determine whether infec\u00ad\ntion is present.\nChange in Surgery.\u2002 It may be difficult to distinguish \nmechanical from septic loosening of a prosthetic joint. If \ninfection is present, drainage or removal of the prosthesis \nmay be indicated and replacement of a prosthesis may be \ndelayed until after treatment.\nEvaluation.\u2002 At least two representative sections of a \nbiopsy of periprosthetic tissue (considered to be the most \ngrossly suspicious area by the surgeon) are examined and \nthe number of polymorphonuclear leukocytes (PMNs) per \nHPF (\u00d7400) is assessed. At least 5 HPFs should be counted \nin the most cellular areas of the section (Table 6-1).\nPitfalls.\u2002 False positives (3% of cases) and false nega\u00ad\ntives (6% of cases) can occur. Surgical management should \nbe based on the preoperative and intraoperative clinical \nassessment as well as on frozen section results.12-15\n\t\u2022\t \u0007False positives: PMNs only seen in surface fibrin should \nnot be included. Patients with rheumatoid arthritis may \nhave acute inflammation not related to sepsis. Perivascu\u00ad\nlar PMNs are usually due to prolonged surgery.\n\t\u2022\t \u0007False negatives: Usually due to sampling error. At least \ntwo blocks of tissue should be frozen. Additional blocks \nshould be frozen if tissue from different sites is provided \nby the surgeon. Tan/pink tissue should be chosen for \nexamination. White fibrous tissue or fibrin is unlikely to \nyield useful material for diagnosis. Some patients with \ndocumented infections will have few or absent PMNs.\nDermatopathology\nCARCINOMA\nReason for Consultation.\u2002 Margin evaluation of basal cell \ncarcinomas or squamous cell carcinomas from the face. \nThe surgeon may desire to take the minimal amount of \nskin necessary to achieve satisfactory cosmetic results.\nThe use of frozen sections for the diagnosis or margin \nevaluation of melanocytic lesions is strongly discouraged. \nIf a clinician requests such an evaluation, the pathologist \nshould inform him or her that frozen section often com\u00ad\npromises definitive diagnosis and that the evaluation should \nbe made on well fixed and oriented permanent sections.\nChange in Surgery.\u2002 Additional tissue may be taken to \nensure clean margins.\nTABLE 6\u20131.\u2003\nEVALUATION OF REVISION TOTAL JOINT ARTHROPLASTY\nCRITERIA\nFEATURE ON FROZEN SECTION\nSENSITIVITY\nSPECIFICITY\nPPV\nNPV\nFeldman\n\u22655 PMN per HPF (count 5 fields)\n28.5%\n100%\n100%\n73.6%\nAthanasou\n\u22651 PMN per HPF (count 10 fields)\n71.4%\n64.2%\n50%\n81.8%\nHPF = \u00d7400.\nFeldman, DS, Lonner, JH, Desai, P, Zuckerman, JD, The role of interoperative frozen sections in revision total joint arthoplasty, J Bone Joint Surg Am 77(12):1807-1813, 1995.\nAthanasou, NA, Pandey, R, de Steiger, R, McLardy Smith, P, The role of intraoperative frozen sections in revision total joint arthroplasty, J Bone Joint Surg Am 79(9):1433-1434, 1997.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_070.png", "summary": "The page discusses common operating room consultations in surgical pathology, including procedures for benign and malignant lesions, evaluation of margins on large resections, and consultation for revision total joint arthroplasty.", "questions": [ "How does the surgeon proceed if a benign diagnosis is confirmed on the initial biopsy?", "What evaluation methods are used for presumptively malignant lesions?", "How are margins on large resections evaluated and what actions are taken if a known malignant tumor is present?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 71, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n53\nEvaluation.\u2002 The specimen is usually an oriented ellipse. \nBecause the main lesion has almost always been biopsied, \nit is often difficult to determine the location of the closest \nmargin. If the paperwork does not indicate which margin(s) \nare to be frozen, contact the surgeon before proceeding.\nDraw a diagram showing the orienting suture, ink col\u00ad\nors, and site of frozen sections. For small ellipses, it is use\u00ad\nful to ink the two margins to be evaluated by frozen section \nin two different colors. Both margins can be evaluated in a \nsingle section. Take perpendicular sections at the margins \nindicated as \u201cclose\u201d by the surgeon. Make sure the sections \nare thin but are full thickness and include the deep margin.\nSkin Exfoliation\nReason for Consultation.\u2002 It is sometimes necessary to \ndistinguish between staphylococcal scalded skin syndrome \n(SSSS) and toxic epidermal necrolysis (TEN) in order to \nguide treatment. Both can present with areas of exfoliated \nskin and can be difficult to differentiate on clinical grounds. \nThis is one of the true dermatopathologic emergencies.\nChange in Treatment.\u2002 SSSS is treated with antibiotics. \nTEN may require steroids or withdrawal of possible sensi\u00ad\ntizing medications.\nEvaluation.\u2002 The specimen will be a fragment of the exfo\u00ad\nliated skin. The skin is rolled as tightly as possible using \na forceps. Cross section(s) are taken for frozen section in \norder to evaluate a perpendicular section.\n\t\u2022\t \u0007TEN: The cleavage plane occurs at the dermal-epidermal \njunction. The presence of full-thickness epidermal cell \nnecrosis is supportive of TEN.\n\t\u2022\t \u0007SSSS: The cleavage plane occurs near the granular cell \nlayer. Therefore, only the most superficial aspect of the \nepidermis and keratin-layer are seen.\nNecrotizing Fasciitis\nReason for Consultation.\u2002 To establish the diagnosis of nec\u00ad\nrotizing fasciitis. This is a rapidly progressive infection that \ncauses death in 25% to 33% of patients. The causative bac\u00ad\nteria are streptococci in about one-third, but polymicrobial \ninfections are common including staphylococci, enterococci, \nenterobacteriaceae (E. coli, Acinetobacter, Pseudomonas, Klebsi\u00ad\nella), Bacteroides, and Clostridium. The initial symptoms (the \ntriad of exquisite pain out of proportion to physical findings, \nswelling, and fever) are difficult to distinguish from cellu\u00ad\nlitis or an abscess. The initial spread is horizontal and small \n\u00adbullae frequently form on the skin. In later stages, large hem\u00ad\norrhagic bullae and necrosis of skin and deep tissues ensue.\nChange in Treatment.\u2002 A definitive diagnosis can aid to \nguide rapid wide surgical debridement and/or amputation \nresulting in a much better prognosis. Useful biopsies must \nbe obtained within 4 days of the onset of symptoms. The \nadvantage of early diagnosis is lost once skin and muscle \nbecome necrotic and the need for debridement is obvious.\nEvaluation.\u2002 An excisional biopsy including skin, subcu\u00ad\ntaneous tissue, and muscle is optimal.\nThe following pathologic features favor necrotizing \n\u00adfasciitis:\n\t\u2022\t \u0007Liquefactive necrosis of superficial fascia.\n\t\u2022\t \u0007Polymorphonuclear leukocyte infiltration of the deep \ndermis and fascia.\n\t\u2022\t \u0007Fibrinous thrombi of arteries and veins passing through \nthe fascia.\n\t\u2022\t \u0007Angiitis with fibrinoid necrosis of arterial and venous walls.\n\t\u2022\t \u0007Microorganisms within the destroyed fascia and dermis \n(Gram stain).\n\t\u2022\t \u0007Absence of muscle involvement. \nThe usual differential diagnosis is with cellulitis or ery\u00ad\nsipelas. In these conditions, inflammation will be present \nbut will be in superficial tissue without significant involve\u00ad\nment of deep soft tissue and fascia.16,17\nBreast Biopsies\nCarcinoma\nReason for Consultation.\u2002 Diagnosis of invasive carcinoma.\nChange in Surgery or Processing.\u2002 Additional tissue may \nbe taken for clear margins and/or an axillary dissection \nmay be performed. If there will be no change in procedure, \nintraoperative consultation is unnecessary.\nEvaluation.\u2002 The most important objective in examining \nbreast biopsies is to make a definitive diagnosis. Therefore, \ntissue must not be used for frozen sections if the diagno\u00ad\nsis could be compromised. Only grossly evident masses \nof sufficient size should be examined by frozen section \n(the recommendation is over 1 cm).18 Smaller masses, \ngrossly benign tissue, or tissue removed for the evaluation \nof calcifications should never be frozen, as freezing can \n\u00adintroduce artifacts in small lesions, precluding a diagnosis \non \u00adpermanent sections.\nIf the specimen has been oriented, care must be taken \nin inking the margins and processing the tissue in order to \nbe able to submit tissue according to this orientation (see \nChapter 15).\nNote the location of any palpable masses. If the mass is \nlarger than 1 cm and suspicious for invasive carcinoma, a \nfrozen section may be performed. Make a careful measure\u00ad\nment of the maximal tumor size to the nearest 0.1 cm. The \nimportant sizes for staging are 0.5 cm, 1 cm, 2 cm, and \n5\u00a0cm. Do not round to the nearest 1 cm. A gross evalu\u00ad\nation of margins for the proximity of invasive carcinoma \nmay also be provided (see later).\nIf a definitive diagnosis cannot be made (e.g., the dif\u00ad\nferential diagnosis includes a complex sclerosing lesion or \ntubular carcinoma) all lesional tissue must be submitted for \nhistologic evaluation.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_071.png", "summary": "The page discusses common operating room consultations for evaluating specimens, distinguishing between staphylococcal scalded skin syndrome and toxic epidermal necrolysis, and establishing the diagnosis of necrotizing fasciitis.", "questions": [ "How can the location of the closest margin be determined in a specimen that has been biopsied?", "What are the differences in treatment between staphylococcal scalded skin syndrome and toxic epidermal necrolysis?", "What are the initial symptoms and causative bacteria associated with necrotizing fasciitis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 72, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n54\nPitfalls.\u2002 False positive rates are low (<1%) but can \noccur.19 Thus, definitive surgery may best be deferred for \nsmall or questionable lesions.\nFalse negative rates are higher, but reported to be less \nthan 10%. The rate will be lower if restricted to lesions \ngrossly suspicious for invasive carcinoma.\nIn general, frozen section evaluation is not useful to \neither diagnosis DCIS or exclude its presence.\nTissue from primary breast biopsies without a doc\u00ad\numented lesion must never be given away for research.\nMargins\nReason for Consultation.\u2002 To grossly evaluate the ade\u00ad\nquacy of margins for invasive carcinoma.\nChange in Surgery.\u2002 Additional tissue may be taken at a \nmargin deemed to be close.\nEvaluation.\u2002 Most invasive carcinomas can be detected \nas grossly palpable masses. Very few cases of DCIS can be \ndetected grossly, and they are difficult to diagnose by frozen \nsection.\nIf there is no prior diagnosis, process the specimen as \ndescribed above.\nIf a diagnosis of invasive carcinoma has been made pre\u00ad\nviously, it is generally unnecessary to perform a frozen \nsection and the margins are evaluated grossly for involve\u00ad\nment. If the carcinoma is present (e.g., after a core biopsy), \nthe distance to each margin is determined and reported to \nthe surgeon. If the carcinoma has been excised (e.g., after \nexcisional biopsy) the rim of the biopsy cavity is examined \nfor areas suspicious for residual invasive carcinoma at the \nmargin. Selected frozen sections of grossly suspicious areas \nmay be helpful.\nMargin involvement by DCIS is difficult to assess by \nfrozen section:\n\t\u2022\t \u0007The marginal tissue usually consists of grossly benign \nadipose tissue, which is difficult to freeze and section \nadequately.\n\t\u2022\t \u0007It may be difficult to distinguish hyperplastic lesions \nfrom DCIS on frozen sections.\n\t\u2022\t \u0007Not all marginal tissue can be evaluated by frozen sec\u00ad\ntion. Additional tissue examined by permanent sections \nmay later be shown to be involved.\nHowever, some institutions do evaluate margins \nby either cytologic means20,21 or frozen section.22 \nThe majority of the cases evaluated have been inva\u00ad\nsive carcinomas and not DCIS alone. The value of \nsuch margin evaluation will depend on the definition \nof a \u201cpositive\u201d margin and institutional criteria for the \nnecessity of further surgical procedures based on margin \nevaluation.\nSentinel Lymph Nodes\nReason for Consultation.\u2002 To determine whether a metas\u00ad\ntasis is present in the node.\nChange in Surgery.\u2002 If a metastasis is found in the sen\u00ad\ntinel lymph node, a completion axillary dissection will be \nperformed.\nEvaluation.\u2002 On average, there will be two sentinel \nlymph nodes. The nodes should be grossly dissected from \nthe tissue received. Separate the fat and ink each node a \ndifferent color. It is very important to be able to keep track \nof the number of involved nodes as this is an important \nprognostic factor and is used to classify women for clinical \ntrials.\nSlice each node into 0.2 to 0.3 cm slices.\nIf there is a grossly evident metastasis, only one repre\u00ad\nsentative section need be frozen.\nIf the nodes are grossly normal, freeze all of the slices. \nAll macrometastases (>0.2 cm) should be identified using \nthis method. If there are multiple nodes, it may be prudent \nto discuss with the surgeon before proceeding.\nTouch preparations can also be used to evaluate the \nnodes. Each node should be scraped and evaluated sepa\u00ad\nrately. Make sure the work area is clean and far away from \nany other specimens with malignancies to avoid contami\u00ad\nnation.\nPitfalls.\u2002 False negatives for macrometastases can occur \nif the entire node is not frozen. Micrometastases (<0.2 cm) \nwill often be missed due to sampling, but there is no prac\u00ad\ntical method to find all such small metastatic deposits. \nMetastases from lobular carcinomas can be very subtle on \nfrozen section and it is helpful to know whether the patient \nhas this type of cancer. If a definite diagnosis cannot be \nmade, it is better to defer the diagnosis. A completion dis\u00ad\nsection can be performed at a later time.\nGastrointestinal Specimens\nEsophagectomies and Gastrectomies\nReason for Consultation.\u2002 To determine whether the \nresection margins are free of malignancy or dysplasia and \nto ensure that the lesion has been resected.\nChange in Surgery.\u2002 Additional esophagus or stomach \nmay be resected to achieve clean margins.\nEvaluation.\u2002 Gross inspection of the opened specimen is \noften sufficient to establish clear margins. However, tumors \n(particularly diffuse-type gastric carcinomas or esophageal \nadenocarcinomas) located close to the resection margins \nmay infiltrate beneath grossly normal mucosa. Therefore, \ncomplete inspection of the margins and selection of appro\u00ad\npriate frozen sections is essential.\nInk the serosa and adventitia along the area to be \nopened.\nOpen the proximal and distal margins by cutting as \nclose as possible to the staple line.\nOpen the specimen longitudinally, but avoid cutting \nthrough the lesion. Esophagectomy and gastrectomy", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_072.png", "summary": "Operating room consultations involve evaluating margins for invasive carcinoma and determining the presence of metastasis in sentinel lymph nodes.", "questions": [ "How accurate are frozen section evaluations in diagnosing DCIS?", "What are the implications of margin involvement by DCIS?", "What is the significance of evaluating sentinel lymph nodes in determining prognosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 73, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n55\nspecimens are best opened by following the greater curva\u00ad\nture of the stomach, unless a lesion is present there.\nRecord the size and location of any lesions and the \ndistance from the proximal and distal margins. Patients \nhave often had prior radiation and/or chemotherapy and \nthe residual tumor may not be grossly evident or quite \nsubtle (e.g., a shallow mucosal ulceration). Avoid touch\u00ad\ning the mucosa, which is fragile and easily abraded. \nIf necessary, the mucosa can be gently rinsed with \nsaline.\nEsophagectomies are often involved by Barrett\u2019s \nesophagus, which is recognizable as granular pink mucosa. \nRecord the length of this segment and its closest approach \nto the proximal margin. If Barrett\u2019s mucosa is present at \nthe proximal margin, a frozen section is essential as dys\u00ad\nplasia may be present and additional resection may be \nnecessary.\nTake the margins en face, unless a gross lesion is \nvery close to the margin and a perpendicular section can \ninclude both the lesion and margin. The margin sec\u00ad\ntion should be taken from the area closest to the site of \nthe tumor. It is important that the en face section is full \nthickness including mucosa, submucosa, and muscularis, \nas carcinoma may involve any of these layers. Because \nthe overlying mucosa may curl over the edge of the \ncut margin, it may be necessary to gently pull back this \nmucosa to line it up over the muscularis before taking the \nsection.\nColonic Malignancy or Polyps\nReason for Consultation.\u2002 To determine whether the mar\u00ad\ngins are free of malignancy or polyps, to accurately mea\u00ad\nsure the length of the margin, and to ensure that the lesion \nhas been resected.\nChange in Surgery.\u2002 Additional colon may be resected.\nEvaluation.\u2002 In the majority of cases, gross evaluation of \nthe margins is sufficient to ensure clear margins. However, \nsince these patients are at risk for multiple lesions, the mar\u00ad\ngins must be completely opened and inspected to establish \nclear margins.\nExamine the segment of bowel externally to determine \nwhether there is evidence of invasive tumor at the serosal \nsurface or puckering of the serosa (indicative of invasion \ninto the muscularis). If the segment is from the rectosig\u00ad\nmoid, examine the mesentery to determine the location of \nthe rectosigmoid junction.\nCompletely open any stapled ends by cutting as close \nas possible to the staple line. Cut along the antimesenteric \nsurface with blunt scissors to open the bowel. However, \nadjust the line of opening to avoid transecting any lesions. \nThe bowel lumen may be rinsed clean with a small amount \nof saline, if necessary. Tap water is hypotonic and will \ndamage tissue.\nThe lesion(s) present are described and the distance \nfrom the proximal and distal margins is measured and \nrecorded on the OR consultation report. The bowel is \noften returned to the OR for the surgeon\u2019s viewing.\nBowel segments can contract up to 40% within 10 to \n20 minutes after excision.23 Because close margins may be \nan indication for postoperative radiation therapy for rectal \ncarcinomas, margin lengths are best measured as soon as \npossible after excision.\nFrozen sections are rarely necessary for margin evalu\u00ad\nation if the uninvolved mucosa is grossly normal. In cases \nof malignancy arising in inflammatory bowel disease (see \nbelow), frozen section evaluation may be indicated in \nselected cases. Evaluation of margins after treatment (typi\u00ad\ncally radiation) or for certain histologic types (i.e., signet \nring cell carcinomas) can also be difficult and may require \nfrozen section.\nIf it is unclear why a segment of bowel was removed (e.g., \nno lesion is apparent), contact the surgeon. For example, if \nthe surgery was performed for a previously biopsied polyp \nwith invasive carcinoma, the \u201clesion\u201d may be a subtle prior \nbiopsy site consisting of \u00admucosal ulceration that must be \nfound and sampled for permanent sections to ensure that a \ncomplete resection has been performed. Alternatively, it is \npossible that a lesion has been missed and additional sur\u00ad\ngery must be performed.\nSample Operating Room Consultation Reports\u2002\nSPECIMEN NO. 2, RECTOSIGMOID RESECTION \n(33 CM) (GROSS EXAMINATION):\nUlcerated lesion (4.4 cm) grossly consistent with adeno\u00ad\ncarcinoma, located 3 cm proximal to the rectosig\u00ad\nmoid junction. The tumor is 5 cm from the distal \nmargin and 24 cm from the proximal \u00admargin.\nThe specimen is returned to the operating room per the \nsurgeon\u2019s request.\nInflammatory Bowel Disease (IBD)\nReason for Consultation.\u2002 In cases of Crohn\u2019s disease \nthe bowel may be inspected for gross ulceration at the \nmargin.\nChange in Surgery.\u2002 The intent is to resect grossly \ninvolved bowel. Additional bowel may be resected if gross \nchanges are present at the margin. The evaluation of mar\u00ad\ngins in Crohn\u2019s disease is very controversial and some \nstudies have found that neither the length of uninvolved \nmucosa nor the presence of microscopic findings at the \nmargin affect recurrence rates.24,25\nEvaluation.\u2002 The outer surface of the bowel is inspected \nfor creeping fat or fistulas indicative of IBD.\nOpen the bowel as described above. Inspect the mucosa \nfor changes of IBD. Look carefully for any areas suspicious \nfor malignancy. In cases of Crohn\u2019s disease, margins should \nbe inspected for gross ulceration. The typical operation for \nulcerative colitis is a total colectomy with removal of all \ncolonic mucosa, and margins are not important.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_073.png", "summary": "The text discusses the proper handling and evaluation of specimens from common operating room consultations, such as stomach and colon specimens.", "questions": [ "How should specimens from the stomach be opened and handled during evaluation?", "What is the significance of Barrett's esophagus in esophagectomies?", "What steps should be taken when evaluating colon specimens for malignancy or polyps?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 74, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n56\nFrozen sections are not needed for the evaluation of \ninflammatory changes. In cases of suspected malignancy \narising in IBD frozen sections may be helpful.\nSample Operating Room Consultation Reports\u2002\nSIGMOID COLON (28 CM) (GROSS \u00adEXAMINATION):\nThickened bowel wall with linear mucosal ulcer\u00ad\nations and fistula tract, consistent with prior diagnosis of \nCROHN\u2019S DISEASE.\nGross ulceration present at the proximal resection \n\u00admargin. The distal resection margin is free of ulceration. \nSurgeon informed.\nThe specimen is returned to the operating room per the \nsurgeon\u2019s request.\nLiver Biopsy\nReason for Consultation.\u2002 A liver lesion is discovered dur\u00ad\ning abdominal surgery.\nChange in Surgery.\u2002 If the liver lesion is a metastasis, the \nextent of surgery may be altered (e.g., palliative as opposed \nto curative surgery may be performed).\nEvaluation.\u2002 The typical specimen is a small biopsy that \ncan be frozen in its entirety. The most common metastatic \ncarcinoma encountered is colon carcinoma.\nPitfalls.\u2002 Small white lesions are often present on the \nliver capsule due to bile duct hamartomas (single lesions) \nor bile duct adenomas (von Meyenberg complexes, often \nmultiple). These lesions consist of relatively orderly pro\u00ad\nliferations of small bile ducts. Care must be taken not to \nmistake them for metastatic \u00adadenocarcinoma.\nPancreas\nReason for Consultation.\u2002 To determine whether malig\u00ad\nnancy is present.\nChange in Surgery.\u2002 If malignancy is present, a major \nresection may be carried out (e.g., a Whipple resection) \nand/or staging biopsies may be performed.\nEvaluation.\u2002 Pancreatic carcinomas can be very difficult \nto detect grossly and microscopically in a background of \nchronic pancreatitis that results in a densely firm nodular \ngland. Biopsies are usually small wedge or needle biopsies \nbut are associated with a significant risk of complications. \nUseful diagnostic criteria for pancreatic carcinoma on fro\u00ad\nzen section have been published.26\nPitfalls.\u2002 False positive diagnoses are rare but false nega\u00ad\ntives have been reported in greater than 30% of cases. \nThese latter cases are due equally to sampling error (i.e., \nthe area of carcinoma was not biopsied for frozen sec\u00ad\ntion) and to interpretation error.27 Sampling error can be \nreduced by examining multiple biopsies. Interpretation \nerror can be minimized by using the \u00adcriteria described \nabove and attention to the following histologic findings:\n\t\u2022\t \u0007Accessory pancreatic ducts can be found in smooth mus\u00ad\ncle of the duodenum, but will consist of groups of glands \nsurrounded by loose connective tissue. Malignant glands \ninvading muscle are present singly and will be in contact \nwith muscle cells.\n\t\u2022\t \u0007The distribution of ducts can become irregular in cases \nof severe pancreatitis. Other criteria of malignancy \nshould be searched for as well.\n\t\u2022\t \u0007Islets become prominent in chronic pancreatitis and may \nmimic clusters of epithelial cells with marked nuclear \nvariation in size.\n\t\u2022\t \u0007Atrophic acini and ductules can appear to have incom\u00ad\nplete lumens.\n\t\u2022\t \u0007Normal ducts can occasionally be seen adjacent to nerves \nand simulate perineural invasion.\nGenitourinary Specimens\nSperm Identification\nReason for Consultation.\u2002 To determine whether sperm \nare being produced by the testis.\nChange in Surgery.\u2002 Men with azoospermia may have pri\u00ad\nmary failure of spermatogenesis or an obstructed vas def\u00ad\nerens. Urologists may send fluid milked from the proximal \nvas deferens for identification of sperm before performing \nanastomotic surgery to correct an obstruction.\nEvaluation.\u2002 The fluid is placed on a slide and cover\u00ad\nslipped. Without staining the slide, the preparation is \nexamined for the presence of spermatozoa. The OR con\u00ad\nsultation report notes whether sperm are present or absent.\nMotility depends on temperature and time since prepa\u00ad\nration of the slide and thus is not a very accurate predictor \nof true motility if absent.\nAfter the diagnosis is rendered, the coverslip is removed \nand the slide placed in 95% ethanol. The slide can be \nstained with H&E and permanently coverslipped.\nMajor criteria (present in all cases of carcinoma):\n \n \n1.\t \u0007Nuclear size variation equal to, or greater than 4:1\n \n2.\t \u0007Incomplete glandular lumens\n \n3.\t \u0007Disorganized duct distribution\nMinor criteria (present in 28% to 70% of cases of \n\u00adcarcinoma): \n \n1.\t \u0007Huge irregular epithelial nucleoli\n \n2.\t \u0007Necrotic glandular debris\n \n3.\t \u0007Glandular mitoses\n \n4.\t \u0007Glands unaccompanied by stroma in smooth mus\u00ad\ncle fascicles\n \n5.\t \u0007Perineural invasion", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_074.png", "summary": "Frozen sections are not typically needed for evaluating inflammatory changes, but may be helpful in cases of suspected malignancy in IBD. Consultations for liver lesions and pancreatic malignancy involve potential changes in surgery and evaluation pitfalls.", "questions": [ "What are the indications for using frozen sections in cases of suspected malignancy in IBD?", "How can the presence of liver lesions impact the extent of surgery?", "What are the pitfalls associated with diagnosing pancreatic carcinoma on frozen section?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 75, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n57\nNephrectomy, Cystectomy, or Ureterectomy \nfor Transitional Cell Carcinoma\nReason for Consultation.\u2002 To evaluate the ureteral mar\u00ad\ngins for the presence of transitional cell carcinoma.\nChange in Surgery.\u2002 The surgeon may take an additional \nportion of the ureter to achieve margins free of carcinoma.\nEvaluation.\u2002 A length of ureter is usually provided sepa\u00ad\nrate from the main excision. A suture may mark the true \nmargin. A complete cross section of the ureter is taken for \nfrozen section. The true margin may be embedded so that \nthe first frozen section is the true margin.\nPartial Nephrectomies\nReason for Consultation.\u2002 To evaluate the margin of a \npartial nephrectomy. Usually the function of the contralat\u00ad\neral kidney is compromised.\nChange in Surgery.\u2002 Additional kidney tissue may be \ntaken or a complete nephrectomy may be performed.\nEvaluation.\u2002 Ink the kidney over the open area of tran\u00ad\nsection. Serially section the kidney perpendicular to the \nmargin and evaluate grossly for any lesions present. The \nmargin closest to the tumor is frozen. About 17% of cases \nwill have positive margins. Frozen section is generally reli\u00ad\nable for diagnosis of carcinomas, but can be difficult for \nunusual tumors.\nGynecologic Pathology\nOvary\nReason for Consultation.\u2002 Evaluation of malignancy of an \novarian tumor.\nChange in Surgery.\u2002 If a malignancy is identified, appro\u00ad\npriate staging biopsies and/or TAH/BSO will be performed \n(e.g., omental biopsies, biopsies of other suspicious areas, \nperitoneal washings, lymph node biopsies). If extensive dis\u00ad\nease is present, and a metastatic carcinoma is identified, only \nthe surgery deemed clinically appropriate will be performed. \nFertility may be preserved if a benign diagnosis is rendered.\nEvaluation.\u2002 All cysts and solid tumors are opened and, if \nnecessary, serially sectioned (see the section on processing \novarian specimens for appropriate procedures for opening \ncysts). In general, ovarian tumors in women over the age of 40 \nare more commonly borderline or malignant, whereas those \nin women under the age of 40 are more commonly benign.\n\t\u2022\t \u0007Unilocular cysts with a smooth inner lining: Almost \nalways benign. Gross examination is sufficient. \u201cEndo\u00ad\nmetriomas\u201d are unusual in postmenopausal women and \nshould be examined by frozen section to exclude carci\u00ad\nnoma in this age group.\n\t\u2022\t \u0007Mature teratomas (dermoid cysts): These cysts are \nfilled with sebaceous material and hair and are almost \nalways benign. Gross examination is sufficient unless \nsubstantial solid areas are present or the tumor has spon\u00ad\ntaneously ruptured.\n\t\u2022\t \u0007Unilocular or multilocular cysts with irregular lin\u00ad\nings: Visually inspect the lining for any areas of irregular\u00ad\nity (e.g., minute papillary excrescences) or solid areas. Do \nnot touch the inner surface, as this may remove diagnos\u00ad\ntic lining cells. Multilocular cysts or cysts with solid areas \nare more suspicious for malignancy. Frozen section(s) \nshould be performed on the most suspicious areas.\n\t\u2022\t \u0007Solid masses: Examine the surface for involvement, as \nthis could affect stage. Multiple nodules may signify met\u00ad\nastatic disease. Frozen sections are routinely performed.\nPitfalls.\u2002 If tumors are divided into benign, malignant, \nand borderline categories, frozen section and permanent \nsections are concordant in greater than 90% of cases.28\nThe following types of tumors are the most difficult to \nevaluate by frozen section:\n\t\u2022\t \u0007Large tumors (> 10 cm). Additional sections may be \nhelpful to look for focal invasive carcinoma.\n\t\u2022\t \u0007Mucinous carcinomas. These carcinomas are often \nheterogeneous and can require extensive sampling, and \noften immunohistochemistry, for correct classification.\n\t\u2022\t \u0007Borderline tumors. Approximately 20% of tumors \nclassified as borderline on frozen section will be reclassi\u00ad\nfied as malignant after more extensive sampling for per\u00ad\nmanent sections.\nUterus\nENDOMETRIAL CARCINOMA\nReason for Consultation.\u2002 Evaluation for presence or absence \nof endometrial carcinoma. If present, the grade, depth of inva\u00ad\nsion and involvement of the cervix (Stage II) is \u00addetermined.\nChange in Surgery.\u2002 If carcinoma invades deeply into the \nmyometrium (beyond 50% of the myometrial thickness), \nand/or the carcinoma is grade II or III, and/or the cervix \nis involved, the surgeon will likely perform pelvic and/or \nparaaortic lymphadenectomy.\nEvaluation.\u2002 The serosa is carefully inspected for areas \nsuspicious for direct tumor invasion or serosal implants. \nSuspicious areas on the serosal and the surgically incised \nparametrial margins are inked. Open the uterus along the \nlateral edges using a scissors (see Chapter 22 for additional \ndetails). Carefully inspect (but do not touch!) the endome\u00ad\ntrial lining for gross evidence of tumor (usually pale yellow/\ntan heaped up/firm areas). Make serial transverse incisions \nfrom the mucosal surface to, but not through, the serosa \n(leaving the specimen intact) at 0.5 cm intervals. Myome\u00ad\ntrial invasion by tumor grossly appears as \u00adeffacement of \nthe normal myometrial texture. Depth of invasion can be", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_075.png", "summary": "The page discusses the evaluation and changes in surgery for nephrectomy, cystectomy, ureterectomy, partial nephrectomies, and gynecologic pathology of the ovary, focusing on the presence of transitional cell carcinoma and malignancy.", "questions": [ "What are the key considerations in evaluating ureteral margins for transitional cell carcinoma?", "How does the presence of malignancy impact the surgical approach for ovarian tumors?", "What are the characteristics of different types of ovarian cysts and tumors that indicate benign or malignant potential?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 76, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n58\ndetermined grossly in some, but not all, cases. A frozen \nsection should be performed in the area most suspicious \nfor the deepest extent of myometrial invasion. The surface \nof the fallopian tubes and ovaries is also carefully inspected, \nand the ovaries are cross-sectioned and examined for areas \nsuspicious for malignancy.\nPitfalls.\u2002 False positive and false negative frozen section \ndiagnoses are reported for all three prognostic factors. \nOverall, grade is accurately determined in 67% to 96% \nof cases, depth of invasion in 85% to 95%, and cervical \ninvolvement in 65% to 96%.29\n\t\u2022\t \u0007False positive: Greater than 50% myometrial invasion is \nreported in about 9% of cases but is not present on perma\u00ad\nnent sections; carcinomatous involvement of adenomyosis \nor deep lymphovascular invasion is mistaken for invasion.\n\t\u2022\t \u0007False negative: Myometrial invasion is not reported in \nabout 10% of cases but is present on the permanent sec\u00ad\ntions; diffusely invasive carcinomas with widely spaced \nglands and a minimal desmoplastic response may not be \nseen grossly or on frozen section. \nLEIOMYOMA\nReason for Consultation.\u2002 Evaluation \nof \npresumed \n\u00adleiomyomata for possible malignancy. Clinical features \nsuspicious for malignancy include ultrasound findings (e.g., \nan irregular border or cystic areas), large size, soft consis\u00ad\ntency, or difficulty in removing the lesion from the uterine \nwall. However, this finding is more commonly associated \nwith adenomyosis than with malignant invasion.\nChange in Surgery.\u2002 If the initial procedure is a myomec\u00ad\ntomy, a total hysterectomy may be performed if a malig\u00ad\nnancy is present. Additional biopsies may be taken of any \nsuspicious peritoneal lesions.\nEvaluation.\u2002 All masses are sectioned at ~1 cm intervals. \nTypical leiomyomas are white, whorled, firm, and without \nnecrosis or hemorrhage. Degenerative changes are com\u00ad\nmon and include a carneous (fleshy) appearance or cystic \nmucoid areas. Features suggestive of malignancy include \na soft consistency, necrosis, hemorrhage, infiltrative bor\u00ad\nders, and vascular invasion. Frozen sections may be per\u00ad\nformed on grossly suspicious lesions.\nPitfalls.\u2002 Infertile \npremenopausal \nwomen \nundergo\u00ad\ning myomectomy to improve uterine function may be \n\u00adreceiving hormonal treatments resulting in an increased \nmitotic rate in benign leiomyomas. A definitive diagnosis \nof malignancy should not be made on frozen section unless \nobvious features of malignancy are present.\nIf there has been a prior recent previous surgical pro\u00ad\ncedure (e.g., a partial myomectomy or endometrial curet\u00ad\ntings), increased mitoses and necrosis may be seen in \nbenign leiomyomas.\nVulvectomy\nReason for Consultation.\u2002 To evaluate the resection mar\u00ad\ngins for carcinoma or dysplasia.\nChange in Management.\u2002 Additional vulvar skin may be \nresected.\nEvaluation.\u2002 If a gross lesion or biopsy site is present, the \nclosest margin may be frozen as a perpendicular section. If \nno gross lesions are evident, it is useful to determine the \nlocation of the clinical lesion (often previously excised) and \nto sample the margin at this site. Frozen sections are discour\u00ad\naged for vulvar specimens containing pigmented lesions.\nProducts of Conception\nReason for Consultation.\u2002 Women who are pregnant \n(positive HCG) who present with vaginal bleeding or pel\u00ad\nvic pain, but without an obvious intrauterine pregnancy by \nultrasound, are at risk for an ectopic pregnancy and its asso\u00ad\nciated complications (e.g., fatal hemorrhage). Endometrial \ncurettings or tissue from the vaginal vault is submitted to \ndetermine whether placental villi and/or a recent implanta\u00ad\ntion site are present, which would confirm that the preg\u00ad\nnancy was intrauterine. Rarely, a gestational sac may be \npresent. The frozen section results should be clearly con\u00ad\nveyed to the clinician as a PRELIMINARY result.\nChange in Management.\u2002 If an intrauterine pregnancy \ncannot be documented, the patient may require pelviscopy \nand methotrexate treatment.\nEvaluation.\u2002 The best method to examine such speci\u00ad\nmens is with a dissecting microscope. Float the specimen in \nsaline in a Petri dish. It may be necessary to rinse the speci\u00ad\nmen free of blood. Frozen section should be performed on \nthe tissue most likely to be villi (Table 6-2).\nPitfalls.\u2002 In a study in which all tissue was frozen, the \ncorrect diagnosis was made in 93% of the cases.30 There \nwas a 5.7% false negative rate due to villi present in deeper \nsections of the tissue that were not seen on frozen section. \nThere was one false positive case (1.1% of total) due to \nmisinterpretation of edematous endocervix as villi. Frozen \nsections of an avillous intrauterine pregnancy are diffi\u00ad\ncult and the diagnosis requires verification of trophoblast \n(\u00adplacental site or isolated). The diagnosis is often missed.\nHead and Neck Resections\nReason for Consultation.\u2002 To determine the adequacy of \nmargins.\nChange in Surgery.\u2002 Additional tissue may be taken to \nachieve clean margins. Often a reconstructive procedure is \nperformed immediately, so the opportunity to resect more \ntissue in the future may not be an option. Postoperative", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_076.png", "summary": "The page discusses common operating room consultations for cases involving myometrial invasion, leiomyoma evaluation, and vulvectomy resection margins.", "questions": [ "What are the pitfalls associated with false positive and false negative frozen section diagnoses in cases of myometrial invasion?", "What clinical features are considered suspicious for malignancy in leiomyomata evaluation?", "What changes in management may occur if malignancy is present during a myomectomy procedure?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 77, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n59\nradiation therapy may compromise the reconstruction and \nis avoided if possible.\nEvaluation.\u2002 It is preferable to review any complicated \nspecimens with the surgeon prior to inking to identify \nanatomic structures, the location of probable tumor, and \nsurgical margins. Perpendicular sections are taken at the \nclosest margins. A very narrow (e.g., less than 0.1 cm) mar\u00ad\ngin may be considered to be an adequate margin.\nEn face margins are sometimes used to sample a larger \narea if the mucosa appears grossly normal. The en face \nmargin is embedded so that the first full thickness frozen \nsection will represent the \u201ctrue\u201d mucosal margin. Multiple \nsections may be made, but must be numbered to identify \nthe first section. If tumor is found only on deeper sec\u00ad\ntions (e.g., in deeper levels of the frozen section or in the \npermanent sections) the tumor is not present at the true \nmargin.\nPitfalls.\u2002 Radiation changes, particularly in minor sali\u00ad\nvary glands, may be difficult to distinguish from invasive \ncarcinoma. First establish whether or not the patient has \nreceived radiation therapy. Look for squamous metaplasia \nand a lobular arrangement which favor benign changes.\nPerineural invasion is common in these tumors and can \nbe responsible for local recurrences if present. The juxta\u00ad\noral organ of Chievitz is found at the angle of the mandible \nand consists of epithelial nests in close proximity to nerves. \nThis normal structure can be mistaken for perineural inva\u00ad\nsion on frozen section.31\nLung and Pleura\nMediastinal Staging of Lung Carcinomas\nReason for Consultation.\u2002 To determine whether a lung \ncarcinoma is resectable (stage I, stage II, or stage IIIA lung \ncarcinomas with involvement of ipsilateral but not contra\u00ad\nlateral mediastinal lymph nodes) or to terminate lymph \nnode sampling once a positive lymph node is found.\nChange in Surgery.\u2002 Patients without lymph node metas\u00ad\ntases may proceed to definitive resection in the same proce\u00ad\ndure. Patients with metastatic disease may have a curtailed \nprocedure as additional nodes are not necessary for staging \nand resection may not be indicated.\nIf positive nodes are found at frozen section, the patient \nmay be kept in the hospital longer for oncologic planning \nand consultation and possibly other radiologic examina\u00ad\ntions. If the nodes are negative, the patient is usually dis\u00ad\ncharged the same day.\nEvaluation.\u2002 The purpose of the node biopsy must be \nknown, as this will alter the processing of the specimen:\n\t\u2022\t \u0007Staging of lung carcinoma: The entire node or nodes \nare frozen. Patients are generally older and have a lung \nmass.\n\t\u2022\t \u0007Evaluation of lymphadenopathy: The differential \ndiagnosis includes lymphoma, infection, and sarcoidosis. \nOnly a portion of the specimen should be frozen or touch \npreparations used. Tissue should be preserved for pos\u00ad\nsible special studies including microbiological culture, \nfrozen tissue, and/or flow cytometry. Patients are usually \nyounger and generally do not have lung involvement.\nPitfalls.\u2002 In one study, 30% of patients undergoing medi\u00ad\nastinal staging had metastatic disease.32\n\t\u2022\t \u0007False positive results (very rare): Pleural adhesions \ncan be mistaken for carcinoma involving the mediasti\u00ad\nnum. Benign mesothelial cells may be present in medi\u00ad\nastinal lymph nodes.\n\t\u2022\t \u0007False negative (1.6% of patients): Macrometastases (>0.2 \ncm) can be missed if the entire node is not frozen. Small \nmetastastic deposits may be missed due to sampling, but \nthere is no practical method to find all micrometastases.\nPulmonary Resections for Lung Masses\nReason for Consultation.\u2002 To identify malignancy in lung \nmasses.\nChange in Surgery.\u2002 If malignancy is present additional \nsurgery may be indicated to ensure clean margins and/or \nfor complete staging.\nEvaluation.\u2002 Lung masses may be resected by wedge \nresection, lobectomy, or pneumonectomy.\nWedge resections.\u2002 This is often the initial procedure for \nthe evaluation of small masses.\nTABLE 6\u20132.\u2003\nDIFFERENTIATION OF PLACENTAL VILLI FROM DECIDUALIZED ENDOMETRIUM\nCOLOR\nSTRUCTURE\nBRANCHING\nCONSISTENCY\nVilli\nWhite (or pink)\nComplex 3-dimensional \narchitecture (like a shrub \nor sea anemone).\nAcute angle branching\nSpringy (rapidly \nre-expand after \nbeing gently \nsqueezed)\nDecidualized \n\u00adendometrium\nPink (but may be white). \nMore opaque than villi.\nGlandular and vascular \n\u00adstructures may mimic villi.\nStructures run in parallel \nand are not branched.\nNot springy", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_077.png", "summary": "The page discusses the importance of reviewing complicated specimens with surgeons prior to inking, the use of en face margins for sampling larger areas, and the challenges in distinguishing radiation changes from invasive carcinoma.", "questions": [ "How can surgeons and pathology assistants collaborate effectively in reviewing complicated specimens?", "What are the advantages and limitations of using en face margins for sampling?", "What are the key factors to consider when distinguishing radiation changes from invasive carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 78, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n60\n \n1.\t \u0007Palpate the specimen to determine the location of \nthe mass or masses.\n \n2.\t \u0007Inspect the pleura for involvement by tumor (and/\nor adhesions) or adherence to the underlying mass. \nPleural involvement is a prognostic factor and is \nused for AJCC T classification. Document whether \nor not the pleura is involved by the mass.\n \n3.\t \u0007If solitary and well defined, the mass is bisected, \navoiding any area of possible pleural involvement \n(which should be preserved for evaluation by perma\u00ad\nnent sections).\n \n4.\t \u0007A representative section of the mass is frozen for \n\u00addiagnosis.\n \n5.\t \u0007In cases of malignancy, the margins of a wedge \nresection are taken by cutting away the staple line \nas close to the staples as possible. The exposed lung \nparenchyma is blotted dry and then inked. A per\u00ad\npendicular or en face section of lung tissue in the \narea closest to the tumor can be used as the margin. \nHowever, check with the surgeon first to determine \nwhether a more extensive resection is going to be \nperformed (e.g., lobectomy), in which case margins \non the wedge resection are irrelevant. Only paren\u00ad\nchymal involvement by tumor should be reported as \na positive margin. Loose tumor cells in air spaces are \nmost likely artifacts and are usually not considered a \ntrue positive margin.\nPitfalls.\u2002\n\t\u2022\t \u0007Bronchioloalveolar carcinoma: The gross appearance \nis of a focal, firmer, ill-defined area of lung parenchyma. \nLymphomas and focal pneumonia can have the same \ngross findings. Microscopically, these carcinomas may \nbe difficult to distinguish from reactive atypia.33\n\t\u2022\t \u0007Carcinoid tumors: These tumors are important to \nidentify, as the indicated surgery may be less extensive. \nOn frozen section, they can be mistaken for lymphoma, \nsquamous cell carcinoma, or metastatic carcinoma.34\n\t\u2022\t \u0007Metastastic tumors: These lesions are critical to identify \nfor accurate patient staging and to determine the extent \nof surgery.35 The surgeon should inform the pathologist \nof any prior diagnoses of malignancy. In some cases (par\u00ad\nticularly for unusual tumors) it may be helpful for the \npathologist to review the slides on the previous tumor.\nLobectomies.\u2002 The mass is evaluated as described above. \nThe distance to the bronchial margin is determined. \n\u00adCarcinomas can extend into the bronchus for varying dis\u00ad\ntances beyond the gross tumor (adenocarcinomas ~ 2 cm, \nsquamous cell carcinomas ~ 1.5 cm). In one study, no car\u00ad\ncinoma >3 cm from the bronchial margin had a positive \nmargin.36 Margins can also appear falsely positive grossly \ndue to fibrous or lymphoid tissue.\nThe margin is taken as an en face section of the bronchus.\n\t\u2022\t \u0007Grossly normal and >3 cm from the tumor: Embed \nthe bronchial ring with the proximal (i.e., \u201ctrue\u201d) \nmargin down. This cut surface is usually flatter and will \nyield a complete section of the margin. Positive \u00admargins \nare rare. In the rare case of an initial section positive \nfor tumor, deeper levels into the block can be made to \ndetermine if the carcinoma is present at the true \u00admargin.\n\t\u2022\t \u0007Grossly suspicious margin or tumor < 3 cm from the \nmargin: Embed the true margin up. The first frozen \nsection will be the \u201ctrue\u201d margin.\nCare should be taken not to include pulmonary paren\u00ad\nchyma away from the bronchial ring in the frozen section, \nas tumor in this area will not be present at the bronchial \nstump in the patient.\nIf tumor is present in the frozen section, the location \nand nature of the tumor must be specified:\n\t \u2022\t \u0007In situ carcinoma in the bronchial mucosa.\n\t \u2022\t \u0007Submucosal invasive carcinoma.\n\t \u2022\t \u0007Peribronchial invasive carcinoma.\n\t \u2022\t \u0007Carcinoma in lymphatics or peribronchial lymph nodes.\nCarcinomas with a salivary gland morphology are rare, \nbut have a high incidence of positive margins. Carcinoid \ntumors may undermine the bronchial mucosa and be dif\u00ad\nficult to see grossly.\nPitfalls.\u2002 Overall, > 95% of margins can be accurately \ndiagnosed. True positive margins are rare (approximately \n6% of cases).\nFalse positive (~ 2%):\n\t \u2022\t \u0007Squamous metaplasia mistaken for carcinoma in situ\n\t \u2022\t \u0007Radiation changes mistaken for carcinoma\n\t \u2022\t \u0007Peribronchial lymphocytes mistaken for small cell \ncarcinoma (in such cases it is helpful to know the his\u00ad\ntologic type of the primary)\nFalse negative (~ 2%):\n\t \u2022\t \u0007Sampling errors\n\t \u2022\t \u0007Carcinoma in situ mistaken for squamous metaplasia\n\t \u2022\t \u0007Carcinoma mistaken for submucosal glands \nLung Biopsies\nReason for Consultation.\u2002 Open lung biopsies are usually \nperformed on critically ill patients with a wide differen\u00ad\ntial diagnosis. Frozen sections are performed to provide a \npreliminary diagnosis (e.g., tumor versus infection) and to \nguide apportionment of tissue. Culture and special stains \non histologic sections are complementary studies for the \nidentification of infectious disease.37\nChange in Management.\u2002 A preliminary diagnosis may \naid in selection of treatment for critically ill patients before \npermanent sections are available.\nEvaluation.\u2002 Apportioning tissue is done with the clini\u00ad\ncal differential in mind and the histologic appearance.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_078.png", "summary": "The page discusses the process of evaluating masses in the operating room, including determining pleural involvement, taking representative sections for frozen diagnosis, and considerations for wedge resections and lobectomies.", "questions": [ "How is pleural involvement by a mass used for prognostic factors?", "What are some pitfalls to be aware of when evaluating bronchioloalveolar carcinoma?", "How are margins handled in lobectomies and what factors can affect their appearance?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 79, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n61\nThe specimen is kept sterile until a block of tissue can be \nremoved for cultures. Evaluation and processing includes:\n 1.\t \u0007Determine whether the specimen is adequate for the \nstudies required. 1 cm3 is marginal, 2 cm3 is optimal. \nIf the specimen is too small for all studies required, call \nback the surgeon and request more tissue.\n 2.\t \u0007Using sterile technique, serially section through the \nspecimen looking for focal lesions. Transfer a block \nof tissue to a sterile container for microbiology. Each \nrequisition form must be labeled with the date and the \ncollection time to conform to Joint Commission guide\u00ad\nlines. The type of specimen should also be provided. \nEach microbiology laboratory will have individualized \nguidelines for the submission of specimens.\n 3.\t \u0007The two major indications for frozen section evaluation are:\n\t \u2022\t \u0007To determine whether a malignancy is present in order \nto do a more definitive procedure or to initiate treatment.\n\t \u2022\t \u0007In lung transplant patients, to guide therapy for pos\u00ad\nsible rejection or infection (e.g., viral).\nIn other cases, valuable diagnostic material is better \nexamined by permanent sections. Smears should be used \nfor OR consultation evaluation, if possible, because of \nthe high rate of infection in these patients.\n 4.\t \u0007The remaining tissue is apportioned for:\n\t \u2022\t \u0007B Plus fixation and snap freezing if lymphoma or leu\u00ad\nkemia is suspected\n\t \u2022\t \u0007Remainder in formalin\n 5.\t \u0007Special stains on smears for infectious organisms may \nbe helpful if they would be available prior to special \nstains on permanent sections. Smears should be fixed in \nmethanol. Air dried slides are potentially infectious and \nshould not be submitted to the laboratory.\nLymph Nodes for Suspected Lymphoproliferative \nDisorders\nReason for Consultation.\u2002 To determine whether sufficient \ntissue is present for eventual diagnosis and special studies.\nChange in Surgery.\u2002 Additional tissue may be provided if \nthe initial specimen is nonlesional or inadequate.\nEvaluation.\u2002 Never freeze an entire specimen. Cytologic \npreparations are often very helpful for evaluating small \nspecimens and are usually superior to frozen sections for \nthe diagnosis of lymphoproliferative diseases. Frozen sec\u00ad\ntions may be performed on larger specimens if cytologic \npreparations are not adequate.\nIf a lymphoproliferative disorder is suspected, tissue \nshould be saved for:\n \n1.\t \u0007B Plus fixation (best for morphology and immuno\u00ad\nperoxidase markers for hematopathology).\n \n2.\t \u0007Snap freezing (some markers are only available for \nfrozen tissue). This tissue can also be used for DNA \nor RNA analysis.\n \n3.\t \u0007Formalin fixation if the differential diagnosis \nincludes carcinoma (keratins not preserved well in \nB5), infectious disease (staining better in formalin), \nor if Hodgkin\u2019s disease is suspected (lacunar cells in \nNS HD seen only in formalin-fixed tissue).\n \n4.\t \u0007Flow cytometry can be helpful in selected cases.\n \n5.\t \u0007Microbiologic culture - Tissue may be sent for \nculture if an infectious process is in the differential \ndiagnosis.\nThe intention of the frozen section is not to provide \na definitive diagnosis. Usually \u201clesional tissue present\u201d or \n\u201csuspicious for a lymphoproliferative disorder\u201d are suffi\u00ad\ncient intraoperative diagnoses.\nNeuropathology \u2013 Stereotactic Brain Biopsies\nReason for Consultation.\u2002 Stereotactic biopsies are per\u00ad\nformed for deep-seated (i.e., thalamic) brain lesions \nnot amenable to open surgical biopsy of resection, or in \npatients with AIDS who have not responded to empiric \ntreatment for presumed toxoplasmosis or primary CNS \nlymphoma. OR consultation is requested to determine \nwhether the specimen is adequate for eventual diagnosis, \nincluding apportioning tissue for special studies (e.g., EM, \ncytogenetics, microbiologic culture).\nChange in Surgery.\u2002 If the specimen is nondiagnostic, \nadditional passes with the stereotactic needle should be \ndone (if considered safe by the surgeon), and repeat frozen \nsections and/or smear preparations should be examined, \nuntil diagnostic material is obtained.\nTreatment will vary with the diagnosis. Primary neo\u00ad\nplasms may be treated with immediate resection, by vari\u00ad\nous forms of intraoperative radiotherapy, or by interstitial \ncatheter implantation for brachytherapy. CNS lymphomas \nmay be treated by nonsurgical modalities such as cortico\u00ad\nsteroids, chemotherapy, or radiation.\nEvaluation.\u2002 The pathologist should be aware of the clin\u00ad\nical setting and neuroimaging characteristics of the lesion, \nas these factors can aid in the differential diagnosis under \nconsideration. Both smears and frozen sections should be \nperformed for maximum accuracy.38 Smears should be \nmade from 0.5 mm samples from each end of the core \nbiopsy specimen (or from one end of each core biopsy if \nmore than one core is provided). If possible, some of the \ncore (or cores) should be preserved unfrozen (i.e., free of \nfrozen artifact) for permanent sections or ancillary studies.\nPitfalls.\u2002 The major pitfall is inadequate sampling. Since \ngliomas can be heterogeneous in cellularity, with the edges", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_079.png", "summary": "Operating room consultations involve ensuring specimens are adequate for studies, serially sectioning specimens for lesions, and saving tissue for various evaluations.", "questions": [ "What are the major indications for frozen section evaluation?", "Why is it important to save tissue for different types of fixation?", "What are the guidelines for submitting specimens to microbiology laboratories?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 80, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n62\nof high-grade tumors often mimicking diffuse, low-grade \ntumors, multiple biopsies are required for accurate diagno\u00ad\nsis. Correlation with the neuroimaging is therefore crucial \nto be sure that the intraoperative diagnosis is consistent \nwith the radiologic findings. Intraoperative bleeding is a \ngrave danger, so that the surgeon may be reluctant to pro\u00ad\nvide additional material in the event of an initial nondi\u00ad\nagnostic pass. Nevertheless, the pathologist must not be \ntempted to \u201covercall\u201d minimal abnormalities on minute \nspecimens, lest the surgeon believe there is adequate diag\u00ad\nnostic material when there is not.\nProbable Sarcomas or Unusual Tumors\nBiopsy\nReason for Consultation.\u2002 To determine whether suffi\u00ad\ncient lesional tissue is present in a diagnostic biopsy for \neventual diagnosis on permanent sections and for special \nstudies.\nChange in Surgery.\u2002 The surgeon may remove additional \ntissue if the tissue is nonlesional or insufficient for needed \nstudies.\nEvaluation.\u2002 A frozen section or touch preparation may \nbe performed to determine whether lesional tissue is pres\u00ad\nent, to give a preliminary diagnosis, and to guide appor\u00ad\ntionment of tissue for special studies. A definitive diagnosis \nis not necessary, as final classification of such lesions often \nrequires examining multiple sections of the lesion and spe\u00ad\ncial studies. Often a diagnosis of \u201clesional tissue present\u201d \nis sufficient. In rare cases (e.g., a lesion is an intraoperative \nincidental finding), a designation of benign vs. malignant \nmay be requested (but this distinction may not always be \npossible).\nThe entire specimen should not be frozen. If only a \nsmall amount of tissue is available (i.e., the surgeon cannot \nprovide more tissue), then the entire specimen should be \nsaved for permanent sections. If the tissue does not appear \nlesional or is necrotic, additional tissue may be requested \nfrom the surgeon.\nThese tumors often require special studies to be clas\u00ad\nsified correctly. For mesotheliomas, see also Chapter 26. \nTumors are serially sectioned and representative sections \ntaken for special studies:\n \n1.\t \u0007Quick fix formalin. Thin sections of the tumor are \nplaced in a sufficient volume of formalin for rapid \nfixation. The fixation of the main tumor mass may be \ndelayed while tissue is taken for other studies, pho\u00ad\ntography, dissection, etc. These sections must be thin \nenough to not require recutting before submission.\n \n2.\t \u0007Electron microscopy. A small portion of tumor is \ncut into small cubes (< 0.1 cm per side) using a sharp \nblade and fixed for possible EM examination.\n \n3.\t \u0007Cytogenetics. Cytogenetic studies can be helpful \nfor classification or diagnosis in some cases. The \ntumor submitted must be viable and sterile. Tis\u00ad\nsue submitted for cytogenetics should be labeled \naccording to the area of the tumor sampled, and \nthis information should be documented in the gross \ndescription. If the tumor is heterogeneous in appear\u00ad\nance, and multiple areas are to be karyotyped, sub\u00ad\nmit each specimen in a separate container with labels \nlinked to histologic sections (e.g., \u201cArea A,\u201d \u201cArea \nB,\u201d \u201cArea C\u201d).\nAll large or deep-seated fatty tumors, mesothe\u00ad\nliomas, and suspected sarcomas are appropriate for \ncytogenetic analysis.\nIn some cases, it may be appropriate to submit \nlesions because of research interest. This should be \nindicated on the requisition sheet.\nApproximately 1 cm3 (if possible) should be \nplaced in transport medium. If the tumor is hetero\u00ad\ngeneous in appearance, submit matched specimens \nfor cytogenetics and fixation\n \n4.\t \u0007Snap freezing. Small sections of tumor (similar to \nthe size used for a frozen section) can be saved fro\u00ad\nzen. Such tissue may be useful for molecular diag\u00ad\nnostic studies (DNA and RNA analysis) as indicated.\n \n5.\t \u0007B Plus. If lymphoma is in the differential diagnosis, \ntissue should also be fixed in B Plus and possibly sent \nfor flow cytometry (see \u201cHematopathology\u201d).\nThe remainder of the specimen is saved for possible \nphotography and routine fixation in formalin.\nMargins\nReason for Consultation.\u2002 To evaluate the adequacy of \n\u00admargins.\nChange in Surgery.\u2002 Additional tissue may be taken at \nclose or positive margins.\nEvaluation.\u2002 Resections of sarcomas and mesotheliomas \nare often large and complicated. If orientation is unclear, \nseek clarification from the surgeon. The specimen is inked \nand serially sectioned. With occasional exceptions, it is \ngenerally inappropriate to freeze margins for sarcomas, \nsince any margin less than 2 cm from the tumor is usu\u00ad\nally an indication for radiotherapy or further surgery, if \n\u00adfeasible. If margins are frozen, they are taken as perpen\u00ad\ndicular margins and not en face margins.\nIn extrapleural pneumonectomies, usually all possible \ntissue has been removed from the thoracic cavity and these \nmargins are not evaluated except by specific request by the \nsurgeon. The bronchial resection margin is usually evalu\u00ad\nated by frozen section.\nThyroid Nodules\nThyroidectomy\nReason for Consultation.\u2002 To determine whether a carci\u00ad\nnoma is present.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_080.png", "summary": "The text discusses the importance of multiple biopsies for accurate diagnosis of high-grade tumors, the need for correlation with neuroimaging, and the challenges of intraoperative bleeding. It also outlines the process for consulting on probable sarcomas or unusual tumors.", "questions": [ "How does correlation with neuroimaging help ensure accurate intraoperative diagnosis?", "What are the risks associated with intraoperative bleeding during biopsies?", "Why is it important not to 'overcall' minimal abnormalities on minute specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 81, "text": "OPERATING ROOM CONSULTATIONS\u2003 Common Operating Room Consultations\n63\nChange in Surgery.\u2002 Additional surgery may be per\u00ad\nformed if a carcinoma is present:\n\t \u2022\t \u0007Papillary carcinoma: Complete thyroidectomy and \npossible lymph node dissection.\n\t \u2022\t \u0007Follicular carcinoma: Complete thyroidectomy. In \ngeneral, follicular carcinomas are not diagnosed on \nfrozen section as the entire capsule must be examined. \nThe diagnosis will be deferred to permanent sections \nfor most follicular neoplasms.\n\t \u2022\t \u0007Medullary carcinoma: Complete thyroidectomy, \npossible lymph node dissection, evaluation of parathy\u00ad\nroids. If previously unsuspected, the operative team \nshould be aware that there is a 10% to 15% chance \nthe patient has a pheochromocytoma.\nEvaluation.\u2002 The use of intraoperative frozen section var\u00ad\nies among institutions. FNA and frozen sections both can \nbe used effectively to guide management if the local accu\u00ad\nracy rates for both techniques are known.\n\t \u2022\t \u0007FNA positive for papillary carcinoma: FNA can \nhave a greater than 95% accuracy rate for this diag\u00ad\nnosis. There is only a small probability that frozen \nsection will yield a definitive benign diagnosis. The \ndiagnosis of papillary carcinoma usually can be easily \ncorroborated by either frozen section or touch prepa\u00ad\nrations, if requested.\n\t \u2022\t \u0007FNA suspicious for papillary carcinoma: 30% to \n50% of these lesions will prove to be malignant. Fro\u00ad\nzen section or touch preparations can be helpful in \nestablishing a definite diagnosis at surgery.\n\t \u2022\t \u0007FNA suggestive of a follicular neoplasm: About \n20% to 30% of these lesions will prove malignant. The \ndetermination of malignancy of follicular lesions is dif\u00ad\nficult and the probability of detecting capsular or vas\u00ad\ncular invasion on a frozen section is low. In one study, \nFS correctly modified the surgical procedure in 3.3% \nof such cases but led to an incorrect procedure in 5% of \ncases.39 If frozen section evaluation is undertaken, the \nsurgeon must be aware that few cancers are detected by \nthis technique and that false positives can occur.\n\t \u2022\t \u0007FNA interpreted as benign: The risk of carcinoma \nin this group is less than 10%. In one study, FS iden\u00ad\ntified only a third of the carcinomas missed by FNA \nin this group and produced an equal number of false \npositive cases.40\n\t \u2022\t \u0007FNA inadequate or not performed: In these cases, \nFS can be helpful. If follicular lesions are excluded, the \nsensitivity is over 95% and the specificity approaches \n100%.\nBefore examining the specimen, any previous FNA \nreports and thyroid ultrasound examinations should be \nreviewed to determine the likely type and site of lesions \npresent.\nThe thyroid is weighed, inked, serially sectioned, and \ngrossly evaluated for the presence of a single nodule or \nmultiple nodules. Whenever possible, the location of nod\u00ad\nules previously sampled by FNA should be identified to \nfacilitate the correlation between histologic and cytologic \nfindings.\nA multinodular gland is more likely to be benign \nwhereas a solitary lesion may be an adenoma or carcinoma.\nCytologic preparations (e.g., touch preparations) are \npreferred, as they preserve the nuclear features of papillary \ncarcinoma (intranuclear inclusions, grooves, large hypo\u00ad\nchromatic nuclei, and small nucleoli). These features are \nmore difficult to evaluate on frozen sections with freezing \nartifacts. If tissue is frozen, the section(s) should be taken \nfrom the edge of the lesion, including capsule if present.\nPitfalls.\u2002 The likelihood of not detecting capsular or \nvascular invasion in follicular carcinomas due to sampling \nerror is high. In addition, distortion introduced by freezing \nartifact may make the evaluation of capsular and vascular \ninvasion difficult. The follicular variant of papillary car\u00ad\ncinoma may be mistaken for a follicular lesion. Cytologic \npreparations are very helpful for evaluating the nuclear \nfeatures in such lesions.\nLymph Node Biopsy\nReason for Consultation.\u2002 Evaluation of a cervical lymph \nnode in a patient with known or suspected thyroid carci\u00ad\nnoma.\nChange in Surgery.\u2002 If metastatic thyroid carcinoma is \ndiagnosed, a total thyroidectomy may be performed or \nadditional lymph nodes taken.\nEvaluation.\u2002 The lymph node is serially sectioned and the \nmost abnormal area frozen.\nPitfalls.\u2002 Multinodular thyroid glands may have parasitic \nnodules that appear to be lymph nodes to the surgeon. If \nthe gland is involved by thyroiditis and germinal centers \nare present, it is possible to mistake such a nodule for met\u00ad\nastatic thyroid carcinoma. However, the nuclear features \nof papillary carcinoma will not be present.\nThe presence of normal thyroid inclusions in cervi\u00ad\ncal nodes is controversial and some pathologists interpret \nthese cases as metastatic thyroid carcinoma. Cases inter\u00ad\npreted as benign inclusions should be limited to a few fol\u00ad\nlicles found beneath the capsule in a single lymph node. \nCytologic features of papillary carcinoma must be absent.\nParathyroid Surgery\nReason for Consultation.\u2002 Parathyroid surgery is under\u00ad\ntaken for either primary hyperparathyroidism (usually due \nto a solitary adenoma) or for secondary hyperparathy\u00ad\nroidism (almost always due to chronic renal failure). The \ndistinction between primary and secondary hyperpara\u00ad\nthyroidism is best made on clinical grounds (i.e., elevated \nserum calcium vs. low serum calcium) and the distinction", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_081.png", "summary": "The page discusses common operating room consultations for thyroid carcinomas, including the surgical procedures and evaluation methods used.", "questions": [ "What are the different surgical procedures recommended for different types of thyroid carcinomas?", "How accurate are FNA and frozen sections in diagnosing thyroid carcinomas?", "What considerations should be taken into account before examining a thyroid specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 82, "text": "64\nOPERATING ROOM CONSULTATIONS\u2003 Infection Precautions in the OR Consultation Room\nbetween an adenoma (a single enlarged gland) vs. pri\u00ad\nmary hyperplasia (two or more enlarged glands) is best \nmade by surgical evaluation of all glands (four or more) \n(Table 6-3).\nSome institutions use rapid serum parathyroid hormone \nassays to guide surgery for adenomas. If the serum level \ndrops after removal of an adenoma, further surgical explo\u00ad\nration and frozen section evaluation may not be necessary. \nSerum calcium also drops rapidly after the removal of a \nhyperfunctioning adenoma.\nChange in Surgery.\u2002 If parathyroid tissue is not demon\u00ad\nstrated, the surgeon may continue to search for additional \nparathyroid glands.\nEvaluation.\u2002 The role of the pathologist is to deter\u00ad\nmine the size and weight of each gland and whether \nparathyroid tissue is present in each specimen submit\u00ad\nted. Each specimen should be identified as a complete \ngland (glands are ovoid, smooth-surfaced structures) or \na biopsy (usually a minute irregular fragment of tissue). \nAlthough normal glands usually have >25% adipose tis\u00ad\nsue and adenomas usually have <5% adipose tissue, this is \nnot an absolutely reliable diagnostic feature. Parathyroid \nglands tend to \u00adcontain more adipose tissue with age (e.g., \na 50-year-old person generally would have glands with \n50% fat).\n\t \u2022\t \u0007Adenomas: The adenoma will be removed in entirety \nand will have a smooth ovoid appearance. Both the \nsize and weight are important diagnostic features. \nDocument parathyroid parenchyma by frozen \n\u00adsection. The three remaining normal glands will be \nvisually inspected and one to three of them may be \nbiopsied. These biopsies will be small and are frozen \nin entirety to document the presence of parathyroid \nparenchyma.\n\t \u2022\t \u0007Secondary hyperplasia: Three glands will be removed \nand the fourth gland partially resected. All glands will \nbe markedly enlarged and should have size and weights \ndocumented. Freeze a representative section of each to \nconfirm the presence of parathyroid parenchyma.\nPitfalls.\u2002 The identification of parathyroid tissue can be \nmade with 99% accuracy.41 The most frequent problem \nin this study was distinguishing thyroid tissue and parathy\u00ad\nroid tissue.\n\t \u2022\t \u0007Parathyroid tissue mistaken for thyroid: Pseudofol\u00ad\nlicular and trabecular structures may be \u00adpresent con\u00ad\ntaining material that looks like colloid and resembles \nnormal thyroid. Parathyroid tissue can also resemble \na follicular thyroid (Hurthle cell) nodule if composed \nof oxyphilic cells. Thyroid follicles frequently contain \ncalcium oxalate crystals, which are easily seen with \npolarization. These crystals are not seen in parathy\u00ad\nroid tissue.\n\t \u2022\t \u0007Thyroid tissue mistaken for normal parathyroid \ntissue: Stromal edema or frozen section artifact can \nmimic adipose tissue. Rarely, adipose metaplasia \nmay be present. In some cases, immunohistochem\u00ad\nistry will be necessary to discriminate between the \ntwo tissues. This problem most frequently arises \nwhen there is a multinodular thyroid gland with \nsmall parasitic nodules or an intrathyroidal para\u00ad\nthyroid gland.\n\t \u2022\t \u0007Lymph node mistaken for parathyroid tissue: Fro\u00ad\nzen section artifact can mimic adipose tissue within a \nlymph node and can be mistaken for parathyroid \u00adtissue.\n\t \u2022\t \u0007Sampling error: Small diagnostic areas of parathy\u00ad\nroid tissue may be missed.\nIt is more difficult to distinguish adenomas from nor\u00ad\nmal parathyroid glands on frozen section. In general, this \ndistinction need not be made by frozen section and is bet\u00ad\nter made based on the size of the gland and intraoperative \nparathyroid hormone (PTH) measurements.\nINFECTION PRECAUTIONS IN THE OR CONSULTATION \nROOM\nPathology personnel handle potentially infectious mate\u00ad\nrial every day. It is estimated that 50% of the patients who \nare HIV positive are undiagnosed at the time of admission \nto the hospital and this is undoubtedly also true of other \npatients with infectious diseases. Therefore pathologists \nmust do their best to limit the risk of infection to them\u00ad\nselves and to the people they work with by handling all \nspecimens with universal precautions.\nOR consultations on tissues from patients with known \ninfectious diseases may be performed if this information is \nimportant for immediate patient management. If the pur\u00ad\npose of the examination is unclear, the surgeon should be \ncontacted to clarify what information would be useful to \nthe clinicians. Frozen sections are avoided if possible.\nTABLE 6\u20133.\u2003\nPRIMARY VERSUS SECONDARY HYPERPARATHYROIDISM\nTYPE\nUSUAL CAUSE\nNUMBER OF INVOLVED GLANDS\nSERUM CALCIUM\nPrimary\nSolitary adenoma\nUsually one, rarely more than one\nElevated\nPrimary hyperplasia (rare)\nTwo or more\nElevated\nSecondary\nRenal failure\nFour\nDecreased", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_082.png", "summary": "The page discusses the differentiation between adenomas and primary hyperplasia in the parathyroid glands, as well as the evaluation and pitfalls in surgical pathology.", "questions": [ "What are the key diagnostic features used to differentiate between adenomas and primary hyperplasia in the parathyroid glands?", "How is the identification of parathyroid tissue made with high accuracy, and what are the common pitfalls in this process?", "When is immunohistochemistry necessary to discriminate between thyroid tissue and normal parathyroid tissue?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 83, "text": "65\nOPERATING ROOM CONSULTATIONS\u2003 Infection Precautions in the OR Consultation Room\nThree cases of conversions to positive tuberculin skin \ntests have been linked to aerosol produced by spraying \na tissue block with a compressed gas coolant.5,6 Thus, \nalthough rare, exposure can occur. These sprays are no \nlonger recommended for use. Cytologic preparations are \nnot as hazardous for infectious specimens and often are \nas good or better than frozen sections for diagnosis. If \na \u00adfrozen section is performed on tissue from a patient \nknown or suspected to be HIV positive, hepatitis B or C \npositive, or to have mycobacterial infection, the cryostat \nmust be clearly marked as contaminated and should be \ndecontaminated before further use.\nGuidelines:\nSee Chapter 8 for more information or if a significant \nexposure should occur.\nREFERENCES\n\t\u2002 1.\t \u0007Ranchod M, editor: Intraoperative Consultations in Surgi\u00ad\ncal Pathology. State of the Art Reviews Vol 3. Philadelphia \nHanley & Belfus, 1996, No. 2.\n\t\u2002 2.\t \u0007Volsi VL. A surgical pathologist views practice parameters. \nAm J Clin Pathol 103:1-2, 1995.\n\t\u2002 3.\t \u0007Weiss SW, et al. Frozen section consultation, utilization pat\u00ad\nterns and knowledge base of surgical faculty at a university \nhospital. Am J Clin Pathol 104:294-298, 1995.\n\t\u2002 4.\t \u0007Zarbo RJ, et al. Indications and immediate patient out\u00ad\ncomes of pathology intraoperative consultations, a College \nof American Pathologists/Centers for Disease Control and \nPrevention Outcomes Working Group Study. Arch Pathol \nLab Med 120:19-25, 1996.\n\t\u2002 5.\t \u0007Tuberculosis infection associated with tissue processing. \nMMWR 30:73-74, 1981.\n\t\u2002 6.\t \u0007Duray PH, Flannery B, Brown S. Tuberculosis infec\u00ad\ntion from preparation of frozen sections. NEJM 305:167, \n1981.\n\t\u2002 7.\t \u0007Sidawy MK, Silverberg SG. Intraoperative cytology. Am \nJ Clin Path 96:1-3, 1991.\n\t\u2002 8.\t \u0007Quality Improvement Manual in Anatomic Pathology, \n\u00adCollege of American Pathologists, 1993.\n\t\u2002 9.\t \u0007Sawady J, et al. Accuracy of and reasons for frozen sections: \nA correlative, retrospective study. Hum Pathol 19:\n1019-1023, 1988.\n\t10.\t \u0007Association of Directors of Anatomic and Surgical Pathology, \nRecommendations on quality control and quality assurance in \nanatomic pathology. Hum Pathol 22:1099, 1991 or Am J Surg \nPathol 15:1007-1009, 1991 or Mod Pathol 5:567-568, 1992.\n\t11.\t \u0007Forrest LA, Schuller DE, Lucas JG, Sullivan MJ. Rapid \nanalysis of mandibular margins. Laryngoscope 105:475-477, \n1995.\n\t12.\t \u0007Abdul-Karim FW, McGinnis MG, Kraay M, et al. Frozen \nsection biopsy assessment for the presence of polymorpho\u00ad\nnuclear leukocytes in patients undergoing revision of arthro\u00ad\nplasties. Mod Pathol 11:427-431, 1998.\n\t13.\t \u0007Bori G, Soriano A, Garcia S, et al. Usefulness of histological \nanalysis for predicting the presence of microorganisms at the \ntime of reimplantation after hip resection arthroplasty for the \ntreatment of infection. J Bone Joint Surg Am 89:1232-1237, \n2007.\n\t14.\t \u0007Lonner JH, et al. The reliability of analysis of intraopera\u00ad\ntive frozen sections for identifying active infection during \nrevision hip or knee arthroplasty. J Bone Joint Surg Am \n78:1553-1558, 1996.\n\t15.\t \u0007Parvizi J, Ghanem E, Menashe S, et al. Periprosthetic infec\u00ad\ntion: what are the diagnostic challenges? J Bone Joint Surg \nAm 88:138-147, 2006.\n\t16.\t \u0007Stamenkovic I, Lew D. Early recognition of potentially \nfatal ne crotizing fasciitis; the use of frozen-section biopsy. \nNEJM 310 :1689-1693, 1984.\n\t17.\t \u0007Majeski J, Majeski E. Necrotizing fasciitis: improved survival \nwith early recognition by tissue biopsy and aggressive surgi\u00ad\ncal treatment. South Med J 90:1065-1068, 1997.\n\t18.\t \u0007Fechner RE. Frozen section examination of breast biopsies, \nPractice parameter. Am J Clin Pathol 103:6-7, 1995.\n\t19.\t \u0007Bianchi S, et al. Accuracy and reliability of frozen section \ndiagnosis in a series of 672 nonpalpable breast lesions. Am \nJ Clin Pathol 103:199-205, 1995.\n\t20.\t \u0007Cox CE, et al. Touch preparation cytology of breast \nlumpectomy margins with histologic correlation. Arch Surg \n126:490-493, 1991.\n\t21.\t \u0007England DW, Chan SY, Stonelake PS, Lee MJR. Assessment \nof excision margins following wide local excision for breast \ncarcinoma using specimen scrape cytology and tumour bed \nbiopsy. Eur J Surg Oncol 20:425-429, 1994.\n\t\u2022\t \u0007Always wear gloves when handling specimens. \n\u00adDouble-gloving (as well as aprons, face masks, and \neye protection) is recommended for known infectious \ncases or for bloody specimens. An OSHA approved TB \nrespirator must be worn for known or suspected cases \nof TB.\n\t\u2022\t \u0007After working a specimen with known or potential \npathogens, immediately remove your gloves. Do \nnot touch anything else in the room (e.g., the \u00adcryostats, \nstaining rack, microscopes, telephones, etc.) with con\u00ad\ntaminated gloves. If you want to \u00adprotect your hands \nfrom these surfaces, use a pair of clean gloves.\n\t\u2022\t \u0007Clean the workstation by removing all blood, tissue, \nand sharps (razor blades, scalpels, syringe needles). \nTissue is placed in appropriately labeled contain\u00ad\ners in formalin or stored in the refrigerator in sealed \nbags or specimen containers. Make sure the \u00adcontainers \nare tightly sealed and leakproof. Sharps and glass \nslides must be discarded in the appropriate desig\u00ad\nnated \u00adcontainers. Used tools (forceps, rulers, scalpel \nhandles, etc.) should be rinsed free of gross blood and \ndisinfected.\n\t\u2022\t \u0007Before removing the scalpel blade from the handle, all \ngross tissue and blood should be cleaned in a disinfec\u00ad\ntant solution. A forceps is used for this procedure.\n\t\u2022\t \u0007Always leave the workstation ready for the next \u00adfrozen \nsection examination.\n\t\u2022\t \u0007Always wash your hands before leaving the OR \n\u00adconsultation room.\n\t\u2022\t \u0007Disposable gowns, aprons, face masks, and eye \n\u00adprotection are recommended whenever exposure to \nblood or tissue is expected.\n\t\u2022\t \u0007Do not eat or drink in the OR consultation room, bring \nfood into the room, or dispose of empty food contain\u00ad\ners in the room. The presence of food or \u00adformer food \ncontainers is against OSHA rules and may result in \npenalties or closure.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_083.png", "summary": "Infection precautions in the operating room consultation room are crucial, with aerosol exposure from spraying tissue blocks being linked to positive tuberculin skin tests. Guidelines recommend avoiding the use of sprays and marking contaminated cryostats.", "questions": [ "What are the risks associated with aerosol exposure in the operating room consultation room?", "Why are cytologic preparations considered less hazardous than frozen sections for infectious specimens?", "What specific precautions should be taken when performing a frozen section on tissue from a patient with certain infections?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 84, "text": "66\nOPERATING ROOM CONSULTATIONS\u2003 Infection Precautions in the OR Consultation Room\n\t22.\t \u0007Sauter ER, et al. Is frozen section analysis of reexcision \nlumpectomy margins worthwhile? Margin analysis in breast \nreexcisions. Cancer 73:2607-2612, 1994.\n\t23.\t \u0007Goldstein JS, Soman A, Sacksner J. Disparate surgical mar\u00ad\ngin lengths of colorectal resection specimens between in vivo \nand in vitro measurements. The effects of surgical resection \nand formalin fixation on organ shrinkage. Am J Clin Pathol \n111:349-351, 1999.\n\t24.\t \u0007McLeod RS. Resection margins and recurrent Crohn\u2019s dis\u00ad\nease. Hepatogastroenterology 37:63-66, 1990.\n\t25.\t \u0007Fazio VW, Marchetti F, Church M, et al. Effect of resection \nmargins on the recurrence of Crohn\u2019s disease in the small \nbowel. A randomized controlled trial. Ann Surg 224:563-\n571, 1996.\n\t26.\t \u0007Hyland C, Kheir SM, Kashlan MB. Frozen section diagnosis \nof pancreatic carcinoma, a prospective study of 64 biopsies. \nAm J Surg Pathol 5:179-191, 1981.\n\t27.\t \u0007Campanale RP, Frey CF, Farias R, et al. Reliability and \nsensitivity of frozen-section pancreatic biopsy. Arch Surg \n120:283-288, 1985.\n\t28.\t \u0007Tangjitgamol S, Jesadapatrakul S, Manusirivithaya S, \nSheanakul C. Int J Gynecol Cancer 14:212-219, 2004.\n\t29.\t \u0007Kir G, Kir M, Cetiner H, et al. Diagnostic problems on fro\u00ad\nzen section examination of myometrial invasion in patients \nwith endometrial carcinoma with special emphasis on the \npitfalls of deep adenomyosis with carcinomatous involve\u00ad\nment. Eur J Gynaecol Oncol 25:211-214, 2004.\n\t30.\t \u0007Spandorfer SD, et al. Efficacy of frozen-section evaluation of \nuterine curettings in the diagnosis of ectopic pregnancy. Am \nJ Obstet Gynecol 175:603, 1996.\n\t31.\t \u0007Tschen JA, Fechner RE. The juxtaoral organ of Chievitz,. \nAm J Surg Pathol 3:147-150, 1979.\n\t32.\t \u0007Gephardt GN, Rice TW. Utility of frozen-section evaluation \nof lymph nodes in the staging of bronchogenic carcinoma \nat mediastinoscopy and thoracotomy. J Thorac Cardiovasc \nSurg 100:853-859, 1990.\n\t33.\t \u0007Gupta R, McKenna R, Marchevsky AM. Lessons learned \nfrom mistakes and deferrals in the frozen section diagno\u00ad\nsis of bronchioloalveolar carcinoma and well-differentiated \npulmonary adenocarcinoma: an evidence-based pathology \napproach. Am J Clin Pathol 130:11-20, 2008.\n\t34.\t \u0007Gupta R, Dastane A, Mckenna RJ Jr, Marchevsky AM. What \ncan we learn from the errors in the frozen section diagnosis of \npulmonary carcinoid tumors? An evidence-based approach. \nHuman Pathol 40:1-9, 2009.\n\t35.\t \u0007Evidence-based criteria to help distinguish metastatic breast \ncancer from primary lung adenocarcinoma on thoracic frozen \nsection. Am J Clin Pathol 131:122-128, 2009.\n\t36.\t \u0007Maygarden SJ, Detterbeck FC, Funkhouser WK. Bronchial \nmargins in lung cancer resection specimens: utility of fro\u00ad\nzen section and gross evaluation. Mod Pathol, 2004:May 7 \n(Epub).\n\t37.\t \u0007Renshaw AA. The relative sensitivity of special stains \nand cultures in open lung biopsies. Am J Clin Pathol 102:\n736-740, 1994.\n\t38.\t \u0007Folkerth RD. Smears and frozen sections in the intraopera\u00ad\ntive diagnosis of central nervous system lesions. Neurosurg Clin \nN Am 5:1-18, 1994.\n\t39.\t \u0007Chen H, Nicol TL, Udelsman R. Follicular lesions of the \nthyroid, Does frozen section evaluation alter operative man\u00ad\nagement? Ann of Surg 222:101-106, 1995.\n\t40.\t \u0007Hamburger JI, Hamburger SW. Declining role of frozen \nsection in surgical planning for thyroid nodules. Surgery \n98:307-312, 1985.\n\t41.\t \u0007Westra WH, Pritchett DD, Udelsman R. Intraoperative \nconfirmation of parathyroid tissue during parathyroid explo\u00ad\nration, a retrospective evaluation of the frozen section. Am \nJ Surg Pathol 22:538-544, 1998.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_084.png", "summary": "This page discusses various studies on frozen section analysis in surgical pathology, including its utility in margin analysis, diagnosis of different types of cancers, and distinguishing between metastatic and primary tumors.", "questions": [ "What are the key findings of the studies mentioned in relation to frozen section analysis?", "How does frozen section analysis impact surgical decision-making in cases of margin assessment?", "What are the limitations or challenges associated with frozen section diagnosis in the studies referenced?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 85, "text": "67\n7\nSpecial Studies\nThe pathologist\u2019s H&E is like the clinician\u2019s H&P (history \nand physical) - basic exams to be performed on every patient \nor specimen forming the cornerstone of diagnosis. However, \nthe pathologist is no longer limited to the H&E; there are \na wide variety of special studies available to evaluate patho\u00ad\nlogic processes, from simple histochemical stains to global \ngene expression patterns. Pathologists are now clinical cell \nbiologists. Familiarity with the types of special studies avail\u00ad\nable is important as the initial processing of the gross speci\u00ad\nmen may limit the types of studies that can be performed.\nHISTOCHEMISTRY\nAlmost all histochemical stains are suitable for formalin-\nfixed tissues. Common stains and their uses are listed in \nTable 7-1. However, numerous other types of stains and \nmodifications are used and pathologists must be aware of \nindividual laboratory practices.\nThe WebPath section of the University of Utah site \n(http://library.med.utah.edu/webpath) has useful descrip\u00ad\ntions of special stains and illustrative photographs.\nTABLE 7\u20131.\u2003\nHISTOCHEMICAL STAINS\nSTAIN\nCOMPONENTS STAINED\nPOSSIBLE USES AND COMMENTS\nAFOG (acid fuschin orange \nG; modified Masson\u2019s \ntrichrome)\nNuclei \u2013 brown\nConnective tissue \u2013 blue\nBasement membrane \u2013 blue\nProteins, fibrin, readsorption droplets in \ncells, immune complexes \u2013 red/orange/\nyellow\nRBCs \u2013 yellow\nEvaluation of renal biopsies\nAlcian blue\nAcid mucins \u2013 blue (e.g., normal intestinal \nglands)\nNuclei \u2013 red\nCytoplasm \u2013 pink\nSometimes used to identify mucosubstances in \nmesotheliomas or intestinal metaplasia. Affected \nby pH. Hyaluronidase digestion can be used to \nidentify hyaluronic acid.\nAlcian blue/PAS\nIntestinal metaplasia \u2013 dark purple\nNormal stomach \u2013 pink\nDemonstrates both acid and neutral mucins\nAlcian yellow\nFree mucus \u2013 yellow\nBacteria \u2013 dark blue\nIdentification of H. pylori in gastric biopsies\nAcid-fast bacilli stains \n(Fite-Faraco, Ziehl-\u00ad\nNeelson, Kinyoun)\nTB \u2013 red and beaded\nMAI \u2013 red\nNocardia \u2013 pink\nTissue \u2013 blue\nIdentification of mycobacteria. Modifications are used \nto demonstrate M. leprae or Nocardia. Carnoy\u2019s \nfixed tissues cannot be used and B-5 is suboptimal. \nSlides must be examined under oil.\nAlizarin red S\nCalcium \u2013 orange red, polarizes\nIdentifies calcium in tissues\nBile\nBile \u2013 dark green on a yellow background\nIdentification of bile\nBodian\u2019s\nNerve fibers and neurofibrils \u2013 black\nNuclei \u2013 black\nTissue \u2013 blue\nNeural tumors, identification of axons\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_085.png", "summary": "Pathologists have a wide variety of special studies available to evaluate pathologic processes beyond the basic H&E stains, including histochemical stains. Familiarity with these special studies is important as initial processing of the specimen may limit the types of studies that can be performed.", "questions": [ "What are some common histochemical stains and their possible uses?", "Where can pathologists find useful descriptions of special stains and illustrative photographs?", "How does the initial processing of the gross specimen affect the types of special studies that can be performed?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 86, "text": "SPECIAL STUDIES\u2003 Histochemistry\n68\nSTAIN\nCOMPONENTS STAINED\nPOSSIBLE USES AND COMMENTS\nChloroacetate esterase \n(Leder; CAE)\nMature myeloid cells, mast cells \u2013 red granules\nNuclei \u2013 blue\nEvaluation of leukemias\nIdentification of mast cells\nCannot be used for tissue fixed in Zenker\u2019s or B-5.\nCongo red\nAmyloid \u2013 orange red with apple green \n\u00adbirefringence after polarization\nNuclei \u2013 blue\nDetection of amyloid. Immunoperoxidase studies can \nbe used to identify specific types. Overstaining can \nresult in false positives.\nDieterle\nSpirochetes, Legionella, other bacteria \u2013 \nbrown to black\nTissue \u2013 pale yellow or tan\nInfectious lesions\nMelanin, chromatin, formalin pigment, and foreign \nmaterial may also stain\nDiff Quik (a modified \nGiemsa stain)\nH. pylori \u2013 dark blue\nOther bacteria \u2013 blue\nNuclei \u2013 dark blue\nCytoplasm \u2013 pink\nEvaluation of chronic gastritis\nElastic stains (Verhoeff\u2013van \nGieson)\nElastic fibers \u2013 blue black to black\nNuclei \u2013 blue to black\nCollagen \u2013 red\nOther tissue \u2013 yellow\nIdentification of arteries and veins, vasculitis, inva\u00ad\nsion of lung tumors into visceral pleura, abnormal \nelastic fibers in elastofibromas\nFibrin (see Phosphotung\u00ad\nstic acid hematoxylin or \nMallory PTAH)\nTo demonstrate fibrin in renal biopsies\nFontana-Masson\nMelanin, argentaffin granules, chromaffin \n\u00adgranules, some lipofuschin \u2013 black\nNuclei \u2013 red\nIdentification of melanin in melanomas and secretory \ngranules in neuroendocrine tumors\nThis stain has largely been replaced by IHC\nGiemsa (May-Grunwald)\nBacteria (e.g., H. pylori) \u2013 blue\nParasites (Leishmania, Plasmodium) \u2013 blue\nMast cells \u2013 red to purple granules\nNuclei \u2013 blue\nCytoplasm of leukocytes \u2013 pink to blue \ndepending on cell type and differentiation\nLymphoproliferative disorders (good nuclear and \ncytoplasmic detail)\nIdentification of bacteria, rickettsias, and Toxoplasma \ngondii\nGram (Brown-Hopps, \nBrown-Brenn)\nGram-positive bacteria \u2013 blue\nGram-negative bacteria \u2013 red\nNuclei \u2013 red\nTissue \u2013 variable\nIdentification of bacteria, some cases of actinomy\u00ad\ncetes, Nocardia, coccidioidomycosis, blastomyco\u00ad\nsis, cryptococcosis, aspergillosis, rhinosporidiosis, \nand amebiasis\nGrimelius\nArgentaffin and argyrophil granules \u2013 dark \nbrown to black\nNuclei \u2013 red\nBackground \u2013 pale yellow-brown\nEvaluation of neuroendocrine tumors (largely \nreplaced by the use of immunohistochemistry for \nchromogranin)\nHematoxylin and eosin \n(H&E)\nNuclei \u2013 dark blue or purple\nCytoplasm \u2013 pink to red\nStandard stain for the routine evaluation of tissues\nIron (colloidal iron)\nFerric iron (e.g., hemosiderin) \u2013 blue\nNuclei \u2013 red\nBackground \u2013 pink\nBone marrow (iron stores, myelodysplasias), liver \n(hemochromatosis)\nChromophobe renal cell carcinomas are positive\nJone\u2019s silver methenamine\nBasement membrane \u2013 dark maroon to black\nEvaluation of renal biopsies\nMelanin bleach\nRemoves melanin from tissue, usually for IHC\nMelanin can be difficult to distinguish from IHC \npositivity\nTABLE 7\u20131.\u2003\nHISTOCHEMICAL STAINS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_086.png", "summary": "The page discusses various histochemical stains used in pathology, including their components, possible uses, and limitations.", "questions": [ "What are some examples of histochemical stains mentioned on this page?", "What is the possible use of the Congo red stain?", "Why is the Dieterle stain used and what can it detect?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 87, "text": "SPECIAL STUDIES\u2003 Histochemistry\n69\nContinued\nSTAIN\nCOMPONENTS STAINED\nPOSSIBLE USES AND COMMENTS\nMethyl green-pyronin Y\nDNA (nuclei) \u2013 green to blue-green\nRNA - red\nGoblet cells - mint green\nPlasma cell and immunoblast cytoplasm - \npink to red\nMast cells - orange\nBackground - pale pink to colorless\nPlasma cell lesions (largely replaced by IHC)\nDoes not work well on tissues decalcified with formic \nacid.\nMucicarmine (Mayer)\nMucin - deep rose to red\nCapsule of Cryptococcus - deep rose to red\nNuclei - black\nTissue - blue or yellow\nIdentification of adenocarcinomas, identification of \nCryptococcus\nOil red O\nFat - red\nNuclei - blue\nRequires frozen sections (lipids are dissolved by most \nfixatives or during processing). Tissue fixed in \n\u00adformalin can be used if tissue is frozen.\nPeriodic acid \u2013 Schiff (PAS)\nGlycogen - red\nBasement membranes (BM) - red\nMucins - red\nColloid - red\nFungi - red\nClassification of tumors with glycogen (e.g., Ewing\u2019s/\nPNET, rhabdomyosarcoma, renal cell carci\u00ad\nnoma), glomerular diseases (BM), identification \nof \u00adadenocarcinomas (mucin), fungal diseases \n(especially in argentophic areas \u2013 neutrophils and \ndebris), spironolactone bodies in adrenal adeno\u00ad\nmas treated with this drug\nPeriodic acid \u2013 Schiff \nwith diastase digestion \n(PAS-D)\nAs above except glycogen that has been \ndigested will not be stained\nIdentification of glycogen in tumors\nIdentification of fungus in glycogen-rich tissue \n(e.g., skin)\nPAS-D resistant deposits in liver are present in alpha-\n1-antitrypsin deficiency\nPhosphotungstic acid \nhematoxylin (Mallory \nPTAH)\nGlial fibers - blue\nNuclei - blue\nNeurons - salmon\nMyelin - blue\nSkeletal muscle cross striations - blue\nFibrin - blue\nCollagen - red brown\nIdentification of neural lesions\nSkeletal muscle differentiation (Zenker\u2019s fixative is \npreferred). This stain has been replaced by IHC for \nmuscle markers.\nReticular fibers (Gomor\u2019s \nreticulin, Gordon and \nSweets, Snook)\nReticulin - black\nMature collagen, type 1 \u2013 brown\nImmature collagen, types 3 and 4 - black\nBone marrow (myelophthisis), liver (fibrosis, \nveno-occlusive disease), carcinoma vs. sarcoma \n(reticular network) (but largely replaced by IHC)\nSilver stain (Grocott \nmethenamine\u2013silver \nnitrate \u2013 GMS)\nFungi - black\nPneumocystis - black\nMucin - taupe to gray\nTissue - green\nEvaluation of infectious diseases\nBacteria will also stain black.\nSteiner\nSpirochetes, H. pylori, Legionella, other \n\u00adbacteria - dark brown to black\nTissue - light yellow\nEvaluation of infectious diseases\nSulfated Alcian blue\nMyocytes \u2013 yellow\nConnective tissue \u2013 red-purple\nAmyloid \u2013 sea-foam green\nIdentification of amyloid in cardiac biopsies\nToluidine blue\nMast cells - deep violet\nBackground - blue\nMast cell diseases, chronic cystitis\nTABLE 7\u20131.\u2003\nHISTOCHEMICAL STAINS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_087.png", "summary": "The page provides information on various histochemical stains used in pathology, including their components, possible uses, and limitations.", "questions": [ "How do the different histochemical stains mentioned in the text differ in terms of what they stain and their possible uses?", "What are the specific uses and limitations of each histochemical stain mentioned?", "Why is it mentioned that some stains are largely replaced by immunohistochemistry (IHC) in certain cases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 88, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n70\nTABLE 7\u20131.\u2003\nHISTOCHEMICAL STAINS\u2014cont\u2019d\nSTAIN\nCOMPONENTS STAINED\nPOSSIBLE USES AND COMMENTS\nTrichrome (Gomori, \n\u00adMasson)\nMature collagen, type 1 \u2013 dark blue\nImmature collagen, types 3 and 4 - light blue\nMucin - green or blue\nNuclei - black\nCytoplasm, keratin, muscle fibers - red\nLiver (fibrosis)\nTrichrome - modified\nViable myocardium - magenta to brick red\nNonviable myocardium -dusky gray \nto mauve\nEvaluation of myocardial biopsies\nVon Kossa calcium\nCalcium - black\nTissue - red\nDemonstration of phosphate and carbonate \u00adradicals \nwith calcium in tissues, identification of malakopla\u00ad\nkia (Michaelis-Gutmann bodies)\nWarthin Starry\nSpirochetes - black\nOther bacteria - black (including Bartonella sp.)\nTissue - pale yellow to light brown\nInfectious lesions (including syphilis, cat scratch fever, \nand bacillary angiomatosis)\nWright\u2019s\nEosinophilic granules - pink\nNeutrophilic granules - purple\nLymphocytic cytoplasm - blue\nNuclei -blue to purple\nBlood smears\nIMMUNOPEROXIDASE STUDIES\nThe development of methods to detect antigens on tissue \nsections with antibodies was a major advance in surgical \npathology. Immunohistochemical (IHC) studies are most \nfrequently used for the following purposes:\n\t\u2022\t \u0007Classification of tumors (e.g., carcinoma vs. lymphoma, \nB cell vs. T cell lymphoma).\n\t\u2022\t \u0007Identification of in situ lesions vs. invasive carcinomas \n(e.g., myoepithelial markers in breast cancers, basal cell \nmarkers in prostate).\n\t\u2022\t \u0007Prognostic factors (e.g., Ki-67 in glioblastomas).\n\t\u2022\t \u0007Predictive factors to guide specific therapy (e.g., c-KIT, \nestrogen and progesterone receptors, HER2/neu).\n\t\u2022\t \u0007Identification of extracellular material (e.g., \u03b2-2 micro\u00ad\nglobulin amyloid).\n\t\u2022\t \u0007Identification of infectious agents (e.g., CMV or HSV).\nUse of Immunohistochemistry.\u2002 A differential diag\u00ad\nnosis is generated after examination of the H&E-stained \nslides. IHC is then used to gain evidence for or against \ndiagnostic possibilities. \u201cTrolling\u201d cases through an immu\u00ad\nnohistochemistry laboratory by ordering numerous anti\u00ad\nbody studies without a clear reason in mind is more likely \nto lead to misguided diagnosis due to aberrant immunore\u00ad\nactivity than to provide an unexpected correct diagnosis.\nPanels.\u2002 There are no absolute rules for immunoreac\u00ad\ntivity in cells and tissues. Aberrant immunoreactivity or \nloss of immunoreactivity is occasionally observed for all \n\u00adantibodies, either due to biologic variability (e.g., occasional \nkeratin-positive melanomas) or technical factors (e.g., \nimpure antibodies, cross-reaction with other antigens, fail\u00ad\nure to preserve antigenicity). Thus, immunohistochemical \nmarkers are used most effectively as panels of markers with \ninterpretation based on an immunohistochemical profile.\nSlides for Immunohistochemistry.\u2002 Tissue is often \ndislodged from normal glass slides during the treatments \nrequired for IHC. Thus, slides must be coated (e.g., with \nglue, poly-L-lysine, gelatin, albumin) or special commercial \nslides must be used. If slides are being prepared by another \nlaboratory, the type of glass slide to be used must be specified.\nFactors Affecting Immunogenicity.\u2002 There \nare \nnumerous variables that can affect antigenicity. The most \ncommon are listed below. Each laboratory must optimize \nits procedures for each antibody used. Studies on tissues or \nslides not prepared in the routine fashion for a laboratory \nmust be interpreted with caution.\n\t\u2022\t \u0007Type of fixative. Some fixatives destroy some antigens \n(e.g., Bouin\u2019s diminishes ER immunoreactivity, keratins \nare not well preserved in B5).1 Most studies are based on \nformalin-fixed tissue. Results cannot be assumed to be \nequivalent for other fixatives.\n\t\u2022\t \u0007Length of time of fixation in formalin causes protein \ncross-linking, and antigenicity generally decreases with \nfixation times over 24 hours. To some extent, this effect \ncan be reversed using antigen retrieval methods. Anti\u00ad\ngenicity can also be reduced if the tissue is fixed for too \nshort a period (e.g., less than 6 hours).\n\t\u2022\t \u0007Prior decalcification in hydrochloric acid. Decreases \nantigenicity of some epitopes (predominantly nuclear)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_088.png", "summary": "Immunohistochemical studies are crucial in surgical pathology for various purposes such as tumor classification, identification of in situ lesions, prognostic factors, and guiding specific therapies.", "questions": [ "How are immunohistochemical studies used in differentiating between carcinoma and lymphoma?", "What are some examples of prognostic factors identified through immunohistochemistry?", "Why is it important to use panels of markers for interpretation in immunohistochemical studies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 89, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n71\nbut not others (predominantly cytoplasmic).2 Decalcify\u00ad\ning agents using EDTA did not alter immunogenicity.\n\t \u2022\t \u0007Decreased: estrogen receptor (ER), progesterone receptor \n(PR), Ki-67, p53, BerEp4 (tumor cells), H blood group.\n\t \u2022\t \u0007Not affected: calcitonin, chromogranin, GCDFP-\n15, HMB 45, thyroglobulin, S100, prostate-specific \nantigen (PSA), keratins (CK 20, CAM5.2, AE1/AE3), \nA and B blood groups, others.\n\t\u2022\t \u0007Temperature of baking the slide.\n\t\u2022\t \u0007Length of time since the glass slide was cut. The \nimmunoreactivity of the majority of antigens declines over \ndays to weeks with potential complete loss at one month.3,4 \nThe loss may be due to exposure of tissue to air with oxi\u00ad\ndation of amino acids, as the immunogenicity of tissue \ndeeper in the block can be preserved for many years. Anti\u00ad\ngen retrieval methods do not completely restore the anti\u00ad\ngenicity of old slides. Coating slides with paraffin, storing \nthe slides in a nitrogen desiccator, and/or storing at lower \ntemperatures can partially preserve antigenicity. However, \nstudies should be performed on newly cut slides, if possible.\n\t\u2022\t \u0007Antigen retrieval procedures (e.g., proteolysis, heat\u00ad\ning [microwave, steam], special incubation fluids). To \nsome extent these methods reverse the effects of forma\u00ad\nlin fixation. Variable effects are observed for different \nantibodies.\n\t\u2022\t \u0007Type of antibody (polyclonal vs. monoclonal vs. mix\u00ad\nture of different monoclonals, epitope detected, mouse \nvs. rabbit). Very different results can be obtained with \ndifferent antibodies to the same protein or different \ncommercial sources of the same antibody.\n\t\u2022\t \u0007Incubation time, incubation temperature, dilution \nof antibody.\n\t\u2022\t \u0007Methods of signal amplification.\nControls.\u2002 Controls are essential for the appropriate \ninterpretation of immunohistochemical studies and ensure \nthat all steps of this complicated procedure have been per\u00ad\nformed adequately.\nPositive controls consisting of tissues known to be \nimmunoreactive should be included each time an antibody \nis used for a test case. Internal positive controls should \nalways be evaluated when present, as they control not only \nfor the technique used but also for the antigenicity of the \ntissue under investigation. The immunoperoxidase table \nlists normal cells that are generally immunoreactive for each \nantibody. Some laboratories have used vimentin as a control \nfor immunogenicity as almost all tissue should demonstrate \npositivity.5 Given the wide and non-specific distribution of \nvimentin, smooth muscle alpha actin may be more useful in \nthis context as pericytes, vascular smooth muscle, and myo\u00ad\nepithelial cells present in most tissues are immunoreactive.\nExamples of internal controls:\n\t\u2022\t \u0007S100: Normal nerves, melanocytes, and Langerhans cells in \nepidermis, cartilage, some myoepithelial cells, skin adnexa\n\t\u2022\t \u0007Estrogen and progesterone receptors: Normal luminal \ncells in ducts and lobules of the breast\n\t\u2022\t \u0007CD31, FVIII: Vascular endothelium\n\t\u2022\t \u0007c-KIT (CD117): Mast cells\n\t\u2022\t \u0007Smooth muscle alpha actin: Blood vessel walls, myoepi\u00ad\nthelial cells in the breast\n\t\u2022\t \u0007Vimentin: Blood vessels, stromal cells\n\t\u2022\t \u0007High molecular weight (MW) keratin: Squamous \u00adepithelium\n\t\u2022\t \u0007Low MW keratin: Glandular epithelium\n\t\u2022\t \u0007CD15: Polymorphonuclear leukocytes\nNegative controls usually consist of replacing the pri\u00ad\nmary antibody with non-immune animal serum diluted \nto the same concentration as the primary antibody. No \npositive reaction should be present. If multiple primary \nantibodies are used reactive with different target antigens, \nthen they may serve as negative controls for each other. \nAlthough the best negative control would be to use anti\u00ad\nbody preabsorbed against the target antigen, this is rarely \npractical in a diagnostic laboratory. Diagnostic slides \nshould also be evaluated for internal negative controls. \nAberrant immunoreactivity of tissues that should not be \npositive is indicative that the immunoreactivity is nonspe\u00ad\ncific and the study should not be used for interpretation.\nEvaluation of Studies\nThe following features must be taken into consideration \nwhen evaluating studies:\nLocation of Immunoreactivity.\u2002 Antigens are pres\u00ad\nent in specific sites. Some antigens may be present in more \nthan one location or be extracellular.\nNonspecific positivity should be suspected when immu\u00ad\nnoreactivity is present in atypical locations:\n\t\u2022\t \u0007Background: Suspect nonspecific positivity if normal \ncells or noncellular components are positive. This can \noccur with suboptimal performance of the assay or sub\u00ad\noptimal antibodies.\n\t\u2022\t \u0007Edge artifact: Antibodies can pool at edges or holes in \ntissue. True positivity should also be present in the cen\u00ad\nter of the tissue.\n\t\u2022\t \u0007Necrosis or crushing of cells: Nonspecific positivity \ncan be seen in disrupted cells. Although keratin is gener\u00ad\nally reliable in necrotic tumors, other markers generally \nshould not be interpreted.\n\t\u2022\t \u0007Inappropriate location (e.g., cytoplasm instead of nucleus): \nOccasionally ER or PR are present in the cytoplasm instead \nof the nucleus. This is not interpreted as a positive result. \nPlasma cells have large amounts of cytoplasmic immuno\u00ad\nglobulins that can crossreact with many antibodies.\n\t\u2022\t \u0007In rare cases, immunoreactivity in an unusual location is \nof diagnostic importance:\n\t \u2022\t \u0007TTF-1: Cytoplasmic (instead of nuclear) positivity in \nhepatocellular carcinomas.\n\t \u2022\t \u0007Ki-67 (MIB1): Cytoplasmic and membrane (instead of \nnuclear) positivity in trabecular hyalinizing adenomas \nof the thyroid and sclerosing hemangiomas of the lung.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_089.png", "summary": "The page discusses immunoperoxidase studies in pathology, highlighting factors that can affect immunoreactivity and the importance of controls for accurate interpretation.", "questions": [ "How do factors like temperature, baking time, and storage conditions affect immunoreactivity in immunoperoxidase studies?", "What are the different methods of antigen retrieval procedures mentioned in the text?", "Why are controls essential in immunohistochemical studies and what are examples of internal controls mentioned?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 90, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n72\n\t \u2022\t \u0007Beta-catenin: Nuclear (instead of cytoplasmic) posi\u00ad\ntivity in solid pseudopapillary tumors of the pancreas \nand pancreatoblastomas. Both nuclear and cytoplas\u00ad\nmic positivity is seen in the majority of colon carci\u00ad\nnomas. Nuclear positivity is present in about 20% of \nendometrioid endometrial carcinomas and 70% of \ncases of desmoid-type fibromatosis.\n\t \u2022\t \u0007ALK: The pattern of immunoreactivity correlates \nwith the different types of chromosomal transloca\u00ad\ntions in anaplastic large cell lymphomas.\n\t \u2022\t \u0007NPM (nucleophosmin) shuttles between the cyto\u00ad\nplasm and nucleus. NPM1 mutations occur in about \n30% of adult AML and cause aberrant cytoplasmic \nexpression of NPM (\u201cNPMc+ AML\u201d). These cases \nhave a specific gene expression profile and distinctive \nclinical and prognostic features.\nExamples of the normal location of antigens are shown \nin Figure 7-1.\nIdentification of Immunoreactive Cells.\u2002 Immu\u00ad\nnoreactivity of tumor cells must be distinguished from \n\u00adimmunoreactivity of normal entrapped cells (e.g., desmin [+] \nskeletal muscle cells infiltrated by tumor, S100 [+] Langer\u00ad\nhans cells in tumors, smooth muscle alpha actin [+] blood \nvessels, etc.). Plasma cells have large amounts of cytoplas\u00ad\nmic immunoglobulin and can react nonspecifically with \nmany antibodies.\nIntensity of Immunoreactivity.\u2002 Some weak immu\u00ad\nnoreactivity may be present as a nonspecific finding. It \nis important to compare positive cells with control slides \nand with normally nonimmunoreactive cells to determine \nwhether the immunoreactivity is significant.\nNumber of Immunoreactive Cells.\u2002 In some cases, \nthe number of positive cells may be important as a crite\u00ad\nrion for positivity or as a prognostic marker (e.g., markers \nof proliferation such as Ki-67, HER2/neu). In other cases, \nrare weakly positive cells must be distinguished from inter\u00ad\nmingled normal cells or just nonspecific immunoreactivity.\nCriteria for a \u201cPositive\u201d Result.\u2002 Specific criteria for \nevaluating IHC have been developed for a few antibod\u00ad\nies (see Tables 7-12 to 7-16). However, criteria do not \nexist for most antibodies or are not universally used by all \nNuclear: ER, TTF-1, P63, Myf4\n(myogenin), Ki-67 (MIB1)\nMembrane: EMA, HER2/neu,\ne-cadherin, EGFR\nCytoplasm:\nGranular: organelles, secretory\nvesicles (chromogranin, HMB-45)\nFibrillary: intermediate filaments\n(actin, keratin)\nDiffuse, patchy: cytosol, large\nvesicles (myoglobin, thyroglobulin)\nExtracellular: Amyloid (\u001f2-micro-\nglobulin, lambda chain, calcitonin)\nFigure 7\u20131.\u2002 Location of immunoreactivity (indicated in blue).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_090.png", "summary": "This page discusses the use of immunoperoxidase studies in pathology, highlighting specific markers and their significance in different types of tumors.", "questions": [ "How do the patterns of immunoreactivity of Beta-catenin differ in different types of tumors?", "What are the clinical implications of NPM1 mutations in adult AML?", "How can the identification of immunoreactive cells be challenging in pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 91, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n73\nTABLE 7\u20132.\u2003\nEVALUATION OF POSITIVITY OF IMMUNOHISTOCHEMICAL STUDIES\nGENERAL MARKERS\nHEMATOPATHOLOGY MARKERS\nCategory\n% of Tumors\nInterpretation\nCategory\n% of Tumors\nInterpretation\nPositive (POS)\n>90%\nAlmost always positive; \na negative result \nwould be unusual\n+\n>90%\nAlmost always \n\u00adpositive\nHigh\n60-90%\nMost tumors are \u00adpositive\n+/\u2212\n>50%\nMajority positive\nModerate (Mod)\n40-60%\nMay or may not be \npositive \u2013 usually the \nleast useful type of \nmarker\n\u2212/+\n<50%\nMinority positive\nLow\n10-40%\nMost tumors are \u00adnegative\n\u2212\n<10%\nRarely positive\nNegative (neg)\n<10%\nAlmost all tumors are \nnegative; a positive \nresult would be unusual\nBlank\nResults unknown or \ntoo few cases to \nquantify\nBlank\nResults unknown or too \nfew cases to quantify\n?=Results based on very \nfew cases (e.g., <10)\n\u00adpathologists. The significance of immunoreactivity varies \nwith the type of lesion, the antibody, and the specific assay. \nStrong positivity in the majority of cells is easily interpreted \nas positive. As the number of positive cells decreases, and the \nintensity of immunoreactivity weakens, the lower threshold \nof a \u201cpositive\u201d result becomes more difficult to \u00addetermine.\nTime.\u2002 Alkaline phosphatase chromogens (red color) \nfade over time. DAB (a brown color) is more permanent. \nThis is not a problem in evaluating current pathology \nspecimens. However, if slides are reviewed after a period of \ntime, some chromogens may fade and once positive results \nmay appear to be negative.\nCommon Panels for Immunohistochemical Studies\nThe following tables include information from the lit\u00ad\nerature as well as the personal experiences of the staff at \nBrigham and Women\u2019s Hospital. Because of the many dif\u00ad\nferences in specific antibodies, laboratory assays, and cri\u00ad\nteria for considering a result \u201cpositive,\u201d results may vary \nfor different institutions. The results have been divided \ninto five categories for general markers and four categories \nfor hematopathology markers. Note that \u201c%\u201d refers to the \nnumber of tumors reported to be positive, not the number \nof cells positive within a tumor (Table 7-2).\nThe actual markers used to evaluate a case will depend \nupon the differential diagnosis based on the H&E appear\u00ad\nance. In some cases, an initial panel, which is often used \nfor typical cases, has been suggested. Not all markers listed \nwould be used for all cases and some markers are included \nto indicate when they would not be useful for distinguish\u00ad\ning the tumors listed in the table.\nPOSITIVE is defined as the presence of immunoreac\u00ad\ntive cells and NEGATIVE as the absence of immunoreac\u00ad\ntive cells. Unfortunately, \u201cpositive\u201d has also been used in \nsome studies to mean \u201cabsence of immunoreactivity\u201d when \nthis finding supports a diagnosis. For example, the absence \nof SMAD4 (DPC4) has been reported as a \u00ad\u201cpositive\u201d result \nfor pancreatic carcinoma, as this marker is absent in the \nmajority of these tumors. This method of reporting results \nbecomes confusing as \u201cpositive\u201d and \u201cnegative\u201d are depen\u00ad\ndent on the expected diagnosis. It is preferable to report \nthe findings (positive = immunoreactivity present; nega\u00ad\ntive = immunoreactivity absent) and then interpret them \nas supporting, or not supporting, the diagnoses in the dif\u00ad\nferential diagnosis.\nCytokeratin 7 and cytokeratin 20 tables\nThe combination of these two cytokeratins have been found \nto be useful to divide carcinomas into four main groups \n(Ck7+/Ck20+, Ck7+/Ck20-, Ck7-/Ck20+, Ck7-/Ck20-).\nIn Tables 7-3 to 7-7, other commonly used antibodies \nhave been included to show differences within each group. \nThe most useful additional antibodies will depend on the \nspecific differential diagnosis.6-8\nSmall blue cell tumors\nSee Table 7-8.\nSpindle cell lesions, soft tissue lesions, and sarcomas\nSee Table 7-9.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_091.png", "summary": "The page discusses the evaluation of positivity in immunohistochemical studies, including general markers and hematopathology markers. It emphasizes the variability in interpretation based on the type of lesion, antibody, and assay used.", "questions": [ "How do different categories of positivity (e.g., high, moderate, low) impact the interpretation of immunohistochemical studies?", "Why is it important to consider the type of lesion, antibody, and assay when interpreting immunoreactivity?", "How can the fading of chromogens over time affect the interpretation of immunohistochemical results?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 92, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n74\nTABLE 7\u20133.\u2003\nPREDOMINANTLY CK7+/CK20+\nTUMOR\nCK7+/ \nCK20+\nCK7+/\nCK20 \u2013\nCK7\u2013/\nCK20+\nCK7\u2013/\nCK20\u2013\n34B \nE12\nCAM-\n5.2\nCK5/6\nEMA\nBER-\nEP4\nCEA m\nCEA p\nTTF 1\np63\nWT1\nS100\nCHRO\nHEP\nOTHER\nCholangio- \ncarcinoma\nHigh\nLow\nLow\nneg\nHigh\nPOS\nLow\nPOS\nPOS\nHigh\nPOS\nneg\nLow\nrare\nTransitional \ncell \n\u00adcarcinoma\nPOS\nLow\nneg\nneg\nMod\nPOS\nHigh\nPOS\nMod\nMod\nneg\nHigh\nneg\nneg\nneg\nneg\nPancreas\nHigh\nLow\nLow\nneg\nPOS\nLow\nPOS\nPOS\nHigh\nPOS\nneg\nMod\nneg\nneg\nneg\nLow\nDPC4 lost in 55%\nOvarian \n\u00admucinous\nPOS\nLow\nneg\nneg\nPOS\nneg\nPOS\nMod\nLow\nneg?\nneg\nHigh\nLow\nEsophageal \nadenocar\u00ad\ncinoma\nPOS\nneg\nneg\nneg\nneg\nLow\nneg\nMod\nTABLE 7\u20134.\u2003\nNO DOMINANT CK7/CK20 PATTERN OR PATTERN UNKNOWN\nCK7+/\nCK20+\nCK7+/\nCK20\u2013\nCK7\u2013/\nCK20+\nCK7\u2013/\nCK20\u2013\n34b\nE12\nCAM- \n5.2\nCK \n5/6\nEMA\nBER-\nEP4\nCEA \nm\nCEA \np\nTTF-1\np63\nWT1\nS100\nCHRO\nHEP\nOTHER\nGastric \nadeno\u00ad\ncarci\u00ad\nnoma\nLow\nLow\nLow\nLow\nneg\nPOS\nneg\nHigh\nPOS\nHigh\nHigh\nneg\nLow\nneg?\nLow\nneg\nLow\nAmelo\u00ad\nblas\u00ad\ntoma/\nada\u00ad\nmanti\u00ad\nnomaa\nPOS\nneg\nneg\nneg?\nneg?\nLymphoepi\u00ad\nthelial car\u00ad\ncinomab\nPOS\nHigh\nMod?\nMod?\nnegc\np63 \nPOS\naAbout 15% of ameloblastomas are positive for Ck7.\nbAbout 50% of nasopharyngeal carcinomas are positive for Ck7. Many cases in Asian and North African patients (less commonly in US patients) are associated with EBV. EBV can be demonstrated by in situ hybridization, PCR, or \n\u00adoccasionally by immunohistochemistry. These carcinomas are also positive for broad-spectrum keratins (AE1/AE3 and PANK).\ncS100-positive dendritic cells are present.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_092.png", "summary": "The page discusses immunoperoxidase studies for tumors with predominantly CK7+/CK20+ pattern and those with no dominant CK7/CK20 pattern or pattern unknown.", "questions": [ "What are the implications of the CK7+/CK20+ pattern in cholangiocarcinoma?", "How does the loss of DPC4 in pancreatic tumors impact their CK7/CK20 pattern?", "What is the significance of S100-positive dendritic cells in lymphoepithelial carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 93, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n75\nTABLE 7\u20135.\u2003\nPREDOMINANTLY CK7+/CK20\u2212\nTUMOR\nCK7+/\nCK20+\nCK7+/\nCK20\u2013\nCK7\u2212/\nCK20+\nCK7\u2212/\nCK20\u2013\n34b\nE12\nCAM \n5.2\nCK 5/6\nEMA\nBER-\nEP4\nCEA m\nCEA \np\nTTF-1\np63\nWT1\nS100\nCHRO\nHEP\nOTHER\nAcinic cell carci\u00ad\nnoma\nneg\nPOS\nneg\nneg\nPOS\nPOS\nMod\nLow\nPOS\nLow\nAdenoid cystic \ncarcinoma\nneg\nPOS\nneg\nneg\nPOS\nHigh\nPOS\nMod\nPOS\nLow\nPOS\nMod\nneg\nGFAP Low\nBreast ductal \ncarcinoma\nLow\nHigh\nneg\nneg\nnega\nPOS\nLow\nPOS\nHigh\nHigh\nMod\nneg\nLowa\nLow\nMod\nLow\nneg\nER/PRb\nGCDFP \nMod\nBreast lobular \ncarcinoma\nLow\nPOS\nneg\nneg\nPOS\nneg\nPOS\nMod\nMod\nMod\nneg\nLow\nLow\nneg\nER/PRc\nGCDFP \nMod\nE-cad neg\nBrenner tumor\nneg\nPOS\nneg\nneg\nPOS\nHigh\nLow\nneg?\nPOS\nCalret low\nNSE POS\nCervical squa\u00ad\nmous cell \ncarcinoma\nneg\nHigh\nneg\nLow\nPOS\nneg\nPOS\nPOS\nPOS\nLow\nneg\nPOS\nneg\nneg\nHPV POS\np16 High\nChoroid plexus\nneg\nHigh\nneg\nLow\nPOS\nLow\nneg\nMod\nGFAP \nHigh\nChordoma\nneg\nPOS\nneg\nneg\nMod\nPOS\nPOS\nneg\nneg\nneg\nPOS\nneg\nGFAP neg\nCraniophar\u00ad-\ny\u00adngioma\nneg\nPOS\nneg\nneg\nPOS\nPOS\nEmbryonal \ncarcinoma\nneg\nPOS\nneg\nneg\nneg\nPOS\nLow\nLow\nLow\nneg?\nneg\nneg\nneg\nneg\nPLAP High\nCD30 \nHigh\nEndometrial \ncarcinoma\nLow\nHigh\nneg\nneg\nPOS\nLow\nPOS\nPOS\nLow\nLow\nneg\nneg?\nHigh\nneg\nneg\nVim POS\nER High\nLung \u2013 adeno\u00ad\ncarcinoma\nLow\nHigh\nneg\nLow\nMod\nPOS\nneg\nPOS\nPOS\nHigh\nHigh\nHigh\nMod\nLow\nLow\nneg\nLow\nLung \u2013 BALc\nnon-mucinous\nneg\nPOS\nneg\nneg\nPOS\nPOS\nHigh\nHigh\nHigh\nMod\nneg\nMod\nneg\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_093.png", "summary": "The table shows the immunoperoxidase studies for predominantly CK7+/CK20\u2212 tumors, with various markers and their expression levels in different types of tumors.", "questions": [ "What is the significance of CK7 and CK20 expression in tumor classification?", "How do the expression levels of different markers vary across different types of tumors?", "Which markers are consistently expressed in CK7+/CK20\u2212 tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 94, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n76\nTUMOR\nCK7+/\nCK20+\nCK7+/\nCK20\u2013\nCK7\u2212/\nCK20+\nCK7\u2212/\nCK20\u2013\n34b\nE12\nCAM \n5.2\nCK 5/6\nEMA\nBER-\nEP4\nCEA m\nCEA \np\nTTF-1\np63\nWT1\nS100\nCHRO\nHEP\nOTHER\nMeningioma\u00a0\u2013 \nsecretory \ntyped\nneg\nPOS\nneg\nneg\nneg\nHigh\nPOS\nPOS\nPOS\nLow\nneg\nPR Mod\nER neg\nMesothelioma\nneg\nHigh\nneg\nLow\nHigh\nPOS\nHigh\nHigh\nneg\nneg\nneg\nneg\nneg\nHigh\nneg\nLow\nneg\nCalret \nHigh\nMixed tumore\nneg\nPOS\nneg\nneg\nPOS\nPOS\nLow\nLow\nneg?\nPOS\nPOS\nneg\nGFAP \nHigh\nSMA POS\nCalp POS\nOvarian - \n\u00adendometrioid\nneg\nPOS\nneg\nneg\nPOS\nLow\nPOS\nPOS\nLow\nLow\nneg?\nLow\nHigh\nLow\nneg\nER Mod\nOvarian \u2013 serous \ncarcinoma\nneg\nPOS\nneg\nneg\nPOS\nLow\nPOS\nPOS\nneg\nneg\nneg?\nLow\nPOS\nHigh\nneg\nER High\nCalret Low\nRenal cell \u2013 \npapillary & \nchromophobe\nneg\nPOS\nneg\nneg\nPOS\nPOS\nModf\nThyroid - \n\u00adpapillary\nneg\nPOS\nneg\nneg\nPOS\nPOS\nMod\nHigh\nneg\nMod\nPOS\nHigh\nHigh\nneg\nneg\nThy POS\nCalci neg\nThyroid - \nfollicular\nneg\nPOS\nneg\nneg\nneg\nneg\nMod\nneg\nLow\nPOS\nMod\nneg\nneg\nThy POS\nCalci neg\nThyroid - \nmedullary\nneg\nPOS\nneg\nneg\nneg\nneg\nneg\nPOS\nMod\nPOS\nPOS\nThy rare\nCalci POS\naP63 may be positive in breast \u201cbasal-like\u201d carcinomas, some spindle cell metaplastic carcinomas, squamous cell carcinomas, and some papillary carcinomas. These subtypes may also have less typical keratin subsets such as Ck14 \n(detected by 34bE12), Ck17 (detected by MNF116), or Ck5/6.\nbMost well- and moderately differentiated ductal carcinomas, and carcinomas of special type (except for medullary) will be positive for hormone receptors. Poorly differentiated carcinomas, metaplastic carcinomas, and medullary \ncarcinomas are usually negative. Well- and moderately differentiated lobular carcinomas are almost always positive for ER, and usually positive for PR. Poorly differentiated lobular carcinomas may be negative for these markers.\ncNon-mucinous bronchioloalveolar carcinomas have an immunophenotype similar to lung adenocarcinomas. Mucinous BALs are more likely to be CK20 positive (about 70% positive), CDX2 positive, MUC2 positive, and less likely to \nbe TTF-1 positive (about 30% positive).\ndSecretory meningiomas are frequently positive for CK7 and CEA, whereas other subtypes are usually negative for Ck7 and CEA. The majority of all types of meningiomas are positive for PR (incuding meningiomas in males).\neMixed tumors (pleomorphic adenomas) occur most frequently in the salivary glands, but can also arise in soft tissues (myoepithelial tumors of soft tissue). These tumors have a similar immunophenotype with keratin (AE1/AE3 77%) \nor PANK (68%) or EMA (63%) present in the majority of tumors and frequent expression of markers associated with myoepithelial cells (e.g., calponin, GFAP, SMA, S100, p63). However, p63 is seen less frequently (23%) as compared to \nsalivary tumors (100%).\nfChromophobe renal cell carcinomas may be positive for WT-1. Other types are negative.\nTABLE 7\u20135.\u2003\nPREDOMINANTLY CK7+/CK20\u2212\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_094.png", "summary": "The page provides a table showing the results of immunoperoxidase studies for various tumors, indicating the presence or absence of specific markers.", "questions": [ "What are some common markers that are positive in secretory meningiomas?", "How do hormone receptor statuses differ between well- and poorly differentiated lobular carcinomas?", "What are some markers associated with non-mucinous bronchioloalveolar carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 95, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n77\nTABLE 7\u20136.\u2003\nCK7\u2212/CK20+\nTUMOR\nCK7+/\nCK20+\nCK7+/\nCK20\u2013\nCK7\u2013/\nCK20+\nCK7\u2013/\nCK20\u2013\n34b \nE12\nCAM \n5.2\nCK \n5/6\nEMA\nBER-\nEP4\nCEA \nM\nCEA p\nTTF-1\np63\nWT1\nS100\nCHRO\nHEP\nOTHER\nMerkel cell \ncarci\u00ad\nnoma\nrare\nneg\nHigh\nLow\nHigh\nneg\nHigh\nPOS\nPOS\nneg\nLow\nHigh\nneg?\nNSE \nHigh\nColon \nadenocar\u00ad\ncinoma\nLow\nneg\nHigh\nLow\nneg\nPOS\nneg\nHigh\nPOS\nPOS\nPOS\nneg\nLow\nneg\nLow\nneg\nneg\nCDX2 \nPOS\nRare colon carcinomas are either CK7 positive or CK20 negative, but they are rarely CK7+ CK20-. Although the majority of colon carcinomas are positive for CK20, almost one third of colon carcinomas with microsatellite instability \n(MSI-H positive) are CK20 negative. (see Table 19-24).\nTABLE 7\u20137.\u2003\nPREDOMINANTLY CK7\u2212/CK20\u2013\nTUMOR\nCK7+/\nCK20+\nCK7+/\nCK20\u2013\nCK7\u2013/\nCK20+\nCK7\u2013/\nCK20-\n34b \nE12\nCAM \n5.2\nCK 5/6\nEMA\nBER-\nEP4\nCEA \nm\nCEA \np\nTTF-1\np63\nWT1\nS100\nCHRO\nHEP\nOTHER\nAdrenal \ncortical \nadenoma\nneg\nneg\nneg\nPOS\nneg\nneg\nneg\nneg\nLow\nneg\nneg\nneg\nLow\nMelanA103 \nPOS\nInhibin \nPOS\nCarcinoid\nneg\nLow\nLow\nHigh\nneg\nPOS\nLow\nLow\nMod\nMod\nVARa\nneg\nVARb\nPOS\nLow\nEpithelioid \nsarcoma\nneg\nLow\nneg\nPOS\nMod\nHigh\nLow \n(foc)\nPOS \n(foc)\nLow \n(foc)\nneg\nneg\nEsophageal \nsquamous \ncell carci\u00ad\nnoma\nneg\nLow\nneg\nHigh\nPOS\nHigh?\nPOS\nPOS\nHigh?\nLow?\nLow\nneg\nPOS\nneg\nneg\nneg?\nSeminoma\nneg\nLow\nneg\nHigh\nneg\nLow\nLow\nneg\nneg\nneg\nneg\nneg\nneg\nPLAP POS\nCD117 POS\nHead and \nneck squa\u00ad\nmous cell \ncarcinoma\nneg\nLow\nLow\nHigh\nPOS\nneg\nPOS\nPOS\nneg\nneg\nPOS\nneg\nneg\nHepatocel\u00ad\nlular carci\u00ad\nnoma\nLow\nLow\nneg\nHigh\nLow\nPOS\nneg\nLow\nLow\nneg\nHighc\nHighd \n(cyt)\nLow\nneg\nneg\nHigh\nAFP Mod\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_095.png", "summary": "The page discusses the immunoperoxidase studies for different tumors, highlighting the expression of CK7 and CK20 markers.", "questions": [ "How do the expressions of CK7 and CK20 markers vary among different types of tumors?", "Why are rare colon carcinomas either CK7 positive or CK20 negative?", "What implications does the expression of CK7 and CK20 markers have on the diagnosis and classification of tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 96, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n78\nTUMOR\nCK7+/\nCK20+\nCK7+/\nCK20\u2013\nCK7\u2013/\nCK20+\nCK7\u2013/\nCK20-\n34b \nE12\nCAM \n5.2\nCK 5/6\nEMA\nBER-\nEP4\nCEA \nm\nCEA \np\nTTF-1\np63\nWT1\nS100\nCHRO\nHEP\nOTHER\nLung \u2013 squa\u00ad\nmous cell \ncarcinoma\nneg\nLow\nLow\nHigh\nPOS\nHigh\nPOS\nMod\nLow\nneg\nPOS\nneg\nLow\nLung \u2013 \nsmall cell \n\u00adcarcinoma\nneg\nLow\nneg\nHigh\nneg\nHigh\nneg\nPOS\nPOS\nMod\nHigh\nPOS\nrare\nneg?\nMod\nneg\nPheo/para\u00ad\nganglioma\nrare\nrare\nrare\nPOS\nneg\nneg\nneg\nneg\nneg\nHigh\nPOS\nInhibin neg\nMelanA103 \nrare\nProstatic \n\u00adcarcinoma\nneg\nneg\nLow\nHigh\nneg\nPOS\nneg\nLow\nPOS\nneg\nMod\nneg\nneg\nneg\nneg\nLow\nneg\nPSA POS\nRenal cell \ncarcinoma \n\u2013clear cell\nneg\nLow\nneg\nHigh\nneg\nHigh\nneg\nPOS\nLow\nLow\nneg\nneg\nLow\nneg?\nLow\nneg\nneg\nVim POS\nSquamous \ncell carci\u00ad\nnomae\nneg\nLow\nHigh\nPOS\nLow\nPOS\nPOS\nneg\nMod\nLow\nLow\nPOS\nneg\nneg\nneg\nThymic carci\u00ad\nnoma\nPOS\nPOS\nPOS\nMod\nHigh\nLow\nneg?\nneg\nPOS\nneg\nneg\nLow\nCD5 Mod\nThymoma\nneg\nLow\nneg\nHigh\nHigh\nHigh\nMod\nLow\nneg?\nneg\nPOS\nneg\nneg\nneg?\nneg?\nCD5 neg\naNon-pulmonary carcinoid tumors are negative for TTF-1. Some pulmonary carcinoids may be positive.\nbSustentactular cells may be positive for S100 and positivity can vary with site.\ncCEA has a canalicular pattern in hepatocellular carcinoma, a diffuse cytoplasmic pattern in other carcinomas.\ndTTF-1 immunoreactivity in HCC is cytoplasmic (not nuclear as in lung and thyroid carcinomas). Positivity can vary with the antibody used to detect TTF-1.\neCervical carcinomas and basaloid squamous cell carcinomas of the tonsil are usually HPV positive. Nasopharyngeal carcinomas are usually EBV positive. Thymic squamous cell carcinomas are often CD5 positive.\nTABLE 7\u20137.\u2003\nPREDOMINANTLY CK7\u2212/CK20\u2212\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_096.png", "summary": "The page provides a table showing the immunoperoxidase studies for various tumors, indicating the presence or absence of specific markers.", "questions": [ "What are the implications of a tumor being CK7+/CK20+ versus CK7+/CK20-?", "How do the immunoperoxidase studies help in distinguishing between different types of lung carcinomas?", "Why is it important to note the specific patterns of CEA immunoreactivity in different carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 97, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n79\nTABLE 7\u20138.\u2003\nSMALL BLUE CELL TUMORS\nTUMOR\nPANK\nCAM \n5.2\nCK20\nEMA\nS100\nHMB \n45\nNSE\nSYN\nCHRO\nCD99\nSMA\nHHF \n35\nDES \nMIN\nMYF-4\nLCA\nNFP\nWT1a\nPASb\nMelanoma\nrare\nrare\nneg\nneg\nPOS\nHighc\nHigh\nLow\nneg\nLow\nLow\nneg\nneg\nneg\nneg\nEsthesioneuro\u00ad\nblastoma\nLow\nMod\nLow\nPOS\nPOS\nHigh\nMod\nLow\nneg\nneg?\nneg\nMod\nNeuroblas\u00ad\ntoma\nneg\nneg\nneg\nLow\nMod\nneg\nPOS\nHigh\nHigh\nneg\nneg\nneg\nneg\nneg\nHigh\nLow\nneg\nSmall cell car\u00ad\ncinomad\nPOS\nMod\nneg\nPOS\nneg\nneg\nHigh\nMod\nMod\nLow\nneg\nneg\nneg\nneg\nMerkel cell car\u00ad\ncinomae\nPOS\nPOS\nPOS\nPOS\nneg\nneg\nHigh\nMod\nHigh\nLow\nneg?\nneg\nMod\nneg\nDesmoplastic \nsmall round \ncell tumor\nPOS\nPOS\nneg\nPOS\nLow\nneg\nHigh\nLow\nLow\nMod\nLow\nLow\nPOS\nneg\nneg\nPOS\nPOS\nEwing\u2019s (PNET)\nLow\nLow\nLow\nLow\nneg\nMod\nLow\nneg\nPOSf\nneg\nLow\nneg\nneg\nLow\nneg\nPOS\nMedulloblas\u00ad\ntoma\nneg\nneg?\nLow\nPOS\nPOS\nLow\nLow\nneg\nRhabdomyo\u00ad\nsarcoma\nneg\nMod\nneg\nLow\nneg\nMod\nneg\nneg\nLow\nLow\nPOS\nPOS\nPOS\nneg\nLow\nMod\nPOS\nAML\nneg\nneg\nneg\nneg\nLow\nneg\nPOS?\nMod\nHigh\nLymphoma\nneg\nneg\nneg\nneg\nneg\nneg\nneg\nneg\nneg\nVar\nneg\nneg\nneg\nneg\nPOS\nnegg\naPolyclonal WT1 \u2013 nuclear immunoreactivity.\nbPAS is a histochemical stain for glycogen. A PAS-D stain confirms the presence of glycogen by treatment of the tissue with diastase, which digests the glycogen and eliminates the positivity. Although used for these tumors in the \npast, these studies are currently not usually performed.\ncMART-1 is also frequently positive in melanomas.\ndSmall cell carcinomas of the lung are positive for TTF-1.\neMerkel cell carcinomas demonstrate a dot like perinuclear pattern for most markers.\nfSignificant immunoreactivity is a membrane pattern in the majority of the cells.\ngSome plasma cell lymphomas may be positive.\nEwing\u2019s (PNET), desmoplastic small round cell tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma have characteristic cytogenetic changes (see Table 7-47).\nEM has some advantages over immunohistochemistry in the evaluation of childhood small round blue cell tumors.9\nInitial panel: Keratin, S100, LCA. Additional studies may be helpful depending on the histologic appearance and the results of the initial studies.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_097.png", "summary": "The page discusses immunoperoxidase studies for small blue cell tumors, listing various markers and their expression levels in different tumor types.", "questions": [ "What are the characteristic cytogenetic changes in Ewing's (PNET), desmoplastic small round cell tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma?", "What is the significance of MART-1 positivity in melanomas?", "Why are PAS-D stains not usually performed for these tumors anymore?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 98, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n80\nTABLE 7\u20139.\u2003\nSPINDLE CELL/SOFT TISSUE LESIONS/SARCOMAS\nTUMOR\nAE1/\nAE3\nCAM \n5.2\nEMA\nS100\nHMB \n45\nHHF-\n35\nSMA\nDES-\nmin\nH-CALDESMON\nCD34\nCD31\nFVIII\nC-kit CD117\nCD99\nOTHER\nNEURAL\nPerineurioma\nneg\nneg\nPOS\nLow\nneg\nMod\nLow\nneg\nMod\nneg\nneg\nneg\nMod\nCLAUD-1 \nLowa\nNeurofibroma\nneg\nneg\nPOSb\nPOS\nneg\nneg\nneg\nneg\nHigh\nneg\nneg\nMPNST\nLow\nLow\nLow\nMod\nneg\nLow\nLow\nneg\nneg\nLow\nneg\nGFAP Mod\nSchwannoma\nLow\nneg\nnegc\nPOS\nneg\nneg\nneg\nneg\nMod\nneg\nneg\nneg\nCD68 POS\nGranular cell \ntumorn\nneg\nneg\nneg\nPOS\nneg\nneg\nneg\nneg\nneg\nCD68 POS\nCalret POS\nInhibin \nPOS\nMELANOMA\nrare\nrare\nneg\nPOS\nHighe\nneg\nneg\nneg\nneg\nneg\nneg\nMod\nLow\nMelanAa \nHigh\nFLI-1 neg\nCLEAR CELL \n\u00adSARCOMA\nneg\nneg\nneg\nHigh\nPOS\nLow\nneg\nneg\nneg\nneg\nneg\nLow\nLow\nMelanA \nMod\nPECOMAF\nneg\nneg\nneg\nLow\nPOS\nPOS\nPOS\nHigh\nMod\nLow\nneg\nneg\nVARh\nMelanA \nPOS\nGIST\nneg\nneg\nneg\nLow\nMod\nLow\nneg\nHigh\nHigh\nneg\nPOS\nPOS\nDOG1 POS\nMUSCLE\nRhabdomyosar\u00ad\ncoma\nLow\nLow\nLow\nneg\nneg\nHigh\nMod\nHigh\nneg\nLow\nneg\nneg\nneg\nLow\nMyf4 POS\nWT1 Mod\nFLI-1 neg\nGlomus \ntumor\nneg\nneg\nneg\nneg\nneg\nPOS\nPOS\nLow\nHigh\nLow\nneg\nneg\nneg\nLeiomyoma or \nleiomyosar\u00ad\ncoma\nLow\nLow\nMod\nneg\nneg\nPOS\nPOS\nHigh\nPOS\nLow\nneg\nneg\nneg\nLow\nER/PR \nHigh\nCD10 Low\nENDOMETRIAL \nSTROMAL \n\u00adSARCOMA\nMod\n(foc)\nLow\n(foc)\nneg\nHigh\nMod\nneg\nneg\nneg\nER/PR \nHigh\nCD10 High", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_098.png", "summary": "The page provides a table of immunoperoxidase studies for spindle cell/soft tissue lesions/sarcomas, indicating the positivity or negativity of various markers for different types of tumors.", "questions": [ "What are the most common markers used in immunoperoxidase studies for spindle cell/soft tissue lesions/sarcomas?", "How do the markers AE1/AE3, CAM 5.2, and EMA differ in their expression among the different tumor types?", "Why is the marker S100 important in differentiating between neural tumors on this table?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 99, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n81\nContinued\nVASCULAR\nAngiosar\u00adcoma\nLowh\nLowh\nrare\nneg\nneg\nLow\nLow\nneg\nHigh\nHigh\nHigh\nLow\nFLI-1 POS\nKaposi\u2019s \n\u00adsarcoma\nneg\nneg\nneg\nneg\nneg\nPOS\nneg\nPOS\nHigh\nMod\nneg\nFLI-1 POS\nHHV 8 POS\nEpithelioid \nhemangioen\u00ad\ndothelioma\nHigh\nneg\nneg\nneg\nneg\nneg\nLow\nneg\nHigh\nHigh\nPOS\nneg\nFLI-1 POS\n\u201cFIBROUS\u201d\nFibrosarcoma\nneg\nLow\nneg\nneg\nneg\nneg\nneg\nneg\nLow\nSolitary \nfibrous \ntumor\nneg\nneg\nLow\nneg\nneg\nLow\nneg\nneg\nPOS\nneg\nneg\nneg\nHigh\nDFSP\nneg\nneg\nneg\nneg\nneg\nHigh\nLow\nneg\nneg\nPOS\nneg\nneg\nneg\nDermatofibroma\nneg\nneg\nneg\nneg\nHigh\nHigh\nnegi\nLowq\nneg\nneg\nFibromatosis\nneg\nneg\nneg\nMod\nHigh\nHigh\nMod\nneg\nneg\nneg\nneg\nER rare\nPost-op \nspindle cell \nnodule\nMod\nMod\nLow\nneg\nHigh\nHigh\nMod\nneg\nneg\nneg\nMyofibroblastic \ntumors\nneg\nneg\nneg\nPOS\nHigh\nMod\nneg\nMod\nneg\nER High\nPR POS\nAtypical \n\u00adfibroxanthoma\nneg\nneg\nneg\nneg\nneg\nLow\nneg\nLow\nCD68 Mod\nLIPOMATOUSr\nWell- or dedif\u00ad\nferentiated \nliposarcoma\nMDM2 \nPOS\nCDK4 POS\nBenign lipoma\u00ad\ntous tumors\nMDM2 rare\nCDK2 rare", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_099.png", "summary": "The page provides immunoperoxidase study results for various vascular tumors, including angiosarcoma, Kaposi's sarcoma, epithelioid hemangioendothelioma, fibrosarcoma, solitary fibrous tumor, DFSP, dermatofibroma, fibromatosis, post-op spindle cell nodule, myofibroblastic tumors, and atypical fibroxanthoma.", "questions": [ "What are the key immunoperoxidase study findings for angiosarcoma?", "How do the immunoperoxidase study results differ between Kaposi's sarcoma and epithelioid hemangioendothelioma?", "What are the distinguishing immunoperoxidase markers for fibrosarcoma and solitary fibrous tumor?", "Are there any common immunoperoxidase markers shared between dermatofibroma, fibromatosis, and post-op spindle cell nodule?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 100, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n82\nAE1/\nAE3\nCAM \n5.2\nEMA\nS100\nHMB45\nHHF-\n35\nSMA\nDES-\nmin\nH-CALDESMON\nCD34\nCD31\nFVIII\nC-kit CD117\nCD99\nOTHER\nOTHER\nOsteosarcoma\nneg\nneg\nLow\nLow\nMod\nHigh\nneg\nneg\nLow\nChondrosarcoma\nneg\nneg\nLow\nPOS\nneg\nneg\nneg\nneg\nneg\nLow\nChrondroblas\u00ad\ntoma\nneg\nneg\nneg\nPOS\nMod\nLow\nneg\nneg?\nPOS\nMesenchymal \nchondrosar\u00ad\ncoma\nneg\nneg\nneg\nPOS\nneg\nrare\nLow\nPOS\nMy4 neg\nExtraskeletal \nmyxoid chon\u00ad\ndrosarcoma\nneg\nneg\nLow\nLow\nneg\nneg\nneg\nLow\nLow\nneg\nAlveolar soft part \nsarcoma\nneg\nneg\nLow\nneg\nLow\nLow\nLow\nLow\nneg\nneg\nLow\nMyoD1 \nneg\nMyogenin \nneg\nTFE3 \nPOSj\nEpithelioid sar\u00ad\ncoma\nPOS\nPOS\nPOS\nneg\nneg\nLow\nLow\nneg\nMod\nneg\nneg\nneg\nLow\nFLI-1 neg\nSynovial sarco\u00ad\nmak\nHigh\nHigh\nHigh\nMod\nneg\nneg\nLow\nneg\nneg\nneg\nneg\nneg\nneg\nHigh\nWT1 neg\nClaudin-1 \nPOSl\nCalret \nMod\nbcl2 High\nADENOMATOID \nTUMOR\nPOS\nPOS\nPOS\nneg\nneg\nneg\nBer-EP4 \nHigh\nCalret \nPOS\nWT1 POS\nTABLE 7\u20139.\u2003\nSPINDLE CELL/SOFT TISSUE LESIONS/SARCOMAS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_100.png", "summary": "The page lists various immunoperoxidase studies and their corresponding results for different types of sarcomas and soft tissue lesions.", "questions": [ "What is the significance of the different immunoperoxidase study results for the various sarcomas?", "How do the results of the immunoperoxidase studies aid in the diagnosis and classification of sarcomas?", "Are there any specific markers that are consistently present or absent in certain types of sarcomas based on the immunoperoxidase studies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 101, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n83\nMESOTHELIOMA \n\u2013 SARCOMATOID \nTYPEm\nHigh\nPOS\nLow\nPOS\nHigh\nLow\nneg\nLow\nWT1n\nD2-40 \nHigh\nCalret Low\nMENINGIOMA\nnego\nnego\nHigh\nLow\nneg\nLow\nLow\nneg\nLow\nneg\nneg\nPOS\nER neg\nPR POS\nPANK Low\nCARCINOMA \u2013 \nSPINDLE CELLP\nVAR\nVAR\nVAR\nVAR\nneg\nrare\nrare\nneg\nneg\nneg\nneg\naSome claudin-1 positive perineurial cells can be present in neurofibromas and schwannomas. About 30% of perineuriomas are positive.\nbPerineural cells are positive for EMA in neurofibromas.\ncEMA may be positive in capsule and perineural cells of schwannomas.\ndCongenital granular cell tumors are positive for CD68 but negative for S100 and NSE.\neHMB-45 is less frequently present in spindle cell melanomas and usually negative in classic desmoplastic melanomas. Other markers for melanoma are also less frequently positive in these subsets.\nfPEComa (perivascular epithelioid cell tumors) includes angiomyolipoma, lymphangioleiomyomatosis, clear cell sugar tumor of the lung, clear cell myomelanocytic tumor of ligamentum teres/falciform ligament, \nand \u00adabdominopelvic sarcoma of perivascular epithelioid cells.\ngResults in the literature are conflicting. Angiomyolipomas are likely not positive for CD117.\nhKeratin positivity may be present in ~25% of epithelioid angiosarcomas.\niCellular dermatofbroma may show focal desmin immunoreactivity and a few will be CD34 positive.\njAlveolar soft part sarcomas are characterized by a translocation that fuses the TFE3 transcription factor gene at Xp11 to a novel gene at 17q25 called ASPL. These sarcomas demonstrate nuclear immunoreactivity for TFE3 (as do \nrare pediatric renal tumors with the same translocation) and this immunoreactivity is not present in other tumors or normal tissues. The characteristic cytoplasmic crystals are composed of monocarboxylate transporter 1 (MCT1) \nand its chaperone CD147. However, these proteins are found in many other cell types and are not specific for this tumor.\nkKeratin and EMA positivity are usually only focal in monophasic synovial sarcomas.\nlClaudin-1 is positive in glandular areas of synovial sarcoma but less so in spindle cell areas.\nmThe immunohistochemical pattern for epithelioid mesotheliomas is given in a separate table.\nnWT-1 may be positive in a minor epithelioid component of sarcomatoid mesotheliomas, but is generally negative in the spindle cells.\noSecretory meningiomas are typically cytokeratin 7 positive (Ck20 negative) and also positive for CEA. Other subtypes are generally negative for keratin. However, malignant meningiomas may be positive for keratin.\npSquamous cell carcinomas with a spindle cell morphology are generally strongly positive for AE1/AE3 (less commonly for CAM5.2), EMA, and p63. Spindle cell carcinomas of the breast often express markers expressed by \n\u00admyoepithelial cells such as \u201cbasal keratins\u201d (including cytokeratin 14, which is included in the group detected by PANK or MNF-116), smooth muscle alpha actin, and p63. Poorly differentiated carcinomas with a spindle cell \n\u00admorphology may only show focal positivity for keratins and EMA.\nqDermatofibromas may have weak peripheral positivity for CD34 which is distinguished from strong diffuse positivity in DFSP.\nrOther sarcomas (e.g., ~60% of MPNST) can be positive for MDM2 or CDK4. These markers are helpful to distinguish between benign and malignant lipomatous tumors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_101.png", "summary": "The page discusses immunoperoxidase studies for mesothelioma, meningioma, and carcinoma - spindle cell type, highlighting various markers and their positivity or negativity.", "questions": [ "How do the immunoperoxidase studies differ between mesothelioma, meningioma, and spindle cell carcinoma?", "What are some specific markers mentioned in the text and their significance in diagnosing these types of tumors?", "Are there any conflicting results or ambiguous findings mentioned in the text regarding the immunohistochemical patterns?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 102, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n84\nMetastatic tumors of unknown origin\nPathologists frequently receive specimens with metastatic \ntumors. Often, the site of origin is known to the clinician, but \nthis information is not provided to the pathologist. A good \nclinical history is frequently more successful for correct \nclassification than a battery of studies.\nThe Ck7/Ck20 pattern is generally helpful to narrow \ndown the potential site of origin of carcinomas (see Tables \n7-3 to 7-7). Additional studies can then be used to identify \nspecific types of carcinoma.\nThe most important tumors to identify are those with \nspecific therapeutic treatments for cure or palliation (Table \n7-10).10\nTABLE 7\u201310.\u2003\nMETASTATIC TUMORS OF UNKNOWN ORIGIN\nTYPE OF TUMOR\nIHC\nCOMMENTS\nPOTENTIAL TREATMENT\nBreast\nER/PR\nHER2/neu\nGCDFP-15\nGyn carcinomas can also be positive. Other carcino\u00ad\nmas are rarely positive.\nIt is unusual for other carcinomas to be strongly \npositive for HER2/neu.\nGCDFP-15 is not very sensitive, as many breast \ncarcinomas are negative.\nThe most common type of breast carcinoma to \npresent as an occult primary is invasive lobular \ncarcinoma.\nRare women present with positive axillary nodes \nand no known primary. Most of these women will \nhave breast cancer. The prognosis is the same, \nwhether or not the primary is detected.\nPalliated with hormonal \n\u00adtreatment.\nHER2/neu-positive carcinomas \ncan be treated with Herceptin.a\nCarcinoid tumor\nChromogranin\nChromogranin positivity should be strong and dif\u00ad\nfuse. Focal and/or weak positivity can be seen in \nmany carcinomas.\nMetastatic breast cancer and prostate cancer can \nclosely resemble carcinoid tumor and both can \nbe positive for chromogranin.\nPalliation with tumor-directed \npharmaceuticals.\nGerm cell tumors\nPLAP\nOCT-4\nPLAP is not specific, but a germ cell tumor is \nunlikely if it is negative. Inhibin is more likely to \nbe positive in choriocarcinomas.\nOCT-4 is highly specific for undifferentiated germ \ncell tumors (embryonal carcinoma and semi\u00ad\nnoma) among epithelioid and round cell malig\u00ad\nnant neoplasms. Other types of germ cell tumors \n(i.e., yolk sac tumor, teratoma, and choriocarci\u00ad\nnoma) are negative.\nFISH can confirm an isochromosome 12p, \neven if the metastasis has the appearance of \n\u00adadenocarcinoma, sarcoma, or neuroendocrine \ncarcinoma\nChemotherapy for possible cure.\nGIST\nc-kit (CD117)\nSpecific mutations are correlated with treatment \nresponse.\nTreatment with Gleevec.b\nLung adenocarci\u00ad\nnoma\nTTF-1\nThyroid carcinoma should be excluded if TTF-1 is \npositive.\nUp to 20% of patients will have \nspecific activating muta\u00ad\ntions in EGFR (detected by \nPCR) and these patients may \nrespond well to treatment with \ngefitinib.c\nLymphoma\nLCA, B and T cell \nmarkers\nTreatment for cure or long-term \npalliation.\nProstate\nPSA or PrAP\nHormonal therapy effective for \npalliation.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_102.png", "summary": "Pathologists often receive specimens with metastatic tumors of unknown origin, where a good clinical history is crucial for correct classification. Immunoperoxidase studies, such as the Ck7/Ck20 pattern, can help narrow down the potential site of origin of carcinomas.", "questions": [ "How important is a good clinical history in correctly classifying metastatic tumors of unknown origin?", "What role do immunoperoxidase studies, specifically the Ck7/Ck20 pattern, play in identifying the potential site of origin of carcinomas?", "Why is it essential to identify specific types of carcinomas, especially those with specific therapeutic treatments, among metastatic tumors of unknown origin?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 103, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n85\nTYPE OF TUMOR\nIHC\nCOMMENTS\nPOTENTIAL TREATMENT\nSmall cell carcinoma\nTTF-1 (if of lung \norigin)\nNeuroendocrine \nmarkers\nDiagnosis made by H&E appearance. P63 is usually \nnegative and can be useful to exclude squamous \ncell carcinoma.\nNot necessary for diagnosis, but can exclude other \ndiagnoses.\nChemotherapy for palliation.\nSquamous cell \n\u00adcarcinomas\nCk5/6, p63\np16 or HPV\nCD5\nNot specific, but characteristic. H&E appearance \nusually sufficient to reveal keratin production or \nintercellular bridges.\nHPV or p16 are most commonly present in \n\u00adcarcinoma of the cervix, but may be seen in \n\u00adcarcinomas at other sites.\nAbout 26-38% of patients with a cervical LN metasta\u00ad\nsis of unknown primary will have an occult tonsillar \ncarcinoma (usually basaloid type and p16 or HPV \npositive). Complete sampling of the tonsil may be \nnecessary to identify these small carcinomas.\nMay be positive in thymic carcinomas.\nRadiation therapy often effective.\nVaccine trials are being \n\u00adconducted.\nThyroid \u2013 \u00adpapillary or \nfollicular carcinoma\nThyroglobulin \nand TTF-1\nLung carcinomas are also TTF-1 positive, but \nwill be thyroglobulin negative.\nHighly effective treatment for \ncure with radioactive iodine.\nThyroid \u2013 \u00admedullary \ncarcinoma\nCalcitonin\nIf familial, important for counseling other family \nmembers.\nPalliative treatment with tumor-\ndirected radionucleotides.\nTrophoblastic \ntumors\nInhibin\nInhibin is not specific, but a trophoblastic \ntumor is unlikely if it is negative.\nChemotherapy for possible cure.\naTrastuzumab (Herceptin) = a monoclonal antibody directed against the HER2/neu receptor.\nbImatinib mesylate (STI571, Gleevec\u2122, Glivec\u2122) is a small molecule tyrosine kinase inhibitor used for CML, ALL (Ph+), and GIST.\nThe KIT protein is encoded by the c-kit proto-oncogene and is a transmembrane receptor protein with tyrosine kinase activity. Mutated proteins may or may not respond to \ntherapy with Imatinib. Mutations that render KIT independent of its ligand, SCF (stem cell factor), have been found in GIST, AML, germ cell tumors and systemic \u00admastocytosis. \nWild-type KIT and KIT with mutations in the juxtamembrane domain (the intracellular segment between the transmembrane and tyrosine kinase domains) are found in GISTs \nand are sensitive to imatinib. Other tumor types are associated with mutations in the enzymatic domain and the altered protein is generally not sensitive to imatinib.\ncGefitinib (Iressa) = a tyrosine kinase inhibitor effective against a small subset of lung adenocarcinomas with specific activating mutations.\nTABLE 7\u201310.\u2003\nMETASTATIC TUMORS OF UNKNOWN ORIGIN\u2014cont\u2019d\nPoorly differentiated tumors\nSee Table 7-11.\nTABLE 7\u201311.\u2003\nPOORLY DIFFERENTIATED TUMORS\nTYPE OF TUMOR\nIMMUNOHISTOCHEMICAL \nMARKER\nCOMMENTS\nCarcinoma\nBroad spectrum keratins\nAE1/AE3 or PANK\n(MNF-116)\nSome carcinomas may express unusual keratin sub-types. If negative, try other \nkeratin types (e.g., CAM5.2). The Ck7/Ck20 pattern may be helpful in deter\u00ad\nmining the likely site of origin.\nSome non-carcinomas can have an epithelioid appearance and strongly express \nkeratins (e.g., epithelioid angiosarcoma, epithelioid sarcoma, mesothelioma).\nMelanoma\nS100 protein\nS100 is strongly positive in the vast majority of melanomas.\nSome carcinomas (especially breast) and sarcomas are also positive for S100 \nand additional markers may be required.\nHMB-45 and MART-1 are expressed by most epithelioid melanomas but \nmay be focal or absent in non-epithelioid melanomas (e.g., spindle cell or \n\u00addesmoplastic melanomas).\nLymphoma\nLeukocyte common antigen \n(LCA)\nPresent in almost all non-Hodgkin\u2019s lymphomas.\nMay be absent in 30% of anaplastic (Ki-1) large cell lymphomas. These lympho\u00ad\nmas are keratin negative but may express EMA. These tumors will be positive \nfor CD30 (Ki-1) and ALK.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_103.png", "summary": "The page discusses special studies, particularly immunoperoxidase studies, for different types of tumors and their potential treatments.", "questions": [ "How are immunoperoxidase studies used in diagnosing different types of tumors?", "What are the specific immunohistochemical markers used for poorly differentiated tumors?", "What are the potential treatments mentioned for different types of tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 104, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n86\nEstrogen and progesterone receptor evaluation\nHormone receptors are routinely determined on all inva\u00ad\nsive breast carcinomas and DCIS. ER and PR are weak \nprognostic markers and are more useful to predict the like\u00ad\nlihood of response to hormonal therapies.\nMany different methods are currently used to report \nthe results of IHC studies for ER and PR. One method \nthat has been used in multiple studies is the Allred score \nmethod (Table 7-12).\nPatients with carcinomas that scored 3 (<1% of cells \nwith intermediate intensity or 1% to 10% of cells with \nweak intensity) or above had improved disease-free sur\u00ad\nvival when treated with endocrine therapy.11 Patients with \ncarcinomas with a total score of 2 (<1% weakly positive \ncells) had a survival rate similar to ER-negative carcinomas \n(total score of 0).\nAbout 80% of DCIS cases are positive for ER using the \nsame method of scoring. Women with ER-positive DCIS \nwere shown to experience fewer local recurrences, contra\u00ad\nlateral recurrences, and distant recurrences when treated \nwith tamoxifen (NSABP B24 study).\nWith optimization of IHC using newer antigen retrieval \nmethods, 99.2% of carcinomas will have scores of 0, 7, or \n8.12 Therefore, many laboratories report results as posi\u00ad\ntive or negative. The value of further subdividing cases by \npercent positive cells, H-score, or image analysis for either \nprognosis or to predict response to tamoxifen has not been \ndemonstrated. Intensity of immunoreactivity is difficult to \nevaluate as most cases show strong reactivity with optimal \nassay methods and most carcinomas show considerable \nvariability in intensity.\nA possible method for reporting results is shown in \nTable 7-13. The same system can be used for reporting \nprogesterone receptor results. The use of both ER and PR \nmay be helpful for determining the likelihood of response \nto tamoxifen, as has been shown with data using the bio\u00ad\nchemical assay (Table 7-14). Presumably, the presence of \nthe ER-regulated gene product PR is more predictive of an \nintact ER regulatory pathway.\nRecent national guidelines for reporting ER and PR \nhave been released and should be consulted for additional \ninformation about performing and interpreting these stud\u00ad\nies (Hammond ME, et al, American Society of Clinical \nOncology/College of American Pathologists Guideline \nRecommendations for Immunohistochemical Testing of \nEstrogen and Progesterone Receptors in Breast Cancer, J \nClin Oncol 2010 Apr 19).\nTABLE 7\u201314.\u2003\nRESPONSE TO TAMOXIFEN\nSTATUS OF \nCARCINOMA\n% OF \nCARCINOMAS\n% OF PATIENTS \nRESPONDING TO \nTAMOXIFEN\nER+ PR+\n63%\n75% to 80%\nER+ PR\u2013\n15%\n25% to 30%\nER\u2013 PR+\n5%\n40% to 45%\nER\u2013 PR\u2013\n17%\n<10%\nTABLE 7\u201312.\u2003\nER AND PR\u2014ALLRED SCORE\nPROPORTION \nSCORE (PS)\n% POSITIVE \nCELLS\nINTENSITY \nSCORE (IS)\nINTENSITY \nOF \nPOSITIVITY\n0\n0\n0\nNone\n1\n<1%\n1\nWeak\n2\n1% to 10%\n2\nIntermediate\n3\n10% to 33%\n3\nStrong\n4\n33% to 66%\n5\n>66%\nThe PS and IS Are Added Together for a Total Score:\nTotal Score (TS) = PS + IS\nInterpretation\n0, 2\nNegative\n3, 4, 5, 6, 7, 8\nPositive\nTABLE 7\u201313.\u2003\n\u0007REPORTING RESULTS OF ER AND PR \nEVALUATION\nRESULT\nCRITERIA\n% OF \nCASES\nCOMMENTS\nPositive\n>10% of \ncells\n70% to \n80%\nThis group corresponds \nto PS scores of 3 and \nabove. The majority \nof these carcinomas \nwill have scores of 7 \nor 8.\nBorderline \nor low \npositive\n>0% to \n10%\n<5% to \n10%\nThe clinical significance \nof this group is \nunclear. This group \nmay be interpreted \nas \u201cnegative\u201d or \u201cposi\u00ad\ntive\u201d by some labo\u00ad\nratories depending \non the cut-off point \nchosen. This group \ncould include cases \nwith Allred scores of \n2, 3, 4, or 5.\nNegative\n0\n20% to \n30%\nThis group corresponds \nto a TS score of 0.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_104.png", "summary": "Hormone receptor evaluation, specifically estrogen and progesterone receptors, is important in predicting response to hormonal therapies in breast carcinomas. Different scoring methods are used to assess receptor status.", "questions": [ "How do hormone receptor evaluations impact treatment decisions for breast carcinomas?", "What are the implications of different scoring methods for estrogen and progesterone receptors?", "What are the potential benefits of using both ER and PR status in predicting response to tamoxifen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 105, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n87\nFalse negative results, and to a lesser extent, false posi\u00ad\ntive results, can also be problems. False negative results \nmay be due to a large number of causes including:\n\t\u2022\t \u0007Low sensitivity of the assay\n\t\u2022\t \u0007Errors in performing the assay\n\t\u2022\t \u0007Delayed fixation of tissue\n\t\u2022\t \u0007Over- or underfixation of tissue\n\t\u2022\t \u0007Overheating of tissue (e.g., with cautery during surgery)\n\t\u2022\t \u0007Decalcification of tissue\nMost cases of false negativity can be suspected, as the \nnormal breast tissue will also be negative. In such cases, \nthe assay should be repeated on the same block, a \u00addifferent \nblock from the same case, or blocks from another case, \nif available. If the normal tissue remains negative, the \n\u00adpossibility of loss of antigenicity in the tissue can be men\u00ad\ntioned in the report.\nFalse positive results are quite unusual, as the anti\u00ad\nbody should not crossreact with other antigens.\n\t\u2022\t \u0007Entrapped normal ducts or lobules misinterpreted as car\u00ad\ncinoma \u2014 this can be a difficult issue for DCIS as some \nducts or lobules may be only partially involved by DCIS.\n\t\u2022\t \u0007Control placed on same slide misinterpreted as the car\u00ad\ncinoma\n\t\u2022\t \u0007Sclerosing adenosis or myofibroblastoma (or other \nbenign lesions) misinterpreted as invasive carcinoma\nHER2/neu score\nThe HER2/neu immunoreactivity scoring system in Table \n7-15 was recommended by an expert panel.13 Other panel \nsuggestions:\n\t\u2022\t \u0007If cytoplasmic positivity obscures the membrane pat\u00ad\ntern, repeat the assay or perform FISH.\n\t\u2022\t \u0007If normal ducts and lobules show definitive positivity, \nrepeat the assay.\n\t\u2022\t \u0007In cases of invasive carcinoma, only the areas of invasion \nshould be scored. In some cases the associated DCIS can \nshow stronger immunoreactivity.\n\t\u2022\t \u0007Fixation must be in neutral buffered formalin and \nshould, ideally, be between 6 and 48 hours for excisions, \nand at least 1 hour for needle biopsies. However, any \neffect from longer fixation has not been shown.\n\t\u2022\t \u0007Unstained slides should not be used if prepared >6 weeks \nearlier. Loss of antigenicity has been shown for other \nantigens, but not specifically for HER2.\nOnly membrane immunoreactivity is scored. Marked \ncytoplasmic immunoreactivity may make interpretation \ndifficult. FISH studies may be preferred for such cases \n(Table 7-16).\nTABLE 7\u201315.\u2003\nHER2-IHC SCORING\nSCORE\nCRITERIA\n% OF \nCASES\n% OF CASES \nTHAT SHOW \nAMPLIFICATION \nBY FISH\n0 (Nega\u00ad\ntive)\nNo immuno\u00ad\nreactivity or \nimmuno\u00ad\nreactivity \nin <10% of \ntumor cells.\n~ 60%\n0% to 3%\n1+ (Nega\u00ad\ntive)\nFaint weak \nimmunoreac\u00ad\ntivity in >10% \nof tumor cells \nbut only a \nportion of the \nmembrane is \npositive.\n~ 10%\n0% to 7%\n2+ (Equivo\u00ad\ncal)\nWeak to moder\u00ad\nate complete \nmembrane \nimmuno\u00ad\nreactivity \nin >10% of \ntumor cells.\n~ 5% \nto \n10%\n25% to 35%\n3+ \n\u00ad(Positive)\nMore than \n30% of the \ntumor cells \nmust show \ncircumferen\u00ad\ntial intense \nand uniform \nmembrane \nstaining. \nA homo\u00ad\ngeneous \n(chicken \nwire) pattern \nshould be \npresent.\n~15% \nto \n20%\n75% to 90%\nTABLE 7\u201316.\u2003\nFISH RESULTS\nRESULT\nCRITERIA\nCOMMENT\nPositive for \namplification\n>6.0 gene copies \nor >2.2 ratio\nEquivocal for \namplification\n4.0 to 6.0 genes or\n1.8 to 2.2 ratio\nGuidelines suggest \ncounting addi\u00ad\ntional cells for \nFISH, retesting, or \nperforming IHC\nNegative for \namplification\n<4.0 genes or\n<1.8 ratio\nPatients with a ratio of 2.0 or greater have been eligible for Herceptin trials.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_105.png", "summary": "The page discusses false negative and false positive results in immunoperoxidase studies, as well as considerations for HER2/neu scoring.", "questions": [ "What are some common causes of false negative results in immunoperoxidase studies?", "What are some potential issues that can lead to false positive results in immunoperoxidase studies?", "What are the recommendations for scoring HER2/neu immunoreactivity and when should FISH studies be considered?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 106, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n88\nIn >90% of carcinomas with protein overexpression, the \nHER2/neu gene has been amplified. In 3% to 5% of cases, \nprotein overexpression can occur due to other mechanisms. \nIn <5% of cases, there may be gene amplification \u00adwithout \nprotein overexpression. In general, there is a 20% to 40% \nresponse to Herceptin alone in patients with cancers \nshowing gene amplification by FISH, and <5% of patients \nrespond if the gene is not amplified. Therefore, FISH \nstudies may be helpful for cases with 2+ positivity or \n\u00addifficult to interpret cases (e.g., with variable positivity or \ncytoplasmic positivity).\nWell- and moderately differentiated lobular carcino\u00ad\nmas are rarely positive (<5%). However, in some cases \nthere may be edge enhancement of individual tumor cells \nthat may be difficult to interpret. FISH studies may be \nhelpful.\nIn rare cases, DCIS overexpresses HER2/neu but the \naccompanying invasive carcinoma does not. This is a \nsource of potential false positive results for IHC or FISH.\nMyoepithelial markers in breast carcinoma\nMyoepithelial markers can be useful for the evaluation of \nbreast lesions (Table 7-17):\n\t\u2022\t \u0007Invasive carcinoma vs. sclerosing adenosis (frequently \ninvolved by DCIS, LCIS, or apocrine metaplasia).\n\t\u2022\t \u0007DCIS vs. DCIS with microinvasion \u2013 Double immuno\u00ad\nlabeling with p63 (brown nuclear) and cytokeratin (AE1/\nAE3 \u2013 red cytoplasm) can be useful to highlight small \nnests of tumor cells lacking myoepithelial cells. A double \nstain with SMMHC and cytokeratin AE1/AE3 can also \nbe helpful.\n\t\u2022\t \u0007DCIS vs. carcinoma invading as circumscribed tumor \nnests vs. lymphovascular invasion.\n\t\u2022\t \u0007Microglandular adenosis is the only \u201cbenign\u201d breast \nlesion that lacks myoepithelial cells. However, this lesion \nmay be a form of well-differentiated non-metastasizing \ninvasive carcinoma. The cells are negative for ER and \nPR and strongly positive for S100.\nEpidermal lesions of the nipple\nSee Table 7-18.\nBreast carcinoma in males versus metastatic prostate \ncarcinoma\nSee Table 7-19.\nTABLE 7\u201317.\u2003\nMYOEPITHELIAL MARKERS IN BREAST CARCINOMA\nMARKER\nLOCATION\nNORMAL \nLUMINAL \nCELLS\nMYOEPITHELIAL \nCELLS\nBLOOD \nVESSELS\nMYOFIBROBLASTS\nCARCINOMASa\nCOMMENT\np63\nNucleus\nneg\nPOS\nneg\nneg\nrare\nOnly \nnuclear \nmarker\nClean back\u00ad\nground\nSMA\nCytoplasm\nneg\nPOS\nPOS\nPOS\nrare\nMost \nsensitive\u00ad\nmarker\nCD10\nMembrane\nneg\nPOS\nneg\nPOS\nrare\nSMM-HC\nCytoplasm\nneg\nPOS\nPOS\nHigh\nrare\nCalponin\nCytoplasm\nneg\nPOS\nPOS\nMod\nrare\naRare carcinomas with myoepithelial features (adenoid cystic carcinomas, some spindle cell carcinomas, some basal-like carcinomas, some carcinomas associated with \nBRCA1 mutations) can show focal to diffuse positivity for myoepithelial markers.\nS100 protein and cytokeratins (e.g., 34\u03b2E12) are not recommended for identifying myoepithelial cells, as fewer myoepithelial cells are positive and luminal cells can also be \npositive.\np63 is a good general marker for myoepithelial cells and is particularly helpful in cases with prominent myofibroblasts (e.g., sclerosing lesions) or with blood vessels closely \napposed to tumor cells (e.g., papillary fronds in papillary DCIS). In some cases, SMA may be positive in more myoepithelial cells than p63.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_106.png", "summary": "Immunoperoxidase studies can help determine HER2/neu gene amplification in carcinomas, with implications for treatment response. Myoepithelial markers are useful in evaluating breast lesions.", "questions": [ "How does gene amplification of HER2/neu in carcinomas impact treatment response?", "What are the implications of rare cases where DCIS overexpresses HER2/neu but the accompanying invasive carcinoma does not?", "Why are myoepithelial markers important in distinguishing different types of breast lesions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 107, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n89\nTABLE 7\u201318.\u2003\nEPIDERMAL LESIONS OF THE NIPPLE AND PAGET DISEASE AT OTHER SITES\nTUMOR\nAE1/AE3\nCAM 5.2 OR CK7\nCK20\nEMA\nS100\nHMB45\nGCDFP-15\nCEA-P\nCEA-M\nHER2\nER OR PR\nMUC1\nMUC2\nPaget disease \nof the \nnipple\nPOS\nPOS\nneg\nPOS\nMod\nneg\nMod\nMod\nLow\nPOS\nLow\nPOS\nneg\nToker cells\nPOS\nPOS\nneg\nMod\nneg\nneg\nneg\nHigh\nPOS\nneg\nSquamous cell \ncarcinoma\nPOS\nLow\nLow\nPOS\nLow\nneg\nneg\nLow\nMod\nLow\nneg\nneg\nMelanoma\nLow\nLow\nneg\nLow\nPOS\nPOS\nneg\nMod\nneg\nneg\nneg\nneg\nVulvar Paget \ndisease\nPOS\nPOS\nHigh\nPOS\n? Low\nPOS\nneg\nPerianal Paget \ndisease\nPOS\nMod\nPOS\nLow\nPOS\nMost cases of Paget disease of the nipple are associated with DCIS deeper in the breast that involves the lactiferous sinuses, and about half will also have areas of invasion. Rare cases may be difficult to interpret due to the absence \nof associated disease in the breast or if the initial biopsy is shallow. In some cases, Paget cells may take up melanin and may be difficult to distinguish from melanoma. Toker cells are present in nipple epidermis in 40% to 80% \nof nipples and are Cam5.2 and Ck 7 positive but are negative for HER2/neu.\nPaget disease of the vulva and perianal region has a similar distribution (i.e., tumor cells are present between an intact basement membrane and an overlying normal epidermal layer) but the tumor cells have different origins.\nInitial panel: Cam5.2 (or Ck7), HER2, and S100 with additional antibody studies based on these findings, if necessary.\nTABLE 7\u201319.\u2003\n\u0007BREAST CARCINOMA IN MALES VERSUS METASTATIC PROSTATE CARCINOMA\nCK7\nER\nPSA\nPAP\nBreast \u00adcarcinoma\nPOS\nHigh\nMod\nProstate \u00adcarcinoma\nneg\nPOS\nPOS\nCarcinomas in the breast of males with prostate carcinoma can be difficult to classify, as these males are at increased risk for breast cancer, prostate carcinomas can mimic \na well- or moderately differentiated breast cancer, and DCIS is often scant or absent. In addition, some breast carcinomas can express prostate markers. A panel of markers \nshould distinguish these two types of carcinoma in most cases.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_107.png", "summary": "The page discusses special studies, specifically immunoperoxidase studies, for epidermal lesions of the nipple and Paget disease at other sites.", "questions": [ "How are Paget cells in the nipple epidermis distinguished from melanoma cells?", "What is the significance of Toker cells in the nipple epidermis?", "Why is a panel of markers necessary to distinguish breast carcinoma in males from metastatic prostate carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 108, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n90\nSignet ring cell carcinomas of the stomach and breast \n(lobular carcinoma)\nSee Table 7-20 and Fig. 7-2.\nTABLE 7\u201320.\u2003\nSIGNET RING CELL CARCINOMAS OF THE STOMACH AND BREAST (LOBULAR CARCINOMA)\nCARCINOMA\nER\nPR\nGDCFP\nMUC1\nMUC2\nFCK7\nCK20\nE-CAD\nCDX2\nHEP PAR\nStomach\nneg\nneg\nneg\nLow\nMod\nMod\nMod\nMod\nHigh\nHigh\nBreast\nHigh\nLow\nHigh\nPOS\nLow\nPOS\nrare\nLow\nneg\nneg\nSee Figure 7-2\nA\nB\nFigure 7\u20132.\u2002 Metastatic lobular carcinoma of the breast can morphologically resemble primary \nsignet ring cell gastric carcinomas. Both typically lack e-cadherin expression. In addition, \nlobular breast carcinomas can be clinically occult or can present as distant metastases many \nyears after the initial presentation. Signet ring cells associated with breast carcinoma more \ncommonly have a central mucin vacuole with a targetoid appearance (cell A). Gastric signet \nring cells usually have many small vacuoles giving the cytoplasm a foamy appearance (cell B). \nThese criteria are not reliable in distinguishing these two carcinomas. However, the presence \nof the first type of signet ring cell in a biopsy from the gastrointestinal tract should raise the \npossibility of metastatic breast carcinoma.14 The majority of lobular breast carcinomas will be \nER positive, and this is a reliable marker to exclude gastric carcinoma. In the minority of ER-\nnegative cases, PR, GCDFP, MUC1, CDX2, and Hep Par may be helpful markers.15", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_108.png", "summary": "Immunoperoxidase studies can help differentiate signet ring cell carcinomas of the stomach and breast, with specific markers indicating the origin of the carcinoma.", "questions": [ "How do signet ring cell carcinomas of the stomach and breast differ in terms of marker expression?", "What are the morphological similarities and differences between metastatic lobular carcinoma of the breast and primary signet ring cell gastric carcinomas?", "Why is ER positivity considered a reliable marker to exclude gastric carcinoma in lobular breast carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 109, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n91\nFibroblastic/myofibroblastic lesions of the breast\nSee Table 7-21.\nOvarian carcinoma versus mesothelioma\nSee Table 7-22.\nTABLE 7\u201321.\u2003\nFIBROBLASTIC/MYOFIBROBLASTIC LESIONS OF THE BREAST\nNAME\nCD34\nSMA\nHHF-35\nDES\nKER*\np63\nS100\nER\nPR\nCOMMENTS\nNormal stroma\n100\n\u2212/+\n\u2212/+\nrare\n0\n0\n0\n0\nrare\nFA/phyllodes\n100\n66\n12\n0\n0\n12\n0\n\u2212/+\nPASH/fibrous\n100\n+/\u2212\n+/\u2212\n0\n0\n+/\u2212\nMyofibroblastoma\n90\n74\n100\n90\n0\n0\n2\n59\n100\nSpindle cell lipoma\n100\n0\n0\n0\n0\n13q 16q rearrangements\nSolitary fibrous tumor\n95\n13\n7\n7\n0\n9\n0\n17\nFibromatosis\n0\n79\n78\n43\n0\n0\nrare\nrare\nSome associated with \u00adFAP \nNuclear beta-catenin\nNodular fasciitis\n0\n97\n91\n4\n0\nTo Be Distinguished From:\nLeiomyoma\n18\n90\n90\n70\n0\n6\n90\n90\nUsually near nipple, long \nfascicles, more cytoplasm\nSpindle cell \u00adcarcinoma\n0\n55\n30\n55\n40\n30\nrare\nrare\nMay have epithelial areas, DCIS\n*Spindle cell carcinomas may express keratins more typical of myoepithelial cells (e.g., CK 14 and CK 17). These keratins may be detected best with MNF-116 \n(= PANK; includes CK 17) or 34betaE12 (includes CK 14) or antibodies specific for these keratins.\nSome epithelioid myofibroblastomas can closely resemble invasive lobular carcinoma. In these cases, the carcinoma will be strongly positive for typical keratins and also \npositive for ER and PR.\nTABLE 7\u201322.\u2003\nOVARIAN CARCINOMA VERSUS MESOTHELIOMA\nCK7\nCK20\nCK5/6\nCEA m\nCEA p\nCD15 (LEUM1)\nER\nWT1\nCALRET\nBER-EP4\nPeritoneal \n\u00admesothelioma\nHigh\nneg\nPOS\nneg\nneg\nrare\nrare\nHigh\nHigh\nneg\nOvarian serous \ncarcinoma\nPOS\nLow\nneg\nneg\nneg\nMod\nPOS\nPOS\nLow\nPOS\nOvarian endome\u00ad\ntrioid carcinoma\nPOS\nneg\nLow\nMod\nLow\nHigh\nHigh\nLow\nPOS\nOvarian mucinous \ncarcinoma\nPOS\nHigh\nneg\nMod\nLow\nLow\nneg\nLow", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_109.png", "summary": "The page discusses special studies, specifically immunoperoxidase studies, for fibroblastic/myofibroblastic lesions of the breast and distinguishing between ovarian carcinoma and mesothelioma.", "questions": [ "How do the immunoperoxidase studies help in differentiating fibroblastic/myofibroblastic lesions of the breast?", "What are the key markers used in distinguishing between ovarian carcinoma and mesothelioma?", "Are there any specific characteristics or markers that indicate a closer resemblance between epithelioid myofibroblastomas and invasive lobular carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 110, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n92\nPrimary ovarian carcinoma versus metastatic carcinomas\nSee Table 7-23.\nEndocervical carcinoma versus endometrial carcinoma\nSee Table 7-24.\nEndometrial stromal sarcoma versus leiomyosarcoma\nSee Table 7-25.\nTABLE 7\u201323.\u2003\nPRIMARY OVARIAN CARCINOMA VERSUS METASTATIC CARCINOMAS\nCK7\nCK20\nDPC4 (SMAD4)\nCDX2\nER\nCEA m\nCEA p\nEndometrioid ovarian \ncarcinoma\nPOS\nneg\nLow\nMod\nMod\nLow\nClear cell ovarian \ncarcinoma\nPOS\nneg\nMod\n?\nMod\nneg\nMucinous ovarian \ncarcinoma\nPOS\n(diffuse)\nHigh (patchy)\nPOS\nMod\nLow\nMod\nLow\nMucinous breast \ncarcinoma\nPOS\nLow\nPOS\nnega\nPOS\nMod\nLow\nPancreatic carcinoma\nPOS\nHigh\nMod\nMod\nneg\nHigh\nPOS\nAppendiceal carcinoma\nLow\n(patchy)\nPOS\nPOS\nHigh\nLow\nMucinous colon carcinoma\nLow\n(patchy)\nPOS\n(diffuse)\nHigh\nPOS\nneg\nPOS\nPOS\naBreast cancers, in general, are negative for CDX2 and MUC2. The results for mucinous breast carcinomas have not been reported.\n18% of mucinous ovarian carcinomas are positive for MUC2.\nTABLE 7\u201324.\u2003\nENDOCERVICAL CARCINOMA VERSUS ENDOMETRIAL CARCINOMA\nCK7\nCK20\nVIM\nCEA m\nCEA p\np16\nHPV(IN SITU)\nER\nPR\nEndocervical \ncarcinoma\nPOS\nrare\nrare\nPOS\nHigh\nPOS\n(diffuse, \nstrong)\nHigh\nLow\n(focal)\nLow\nEndometrial \ncarcinoma\nPOS\nrare\nPOS\nLowa\nMod\nLow\n(patchy, weak)\nneg\nHigh\n(diffuse)\nHigh\na27% of cases have some positivity but primarily in squamous areas and only focal in glandular areas.\nTABLE 7\u201325.\u2003\nENDOMETRIAL STROMAL SARCOMA VERSUS LEIOMYOSARCOMA\nCD10\nDESMIN\nH-CALDESMON\nER/PR\nEndometrial stromal sarcoma\nHigh\nMod\nneg\nHigh\nLeiomyosarcoma\nLow\nHigh\nPOS\nHigh", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_110.png", "summary": "The page discusses special immunoperoxidase studies to differentiate between primary ovarian carcinoma and metastatic carcinomas, endocervical carcinoma and endometrial carcinoma, and endometrial stromal sarcoma and leiomyosarcoma.", "questions": [ "What are the key markers used to differentiate between primary ovarian carcinoma and metastatic carcinomas?", "How do the immunoperoxidase studies help in distinguishing between endocervical carcinoma and endometrial carcinoma?", "What markers are crucial in differentiating endometrial stromal sarcoma from leiomyosarcoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 111, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n93\nTrophoblastic lesions\nSee Table 7-26.\nTABLE 7\u201326.\u2003 TROPHOBLASTIC LESIONS\nKERATIN\nALPHA-\nINHIBIN\nHPLa\nHCGa\nCD146b\n(MELCAM)\nP63\nKI67c\nP57d\nDNA \nPLOIDYe\nChoriocarci\u00ad\nnoma\nPOS\nPOS\nweak \n(focal)\nstrong \n(diffuse)\nPOS\nMod (few \ncells +)\n69%\nPlacental site \ntrophoblas\u00ad\ntic tumor\nPOS\nPOS\nMod \n(greater \nthan \nhCG)\nfocal (less \nthan \nHhPL)\nPOS\nneg\n>14%\nEpithelioid \ntrophoblas\u00ad\ntic tumor\nPOS\nPOS\nfocal\nfocal\nfocal\nPOS\n>14%\nPlacental site \nnodule\nPOS\nPOS\nweak \n(focal)\nfocal\nfocal\nPOS\n<1%\nExaggerated \nplacental \nsite\nPOS \n(diffuse)\nfocal\nPOS\nneg\n0%\nPartial mole\nPOS\nPOS\nweakb \n(diffuse)\nweak \n(diffuse)\nPOS\nTriploid\nComplete \nmole\nPOS\nPOS\nweakb \n(focal)\nstrong \n(diffuse)\nraref\nDiploid \n(paternal)\nHydropic fetus\nPOS\nPOS\nPOS\nDiploid \n(60%)\nTriploid \n(40%)\naEvaluated in syncytiotrophoblast.\nbIncreases with advancing pregnancy.\ncImplantation-site intermediate trophoblastic cells are evaluated for the number of Ki67 positive cells. CD146 can be used to help identify these cells using a double label \ntechnique. Lymphocytes can also be positive for Ki67 and should not be counted.\ndp57 is a paternally imprinted gene, expressed from the maternal gene, which shows decreased expression in complete moles, whose DNA is completely derived from \npaternal DNA.\nePloidy is usually determined by flow cytometry.\nfIn complete moles, p57 positivity is present in villous stromal cells and extravillous trophoblast but absent in intermediate trophoblast lining the villi.\nCytokeratin and alpha-inhibin (syncytiotrophoblastic cells and some intermediate trophoblastic cells) are not useful for the differential diagnosis of these lesions, but may \nbe helpful if other types of tumors are in the differential diagnosis.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_111.png", "summary": "The page discusses special immunoperoxidase studies for trophoblastic lesions, including markers like keratin, inhibin, HPL, HCG, CD146, P63, KI67, P57, and DNA ploidy.", "questions": [ "How are trophoblastic lesions differentiated based on immunoperoxidase studies?", "What role do markers like KI67 and P57 play in the evaluation of trophoblastic lesions?", "Why is DNA ploidy important in the assessment of complete moles?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 112, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n94\nTABLE 7\u201327.\u2003\nMETASTATIC ADENOCARCINOMAS IN THE ABDOMEN\nSITE OF \nORIGIN\nCK7\nCK20\nMUC2\nMUC5AC\nSMAD4*\nCDX2\nB-CAT\nWT-1\nStomach\nHigh (75)\nMod (45)\nMod (50)\nMod (55)\nPOS (100)\nMod (12-50)\nHigh (63)\nMod (47)\nColon\nneg (10)\nPOS (95)\nHigh (60-100)\nLow (25-40)\nPOS (95)\nPOS (90-100)\nHigh (60-100)\nHigh (63)\nAppendix\nLow (30)\nPOS (96)\nPOS (96)\nHigh \n(85-100)\nHigh \n(80-90)\nPOS (100)\nVery low (9)\nPancreas\nPOS (95)\nHigh (75)\nPOS (100)\nHigh \n(73-92)\nMod (45)\nMod (15-60)\nMod (54)\nUterus\nPOS (100)\nLow (15)\nneg (0)\nLow (31)\nPOS (100)\nVery low (7)\nMod (48)\nMod (50)\nOvary, \nserous\nPOS (100)\nLow (15)\nLow \n(12-38)\nHigh\nPOS (95)\nMod (29-50)\nVery low \n(0-10)\nHigh\nOvary, \nmucinous\nPOS\nHigh\nLow (18)\nPOS\nPOS\nMod (34)\nLow (12)\nBreast, NST\nPOS (95)\nneg (4)\nVery low (9)\nLow (37)\nPOS\nneg (0)\nLow\nBreast, \nmucinous\nPOS\nLow\nPOS (100)\nLow (23)\nPOS\nHigh (64)\n*The lack of SMAD4 is found in about half of pancreatic carcinomas and is highly suggestive of this primary site.\nIn some published tables a \u201cpositive\u201d result is the absence of positivity. In this table, \u201cpositive\u201d signifies that the carcinoma shows immunoreactivity for SMAD4.\nMetastatic adenocarcinomas in the abdomen\nSee Table 7-27.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_112.png", "summary": "The table provides immunoperoxidase study results for metastatic adenocarcinomas in the abdomen, showing the expression levels of various markers in different sites of origin.", "questions": [ "What is the significance of the different expression levels of CK7 and CK20 in the stomach and colon?", "How does the presence or absence of SMAD4 relate to the primary site of pancreatic carcinomas?", "Why is it noted that a 'positive' result in this table signifies immunoreactivity for SMAD4?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 113, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n95\nCNS neoplasms\nSee Table 7-28.\nHemangioblastoma versus metastatic renal cell \ncarcinoma\nSee Table 7-29.\nTABLE 7\u201328.\u2003\nCNS NEOPLASMS\nOLIG2a\nGFAP\nSYNb\nNEUN\nEMA\nOTHER MARKERS\nAstrocytoma\nPOS\nPOS\nneg\nneg\nneg\nOligodendroglioma\nPOS\nLow (focal)\nneg\nneg\nneg\nEpendymoma\nLow\nLow (focal)\nneg\nLow\nLow\nPilocytic astrocytoma\nPOS\nPOS\nneg\nneg\nneg\nGanglioglioma\nPOS\nPOS\nPOS\nPOS\nCentral neurocytoma\nLow\nneg\nPOS\nPOS\nMedulloblastoma\nLow\nLow\nPOS\nPOS\nneg\nChoroid plexus tumors\nneg/rare\nneg\nneg\nLow\nCK POS\nMeningioma\nneg\nneg\nneg\nneg\nPOS\nHMB-45 POS in melanocytic variant\nCD34 neg\nHemangiopericytoma/\nsolitary fibrous tumor\nneg\nLow\nCD34 POS\nAtypical teratoid/rhabdoid \ntumor\nLow\nLow\nLow\nLow\nINI1 negc\nVIM POS\nSchwannoma\nneg\nneg\nLymphoma\nneg\nneg\nneg\nnegd\nLCA POS\nMelanoma\nneg\nneg\nLow\nneg\nHMB-45 POS\nMetastatic carcinoma\nneg\nneg\nLow\nPOS\nCK POS\naOLIG2: The majority of cells will be positive in diffuse gliomas. Other tumors can show smaller numbers of positive cells (typically much less than 50%).\nbSYN: Any neural tumor can show focal positivity for synaptophysin.\ncINI1/SMARCB1 protein: The absence of this protein is highly specific for atypical teratoid/rhabdoid tumor.\ndEMA can be positive in myelomas\nTABLE 7\u201329.\u2003\nHEMANGIOBLASTOMA VERSUS METASTATIC RENAL CELL CARCINOMA\nINHIBIN\nRCC\nCD10\nHemangioblastoma\nPOS\nneg\nneg\nMetastatic renal cell \ncarcinoma\nneg\nPOS\nPOS", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_113.png", "summary": "The page provides immunoperoxidase studies for CNS neoplasms and a comparison between hemangioblastoma and metastatic renal cell carcinoma.", "questions": [ "What are the key markers used in immunoperoxidase studies for different CNS neoplasms?", "How can immunoperoxidase studies help differentiate between hemangioblastoma and metastatic renal cell carcinoma?", "Why is the absence of INI1/SMARCB1 protein specific for atypical teratoid/rhabdoid tumor?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 114, "text": "96\nSPECIAL STUDIES\u2003 Immunoperoxidase Studies\nTumors of germ cells and sex-cord stromal tumors\nSee Table 7-30.\nTABLE 7\u201330.\u2003 TUMORS OF GERM CELLS AND SEX-CORD STROMAL TUMORS\nAE1/\nAE3\nCAM5.2\nNSE\nEMA\nPLAPa \n(MEM)\nOCT4\nNANOG\nAFP\nCD30(Ki-1, \nBER-H2)\nCD117 \n(CKIT)\nSOX2e\nVIM\nHCG\nHPL\nINHIBIN\nMELAN \nA103\nOTHER\nSeminoma\nMod\nLowb\nHigh\nneg\nPOS\nPOS\nPOS\nneg\nLow\nPOS\nneg\nMod\nLowc\nneg\nneg\nneg\nIntratubular \ngerm\ncell neopla\u00ad\nsia\nneg\nPOS\nPOS\nPOS\nPOS\nneg\nEmbryonal \ncarci\u00ad\nnoma\nPOS\nPOS\nHigh\nLow\nHigh\nPOS\nPOS\nLow\nHighd\nneg\nPOS\nLow\nLow\nneg\nneg\nneg\nYolk sac \ntumor\nPOS\nPOS\nHigh\nneg\nMod\nneg\nneg\nHigh\nLow\nneg\nneg\nLow\nneg\nneg\nneg\nneg\nChoriocarci\u00ad\nnoma\nPOS\nPOS\nMod\nMod\nMod\nneg\nneg\nneg\nneg\nneg\nneg\nPOS\nPOS\nPOS\nneg\nSpermato\u00ad\ncytic sem\u00ad\ninoma\nMod\n(focal)\nneg\nneg\nneg\nMod?\nVariable\nLeydig cell \ntumor\nMod\nMod\nLow\nLow\nneg\nneg\nPOS\nPOS\nHigh\nGranulosa \ncell tumor\nLow\nMod\nLow\nneg\nneg\nneg\nneg\nneg\nPOS\nPOS\nHigh\nWT1 \nHigh\nHHF35 \nHigh\nS100 \nMod\nSertoli cell \ntumor\nMod\nMod\nPOS\nneg\nneg\nneg\nHigh\nPOS\naPLAP is expressed in embryonic germ cells, but not in normal spermatogonia, spermatocytes, and spermatids.\nbCAM5.2 is present as a strong dot-like paranuclear positivity. 80% of mediastinal seminomas are positive for CAM5.2 compared to 20% to 30% of testicular seminomas.\ncHCG may be positive in trophoblasts in seminomas.\ndOnly 35% of metastatic embryonal carcinomas to lymph nodes after chemotherapy are positive for CD30.\neSOX2 is not specific for embryonal carcinoma, as many carcinomas can be positive for this marker.\nFISH for 12p can be used to identify germ cell tumors and their metastases.\nD2-40 (podoplanin) is strongly expressed in seminomas and ITGCN. It is also expressed in lymphatic endothelium, epithelioid mesotheliomas, and hemangioblastomas.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_114.png", "summary": "The page discusses special immunoperoxidase studies for tumors of germ cells and sex-cord stromal tumors, listing various markers and their expression levels for different types of tumors.", "questions": [ "How do the expression levels of different markers vary among the different types of tumors mentioned?", "What is the significance of CAM5.2 positivity in mediastinal seminomas compared to testicular seminomas?", "Why is FISH for 12p recommended for identifying germ cell tumors and their metastases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 115, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n97\nAdrenal and kidney tumors\nSee Table 7-31.\nTABLE 7\u201331.\u2003\nADRENAL AND KIDNEY TUMORS\nAE1/\nAE3\nCK7\nCK20\nPANK\nCAM5.2\nMUC-1 \n(EMA)\nS100\nCHROM\nSYN\nMART1 \nA103C\nINHIBIN\nNSE\nNFP\nAMACR\nVIM\nOTHER\nIRON \nSTAIN\nAdrenal Tumorsd\nCortical adenoma\nneg\nneg\nneg\nLow\nLow\nneg\nneg\nneg\nPOS\nPOS\nHigh\nHigh\nneg\nneg\nHigh\nTTF1 neg\nCD10 neg\nCortical \n\u00adcarcinoma\nneg\nneg\nneg\nHigh\nPOS\nPOS\nneg\nPheo/\u00ad\nparaganglioma\nneg\nneg\nneg\nneg\nneg\nHigha\nPOS\nPOS\nneg\nneg\nPOS\nPOS\nMod\nGFAP mod\nKidney Tumors\nRCC \u2013 clear cell\nHigh\nLow\nneg\nHigh\nHigh\nHigh \n(diff)\nLow\nneg\nneg\nneg\nneg\nMod\nneg\nHigh\np63 neg\nTTF1 neg\nGFAP low\nRCC POS\nCD10 POS\nFocal, \ncoarse\nRCC - papillary\nPOS\nHigh\nLow\nPOS\nMod \n(mem)\nPOS\nRCC POS\nCD10 POS\nFocal, \ncoarse\nRCC - chromo\u00ad\nphobe\nHigh\nHigh\nneg\nPOS\nPOS \n(mem)\nneg\nneg\nRCC Mod\nCD10 neg\nDiff, \nstrong\nOncocytomab\nMod\nHigh\nneg\nPOS\nRCC neg\nCD10 low\nFocal, \nweak\nTransitional cell \ncarcinoma\nMod\nPOS\nHigh\nPOS\nPOS\nPOS\nneg\nneg\nneg\nneg\nLow\nLow\nLow\np63 POS\nCD10 mod\naPositivity is present in sustentacular cells. These cells may be absent in malignant tumors.\nb50% of oncocytomas have a punctate/dot-like pattern for CK 8 or 18 which is not seen in RCC. EM may be helpful to distinguish oncocytoma from chromophobe RCC (see Table 7-46).\ncAntibody A103 is positive in adrenal cortical carcinomas. Another antibody to the same antigen, M2-7C10 is not positive in adrenal cortical carcinomas.\ndClear cell renal cell carcinoma metastatic to the adrenal can sometimes be confused with an adrenal cortical tumor (thus, the older term for clear cell carcinoma of \u201chypernephroma\u201d). RCC has clear cytoplasm (compared to the \n\u00adbubbly cytoplasm of the adrenal cortex) and blood lakes are typically present. Glycogen is present in RCC and absent in adrenal lesions (demonstrated by PAS with and without diastase). Cytokeratin and EMA are useful IHC markers.\nDiff = diffuse positivity; mem = positivity located on membrane.\nRenal cell carcinoma subtypes have typical cytogenetic abnormalities (see Table 7-47).\nCD117 (c-kit) has been reported to be positive in almost all papillary renal cell carcinomas (cytoplasmic) and chromophobe carcinomas (membrane) but is not present in clear cell carcinomas. Mutations in c-kit were only found in \npapillary carcinomas.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_115.png", "summary": "The page discusses special immunoperoxidase studies for adrenal and kidney tumors, listing various markers and their expression levels in different tumor types.", "questions": [ "How do the expression levels of AE1/AE3, CK7, CK20, and other markers differ between adrenal cortical adenoma and carcinoma?", "What are the distinguishing features between clear cell renal cell carcinoma and oncocytoma?", "Why is CD117 (c-kit) positivity significant in papillary renal cell carcinomas and chromophobe carcinomas but not in clear cell carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 116, "text": "98\nSPECIAL STUDIES\u2003 Immunoperoxidase Studies\nTumors of bladder, prostatic, and renal origin\nSee Table 7-32.\nProstate carcinoma versus other lesions\nSee Table 7-33.\nTABLE 7\u201332.\u2003 TUMORS OF BLADDER, PROSTATIC, AND RENAL ORIGIN\nCK7\nCK20\nKERATIN \nHMW\nPSA\nPAP\nAMACR\nCEA m\nCEA p\nP63\nCA125\nMUCI\nProstatic \ncarcinoma\nLow\nLow\nneg\nHigh\nPOS\nPOS\nneg\nMod\nneg\nneg\nneg\nTransitional cell \ncarcinoma\nPOS\nHigh\nMod\nneg\nneg\nLow\nMod\nMod\nHigh\nneg\nneg\nBladder adenocar\u00ad\ncinoma\nHigh\nHigh\nneg\nneg\nneg\nMod\nHigh\nLow\nPOS\nRenal cell \ncarcinoma \u2013 \nclear cell\nLow\nneg\nneg\nneg\nLow\nneg\nLow\nneg\nneg\nRectal adenocarci\u00ad\nnoma\nLow\nPOS\nneg\nneg\nneg\nPOS\nPOS\nneg\nPOS\nSeminal vesicle \ncarcinoma\nHigh\nneg\nneg\nneg\nVAR\nPOS\nHigh\nTABLE 7\u201333.\u2003\nPROSTATE CARCINOMA VERSUS OTHER LESIONS\n34\u03b2E12 (BASAL CELLS)\nP63 (BASAL CELLS)\nAMACR (504S) \n(GLANDULAR CELLS)\nPSA\nBenign glands\nPOS\nPOS\nneg\nPOS\nPIN\nPOS\nPOS\nHigh\nPOS\nInvasive carcinoma\nneg\nneg\nPOS\nPOS\nNephrogenic adenoma\nMod\nneg\nHigh\nneg\nAntibody cocktails: These antibodies can be combined to facilitate the evaluation of small lesions:\n34\u03b2E12 + p63 = labels a greater number of basal cells than either marker alone.\nAMACR + p63 and/or 34\u03b212 = facilitates the identification of small foci of invasive carcinoma.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_116.png", "summary": "The page discusses immunoperoxidase studies for tumors of bladder, prostatic, and renal origin, including specific markers for different types of carcinomas.", "questions": [ "How do the immunoperoxidase markers differ between prostatic carcinoma, transitional cell carcinoma, and bladder adenocarcinoma?", "What are the key differences in immunoperoxidase markers between prostatic carcinoma and other lesions?", "How can antibody cocktails be used to aid in the evaluation of small lesions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 117, "text": "99\nSPECIAL STUDIES\u2003 Immunoperoxidase Studies\nHepatic tumors\nSee Table 7-34.\nTABLE 7\u201334.\u2003\nHEPATIC TUMORS\nCK7\nCK20\nAE1/\nAE3\nCAM5.2\nKERATIN \nHMW\nCEA \nm\nCEA p\nTTF-1\nHEP\nAFP\nCD10\nCHROM\nMUC1D\nBILE\nCIRRHOSIS\nHBV\nHepatocellular \ncarcinoma\nLow\nneg\nLow\nPOS\nneg\nneg\nHigha\nHighb \n(cyt)\nHigh\nMod\nHigha\nneg\nneg\nmay be \npres\u00ad\nent\n65-90%\n50%\nHepatoblas\u00ad\ntoma\nLow\nPOS\nLow\nHigha\nPOS\nHigh\nLow\nabsent\nrare\nHCC \u2013 \n\u00adfibrolamellar\nMod?\nneg\nPOSa\nPOS\nneg?\nmay be \npres\u00ad\nent\nabsent\nrare\nCholangiocarci\u00ad\nnoma\nPOS\nMod\nPOS\nPOS\nHigh\nHigh\nPOS\nneg\nneg\nneg\nneg\nHigh\nnega\u00ad\ntive\nrare\nrare\nMetastatic \ncarcinoid \ntumor\nLow\nLow\nHigh\nPOS\nMod\nMod\nLowc \n(nuc)\nneg\nLow\nPOS\nnega\u00ad\ntive\nabsent\nabsent\naBile canalicular pattern. Other carcinomas have a membrane or cytoplasmic pattern.\nbTTF-1 is seen in the cytoplasm (unlike the nuclear pattern seen in lung and thyroid carcinomas)\ncCarcinoids arising at sites other than lung are very unlikely to be positive for TTF-1. Lung carcinoids may be positive and are more likely to express Ck7.\ndMucin histochemical stains can also be used. HCCs will be negative and 75% to 100% of cholangiocarcinomas will be positive.\nCyt = cytoplasmic immunoreactivity; nuc = nuclear immunoreactivity.\nSinusoids of HCC show diffuse CD34 positivity in 80% to 90% of cases, but this is not seen in normal liver. CD34 positivity can also be seen in focal nodular hyperplasia. Metastatic carcinomas can show diffuse positivity in 20% of \ncases, but the positive endothelial cells are present throughout the tumor and the cells do not surround nests of tumor cells, as is seen in HCC.\nReticulin stains can be helpful in the evaluation of fine needle aspirates or core needle biopsies of liver lesions. HCC has an abnormal pattern of absent, decreased, or expanded trabecula, whereas benign lesions will show a normal \ntrabecular pattern.\nMetastatic carcinomas can usually be distinguished from HCC by frequent expression of Ck7, only rare expression of HepPar1, the absence of a bile canicular pattern for CEAp and CD10, and the absence of cytoplasmic positivity for \nTTF-1.\nMetastatic carcinomas to the liver often cannot be reliably distinguished from cholangiocarcinomas by histologic appearance or immunohistochemical pattern, with the exception of colorectal carcinomas. If the patient has a known \nprimary carcinoma, it is most helpful to compare the two tumors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_117.png", "summary": "The page provides a table of immunoperoxidase studies for hepatic tumors, including markers such as CK7, CK20, AFP, and CEA, with different levels of expression for various types of liver tumors.", "questions": [ "How can immunoperoxidase studies help in the diagnosis of hepatic tumors?", "What are the key differences in marker expression between hepatocellular carcinoma and cholangiocarcinoma?", "Why is it important to compare the immunohistochemical patterns of metastatic carcinomas to the liver with the patient's known primary carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 118, "text": "Thyroid and parathyroid lesions\nSee Table 7-35.\nTABLE 7\u201335.\u2003 THYROID AND PARATHYROID LESIONS\nKER\u00ad\nHMW\nCK19\nHBMEa\nGALECTIN-3\nCALCI-\nTONIN\nSYN\nCHRO\nRET\nP27\nPPAR \nGAMMA\nTHY\nTTF-1\nS100b\nCEA \nm\nCEA \np\nCD57\nRBPRO\u00ad\nTEIN\nVIM\nOTHER\nThyroid Lesions:\nHyperplastic \nnodule\nLow\nLow\nLow\nneg\nPOS\nneg\nPOS\nPOS\nLow\nPOS\nFollicular \nadenoma\nneg\nLow\nLow\nLow\nneg\nMod\nneg\nneg\nPOS\nLow 10%\nPOS\nPOS\nLow\nLow\nPOS\nPOS\nFollicular \ncarcinoma\nneg\nLow\nMod\nLow\nneg\nHigh\nneg\nneg\nPOS\nLow 30%\nPOS\nPOS\nMod\nneg\nLow\nMod\nneg?\nPOS\nPapillary \n\u00adcarcinoma \n\u2014 follicular \nvariant\nPOS\nPOS\nMod\nneg\nLow\nMod\nLow 10%\nPOS\nPOS\nHigh\nneg\nPapillary carci\u00ad\nnoma\nPOS\nPOS\nHigh\nHigh\nneg\nHigh\nneg\nLow\nPOS\nLow 10%\nPOS\nPOS\nHigh\nneg\nMod\nPOS\nneg\nPOS\np63 POS\nMedullary \ncarcinoma\nneg\nMod\nPOS\nPOS\nPOS\nneg\nLow\nPOS\nPOS\nMod\nMod\nMod\nHighc\nCk7 POS\nPANK POS\nAnaplastic \ncarcinomad\nMod\nrare\nrare\nP53, Cyclin \nD1, High \nMIB1 \nindex, \nBCL2 \nneg\nParathyroid \nadenomas \nand carci\u00ad\nnomas\nPOS\nLow\nLow\nPOS\nHighe\nneg\nneg\nneg\nLow\nPOS\nneg/\nweak\nPTh POS\nRCC POS\nCyclin D1 \nPOS\naTumors with Hurthle cell changes may be negative for HBME. bHurthle cells (both benign and neoplastic) are positive for S100 (nuclear and cytoplasmic). cSpindle cells may be positive for vimentin.\ndAnaplastic thyroid carcinomas are frequently negative for TTF-1, thyroglobulin, and Ck20 but positive for p53 and Cyclin D1. ep27 is low in parathyroid carcinomas.\nThyroid adenomas, follicular carcinomas, papillary carcinomas, and medullary carcinomas are Ck7+ and Ck20-. Variable immunoreactivity has been reported for Ck7 in anaplastic carcinomas.\nMetastatic carcinomas to the thyroid will be negative for thyroglobulin, TTF-1 (except for lung carcinomas), and calcitonin.\nDDIT3 and ARG2 are new markers that may prove helpful for distinguishing follicular carcinoma (~ 70-80% positive) from adenoma (90% negative)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_118.png", "summary": "The table provides immunohistochemical markers for different thyroid and parathyroid lesions, aiding in their diagnosis and classification.", "questions": [ "How do the immunohistochemical markers vary among different types of thyroid lesions?", "What role do markers like P27, PPAR GAMMA, and CEA play in distinguishing between thyroid lesions?", "Why are Hurthle cell changes important to consider when interpreting HBMEa results in thyroid lesions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 119, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n101\nDifferential diagnosis of epithelial mesothelioma \nand lung adenocarcinoma\nSee Table 7-36.\nInitial panel: AE1/AE3, calretinin, WT-1 (clone \n6F-H2), CEA, Leu-M1, and TTF-1 with additional stud\u00ad\nies ordered in difficult cases.\nOther antibodies generally reported as negative in epi\u00ad\nthelial mesotheliomas and positive in lung adenocarci\u00ad\nnomas include the following: MOC-1, B72.3, Ber-EP4, \nand BG-8. Cytokeratins 5/6 are reported to be positive in \nmesotheliomas and negative in lung carcinomas. However, \nin our experience, these markers have proven less useful \nthan the ones listed earlier. The use of EMA is contro\u00ad\nversial. Strong membrane positivity is characteristic of \nepithelial mesothelioma, whereas cytoplasmic positivity is \ncharacteristic of adenocarcinomas.\nLess is known about the immunophenotype of pure sar\u00ad\ncomatoid mesotheliomas. The spindle cells are positive for \ncytokeratin, but are less frequently positive for the other \nmarkers as compared to the epithelioid cells. Tumors that \ncan, on occasion, resemble mesotheliomas are generally \nnegative for cytokeratins, with the notable exceptions of \nsome cases of angiosarcoma, epithelioid hemangioendo\u00ad\nthelioma, synovial sarcoma, epithelioid sarcoma, and leio\u00ad\nmyosarcoma (see Table 7-9).16\nTABLE 7\u201336.\u2003\nDIFFERENTIAL DIAGNOSIS OF EPITHELIAL MESOTHELIOMA AND LUNG ADENOCARCINOMA\nEPITHELIAL MESOTHELIOMA\nLUNG ADENOCARCINOMA\nImmunohistochemistry\nAE1/AE3 keratin\nPOS (perinuclear)a\nPOS (membrane)b\nCalretinin\nPOS\nNEG\nWT-1 (clone 6F-H2)\nPOS (nuclear)c\nNEGd\nCEA (polyclonal)\nNEG\nHIGHe\nLeu-M1 (CD15)\nNEG\nHIGH\nTTF-1\nNEG\nHIGH\nMucins\nMucicarmine\n3-4%\n60%\nPAS-D\n<3%\n65%\nAlcian blue\n30%\nPos ?%\nAlcian blue + hyaluronidase\nStaining lost\nStaining preserved\nUltrastructure (EM)\nMicrovilli\nElongated, serpiginous, and branched\nShort, blunt, rigid appearing\nLength to diameter ratio\n10 to 16:1\n4 to 7:1\nCytogenetics\nDeletions of 1p, 3p, 17p, loss of 9 and 22\nDeletions of 3p, highly variable changes\naKeratin immunoreactivity is accentuated around the nucleus and is present in the cytoplasm, without a prominant membrane accentuation.\nbKeratin immunoreactivity is diffusely present in the cytoplasm with membrane accentuation in some cells.\ncWT-1 immunoreactivity is nuclear.\ndMetastatic adenocarcinomas are generally negative for WT-1 except for ovarian serous carcinomas and some renal carcinomas (see Table 7-5).\neMost metastastic adenocarcinomas will be positive for CEA, but there are some exceptions (see Table 7-5).\nTissue should be obtained for EM and cytogenetics, if possible.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_119.png", "summary": "Immunoperoxidase studies are essential in differentiating between epithelial mesothelioma and lung adenocarcinoma, with specific antibody markers showing differential expression.", "questions": [ "What are the initial panel of antibodies used in differentiating between epithelial mesothelioma and lung adenocarcinoma?", "Why are cytokeratins 5/6 considered less useful in distinguishing between mesotheliomas and lung carcinomas?", "What is the immunophenotype of pure sarcomatoid mesotheliomas compared to epithelioid mesotheliomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 120, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n102\nTABLE 7\u201337.\u2003\nLUNG CARCINOMAS\nKERATIN 7\nKERATIN 20\nTTF-1\nP63\nCHROMO-\nGRANIN\nSYNAPTO-\nPHYSIN\nCDX2\nER/PR\nAdenocarcinoma\nPOS\nLow\nHIGH\nLow\nneg\nLow\nneg\nLow/mod\nBronchioloalveolar \ncarcinoma \u2014 nonmucinous\nPOS\nLow\nHIGH\nHIGH\nneg\nneg\nneg\nBronchioloalveolar \ncarcinoma \u2014 mucinous\nHIGH\nHIGH\nLow\nnegc\nSquamous cell carcinoma\nLow\nneg\nneg\nPOS\nneg\nneg\nneg\nLarge cell carcinoma (\u201cnon \nsmall cell\u201d)\nHigh\nLow\nMod\nMod\nneg\nLow\nneg\nSmall cell carcinomaa\nLow\nneg\nPOS\nneg\nMod\nMod\nneg\nneg\nCarcinoid tumor\nMod\nneg\nLow/\nneg\nneg\nPOS\nPOS\nneg\nMetastatic colon carcinoma\nPOS\nLow\nneg\nneg\nneg\nneg\nPOS\nMetastatic breast carcinomab\nPOS\nneg\nneg\nnegb\nnegb\nLow\nneg\nVariable\naSmall cell carcinomas arising at other sites can also be TTF-1 positive.\nbIf metastatic breast cancer is suspected, the lung lesion should be compared with the breast primary. Most metastatic breast cancers will have the same pattern of ER, PR, \nand HER2/neu expression. Some breast carcinomas can be strongly chromogranin positive. Rare breast cancers can be p63 positive (squamous cell carcinomas, metaplastic \ncarcinomas [including spindle cell carcinomas] or triple negative carcinomas).\ncThe mucinous type of bronchioloalveolar carcinoma (BAC) may be difficult to distinguish from metastatic colon carcinoma as some cases are CK7 negative, CK20 positive, \nTTF-1 negative, and can be focally positive for CDX2. However, colon carcinomas are usually diffusely positive for CDX2.\nLung carcinoma\nSee Tables 7-37 and 7-38.\nTABLE 7\u201338.\u2003\nDIFFERENTIAL DIAGNOSIS OF LUNG CARCINOMAS\nDIFFERENTIAL DIAGNOSIS\nMOST USEFUL MARKERS\nAdenocarcinoma vs. squamous cell carcinoma\nKeratin 7, keratin 20, TTF-1, p63\nSmall cell carcinoma vs. basaloid squamous cell carcinoma\nP63, TTF-1\nSmall cell carcinoma vs. carcinoid tumor\nMitoses, necrosis, amount of cytoplasm\nLarge cell neuroendocrine carcinoma vs. carcinoid tumor\nMitoses, necrosis\nMucinous lung carcinoma vs. metastatic colon cancer\nTTF-1, CDX2 (mucinous BAC can be focally positive for CDX2)\nLung carcinoma vs. metastatic breast carcinoma\nTTF-1, compare ER/PR/HER2 pattern in primary breast carcinoma \nand lung tumor", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_120.png", "summary": "This page discusses the use of immunoperoxidase studies in diagnosing different types of lung carcinomas, highlighting specific markers for each subtype.", "questions": [ "How do immunoperoxidase studies help in distinguishing between different types of lung carcinomas?", "What are the key markers used to differentiate adenocarcinoma from squamous cell carcinoma?", "Why is it important to compare the ER/PR/HER2 pattern in primary breast carcinoma and lung tumor when differentiating between lung carcinoma and metastatic breast carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 121, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n103\nTABLE 7\u201339.\u2003\nB-CELL NEOPLASMS\nB-CELL MARKERS\nCD45 \nLCA\nCD19 \nB4\nCD20 \nL26\nCD22\nCD79a\nSIG\nCIG\nCD5 \nLEU1\nCD10 \nCALLA\nCD23\nCD43 \nLEU22\nCD34\nBCL-2\nBCL-6\nCD138 \nSYNDECAN\nCYCLIN \nD1\nOTHER\nPrecursor \n\u00adlymphoblastic \nlymphoma/\nleukemia\n+/\u2212\n+\n+/\u2212\n+/\u2212\n+ cyt\n\u2212\n+M\n\u2212\n+a\n\u2212\n+/\u2212\n+/\u2212\n\u2212\n\u2212\n\u2212\n\u2212\nTdT +\nCD99 +\nSmall lympho\u00ad\ncytic lym\u00ad\nphoma/CLL\n+\n+\n+ wk\n+ wk\n+\n+ M/D\nwk\n\u2212/+\n+\n\u2212\n+\n+/\u2212\n\u2212\n+\n\u2212\n\u2212\n\u2212\nCD11c+ wk\nCD79b \u2013\nFMC7 \u2212\nMantle cell \nlymphoma\n+\n+\n+\n+\n+\n+M/D\n\u2212\n+\n\u2212\n\u2212\n+\n\u2212\n+\n\u2212\n\u2212\n+\nCyclinD +\nFMC +\nMarginal zone \nlymphoma \n(MALT)\n+\n+\n+\n+\n+\n+\n+/\u2212\n\u2212\n\u2212\n\u2212\n+/\u2212\n\u2212\n+\n\u2212\n\u2212/+b\n\u2212\nCD11c +/\u2212\nCD21+\nCD35+\nFollicular \n\u00adlymphoma\n+\n+\n+\n+\n+\n+M\n\u2212\n\u2212\n+\n\u2212/+\n\u2212/+\n\u2212\n+/\u2212\n+\n\u2212\n\u2212\nCDw75 +\nBurkitt \n\u00adlymphoma \nand \nBurkitt-like \n\u00adlymphoma\n+\n+\n+\n+\n+\n+M\n+/\u2212\n\u2212\n+\n\u2212\n+/\u2212\n\u2212\n\u2212\n+\n\u2212\nTdT-\nMIB-1 100%\nEBER in situ \nin 52%\nMYCc\nMediastinal \nlarge B-cell \nlymphoma\n+\n+\n+\n+\n+/\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n+\n\u2212\n\u2212\nCD30+/\u2212 \nwk\ntraf1 60%\nB-cell neoplasms\nSee Table 7-39.\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_121.png", "summary": "The page discusses B-cell neoplasms and the specific markers used for their identification through immunoperoxidase studies.", "questions": [ "What are the different B-cell markers mentioned in the table?", "How are the B-cell neoplasms differentiated based on the markers listed?", "Why are immunoperoxidase studies important in the diagnosis of B-cell neoplasms?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 122, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n104\nLarge B-cell \nlymphoma\n+/\u2013\n+\n+\n+\n+\n+/\u2212\n+/\u2212\n\u2212/+\n\u2212/+\n\u2212/+\n\u2212\n\u2212/+\n+/\u2212\n\u2212\nCD30 +/\u2212\nMIB-1 \n>40%\ntraf1 <5%\nLymphoplas\u00ad\nmacytic \n\u00adlymphoma\n+/\u2212\n+\n+\n+\n+\n+M/D\n+M/G\nst\n\u2212\n\u2212\n\u2212\n+/\u2212\n\u2212/+b\n\u2212\nHairy cell \n\u00adleukemia\n+\n+\n+\n+\n+\n+\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212/+\nDBA.44+\nCD79b \u2013\nCD11c +\nCD103+\nCD25+ st\nFMC7 +\nPrimary effusion \nlymphoma\n+\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n+\n\u2212\nCD30 (Ki-\n1)+\nHHV8+\nEBER +/\u2212\nPlasmacytoma/\nmyeloma\n\u2212/+\n\u2212\n\u2212/+\n\u2212\n+\n\u2212\n+G/A \nst\n\u2212\n\u2212/+\n\u2212\n+/\u2212\n\u2212\n+\n\u2212/+\nCD56+\nCD38 +\nEMA +\naLymphoblasts in t(4;11)(q21;q23) ALL are CD10 negative and frequently CD24 negative.\nbPositive in plasma cell component.\ncThe myc gene (8q24) is translocated to Ig genes:\nt(8;14) (heavy chains) 85% of cases.\nt(2;8) (kappa light chain)\nt(8;22) (lambda light chain)\nCyt = cytoplasmic immunoreactivity; st = strong immunoreactivity; M, D, G, A = type of heavy Ig chain present; wk = weak immunoreactivity.\nTABLE 7\u201339.\u2003\nB-CELL NEOPLASMS\u2014cont\u2019d\nB-CELL MARKERS\nCD45 \nLCA\nCD19 \nB4\nCD20 \nL26\nCD22\nCD79a\nSIG\nCIG\nCD5 \nLEU1\nCD10 \nCALLA\nCD23\nCD43 \nLEU22\nCD34\nBCL-2\nBCL-6\nCD138 \nSYNDECAN\nCYCLIN \nD1\nOTHER", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_122.png", "summary": "The page discusses special studies, specifically immunoperoxidase studies, for various B-cell neoplasms, including large B-cell lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, primary effusion lymphoma, and plasmacytoma/myeloma.", "questions": [ "What are the key markers used in immunoperoxidase studies for B-cell neoplasms?", "How do the immunoperoxidase study results differ among the different B-cell neoplasms mentioned?", "What are the implications of the specific translocations mentioned in the text for B-cell neoplasms?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 123, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n105\nT-cell neoplasms\nSee Table 7-40.\nTABLE 7\u201340.\u2003 T-CELL NEOPLASMS\nCD45 \nLCA\nTCR\nCD2 \nTE/\nT11\nCD3 T3\nCD43 \nLEU22\nCD5 \nLEU1\nCD7 \nLEU9\nCD4 \nT4\nCD8 T8\nCD25 \nIL2R\nTIA-1\nGRAN-\nZYME \nb\nCD56 \nNCA \nm\nCD30 \nKI-1\nTDT\nALK\nOTHER\nPrecursor \n\u00adlymphoblastic \nlymphoma/\u00ad\nleukemia\n+\n\u2212\n+/\u2212\n+\n+/\u2212\n+/\u2212\n+\n+/\u2212\n+/\u2212\n+/\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n+\n\u2212\nCD34+\nCD99+\nCD1a +/\u2212\nT-cell prolympho\u00ad\ncytic leukemia\n+\n+\n+\n+wk\n+\n+\n+\n+/\u2212\n\u2212/+\n+/\u2212\n\u2212\n\u2212\n\u2212\n\u2212\n\u2212\nCD1a-\nAdult T-cell \nlymphoma/\u00ad\nleukemia\n+\n+\n+\n+\n+\n+\n\u2212/+\n+\n\u2212\n+\n\u2212\n\u2212\n\u2212\n+/\u2212\n\u2212\nMycosis fungoi\u00ad\ndes and Sezary \nsyndrome\nTCR\u03b2+\n+\n+\n+\n+\n\u2212\n+\n\u2212/+\n\u2212/+\n\u2212/+\n+/\u2212\n\u2212\n\u2212\n\u2212\n\u2212\nHECA+\nPeripheral T-cell \nlymphoma, \nNOS\n+\n+\n+/\u2212\n+/\u2212\n+\n+/\u2212\n\u2212/+\n+/\u2212\n\u2212/+\n+\n+/\u2212\n\u2212/+\n+(large \ncells)\n\u2212\n\u2212\nHepatosplenic \nT-cell \n\u00adlymphoma\nTCR\u03b41+\nTCR\u03b1\u03b2\u2212\n+\n+\n+\n\u2212\n+/\u2212\n\u2212\n\u2212\n\u2212\n+\n\u2212\n+/\u2212\n\u2212\n\u2212\n\u2212\nCD57-\nCD16\u2212/+\nLMP-1-\nPerforin \u2212\nPanniculitis-\nlike T-cell \n\u00adlymphoma\nCD56+\n\u2212\n+\n+\n+\n\u2212\n\u2212\n\u2212\n+\n+\n+\n\u2212\n\u2212\n\u2212\nCD95+\nCD56\u2013\n+\n\u2212\n\u2212\n+\n\u2212\n+\n\u2212\n\u2212/+\n+\n\u2212\n\u2212\n\u2212\n\u2212\nCD95\u2212\nAngioimmuno-\nblastic \n\u00adlymphoma\n+\n+\n+\n+\n+\n+\n+\n+\n\u2212/+\n\u2212\n+\n+\n\u2212\n\u2212\n\u2212\n\u2212\nCD10+/\u2212\nCD57+\nbcl\u22126+/\u2212\nEnteropathy-\ntype T-cell \n\u00adlymphoma\n+\n+\n+\n\u2212\n+\n\u2212\n\u2212/+\n\u2212\n+/\u2212\n+/\u2212\n+(small \ncells)\n+ (large \ncells)\n\u2212\n\u2212\nCD103+\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_123.png", "summary": "The page provides a table of special studies for T-cell neoplasms, listing various markers such as CD markers, TCR, and other specific proteins.", "questions": [ "What are the key markers used in immunoperoxidase studies for T-cell neoplasms?", "How are the markers CD3, CD4, and CD8 differentially expressed in T-cell neoplasms?", "What is the significance of CD56, CD30, and TDT markers in the diagnosis of T-cell neoplasms?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 124, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n106\nAnaplastic large \ncell lymphoma\n(Ki-1 lymphoma)\n+/\u2013\n+/\u2212\n+/\u2212\n\u2212/+\n+/\u2212\n\u2212/+\n\u2212/+\n+/\u2212\n\u2212/+\n+/\u2212\n+/\u2212\n+/\u2212\n\u2212/+\n+(mem,\ngolgi)\n\u2212\n+/\u2212b\n(cyt, \nnuc)\nClusterin+a\nEMA+/\u2212\nPerforin +/\u2212\nEBER-\nBSAP\u2212\nExtranodal NK/T-\ncell lymphoma, \nnasal type\n+\n\u2212\n+\n\u2212\nCD3\u03b5+ \n(cyt)\n+\n\u2212\n\u2212/+\n\u2212\n\u2212\n\u2212\n+\n+\n+\n\u2212/+\n\u2212\n\u2212\nEBER+\nCD16+\nCD57\u2212\nBlastic NK-cell \nlymphoma\n\u2212\n\u2212/+\n\u2212\n+/\u2212\n\u2212/+\n+/\u2212\n\u2212\n+\n\u2212\n+/\u2212\n\u2212\nCD33-\nMyelo-\naExpressed in all cases of systemic ALCL but less commonly in primary cutaneous ALCL and very rarely in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, and NS HD.\nbOnly positive in systemic ALCL (subset); negative in primary cutaneous ALCL.\nCyt = cytoplasmic; nuc = nuclear; wk = weak immunoreactivity.\nTABLE 7\u201340.\u2003 T-CELL NEOPLASMS\u2014cont\u2019d\nCD45 \nLCA\nTCR\nCD2 \nTE/\nT11\nCD3 T3\nCD43 \nLEU22\nCD5 \nLEU1\nCD7 \nLEU9\nCD4 \nT4\nCD8 T8\nCD25 \nIL2R\nTIA-1\nGRAN-\nZYME \nb\nCD56 \nNCA \nm\nCD30 \nKI-1\nTDT\nALK\nOTHER\nHodgkin lymphoma\nSee Table 7-41.\nTABLE 7\u201341.\u2003\nHODGKIN LYMPHOMA\nCD45 \nLCA\nCD20 \nL26\nCD3 \nT3\nCD15 \nLEUM1\nCD30 \nKi-1\nEMA\nSIG\nCD79A\nCDW75\nOCT2\nBOB.1\nBSAP\nLMP1\nOTHER\nClassical Hodgkin \nlymphoma (HL)\n\u2212\n\u2212/+\n\u2212\n+/\u2212\n+\n\u2212 rare\n\u2212\n\u2212/+\n\u2212\n\u2212\n\u2212/+\n+\n+/\u2212\ntraf-1 +\nbcl2 +\nNodular sclerosis HL\n\u2212\n\u2212/+\n\u2212\n+/\u2212\n+\n\u2212 rare\n\u2212\n\u2212/+\n\u2212\n\u2212\n\u2212/+\n+\n\u2212/+\nLymphocyte-rich HL\n\u2212\n\u2212/+\n\u2212\n+/\u2212\n+\n\u2212 rare\n\u2212\n\u2212/+\n\u2212\n\u2212\n+/\u2212\n+\n+/\u2212\nMixed cellularity HL\n\u2212\n\u2212/+\n\u2212\n+/\u2212\n+\n\u2212 rare\n\u2212\n\u2212/+\n\u2212\n\u2212\n\u2212/+\n+\n++/\u2212\nLymphocyte-\ndepleted HL\n\u2212\n\u2212/+\n\u2212\n+/\u2212\n+\n\u2212 rare\n\u2212\n\u2212/+\n\u2212\n\u2212\n\u2212/+\n+\n+ (if HIV +)\nNodular lymphocyte-\npredominant HL\n+\n+\n\u2212\n\u2212\n\u2212/+\n+/\u2212\n+\n+ wk\n+/\u2212\n+\n+\n+\n\u2212\nbcl-6 +\nbcl 2 \u2212\nWk = weak.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_124.png", "summary": "The page provides immunoperoxidase studies results for different types of lymphomas, including anaplastic large cell lymphoma, extranodal NK/T-cell lymphoma, and blastic NK-cell lymphoma.", "questions": [ "What are the key markers used in immunoperoxidase studies for these lymphomas?", "How do the results of immunoperoxidase studies differ among the different types of lymphomas mentioned?", "Are there any specific markers that are consistently positive or negative across all types of lymphomas listed?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 125, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n107\nAmyloid\nAmyloidosis (Greek for amylon = starch plus eidos = resem\u00ad\nblance) is seen in many different clinical settings and is \nassociated with many diseases. Pathologists can narrow \ndown the differential diagnosis considerably to help guide \nclinical decision making. Finding an amyloid deposit in \nany tissue is similar to finding metastatic carcinoma in a \nlymph node \u2013 in both settings clinical information (e.g., \nhistory, physical examination, radiology studies, results \nof laboratory tests) is essential in arriving at the correct \ninterpretation. A little immunohistochemistry and a lot of \nclinical judgment by the pathologist can help establish the \ncause with a greater degree of certainty.17\nFinding and characterizing amyloid deposits:\n\t1.\t \u0007Examine the H&E slide for noncellular material in the \ncorrect location for the suspected disease (Table 7-42).\nTABLE 7\u201342.\u2003\nAMYLOID\nTYPE OF \nAMYLOID-RELATED \nDISEASE\nTYPE OF PROTEIN \n(AVAILABLE TESTS)\nUNDERLYING \nDISEASE\nORGAN \nINVOLVEMENT\nOTHER FEATURES\nPrimary AL\nKappa and lambda \nlight chains (IF \nand IHC)\nMultiple myeloma \n(15% have amyloid)\nBenign monoclonal \ngammopathy\nHeart, bone marrow \n(only amyloid at this \nsite), kidney, neu\u00ad\nromuscular, joints, \nliver, spleen, tongue, \nlarynx\nMay have Factor X defi\u00ad\nciency (binds to light \nchains)\nLocalized forms of amy\u00ad\nloid are not associated \nwith systemic disease\nSecondary AA\nSerum amyloid \nprotein A (IFb)\nChronic inflammation: \ninfection, RA, Crohn\u2019s \ndisease, sarcoid, \nfamilial Mediterranean \nfever, malignancy \n(RCC, HD)\nSpleen (100% \u2013 sago \n[tapioca] or larda\u00ad\nceous), kidneys \n(75%), adrenals \n(40%), heart (symp\u00ad\ntoms rare), joints \n(rare)\nDialysis-associated\nBeta-2-microglobulin \n(IHC)\nLong-term hemodialysis, \nrarely seen in perito\u00ad\nneal dialysis or with \nchronic renal failure\nJoints (periarticular \ntissue), carpal tun\u00ad\nnel, rarely systemic \n(GI, vessels), rarely \ninvolves fat, does not \ninvolve spleen\nMedullary \ncarcinoma-\nassociated\nCalcitonin \n(IHC)\nMedullary carcinoma \nof the thyroid\nAssociated with the \ntumor\nCalcitonin can also be \nused to detect C cell \nhyperplasia\nOther tumor-\nassociated amyloid\nPeptide hormones\nEndocrine tumors\nAssociated with the \ntumor\nAlzheimer\u2019s\nBeta amyloid \n(IHC)\nAlzheimer\u2019s disease\nBrain \u2013 senile plaque \ncores, neuritic \nplaques, neurofibril\u00ad\nlary tangles\nAlso seen in Lewy body \ndementia, Down\u2019s \nsyndrome, hereditary \ncerebral amyloidosis \n(Dutch type)\nOther hereditary \ndieases\nTransthyretin \n(IHC)\nFamilial amyloid poly\u00ad\nneuropathy, senile/\ncardiac amyloidosis\nHeart (usually without \nsymptoms), joints, \nprostate\nAmyloid P \ncomponent AP\nAssociated with all forms \nof amyloid. May be \nused to detect amyloid \nradiologically.\naLight chains are detected best by immunofluorescence (IF) on unfixed frozen tissue. IF and IHC can be performed on paraffin sections, but with less specificity. Only 50% of \ncases of light chain disease amyloid will be positive because the amyloid protein is often derived from the variable domain whereas antibodies detect the common domain.\nbSerum amyloid protein A can only be detected by IF on unfixed frozen tissue.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_125.png", "summary": "Amyloidosis presents in various clinical settings and is associated with multiple diseases. Pathologists utilize immunohistochemistry and clinical judgment to identify and characterize amyloid deposits.", "questions": [ "How do pathologists differentiate between primary AL amyloidosis and secondary AA amyloidosis?", "What are the common organs involved in dialysis-associated amyloidosis?", "How does the presence of amyloid deposits impact the diagnosis and treatment of associated diseases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 126, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n108\n\t2.\t \u0007Amyloid deposits will be orange-pink on Congo Red \nstains or sea-foam green on Sulfated Alcian blue stains. \nAmyloid may be more apparent on these stains. HOW\u00ad\nEVER, beware of overcalling cases in which there is not \na histologic correlate for amyloid in the stained tissue. \nIf there is background positivity in normal tissue due to \noverstaining, the slide cannot be interpreted. Positive \ncontrols must show appropriate specific positivity.\n\t3.\t \u0007Congo red-positive amyloid should become an apple \ngreen color when viewed under polarized light. This \nmay require the high-quality polarizers that are built \nin to the microscope. Lower quality polarizers (i.e., the \ncut squares of polarizing material) may not be adequate. \nCollagen (silver when H&E is polarized) and fibrin \n(does not polarize) may mimic amyloid.\n\t4.\t \u0007The amyloid deposits can be further characterized \nusing immunohistochemistry or immunofluorescence \n(see Table 7-42) based on the clinical information, \nthe organ or structures involved, and the distribution \nof amyloid deposits in the tissue. Amyloid can also \nbe identified using EM (non-branching fibrils, 7.5 to \n10\u00a0nm width and up to 1 micron in length).\n\t5.\t \u0007A firm diagnosis is not always possible. The final diag\u00ad\nnosis should be based on a combination of histologic, \nimmunohistochemical, and clinical data.\nAntibodies for immunohistochemistry\nSee Tables 7-43 and 7-44.\nResults\nThe results of studies are incorporated into the surgical \npathology report. The following information is included:\n\t1.\t \u0007The type of tissue studied: formalin-fixed (or other \n\u00adfixatives) tissue, cryostat sections, cytology prepara\u00ad\ntions, etc.\n\t2.\t \u0007The type of immunoagents used, being as specific as \npossible. For example, do not just list keratin but specify \nthe type of keratin (e.g., AE1/AE3).\n\t3.\t \u0007The results of the studies in great enough detail to \nallow interpretation. For example the type of cell that \nis immunoreactive (e.g., tumor vs. nontumor), inten\u00ad\nsity of immunoreactivity (e.g., weak, strong) and/or \nthe number of cells immunoreactive (e.g., focal vs. \ndiffuse).\n\t4.\t \u0007Integration of the results into the final diagnosis speci\u00ad\nfying whether they confirm or support a diagnosis, \nmake one diagnosis more likely than others, or exclude \none or more diagnoses.\nText continues on page 157.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_126.png", "summary": "This page discusses the use of special studies, specifically immunoperoxidase studies, in identifying and characterizing amyloid deposits. It emphasizes the importance of correlating histologic, immunohistochemical, and clinical data for a firm diagnosis.", "questions": [ "How can amyloid deposits be further characterized using immunohistochemistry or immunofluorescence?", "What precautions should be taken when interpreting Congo red-positive amyloid under polarized light?", "What information is included in the results of immunoperoxidase studies in the surgical pathology report?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 127, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n109\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nActin (alpha \nsmooth muscle \nactin) (SMA, \nSM-ACT)\nSmooth muscle iso\u00ad\nform of actin\n(Cytoplasm or mem\u00ad\nbrane)\nSmooth muscle, myoepithe\u00ad\nlial cells, blood vessel walls, \npericytes, some stromal cells \nof intestine, testis, and ovary, \nmyofibroblasts in desmoplastic \nstroma.\nNot in striated muscle or myocar\u00ad\ndium.\nSmooth muscle tumors, myofi\u00ad\nbroblastic tumors, PEComas, \nglomus tumors, KS, some \nspindle cell carcinomas (e.g., \nwith features of myoepithe\u00ad\nlial cells)\nID of smooth muscle differen\u00ad\ntiation (muscle or myofibro\u00ad\nblasts) in tumors.\nNoninvasive lesions of breast \n(myoepithelial cells present \nif benign or DCIS) vs. invasive \ncarcinoma. Microglandular \nadenosis also lacks myoepi\u00ad\nthelial cells.\nGood marker for myoepi\u00ad\nthelial cells of the breast \nbut also positive in myo\u00ad\nfibroblasts in stroma. P63 \nis more specific, but less \nsensitive for myoepithe\u00ad\nlial cells.\nActin (muscle-\nspecific actin) \n(HHF35, MSA, \nmuscle common \nactin, EM ACT)\nAlpha and gamma \nsmooth muscle \nactins, recognizes \na common epitope \nof alpha skeletal, \ncardiac, and smooth \nmuscle\n(Cytoplasm)\nSmooth, striated, and cardiac \nmuscle, smooth muscle of \nblood vessels, pericytes, myo\u00ad\nepithelial cells, myofibroblasts\nNumerous tumors including \ntumors of muscle, glomus \ntumor, PEComa, GIST, DFSP, \ndermatofibroma, myofibro\u00ad\nblastic tumors, spindle cell \ncarcinomas, salivary gland \ntumors, mesothelioma, \nothers\nID of muscle differentiation in \ntumors.\nSensitive but not specific. \nPresent in tumors not of \nmuscle origin.\nAlpha \u00adfetoprotein \n(AFP, alpha \n1-fetoprotein)\nGlycoprotein present \nin fetal liver\n(\u200a\u200aCytoplasm, granular)\nFetal liver, regenerating liver cells\nHCC (but not the fibrolamellar \nvariant), hepatoblastomas, \nyolk sac tumors, embryonal \ncarcinoma (but less com\u00ad\nmonly)\nHCC (+/\u2212) vs. other cell types \n(however, AFP is rarely pres\u00ad\nent in other carcinomas such \nas breast and ovary).\nYolk sac tumors (+) vs. other \ngerm cell tumors (\u2212/+).\nCorrelates with extracel\u00ad\nlular hyaline eosinophilic \nglobules in yolk sac \ntumors\nAlpha 1-antitryp\u00ad\nsin (AAT, alpha-\n1-AT)\nGlycoprotein that \ninhibits proteolytic \nenzymes produced \nin the liver\n(Cytoplasm)\nHistiocytes, reticulum cells, mast \ncells, Paneth cells, salivary \ngland\nHCC, germ cell tumors, true \nhistiocytic neoplasms, colon \nand lung carcinoma, others\nAccumulates in liver cells in AAT \ndeficiency\nNot specific for tumor type.\nCD68 is somewhat more \nspecific for macrophages.\nAMACR (P504S, \nalpha-meth\u00ad\nylacyl-CoA \nracemase)\nMitochondrial and \nperoxisomal \nenzyme involved \nin the metabolism \nof branched-chain \nfatty acid and bile \nacid intermediates\n(\u200a\u200aCytoplasm)\nNot present in normal tissues\nColorectal carcinoma (92%), \ncolonic adenomas (75%), \nprostate carcinoma (83%), \nPIN (64%), nephrogenic ade\u00ad\nnoma (58%), breast cancer \n(44%), ovarian carcinoma, \nTCC, lung carcinoma, RCC, \nlymphoma, melanoma\nCan be combined with p63 to \ndistinguish prostate carci\u00ad\nnoma (AMACR +, p63 absent \nin basal cells) from benign \nmimics (AMACR -, p63 present \nin basal cells). However, ~20% \nof small cancers on core may \nbe negative for AMACR.\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_127.png", "summary": "The page discusses various antibodies used in immunohistochemistry studies, including their normal cellular locations, tumor associations, and specific uses.", "questions": [ "How do the antibodies mentioned in the table help in identifying specific tumor types?", "What are some limitations or drawbacks of using these antibodies in immunohistochemistry studies?", "Are there any alternative markers or techniques that can be used in conjunction with these antibodies for better accuracy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 128, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n110\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nAndrogen \n\u00adreceptor (AR)\nMediates the function \nof androgens\n(Nucleus)\nProstate, skin, oral mucosa\nOsteosarcoma, prostatic car\u00ad\ncinoma, breast carcinoma, \novarian carcinoma, others\nB72.3 (Tumor-asso\u00ad\nciated glycopro\u00ad\ntein 72, TAG-72, \nCA 72-4)\nOncofetal glyco\u00ad\nprotein, may be a \nprecursor of the \nMN blood group \nsystem, sialosyl-Tn \nantigen (Cytoplasm, \nmembrane)\nNot present in most benign adult \nepithelial cells (may be present \nin secretory endometrium), \napocrine metaplasia, and fetal \nGI tract\nAdenocarcinomas (especially \novary, colon, breast)\nAdenocarcinoma (+ >90%) vs. \nmesothelioma (5%) or meso\u00ad\nthelial cells (-)\nOther markers are more \nuseful for mesothelioma \nvs. adenocarcinoma.\nbcl-2 (B-cell lym\u00ad\nphoma 2)\nProtein involved in \ninhibition of apop\u00ad\ntosis (Membrane, \ncytoplasm)\nMedullary lymphocytes and \nepithelial cells of the normal \nthymus, mantle and T zone \nsmall lymphocytes\nSynovial sarcoma, solitary \nfibrous tumor, \n\u00admyofibroblastic tumors, \nschwannoma, neurofibroma, \ngranular cell tumor, GIST, KS, \nmelanoma\nSmall lymphocytic lymphoma/\nCLL, mantle cell lymphoma, \nfollicular lymphoma, \nmarginal zone lymphoma \n(MALT), some large B-cell \nlymphoma\nSynovial sarcoma (+/-) vs. meso\u00ad\nthelioma (-)\nThymic carcinomas strongly \nexpress bcl-2 compared to \nthymomas.\nSmall lymphocytic lymphoma, \nmantle cell lymphoma, and \nmarginal zone lymphoma \n(MALT) (+) vs. reactive \nfollicles (-).\nThe bcl-2 gene is involved \nin the t(14;18) found in \nfollicular lymphomas.\nBer-EP4 (Epithelial-\nspecific antigen \n[ESA], Ep-CAM)\nGlycoprotein\n(\u2009Membrane)\nAll epithelial cells except superfi\u00ad\ncial layers of epidermis\nMost carcinomas\nAdenocarcinoma (+; strong and \ndiffuse in 60 to 100%) versus \nmesothelioma (- or focal in \n26%)\nOther markers are better \nfor distinguishing adeno\u00ad\ncarcinoma vs. mesothe\u00ad\nlioma\nBeta-amyloid \n(6F/3D)\nAmyloid present \nin Alzheimer\u2019s \ndisease (AD) and in \ncerebral amyloid \nangiopathy\n(Extracellular)\nNone\nSenile plaque core in AD, amy\u00ad\nloid cores, neuritic plaques, \nneurofibrillary tangles\nDiagnosis of AD, other diseases\nFound in AD, Lewy body \ndementia, Down\u2019s \nsyndrome, hereditary \ncerebral amyloidosis \n(Dutch type)\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_128.png", "summary": "This page discusses various immunoperoxidase studies used in pathology, including markers like androgen receptor, B72.3, bcl-2, Ber-EP4, and beta-amyloid.", "questions": [ "How do the different markers discussed in the text help in distinguishing between different types of tumors?", "What are the normal cells and tissues where these markers are typically found?", "What are some specific uses and applications of these immunoperoxidase studies in pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 129, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n111\nContinued\nBeta-catenin\nComponent of the \nadherens \u00adjunction \nthat binds to \ne-\u00adcadherin and \nfunctions in cell \nadhesion and \nanchoring the \n\u00adcytoskeleton; \n\u00adsignaling mol\u00ad\necule of the Wnt/\u00ad\nwingless pathway\n(Membrane, \n\u00adcytoplasm)\nUrothelium, breast epithelium, \ncolon, esophagus, stomach, \nthyroid\nTCC, colonic adenocarcino\u00ad\nmas and adenomas, breast \ncarcinoma, esophageal \nsquamous cell carcinoma, \nhead and neck squamous \ncell carcinomas, gastric car\u00ad\ncinoma, ovarian carcinoma, \nthyroid carcinoma, pros\u00ad\ntate carcinoma, HCC, brain \nneoplasms\nNuclear positivity in solitary \nfibrous tumor (40%), endo\u00ad\nmetrial stromal sarcoma \n(40%), synovial sarcoma \n(28%)\nAberrant nuclear expression in \nsolid-pseudopapillary tumors \nof the pancreas (95%) and \npancreatoblastomas (78%)\nAberrant nuclear expression in \ndesmoid fibromatosis (80% \ndeep, 56% superficial) vs. low \ngrade myofibroblastic sar\u00ad\ncoma (30%), solitary fibrous \ntumor (22%), infantile fibro\u00ad\nsarcoma (20%), desmoplastic \nfibroblastomas (6%)\nBeta-2 micro-\nglobulin\nImmunoglobulin-\nassociated protein\n(Extracellular depos\u00ad\nits of amyloid)\nPlasma cells\nIdentification of amyloid in \npatients on dialysis\nAmyloid tends to accumu\u00ad\nlate around joints and in \nthe GI tract\nBG8\nLewis blood group y \nantigen\n(Cytoplasm)\nRed blood cells, \nendothelial cells\nAdenocarcinomas (95%), rare \nmesotheliomas (about 5%)\nOther markers are better \nfor distinguishing adeno\u00ad\ncarcinoma vs. mesothe\u00ad\nlioma\nBlood group \nantigens\nA, B, and H antigens\n(Membrane)\nEpithelial cells and \nred blood cells, \nendothelial cells\nLost or abnormally expressed \nin many carcinomas\nCan be helpful to identify poten\u00ad\ntially misidentified specimens \nif patients\u2019 blood types are \nknown.\nH is diminished by decalci\u00ad\nfication but not A and B \nantigens.\nCA 125 (OC125)\nMucin-like glycopro\u00ad\ntein, antibody to \novarian carcinoma \nantigen\n(Luminal surface)\nEpithelial cells, \nmesothelial cells\nAdenocarcinomas of ovary, \nbreast, lung (bronchioloal\u00ad\nveolar), and others (rarely \ncolon), TCC, adenoma\u00ad\ntoid tumor of the uterus, \nsquamous cell carcinoma, \nseminal vesicle carcinoma, \nanaplastic lymphoma\nSeminal vesicle carcinoma (+) vs. \nprostate carcinoma (-)\nUsed as a serum marker \nfor monitoring ovarian \ncancer", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_129.png", "summary": "The page discusses various immunoperoxidase studies including beta-catenin, beta-2 microglobulin, BG8, blood group antigens, and CA 125, highlighting their expression in different tissues and tumors.", "questions": [ "How do the expression patterns of beta-catenin differ in various tumors?", "What is the significance of identifying amyloid in patients on dialysis?", "How can blood group antigens be helpful in distinguishing different types of carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 130, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n112\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nCA19-9 (Carbo\u00ad\nhydrate antigen \n19-9)\nAntigen of sialyl \nLewisa-containing \nglycoprotein; \nantibody to colon \ncarcinoma\n(Cytoplasm)\nEpithelial cells of breast, colon, \nkidney, liver, lung, pancreas, \nsalivary gland, others\nAdenocarcinomas of GI tract, \npancreas, ovary, lung, and \nbladder, rare in mesothe\u00ad\nliomas\nChronic pancreatitis\nUsed as a serum marker \nfor monitoring gastroin\u00ad\ntestinal and pancreatic \ncarcinomas\nCalcitonin\nPeptide hormone \nproduced by C cells\n(Cytoplasm and \nextracellular \namyloid)\nC cells of the thyroid\nMedullary carcinoma of the \nthyroid (within tumor cells \nand in amyloid)\nID of C-cell hyperplasia\nID of medullary thyroid carci\u00ad\nnoma\nUsed as a serum marker for \nmedullary carcinoma.\nCaldesmon \n(h-caldesmon)\nActin and calmodulin \nbinding protein in \nsmooth muscle\n(Cytoplasm)\nVascular and visceral smooth \nmuscle cells, some myoepithe\u00ad\nlial cells of the breast\nSmooth muscle tumors, \nPEComa, GIST\nSmooth muscle tumors (+) vs. \nmyofibroblastic lesions (-) \nor endometrial stromal \ntumors (-)\nCalponin (CALP)\nProtein that binds to \ncalmodulin, F-actin, \nand tropomyosin \nto regulate smooth \nmuscle contraction\n(Cytoplasm)\nVascular and visceral smooth \nmuscle cells, myoepithelial cells \nof the breast, periacinar and \nperiductal myoepithelial cells \nof the salivary gland\nMyoepithelioma, some smooth \nmuscle tumors, myofibro\u00ad\nblastic lesions\nCan be helpful to identify \nmyoepithelial cells in breast \nlesions\nCalretinin\nIntracellular calcium-\nbinding protein \nof the troponin C \nsuperfamily with \nan EF-hand domain\n(Cytoplasm, \nnucleus)\nSubsets of neurons, pineal cells, \ngerminal epithelium of ovary, \nmesothelial cells, keratinocytes, \nbreast, sweat glands, neuroen\u00ad\ndocrine cells, thymus\nEpithelial mesotheliomas (less \n+ in sarcomatoid type), \nadenomatoid tumor, some \nlung squamous cell carcino\u00ad\nmas, rare adenocarcinomas, \nmesenchymal tumors (e.g., \nsynovial sarcoma), granular \ncell tumor, Leydig cell tumor, \ngranulosa cell tumor\nEpithelial mesotheliomas \n(>90%) versus adenocarci\u00ad\nnoma (<10%)\nUseful positive marker for \nmesotheliomas.\nCarcinoembry\u00ad\nonic antigen \n(CEA. CD66e)\nGlycoproteins with \nimmunoglobulin-\nlike regions found \nin fetal tissues\n(Cytoplasm)\nFetal tissues\nAdenocarcinomas (liver, colon, \npancreas, bile duct, and lung \nmore than breast, ovary), \nTCC, medullary carcinoma of \nthe thyroid\nUsually absent in RCC, prostate \ncarcinoma, and papillary or \nfollicular thyroid carcinomas\nAdenocarcinoma (+) versus \nmesothelioma (\u2013)\nHCC: polyclonal CEA has a cana\u00ad\nlicular pattern\nDifferent reactivity patterns \noccur with different \nantibodies and with \npolyclonal versus mono\u00ad\nclonal antibodies\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_130.png", "summary": "This page provides information on various immunoperoxidase studies, including markers such as CA19-9, calcitonin, caldesmon, calponin, calretinin, and carcinoembryonic antigen, their locations, normal cells and tissues they are found in, associated tumors, and their uses in pathology.", "questions": [ "What are some examples of tumors associated with the marker CA19-9?", "How is calcitonin used as a serum marker in pathology?", "What is the significance of calretinin in identifying mesotheliomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 131, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n113\nContinued\nCD5 (Leu 1)\nTransmembrane \nglycoprotein\n(Membrane)\nT cells and B cell subsets (mantle \nzone)\nThymic carcinoma, adeno\u00ad\ncarcinomas, mesothelioma \n(cytoplasmic)\n\t\u0007T-cell leukemias and \n\u00adlymphomas, aberrantly \nexpressed in low-grade \nB-cell lymphomas (CLL or \nmantle cell lymphoma).\nThymic carcinoma (+/-) vs. thy\u00ad\nmoma (-).\nThymic carcinoma (+/-) vs. \nmetastatic squamous \n\u00adcarcinoma (-)\nClassification of low grade B-cell \nlymphomas.\nEvaluation of T-cell lymphomas \n(this marker is frequently lost).\nCD10 (CALLA [com\u00ad\nmon acute leuke\u00ad\nmia antigen], J5)\nCell surface metal\u00ad\nloendopeptidase \nthat inactivates \npeptides\n(Membrane)\nPrecursor B cells, granulocytes, \nrare cells in reactive follicles, \nmyoepithelial cells of breast, \nbile canaliculi, fibroblasts, \nbrush border of kidney and gut\nEndometrial stromal sarcoma, \nRCC (clear cell and papillary \ntypes), HCC, TCC, rhabdo\u00ad\nmyosarcoma, pancreatic \ncarcinoma, schwannoma, \nmelanoma\nPrecursor lymphoblastic \nlymphoma/leukemia, fol\u00ad\nlicular lymphoma, Burkitt \nlymphoma, CML, angioim\u00ad\nmunoblastic lymphoma\nMyoepithelial cell marker in \nbreast\nEndometrial stromal sarcoma (+) \nvs. leiomyosarcoma (-/+) (but \ncaldesmon is preferred for this \npurpose)\nEvaluation of low-grade \n\u00adlymphomas.\nEvaluation of leukemias\nNot specific for \n\u00adnonlymphoid \nneoplasms.\nCD15 (LeuM1)\n3-fucosyl-N-acetyl\u00ad\nlactos-amine, \nX-hapten - CHO \nmoiety linked to cell \nmembrane protein \n(Membrane and \n\u00adcytoplasm)\nGranulocytes, monocytes\nAdenocarcinomas\nCMV-infected cells\nRS cells (not LP HD) in a \n\u00admembranous and golgi \npattern, some large T-cell \nlymphomas, MF, some \nleukemias\nAdenocarcinomas (+) versus \nmesotheliomas (-)\nEvaluation of HD\nCD30 (Ki-1)\nSingle-chain \ntransmembrane \nglycoprotein \nhomologous to \nthe nerve growth \n\u00adfactor superfamily\n(Cytoplasm, \n\u00admembrane, and \ngolgi)\nActivated B and T cells, some \nplasma cells, immunoblasts, \ninterdigitating cells, histiocytes, \nfollicular center cells, decidual\u00ad\nized endometrium, reactive \nmesothelial cells, most other \ntissues negative\nEmbryonal carcinoma, some \nvascular tumors (not KS), \nsome mesotheliomas\nAnaplastic large cell (CD30+) \nlymphomas, mediastinal \nlarge B-cell lymphoma, \nprimary effusion lymphoma, \nHD (but not LP HD), some \nother B- and T-cell lympho\u00ad\nmas, EBV transformed B cells\nID of anaplastic large cell \n(CD30+) lymphomas.\nEvaluation of HD (RS cells are \npositive except in LP HD).\nID of peripheral T-cell lymphoma \n(large cells may be positive).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_131.png", "summary": "The page discusses the use of immunoperoxidase studies for CD5, CD10, CD15, and CD30 markers in identifying various cell types and neoplasms.", "questions": [ "How are immunoperoxidase studies used in distinguishing between thymic carcinoma and thymoma?", "What are the implications of CD10 marker expression in different types of lymphomas and leukemias?", "How can CD30 marker be helpful in identifying specific types of lymphomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 132, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n114\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nCD31 (PECAM-1, \nplatelet-endothe\u00ad\nlial cell adhesion \nmolecule)\nTransmembrane gly\u00ad\ncoprotein function\u00ad\ning in cell adhesion\n(Cytoplasm, \nmembrane)\nEndothelial cells, platelets, \nmegakaryocytes, plasma cells, \nhistiocytes, other hematopoi\u00ad\netic cells\nVascular tumors (> 80% of \nangiosarcomas), KS, histio\u00ad\ncytic neoplasms, PEComa, \nvery rarely other tumors\nID of endothelial differentiation \nin tumors\nEvaluation of angiogenesis\nMost sensitive and specific \nmarker for endothelial \ncells\nCD34 (HPCA-1, \nhematopoietic \nprogenitor cell, \nclass 1, QBEnd10)\nSingle-chain trans\u00ad\nmembrane glyco\u00ad\nprotein, leukocyte \ndifferentiation \nantigen \n(Cytoplasm, \n\u00admembrane)\nHematopoietic progenitor cells \n(decreases with maturation), \nendothelial cells, fixed connec\u00ad\ntive tissue cells (e.g., in skin), \nfibroblasts\nAcute leukemia, sarcomas of \nvascular origin, KS, epithe\u00ad\nlioid sarcoma, GIST, DFSP, \nsolitary fibrous tumor, \nneurofibroma, schwannoma, \nspindle cell lipoma, phyl\u00ad\nlodes tumor, fibroadenoma\nID of endothelial or fibroblastic \ndifferentiation in tumors.\nEvaluation of angiogenesis.\nEvaluation of the number of \nblasts in bone marrow in \nacute leukemia.\nSolitary fibrous tumor (+) vs. \nsarcomatoid mesothelioma (-)\nDFSP (+) vs. dermatofibroma (-)\nNot specific but can be use\u00ad\nful in context with other \nfeatures\nCD44v3 (CD44 \nvariant 3, H-CAM)\nTransmembrane \nglycoprotein that \nmediates cell \n\u00adadhesion\n(Membrane)\nMany, including myometrium\nMany, including endometrial \ncarcinomas\nPossibly helpful to distinguish \ncellular leiomyoma (+) \nfrom endometrial stromal \nsarcoma (-)\nMany splice variants of \nCD44 are present in nor\u00ad\nmal and malignant cells.\nCD57 (Leu 7, \nHNK-1)\nLymphocyte anti\u00ad\ngen that cross \nreacts with a \nmyelin-\u00adassociated \n\u00adglycoprotein\n(Membrane)\nT-cell subsets, NK cells, myelin\u00ad\nized nerves, neuroendocrine \ncells, prostate, pancreatic islets, \nadrenal medulla\nNerve sheath tumors \n(occasional), leiomyosar\u00ad\ncoma, synovial sarcoma, \nrhabdomyosarcoma, \nneuroblastoma, gliomas, \nneuroendocrine carcinomas, \nneurofibromas, some pros\u00ad\ntate carcinomas\nAngioimmunoblastic lym\u00ad\nphoma, T gamma lympho\u00ad\nproliferative disorder (large \ngranular cell lymphocytic \nleukemia)\nID of neuroendocrine differen\u00ad\ntiation in tumors\nID of angioimmunoblastic T-cell \nlymphoma\nEvaluation of NK neoplasms.\nNot very specific for solid \ntumors\nCD63 (NKI/C3, \nmelanoma-asso\u00ad\nciated antigen, \nME491)\nMember of the \ntetraspanin or \ntransmembrane \n4 superfamily \n(TM4SF) found on \nlysosomes\n(Cytoplasm or \n\u00admembrane)\nMelanocytes, mast cells, histio\u00ad\ncytes, salivary gland cells, sweat \ngland cells, pancreatic cells, \nislets of Langerhans, prostatic \ncells, Paneth cells, peribronchial \nglands, pituitary\nNevi, melanomas, carcinoids, \nmedullary carcinomas \nof the thyroid, some \n\u00adadenocarcinomas\nCellular neurothekoma (NKI/C3 \n+ and S100 -) versus mela\u00ad\nnocytic lesions (NKI/C3 and \nS100 +)\nID of melanocytic lesions\nMay be negative in desmo\u00ad\nplastic melanomas\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_132.png", "summary": "The page discusses various immunoperoxidase studies, including markers like CD31, CD34, CD44v3, CD57, and CD63, their normal cellular locations, associated tumors, and potential uses in pathology.", "questions": [ "How do CD31 and CD34 markers help in identifying endothelial differentiation in tumors?", "What are some examples of tumors where CD44v3 marker may be helpful in distinguishing between different types of cells?", "What is the significance of CD57 marker in identifying neuroendocrine differentiation in tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 133, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n115\nContinued\nCD68 (KP1, CD68-\nPG-M1, Mac-M)\nIntracellular glyco\u00ad\nprotein associated \nwith lysosomes\n(Cytoplasm, \n\u00admembrane)\nMacrophages, monocytes, \nneutrophils, basophils, large \nlymphocytes, Kupffer cells, \nmast cells, osteoclasts\nNeurofibroma, schwannoma, \nMPNST, granular cell tumors, \nPEComa, melanomas, atypi\u00ad\ncal fibroxanthoma, RCC\nSome lymphomas, histiocytic \nsarcomas, APML, Langer\u00ad\nhans proliferative disorders\nBest general marker for macro\u00ad\nphages, although not specific \nto this cell type.\nThe antibody PG-M1 does \nnot react with granulo\u00ad\ncytes.\nNot very specific for solid \ntumors.\nCD99 (MIC-2, 12E7, \nEwing\u2019s sarcoma \nmarker, E2 anti\u00ad\ngen, HuLy-m6, \nFMC 29, O13 [dif\u00ad\nferent epitope])\nMIC2 gene product \u2013 \nglycoproteins (p30 \nand p32) involved \nin rosette forma\u00ad\ntion with erythro\u00ad\ncytes (Membrane)\n(Membrane \n\u00ad[immunoreactivity \nis more specific \nthan cytoplasmic])\nCortical thymocytes, T lympho\u00ad\ncytes, granulosa cells of ovary, \npancreatic islet cells, Sertoli \ncells, some endothelial cells, \nurothelium, ependymal cells, \nsquamous cells\nPNET/Ewing\u2019s sarcoma, chon\u00ad\ndroblastoma, mesenchymal \nchondrosarcoma, synovial \nsarcoma, solitary fibrous \ntumors, GIST, some alveolar \nrhabdomyocarcomas, des\u00ad\nmoplastic small cell tumors, \nsmall cell carcinomas, \ngranulosa cell tumors, yolk \nsac components of germ cell \ntumors, Sertoli-Leydig cell \ntumors, atypical fibroxan\u00ad\nthoma, meningioma\n\tB- and T-cell precursor lympho\u00ad\nblastic lymphoma/leukemia\nThymic carcinomas (lympho\u00ad\ncytes +) versus other carcino\u00ad\nmas.\nID of PNET/Ewing\u2019s sarcoma \n(immunoreactivity should be \nclearly membranous in the \nmajority of the cells)\nEvaluation of lymphoblastic \nlymphoma/leukemia\nO13 is the most commonly \nused antibody.\nImmunoreactivity is highly \ndependent upon the \nantigen retrieval system \nused\nCD117 (c-kit, \nstem cell factor \n\u00adreceptor)\nTransmembrane \ntyrosine kinase \nreceptor (ligand \nis stem cell fac\u00ad\ntor) - apoptosis is \ninhibited when the \nligand is bound\n(Cytoplasm, mem\u00ad\nbrane)\nMast cells, interstitial cells of Cajal \n(ICC - pacemaker cells of the \nGI tract found through-out \nthe muscle layers and in the \nmyenteric plexus), epidermal \nmelanocytes, mononuclear \nbone marrow cells (4%), Leydig \ncells, early spermatogenic cells, \ntrophoblast, breast epithelium\nGIST (>95%), seminomas \n(>70%), intratubular germ \ncell neoplasia, mature \n\u00adteratomas (>70%), papillary \nrenal cell (cytoplasmic \u2013 \nassociated with mutations), \nchromophobe renal cell \n(membrane - not associ\u00ad\nated with mutations), some \nmelanomas (focal), mast cell \ntumors, some carcinomas \n(including adenoid cystic car\u00ad\ncinoma), some brain tumors, \nsome PNET/Ewing\u2019s sarcoma, \nsome angiosarcomas\nAML (>50%), CML in myeloid \nblast crisis\nID of GIST (+) vs. leiomyomas (-) \nand schwannomas (-).\nID of seminomas\nID of mast cells (mastocytosis) \u2013 \nabnormal mast cells com\u00ad\nmonly have the imatinib \n\u00adresistant mutation D816V.\nMast cells are an excellent \ninternal control.\nCD117 (+) does not corre\u00ad\nlate with mutations and/\nor oncoprotein activity \nin tumors not known to \nhave activating muta\u00ad\ntions and is, in general, \nnot of clinical or thera\u00ad\npeutic significance in this \nsetting (e.g., to detect \ntumors likely to respond \nto therapy directed \nagainst the protein, such \nas Gleevec.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_133.png", "summary": "The page discusses the immunoperoxidase studies CD68, CD99, and CD117, highlighting their associated glycoproteins, cell types they react with, and their utility in identifying various tumors.", "questions": [ "How does the immunoreactivity of CD68 differ from CD99 and CD117?", "What are the specific cell types that CD117 reacts with and in what types of tumors is it commonly expressed?", "What are the key differences in the utility of CD117 in identifying different types of tumors compared to CD68 and CD99?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 134, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n116\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nCD123 (interleu\u00ad\nkin-3 receptor \nalpha chain)\nAlpha chain of the \nIL-3 receptor\n(Membrane)\nMyeloid precursors, macro\u00ad\nphages, dendritic cells, \nmast cells, basophils, \n\u00admegakaryocytes\nPlasmacytoid dendritic cell \ntumors\nCD141 (thrombo\u00ad\nmodulin, TM)\nTransmembrane gly\u00ad\ncoprotein, receptor \nfor thrombin\n(Cytoplasm \n[epithelial cells], \nmembrane [meso\u00ad\nthelial cells])\nEndothelium, platelets, mono\u00ad\ncytes, synovial cells, syncytio\u00ad\ntrophoblast, mesothelial cells, \ndermal keratinocytes, islet cells, \nperipheral nerves\nMesotheliomas, TCC, KS, \nsquamous cell carcinomas, \nchoriocarcinomas, rarely \nadenocarcinomas, benign \nand malignant vascular \ntumors\nMesothelioma (+ 80%) vs. \nadenocarcinoma (+ 10%) (but \nvariable results have been \nreported in other studies)\nOther markers are better \nfor distinguishing adeno\u00ad\ncarcinoma vs. mesothe\u00ad\nlioma.\nCD146 (melanoma \ncell adherin mol\u00ad\necule, MELCAM, \nMCAM, MN-4, \nMUC18, A32 anti\u00ad\ngen, S-Endo-1)\nMembrane cell adhe\u00ad\nsion glycoprotein \nof the Ig gene \nsuperfamily\n(Membrane)\nImplantation site intermediate \ntrophoblast, myofibroblasts, \nendothelium, pericytes, \nSchwann cells, ganglion cells, \nsmooth muscle, cerebellar \ncortex, breast luminal and \n\u00admyoepithelial cells, external \nroot sheath of hair follicle, \n\u00adsubcapsular epithelium of thy\u00ad\nmus, follicular dendritic cells, \nbasal cells of bronchus and \nparathyroid, subpopulations \nof activated T cells\nMelanoma, angiosarcoma, KS, \nleiomyosarcoma, placental \nsite trophoblastic tumor, \nchoriocarcinoma\nMay be focally positive in \nsquamous cell carcinoma \nand small cell carcinoma \nof the lung, mucoepider\u00ad\nmoid carcinoma, breast \ncarcinoma, some leukemias, \nneuroblastoma\nID of placental site trophoblastic \ntumors\nCD163 (M130)\nEndocytic receptor to \nscavenge hapto\u00ad\nglobin and hemo\u00ad\nglobin complexes\n(Membrane, \ncytoplasm)\nTissue macrophages (high expres\u00ad\nsion), monocytes (low expres\u00ad\nsion) including Kupffer cells, \nHofbauer cells but not follicular \ndendritic cells or plasmacytoid \nmonocytes\nNeoplasms of histiocytic dif\u00ad\nferentiation\nLeukemias of monocytic dif\u00ad\nferentiation\nSynovial type giant cell tumors \nof the vertebral column\nLangerhans cell histiocytosis \n(~60%), benign fibrous \nhistiocytoma (~67%)\nLittoral cell angioma of the \nspleen\nID of true histiocytic derivation \nof tumors\nMore specific for mono\u00ad\ncyte/histiocyte deriva\u00ad\ntion than CD68\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_134.png", "summary": "This page provides information on immunoperoxidase studies, including markers such as CD123, CD141, CD146, and CD163, their normal cell/tissue locations, associated tumors, and uses.", "questions": [ "How do the markers CD123, CD141, CD146, and CD163 differ in terms of their normal cell and tissue locations?", "What types of tumors are associated with the markers CD123, CD141, CD146, and CD163?", "What are the specific uses of CD163 in immunoperoxidase studies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 135, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n117\nContinued\nCDK4 (cylin-depen\u00ad\ndent kinase 4)\nA \u0007kinase involved in \ncell cycle regulation \n(Nuclear)\nNone\nLiposarcoma, glioblastoma, \nanaplastic astrocytoma, \nlarge B-cell lymphoma, \nosteosarcoma, breast carci\u00ad\nnoma\nAtypical lipomatous tumor/well-\ndifferentiated liposarcoma \nand dedifferentiated liposar\u00ad\ncoma (>90% +) vs. benign \nadipose tumors (<5% +)\nMDM2 can also be used for \nthis differential diagnosis\nCDX2 (caudal-\nrelated homeo\u00ad\nbox transcription \nfactor, CDX-88)\nHomeobox nuclear \ntranscription factor \nspecific for the \nintestinal tract that \nregulates MUC2 \nexpression\n(Nucleus)\nSmall intestine, colon, and endo\u00ad\ncrine pancreas\nColon carcinomas (usually \nstrong and diffuse), small \nintestine carcinomas, muci\u00ad\nnous ovarian carcinomas, \nbladder adenocarcinomas, \nsome gastric, esophageal, \npancreatic, and bile duct \ncarcinomas\nHCC, breast, lung, and head \nand neck carcinomas are \nusually negative\nID of colon carcinomas and \nother carcinomas of the \n\u00adgastrointestinal tract. \nHowever, other carcinomas \n(e.g., mucinous ovarian \ncarcinoma or mucinous lung \n\u00adbronchioloalveolar carci\u00ad\nnoma) can also be positive\nChromogranin A\nAcidic glycoprotein \nin neurosecretory \ngranules\n(\u00adCytoplasm, \ngranular)\nIslet cells of pancreas, bronchial \nKulchitsky cells, parathyroid, \nadrenal medulla, anterior \n\u00adpituitary, C-cells of thyroid\nPheochromocytoma, carci\u00ad\nnoids (not rectal), small cell \ncarcinoma, neuroblastoma, \nsome breast and prostatic \ncarcinomas, Merkel cell \ntumors, islet cell tumors, \nmedullary carcinoma of the \nthyroid, parathyroid lesions, \nBrenner tumor\nID of neuroendocrine differen\u00ad\ntiation in tumors. Not present \nin pituitary prolactinomas.\nPheochromocytoma (+) versus \nadrenal cortical carcinoma (\u2013).\nParathyroid (+) vs. thyroid (\u2013)\nMost specific marker of \nneuroendocrine differen\u00ad\ntiation\nAlso can be detected in \nserum\nBouin\u2019s solution or B5 \nfixation may increase \nimmunogenicity\nClaudin-1 (CLDN1)\nProtein component of \nthe tight junction \ncomplex\n(Membrane \u2013 not \ncytoplasmic)\nEpithelial cells, perineurial \ncells, some endothelial cells \n(venules)\nPerineurioma (30%), synovial \nsarcoma (epithelioid areas, \nlower in spindle cell areas), \ncarcinomas\nSome perineurial cells may be \npresent in neurofibromas \nand schwannomas\nPerineurioma (+ 30%) vs. DFSP \n(-), fibromatosis (-), low grade \nfibromyxoid sarcoma (\u2013)\nMeningiomas \u2013 50% +\nCollagen IV\nMajor constituent of \nbasement mem\u00ad\nbranes \n(Basement \n\u00admembrane)\nMesangial cells within glomeruli, \nbasement membranes, basal \nlamina of capillaries\nTumors with external lamina \n(schwannomas, smooth \nmuscle tumors)\nAbsence or loss may be associ\u00ad\nated with stromal invasion by \ncarcinomas", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_135.png", "summary": "The page discusses various immunoperoxidase studies including CDK4, CDX2, Chromogranin A, Claudin-1, and Collagen IV, highlighting their roles in differentiating between various tumors.", "questions": [ "How do CDK4 and MDM2 aid in the differential diagnosis of liposarcomas?", "What is the significance of CDX2 in identifying colon carcinomas and other gastrointestinal tract carcinomas?", "How is Chromogranin A used to identify neuroendocrine differentiation in tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 136, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n118\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nD2-40 (podoplanin, \nM2A)\nOncofetal Membrane \nO-linked sialogly\u00ad\ncoprotein \n(\u00adMembrane)\nLymphatic endothelium, germ \ncells of testis, interstitial cells of \nCajal, follicular dendritic cells, \nmyoepithelial cells of the breast\nLymphatic tumors, some \nangiosarcomas, some \nepithelioid hemangioen\u00ad\ndotheliomas, epithelioid \nmesotheliomas, seminomas, \nITGCN, KS, GIST, ovarian \nserous carcinomas\nIdentification of LVI\nID of seminoma (+, diffuse) vs. \nembryonal carcinoma (- or \nfocal)\nEpithelioid meso (+) vs. adeno\u00ad\ncarcinoma (\u2013)\nID of follicular dendritic cell \nsarcoma\nMyoepithelial cells of \nthe breast can show \ncytoplasmic positivity \u2014 \nlimiting usefulness in the \nbreast for LVI\nDesmin\nIntermediate \nfilament in muscle \n(\u00adCytoplasm)\nAll striated muscle (Z bands) and \nmany smooth muscle cells, \nmyofibroblasts, smooth muscle \nof some BVs\nRhabdomyosarcoma (80% +), \nleiomyosarcoma (50-70% +), \nPEComa, desmoplastic small \nround cell tumors (usually \ndot-like), some myofibro\u00ad\nblastic tumors, endometrial \nstromal sarcoma\nID of muscle differentiation in \ntumors\nDOG1 (discovered \nOn GIST-1)\nProtein of unknown \nfunction expressed \nin GIST\n (Cytoplasm or \nmembrane)\nInterstitial cells of Cajal\nGIST (positivity in other tumor \ntypes is <10%)\nID of GIST (may be + in some \nCD117 neg GIST)\nPositive in 79% of GIST with PDG\u00ad\nFRA mutations, whereas CD117 \nis positive in 9% of this group\nDPC4 (homozy-\ngously deleted \nin pancreatic \ncarcinoma, locus \n4, Smad4)\nTranscriptional regu\u00ad\nlator interacting \nwith the TGFbeta \nsignaling pathway\n(Nucleus)\nNormal tissues\nExpressed in most carcinomas\nLost in 31% of Pan IN-3, 55% \nof pancreatic carcinomas, \nand 22% of stage IV colon \ncarcinomas\nMucinous ovarian carcinoma \n(+) vs. metastatic pancreatic \ncarcinoma (negative in 55%)\nMutated in familial juvenile \npolyposis in 25% to 60% \nof cases\nE-cadherin\nTransmembrane cell \nadhesion molecule \nthat binds to caten\u00ad\nins for cell polar\u00ad\nization, glandular \ndifferentiation, \nand stratification\n(Membrane)\nEpithelial cells\nMost carcinomas \u2013 may be \nlost in poorly differentiated \ncarcinomas\nNot present in LCIS and inva\u00ad\nsive lobular carcinoma of \nbreast or gastric signet ring \ncell carcinomas\nDuctal (+) vs. lobular (\u2013) lesions \nof the breast\nCan be helpful to distin\u00ad\nguish DCIS from LCIS.\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_136.png", "summary": "This page provides information on various immunoperoxidase studies used in pathology, including markers like D2-40, Desmin, DOG1, DPC4, and E-cadherin, their normal cellular locations, associated tumors, and their diagnostic uses.", "questions": [ "How do immunoperoxidase studies like D2-40, Desmin, DOG1, DPC4, and E-cadherin help in the identification of specific tumors?", "What are the differences in expression patterns of these markers in normal cells and tissues compared to tumors?", "How can the loss or mutation of markers like DPC4 and E-cadherin be used in diagnosing specific types of carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 137, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n119\nContinued\nEGFR (epidermal \ngrowth factor \nreceptor, HER1)\nTransmembrane \nprotein receptor of \nthe type 1 growth \nfactor family with \ntyrosine kinase \nactivity\n (Membrane positiv\u00ad\nity scored, cytoplas\u00ad\nmic positivity is not \nscored)\nMany types of epithelium, skin \neccrine and sebaceous glands, \nmesenchymal cells, perineurium \nThe strongest membrane posi\u00ad\ntivity is present in hepatocytes, \nbile ducts, basilar squamous \ncells, pancreatic ducts, breast \nepithelium, lung alveolar lining \ncells, mesothelial cells, prostate \nepithelium, endometrial glands \nand stroma\nAdenocarcinomas (esp. colon), \nsquamous cell carcino\u00ad\nmas, TCC, neural tumors, \n\u00adsarcomas\nExpression is increased in \ntumors of higher grade and \npoorer prognosis\nColon carcinomas (80-90% posi\u00ad\ntive) \u2013 response to cetuximab \nis not related to IHC score\nLung adenocarcinoma \u2013 specific \nmutations (but not IHC) pre\u00ad\ndict response to TK inhibitors\nGBM \u2013 40% show gene amplifica\u00ad\ntion and overexpression by IHC. \nTK domain mutations are rare\nEpithelial mem\u00ad\nbrane antigen \n(EMA, MUC1, \nHMFG, DF3, CA \n15-3, CA 27.29, \nPEM, many \n\u00adothers)\nEpisialin, glycoprotein \nfound in human \nmilk fat \u00adglobule \n\u00admembranes\n (\u00adCytoplasm \n[more common in \nmalignant cells], \nmembrane [more \ncommon in benign \ncells])\nEpithelial cells, perineurial cells, \nmeningeal cells, plasma cells, \nusually negative in non-neo\u00ad\nplastic mesothelial cells\nCarcinomas, mesotheliomas \n(thick membrane pattern), \nsome sarcomas (syno\u00ad\nvial sarcoma, epithelioid \nsarcoma, leiomyosarcoma, \nsome osteosarcomas), \nadenomatoid tumor, \nchordoma, perineurioma, \nneurofibroma, meningioma, \ndesmoplastic small round \ncell tumor, Sertoli cell tumor \nSome anaplastic large \ncell \u00adlymphomas (CD30 +), \nplasma cell neoplasms\nID of epithelial differentiation in \ntumors \u2013 however, keratin is \nmore specific for this purpose\nSynovial sarcoma (typically focal \npositivity) vs. other sarcomas\nDemonstrates the \u201cinside out\u201d \nglands of invasive micropapil\u00ad\nlary breast carcinoma\nThere are over 50 mono\u00ad\nclonal antibodies \nrecognizing different \nglycosylation patterns \nin normal tissues and \ntumors18\nEpstein-Barr virus\nEBV-encoded \nnonpolyade\u00ad\nnylated early \nRNAs\n(EBERS)\nRNA produced by EBV\n(Nucleus)\nEBV-infected B cells\nAll EBV-related tumors\nMost sensitive marker for EBV\nDetected by in situ \n\u00adhybridization for RNA on \nparaffin sections\nLMP-1\nLatent membrane \nprotein\n(Membrane)\nEBV-infected B cells\nNasopharyngeal carcino\u00ad\nmas, RS cells (not LP HD), \ntransplant lymphomas, \nAIDS-related lymphomas, \nendemic Burkitt lymphoma \n(rare in sporadic cases)\nEvaluation of EBV-related neo\u00ad\nplasms\nEBNA 2 (nuclear \nantigen 2)\nNuclear protein\n(Nucleus)\nEBV-infected B cells\nTransplant-related lymphomas, \nAIDS-related lymphomas \nNot present in Burkitt \nlymphoma, nasopharyngeal \ncarcinomas, or HD\nEvaluation of transplant- and \nAIDS-related lymphomas", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_137.png", "summary": "This page discusses the use of immunoperoxidase studies for EGFR, EMA, and Epstein-Barr virus in identifying various types of tumors and neoplasms.", "questions": [ "What are some examples of tissues or cells that show strong membrane positivity for EGFR?", "How is EMA used in identifying different types of tumors?", "What are the specific markers used for detecting Epstein-Barr virus and in what types of tumors are they commonly found?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 138, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n120\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nEstrogen receptor \n(ER, 1D5, SP1, \n6F11, H222, \nothers)\nSteroid-binding \nprotein\n(Nucleus)\nBreast epithelial cells (not \n\u00admyoepithelial cells), epithelial \nand myometrial cells of the \nuterus\nBreast carcinomas (>70%), \nmyofibroblastoma of breast, \ngynecologic carcinomas, \nsome skin appendage \ntumors, rare in other \n\u00adcarcinomas, present in \nsome meningiomas, smooth \nmuscle tumors, some \nmelanomas, some thyroid \ntumors, desmoid tumors, \nvulvovaginal stromal tumor\nPrognosis and prediction of \nresponse to hormonal therapy \nof breast cancer. Only nuclear \npositivity is scored\nID of metastatic breast cancer\nABs recognize different epi\u00ad\ntopes and have varying \nsensitivities in formalin \nfixed tissue. Antigenic\u00ad\nity may be diminished \nafter decalcification or \nexposure to heat during \nsurgery.\nFactor VIII-related \nantigen (VWF, \nFVIII:RAg, von \nWillebrand \n\u00adfactor)\nGlycoprotein involved \nin coagulation, part \nof FVIII complex\n(Cytoplasm)\nEndothelial cells, megakaryo\u00ad\ncytes, platelets, and mast cells, \nendocardium\nVascular tumors (often absent \nin angiosarcomas)\nNot present in KS, PEComa\nMegakaryocytic AML (M7)\nID of endothelial differentiation \nin tumors (specific but not \nvery sensitive)\nEvaluation of angiogenesis\nEvaluation of M7 (megakaryo\u00ad\ncytic) leukemias\nMay not detect smaller \nblood vessels (see CD \n31 and 34). Present in \nWeibel-Palade bodies. \nNot a sensitive marker for \nvascular neoplasms.\nFactor XIIIa (Factor \nXIII subunit A)\nTransglutaminase \ninvolved in the \ncoagulation path\u00ad\nway \n(Cytoplasm)\nFibroblasts, dendritic reticulum \ncells in reactive follicles, \ndermal dendrocytes, liver, \nplacenta, platelets, megakaryo\u00ad\ncytes, monocytes, macro\u00ad\nphages\nFibroblastic neoplasms, derma\u00ad\ntofibroma\nNot very specific\nFascin (p55)\nActin binding protein \nthought to be \ninvolved in the for\u00ad\nmation of microfila\u00ad\nment bundles and \ncell motility\n(Cytoplasm)\nInterdigitating reticulum cells in \nlymph nodes, dendritic cells of \nlymph node, thymus, spleen \nand peripheral blood, histio\u00ad\ncytes, smooth muscle, endo\u00ad\nthelial cells, squamous mucosal \ncells, lining cells of splenic \nsinuses, neurons\nRS cells and their variants (but \nnot LP HD), rare non HD \nlymphomas\nReticulum cell tumors\nSome sarcomas\nMany carcinomas, especially \nthose of advanced stage\nGlial tumors (more common in \nhigh-grade tumors)\nNot very specific\nFibronectin\nGlycoproteins found \nin BMs and extra\u00ad\ncellular matrix, \nbind to integrins\n(Extracellular)\nStroma of many tumors\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_138.png", "summary": "The page discusses various immunoperoxidase studies including markers like estrogen receptor, Factor VIII-related antigen, Factor XIIIa, Fascin, and Fibronectin, their locations, normal cells and tissues, tumors they are associated with, and their uses.", "questions": [ "How do immunoperoxidase studies like estrogen receptor and Factor VIII-related antigen help in the diagnosis and prognosis of breast cancer?", "What are some limitations or challenges associated with using immunoperoxidase studies for identifying specific markers in tumors?", "How do the different antigens discussed on this page vary in terms of specificity and sensitivity for different types of tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 139, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n121\nContinued\nFLI-1 (Friend leuke\u00ad\nmia integrin-\nsite 1)\nTranscription factor \n(ETS family) \u2013 trans\u00ad\nlocation in Ewing\u2019s \ncan result in an \nEWS-FLI-1 fusion \nprotein\n(Nucleus)\nEndothelial cells (hemangioblasts, \nangioblasts), small lympho\u00ad\ncytes\nEwing\u2019s sarcoma/PNET, vascular \ntumors (including KS), Merkel \ncell carcinoma, melanoma\nCan also be weakly\n present in lymphomas, \nsynovial \u00adsarcoma, some \ncarcinomas\nID of vascular tumors (unlike \nother vascular markers, FLI-1 \nis nuclear).\nID of Ewings/PNET \u2013 not specific \nbut very sensitive (70%)\nReactivity can be variable \nwith high background \nand may be difficult to \ninterpret\nGalectin-3 (Gal-3)\nLectin with anti-\napoptosis function \n(galactoside-bind\u00ad\ning protein)\n(Nucleus, cytoplasm, \nmembrane, extracel\u00ad\nlular matrix)\nMany epithelial cells, lympho\u00ad\ncytes, mesenchymal cells, mac\u00ad\nrophages, activated endothelial \ncells\nMany carcinomas, adenomas, \nlymphomas, soft tissue \ntumors\nThyroid carcinomas (papillary \nand to a lesser extent follicu\u00ad\nlar) show higher expression \nthan benign lesions\nIn some carcinomas, expression \nis diminished in higher grade \nlesions\nGlial fibrillary \nacidic protein \n(GFAP)\nIntermediate filament\n(Cytoplasm)\nNormal and reactive astrocytes, \ndeveloping and reactive \nependymal cells, developing \noligodendrocytes, choroid \nplexus, Schwann cells, enteric \nglial cells, pituitary cells, chon\u00ad\ndrocytes\nTumors of astrocytes, epen\u00ad\ndymal cells, and oligo\u00ad\ndendrocytes, MPNST, \nmyoepitheliomas (salivary \nglands and soft tissue), \nsweat gland tumors, Merkel \ncell carcinomas, chordomas\nID of neural differentiation in \ntumors (30% of MPNSTs are \n+). Neuroblastomas are nega\u00ad\ntive, schwannomas may be \nfocally +.\nMerkel cell carcinoma (+) versus \nsmall cell carcinoma (\u2013) (but \nCk20 is a better marker for this \npurpose).\nID of myoepithelial neoplasms.\nGLUT-1 (glucose \ntransporter 1)\nComponent of trans\u00ad\nmembrane glucose \ntransport \n(Membrane)\nErythrocytes, perineurium, blood \nvessels, trophoblasts, renal \ntubules, germinal center cells\nTCC, lung carcinoma, squa\u00ad\nmous cell carcinoma, \nadenocarcinomas of colon, \nlung, bile ducts, kidney, \novary, pancreas, stomach, \nand endometrium, germ cell \ntumors\nNot very specific\nGross cystic \ndisease fluid \nprotein-15 \n(GCDFP, CDP, \nBR-2, BRST-2)\nProtein found in \nbreast fluid\n(Cytoplasm)\nApocrine sweat glands, apocrine \nmetaplasia of the breast\nBreast carcinomas (60%), sweat \ngland carcinomas, some \nsalivary gland tumors, some \nprostate carcinomas\nID of apocrine differentiation in \ntumors\nID of breast metastases (how\u00ad\never, only positive in about \n60%)\nHepPar-1 (hepato\u00ad\ncyte paraffin-1, \nHP1)\nMitochondrial protein\n(Cytoplasm, coarsely \ngranular)\nLiver\nHCC, some cases of gastric \nadenocarcinoma, \nesophageal adenocarci\u00ad\nnoma, others negative or \nonly rarely positive\nHCC (80\u201395%) vs. metastatic \ncarcinomas to the liver", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_139.png", "summary": "This page discusses the use of immunoperoxidase studies for special staining in pathology, focusing on markers like FLI-1, Galectin-3, GFAP, GLUT-1, GCDFP-15, and HepPar-1.", "questions": [ "How can FLI-1 be used to identify Ewing's sarcoma/PNET and vascular tumors?", "What is the significance of Galectin-3 expression in thyroid carcinomas?", "How is GFAP used to identify neural differentiation in tumors?", "What types of carcinomas show positive staining for GLUT-1?", "In what types of tumors is HepPar-1 expression commonly seen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 140, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n122\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nHBME-1\nAntigen to microvilli \non mesothelioma \ncells \n(Membrane and \ncytoplasm)\nMesothelial cells, epithelial cells\nMesotheliomas (epithelial type - \nthick, membrane staining), \nadenocarcinomas, chordo\u00ad\nmas, chondrosarcomas\nPositivity higher in thyroid carci\u00ad\nnomas than in adenomas\nMay be absent in thyroid \ncarcinomas with Hurthle cell \nfeatures\nNot a specific marker for \nmesotheliomas\nHER-2/neu \n(c-erbB2, A0485, \nSp3)\nGrowth factor recep\u00ad\ntor (tyrosine kinase) \nhomologous to \nepidermal growth \nfactor receptor\n(Membrane, some \ncytoplasm)\nAbsent or rare in normal cells\nBreast carcinomas (20 to 30%), \nPaget disease of nipple \n(>90%), less frequently in \nother carcinomas (ovary, \nuterus, GI, pancreas), some \nsynovial sarcomas\nPoor prognostic factor in breast \ncancer\nMembrane positivity used to \nselect patients for treatment \nwith Herceptin (scored from 0 \nto 3+) (see separate table)\nOnly membrane \u00adpositivity \nis scored. Gene \n\u00adamplification (detected \nby FISH) correlates \nwith strong \n\u00adcomplete membrane \n\u00adimmunoreactivity in \n>90% of cases\nHHV8\nLatent nuclear \nantigen of human \nherpes virus type 8\n(Nucleus)\nAbsent in normal tissue\nKS (endothelial cells and some \nperivascular cells)\nPrimary effusion lymphoma \n(PEL), AIDS-associated multi\u00ad\ncentric Castleman\u2019s disease\nEvaluation of KS and PEL\nHMB-45 (E-MEL, \nmelanoma spe\u00ad\ncific antigen)\nOligosaccharide side-\nchain of a mela\u00ad\nnosomal antigen, \ngp100/pmel17\n(Cytoplasm)\nFetal melanocytes and some \nnormal adult superficial \nmelanocytes, retinal pigment \nepithelium\nMelanoma (epithelioid but not \nspindle cell or desmoplastic \ntype), clear cell sarcoma, \nPEComa, tumors associated \nwith tuberous sclerosis, \nmelanotic schwannoma, \nothers\nID of metastatic melanoma. \nMelanophages can also be \npositive. Melan-A may be \nmore specific.\nID of PEComa.\nNKI-betab detects the \nsame protein.\nTissues fixed in B5 may \nhave high background \nstaining\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_140.png", "summary": "The page discusses various immunoperoxidase studies, including markers like HBME-1, HER-2/neu, HHV8, and HMB-45, their antigens, normal cells and tissues they are found in, associated tumors, and their uses.", "questions": [ "What are some tumors that show positivity for HBME-1?", "How is HER-2/neu used as a prognostic factor in breast cancer?", "What is the significance of HHV8 in the evaluation of KS and PEL?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 141, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n123\nContinued\nhMLH1 (human \nmutS homologue \n2), hMSH2 \n(human mutL \nhomologue 1), \nMSH6, PMS2\nProteins involved in \nmismatch repair of \nDNA (the first two \ngenes account for \n95% of HNPCC)\n(Nucleus)\nMost normal tissues\nMay be lost in areas of chronic \ninflammation\nExpression (or non-\nexpression) is not specific \nfor tumor type\nAbsence is associated with \ngermline mutations in \nHNPCC patients and with \ngene \u00adsilencing by methyla\u00ad\ntion in 15% of sporadic colon \ncarcinomas \u2013 correlated with \ncharacteristic clinical, patho\u00ad\nlogic, and treatment response \nfeatures\nIHC will not detect the 5% of \npatients with mutations in \nother genes or rare patients \nwith mutated gene products \nthat are immunoreactive\nOther assays for microsat\u00ad\nellite instability utilize \nPCR (90% sensitive for \nMSI)\nHormones \n(ER and PR are \nlisted separately)\nInsulin, gastrin, gluca\u00ad\ngon, somatostatin, \ncalcitonin, ACTH, \nFSH, LH, PRL, TSH, \nothers \n(Cytoplasm)\nHormone-producing cells\nHormone-producing tumors\nID of hormone products in \ntumors.\nMay not correlate well \nwith serum levels of the \nsame markers.\nHuman chorionic \ngonado tropin \n(hCG, B-HCG)\nBeta chain of the \nhormone\n(Cytoplasm)\nSyncytiotrophoblasts\nChoriocarcinoma, giant cells \nin seminomas, placental site \ntumors (weak)\nID of trophoblastic differentia\u00ad\ntion in tumors\nHuman placental \nlactogen (HPL, \nhPL)\nHormone\n(Cytoplasm)\nTrophoblast\nChoriocarcinoma (may be \nweak), complete moles \n(strong), partial moles \n(weak), some lung and stom\u00ad\nach carcinomas\nID of trophoblastic differentia\u00ad\ntion in tumors.\nInhibin\u2014 alpha \nsubunit\nHormone pro\u00ad\nduced by ovarian \ngranulosa cells and \nprostate, inhibits \nFSH production\n(Cytoplasm)\nOvarian granulosa cells, Sertoli \ncells, pregnancy luteomas, \novarian follicles, syncytio\u00ad\ntrophoblast, adrenal cortex, \nhepatocytes\nGranulosa cell tumors, juvenile \ngranulosa cell tumors, Ser\u00ad\ntoli and Leydig cell tumors, \novarian stromal cells around \nother tumors, hydatidiform \nmoles, choriocarcinoma, \nthecofibroma, adrenal \ncortical tumor, granular cell \ntumor\nID of sex cord stromal \n\u00addifferentiation in ovarian \ntumors.\nDistinguishes adrenal cortical \ntumors (>70% +) vs. HCC \n(<5% +) and RCC (<5% +)\nINI-1 (BAF47/Snf5)\nChromatin remodel\u00ad\ning complex\n(Nucleus)\nAll normal cells\nDeleted or mutated in pediat\u00ad\nric rhabdoid tumors (tumors \nare negative) and CNS \natypical teratoid/rhabdoid \ntumors\nLost in 90% of epithelioid \nsarcomas (conventional and \nproximal) and lost in 50% of \nepithelioid MPNST\nID of rhabdoid tumors and atypi\u00ad\ncal teratoid/rhabdoid tumors", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_141.png", "summary": "The page discusses various special studies including immunoperoxidase studies for proteins involved in DNA mismatch repair, hormone assays, and INI-1 chromatin remodeling complex.", "questions": [ "How can the absence of hMLH1 and hMSH2 proteins be correlated with clinical, pathologic, and treatment response features?", "What are the implications of IHC not detecting mutations in other genes or rare patients with immunoreactive gene products?", "How is INI-1 used in identifying rhabdoid tumors and atypical teratoid/rhabdoid tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 142, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n124\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nKeratins\n\u00adIntermediate \n\u00adfilaments \n(\u00adCytoplasm)\nEpithelial cells\nCarcinomas, mesotheliomas, \ndesmoplastic small round \ncell tumors (dot-like \u00adpattern), \n\u00adthymomas, \u00adchordomas, \nsynovial sarcomas, epithe\u00ad\nlioid sarcoma, leiomyosar\u00ad\ncoma, \u00adtrophoblastic tumors, \nsome \u00adother sarcomas, rarely \n\u00admelanomas\nID of poorly differentiated carci\u00ad\nnomas\nCytokeratins 7 and 20 can be \nused to help identify the site \nof origin of carcinomas\nAE1/AE3\nTwo monoclonal anti\u00ad\nbodies. AE1 detects \n10, 15, 16, and 19. \nAE3 detects 1 to 8.\n(Cytoplasm)\nEpithelial cells, mesothelial cells\nMost carcinomas. The only \ncommon carcinomas that \nare frequently negative are \nHCC (70% negative) and \nRCC, clear cell type (20% \nnegative)\nEpithelioid \n\u00adhemangioendothelioma, \nepithelioid sarcoma, \u00adsynovial \nsarcoma, \u00admesothelioma, \nadenomatoid tumor, germ \ncell tumors\nID of epithelial differentiation in \ntumors\nHCC (\u2013/+) versus cholangio\u00ad\ncarcinoma and metastatic \ncarcinomas (+)\nGood broad spectrum \nkeratin\nCAM 5.2\n8, 18\n(Cytoplasm)\nSimple and glandular epithelium\nMost carcinomas \u00adincluding \nthose usually negative \nfor Ck7 and 20: HCC, \n\u00adprostatic carcinoma, thymic \n\u00adcarcinoma, gastric \u00adcarcinoma, \nrenal cell \u00adcarcinoma, small \ncell \u00adcarcinoma\nCarcinoid tumor, thymoma, \ngerm cell tumors, mesothe\u00ad\nlioma, dendritic cells\nSynovial sarcoma, epithelioid \nsarcoma\nMany squamous cell carcino\u00ad\nmas are negative\nID of carcinomas that may be \nnegative for Ck7 and Ck20\nPaget disease (+) versus squa\u00ad\nmous cell carcinoma (-)\nPositivity for dendritic cells in \nlymph nodes and elsewhere \nmay be confused for micro\u00ad\nmetastases\nMay be positive when \nother keratins are nega\u00ad\ntive\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_142.png", "summary": "This page discusses the use of immunoperoxidase studies, specifically focusing on general markers such as keratins and their role in identifying poorly differentiated carcinomas.", "questions": [ "How can cytokeratins 7 and 20 be used to help identify the site of origin of carcinomas?", "What are some common carcinomas that are frequently negative for AE1/AE3?", "What is the significance of CAM 5.2 in identifying carcinomas that may be negative for Ck7 and Ck20?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 143, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n125\nContinued\nKeratin 5/6\n5/6\n(Cytoplasm)\nBasal cells, stratum spinosum of \nepidermis, mesothelial cells\nSquamous cell carcinomas, \nTCC, epithelioid mesothelio\u00ad\nmas, squamous metaplasia \nin adenocarcinomas, thymic \ncarcinoma\nLess frequently present in \n\u00adnon-squamous cell carcino\u00ad\nmas\nEpithelioid mesothelioma (+) vs. \npulmonary adeno (\u2013)\nPresent in some \u201ctriple negative\u201d \nbreast cancers \u2014 may identify \na poor prognostic group\nHas limited use in routine \npractice\nKeratin 7\n7 \n(Cytoplasm)\nSimple epithelia, respiratory \nepithelium, transitional \n\u00adepithelium, endothelial cells of \nsmall veins and lymphatics\nNot present in squamous \n\u00adepithelium\nMost adenocarcinomas of \nglandular epithelial origin, \nTCC, mesothelioma, neuro\u00ad\nendocrine neoplasms\nNot Merkel cell carcinoma or \ncolon carcinoma\nRare in clear cell RCC (but \npresent in other variants), \nprostate carcinoma, HCC, \nlung small cell carcinoma, \nthymoma, carcinoid\nNot present in squamous cell \ncarcinomas of the skin, but \nmay be present in squamous \ncell carcinomas arising from \nnon-keratinizing epithelium \n(e.g., cervical carcinoma)\nThe combination of Ck7 and \nCk20 is used to distinguish \ncarcinomas arising at different \nsites (see Tables 7-3 to 7-7)\nKeratin 14\n14 \n(\u200a\u200aCytoplasm)\nSquamous cells, myoepithelial \ncells\nSquamous cell carcinomas, \nthymoma, myoepithelial \nneoplasms, oncocytic \nneoplasms (Hurthle cell \nadenoma of the thyroid), \nsome triple negative (\u201cbasa\u00ad\nloid\u201d) breast cancers\nID of keratin in spindle cell \nbreast carcinomas and other \ntriple negative breast cancers\nKeratin 20\n20\n(Cytoplasm)\nGastric foveolar epithelium, \nintestinal villi and crypt epithe\u00ad\nlium, Merkel cells, taste buds, \numbrella cells of urothelium, \nsubsets of epithelial cells\nNot present in nonepithelial cells\nColon carcinoma, Merkel cell \ncarcinoma, TCC, adeno\u00ad\ncarcinoma of the bladder, \npancreatic carcinoma, chol\u00ad\nangiocarcinoma, mucinous \novarian carcinoma, esopha\u00ad\ngeal adenocarcinoma\nMerkel cell carcinomas Ck20 \npositive, whereas most similar \ntumors are negative\nID of metastatic colon carci\u00ad\nnomas (the pattern of Ck7 \nnegative, Ck20 positive, is \nmost frequently seen in this \ncarcinoma, but can rarely be \nseen in other types)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_143.png", "summary": "The page discusses the use of immunoperoxidase studies for Keratin 5/6, Keratin 7, Keratin 14, and Keratin 20 in identifying various types of carcinomas and neoplasms.", "questions": [ "How are immunoperoxidase studies for Keratin 5/6, Keratin 7, Keratin 14, and Keratin 20 used in distinguishing different types of carcinomas?", "What are some specific types of carcinomas and neoplasms that can be identified using Keratin 5/6, Keratin 7, Keratin 14, and Keratin 20?", "Why is the combination of Ck7 and Ck20 used to distinguish carcinomas arising at different sites?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 144, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n126\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nPAN-K (MNF-\n116)\nBroad-spectrum dec\u00ad\ntection of keratins \nincluding 5, 6, 8, 17, \nand 18\n(Cytoplasm)\nEpithelial cells including simple \nepithelium and squamous cells\nDetection of keratin in all \ncarcinomas, including poorly \ndifferentiated carcinomas \n(especially spindle cell squa\u00ad\nmous cell carcinomas)\nMay be more sensitive than AE1/\nAE3 for carcinomas with myo\u00ad\nepithelial (\u201cbasal\u201d) \u00adfeatures \ndue to inclusion of the \u201cbasal\u201d \nkeratin Ck17\n34\u03b2E12 (903)\nHMW keratins includ\u00ad\ning 1, 5, 10, 14\n(Cytoplasm)\nComplex epithelia, basal cells, \nmyoepithelial cells\nTCC, cholangiocarcinoma, \nsquamous cell carcinoma, \nnon-mucinous bronchioloal\u00ad\nveolar lung carcinoma, RCC \n(papillary and chromophobe \ntypes), mesothelioma, \npapillary thyroid carcinoma, \nthymic carcinoma, lympho\u00ad\nepithelial carcinoma\nTCC (+) versus prostate \n\u00adcarcinoma (-) or RCC (-).\nProstate carcinoma (no basal \ncells) versus benign lesions \n(with some + basal cells \n\u00adpresent). Can be combined \nwith p63 for this use.\nID of keratin 14 in triple negative \n(\u201cbasaloid\u201d) breast cancers \n(Ck14 is also available sepa\u00ad\nrately).\nKi-67 (MIB-1)\nProtein found \u00adduring \nthe entire cell \ncycle but not in G0 \n(Nucleus)\nAny cycling cell\nAny cycling tumor\nUsed as a prognostic marker for \nsome tumors\nDetects number of cycling cells \nin Burkitt lymphoma and \nlarge B-cell lymphoma\nAberrant membrane and \n\u00adcytoplasmic \u00adimmunoreactivity \nis \u00adpresent in trabecular hyalin\u00ad\nizing adenoma of the thyroid \nand sclerosing \u00adhemangioma \nof the lung\nMIB-1 recognizes an \nepitope preserved in \nformalin-fixed tissue\nLaminin\nComponent of base\u00ad\nment \u00admembranes \n(Basement \n\u00admembrane)\nBasement membranes\nNerve sheath tumors, smooth \nmuscle tumors\nLoss associated with stromal \ninvasion by carcinomas\nPresent in microglandular \nadenosis of the breast.\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_144.png", "summary": "The page discusses various immunoperoxidase studies, including general markers like PAN-K and 34\u03b2E12, Ki-67 as a prognostic marker, and Laminin as a component of basement membranes.", "questions": [ "How are immunoperoxidase studies used in the detection of different types of tumors?", "What is the significance of Ki-67 as a prognostic marker for some tumors?", "How does the loss of Laminin relate to stromal invasion by carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 145, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n127\nContinued\nLysozyme (Ly)\nMuramidase (muco\u00ad\nlytic enzyme)\n(Cytoplasm)\nCirculating monocytes, some \ntissue macrophages, granulo\u00ad\ncytes, salivary gland, lacrimal \ngland, stomach and colon \nepithelial cells (inflamed or \nregenerative), apocrine glands, \nPaneth cells, some other epi\u00ad\nthelial cells\nSalivary gland tumors, \u00ad\nstomach and colon \n\u00adcarcinomas\nAML with monocytic \n\u00addifferentiation\nMarker for histiocytes but not \nspecific. May mark activated \nphagocytic macrophages.\nEvaluation of myeloid \u00adleukemias.\nNot specific for identifica\u00ad\ntion of solid tumors\nMAC 387 (L1 anti\u00ad\ngen, calprotectin, \ncalgranulin, \ncystic fibrosis \nantigen)\nThree polypeptide \nchains released \nwith activation or \ndeath of neutro\u00ad\nphils \n(Cytoplasm)\nNeutrophils, monocytes, some tis\u00ad\nsue macrophages, eosinophils, \nsquamous mucosa, reactive \nskin, synovial lining cells\nLung carcinomas (not small \ncell or carcinoid), squamous \ncell carcinomas\nHistiocytic neoplasms (but not \nLangerhans cells)\nMarker for macrophages (but \nnot as specific as CD68)\nBelongs to the S100 \n\u00adprotein family\nCells can passively take \nup antigen resulting in \nfalse positive results\nMammaglobin \n(MGB1)\nSecretory glycopro\u00ad\ntein \n(Cytoplasm)\nBreast epithelium, sweat glands, \nendocervix, endometrium\nBreast cancer (50%), endo\u00ad\nmetrioid adenocarcinoma \n(~40%), salivary gland car\u00ad\ncinoma (~20%), melanoma \n(~6%)\nID of metastatic breast cancer (+ \nin about 50%)\nMDM2 (mouse \ndouble minute 2 \nhomolog)\nA \u0007ubiquitin protein \nligase that regu\u00ad\nlates p53 stability\n(Nucleus)\nNot seen in normal cells\nLiposarcomas (>90%) and \nMPNST (60%)\nAtypical lipomatous tumor/well-\ndifferentiated liposarcoma \nand dedifferentiated liposar\u00ad\ncoma (>90% +) vs. \nbenign adipose tumors \n(<5% +)\nCDK4 has a similar pattern\nMELAN-A or \nMART-1 (mela\u00ad\nnoma antigen \nrecognized by \nT cells, A103, \nM2-7C10)\nMelanocyte differen\u00ad\ntiation antigen\n(Cytoplasm)\nAntibody MC-7C10 is positive in \nmelanocytes of skin, uvea, and \nretina\nAntibody A103 is also positive in \nadrenal cortex, granulosa and \ntheca cells of the ovary, Leydig \ncells\nMelanomas (but < 50% of \nspindle cell or desmoplastic \nmelanomas), PEComas\nAntibody A103 is also positive \nin adrenocortical tumors, \nLeydig cell tumor, granulosa \ncell tumor\nID of melanomas. The antibodies \nare not positive in melano\u00ad\nphages and may be more \nspecific for the detection of \nmicrometastases in lymph \nnodes.\nAntibody A103 distinguishes \nadrenocortical tumors \n(\u226550% +) vs. HCC (-) and \nRCC (-).\nMore sensitive than \nHMB45\nPeptides are used for \nmelanoma immuno\u00ad\ntherapy \nA103 has a broader \nspectrum of immuno-\u00ad\nreactivity than MC-7C10", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_145.png", "summary": "The page discusses various immunoperoxidase studies including markers like Lysozyme, MAC 387, Mammaglobin, MDM2, and Melan-A/MART-1 for differentiating cell types and identifying specific tumors.", "questions": [ "How do the markers discussed on this page help in the identification of specific cell types and tumors?", "What are the limitations or potential pitfalls associated with using immunoperoxidase studies for tumor identification?", "Why is MELAN-A or MART-1 considered more sensitive than HMB45 for identifying melanomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 146, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n128\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nMITF (microphthal\u00ad\nmia transcription \nfactor, Mit-f, D5, \nMiTF)\nBasic-helix-\u00adloop-\nhelix-leucine zipper \ntranscription factor \nthat regulates \ntyrosinase and \nother melanogenic \nproteins\n(Nucleus)\nMelanocytes, pigmented cells \nof the retina, mast cells, \nosteoclasts\nMelanoma, PEComa, \n\u00adangiomyolipoma, clear \ncell sarcoma\nMelanoma vs. other tumors \u2013 \nnot as specific as other mela\u00ad\nnoma markers (also present in \nother tumors)\nMutations result in autoso\u00ad\nmal dominant Waarden\u00ad\nburg syndrome type 2a \n(hereditary deafness \nand skin hypopigmen\u00ad\ntation)\nMUC2 and MUC1\nMucins\n(Cytoplasm)\nMUC1 is typical of pancreaticobili\u00ad\nary-type differentiation \nand MUC2 of intestinal \n\u00addifferentiation\nMany adenocarcinomas\nIdentification of colonic \nmetastases (expression more \nconmmon than in lung or \novary)\nFor pancreatic/ampullary \ntumors, MUC2 positive tumors \nmay have better prognosis \nthan MUC1 tumors\nCholangiocarcinoma (MUC1 \n80%) vs. HCC (negative)\nIPMN is usually MUC2+/MUC1\u2013, \nmost PanIN are MUC2-/\nMUC1+, ductal adenoca is \nMUC1+ except colloid type \nwhich is MUC2+\nMUC2 is a marker of \nintestinal cells \u2013 similar \npattern as CDX2\nMyf-4 (MRF4, myo\u00ad\ngenin)\nHuman homologue of \nmyogenin - muscle \nregulatory protein\n(Nucleus)\nStriated muscle\nRhabdomyosarcoma\nID of skeletal muscle differentia\u00ad\ntion in tumors\nBetter than MyoD1\nMyoD1\nNuclear phosphopro\u00ad\ntein, role in myo\u00ad\ngenic regulation\n(Nucleus)\nDeveloping muscle tissues (myo\u00ad\nblasts), adult muscle is negative\nRhabdomyosarcoma (espe\u00ad\ncially poorly differentiated \ntumors), mixed Mullerian \ntumors\nID of skeletal muscle differentia\u00ad\ntion in tumors\nBackground positivity \nis often high, making \ninterpretation difficult\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_146.png", "summary": "This page discusses various immunoperoxidase studies including markers such as MITF, MUC2, MUC1, Myf-4, and MyoD1, their locations, normal cells and tissues they are found in, associated tumors, and their uses.", "questions": [ "How do mutations in MITF relate to Waardenburg syndrome type 2a?", "What are the differences in expression patterns of MUC2 and MUC1 in pancreatic/ampullary tumors?", "Why is Myf-4 considered better than MyoD1 in identifying skeletal muscle differentiation in tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 147, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n129\nContinued\nMyoglobin\nOxygen-binding \nprotein\n(Cytoplasm)\nStriated muscle (including cardiac \nmuscle), not smooth muscle\nTumors of striated muscle \n(rhabdomyosarcoma + 50%), \nbut often negative in poorly \ndifferentiated tumors\nID of skeletal muscle differentia\u00ad\ntion in tumors\nMore specific but less \nsensitive than actin and \ndesmin\nMyosin \u2013 smooth \nmuscle myosin \nheavy chain \n(SM-MHC; SMMS-\n1, M3558)\nContractile protein \nin smooth muscle \nthat interacts with \nactin \n(Cytoplasm)\nVisceral and vascular smooth \nmuscle, myoepithelial cells of \nthe breast\nTumors with myoepithelial \ncells\nMarker for myoepithelial cells \nin the breast \u2013 may have less \npositivity in vascular smooth \nmuscle cells and myofibro\u00ad\nblasts\nAntibodies to different \nisoforms will detect dif\u00ad\nferent types of muscle \nfibers\nMyosin \u2013 fast \nmyosin (MY-32, \nM4276)\nContractile protein \nin skeletal muscle \nthat interacts with \nactin \n(Cytoplasm)\nStriated muscle - Type 2 fibers \n(not present in cardiac or \nsmooth muscle)\nRhabdomyosarcoma (some; \nespecially pleomorphic \nvariant)\nID of skeletal muscle differentia\u00ad\ntion in tumors\nNANOG\nEmbryonic stem cell \ntranscription factor\n(Nucleus)\nEmbryonic cells\nEmbryonal carcinoma, \n\u00adseminoma, CNS \u00adgerminoma\nSeminoma and embryonal \ncarcinoma vs. other germ cell \ntumors\nMay detect \u201cstem cells\u201d in tumors\nStronger and more \ndiffusely positive \ncompared to OCT3/4. \nNamed after Tir Na Nog, \nthe mythologic Celtic \nland of eternal youth\nNestin\nIntermediate \u00adfilament\n(Cytoplasm)\nNeural stem/progenitor cells, \nembryonic neural cells, \n\u00adneuronal and glial cells\nRetina, striated muscle, cardiac \nmuscle, skin, liver, pancreas, \nkidneys, testes, adrenals\nNeurocytomas, \n\u00adneuroblastomas, gliomas, \nglioblastomas, astrocyto\u00ad\nmas, ependymomas, medul\u00ad\nloblastomas, Schwannomas \nCarcinomas, GIST, others\nNeuN (NEUronal \nNuclei, A60)\nDNA binding neuron-\nspecific protein \nexpressed at termi\u00ad\nnal \u00addifferentiation\n(Nucleus)\nNeuronal cells including \n\u00adcerebellum, cerebral cortex, \nperipheral ganglion cells\nNot glia, pineocytes, Schwann \ncells\nCentral neurocytomas\nMay be focally positive in other \nCNS neoplasms\nID of neuronal differentiation\nNeurofilaments \n(70 + 200kD, NFP)\nIntermediate \n\u00adfilaments with \nthree subunits\n(Cytoplasm)\nNeuronal cells, adrenal medulla\nTumors of neuronal \u00adorigin or \nwith \u00adneuronal \u00addifferentiation, \n\u00adneuroblastoma, medullo\u00ad\nblastoma, retinoblastoma, \nEwing\u2019s/PNET, esthesio\u00ad\nneuroblastoma, Merkel cell \ncarcinoma, some endocrine \ntumors (carcinoids, pheochro\u00ad\nmocytomas)\nID of neuronal differentiation in \ntumors\nID of Merkel cell carcinomas", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_147.png", "summary": "The page discusses various immunoperoxidase studies related to myoglobin, myosin, NANOG, Nestin, NeuN, and neurofilaments, highlighting their roles in differentiating various types of muscle and neuronal cells in tumors.", "questions": [ "How do myoglobin immunoperoxidase studies aid in identifying tumors of striated muscle?", "What is the significance of myosin immunoperoxidase studies in detecting smooth muscle differentiation in tumors?", "How does the expression of NANOG and Nestin help in identifying specific types of tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 148, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n130\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nNeuron- specific \nenolase \n\u00ad(NSE \u2013 do not \nconfuse with \nthe enzyme \n\u00adnon-specific \nesterase)\nGamma-gamma eno\u00ad\nlase \u00adisoenzyme\n(Cytoplasm)\nNeuroectodermal and \n\u00adneuroendocrine cells, more \nweakly striated and smooth \nmuscle, megakaryocytes, \nT cells, some platelets, neurons, \npituitary cells, hepatocytes\nNeuroectodermal and neuro\u00ad\nendocrine tumors, melano\u00ad\nmas (including desmoplastic \nmelanomas), many breast \ncarcinomas, germ cell \ntumors, alveolar soft part \nsarcoma\nID of neuronal or neuroendo\u00ad\ncrine differentiation in tumors\nLacks specificity\nOCT4 (OCT3, \nOCT3/4, POU5F1)\nPOU-domain \n\u00adtranscription \u00adfactor \n(POU5F1 gene)\n(Nucleus)\nEmbryonic stem cells and \n\u00adpluripotent germ cells\nSeminoma, intratubular germ \ncell neoplasia, embryonal \ncarcinoma\nIdentification of seminoma and \nembryonal carcinoma. Other \nepithelioid and round cell \nneoplasms are negative\nMore specific than PLAP \nfor this purpose\nOLIG2\nMember of the basic \nhelix-loop-helix \ntranscription \u00adfactor \nfamily\n(Nucleus)\nOligodendrocytes\nDiffuse glioma (100%), may \nbe positive in other CNS \ntumors. Sparse positivity in \nependymomas\nT-ALL with OLIG2 \u00adtranslocation\nPrimary CNS tumor (+) vs. \nmetastasis (-)\np16 (MTS1, CDKN2)\nBinds to and inhib\u00ad\nits the cyclin-\ndependent kinases \ncdk4 and cdk6 \n\u00ad(Cytoplasm and \nnucleus)\nAbsent\nCervical squamous cell carcino\u00ad\nmas and \u00adadenocarcinomas \n(both in situ and invasive), \n\u00adendocervical carcinoma, \nendometrial carcinoma\nSome basaloid squamous cell \ncarcinomas of the tonsil \nin young patients that are \nassociated with HPV16.\nEvaluation of cervical lesions\nPossible use predicting tonsillar \nsite for metastatic squamous \ncell carcinoma of the head \nand neck\nOverexpression is due to \nHPV-induced cell cycle \ndysregulation\np53 (multiple \nantibodies to wild \ntype and mutant \nforms)\nTumor \u00adsuppressor \ngene product \u2013 \nprobably most \nfrequently mutated \ngene in malignancy\n(Nucleus)\nOverexpression uncommon \nor absent in normal cells or \nbenign tumors\nMany malignant tumors \u2013 but \nnot specific for malignancy\nOverexpression may be used as \na prognostic factor\nDifferent antibodies \n\u00adrecognize different wild \ntype and mutant forms \nof the protein and will \ngive different results\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_148.png", "summary": "The page discusses various immunoperoxidase studies including markers like Neuron-specific enolase, OCT4, OLIG2, p16, and p53, their normal cells and tissues, associated tumors, and uses in pathology.", "questions": [ "What are some examples of tumors that can be identified using Neuron-specific enolase?", "How is OCT4 used in identifying specific types of tumors?", "What is the significance of p53 overexpression in malignancy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 149, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n131\nContinued\np57 (kip2, p57KIP2)\nCyclin-dependent \nkinase inhibitor \n(CDKI) acting to \ninhibit cell prolif\u00ad\neration, paternally \nimprinted\n(Nucleus)\nCytotrophoblast, intermediate \ntrophoblast, villous stromal \ncells, decidual stromal cells, \nabsent in syncytiotrophoblast\nDiploid complete moles show \nabsent or low expression in \ncytotrophoblast and villous \nstromal cells (may be pres\u00ad\nent in villous intermediate \ntrophoblast and decidual \nstromal cells), partial moles \nand hydropic abortions have \nnormal expression\np63\nProtein with at \nleast six major \nisotypes, includ\u00ad\ning delta\u00adNp63, \nmember of the p53 \nfamily\n(Nucleus)\nProliferating basal cells of cervix, \nurothelium, prostate, and myo\u00ad\nepithelial cells of breast, basal \nsquamous cells, \u00adsquamous \nmetaplasia\nSquamous cell \u00adcarcinomas, \nTCC, adenomyoepithelioma, \nadenoid cystic carcinoma, \nnasopharyngeal carcinoma, \n\u201cbasal type\u201d breast carcino\u00ad\nmas, papillary carcinoma of \nthe thyroid, others\nID of myoepithelial cells in \nbreast lesions\nDiagnosis of prostatic \u00adcarcinoma \nby showing absence of basal \ncells (more sensitive when \ncombined with 34BE12)\nBasaloid squamous lung \u00adcancer \n(+) vs. small cell (-)\nID of metastatic poorly \n\u00addifferentiated squamous \ncell carcinomas\nEasier to interpret than \nSMA in breast lesions \nas myofibroblasts are \nnegative\nPlacental alkaline \nphosphatase \n(PLAP)\nAlkaline \u00adphosphatase \nsecreted by \n\u00adtrophoblast\n(Cytoplasm)\nPlacenta (trophoblast)\nGerm cell tumors (but not \nspermatocytic seminoma), \nintratubular germ cell \nneoplasia, partial moles, \nsome carcinomas of breast, \novary, lung, stomach, and \npancreas, some rhabdomyo-\nsarcomas (esp. alveolar type)\nAbsence of immunoreactiv\u00ad\nity makes a germ cell tumor \nunlikely. However, spermato\u00ad\ncytic seminomas and imma\u00ad\nture teratomas are negative.\nID of intratubular germ cell \nneoplasia.\nProgesterone \nreceptor (PR, \nPgR, PgR636)\nSteroid binding \nprotein\n(Nucleus)\nNormal breast epithelial cells, \nendometrial cells, many \nsmooth muscle cells, breast \nlobular stroma\nBreast carcinomas, gyneco\u00ad\nlogic carcinomas, some skin \nadnexal tumors, secretory \nmeningiomas, endometrial \nstromal sarcomas, some \nleiomyomas, myofibroblastic \ntumors, rarely other \ntumors\nPrognosis and treatment of \nbreast cancer\nID of metastatic breast cancer\nPrealbumin \n(Transthyretin, \nTTR)\nPlasma transport \nprotein for retinol \nand thyroxine\n(Cytoplasm)\nPancreatic islet cells, choroid \nplexus, retinal pigment \n\u00adepithelium, liver\nPancreatic islet cell tumors, \ncarcinoid tumors, choroid \nplexus papillomas, choroid \nplexus carcinomas (may be \nfocal or absent)\nID of choroid plexus neoplasms\nEvaluation of some forms of \namyloidosis\nMajor subunit protein in \nsome forms of inherited \nsystemic amyloidosis", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_149.png", "summary": "The page discusses the use of immunoperoxidase studies for identifying specific proteins in various tissues, such as p57, p63, placental alkaline phosphatase, progesterone receptor, and prealbumin.", "questions": [ "What are the specific tissues or cells where p57 is expressed and how does its expression vary in different conditions?", "How can the identification of p63 help in diagnosing different types of cancers?", "What are the clinical implications of detecting placental alkaline phosphatase in different types of tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 150, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n132\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nProstate specific \nantigen (PSA)\nMember of kallikrein \nfamily of serine \nprotease isolated \nfrom human semi\u00ad\nnal plasma\n(Cytoplasm)\nNormal prostatic \u00adepithelium, \n\u00adurachal remnants, \n\u00adendometrium, transitional cells \nof bladder\nProstatic carcinomas, some \nbreast carcinomas\nID of prostatic carcinomas \n(may be lost in some poorly \ndifferentiated carcinomas). \nSeminal vesicle carcinomas \nare negative\nMore specific than PAP\nUsed as a serum screening \ntest for prostate cancer\nProstate acid \nphosphatase \n(PrAP, PAP)\nIsoenzyme of acid \nphosphatase\n(Cytoplasm)\nNormal prostatic epithelium, peri\u00ad\nurethral glands, anal glands, \nmacrophages\nProstatic carcinomas, TCC, \n\u00adrectal carcinoids\nID of prostatic carcinomas (may \nbe lost in some poorly differ\u00ad\nentiated carcinomas)\nRCC (Renal cell car\u00ad\ncinoma marker, \ngp200)\nGlycoprotein on \nsurface of renal \ntubules, breast \nepitethelial \ncells, \u00adepididymis \n(\u00adCytoplasm, \n\u00admembrane)\nRenal tubules, breast, epididymis\nClear cell and papillary RCC, \nbreast carcinoma, embryo\u00ad\nnal carcinoma\nClear cell and papillary RCC (+) \nvs. chromophobe carcinoma \n(\u2013/+) and oncocytoma (-)\nRET (Rearranged \nduring transfec\u00ad\ntion)\nRET-proto-\noncogene \u2013 surface \nglycoprotein \nof the receptor \ntyrosine kinase \nfamily\n(Cytoplasm)\nNeurons, embyronic kidney\nPapillary thyroid carcinomas \n(78%), follicular variant of \npapillary carcinoma (63%), \nHurthle cell carcinoma \n(57%), insular carcinoma \n(50%), medullary carcinoma, \nnot present in follicular car\u00ad\ncinomas or benign lesions\nNeuroblastoma, \n\u00adpheochromocytoma\nEvaluation of thyroid tumors\nGermline mutations \noccur in MEN2A and \n2B (10q11.2), familial \nmedullary thyroid \ncarcinoma, and some \ncases of Hirschsprung\u2019s \ndisease\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_150.png", "summary": "This page discusses various immunoperoxidase studies used in pathology, including markers like prostate specific antigen and prostate acid phosphatase.", "questions": [ "How are immunoperoxidase studies used in identifying different types of tumors?", "What are the normal cells and tissues that express the markers discussed on this page?", "Are there any specific comments or limitations mentioned for each marker?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 151, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n133\nContinued\nS-100 protein\nCalcium-binding pro\u00ad\ntein isolated from \nthe CNS (member \nof the EF hand \nfamily)\n(Nucleus and cyto\u00ad\nplasm)\nGlial and Schwann cells, melano\u00ad\ncytes, chondrocytes, adipo\u00ad\ncytes, myoepithelial cells, \nLangerhans cells, macrophages, \nreticulum cells of lymph nodes, \neccrine glands, others\nMelanoma (including spindle \ncell and desmoplastic \ntypes), clear cell sarcoma, \nschwannoma, chordoma, \nependymoma, astroglioma, \nLangerhans proliferative \ndisorders, some carcinomas \n(e.g., breast, ovary endome\u00ad\ntrial, thyroid), granular cell \ntumor, histiocytic sarcoma, \nmyoepithelioma\nID of melanoma (if negative, \nmelanoma is highly unlikely)\nID of Langerhans proliferative \ndisorders\nSustentacular cells in pheochro\u00ad\nmocytomas (loss may be poor \nprognostic factor)\nID of neural tumors\nID of cellular schwannomas \n(more strongly and diffusely \npositive than in MPNST)\nLangerhans cells and mac\u00ad\nrophages in tumors may \nbe misinterpreted as \npositivity in the tumor \nitself\nS100 is very soluble and \nmay be eluted from \nfrozen tissues\nSmoothelin\nSmooth muscle spe\u00ad\ncific cytoskeletal \nprotein\n(Cytoplasm)\nFully differentiated smooth \nmuscle cells (not present in \nnoncontractile smooth muscle \ncells or myofibroblasts), weak in \nperivascular smooth muscle\nMay distinguish muscularis \npropria (+, strong, diffuse) vs. \nmuscularis mucosaae (\u2212 or \nweak and focal) in urinary \nbladder biopsies\nSOX2\nEmbryonic stem cell \ntranscription \u00adfactor \n(Nucleus)\nEmbryonal carcinoma\nEmbryonal carcinoma (+) vs. \nseminoma (\u2013)\nSynaptophysin\nTransmembrane \n\u00adglycoprotein found \nin \u00adpresynaptic \nvesicles\n(Cytoplasm)\nNeuroectodermal and neuroen\u00ad\ndocrine cells, neurons\nMedulloblastoma, neuroblas\u00ad\ntoma, pheochromocytoma, \nparagangliomas, carci\u00ad\nnoids, small cell carcinoma, \nmedullary carcinoma of the \nthyroid, neural neoplasms, \npancreatic islet cell tumors\nID of neuroendocrine differen\u00ad\ntiation in tumors\nID of neuronal differentiation in \nCNS tumors\nSynuclein-1\nNeuron-specific \nprotein \u00adassociated \nwith \u00adsynaptosomes\n(Lewy bodies)\nBrain\nPresent in Lewy bodies \n(Lewy body dementia and \n\u00adParkinson\u2019s disease)\nTau\nMicrotubule-\u00ad\nassociated protein \n(Cytoplasm, \n\u00adextracellular)\nNormal neuronal cell bodies and \ndendrites, neuropil, glial cells\nAbnormal amounts in Alzheim\u00ad\ner\u2019s disease in neurofibrillary \ntangles and senile plaques\nEvaluation of Alzheimer\u2019s \n\u00addisease, Pick\u2019s disease, \n\u00adsupranuclear palsy cortico\u00ad\nbasal degeneration, others\nTFE3\nTranscription factor\n(Nucleus)\nNot reported\nAlveolar soft part sarcoma, \nXp11.2 or TFE3 translocation \nrenal carcinomas in children \nand young adults\nOther tumors and normal adult \ntissues are negative\nThese carcinomas have \ntranslocations involving \nthe TFE3 gene resulting \nin its overexpression", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_151.png", "summary": "This page discusses the use of immunoperoxidase studies, focusing on the S-100 protein, Smoothelin, SOX2, Synaptophysin, Synuclein-1, Tau, and TFE3 in identifying various cell types and diseases.", "questions": [ "How is the S-100 protein used in identifying different cell types and diseases?", "What role does Smoothelin play in distinguishing between different types of smooth muscle cells?", "In what conditions or diseases is Synuclein-1 typically found, and how is it useful in diagnosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 152, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n134\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nGeneral Markers\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d\nThyroglobulin\nGlycoprotein pro\u00ad\nduced by thyroid \nfollicular cells\n(Cytoplasm)\nThyroid follicles\nThyroid carcinomas (papil\u00ad\nlary, follicular, and Hurthle \ncell types, rarely present in \nmedullary carcinomas)\nID of metastatic thyroid \n\u00adcarcinoma\nLoss may be a poor prognostic \nfactor\nThyroglobulin can diffuse \ninto metastatic tumors \nto the thyroid.\nTTF-1 (thyroid \ntranscription \nfactor 1)\nTranscription factor \nfor thyroglobulin, \nthyroid peroxidase, \nClara cell secretory \nprotein, and surfac\u00ad\ntant proteins\n(Nucleus; aberrant \ncytoplasm \npositivity in HCC)\nThyroid, lung, and some brain \ntissues\nThyroid carcinomas (including \nmedullary carcinoma; may \nbe negative in anaplastic \ncarcinoma), lung adenocar\u00ad\ncinomas (75% \u2013 but lower in \nmucinous bronchioloalveo\u00ad\nlar carcinomas), small cell \ncarcinoma of lung (>90%), \nHCC (cytoplasmic), absent or \nfocal in most other adeno\u00ad\ncarcinomas\nMesothelioma (\u2013) vs. \n\u00adadenocarcinoma (+/\u2013)\nLung adenocarcinoma \n(+/\u2013) vs. metastatic breast \ncarcinoma (\u2013)\nSmall cell carcinoma of lung (+) \nvs. metastasis from other sites \n(\u2013), but some \u00adextrapulmonary \nsmall cell carcinomas can also \nbe (+)\nHCC (cytoplasmic 71%), rare in \nother tumor types\nThe detection of cytoplas\u00ad\nmic TTF-1 may depend \non the specific antibody \nused and the antigen-\nretrieval method\nTyrosinase\nMelanogenic protein \n(Cytoplasm)\nMelanocytes\nMelanoma vs. other tumors \n(sensitivity similar to MART-1 \nand HMB-45)\nUlex (Ulex \nEuropaeus I \nlectin, UEA 1)\nLectin, fucose \nresidues on blood \ngroup H \n(Cytoplasm)\nEndothelial cells\nVascular tumors, some \ncarcinomas\nEvaluation of angiogenesis\nNot very specific\nVimentin\nIntermediate \nfilament \n(Cytoplasm)\nMesenchymal cells, \nfibroblasts, endothelial cells, \nchondrocytes, histiocytes, \nlymphocytes, many glial cells, \nmyoepithelial cells, smooth \nmuscle\nAll mesenchymal tumors, \nneural tumors, melanomas, \nmeningiomas, chordoma, \nLeydig cell tumor, granulosa \ncell tumor, Sertoli cell tumor, \nadrenal cortical adenoma\nMay be co-expressed with \nkeratin in carcinomas of \nendometrium, thyroid, \nkidney (clear cell), adrenal \ncortex, lung, salivary gland, \novary, and liver\nMay be poor prognostic factor \nif co-expressed with keratin \nor GFAP\nCan be used as an internal \ncontrol for immunoge\u00ad\nnicity\nNot a specific marker for \ntumor type or line of \ndifferentation", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_152.png", "summary": "The page discusses various immunoperoxidase studies used in surgical pathology, including markers like Thyroglobulin, TTF-1, Tyrosinase, Ulex, and Vimentin, their normal cellular locations, tumor associations, and uses.", "questions": [ "How do Thyroglobulin and TTF-1 markers help in identifying thyroid carcinomas?", "What are the differences in marker expression between lung adenocarcinomas and metastatic breast carcinomas?", "Why is Vimentin not considered a specific marker for tumor type or line of differentiation?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 153, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n135\nContinued\nWT1 (Wilms tumor \n1 protein)\nZinc finger transcrip\u00ad\ntion factor \n(Cytoplasm, \nnucleus)\nSertoli cells, decidual cells \nof uterus, granulosa cells \nof ovary, blood vessels, \nmyelocytic cells\nWilms tumors (epithelial and \nblastemal components), \nepithelial mesotheliomas \n(nuclei \u2013 80% to 90%), acute \nleukemia (nuclei), adeno\u00ad\ncarcinomas (cytoplasmic; \nespecially breast (mucinous \nbreast cancers can have \nnuclear positivity (64%), \novary), desmoplastic small \ncell tumors (nuclear and \ncytoplasmic), rhabdomyo\u00ad\nsarcoma\nMesothelioma (+, nuclear) vs. \nadenocarcinoma (adenocar\u00ad\ncinoma usually negative for \nnuclear positivity except for \novarian) \u2013 use mouse mono\u00ad\nclonal antibody\nDesmoplastic small cell \ntumors\nGene located on 11p13 \nand is inactivated in 5 to \n10% of sporadic Wilms \ntumors and nearly \n100% of Denys-Drash \nsyndrome patients\nABs detect epitopes at \ndifferent ends of the \nprotein and may give \ndifferent results. Not \nvery specific.\nHematopathology Markers\nALK protein \n(Anaplastic \nlymphoma \nkinase, ALK-1, \np80, CD246)\nThe ALK gene (2p23) \n(a tyrosine kinase \nreceptor) \nis translocated \nto part of the \nnucleophosmin \n(NPM) gene (5q35) \nto form the fusion \nprotein p80 and is \noverexpressed\n(Cytoplasm, nucleus)\nNervous system, T cells\nAnaplastic (CD30+) large cell \nlymphomas (about one third \nhave t[2;5][p23; q35]). ALK \nnegative anaplastic lympho\u00ad\nmas may have trisomy 2.\nSome inflammatory myofibro\u00ad\nblastic tumors\nID of anaplastic large cell \nlymphomas\nThe pattern of \nimmunoreactivity varies \nwith the translocation \npresent\nAlpha-1-\nantichymo-\ntrypsin (ACH)\nSerine protease \ninhibitor\n(Cytoplasm)\nHistiocytes, granulocytes, others\nHistiocytic tumors, many \nadenocarcinomas, \nmelanomas, many sarcomas\nMarker for histiocytes but CD68 \nis more specific\nNot specific for tumor type\nAlpha-1-\nantitrypsin (AAT, \nalpha-1-AT)\nGlycoprotein \nsynthesized in the \nliver that inhib\u00ad\nits proteolytic \nenzymes (espe\u00ad\ncially elastase)\n(Cytoplasm)\nHistiocytes, reticulum cells, mast \ncells, Paneth cells, salivary \ngland\nHCC, germ cell tumors, histio\u00ad\ncytic neoplasms, colon and \nlung carcinomas, others\nAccumulates in liver cells in AAT \ndeficiency\nNot specific for tumor type\nCD68 is a more specific \nmarker for macro\u00ad\nphages", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_153.png", "summary": "The page discusses the use of immunoperoxidase studies for detecting specific proteins in various cells and tumors, including WT1, ALK protein, Alpha-1-antichymotrypsin, and Alpha-1-antitrypsin.", "questions": [ "How do immunoperoxidase studies help in identifying specific proteins in different cell types and tumors?", "What are the implications of the gene inactivation of WT1 in Wilms tumors and Denys-Drash syndrome patients?", "Why is CD68 considered a more specific marker for macrophages compared to Alpha-1-antichymotrypsin and Alpha-1-antitrypsin?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 154, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n136\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nHematopathology Markers\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d\nBcl-2\nProtein involved in \ninhibition \nof apoptosis\n(Membrane, \ncytoplasm)\nMedullary lymphocytes and \nepithelial cells of the normal \nthymus, mantle and T zone \nsmall lymphocytes\nCLL, mantle cell lymphoma, \nfollicular center cell (FCC) \nlymphoma, marginal zone \nlymphoma\nSynovial sarcoma, other soft \ntissue tumors\nFCC lymphomas (+) vs. reac\u00ad\ntive follicles (\u2013). Hyperplastic \nmarginal zones of the \nspleen, abdominal LNs, and \nilial lymphoid tissue are (+)\nMalignant thymomas may have \ngreater reactivity than other \nthymomas\nSynovial sarcoma is more \nfrequently positive \ncompared to mesothelioma\nInvolved in the t(14;18) \nfound in 90% of FCC \nlymphomas\nNot specific for ID of solid \ntumors\nBcl-6\nProto-oncogene \u2013 \nKruppel-type zinc \nfinger protein with \nhomology to tran\u00ad\nscription factors \n(Nucleus)\nNormal germinal center B cells\nFollicular lymphomas, diffuse \nlarge B-cell lymphomas, \nBurkitt lymphoma, \nmediastinal large B-cell \nlymphoma, LP HD\nNot present in B-CLL, hairy cell \nleukemia, mantle cell lym\u00ad\nphoma, and marginal zone \nlymphomas\nEvaluation of B-cell lymphomas\nInvolved in gene \nrearrangements at \n3q27 in lymphomas\nBlood group \nantigens\nA, B, and H antigens\n(Membrane)\nEpithelial cells, endothelial cells, \nerythrocytes\nAbnormally expressed or lost \nin many carcinomas\nSometimes helpful in \nidentifying specimens\nH is diminished by \ndecalcification but not \nA and B antigens\nBOB.1 (B-cell \nOct-binding \nprotein 1)\nCoactivator that \ninteracts with \nOct transcription \nfactors in B cells \n(Cytoplasm)\nB cells (including plasma cells)\nB-cell lymphomas and leuke\u00ad\nmias\nReed-Sternberg cells in LP HD, \nusually absent in other HD \ntypes\nEvaluation of HD\nBOB.1 and Oct2 are neces\u00ad\nsary (but not sufficient) \nfor Ig expression\nBSAP (B-cell \nspecific activator \nprotein, Pax-5)\nTranscription factor \nencoded by the \nPax-5 gene that \nregulates B-lineage \nspecific genes \n(? Nuclear)\nB cells\nAll B-cell neoplasms and HD\nMerkel cell tumors and pulmo\u00ad\nnary small cell carcinomas \nhave been reported to be \npositive\nNot reliable in Zenker\u2019s \nfixed tissue", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_154.png", "summary": "The page discusses various immunoperoxidase studies including markers like Bcl-2, Bcl-6, blood group antigens, BOB.1, and BSAP, their normal locations, associated tumors, and uses in pathology.", "questions": [ "How do Bcl-2 and Bcl-6 differ in terms of their locations and associated tumors?", "What is the significance of blood group antigens in identifying carcinomas?", "Why are BOB.1 and Oct2 considered necessary for Ig expression in B-cell lymphomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 155, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n137\nContinued\nCD1a (T6)\nMembrane \nglycoprotein\n(Membrane)\nCortical thymocytes (immature \nT cells), Langerhans cells, den\u00ad\ndritic cells\nLangerhans proliferative \ndisorders, lymphoblastic \nlymphoma\nEvaluation of Langerhans prolif\u00ad\nerative disorders\nEvaluation of lymphoblastic \nlymphoma\nCD2 (TE, T11, rT3, \nLeu 5a + b, LFA-2)\nGlycoprotein mediat\u00ad\ning adhesion of \nactivated T cells \nand thymocytes \nwith antigen \npresenting cells \nand target cells, \nfunctions in E \nrosette formation \n(Membrane)\nT cells, NK cells, cortical \nthymocytes\nT-cell neoplasms, may be aber\u00ad\nrantly lost in peripheral T-cell \nneoplasms\nPan T-cell marker\nCD3 (T3)\nC3 \u0007antigen (five \npolypeptide \nchains) \n(Membrane, \ncytoplasm)\nT cells, cortical thymocytes\nT-cell neoplasms, may be aber\u00ad\nrantly lost in peripheral \nT-cell neoplasms\nAnaplastic large cell \nlymphoma is often \nnegative\nBest pan T-cell marker\nIn paraffin sections, \nNK cells may also be \npositive\nCD4 (TH, T4, Leu 3)\nTransmembrane \nglycoprotein, HIV \nreceptor \n(Membrane)\nT helper/inducer cells, \nmacrophages, Langerhans \ncells\nMF, other T-cell neoplasms\nEvaluation of MF\nEvaluation of T-cell neoplasms\nCD5 (Leu 1)\nTransmembrane \nglycoprotein \n(Membrane)\nT cells and B cell subsets \n(mantle zone)\nT-cell leukemias and \nlymphomas, aberrantly \nexpressed in low-grade \nB-cell lymphomas (CLL or \nmantle cell lymphoma)\nThymic carcinoma, \nadenocarcinomas, \nmesothelioma \n(cytoplasmic)\nClassification of low-grade B-cell \nlymphomas\nEvaluation of T-cell lymphomas \n(this marker is frequently lost)\nThymic carcinoma (~40%) vs. \nthymoma (<10%) vs. pulmo\u00ad\nnary squamous cell carcinoma \n(<5%)\nCD7 (Leu 9)\nMembrane-bound \nglycoprotein \n(Membrane)\nPrecursor T cells, T cell subsets, NK \ncells, thymocytes\nT-cell lymphomas and \nleukemias\nFrequently (50%) lost in T-cell \nlymphomas versus reactive T \ncells (+)\nEvaluation of T-cell leukemias", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_155.png", "summary": "This page discusses the use of immunoperoxidase studies for evaluating various types of lymphomas and neoplasms, focusing on specific markers such as CD1a, CD2, CD3, CD4, CD5, and CD7.", "questions": [ "How are immunoperoxidase studies used in the evaluation of lymphomas and neoplasms?", "What are the specific functions and cell targets of markers CD1a, CD2, CD3, CD4, CD5, and CD7?", "Why is the loss of certain markers, such as CD5 and CD7, significant in the diagnosis of T-cell lymphomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 156, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n138\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nHematopathology Markers\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d\nCD8 (T8, Leu 2)\nTwo glycoprotein \nchains \n(Membrane)\nT cell subsets, NK cells, T \ncytotoxic/suppressor cells\nT-cell lymphomas and \nleukemias\nEvaluation of MF and T-cell \nlymphomas (this marker is \nfrequently lost)\nCD10 (CALLA \n[common \nacute leukemia \nantigen], J5, \nneprilysin)\nCell surface metal\u00ad\nloendopeptidase \nthat inactivates \npeptides \n(Membrane)\nPrecursor B cells, granulocytes, \nrare cells in reactive follicles, \nmyoepithelial cells of breast, \nbile canaliculi, fibroblasts, \nbrush border of kidney and gut\nFollicular lymphomas, pre-\nB-ALL, Burkitt lymphoma, \nCML, angioimmunoblastic \nlymphoma\nRCC (clear cell and papillary), \nHCC, rhabdomyosarcoma, \nendometrial stromal sar\u00ad\ncoma\nEvaluation of follicular center \ncell lymphomas\nEvaluation of leukemias\nMyoepithelial cell marker in \nbreast\nEndometrial stromal sarcoma (+) \nvs. leiomyosarcoma (\u2212) (but \ncaldesmon is preferred for this \npurpose)\nCD11b (Mac-1)\nCell surface recep\u00ad\ntor for the C3bi \ncomplement \nfragment \n(Membrane)\nGranulocytes, monocytes, \nmacrophages\nMyelomonocytic leukemias\nCD11c\nMember of the \nbeta(2) integrin \nfamily that medi\u00ad\nates adhesion to \nvascular endothe\u00ad\nlium, transendo\u00ad\nthelial migration, \nchemotaxis, and \nphagocytosis \n(Membrane)\nMyeloid cells, NK cells, dendritic \ncells, activated lymphoid cells\nHairy cell leukemia, B-cell \nprolymphocytic leukemia, \nsome B-CLL, marginal zone \nlymphoma (MALT)\nCD13 (My 7)\nAminopeptidase-N, \na type II inte\u00ad\ngral membrane \nmetalloprotease \nfunctioning in cell \nsurface antigen \npresentation, \nreceptor for \ncoronaviruses \n(Membrane, \ncytoplasm)\nGranulocytes, macrophages, bone \nmarrow stromal cells, osteo\u00ad\nclasts, renal tubules, intestinal \nbrush border, cells lining bile \nduct canaliculi, endothelial \ncells, fibroblasts, brain cells\nAML, CML with blast crisis, \nsome ALL\nClassification of leukemias\nRequires frozen tissue", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_156.png", "summary": "This page discusses various antibodies used in immunohistochemistry studies, including their antigens, normal cells and tissues they are found in, tumors they are associated with, and their uses in pathology.", "questions": [ "What are some examples of tumors associated with CD10?", "Why is CD11c important in evaluating certain types of leukemia?", "What is the significance of CD13 in the classification of leukemias?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 157, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n139\nContinued\nCD15 (Leu-M1)\n3-fucosyl-N-\nacetyllactosa-\nmine, X-hapten - \nCHO moiety linked \nto cell membrane \nprotein \n(Membrane and \ngranular perinuclear)\nGranulocytes, monocytes\nReed-Sternberg cells (not \nLP HD), some large T-cell \nlymphomas, MF, some \nleukemias, some epithelial \ncells (adenocarcinomas), \nCMV-infected cells\nAdenocarcinomas (+) versus \nmesotheliomas (\u2212)\nEvaluation of HD\nCD16\nLow affinity trans\u00ad\nmembrane Fc \nreceptor for IgG \n(Membrane)\nNK cells, granulocytes, activated \nmacrophages, subsets of T cells\nExtranodal NK/T-cell \nlymphoma, some \nhepatosplenic T-cell \nlymphomas\nCD19 (B4)\nB cell type I integral \nmembrane glyco\u00ad\nprotein\n(Membrane)\nB cells, follicular dendritic cells, \nearly myelomonocytic cells\npre-B-ALL and B-cell \nneoplasms (but not \nplasma cell lesions)\nGood pan B-cell marker\nFresh or frozen tissue \nrequired\nCD20 (L26, B1, \nLeu16)\nB \u0007cell non-\nglycosylated \nphosphoprotein \nfunctioning as a \nreceptor during \nB cell activation \nand differentiation \n(Membrane, \ncytoplasm)\nB cells, monocytes, not plasma \ncells\nB-cell lymphomas, Reed-\nSternberg cells in LP HD, not \nplasmacytomas\nBest pan B-cell marker\nEvaluation of B-cell lymphomas\nEvaluation of HD\nUnder investigation as a \ntarget for clinical treat\u00ad\nment of B-cell lympho\u00ad\nmas\nL26 is best for formalin-\nfixed tissue\nMay be preserved in \nnecrotic tissue\nCD21 (B2)\nType I integral \nmembrane \nglycoprotein \nfunctioning as the \nreceptor for the C3d \nfragment of comple\u00ad\nment C3, CR2, \nreceptor for EBV \n(Membrane)\nFollicular dendritic cells, mature \nB cells\nMarginal zone (MALT) lympho\u00ad\nmas, CLL (B cell), some T-cell \nALL, follicular dendritic cell \ntumors\nID of residual follicular structure \nin LP HD and other diseases\nEvaluation of low-grade B-cell \nlymphomas\nID of follicular dendritic cell \nsarcoma", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_157.png", "summary": "This page discusses various immunoperoxidase studies, including the markers CD15, CD16, CD19, CD20, and CD21, their associated cell types, and their applications in different diseases.", "questions": [ "What are the specific cell types that express CD15, CD16, CD19, CD20, and CD21?", "How are these immunoperoxidase markers used in the evaluation of Hodgkin's disease?", "What is the significance of CD20 being under investigation as a target for clinical treatment of B-cell lymphomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 158, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n140\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nHematopathology Markers\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d\nCD22 (BL-CAM)\nType I integral \nmembrane \nglycoprotein \n(Membrane. \ncytoplasm)\nB cells, precursor B cells\nB-cell neoplasms (but not \nplasma cell lesions)\nPan B-cell marker\nCD23\nMembrane \nglycoprotein, low \naffinity IgE receptor \n(Membrane)\nSubpopulation of peripheral B \ncells, follicular dendritic cells\nCLL, but usually not mantle \nzone lymphoma, Maltomas, \nor follicular lymphomas\nEvaluation of low-grade B-cell \nlymphomas\nCD25 (IL-2 receptor)\nInterleukin-2 receptor \n(Membrane, \ncytoplasm)\nSubpopulation of T cells, myeloid \nprecursors, oligodendrocytes\nHTLV-1 transformed T and B cells\nHairy cell leukemia, adult \nT-cell lymphoma/leukemia, \nsome T-cell prolympho\u00ad\ncytic leukemia, precursor \nlymphoblastic lymphoma, \nand anaplastic large cell \nlymphoma\nEvaluation of cutaneous T-cell \nlymphomas for potential anti-\nCD25 therapy\nAberrant expression by a subset \nof neoplastic mast cells\nCD30 (Ki-1, BERH2)\nSingle chain trans\u00ad\nmembrane \nglycoprotein, \nhomologous to \nthe nerve growth \nfactor superfamily \n(Cytoplasm, \nmembrane and \ngolgi)\nActivated B and T cells, some \nplasma cells, immunoblasts, \ninterdigitating cells, histiocytes, \nfollicular center cells, decidual\u00ad\nized endometrium, reactive \nmesothelial cells, most other \ntissues negative\nAnaplastic (CD30+) large cell \nlymphomas, large B-cell \nlymphoma, primary effusion \nlymphoma, mediastinal \nlarge B-cell lymphoma, \nReed-Sternberg cells (not \nLP HD), enteropathy T-cell \nlymphoma, peripheral T-cell \nlymphoma, EBV transformed \nB cells\nEmbryonal carcinoma, vascular \ntumors (not KS), some meso\u00ad\ntheliomas, rarely carcinomas \nare positive\nEvaluation of anaplastic (CD30+) \nlymphomas\nEvaluation of HD (Reed-Stern\u00ad\nberg cells are positive except \nin LP HD)\nEvaluation of peripheral T-cell \nlymphoma (large cells may be \npositive)\nCD33 (My 9)\nMyeloid specific \nreceptor (sialic \nacid\u2013binding \nimmunoglobulin-\nlike lectin or \nSiglec-3) \n(Membrane)\nGranulocytes, monocytes\nAML\nEvaluation of leukemias\nGemtuzumab ozogamicin \nis a humanized CD33 \nantibody linked to an \nantitumor antibiotic \ncalicheaminin for the \ntreatment of AML", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_158.png", "summary": "The page discusses various immunoperoxidase studies including markers like CD22, CD23, CD25, CD30, and CD33 used in hematopathology for evaluating different types of lymphomas and leukemias.", "questions": [ "What are the normal cells and tissues that express CD22?", "How is CD25 used in the evaluation of cutaneous T-cell lymphomas?", "What is the significance of CD33 expression in AML and how is it targeted for treatment?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 159, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n141\nContinued\nCD34 (HPCA-1, \nQBEnd10)\nSingle chain \n\u00adtransmembrane \nglycoprotein \n(Cytoplasm, \n\u00admembrane)\nLymphoid and myeloid hema\u00ad\ntopoietic progenitor cells, \nendothelial cells, some skin \ncells, myofibroblasts\nAcute leukemia\nNeurofibroma, \nangiosarcoma,KS, epitheli\u00ad\noid hemangioendothelioma, \nsolitary fibrous tumor, DFSP, \nepithelioid sarcoma, GIST, \nmyofibroblastic tumors\nID of endothelial or myofi\u00ad\nbroblastic differentiation in \ntumors\nEvaluation of angiogenesis\nEvaluation of the number of \nblasts in bone marrow in \nacute leukemia\nNot specific for endothe\u00ad\nlial cells\nCD35 (CR1, C3b/\nC4b R)\nTransmembrane \nprotein that binds \ncomplement \ncomponents C3b \nand C4b and medi\u00ad\nates phagocytosis \n(Membrane)\nErythrocytes, B cells, a subset of T \ncells, monocytes, neutrophils, \neosinophils, glomerular podo\u00ad\ncytes, follicular dendritic cells\nMarginal zone (MALT) \nlymphoma, follicular \ndendritic cell tumors\nDetects follicular dendritic cells\nID of follicular dendritic cell \nsarcomas\nCD38\nType II transmem\u00ad\nbrane glycoprotein \nwith enzymatic \naction for the \nformation and \nhydrolysis of cADPR \n(Membrane)\nImmature B and T lymphocytes, \nthymocytes, mitogen-activated \nT cells, Ig-secreting plasma \ncells,monocytes, NK cells, \nerythroid and myeloid progeni\u00ad\ntors, brain cells\nAcute leukemias, plasma cell \nlesions\nNeurofibrillary tangles in \nAlzheimer\u2019s disease\nID of plasma cell lesions\nImmunoreactivity may \nbe a poor prognostic \nmarker for patients with \nCLL\nCD43 (Leu 22, L60)\nCell surface \nglycoprotein \n(Membrane)\nT cells, macrophages, \ngranulocytes\nAML (chloromas), T cell neo\u00ad\nplasms, aberrant expression \nin some low-grade B-cell \nneoplasms (e.g., mantle \ncell lymphoma, SLL/CLL, \nmarginal zone lymphoma), \nsome MALT lymphomas\nEvaluation of T-cell lymphomas \nand leukemias\nEvaluation of low-grade B-cell \nlymphomas\nLess specific than UCHL-1 \nfor T cells\nCD45, Leukocyte \ncommon anti\u00ad\ngen (LCA, CLA) \nNote: CLA also \nrefers to a dif\u00ad\nferent antigen, \nHECA-452\nFive or more \nmembrane \nglycoproteins \n(Membrane, \ncytoplasm)\nLymphocytes, leukocytes, \nhistiocytes, not plasma cells, \nerythrocytes, platelets\nNon-Hodgkin\u2019s lymphomas, \nsome anaplastic (CD30+) \nlarge cell lymphomas, Reed-\nSternberg cells in LP HD (but \nnot other types)\nID of poorly differentiated \nneoplasms as lymphomas. \nHowever, some anaplastic \nlymphomas and \nplasmacytomas may be \n\u00adnegative\nPreserved in necrotic \ntissue\nBest general marker for \nhematologic neoplasms", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_159.png", "summary": "This page discusses the use of immunoperoxidase studies, specifically focusing on CD34, CD35, CD38, CD43, and CD45 markers in identifying various cell types and diseases.", "questions": [ "What are the specific cell types that CD34, CD35, CD38, CD43, and CD45 markers can identify?", "How are immunoperoxidase studies helpful in evaluating acute leukemias?", "What is the significance of CD45 as a marker for hematologic neoplasms?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 160, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n142\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nHematopathology Markers\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d\nCD45RA (DPB)\nRestricted form of \nleukocyte \ncommon antigen \n(Membrane, \ncytoplasm)\nB cells, monocytes, some T cells\nB-cell neoplasms, Hairy cells \n(not specific)\nPan B-cell marker that can be \nused in Zenker\u2019s fixed tissue\nNot completely specific - \nother B-cell markers are \npreferred\nCD45RO (UCHL-1)\nIsoform of CD45 \n(leukocyte \ncommon antigen) \n(Membrane, \ncytoplasm)\nT cells (memory), granulocytes, \nmonocytes\nT-cell neoplasms, histiocytic \nsarcoma, some B-cell \nlymphomas (plasmacytic, \nHIV-associated)\nGood pan T-cell marker (CD3 is \nmore specific)\nCD56 (NCAM)\nNeural cell adhesion \nmolecule \u2013 cell \nsurface \nglycoprotein \n(Membrane)\nNeurons, astrocytes, Schwann \ncells, NK cells, subset of \nactivated T cells\nSome T/NK-cell lymphomas, \nplasmacytomas\nNeuroblastoma\nEvaluation of panniculitis-like \nT-cell lymphoma (both CD56+ \nand CD56-) and T/NK lympho\u00ad\nmas\nCD57 (Leu 7, \nHNK-1)\nLymphocyte antigen \nthat cross reacts \nwith a myelin-asso\u00ad\nciated glycoprotein \n(Membrane)\nT cell subsets, NK cells, myelin\u00ad\nized nerves, neuroendocrine \ncells, prostate, pancreatic islets, \nadrenal medulla\nAngioimmunoblastic T-cell \nlymphoma\nNerve sheath tumors \n(occasional), leiomyosar\u00ad\ncoma, synovial sarcoma, \nrhabdomyosarcoma, \nneuroblastoma, gliomas, \nneuroendocrine carcinomas, \nneurofibromas, some pros\u00ad\ntate carcinomas\nID of T gamma lymphoprolifera\u00ad\ntive disorder (large granular \ncell lymphocytic leukemia)\nID of neuroendocrine differen\u00ad\ntiation in tumors\nEvaluation of NK neoplasms\nNot very specific for solid \ntumors\nCD61 (GPIIIa, plate\u00ad\nlet glycoprotein \nIIIa)\nGlycoprotein, recep\u00ad\ntor for fibrinogen, \nfibronectin, von \nWillebrand factor, \nand vitronectin \n(Cytoplasm)\nMegakaryocytes, platelets\nMegakaryocytic leukemias\nID of megakaryocytic \ndifferentiation", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_160.png", "summary": "This page discusses various immunoperoxidase studies, including markers such as CD45RA, CD45RO, CD56, CD57, and CD61, their antigens, normal cells and tissues they are found in, associated tumors, and uses in pathology.", "questions": [ "What are the normal cells and tissues that express CD45RA?", "How specific is CD56 as a marker for neuroblastoma?", "What is the significance of CD57 in identifying nerve sheath tumors?", "How is CD61 used in identifying megakaryocytic leukemias?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 161, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n143\nContinued\nCD68 (KP1, CD68-\nPGM1, Mac-M)\nIntracellular \nglycoprotein \nassociated with \nlysosomes \n(Cytoplasm, \nmembrane)\nMacrophages, monocytes, \nneutrophils, basophils, large \nlymphocytes, Kupffer cells, \nmast cells, osteoclasts\nSome lymphomas, histiocytic \nsarcomas, APML, Langer\u00ad\nhans proliferative disorders\nNeurofibroma, schwannoma, \nMPNST, granular cell \ntumors, PEComa, \nmelanomas, atypical \nfibroxanthoma, RCC\nBest general marker for macro\u00ad\nphages, although not specific \nto this cell type\nThe antibody PG-M1 does \nnot react with granulo\u00ad\ncytes\nCD74 (LN2)\nSubunit of MHC II\u2013\nassociated \ninvariant chain \n(Membrane)\nB cells, monocytes, histiocytes\nB-cell neoplasms, hairy cell \nleukemia, plasma cell lesions\nPan B-cell marker\nCDw75 (LN1)\nSialylated glycocon\u00ad\njugate present in \nsurface Ig-positive \nB cells \n(Membrane, \n\u00adcytoplasm)\nMature B cells, T-cell subsets, fetal \ncolon, epithelial cells\nReed-Sternberg cells of LP HD \n(not other types), follicular \nlymphomas\nColon carcinomas (50%), gas\u00ad\ntric carcinomas\nEvaluation of HD\nCD77 (BLA.36, PK \nantigen)\nGlobotriaosylce\u00ad\nramide, glycolipic \nmembrane from \nBurkitt lymphoma \ncell line \n(Cytoplasm, \nmembrane)\nTonsillar B cells, dendritic reticu\u00ad\nlum cells, sinus-lining cells, \nmacrophages, endothelial cell, \nepithelial cells\nHD, Burkitt lymphoma, \nrarely other B- and T-cell \nlymphomas\nEvaluation of RS cells\nCD79a (mb-1 \nprotein)\nHeterodimer of mb-1 \n(CD79a) and B29 \n(CD79b) polypep\u00ad\ntides, B cell antigen \nreceptor \n(Membrane)\nB cells, plasma cells\nPrecursor B-cell ALL, B-cell lym\u00ad\nphomas, plasma cell lesions, \nbut not primary effusion \nlymphoma\nEvaluation of B-cell neoplasms \n(may be the only B-cell marker \npresent)\nCD79b\nSee above \n(Membrane)\nAbsent from CLL, hairy cell \nleukemia\nCD95\nTransmembrane gly\u00ad\ncoprotein member \nof the nerve growth \nfactor receptor/\ntumor necrosis fac\u00ad\ntor superfamily \u2013 \nmediates apoptosis \n(Membrane)\nActivated T and B cells, epithelial \ncells\nPanniculitis-like T-cell lym\u00ad\nphoma (if CD56+)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_161.png", "summary": "The page discusses various immunoperoxidase studies including markers like CD68, CD74, CDw75, CD77, CD79a, CD79b, and CD95, their associated cells, and their significance in different neoplasms.", "questions": [ "What are the main cell types associated with CD68 marker?", "How is CD74 marker related to B-cell neoplasms?", "What is the significance of CD95 marker in mediating apoptosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 162, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n144\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nHematopathology Markers\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d\nCD99 (MIC-2, 12E7, \nEwing\u2019s sarcoma \nmarker, E2 anti\u00ad\ngen, HuLy-m6, \nFMC 29, O13 [dif\u00ad\nferent epitope])\nMIC2 gene product \u2013 \nglycoproteins (p30 \nand p32) involved \nin rosette forma\u00ad\ntion with \nerythrocytes \n(Membrane \n[immunoreactivity \nis more specific than \ncytoplasmic])\nCortical thymocytes, T lympho\u00ad\ncytes, granulosa cells of ovary, \npancreatic islet cells, Sertoli \ncells, some endothelial cells, \nurothelium, ependymal cells, \nsquamous cells\nB \u0007and T cell precursor lympho\u00ad\nblastic lymphoma/leukemia\nPNET/Ewing\u2019s sarcoma, \nchondroblastoma, synovial \nsarcoma, solitary fibrous \ntumors, GIST, some alveolar \nrhabdomyocarcomas, des\u00ad\nmoplastic small cell tumors, \nsmall cell carcinomas, \ngranulosa cell tumors, yolk \nsac components of germ cell \ntumors, Sertoli-Leydig cell \ntumors, atypical fibroxan\u00ad\nthoma, meningioma\nEvaluation of lymphoblastic \nlymphoma/leukemia\nThymic carcinomas \n(lymphocytes +) versus \nother carcinomas\nID of PNET/Ewing\u2019s sarcoma \n(immunoreactivity should be \nclearly membranous in the \nmajority of the cells)\nO13 is the most commonly \nused antibody\nImmunoreactivity is highly \ndependent upon the \nantigen retrieval system \nused\nCD103\nMucosal integrin \nalphaEbeta7 with \nspecificity for \ne-cadherin \n(Cytoplasm)\nT cells\nEnteropathy type T-cell \nlymphoma, hairy cell \nleukemia\nRequires frozen tissue or \ncell suspension\nCD117 (c-kit, \nstem cell factor \nreceptor)\nTransmembrane \ntyrosine kinase \nreceptor (ligand \nis stem cell \nfactor) \u2013 apoptosis \nis inhibited when \nthe ligand is bound \n(Cytoplasm, \nmembrane)\nMast cells, interstitial cells of \nCajal (ICC \u2013 pacemaker cells of \nthe GI tract found throughout \nthe muscle layers and in the \nmyenteric plexus), epidermal \nmelanocytes, mononuclear \nbone marrow cells (4%), Leydig \ncells, early spermatogenic cells, \ntrophoblast, breast epithelium\nGIST (>95%), seminomas \n(>70%), intratubular germ \ncell neoplasia, mature \nteratomas (>70%), some \nmelanomas (focal), mast cell \ntumors, some carcinomas, \nsome brain tumors, some \nPNET/Ewing\u2019s sarcoma, \nsome angiosarcomas\nAML (>50%), CML in myeloid \nblast crisis\nID of GIST (+) vs. leiomyomas (\u2212) \nand schwannomas (\u2212)\nID of seminomas\nID of mast cells (mastocytosis)\nMast cells are an excellent \ninternal control\nCD117 positivity does not \ncorrelate with muta\u00ad\ntions and/or oncopro\u00ad\ntein activity in tumors \nnot known to have \nactivating mutations \nand is, in general, not \nof clinical or therapeu\u00ad\ntic significance in this \nsetting (e.g., to detect \ntumors likely to respond \nto therapy directed \nagainst the protein (e.g., \nGleevec)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_162.png", "summary": "This page discusses special studies in pathology, specifically focusing on immunoperoxidase studies and various antibodies used in immunohistochemistry.", "questions": [ "What are some examples of tumors that can be identified using CD99 immunohistochemistry?", "Why is O13 considered the most commonly used antibody?", "What is the significance of CD117 positivity in tumors not known to have activating mutations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 163, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n145\nContinued\nCD123\nAlpha chain of the \nIL-3 receptor \n(Membrane)\nMyeloid precursors, \nmacrophages, dendritic cells, \nmast cells, basophils, \nmegakaryocytes\nPlasmacytoid dendritic cell \ntumors\nCD138 \n(Syndecan-1)\nTransmembrane \nheparin sulphate \nglycoprotein that \ninteracts with \nextracellular matrix \nand growth factors \n(Membrane)\nPre-B cells, immature B cells, \nIg-producing plasma cells, \nbasolateral surface of \nepithelial cells, vascular \nsmooth muscle, endothelium, \nneural cells\nPlasma cell lesions, primary \neffusion lymphoma, plasma \ncell component of other \nB-cell lymphomas\nSquamous cell carcinomas, \nother carcinomas\nID of plasma cells and their \nneoplasms\nExpression may be diminished \nor lost in poorly differentiated \ncarcinomas\nCD163 (M130)\nEndocytic receptor \nto scavenge \nhaptoglobin and \nhemoglobin \ncomplexes \n(Membrane, \ncytoplasm)\nTissue macrophages (high expres\u00ad\nsion), monocytes (low expres\u00ad\nsion) including Kupffer cells, \nHofbauer cells but not follicular \ndendritic cells or plasmacytoid \nmonocytes\nNeoplasms of histiocytic \ndifferentiation\nLeukemias of monocytic \ndifferentiation\nSynovial type giant cell tumors \nof the vertebral column\nLangerhans cell histiocytosis \n(~60%), benign fibrous \nhistiocytoma (~67%)\nLittoral cell angioma of the \nspleen\nID of true histiocytic derivation \nof tumors\nMore specific for \nmonocyte/histiocyte \nderivation than CD68\nCD207 (langerin)\nLangerhans cell \nspecific C-type \nlectin \n(Cytoplasm)\nLangerhans cells of epidermis and \nepithelia\nLangerhans cell histiocytosis\nInduces formation of \nBirbeck granules\nClusterin \n(Apolipoprotein \nJ, complement \nlysis inhibitor, \ngp80, SGP-2, \nSP40, TRPM2, \nT64, ApoJ)\nMultifunctional \nprotein involved \nin lipid transport, \ncomplement regu\u00ad\nlation, immune \nregulation, cell \nadhesion, other \nfunctions\n(Membrane, cyto\u00ad\nplasm, nucleus)\nMany tissues\nAnaplastic large cell \nlymphoma (Golgi pattern)\nAlzheimer\u2019s disease \u2013 pres\u00ad\nent in amyloid plaques and \ncerebrovascular deposits\nMany types of carcinomas", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_163.png", "summary": "The page discusses various immunoperoxidase studies including CD123, CD138, CD163, CD207, and Clusterin, highlighting their expression patterns and diagnostic utility in different cell types and diseases.", "questions": [ "What are the main cell types expressing CD123 and CD138?", "In which diseases are CD163 and CD207 markers particularly useful for diagnosis?", "What are the different functions of Clusterin in various tissues and diseases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 164, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n146\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nHematopathology Markers\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d\nCyclin D1 (PRAD1, \nbcl-1)\nCyclin regulating \ncyclin dependent \nkinases during G1 \nin the cell cycle, \nphosphorylates \nand inactivates the \nretinoblastoma \ntumor suppressor \nprotein\n(Nucleus)\nCycling cells (however, \nlymphocytes usually express \nonly cyclins D2 and D3)\nMantle cell lymphoma\nBreast cancer (especially \nlobular carcinomas and \nother ER positive carcino\u00ad\nmas), esophageal cancer, \nbladder cancer, lung cancer, \nHCC, colon carcinoma, \npancreatic carcinoma, head \nand neck squamous cell car\u00ad\ncinomas, pituitary tumors, \nsarcomas\nParathyroid adenomas \n(inversion involving cyclin \nD1 gene and the \nparathormone receptor)\nID of mantle cell lymphoma\nInvolved in t(11;14)\n(q13;q32) translocation \nin mantle cell lym\u00ad\nphoma\nDBA.44 (HCL)\nB-\u0007cell antigen \n(Cytoplasm, \nmembrane)\nMantle zone B cells, some \nimmunoblasts\nHairy cell leukemia (>95%), \nB-cell lymphomas (30%)\nEvaluation of hairy cell \nleukemia\nEpithelial mem\u00ad\nbrane antigen \n(EMA, MUC1, \nHMFG, DF3, \nCA 15-3, CA \n27.29, PEM, \nmany others)\nEpisialin, glycoprotein \nfound in human \nmilk fat globule \nmembranes \n(Cytoplasm [more \ncommon in \nmalignant cells], \nmembrane [more \ncommon in benign \ncells])\nEpithelial cells, perineurial cells, \nmeningeal cells, plasma cells, \nusually negative in mesothelial \ncells, monocytes\nSome anaplastic large cell \nlymphomas (CD30+), plasma \ncell neoplasms, malignant \nhistiocytosis, erythroleuke\u00ad\nmia, AML (M4 and M5), LP \nHD\nCarcinomas, mesotheliomas, \nsome sarcomas (synovial \nsarcoma, epithelioid sar\u00ad\ncoma), adenomatoid tumor, \nchordomas, perineurioma, \nneurofibroma, menin\u00ad\ngiomas, desmoplastic small \nround cell tumor, Sertoli cell \ntumor\nID of epithelial differentiation in \ntumors \u2013 however, keratin is \nmore specific for this purpose. \nBeware of EMA in some large \ncell lymphomas\nSynovial sarcoma typically \nshows focal positivity\nThere are over 50 \nmonoclonal antibodies \nrecognizing different \nglycosylation patterns \nin normal tissues and \ntumors18", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_164.png", "summary": "This page discusses special immunoperoxidase studies, including specific antibodies used for immunohistochemistry and their relevance in identifying various tumors.", "questions": [ "What is the significance of Cyclin D1 in identifying mantle cell lymphoma?", "How is the DBA.44 antibody used in the evaluation of hairy cell leukemia?", "Why is Epithelial membrane antigen (EMA) important in identifying epithelial differentiation in tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 165, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n147\nContinued\nEpstein-Barr virus\nEBV-encoded \nnonpolyade\u00ad\nnylated early \nRNAs (EBERS)\nRNA produced \nby EBV \n(Nucleus)\nEBV-infected B cells\nAll EBV-related tumors\nMost sensitive marker for EBV\nDetected by in situ hybrid\u00ad\nization for RNA on paraf\u00ad\nfin sections\nLMP-1\nLatent membrane \nprotein \n(Membrane)\nEBV-infected B cells\nNasopharyngeal carcinomas, \nReed-Sternberg cells (not LP \nHD), transplant lymphomas, \nAIDS-related lymphomas, \nendemic Burkitt lymphoma \n(rare in sporadic cases)\nEvaluation of EBV-related neo\u00ad\nplasms\nEBNA 2 (nuclear \nantigen 2)\nNuclear protein \n(Nucleus)\nEBV-infected B cells\nTransplant-related lymphomas, \nAIDS-related lymphomas. \nNot present in Burkitt lym\u00ad\nphoma or nasopharyngeal \ncarcinomas\nEvaluation of transplant- and \nAIDS-related lymphomas\nFascin\nActin bundling \nprotein regulated \nby phosphorylation \n(Cytoplasm)\nInterdigitating reticulin cells from \nthe T-cell zones, dendritic cells, \nreticular network, histiocytes, \nsmooth muscle, endothelium, \nsquamous cells, splenic sinuses\nReed-Sternberg cells (but not \nin LP HD)\nHigh-grade breast carcinomas\nID of Reed-Sternberg cells in \nclassical HD. Fascin \npositivity has also been \nreported in anaplastic \nlarge cell lymphoma\nFMC7\nAntigen on sub\u00ad\ngroups of mature \nB cells, epitope of \nCD20 \n(Cytoplasm)\nB cells\nB-cell lymphomas\nNot expressed by CLL\nPan B-cell marker\nEpitope of CD20 but reac\u00ad\ntivity low in cells with \nlow cholesterol\nGlycophorin A \n(GPA)\n A \u0007glycosylated \nerythrocyte \nmembrane protein \n(Membrane)\nErythroid elements at all stages\nErythroleukemia\nID of erythroid elements \n(normal and neoplastic)\nGranzyme B\nNeutral serine \nproteases stored \nin granules in \ncytotoxic T cells \nand in NK cells \ninvolved in target \ncell apoptosis by \nexocytosis \n(Cytoplasm)\nCytotoxic T cells and NK cells\nSome T-cell lymphomas, Reed-\nSternberg cells of some \ncases of EBV-positive HD", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_165.png", "summary": "This page discusses various special studies, including immunoperoxidase studies for Epstein-Barr virus markers and other proteins in different cell types.", "questions": [ "What are the most sensitive markers for Epstein-Barr virus?", "Which types of tumors are associated with LMP-1 expression?", "What is the significance of Fascin positivity in Reed-Sternberg cells?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 166, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n148\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nHematopathology Markers\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d\nHeavy immuno-\nglobulin chains \n(G, A, M, D)\nHeavy chain of \nimmunoglobulins \n(Cytoplasm [plasma \ncells], membrane \n[lymphocytes])\nPlasma cells (G>A>M>D)\nPlasma cell tumors (monotypic \nexpression of usually G or A),\n mantle zone lymphomas \nand WDLL/CLL may coex\u00ad\npress M and D, lymphoplas\u00ad\nmocytic lymphoma (M)\nID of monoclonal populations of \nplasma or plasmacytoid cells\nHECA-452 \n(endothelial \ncell antigen, \ncutaneous \nlymphocyte-\nassociated \nantigen, CLA)\nCell surface \nglycoprotein \n(Membrane)\nT cells, more common in \ncutaneous T cells\nMycosis fungoides and \nother cutaneous T-cell \n\u00adlymphomas\nNote: CLA is also used to \nrefer to CD45\nHemoglobin (Hb)\nHemoglobin \n(Cytoplasm)\nErythroid cells\nSome leukemias\nMarker for erythroid cells\nHHV8\nLatent nuclear \nantigen of human \nherpes virus type 8 \n(Nucleus)\nAbsent in normal tissue\nPrimary effusion lymphoma \n(PEL), AIDS-associated multi\u00ad\ncentric Castleman\u2019s disease\nKaposi\u2019s sarcoma (endothelial \ncells and some perivascular \ncells)\nEvaluation of Kaposi sarcoma \nand primary effusion \nlymphoma\nHLA-DR\nMajor histocompati\u00ad\nbility complex Class \nII gene (\u00adMembrane)\nB lymphocytes, macrophages, \nLangerhans cells, dendritic \ncells, activated T cells, some \nendothelial and epithelial cells\nLeukemic myeloblasts\nNot very specific for cell \ntype\nLight immuno-\nglobulin chains \n(lambda [L], \nkappa [K])\nLight chain of \nimmunoglobulins \n(Cytoplasm)\nPlasma cells (normally K > L), B \ncells\nPlasma cell tumors, B-cell \nlymphomas\nID of monoclonal populations of \nplasma cells and B cells\nID of some types of amyloid\nMay require frozen tissue \nfor assessment of B \nlymphoid cells\nExcellent Ig preservation \nin plasma cells in B5 or \nZenker\u2019s fixed tissue", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_166.png", "summary": "This page discusses various immunoperoxidase studies used in hematopathology, including markers for plasma cells, T cells, erythroid cells, human herpes virus type 8, and B cells.", "questions": [ "How are immunoperoxidase studies used in the identification of monoclonal populations of plasma cells and B cells?", "What are the specific uses of HECA-452 and HLA-DR markers in immunohistochemistry?", "Why may frozen tissue be required for the assessment of B lymphoid cells in some cases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 167, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n149\nContinued\nLysozyme (Ly)\nMuramidase \n(Cytoplasm)\nCirculating monocytes, some \ntissue macrophages, granulo\u00ad\ncytes, salivary gland, lacrimal \ngland, stomach and colon \nepithelial cells (inflamed or \nregenerative), apocrine glands, \nsome other epithelial cells\nAML with monocytic \ndifferentiation, salivary \ngland tumors, stomach \nand colon carcinomas\nMarker for histiocytes but not \nspecific. May mark activated \nphagocytic macrophages\nEvaluation of myeloid \nleukemias\nStrongly positive in \nmonocytoid leukemias\nNot specific for solid \ntumor identification\nMast cell tryptase\nSerine protease \n(Cytoplasm)\nMast cells\nMast cell neoplasms\nID of mast cell differentiation\nMyeloperoxidase \n(MPO)\nEnzyme in primary \ngranules of myeloid \ncells\n (Cytoplasm)\nMyeloid cells, monocytes\nAML, chloromas\nClassification of leukemias\nCan be used with tissue \nfixed in Zenker\u2019s fixative\nOct2 (Octomer \ntranscription \nfactor)\nTranscription factor \nof the POU homeo-\ndomain family \nbinding to the \nIg gene octomer \nsites regulating \nB-specific genes \n(Nucleus)\nB cells\nB-\u0007cell lymphomas and \nleukemias\nReed-Sternberg cells in LP HD \n(but not other types)\nEvaluation of HD\nInteracts with the tran\u00ad\nscriptional coactivator \nBOB.1. BOB.1 and Oct \nare necessary (but \nnot sufficient) for Ig \nexpression\nPerforin\nPore-forming protein \nin cytoplasmic \ngranules of \ncytotoxic T cells \n(Cytoplasm)\nNK cells, large granular \nlymphocytes, gamma/delta \nT cells\nNK-cell lymphomas, \nanaplastic large cell \nlymphoma\nEvaluation of T-cell lymphomas\nTCR (T-cell antigen \nreceptor, JOVI 1)\nTwo polypeptide \nchains (alpha and \nbeta)\nPeripheral T cells\nMany T-cell lymphomas\nEvaluation of T-cell lymphomas\nAlpha/beta and gamma/\ndelta T-cell receptors \ncan be evaluated in \nfrozen tissue", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_167.png", "summary": "The page discusses various immunoperoxidase studies including lysozyme, mast cell tryptase, myeloperoxidase, Oct2, perforin, and TCR, highlighting their presence in different cell types and their significance in diagnosing specific conditions.", "questions": [ "How do immunoperoxidase studies like lysozyme, mast cell tryptase, and myeloperoxidase help in the evaluation of leukemias and lymphomas?", "What are the specific cell types and conditions where Oct2 and TCR are particularly useful markers?", "Why is it important to evaluate alpha/beta and gamma/delta T-cell receptors in frozen tissue samples?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 168, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n150\nNAME \n(ALTERNATE \nNAME)\nANTIGEN \n(LOCATION)\nNORMAL CELLS AND TISSUES\nTUMORS\nUSES\nCOMMENTS\nHematopathology Markers\nTABLE 7\u201343.\u2003\nANTIBODIES FOR IMMUNOHISTOCHEMISTRY\u2014cont\u2019d\nTerminal deoxy\u00ad\ntransferase \n(TdT)\nEnzyme that catalyzes \naddition of nucleo\u00ad\ntides to ss DNA \n(Nucleus)\nImmature T and B cells\nLymphoblastic lymphoma/ALL\nLymphoblastic lymphoma (+) vs. \nBurkitt lymphoma (-)\nTIA-1 (T-cell intra\u00ad\ncellular antigen)\n A \u0007cytolytic granule-\nassociated protein \nexpressed in some \nCD8+ T cells\n(Cytoplasm)\nT cells, mast cells, polymorpho\u00ad\nnuclear leukocytes, eosinophils\nMany T-cell lymphomas\nEvaluation of T-cell lymphomas\ntraf-1 (Tumor \nnecrosis factor \nreceptor-associ\u00ad\nated factor)\nMembrane-bound \nproteins that \nactivate the nuclear \nfactor-\u043aB (NF-\u043aB) \ntranscription factor \nresulting in cell \nproliferation\n(Cytoplasm)\nUsually absent\nHodgkin lymphoma, primary \nmediastinal large B-cell \nlymphoma\nNegative in most DLBCL and \nALCL\nMay interact with LMP1\nNotes:\nNAME: The most common name used to refer to the marker. The name may refer to the antigen, a CD number, or a specific antibody raised to the antigen. In some cases more than one name is commonly used. Underlined \n\u00adantibodies appear in the tables. Most CD numbers correspond to a specific gene product. However, some correspond to antigens from post-translational modifications. For example, CD15 (LeuM1) is a carbohydrate side chain \nlinked to a protein.\nALTERNATE NAME: This list includes abbreviations, antibody names (sometimes recognizing different epitopes), or other terms for the marker.\nANTIGEN: The antigen recognized by the antibody.\nLOCATION: The normal location of the antigen. In some cases, only certain locations of the antigen are considered a positive result (e.g., nuclear immunoreactivity for estrogen receptor, membrane immunoreactivity for HER2/neu).\nNORMAL CELLS AND TISSUES: The presence of the marker in normal cells and tissues. These cells serve as important internal positive controls. Abnormal positive immunoreactivity is also an important control for the specificity of \nthe study.\nTUMORS: The tumors in which immunoreactivity is typically expected. Refer to the Tables for additional information.\nUSES: The most common uses for the marker. Different pathologists and institutions will often have preferences for the use of certain markers.\nCOMMENTS: Additional comments regarding the marker.\nAdditional information on CD antigens can be found at http://www.ncbi.nlm.nih.gov/prow/guide/45277084.htm.\nAbbreviations: AD, Alzheimer\u2019s disease; AIDS, acquired immunodeficiency syndrome; ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; APML, acute promyelogenous leukemia; BM, basement membrane; CML, \nchronic myelogenous leukemia; CMV, cytomegalovirus; DFSP, dermatofibrosarcoma protuberan; EBV, Epstein Barr virus; FISH, fluorescence in situ hybridization; GIST, gastrointestinal stromal tumor; HCC, hepatocellular carcinoma; \nHD, Hodgkin\u2019s disease; HNPCC, hereditary non-polyposis colorectal cancer; ID, identification; KS, Kaposi\u2019s sarcoma; LP HD, lymphocyte predominant Hodgkin\u2019s disease; MF, mycosis fungoides; MPNST, malignant peripheral nerve \nsheath tumor; NK, natural killer; PIN, prostatic intraepithelial neoplasia; PNET, primitive neuroectodermal tumor; RCC, renal cell carcinoma; RS, Reed Sternberg; TCC, transitional cell carcinoma.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_168.png", "summary": "This page provides information on immunoperoxidase studies, specifically focusing on hematopathology markers and antibodies used for immunohistochemistry.", "questions": [ "What are the normal cells and tissues where the antigen Terminal deoxytransferase (TdT) is found?", "What are the tumors in which TIA-1 is typically expected to be present?", "How does traf-1 function in relation to cell proliferation?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 169, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n151\nTABLE 7\u201344.\u2003\nALTERNATIVE NAMES FOR ANTIGENS\nLOOKING FOR?\nFIND IT UNDER:\n1D5\nEstrogen receptor (G)\n6F/3D\nBeta-amyloid\n12E7\nCD99 (G, H)\n34\u03b2E12\nKeratins (G)\n38.13\nCD77(H)\n70 kD NF\nNeurofilaments (G)\n200 kD NF\nNeurofilaments (G)\n903\nKeratins--34\u03b2E12 (G)\nA (blood group antigen)\nBlood group antigens (G)\nA (Ig heavy chain alpha)\nHeavy chain immuno\u00ad\nglobulins (H)\nA32 antigen\nCD146 (G)\nA103\nMELAN-A (G)\nAAT\nAlpha 1-antitrypsin (G, H)\nACH\nAlpha-1 antichymotrypsin (H)\nAE1/AE3\nKeratins (G)\nAFP\nAlpha-fetoprotein (G)\nAlpha 1-antitrypsin\nAlpha 1-antitrypsin (G, H)\nAlpha 1-antichymotrypsin\nAlpha 1-antichymotrypsin (H)\nAlpha 1-fetoprotein\nAlpha fetoprotein (G)\nAlpha fetoprotein\nAlpha fetoprotein (G)\nAlpha-methylacyl-CoA \nracemase\nAMACR (G)\nAlpha smooth muscle actin\nAlpha smooth muscle actin (G)\nAMACR\nAMACR (G)\nAmyloid\nBeta-amyloid (G)\nAndrogen receptor\nAndrogen receptor (G)\nApolipoprotein J\nClusterin (H)\nAR\nAndrogen receptor (G)\nB (blood group antigen)\nBlood group antigens (G)\nB1\nCD20 (H)\nB2\nCD21 (H)\nLOOKING FOR?\nFIND IT UNDER:\nB4\nCD19 (H)\nB72.3\nB72.3 (G)\nbcl-1\nCyclin D1 (H)\nbcl-2\nbcl-2 (H, G)\nB-cell specific activator \nprotein\nBSAP (H)\nBER-EP4\nBER-EP4 (G)\nBERH2\nCD30 (G, H)\nBeta-amyloid\nBeta-amyloid (G)\nBeta-catenin\nBeta-catenin (G)\nBeta-2 microglobulin\nBeta-2 microglobulin (G)\nBG8\nBG8 (G)\nB-HCG\nHuman chorionic \u00adgonadotropin (G)\nBLA.36\nCD77 (H)\nBL-CAM\nCD22 (H)\nBlood group antigens\nBlood group antigens (G, H)\nBR-2\nGross cystic disease fluid \n\u00adprotein-15 (G)\nBRST-2\nGross cystic disease fluid \n\u00adprotein-15 (G)\nC3b/C4bR\nCD35 (H)\nC5b-9\nC5b-9 (G)\nc-kit\nCD117 (G)\nCA 15-3\nEpithelial membrane antigen (G, H)\nCA 19-9\nCA 19-9 (G)\nCA 27.28\nEpithelial membrane antigen \n(G, H)\nCA 72-4\nB72.3 (G)\nCA125\nCA125 (G)\nCA19-9\nCA19-9 (G)\nCalcitonin\nCalcitonin (G), Hormones (G)\nCaldesmon\nCaldesmon (G)\nCalgranulin\nMAC 387 (G)\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_169.png", "summary": "This page lists alternative names for various antigens and the corresponding codes used in immunoperoxidase studies.", "questions": [ "How are the alternative names for antigens helpful in immunoperoxidase studies?", "Why are codes used for antigens in immunoperoxidase studies?", "What is the significance of identifying specific antigens in pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 170, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n152\nLOOKING FOR?\nFIND IT UNDER:\nCALLA\nCD10 (G, H)\nCALP\nCalponin (G)\nCalponin\nCalponin (G)\nCalprotectin\nMAC 387 (G)\nCalretinin\nCalretinin (G)\nCAM5.2\nKeratins (G)\nCarbohydrate antigen 19-9\nCA19-9 (G)\nCarcinoembryonic antigen\nCarcinoembryonic antigen (G)\nCD1a\nCD1a (H)\nCD2\nCD2 (H)\nCD3\nCD3 (H)\nCD4\nCD4 (H)\nCD5\nCD5 (G, H)\nCD7\nCD7 (H)\nCD8\nCD8 (H)\nCD10\nCD10 (G, H)\nCD11b\nCD11b (H)\nCD11c\nCD11c (H)\nCD13\nCD13 (H)\nCD15\nCD15 (G, H)\nCD16\nCD16 (H)\nCD19\nCD19 (H)\nCD20\nCD20 (H)\nCD21\nCD21 (H)\nCD22\nCD22 (H)\nCD23\nCD23 (H)\nCD25\nCD25 (H)\nCD30\nCD30 (G, H)\nCD31\nCD31 (G)\nCD33\nCD33 (H)\nCD34\nCD34 (G, H)\nCD35\nCD35 (H)\nLOOKING FOR?\nFIND IT UNDER:\nCD38\nCD38 (H)\nCD43\nCD43 (H)\nCD44v3\nCD44v3 (G)\nCD45\nCD45 (H)\nCD45RA\nCD45RA (H)\nCD45Ro\nCD45Ro (H)\nCD56\nCD56 (H)\nCD57\nCD57 (G)\nCD61\nCD61 (H)\nCD68\nCD68 (G, H)\nCD74\nCD74 (H)\nCDw75\nCDw75 (H)\nCD77\nCD77 (H)\nCD79a\nCD79a (H)\nCD79b\nCD79b (H)\nCD95\nCD95 (H)\nCD99\nCD99 (G, H)\nCD117\nCD117 (G)\nCD141\nCD141 (G)\nCDX\nCDX (G)\nCDKN2\np16 (G)\nCDP\nGross cystic disease fluid \nprotein-15 (G)\nCEA\nCarcinoembryonic antigen (G)\nc-erbB2\nHER-2/neu (G)\nChromogranin A\nChromogranin A (G)\nc-kit\nCD117 (G)\nCLA\nCD45 (H) or HECA-452 (H)\nCLDN1\nClaudin (G)\nClusterin\nClusterin (H)\nCollagen IV\nCollagen IV (G)\nCommon acute leukemia \nantigen\nCD10 (G, H)\nTABLE 7\u201344.\u2003\nALTERNATIVE NAMES FOR ANTIGENS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_170.png", "summary": "This page lists various immunoperoxidase studies and the corresponding antigens they are used to detect.", "questions": [ "What is the significance of using immunoperoxidase studies in pathology?", "How are these antigens selected for specific studies?", "Are there any limitations or challenges associated with immunoperoxidase studies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 171, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n153\nTABLE 7\u201344.\u2003\nALTERNATIVE NAMES FOR ANTIGENS\u2014cont\u2019d\nLOOKING FOR?\nFIND IT UNDER:\nComplement lysis inhibitor\nClusterin (H)\nCR1\nCD35 (H)\nCyclin D1\nCyclin D1 (H)\nCystic fibrosis antigen\nMAC 387 (G)\nD (Ig heavy chain delta)\nHeavy chain immunoglobulins \n(H)\nDBA.44\nDBA.44 (H)\nDesmin\nDesmin (G)\nDF3\nEpithelial membrane antigen \n(G, H)\nDPB\nCD45RA (H)\nE2 antigen\nCD99 (G, H)\nEBERS\nEpstein-Barr virus (G, H)\nEBNA\nEpstein-Barr virus (G, H)\nE-cadherin\nE-cadherin (G)\nEGFR\nEGFR (G)\nEM ACT\nHHF-35 (G)\nEMA\nEpithelial membrane antigen (G)\nE-MEL\nHMB-45 (G)\nEndothelial cell antigen\nHECA-452 (H)\nEp-CAM\nBER-EP4 (G)\nEpidermal growth factor \nreceptor\nEGFR (G)\nEpithelial membrane \nantigen\nEpithelial membrane antigen \n(G, H)\nEpithelial specific antigen\nBER-EP4 (G)\nEpstein-Barr virus\nEpstein-Barr virus (G, H)\nER\nEstrogen receptor (G)\nerbB2\nHER-2/neu (G)\nESA\nBER-EP4 (G)\nEstrogen receptor\nEstrogen receptor (G)\nEwing\u2019s sarcoma marker\nCD99 (G, H)\nFactor VIII related antigen\nFactor VIII (G)\nFVIII:RAg\nFactor VIII (G)\nLOOKING FOR?\nFIND IT UNDER:\nFactor XIIIa\nFactor XIIIa (G)\nFascin\nFascin (H)\nFast myosin\nMyosin heavy chain (G)\nFibronectin\nFibronectin (G)\nFli-1\nFli-1 (G)\nFMC7\nFMC7 (H)\nFMC 29\nCD99 (G, H)\nFriend leukemia integrin-\nsite 1\nFli-1 (G)\nFVIII:g\nFactor VIII (G)\nG (Ig heavy chain gamma)\nHeavy chain immunoglobulins \n(H)\nGal-3\nGalectin-3 (G)\nGalectin-3\nGalectin-3 (G)\nGastrin\nHormones (G)\nGCDFP\nGross cystic disease fluid \nprotein-15 (G)\nGFAP\nGlial fibriallary acidic \nprotein (G)\nGlial fibrillary acidic protein\nGlial fibriallary acidic protein (G)\nGlucagon\nHormones (G)\nGlucose transporter 1\nGLUT-1 (G)\nGLUT-1\nGLUT-1 (G)\nGPIIIa\nCD61 (H)\ngp80\nClusterin (H)\ngp200\nRCC (G)\nGPA\nGlycophorin A (H)\nGranzyme B\nGranzyme B (H)\nGross cystic disease fluid \ndisease-15\nGross cystic disease fluid \nprotein-15 (G)\nH (blood group antigen)\nBlood group antigens (G)\nH222\nEstrogen receptor (G)\nHb\nHemoglobin (H)\nHBME-1\nHBME-1 (G)\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_171.png", "summary": "This page lists alternative names for various antigens and the corresponding markers used in immunoperoxidase studies.", "questions": [ "What is the significance of using alternative names for antigens in immunoperoxidase studies?", "How are these alternative names helpful in identifying specific antigens?", "Are there any limitations or challenges associated with using alternative names for antigens in pathology studies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 172, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n154\nTABLE 7\u201344.\u2003\nALTERNATIVE NAMES FOR ANTIGENS\u2014cont\u2019d\nLOOKING FOR?\nFIND IT UNDER:\nh-caldesmon\nCaldesmon (G)\nH-CAM\nCD44v3 (G)\nHCG\nHuman chorionic gonadotropin \n(G)\nHCL\nDBA.44 (H)\nHBME-1\nHBME-1 (G)\nHeavy chain immuno\u00ad\nglobulins\nHeavy chain immunoglobulins \n(H)\nHECA-452\nHECA-452 (H)\nHematopoietic progenitor \ncell, class 1\nCD34\nHemoglobin\nHemoglobin (H)\nHepPar-1\nHepPar-1 (G)\nHepatocyte paraffin-1\nHepPar-1 (G)\nHER-2/neu\nHER-2/neu (G)\nHHF-35\nHHF-35 (G)\nHHV8\nHHV8 (H)\nHLA-DR\nHLA-DR (H)\nHMB-45\nHMB-45 (G)\nHMFG\nEpithelial membrane antigen (G, \nH)\nhMLH1\nhMLH1 (G)\nhMSH2\nhMLH1 (G)\nHNK-1\nCD57 (G)\nHP1\nHepPar-1 (G)\nHPCA-1\nCD34 (G, H)\nHPL\nHuman placental lactogen (G)\nHuLy-m6\nCD99 (G, H)\nHuman chorionic \ngonadotropin\nHuman chorionic \ngonadotropin (G)\nHuman herpes virus 8\nHHV8 (G, H)\nHuman mutL homologue 1\nhMLH1 (G)\nHuman mutS homologue 2\nhMLH1 (G)\nHuman placental lactogen\nHuman placental lactogen (G)\nLOOKING FOR?\nFIND IT UNDER:\nIL-2 receptor\nCD25 (H)\nInhibin-alpha subunit\nInhibin-alpha subunit (G)\nInsulin\nHormones (G)\nJ5\nCD10 (G, H)\nJOVI 1\nTCR (H)\nK (Ig lighit chain kappa)\nLight chain immunoglobulins (H)\nKeratin 5/6\nKeratins (G)\nKeratin 7\nKeratins (G)\nKeratin 20\nKeratins (G)\nKeratins\nKeratins (G)\nKi-1\nCD30 (G, H)\nKi-67\nKi-67 (G)\nkip2\np57 (G)\nKit\nCD117 (G)\nKP-1\nCD68 (G, H)\nL (Ig light chain lambda)\nLight chain immunoglobulins (H)\nL1 antigen\nMAC 387 (G)\nL26\nCD20 (H)\nL60\nCD43 (H)\nLaminin\nLaminin (G)\nLCA\nCD45 (H)\nLeu 1\nCD5 (H)\nLeu 2\nCD8 (H)\nLeu 3\nCD4 (H)\nLeu 5a + b\nCD2 (H)\nLeu 7\nCD57 (G, H)\nLeu 9\nCD7 (H)\nLeu16\nCD20 (H)\nLeu 22\nCD43 (H)\nLeukocyte common \nantigen\nCD45 (H)\nLeu-M1\nCD15 (G, H)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_172.png", "summary": "This page lists alternative names for various antigens used in immunoperoxidase studies.", "questions": [ "What is the significance of using alternative names for antigens in immunoperoxidase studies?", "How are these alternative names helpful in the context of pathology?", "Are there specific reasons why certain antigens have multiple alternative names?", "How are these alternative names standardized and recognized within the field of pathology?", "What implications do these alternative names have on the interpretation of immunoperoxidase study results?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 173, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n155\nTABLE 7\u201344.\u2003\nALTERNATIVE NAMES FOR ANTIGENS\u2014cont\u2019d\nLOOKING FOR?\nFIND IT UNDER:\nLight chain immunoglobu\u00ad\nlins\nLight chain immunoglobulins (H)\nLFA-2\nCD2 (H)\nLMP-1\nEpstein-Barr virus (G, H)\nLN1\nCDw75 (H)\nLN2\nCD74 (H)\nLysozyme\nLysozyme (H, G)\nM (Ig heavy chain mu)\nHeavy chain immunoglobulins \n(H)\nMac-1\nCD11b (H)\nMAC 387\nMAC 387 (G)\nMac-M\nCD68 (G, H)\nMART 1\nMELAN A (G)\nMast cell tryptase\nMast cell tryptase (H)\nmb-1\nCD79a (H)\nMCAM\nCD146 (G)\nME491\nCD63 (G)\nMELAN-A\nMELAN-A (G)\nMelanoma antigen recog\u00ad\nnized by T cells\nMELAN-A (G)\nMelanoma-associated \nantigen\nCD63 (G)\nMelanoma cell adhesion \nmolecule\nCD146 (G)\nMelanoma-specific antigen\nHMB-45 (G)\nMELCAM (or Mel-CAM)\nCD146 (G)\nMIB-1\nKi-67 (G)\nMIC-2\nCD99 (G, H)\nMLH1\nhMLH1\nMN-4\nCD146 (G)\nMNF-116\nKeratin--Pan-K (G)\nMPO\nMyeloperoxidase (H)\nMRF4\nMyf-4 (G)\nMSA\nHHF-35 (G)\nLOOKING FOR?\nFIND IT UNDER:\nMSH2 or MSH6\nhMLH1\nMTS1\np16 (G)\nMUC1\nEpithelial membrane antigen (G, \nH)\nMUC18\nCD146 (G)\nMuscle common actin\nHHF-35 (G)\nMuscle specific actin\nHHF-35 (G)\nMy 7\nCD13 (H)\nMy 9\nCD33 (H)\nMyeloperoxidase\nMyeloperoxidase (H)\nMyf-4\nMyf-4 (G)\nMyoD1\nMyoD1 (G)\nMyogenin\nMyf-4 (G)\nMyoglobin\nMyoglobin (G)\nMyosin heavy chain\nMyosin heavy chain (G)\nNCAM\nCD56 (H)\nNeprilysin\nCD10 (G, H)\nNEU N\nNEU N (G)\nNeurofilaments\nNeurofilaments (G)\nNeuron specific enolase\nNeuron specific enolase (G)\nNFP\nNeurofilaments (G)\nNKI-betab\nHMB-45 (G)\nNKI/C3\nCD63 (G)\nNSE\nNeuron specific enolase (G)\nO13\nCD99 (G, H)\nOC125\nCA125 (G)\nOct2\nOct2 (H)\nOctomer transcription factor\nOct2 (H)\np16\np16 (G)\np27kip1\np27kip1 (G)\np53\np53 (G)\np57\np57 (G)\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_173.png", "summary": "This page lists alternative names for various antigens and the corresponding markers used in immunoperoxidase studies.", "questions": [ "What is the significance of using alternative names for antigens in immunoperoxidase studies?", "How do researchers determine which marker to use when looking for a specific antigen?", "Are there any limitations or challenges associated with using immunoperoxidase studies for antigen detection?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 174, "text": "SPECIAL STUDIES\u2003 Immunoperoxidase Studies\n156\nTABLE 7\u201344.\u2003\nALTERNATIVE NAMES FOR ANTIGENS\u2014cont\u2019d\nLOOKING FOR?\nFIND IT UNDER:\np63\np63 (G)\nP504S\nAMACR (G)\nPAN-K\nKeratins (G)\nPAP\nProstate acid phosphatase (G)\nPECAM-1\nCD31 (G)\nPEM\nEpithelial membrane antigen (G, \nH)\nPerforin\nPerforin (H)\nPGM1\nCD68 (G, H)\nPgR\nProgesterone receptor (G)\nPK antigen\nCD77 (H)\nPlacental alkaline \nphosphatase\nPlacental alkaline phosphatase \n(G)\nPLAP\nPlacental alkaline phosphatase \n(G)\nPlatelet glycoprotein IIIa\nCD61 (H)\nPMS2\nhMLH1\nPodoplanin\nD2-40\nPR\nProgesterone receptor (G)\nPRAD1\nCyclin D1 (H)\nPrAP\nProstate acid phosphatase (G)\nPrealbumin\nPrealbumin (G)\nProgesterone receptor\nProgesterone receptor (G)\nProstate acid phosphatase\nProstate acid phosphatase (G)\nProstate specific antigen\nProstate specific antigen (G)\nPSA\nProstate specific antigen (G)\nQBEnd10\nCD34 (G, H)\nRenal cell carcinoma marker\nRCC (G)\nret\nret (G)\nRCC\nRCC (G)\nrT3\nCD2 (H)\nS-100\nS-100 (G)\nLOOKING FOR?\nFIND IT UNDER:\nS-Endo-1\nCD146 (G)\nSGP-2\nClusterin (H)\nSMA\nAlpha smooth muscle \nactin (G)\nSM-ACT\nAlpha smooth muscle \nactin (G)\nSmad4\nDPC4 (G)\nSM-MHC\nMyosin heavy chain (G)\nSomatostatin\nHormones (G)\nSP40\nClusterin (H)\nStem cell factor receptor\nCD117 (G)\nSynaptophysin\nSynaptophysin (G)\nSyndecan-1\nCD138 (H)\nSynuclein-1\nSynuclein-1 (G)\nT3\nCD3 (H)\nT4\nCD4 (H)\nT6\nCD1a (H)\nT8\nCD8 (H)\nT11\nCD2 (H)\nT64\nClusterin (H)\nTAG-72\nB72.3 (G)\nTau\nTau (G)\nT cell antigen receptor\nTCR (H)\nT cell intracellular antigen\nTIA-1 (H)\nTCR\nTCR (H)\nTdT\nTerminal deoxytransferase (H)\nTE\nCD2 (H)\nTerminal deoxytransferase\nTerminal \ndeoxytransferase (H)\nTH\nCD4 (H)\nThrombomodulin\nCD141 (G)\nThyroglobulin\nThyroglobulin (G)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_174.png", "summary": "This page lists alternative names for various antigens used in immunoperoxidase studies.", "questions": [ "What is the significance of using alternative names for antigens in immunoperoxidase studies?", "How are these alternative names helpful in the context of pathology?", "Are there specific reasons why certain antigens have multiple alternative names?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 175, "text": "SPECIAL STUDIES\u2003 Electron Microscopy\n157\nTABLE 7\u201344.\u2003\nALTERNATIVE NAMES FOR ANTIGENS\u2014cont\u2019d\nLOOKING FOR?\nFIND IT UNDER:\nThyroid transcription \nfactor 1\nTTF-1 (G)\nTIA-1\nTIA-1 (H)\nTM\nCD141 (G)\ntraf-1\ntraf-1 (H)\nTransthyretin\nPrealbumin (G)\nTRPM2\nClusterin (H)\nTTF-1\nTTF-1 (G)\nTTR\nPrealbumin (G)\nTumor-associated \n\u00adglycoprotein 72\nB72.3 (G)\nLOOKING FOR?\nFIND IT UNDER:\nTumor necrosis factor \nreceptor\u2013associated \nfactor\ntraf-1 (H)\nUCHL-1\nCD45Ro (H)\nUEA 1\nUlex (G)\nUlex\nUlex (G)\nVimentin\nVimentin (G)\nvon Willebrand\u2019s factor\nFactor VIII (G)\nVWF\nFactor VIII (G)\nWilms\u2019 tumor 1 protein\nWT1 (G)\nWT1\nWT1 (G)\nG, general markers; H, hematopathology markers.\nELECTRON MICROSCOPY\nIndications for EM Studies.\u2002\n\t\u2022\t \u0007Diagnostic renal biopsies for glomerular disease\n\t\u2022\t \u0007Adenocarcinoma versus mesothelioma (see Table 7-36)\n\t\u2022\t \u0007Difficult to classify tumors (Tables 7-45 and 7-46)\n\t\u2022\t \u0007Nerve (e.g., toxic or drug-induced neuropathy) and \nmuscle biopsies (e.g., inclusion body or nemaline myop\u00ad\nathy)\n\t\u2022\t \u0007Bullous skin diseases (e.g., epidermolysis bullosa)\n\t\u2022\t \u0007Ciliary dysmorphology (primary ciliary dyskinesia or \nKartagener syndrome)\n\t\u2022\t \u0007Endomyocardial biopsies (e.g., adriamycin toxicity, \namyloid, nemaline myopathy)\n\t\u2022\t \u0007Liver biopsies for microvesicular fat in acute fatty liver \nof pregnancy\n\t\u2022\t \u0007Small bowel biopsies to look for pathogens (e.g., Whip\u00ad\nple disease)\n\t\u2022\t \u0007Congenital, inherited, and metabolic diseases (e.g., \nceroid lipofuscinoses)\n\t\u2022\t \u0007Prion diseases\nMethod.\u2002 Ultrastructural details of tissues are lost rap\u00ad\nidly. Therefore, fresh tissue must be fixed rapidly and well \nfor EM. Tissues are usually fixed in special fixatives for EM \nto preserve lipids and glycogen (e.g., 2% paraformalde\u00ad\nhyde and 2.5% glutaraldehyde in 0.1 M cacodylate buffer, \npH 7.4).\n\t\n1.\t \u0007Place a small fragment of tissue in a drop of fixative \non a cutting surface.\n\t\n2.\t \u0007Cut the tissue into multiple tiny fragments, each no \ngreater than 0.1 cm in any dimension.\n\t\n3.\t \u0007Place the tissue into the vial of fixative. Shake the \nvial to make sure all the tissue fragments are covered \nby fixative.\nNote: If tissue from a small biopsy is found to be non\u00ad\ndiagnostic on H&E, any tissue saved for EM should be \nretrieved for examination by light microscopy.\nResults.\u2002 A separate electron microscopy report is usu\u00ad\nally issued. The results should be incorporated into the \nfinal diagnosis.19", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_175.png", "summary": "The page discusses the use of electron microscopy for various diagnostic purposes, including renal biopsies, tumor classification, nerve and muscle biopsies, skin diseases, and metabolic diseases.", "questions": [ "What are some common indications for using electron microscopy in diagnostic pathology?", "Why is it important to fix tissues rapidly and well for electron microscopy?", "How are the results of electron microscopy studies typically reported and utilized in the final diagnosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 176, "text": "SPECIAL STUDIES\u2003 Electron Microscopy\n158\nTABLE 7\u201346.\u2003\n\u0007CELLS, TUMORS, AND STRUCTURES WITH CHARACTERISTIC FINDINGS \nBY ELECTRON MICROSCOPY\nTUMOR\nEM FINDINGS\nCORRELATIONS AND OTHER DIAGNOSTIC TESTS\nAlveolar soft part \nsarcoma\nRhomboid, rod-shaped, or spiculated crystals in a \nregular latttice pattern.\nThe characteristic cytoplasmic crystals are composed \nof monocarboxylate transporter 1 (MCT1) and its \nchaperone CD147. These proteins are found in many \nother cell types and are not specific for this tumor.\nCytogenetics: t(X;17) creates a ASPL-TFE3 fusion \nprotein.\nIHC: TFE3 positive (as well as rare pediatric renal \ntumors with the same translocation). Nuclear immu\u00ad\nnoreactivity is not present in other tumors or normal \ntissues.\nHisto: The crystals are PAS with diastase positive.\nTABLE 7\u201345.\u2003\nELECTRON MICROSCOPIC FEATURES OF POORLY DIFFERENTIATED TUMORS\nTUMOR\nULTRASTRUCTURE\nADDITIONAL TESTS\nCOMMENTS\nCarcinoma\nWell-developed desmosomes (pentalay\u00ad\nered with a dense central line in the \nintracellular space) with intermediate \nfilament attachment.\nTonofilaments and bundles of filaments \n(keratin).\nAdenocarcinomas:\n\u2022\t \u0007Intercellular lumina (but also present in \nvascular tumors)\n\u2022\t \u0007Microvilli\n\u2022\t \u0007Intracellular lumina (mucin vacuoles in \nsignet ring cells)\nSquamous cell carcinomas\n\u2022\t \u0007Numerous intermediate filaments \n(keratin) and desmosomes\nIHC: Cytokeratins are \npresent in almost all \ncarcinomas if broad \nspectrum antibodies \nare used.\nEMA is present in almost all \ncarcinomas, but is less \nspecific and sensitive.\nAdditional markers can be \nused to identify specific \ncarcinomas.\nOther tumors can also be keratin \npositive and have desmosomes, \n\u00adfilaments, and \u00adcytokeratin \n\u00ad(mesothelioma, meningioma, \n\u00adsynovial sarcoma, and epithelioid \nsarcoma)\nMelanoma\nMelanosomes in various stages of \ndevelopment \u2013 indicative of a melanin-\nforming cell type.\nAbnormal pleomorphic melanosomes may \nbe present in melanomas.\nDesmoplastic melanomas lack \nmelanosomes.\nIHC: S100, HMB45, MART-1\nHMB45 and MART-1 may be \nabsent in non-epithelioid \nmelanomas.\nThe HMB-45 epitope \n(gp100) is present in \nimmature melanosomes \nor premelanosomes, but \nis not specific to these \nstructures.\nMelanosomes are also seen in clear cell \nsarcoma, pigmented schwannomas, \nPEComa, and other rare tumors. \nMature forms can be taken up by \nmelanophages, keratinocytes, and \ncarcinomas.\nLymphoma\nNo specific features are present. The \ncells lack cellular junctions and there \nis a paucity of cytoplasmic organelles.\nIHC: LCA\nLCA may be absent in 30% of anaplas\u00ad\ntic (ALK1) lymphomas. These tumors \ncan be EMA (+) but are keratin (-).\nSarcoma\nSome types have specific diagnostic \nfeatures of cell type (e.g., neural, smooth \nmuscle, striated muscle).\nNo well-developed desmosomes.\nIHC: May be helpful for \nidentifying specific types.\nKeratin negative except for synovial \nsarcoma and epithelioid sarcoma (or \nrarely in other types).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_176.png", "summary": "This page discusses the electron microscopic findings and additional diagnostic tests for various tumors, including alveolar soft part sarcoma, poorly differentiated carcinomas, melanoma, lymphoma, and sarcoma.", "questions": [ "How can electron microscopy findings aid in the diagnosis of alveolar soft part sarcoma?", "What are some common additional diagnostic tests used in identifying poorly differentiated carcinomas?", "Are there any specific electron microscopic features that can help differentiate between different types of sarcomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 177, "text": "SPECIAL STUDIES\u2003 Electron Microscopy\n159\nContinued\nTUMOR\nEM FINDINGS\nCORRELATIONS AND OTHER DIAGNOSTIC TESTS\nAmyloid\nNon-branching fibrils, 7.5 to 10 nm in width and \nup to 1 micron in length.\nMay be present associated with plasma cell tumors, \nmedullary carcinoma of the thyroid, Alzheimer\u2019s dis\u00ad\nease, or as an isolated finding (primary amyloidosis).\nIHC: Can be used to identify specific types of amyloid \n(e.g., lambda or kappa chains, beta2 microglobulin, \ncalcitonin, tau)\nBronchioloalveolar \ncarcinoma of the \nlung (BAL)\nLamellar (surfactant) \u201cmyelin-like\u201d granules in \nthe supranuclear cytoplasm (typical of Type II \npneumocytes).\nClara-like electron-dense granules in supranu\u00ad\nclear cytoplasm.\nIntranuclear inclusions comprised of parallel \nmicrotubular arrays.\nThese features can also be seen in metastatic BAL.\nCytogenetics: These carcinomas are less likely to be associ\u00ad\nated with smoking and have fewer cytogenetic changes.\nBronchioloalveolar carcinomas or adenocarcinomas \nwith features of BAL are more likely to respond to \nIressa (38%) as compared to other lung carcinomas \n(14%) due to specific mutations in EGFR.\nMucinous BAL has intranuclear inclusions but generally \nlacks the other EM features.\nChordoma\nDesmosomes, large vacuoles, glycogen, \ndilated ER, cytoplasmic invaginations, \nand intermediate filaments\nThe physaliphorous (= having bubbles or \nvacuoles) appearance is due to dilated ER, \nglycogen, and cytoplasmic invaginations.\nIHC: Keratin (corresponds to intermediate filaments), \nEMA, S100\nClear cell sarcoma\nMelanosomes in various stages of development.\nGlycogen (resulting in clear cytoplasm).\nCytogenetics: t(12;22) EWS;ATF1 fusion protein\nIHC: S100, HMB45\nDense core granules\nDense core granules (vesicle bound by a \nsingle membrane with a dense center \u2013 60 to \n300 nm) \u2013 cytoplasmic organelles involved in \nregulated exocytosis of cell products.\nExamples:\nPancreatic beta cells (insulin): angular crystalline \ninclusions\nPheochromocytoma (epinephrine and norepi\u00ad\nnephrine): Large, pleomorphic, often clear or \nonly partially filled\nCarcinoid:\n\u2022\t \u0007Foregut \u2013 small, round\n\u2022\t \u0007Midgut \u2013 larger, pleomorphic\n\u2022\t \u0007Hindgut \u2013 mixed\nFound in tumors of neuronal or neuroendocrine origin.\nVesicles are comprised of granins (predominantly \nchromogranin A, chromogranin B, and secretogranin \nII) and various peptide hormones and transmitters, \nATP, and biogenic amines\nIHC: Chromogranin A (most specific). Specific products \nof tumors can also be detected.\nNote: Prostate cancers and breast cancers can also show \nstrong chromogranin positivity and can be mistaken \nfor neuroendocrine tumors, particularly at metastatic \nsites.\nDesmoplastic small \nround cell tumor\nNumerous desmosomes and tight junctions, \nnumerous cell processes, large number \nof organelles (mitochondria and RER), \nmicrofilaments, small neurosecretory granules\nCytogenetics: t(11;22) EWS;WT1 fusion protein\nIHC: Keratin, desmin, WT-1, actin, EMA, NSE\nEndothelial cells\nWeibel-Palade bodies (cigar-shaped membrane-\nbound structures filled with tubules in parallel \narrays).\nIntracytoplasmic lumina may be present in \nnormal cells and in epithelioid vascular \nneoplasms.\nWeibel-Palade bodies are frequently absent in tumors \narising from endothelial cells (e.g., angiosarcomas). \nIHC markers are more sensitive to detect endothelial \nderivation. The membranes are formed by P-selectin \nand the tubules contain FVIII.\nIHC: Vascular markers (CD34, CD31, FVIII)\nEwing sarcoma \n(PNET)\nHomogeneous cell population characterized by \nthe lack of specialized features, large pools \nof glycogen, no organelles, no extracellular \nmatrix, variable numbers of neurosecretory \ngranules and cell processes.\nCytogenetics: t(11;22) EWS;FLI1 fusion protein (and \nother less common variants)\nIHC: CD99. FLI1 is also present, but is less specific.\nHisto: PAS +/\u2212 diastase can detect glycogen, but is not \ncurrently used for diagnosis.\nTABLE 7\u201346.\u2003\n\u0007CELLS, TUMORS, AND STRUCTURES WITH CHARACTERISTIC FINDINGS \nBY ELECTRON MICROSCOPY\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_177.png", "summary": "The page discusses electron microscopy findings in various tumors, including amyloid, bronchioloalveolar carcinoma, chordoma, clear cell sarcoma, and dense core granules.", "questions": [ "How can electron microscopy findings help in the diagnosis of amyloidosis?", "What are the specific features seen in bronchioloalveolar carcinoma of the lung?", "What diagnostic markers are commonly used in the identification of clear cell sarcoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 178, "text": "SPECIAL STUDIES\u2003 Electron Microscopy\n160\nTUMOR\nEM FINDINGS\nCORRELATIONS AND OTHER DIAGNOSTIC TESTS\nGranular cell tumor\nNumerous lysosomes (filled with tubular, \nvesicular, and amorphous material), \nphagosomes, and granules (correlating with \nthe \u201cgranular\u201d cytoplasm), reduplicated basal \nlamina surrounding groups of cells.\nIHC: S100, inhibin, CD68, calretinin\nLangerhans cell \nhistiocytosis\nBirbeck granules (rod-or tennis racket-shaped) \nstructures of variable length with a central \nperiodically striated lamella.\nMay serve as a reservoir for Langerin (a transmembrane \ntype II Ca2+-dependent lectin) and CD1a in the \nendosomal recycling compartment.\nIHC: CD1a, Langerin, S100\nMast cells\nLameller or scroll-like membrane pattern, \ngranules of variable size.\nIHC: CD117 (c-kit), mast cell tryptase\nMedullary carcinoma \nof the thyroid\nNumerous neurosecretory granules (calcitonin) \nassociated with stromal amyloid (calcitonin).\nCytogenetics: Mutations in the RET gene (sporadic \nand germline)\nIHC: Calcitonin (in tumor cells and amyloid), \nchromogranin\nMerkel cell \ncarcinoma\nNeurosecretory granules in processes or along \ncell membranes (subplasmalemmal).\nIHC: Chromogranin, NSE, cytokeratin 20\nMesothelioma\nElongated, serpiginous, and branched microvilli \n(generally 10 to 16 length: 1 width) apical \nwithout a glycocalyx or actin rootlets.\nCytogenetics: Characteristic chromosome deletions and \nloss of 9 and 22\nIHC: Calretinin, WT-1\nNeuroblastoma\nCellular processes with microtubules (neuropil), \ndense core granules, Homer-Wright rosettes \n(the center is comprised of a tangle of cell \nprocesses), synaptic vesicles, no glycogen\nCytogenetics: Changes are linked to prognosis\nIHC: Chromogranin, NSE, NFP, synaptophysin\nOncocytoma\nNumerous mitochondria packed in the \ncytoplasm (correlating with the granular \nappearance of the cytoplasm). In contrast, \nchromophobe renal cell carcinoma has fewer \nmitochondria and more microvesicles.\nCytogenetics: Monosomy with loss of X or Y, 11q13. \nChromophobe carcinomas have different cytogenetic \nchanges.\nIHC: RCC is negative in oncocytomas but positive in 45% \nto 50% of chromophobe renal cell carcinomas.\nPerineurioma\nLong cell processes wrapping around adjacent cells\nIHC: Claudin-1 (a component of tight junctions), EMA\nRhabdoid tumor of \nthe kidney\nLarge paranuclear whorls of intermediate \nfilaments (corresponding to cytokeratin and \nvimentin) and occasional tonofilaments\nCytogenetics: hSNF5/INI1 deletions and mutations on \nchromosome 22\nIHC: Cytokeratin (+), vimentin (+), absence of INI1 \nnuclear protein\nRhabdomyosarcoma\nParallel thick (12 to 15 cm) and thin (6 to 8 nm) \nmyosin-actin filaments, Z-bands, filament \nribosomal complexes.\nSpider cells may be seen in cardiac tumors (clear \ncytoplasm divided by cytoplasmic processes \nand cross striations formed by leptofibrils).\nCytogenetics: Characteristic changes in alveolar and \nembryonal types\nIHC: Muscle markers (HHF-35, desmin, myf4)\nSchwannoma\nBasal lamina prominent, often reduplicated. Luse \nbodies (long spacing collagen, extracellular), \nmyelin figures, long cell processes wrapping \naround collagen, may rarely have melano\u00ad\nsomes (melanotic schwannoma)\nCytogenetics: Deletion of 2q (NF2 inactivation)\nIHC: S100\nTABLE 7\u201346.\u2003\n\u0007CELLS, TUMORS, AND STRUCTURES WITH CHARACTERISTIC FINDINGS \nBY ELECTRON MICROSCOPY\u2014cont\u2019d\nSee Tables 7-8, 7-9, 7-22, and 7-47 for additional information.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_178.png", "summary": "The page discusses special studies using electron microscopy for various tumors, detailing their specific findings and correlations with other diagnostic tests.", "questions": [ "How do the electron microscopy findings differ among different types of tumors?", "What are the common immunohistochemical markers used for tumor diagnosis in electron microscopy studies?", "How do cytogenetic changes play a role in the diagnosis of certain tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 179, "text": "SPECIAL STUDIES\u2003 Molecular Genetic Pathology\n161\nSNAP FROZEN TISSUE\nFrozen tissue is useful for staining (some antibodies only \ndetect antigens in frozen tissue), enzyme studies (muscle \nbiopsies), and to save tissue for DNA or RNA studies.\nIndications.\u2002 All specimens with a question of a lym\u00ad\nphoproliferative disorder, sarcomas, unusual tumors, mus\u00ad\ncle biopsies.\nMethods.\u2002 Small (approximately 0.5 \u00d7 0.5 \u00d7 0.3 cm3) \nportions of tissue are placed in a clean specimen container \nmoistened with a small amount of normal saline until they \ncan be frozen. Specimens should be snap frozen using liq\u00ad\nuid nitrogen or dry ice and stored at \u201320\u00b0C.\nResults.\u2002 The results of studies on frozen tissue are \n\u00adusually incorporated into the surgical pathology report.\nIMMUNOFLUORESCENCE\nLike immunoperoxidase studies, immunofluorescence (IF) \ndetects antigens in tissues. However, because amplifica\u00ad\ntion of the signal is not used, it is better suited for precise \nlocalization of antigen/antibody complexes in tissues or \nfor determining the deposition pattern of immune com\u00ad\nplexes (e.g., linear vs. granular). Thus, it is most useful for \nthe investigation of diseases related to immune complex \n\u00addeposition such as glomerular diseases and bullous diseases \nof the skin.\nTissue for IF may be snap frozen (see instructions ear\u00ad\nlier) or stored in special fixatives for IF. If the specimen is \nnot frozen, special care must be taken to ensure that the \nbiopsy is kept moist in a sealed container.\n\t\u2022\t \u0007Direct IF: Uses antibodies to detect antigens in the \npatient\u2019s tissues.\n\t\u2022\t \u0007Indirect IF: Uses control tissues to detect antibodies \n(e.g., anti-BM) in the patient\u2019s serum.\nIndications.\u2002 Some skin biopsies (e.g., lupus, pem\u00ad\nphigus, pemphigoid, and dermatitis herpetiformis), all \ndiagnostic nontransplant renal biopsies, some trans\u00ad\nplant renal biopsies, identification of amyloid in car\u00ad\ndiac biopsies, and the evaluation of vasculitis in nerve \nbiopsies.\nMethod.\u2002 Tissue must be submitted fresh.\nResults.\u2002 The results of the examination are usually \nincorporated into the surgical pathology report.\nImmunofluorescence of Skin Lesions\n\t\u2022\t \u0007SLE (lupus band test): linear or granular staining \nalong dermal epidermal junction for multiple immuno\u00ad\nreactants in about 80% of cases (most commonly IgG \nand less often IgM or C3). The specificity increases with \nthe number of positive immunoreactants. Uninvolved \nsun-exposed skin shows positivity in most patients with \nactive systemic lupus. Uninvolved skin in patients with \ndiscoid lupus is usually negative for this test.\n\t\u2022\t \u0007Herpes gestationis: perilesional skin shows linear BM \nzone C3 and sometimes IgG.\n\t\u2022\t \u0007Dermatitis herpetiformis: granular IgA at tips of der\u00ad\nmal papillae of uninvolved skin.\n\t\u2022\t \u0007Pemphigus: IgG and C3 between epidermal cells creat\u00ad\ning a net-like pattern. In pemphigus vulgaris, a split just \nabove the basal cell layer creates a \u201ctombstone\u201d appear\u00ad\nance to the row of basal cells at the base of the vesicle. \nIn pemphigus foliaceus and related disorders, the split \noccurs near the granular cell layer.\n\t\u2022\t \u0007Pemphigoid: Ig and C3 along basement membrane but \nnot between cells. Indirect IF reveals an anti-BM anti\u00ad\nbody.\nMOLECULAR GENETIC PATHOLOGY\nMolecular genetic pathology is the newest subspeciality in \npathology with board certification. Molecular diagnostics \nincorporates many types of techniques for the investiga\u00ad\ntion of genetic alterations in cells and viruses (e.g., South\u00ad\nern blotting, PCR analysis, FISH). It has applications in \nthree main areas:\nInherited diseases:\n\t\u2022\t \u0007Identification of inherited diseases (e.g., cystic fibro\u00ad\nsis, hemochromatosis, Factor V Leiden, Prothrombin \n20210A, Fragile X syndrome).\n\t\u2022\t \u0007Identification of genes conferring susceptibility to dis\u00ad\neases (e.g., microsatellite instability [MSI], BRCA1 and 2)\nInfectious diseases:\n\t\u2022\t \u0007Detection of organisms\n\t\u2022\t \u0007Identification of specific organisms\n\t\u2022\t \u0007Quantitation of viral infection (e.g., HIV viral load)\nCancer:\n\t\u2022\t \u0007Identification of specific genetic alterations associated \nwith tumors\n\t\u2022\t \u0007Identification of gene mutations associated with suscep\u00ad\ntibility to treatment (e.g., EGFR mutations in lung can\u00ad\ncer, c-kit mutations in GIST)\n\t\u2022\t \u0007Identification of clonality in hematolymphoid prolifera\u00ad\ntions\n\t\u2022\t \u0007Detection of minimal residual disease after treat\u00adment\nThese studies are especially helpful for hematolym\u00ad\nphoid proliferations that are difficult to classify because \nof the frequent and characteristic rearrangements that \noccur in many of these disorders. Unlike cytogenetics, \nthe cells need not be viable. However, it is preferable \nthat the nucleic acids are relatively intact. Southern \nblot and RNA-based PCR (RT-PCR) assays are best \nperformed on fresh or frozen tissues. \u00adFormalin-fixed,", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_179.png", "summary": "Frozen tissue is useful for staining, enzyme studies, and DNA or RNA studies. Immunofluorescence is used for precise localization of antigen/antibody complexes in tissues.", "questions": [ "What are the indications for using snap frozen tissue?", "How is tissue for immunofluorescence prepared?", "What are some examples of skin lesions that can be evaluated using immunofluorescence?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 180, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n162\nparaffin-embedded tissue is amenable to DNA-\nbased PCR assays. Some fixatives (e.g., Bouin\u2019s) cause \nextensive breakage of DNA and may preclude genetic \nanalysis of the tissue.\nIndications.\u2002\n\t\u2022\t \u0007B-cell proliferations \u2013 clonal rearrangements of the \nimmunoglobulin heavy and light chain genes; specific \ntranslocations\n\t\u2022\t \u0007T-cell proliferations \u2013 rearrangements of the \u03b3 and \u03b2 \nT-cell receptor genes\n\t\u2022\t \u0007Leukemias\n\t\u2022\t \u0007Post-transplant lymphoproliferative disorders \u2013 clonal \npopulations of EBV-infected cells\n\t\u2022\t \u0007Oligodendrogliomas \u2013 PCR-based LOH analysis for \n1p/19q deletions.\n\t\u2022\t \u0007Colon cancers possibly associated with hereditary non-\npolyposis colorectal carcinoma syndrome (HNPCC): \nmicrosatellite instability (MSI) testing of colon cancers \noccurring in patients 50 years of age or younger.\n\t\u2022\t \u0007Human papilloma virus testing: cervical PAP smears, \nsquamous cell carcinomas of the head and neck (see sub\u00ad\nsequent section).\n\t\u2022\t \u0007GIST \u2013 most have mutations in the KIT tyrosine kinase \ngene. A smaller group (5% to 7%) have mutations in \nthe KIT-homologous tyrosine kinase PDGFRA. About \n10% to 15% of GISTs are negative for KIT and PDG\u00ad\nFRA mutations (termed \u201cwild-type GISTs\u201d). The spe\u00ad\ncific type of mutation is correlated with prognosis and \nthe respone to specific types of treatment.\n\t\u2022\t \u0007Lung adenocarcinoma \u2013 some cancers have mutations \nin EGFR that predict response to the tyrosine kinase \ninhibitor gefitinib.\nMethod of Submitting Tissue.\u2002 Fresh or frozen tis\u00ad\nsue (e.g., snap frozen tissue) as well as fluids may be used. \nCytologic preparations can be used for FISH. Paraffin \nblocks can also be used.\nResults.\u2002 The results are usually either reported sepa\u00ad\nrately or incorporated into the surgical pathology report.\nCYTOGENETICS\nCytogenetic studies have been demonstrated to be useful \nin several areas important to pathology:\n\t\u2022\t \u0007Tumor classification: Particularly sarcomas (e.g., Ewing\u2019s \nsarcoma and synovial sarcoma), lymphomas, leukemias, \nkidney tumors, brain tumors, and other unusual tumors.\n\t\u2022\t \u0007Benign vs. malignant lesions:\n\t \u2022\t \u0007Reactive mesothelial cells vs. mesothelioma\n\t \u2022\t \u0007Lipoma vs. liposarcoma\n\t\u2022\t \u0007Prognosis: Neuroblastoma, oligodendroglioma, mul\u00ad\ntiple myeloma, chronic lymphocytic leukemia.\n\t\u2022\t \u0007Treatment: Amplification of HER2/neu to predict \nresponse to Herceptin.\n\t\u2022\t \u0007Research: Translocations are common to many tumors \nand usually identify genes important to the pathogenesis \nof the tumor\nCells may be cultured to perform complete karyotype \nanalysis or tissues can be analyzed for specific chromosomal \nalterations by fluorescence in situ hybridization (FISH).\nFISH studies can be performed on cultured cells, cytol\u00ad\nogy specimens, touch preparations, and paraffin-embed\u00ad\nded tissues.\nIndications.\u2002\n\t\u2022\t \u0007For karyotype analysis: Soft tissue tumors, mesothe\u00ad\nliomas (tissue or pleural fluid), unusual tumors, poorly \ndifferentiated tumors, all subcutaneous lipomas >10 cm \nor of unusual gross appearance, all deep-seated lipomas \n(subfascial, intramuscular, intraabdominal, retroperito\u00ad\nneal, clinically apparent cord tumors), unusual uterine \nmasses.\n\t\u2022\t \u0007For FISH: Oligodendroglioma, neuroblastoma.\nMethod for Submitting Tissue.\u2002 Tissue for karyotyp\u00ad\ning must be fresh, viable, and relatively sterile. However, \ntissue may be submitted even if it has not been handled \nunder strictly sterile conditions (contamination is not usu\u00ad\nally a problem). If specimens are to be held overnight, the \ntissue should be minced (into 0.1 cm cubes) in a sterile \nspecimen container, covered with culture medium, and \nheld overnight in the refrigerator. Fluids may also be sub\u00ad\nmitted for analysis (especially pleural effusions with a sus\u00ad\npicion of mesothelioma).\nResults.\u2002 The results of the cytogenetic analysis should \nbe incorporated into the final diagnosis or reported sepa\u00ad\nrately (Tables 7-47 and 7-48).\nText continues on page 178.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_180.png", "summary": "Paraffin-embedded tissue can be used for DNA-based PCR assays, but some fixatives may prevent genetic analysis. Cytogenetic studies are useful in tumor classification, distinguishing benign vs. malignant lesions, predicting prognosis, guiding treatment, and research purposes.", "questions": [ "How do different fixatives affect the ability to perform genetic analysis on paraffin-embedded tissue?", "What are the specific indications for cytogenetic studies in various types of proliferations and tumors?", "How can cytogenetic studies help in distinguishing between benign and malignant lesions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 181, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n163\nTABLE 7\u201347.\u2003\n\u0007COMMON CYTOGENETIC AND GENETIC CHANGES IN SOLID TUMORS OF DIAGNOSTIC \nOR THERAPEUTIC SIGNIFICANCE\nTUMOR TYPE\nCHARACTERISTIC \nCYTOGENETIC \nCHANGES\nGENETIC CHANGES\nFREQUENCY\nCOMMENTS\nAdenoid cystic \ncarcinoma\n6q translocations \nand deletions\n>50%\nAdrenal cortical \ncarcinomas\n2p16 loss\n>90%\nThis area is close to the region \n\u00adassociated with Carney complex \ntype 2.\n17p13 LOH\n85%\nThese changes are less common in \n\u00adlocalized tumors (25% to 35%) but, \nif present, such tumors are more \nlikely\u00a0to metastasize. The 11p15 \nimprinted region is also involved in \nBeckwith-Wiedemann syndrome.\n11p15 LOH with duplication \nof the active paternal \nallele leading to IGF-II \noverexpression\n85%\nAggressive angi\u00ad\nomyxoma\nt (12q15)\nHMGA2 involvement\n>20%\nAlveolar soft \npart sarcoma\nt(X;17)(p11.2;q25)\nASPL-TFE3 fusion\n>90%\nTFE3 can be detected by IHC. This \ntranslocation is also present in rare \npapillary-like renal tumors in young \nadults (see \u201cRenal tumors\u201d).\nAneurysmal \nbone cyst\nt(16;17)(q22;p13)\nCDH11-USP6 fusion\n20%\nt(17p13.2)\nUSP6 fusions\n>50%\nAngiomatoid \nfibrous \n\u00adhistiocytoma\nt(12;16)(q13;p11)\nFUS-ATF1 fusion\nUnknown\nt(12;22)(q13;q12)\nEWSR1-ATF1 fusion\nEWSR1-ATF1 translocation also present \nin clear cell sarcoma\nt(2;22)(q33;q12)\nCREB1-EWSR1 fusion\nBizarre \nparosteal \nosteochon\u00ad\ndromatous \nproliferation \n(Nora\u2019s lesion)\nt(1;17)(q32;q21)\nA breakpoint in 1q32 was found in 100% \nof lesions. A breakpoint in 17q21 was \nfound in 4 or 5 cases.\nt(1;17)(q42;q23)\nOnly one case with different breakpoints\nBreast \n\u00adcarcinoma\nHER2/neu amplification\n15-20%\nDetected by FISH (gene amplification) or \nIHC (protein overexpression). Positive \ncarcinomas are more likely to respond \nto Herceptin.a\nBRCA1 and BRCA2 germline \nmutations\n<5%\nPatients are more likely to be young \nand have multiple carcinomas. BRCA1 \ncarcinomas are frequently high grade, \nhave \u201cmedullary\u201d features, and lack ER, \nPR, HER2. BRCA2 carcinomas have no \nspecific pathologic features.\nt(12;15)\nETV6-NTRK3 fusion\n100% \n(\u00adsecretory \ncarcinoma)\nThis translocation is found in secretory \ncarcinomas. The same translocation \nis found in infantile fibrosarcoma and \ncellular mesoblastic nephroma.\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_181.png", "summary": "The page discusses common cytogenetic and genetic changes in various solid tumors of diagnostic or therapeutic significance, highlighting specific alterations and their frequencies.", "questions": [ "How do the cytogenetic and genetic changes mentioned in the table impact the diagnosis and treatment of solid tumors?", "What are the implications of the frequency of certain changes, such as the 2p16 loss in adrenal cortical carcinomas?", "Are there any specific diagnostic tests or techniques mentioned for detecting these cytogenetic and genetic changes in solid tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 182, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n164\nTUMOR TYPE\nCHARACTERISTIC \nCYTOGENETIC \nCHANGES\nGENETIC CHANGES\nFREQUENCY\nCOMMENTS\nCarcinoma of \nthe upper \n\u00adaerodigestive \ntract in \n\u00adchildren\nt(15;19)(q13;p13.2)\nBRD4-NUT fusion\nPatients with this translocation have a \npoor prognosis.\nChondromyx\u00ad\noid fibroma\nDeletion of 6q\n>75%\nClear cell \nhidradenoma\nt(11;19)(q21;p13)\nMECT1-MAML 2 fusion\nSame translocations as \nmucoepidermoid carcinoma \nand Warthin tumor\nClear cell \n\u00adsarcoma\nt(12;22)(q13;q12)\nEWSR1-ATF1 fusion\n>75%\nt(2;22)(q33;q12)\nEWSR1-CREB1 fusion\nUnknown\nColon \n\u00adcarcinoma\nhMLH1 and hMSH2 \n\u00admutations\n15% of \nsporadic \ncarcinomas\n95% of HNPCC patients have germline \nmutations in these genes. Absence \ncan be detected by IHC or by PCR \nassays for microsatellite instabil\u00ad\nity. Mutations are correlated with \ncharacteristic clinical, pathologic, and \ntreatment response features.\nEGFR (HER1) \n\u00adoverexpression\n82% of all car\u00ad\ncinomas\nApproximately 23% of patients treated \nwith cetuximabb and chemotherapy \nrespond.\nAPC mutations\n80% of all car\u00ad\ncinomas\nAlso present as a germline mutation \nin familial adenomatous polyposis \nsyndrome.\nLKB1/STK11 LOH\n~ 15%\nGermline mutations occur in some cases \nof Peutz-Jeghers syndrome. Mutations \nappear to be rare in sporadic colon \ncarcinoma but LOH is observed in \nsome.\nDPC4 (Smad4 or MADH4) \nmutations (18q21.1)\n10\u201320%\nGermline mutations in occur in some \ncases of juvenile polyposis syndrome. \nMutations in sporadic carcinomas are \nuncommon.\nDesmoplastic \nfibroblastoma\nt(2;11)(q31;q12)\nUnknown\nDesmoplastic \nsmall round \ncell tumor\nt(11;22)(p13;q12)\nEWSR1-WT1 fusion\n>95%\nWT1 can be detected by IHC.\nDermatofi\u00ad\nbrosarcoma \nprotuberans/\ngiant cell \nfibroblastoma\n+r(17;22)(q21;q13) \nt(17;22)(q21;q13),\nCOL1A1-PDGFB fusion\nCOL1A1-PDGFB fusion\n>75%\nThe same translocation is present in \ngiant cell fibroblastoma, but without \nformation of a ring chromosome.\nTABLE 7\u201347.\u2003\n\u0007COMMON CYTOGENETIC AND GENETIC CHANGES IN SOLID TUMORS OF DIAGNOSTIC \nOR THERAPEUTIC SIGNIFICANCE\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_182.png", "summary": "The page provides information on common cytogenetic and genetic changes in various solid tumors, including specific translocations and mutations associated with different tumor types.", "questions": [ "How do these cytogenetic and genetic changes impact the prognosis of patients with these solid tumors?", "What are the diagnostic methods used to detect these specific translocations and mutations in solid tumors?", "Are there any targeted therapies or treatment approaches based on these cytogenetic and genetic changes in solid tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 183, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n165\nTUMOR TYPE\nCHARACTERISTIC \nCYTOGENETIC \nCHANGES\nGENETIC CHANGES\nFREQUENCY\nCOMMENTS\nEndometrial \nstromal \n\u00adsarcoma\nt(7;17)(p15;q21)\nJAZF1-JJAZ1 fusion\n30%\nt(6;7)(p21;p15)\nJAZF1-PHF1 fusion\n10%\nt(6;10)(p21;p11)\nEPC1-PHF1 fusion\nRare\nEpithelioid \nhemangioen\u00ad\ndothelioma\nt(1;3)((p36.3;q25)\nEpithelioid \nsarcoma\nt/del(22q11.2)\nINI1 deletion, mutations\nAbsence can be detected by IHC.\nEwing sarcoma/\nPNET\nt(11;22)(q24;q12)\nEWSR1-FLI1 fusion\n>80%\nFLI1 can be detected by IHC but is not \nspecific for Ewing\u2019s. FISH can detect \nfusion genes.\nThe type of fusion is correlated with \nprognosis (e.g., Type I exon 6 has >100 \nmonth survival, Type II exon 5 has 2 \nyear survival).\nt(21;22)(q22;q12)\nEWSR1-ERG fusion\n5-10%\nt(2;22)(q33;q12)\nEWSR1-FEV fusion\n<5%\nt(7;22)(p22;q12)\nEWSR1-ETV1 fusion\n<5%\nt(17;22)(q12;q12)\nEWSR1-E1AF fusion\n<5%\ninv(22)(q12)(q12)\nEWSR1-ZSG fusion\n<5%\nt(16;21)(p11;q22)\nFUS-ERG fusion\nUnknown\nt(2;22)(q31;q12)\nEWSR1-SP3 fusion\nt(2;16)(q33;p11)\nFUS-FEV fusion\nExtraskeletal \nmyxoid \nchondrosar\u00ad\ncoma\nt(9;22)(q22;q12)\nEWS-NR4A3 fusion\n>75%\nt(9;17)(q22;q11)\nTAF2N-NR4A3 fusion\n<10%\nt(9;15)(q22;q21)\nTCF12-NR4A3 fusion\n<10%\nt(3;9)(q11;q22)\nTGF-NR4A3 fusion\nFibromatosis \n(desmoid)\nTrisomies of 8 and \n20\n30%\nDeletion of 5q21\nAPC inactivation\n10%\nBeta-catenin mutations\n50%\nNuclear beta-catenin can be detected \nby IHC.\nFibromyxoid \nsarcoma, low \ngrade\nt(7;16)(q32-34; \np11.2)\nFUS-CREB3L2 fusion\n96%\nt(11;16)(p11;p11)\nFUS-CREB3L1 fusion\nRare\nTABLE 7\u201347.\u2003\n\u0007COMMON CYTOGENETIC AND GENETIC CHANGES IN SOLID TUMORS OF DIAGNOSTIC \nOR THERAPEUTIC SIGNIFICANCE\u2014cont\u2019d\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_183.png", "summary": "The page lists common cytogenetic and genetic changes in solid tumors, including fusion genes and specific chromosomal translocations associated with different tumor types.", "questions": [ "How do cytogenetic and genetic changes play a role in the diagnosis and prognosis of solid tumors?", "What are the implications of detecting specific fusion genes or chromosomal translocations in tumor samples?", "How can techniques like immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) be used to detect these genetic changes in solid tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 184, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n166\nTUMOR TYPE\nCHARACTERISTIC \nCYTOGENETIC \nCHANGES\nGENETIC CHANGES\nFREQUENCY\nCOMMENTS\nFibrosarcoma, \ninfantile\nt(12;15)(p13;q25)\nETV6-NTRK3 fusion\n>75%\nThe same translocation is seen in cellular \nmesoblastic nephroma and secretory \nbreast carcinoma.\nTrisomies 8, 11, \n17,20\n>75%\nGastrointesti\u00ad\nnal stromal \ntumor\nMonosomies 14 \nand 22\n>75%\nDeletion of 1p\n>25%\nKIT or PDGFRA mutation\n>90%\nCD117 (KIT) is detected by IHC and \nis useful for diagnosis. Gleevecc \nis effective against tumors with \n\u00adactivating mutations in either gene. \nThe type of mutation correlates with \ntreatment response.\nGerm cell \ntumors\nIsochromosome 12p\n>80-90%\nIncludes all histologic subtypes in males \nand dysgerminomas of ovary\nKIT mutations\n25-70%\nSeminomas\nGiant cell tumor\nTelomeric changes\n>50%\nGiant cell \ntumor, diffuse \ntype (PVNS)\nt(1;2)(p13;q37) \nCOL6A3-CSF1 fusion\n>25% \n\u00adTrisomies 5 and 7\nUnknown\nGlioblastoma \nmultiforme \n(anaplastic \nmixed glioma)\nEGFR (HER1) amplification\n40%\nDetected by ISH. IHC is not helpful \nfor detecting overexpression. The \nco-deletion of 1p36 and 19q13.3 is \nabsent.\nHepatoblas\u00ad\ntoma\nTrisomies 2q and 20\n>75%\nHibernoma\n11q13 rearrange\u00ad\nment\n>50%\nInflammatory \nmyofibro\u00ad\nblastic tumor\nt(1;2)(q22;p23)\nTPM3-ALK fusion\nUnknown\nALK can be detected by IHC in one third \nof cases. There are other partners for \nALK fusion.\nt(2;19)(p23;p13)\nTPM4-ALK fusion\nt(2;17)(;23;q13)\nCLTC-ALK fusion\nt(2;2)(p23;q13)\nRANB2-ALK fusion\nLeiomyoma, \nuterine\nt(12;14)(q15;q24) \nDeletion of 7q \n\u00adDeletion of 1p\nHMGA2 rearrangement\n40%\nUterine leiomyosarcomas have more \ncomplex karyotypes.\nThese tumors are cellular and have \ngene expression patterns similar to \nleiomyosarcomas.\nTABLE 7\u201347.\u2003\n\u0007COMMON CYTOGENETIC AND GENETIC CHANGES IN SOLID TUMORS OF DIAGNOSTIC \nOR THERAPEUTIC SIGNIFICANCE\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_184.png", "summary": "The page provides information on common cytogenetic and genetic changes in various solid tumors, including fibrosarcoma, gastrointestinal stromal tumor, germ cell tumors, and glioblastoma multiforme.", "questions": [ "What is the significance of the ETV6-NTRK3 fusion in fibrosarcoma, infantile?", "How do KIT or PDGFRA mutations affect the diagnosis and treatment of gastrointestinal stromal tumors?", "What are the key genetic changes associated with leiomyoma, uterine, and leiomyosarcomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 185, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n167\nTUMOR TYPE\nCHARACTERISTIC \nCYTOGENETIC \nCHANGES\nGENETIC CHANGES\nFREQUENCY\nCOMMENTS\nLipoblastoma\n8q12 rearrange\u00ad\nment\nPLAG1 oncogene\n>80%\nPolysomy 8\nLipoma\nTypical\nt(12q15)\nHMGA2 rearrangement\n40%\nt(6p21)\nHMGA1 rearrangement\n10%\nt(8q12)\nPLAG1\n5%\nDeletion 13q\n5%\nSpindle cell or \npleomor\u00ad\nphic\nDeletion of 13q or \n16q\n>75%\nt(11;16)(q13;p12-13)\nUnknown\nLiposarcoma\nWell-\u00ad\ndifferentiated\nRing /giant markers \n(12q13-q15)\nHMGA2, MDM2 \n\u00adamplification\n>75%\nSimilar ring/giant markers are seen in \ndedifferentiated liposarcomas, with \nadditional aberrations\nMyxoid/round \ncell\nt(12;16)(q13;p11)\nt(12;22)(q13;q12)\nFUS-DDIT3(CHOP) fusion\nEWS-CHOP fusion\n>75%\n<5%\nPleomorphic\nComplex\n90%\nDedifferenti\u00ad\nated\nRing /giant markers \n(12q13-q15)\nHMGA2, MDM2 \n\u00adamplification\nLung adeno\u00ad\ncarcinomas \nthat respond \nto gef\u200aitinib \n(most in \nwomen, \nnonsmokers, \nwith features \nof BAC)\nFewer changes than \nseen in carcino\u00ad\nmas associated \nwith smoking\nEGFR - small deletions or \namino acid substitutions\n10-20% of \nall lung \n\u00adcarcinomas\nMutations predict response (gain of \nfunction) to the tyrosine kinase inhibi\u00ad\ntor gefitinib (Iressa).d \n40% to 80% of lung carcinomas show \nEGFR overexpression by IHC, but only \ncarcinomas with specific mutations \nrespond to gefitinib.\nMedulloblas\u00ad\ntoma\nIsochromosome 17q\n>25%\nMeningioma\nMonosomy 22\n90%\n1p deletion\n25%\nTABLE 7\u201347.\u2003\n\u0007COMMON CYTOGENETIC AND GENETIC CHANGES IN SOLID TUMORS OF DIAGNOSTIC \nOR THERAPEUTIC SIGNIFICANCE\u2014cont\u2019d\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_185.png", "summary": "The page provides a list of common cytogenetic and genetic changes in various solid tumors, including lipoblastoma, lipoma, liposarcoma, lung adenocarcinomas, medulloblastoma, and meningioma.", "questions": [ "What are the characteristic cytogenetic changes associated with lipoblastoma?", "How do the genetic changes differ between well-differentiated and dedifferentiated liposarcomas?", "What is the significance of EGFR mutations in lung adenocarcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 186, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n168\nTUMOR TYPE\nCHARACTERISTIC \nCYTOGENETIC \nCHANGES\nGENETIC CHANGES\nFREQUENCY\nCOMMENTS\nMesothelioma\nDeletion of 1p\n? \u0007BCL10 inactivation\n>50%\nCytogenetic changes are less complex \nthan those seen in carcinomas.\nCytogenetic analysis of cytologic \nspecimens (e.g., pleural fluid) can \nbe of value if larger biopsies are not \navailable.\nDeletion of 9p\np15, p16, and p19 \n\u00adinactivation\n>75%\nDeletion of 22q\nNF2 inactivation\n>50%\nDeletions of 3p and \n6q\n>50%\nMucoepi\u00ad\ndermoid \n\u00adcarcinoma\nt(11;19)(q21;p13)\nMECT1-MAML 2 fusion\n>50%\nSame translocation as Warthin tumor \nand clear cell hidradenoma\nNeuroblastoma\nHyperdiploid, no 1p \ndeletion\n40%\nGood prognosis\n1p deletion\n40%\nPoor prognosis\nDouble minute \nchromosomes\nN-MYC amplification\n>25%\nPoor prognosis\nOligodendro\u00ad\nglioma\nCo-deletion of 1p36 \nand 19q13.3\n50%\nUseful for diagnosis and to predict \nresponse to radiation and/or \n\u00adchemotherapy. EGFR amplification is \nabsent.\n9p21 deletion\nCDKN2A (p16) deletion\nOccurs in some anaplastic \n\u00adoligodendrogliomas. Poor \nprognostic factor.\nOsteochon\u00ad\ndroma\nDeletion of 8q\nEXT1 inactivation\n>25%\nOsteosarcoma\nLow grade\nRing chromosomes\n>50%\nHigh grade\nComplex\nRB and P53 inactivation\n>80%\nPheochromocytoma\nSporadic (70%)\nLosses on 1p\n>80%\nHereditary \n(30%)\nGermline mutations in RET, \nVHL, NF1, SDHB, SDHD, \nMEN2A, MEN2B\n>90% of \nhereditary \ncases\nPatients are more likely to be young \n(<50), have multiple tumors, and \nhave a family history of \n\u00adpheochromocytoma, paraganglioma, \nor medullary carcinoma of the \nthyroid.\nPleomorphic \nadenoma \n(salivary)\nt(3;8)(p21;q12)\nCTNNB1-PLAG1 fusion\n>50%\nt(8q12)\nPLAG1 fusions\n<20%\nt(9;12)(p12;q15)\nNFB1-HMGA2 fusion\nTABLE 7\u201347.\u2003\n\u0007COMMON CYTOGENETIC AND GENETIC CHANGES IN SOLID TUMORS OF DIAGNOSTIC \nOR THERAPEUTIC SIGNIFICANCE\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_186.png", "summary": "The page discusses common cytogenetic and genetic changes in various solid tumors, including mesothelioma, mucoepidermoid carcinoma, neuroblastoma, oligodendroglioma, osteosarcoma, pheochromocytoma, and pleomorphic adenoma.", "questions": [ "How do cytogenetic changes differ between different tumor types?", "What are the prognostic implications of specific genetic changes in these tumors?", "How can cytogenetic analysis of cytologic specimens be useful in the absence of larger biopsies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 187, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n169\nTUMOR TYPE\nCHARACTERISTIC \nCYTOGENETIC \nCHANGES\nGENETIC CHANGES\nFREQUENCY\nCOMMENTS\nProstate cancer\nt(21;21)(q22.2;q22.3)\nTMPRS2-ERG fusion\nUnknown\nt(7;21)(p21.2;q22.2)\nTMPRSS2-ETV1 fusion\nUnknown\nRenal Tumors\nClear cell \n\u00adcarcinoma\nDeletion of 3p\n90%\nVHL\n70%\nDeletion or inactivation\nPapillary \n\u00adcarcinoma\u00a0\u2013 \nadult\nTrisomies 3, 7, 12, \n16, 17, and 20\n>90%\nKIT mutations\n>90%\nCD117 (c-kit) present by IHC in \n\u00adcytoplasm and is associated with \nactivating mutations.\nXp11.2 or TFE3 \ntranslocation \ncarcinomas \n(young adults \n[<1% of all \nadults] and \nchildren \n[30% to 50% \nof pediatric \ncases], female \n> male, \n10% to 15% \nhave prior \n\u00adtreatment)\nt(X;17)(p11.2;q25.3)\nASPL/TFE3 fusion\nTumors have voluminous cytoplasm.\nThe ASPL-TFE3 fusion is also present in \nalveolar soft part sarcoma. TFE3 and \nTFEB can be detected by IHC.\nTumors have a more solid, compact \narchitecture, less voluminous cyto\u00ad\nplasm, less frequent psammoma \nbodies and hyaline nodules, and less \nprominent nucleoli.\nt(X;1)(p11.2;q21)\nPRCC/TFE3 fusion\nt(X;1)(p11.2;p34)\nTFE3-PSF fusion\ninv(X)(p11.2q12)\nTFE3/NonO fusion\nt(6;11)(p21.1;q12)\nTFEB-Alpha fusion\nOncocytoma\n-1, -X or -Y\n>25%\n11q13 rearrange\u00ad\nment\n>25%\nChromophobe \ncarcinoma\nMonosomies 1, 2, \n3, 6, 10, 13, 17, \nand 21\n>75%\nCD117 (c-kit) is present by IHC \non membranes, but activating \n\u00admutations have not been \ndetected.\nMesoblastic \nnephroma\nt(12;15)(p13;q25)\nETV6-NTRK3 fusion\nThe same translocation is seen in \n\u00adinfantile fibrosarcoma and secretory \nbreast carcinoma.\nRetinoblas\u00ad\ntoma\n13q14 deletion\nRB1 inactivation\n>75%\n40% of cases are due to germline \n\u00admutations in RB1.\nIsochromosome 6p\n25%\nTABLE 7\u201347.\u2003\n\u0007COMMON CYTOGENETIC AND GENETIC CHANGES IN SOLID TUMORS OF DIAGNOSTIC \nOR THERAPEUTIC SIGNIFICANCE\u2014cont\u2019d\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_187.png", "summary": "The page provides information on common cytogenetic and genetic changes in solid tumors, including prostate cancer, renal tumors, Xp11.2 or TFE3 translocation carcinomas, oncocytoma, chromophobe carcinoma, mesoblastic nephroma, and retinoblastoma.", "questions": [ "What are the characteristic cytogenetic changes associated with prostate cancer?", "How do genetic changes differ between clear cell carcinoma and papillary carcinoma of the renal tumors?", "What is the significance of the ETV6-NTRK3 fusion in mesoblastic nephroma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 188, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n170\nTUMOR TYPE\nCHARACTERISTIC \nCYTOGENETIC \nCHANGES\nGENETIC CHANGES\nFREQUENCY\nCOMMENTS\nRhabdoid \ntumor of the \nkidney and \natypical tera\u00ad\ntoid/rhabdoid \ntumor (AT/RT)\nNormal karyotype\nhSNF5/INI1 (22q11.2) \n\u00addeletions and mutations\n>90%\nInfants and children with both tumors \nhave a germline mutation in INI1 \n(rhabdoid predisposition syndrome).\nChoroid plexus carcinomas are also \nassociated with non-function of this \ngene (70%).\ndel/t(22)(q11.2)\nhSNF5/INI1 deletions and \nmutations\nRhabdomyosarcoma\nAlveolar\nt(2;13)(q35;q14)\nPAX3-FKHR fusion\n>75%\nPoor 4-yr survival if metastatic (8%)\nt(1;13)(p36;q14), \ndouble minutes\nPAX7-FKHR fusion\n10-20%\nBetter 4-yr survival if metastatic (75%)\nt(2:2)(q35;23)\nPAX3-NCOA1 fusion\nrare\nt(X;2)(q35;q13)\nPAX3-AFX fusion\nrare\nEmbryonal\nTrisomies 2q, 8, and \n20\n>75%\nLOH 11p15.5\n>75%\nSchwannoma \nand perineu\u00ad\nrioma\nDeletion of 22q\nNF2 inactivation\n>80%\n5% of cases of vestibular schwannomas \nare associated with neurofibromatosis \ntype 2 (germline NF2 mutations).\nSubungual \nexostosis\nt(X;6)(q13-14;q22)\nCOL4A5 and COL12A1 \ninvolvement\nSynovial \u00adsarcoma\nMonophasic\nt(X;18)(p11;q11)\nSYT with SSX1, SSX2, or \nSSX4 fusion\n>90%\nBiphasic\nt(X;18)(p11;q11)\nSYT-SSX1 fusion\n>90%\nTABLE 7\u201347.\u2003\n\u0007COMMON CYTOGENETIC AND GENETIC CHANGES IN SOLID TUMORS OF DIAGNOSTIC \nOR THERAPEUTIC SIGNIFICANCE\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_188.png", "summary": "The page discusses common cytogenetic and genetic changes in solid tumors, such as rhabdoid tumor of the kidney, rhabdomyosarcoma, schwannoma, and synovial sarcoma.", "questions": [ "What are the characteristic cytogenetic changes associated with rhabdoid tumor of the kidney and atypical teratoid/rhabdoid tumor?", "How do genetic changes in PAX3 and PAX7 affect the prognosis of rhabdomyosarcoma?", "What is the significance of NF2 inactivation in schwannoma and perineurioma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 189, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n171\nTUMOR TYPE\nCHARACTERISTIC \nCYTOGENETIC \nCHANGES\nGENETIC CHANGES\nFREQUENCY\nCOMMENTS\nThyroid \u00adcarcinoma\nPapillary\n10q11 rearrange\u00ad\nment\nRET/PTC rearrangements\n20%\nMost common in younger patients (avg \n26) and radiation-associated carcino\u00ad\nmas, all have psammoma bodies\nRAS mutations\n15%\nAll follicular variant, rare LN mets, 6 \nwomen to 1 man, larger tumors\n1q21 rearrange\u00ad\nment\nNTRK1 fusion oncogenes\n>10%\nBRAF point mutation\n44%\nOlder patients (avg 48), some anaplastic \nand poorly differentiated carcinomas \n(15% are tall cell), higher stage, more \nextrathyroidal invasion\nFollicular\nt(2;3)(q13;p25)\nPAX8-PPARG fusion\n>40%\n45% have RAS mutations\nMedullary\nSporadic \n(75%)\nRET activating mutations\n>90%\nHereditary \n(25%)\nGermline RET, MEN2A, or \nMEN2B mutations\n>90%\nIndication for screening for \n\u00adpheochromocytoma and screening \nfamily members\nWilms tumor, \npediatric\nDeletion 11p13\nWT1 inactivation\n25%\nGermline mutations occur in several \nsyndromes. WT1 mutations also occur \nin sporadic tumors.\nTrisomy 12\n40%\nWTX\nWTX is inactivated in approximately one-\nthird of Wilms tumors \naTrastuzumab (Herceptin) = a monoclonal antibody directed against the HER2/neu receptor. Patients are selected for treatment by testing carcinomas with IHC or FISH.\nbCetuximab (C225, Erbitux) = a monoclonal antibody directed against the EGFR receptor. A test has been approved by the FDA for the determination of EGFR (DakoCyoma\u00ad\ntion, EGFR PharmDX). This test is not used for lung carcinomas.\ncaImatinib mesylate (STI571, Gleevec, Glivec) is a small molecule tyrosine kinase inhibitor that may be used for the treatment of tumors overexpressing tyrosine kinases:\nBcr-Abl tyrosine kinase: CML, ALL (Ph+)\nKIT tyrosine kinase: GIST, systemic mastocytosis, some types of AML\nPDGFR kinase: CMML, chronic eosinophilic leukemia, rare cases of GIST\nThe KIT protein (CD117) is encoded by the c-kit proto-oncogene and is a transmembrane receptor protein with tyrosine kinase activity. Mutations may render KIT indepen\u00ad\ndent of its ligand, SCF (stem cell factor). Mutated proteins may or may not respond to therapy with Imatinib. Wild-type KIT and KIT with mutations in the juxtamembrane \ndomain (the intracellular segment between the transmembrane and tyrosine kinase domains) are found in GISTs and are sensitive to imatinib. Other tumor types are \nassociated with mutations in the enzymatic domain and the altered protein is generally not sensitive to imatinib. Overexpression of the protein is detected by IHC.\ndGefitinib (Iressa) = a tyrosine kinase inhibitor effective against a small subset of lung adenocarcinomas with specific activating mutations in EGFR. IHC for EGFR is not help\u00ad\nful for identifying carcinomas likely to respond to treatment.\nFor additional information on specific genes, see Online Mendelian Inheritance in Man (OMIM; www.ncbi.nlm.nih.gov).\nTABLE 7\u201347.\u2003\n\u0007COMMON CYTOGENETIC AND GENETIC CHANGES IN SOLID TUMORS OF DIAGNOSTIC \nOR THERAPEUTIC SIGNIFICANCE\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_189.png", "summary": "The page discusses common cytogenetic and genetic changes in solid tumors, including thyroid carcinoma, Wilms tumor, and medullary carcinoma, among others.", "questions": [ "What are the characteristic cytogenetic changes seen in papillary thyroid carcinoma?", "How do genetic changes in Wilms tumor differ between sporadic and hereditary cases?", "What is the significance of screening for pheochromocytoma in patients with hereditary medullary carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 190, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n172\nTABLE 7\u201348.\u2003\nCOMMON CYTOGENETIC CHANGES IN LYMPHOMAS AND LEUKEMIAS\nTUMOR TYPE\nCYTOGENETIC \nCHANGES\nMOLECULAR EVENTS\nFREQUENCY\nCOMMENTS\nChronic Leukemias and Mastocytosis\nCML (Ph1)\nt(9;22)(q34;q11.2)\nBCR-ABL fusion \u00ad(usually \np210, but also p190 \nand p230 fusion \n\u00adproteins)\n90-95%\nPhiladelphia chromosome. Also \u00adpresent \nin 5% of children and 15-30% of \nadults with ALL and 2% of patients \nwith AML.\nTreated with the ABL tyrosine kinase \ninhibitor imatinib (Gleevec)a. \n\u00adMutations in BCR-ABL are associated \nwith resistance. RT-PCR is used to \ndetect minimal residual disease.\nOther variants or \ncryptic transloca\u00ad\ntions\nBCR-ABL fusion \u00ad(usually \np210, but also p190 \nand p230 fusion \n\u00adproteins)\n5-10%\nCML, accelerated \nphase or blast \nphase\nAdditional changes: \nextra Ph, +8, or \ni(17)(q10)\n80%\nMay be myeloid (70%) or lymphoid \n(30%).\nJuvenile \nmyelomonocytic \nleukemia\nPTPN11 mutation\n35%\n11% of patients have neurofibromatosis \ntype 1.\nNF1 mutation\n20%\nNRAS and KRAS2 muta\u00ad\ntions\n20%\nChronic eosinophilic \nleukemia\nt(5;12)(q33;p13)\nETV6 (also called TEL) - \n\t\u0007PDGFRB fusion\nRare\nWith eosinophilia.\nExcellent response to imatinib.a\nt(5q33)\nSeveral PDGFRB fusions\n?rare\nExcellent response to imatinib.a\nCryptic del(4)(q12) \u2013 \ninterstitial 800 kb \ndeletion\nFIP1L1-PDGFRA fusion\n~ 50%\nThe fusion protein is an activated \ntyrosine kinase. Excellent response \nwith the tyrosine kinase inhibitor \nimatinib.a\nFIP1L1-PDGFRA muta\u00ad\ntion (T6741)\nDetected by FISH.\nHomologous to the resistance-\ninducing T3151 mutation in \nBCR-ABL.\nt(4q12)\nSeveral PDGFRA fusions\n?rare\nStem cell \u00adleukemia- \nlymphoma \nsyndrome\nt(8;13)(p11;q11-12)\nFGFR1-ZNF198 fusion\nUnknown\nFeatures of both lymphoma and \neosinophilic MPD.\nt(8p11)\nSeveral FGFR1 fusions\nRare\nClassic MPD\nPolycythemia\nJAK2V617F\n95%\nJAK2 exon 12 mutation\n5%\nEssential \nthrombocythe\u00ad\nmia\nJAK2V617F\n50%\nMPLW515L/K\n1%\nPrimary \n\u00admyelofibrosis\nJAK2V617F\n50%\nMPLW515L/K\n5%", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_190.png", "summary": "The page discusses common cytogenetic changes in lymphomas and leukemias, including specific translocations, fusions, and mutations associated with different types of chronic leukemias and mastocytosis.", "questions": [ "What is the significance of the t(9;22)(q34;q11.2) translocation in CML?", "How does the BCR-ABL fusion protein play a role in treatment and disease progression?", "What are some key molecular events associated with chronic eosinophilic leukemia?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 191, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n173\nTUMOR TYPE\nCYTOGENETIC \nCHANGES\nMOLECULAR EVENTS\nFREQUENCY\nCOMMENTS\nChronic Leukemias and Mastocytosis\nUnclassified MPD\nt(9;21)(p24;p13)\nETV6-JAK2\nt(9;22)(p24;q11.2)\nBCR-JAK2 fusion\nt(8;9)(p22;p24)\nPCM1-JAK2 fusion\nSystemic \n\u00admastocytosis\nc-KIT point mutations \n(Asp816Val)\n100%\nCD117 (c-kit) is detected by \nIHC in normal and abnormal mast \ncells. The most common mutations \ndo not result in proteins sensitive to \nimatinib.\nCryptic del(4)(q12) \u2013 \ninterstitial 800 kb \ndeletion\nFIP1L1-PDGFRA fusion\n~60% of \npatients \nwith \neosinophilia\nFound in mastocytosis with associ\u00ad\nated eosinophilia. These patients do \nnot have the typical c-KIT mutation. \nExcellent response to treatment with \nimatinib a.\nAcute Myeloid Leukemia\nAML\nNormal karyotype\n40-50%\nFLT3 (13q12) internal \ntandem duplications \n(ITD, 20%) or point \nmutations (7%)\n20 -30%\nMore common in monocytic AML \n(M5), less common in myeloblastic \nleukemia with maturation (M2) or \nerythroleukemia (M6). Less common \nin AML with cytogenetic changes \n(10%). Poor prognostic factor.\nResults in an activated tyrosine kinase. \nCurrent trials are evaluating response \nto a kinase inhibitor \u2013 PKC412.\nPartial tandem duplica\u00ad\ntion MLL (11q23)\n10%\nExon 2 through 6 \nalso carry FLT3-IDT mutation.\nHigh expression BAALC \n(8q22.3)\nAdult younger than 60 yrs with de novo \nAML, unfavorable prognostic impact\nIndependent adverse \u00adprognostic \n\u00adfactor for resistance to initial \n\u00adinduction chemotherapy.\nCEBPA (19q13.1) \n\u00admutation\n4-15%\nFavorable prognostic significance.\nNPM1(5q35) mutation\n45-62%\nCytoplasmic localization of \n\u00adnucleophosmin 956dupTCTG in exon \n12 (type A).\nFemale, higher WBC, low/absence \nCD34+, 40% also carry FLT3-IDT or \nTKD mutation.\nPatients with NPM1 mutations lacking \nFLT3-IDT had significantly better CR \nrates.\nOverexpression ERG \n(21q22)\nAdverse prognosis.\nTABLE 7\u201348.\u2003\nCOMMON CYTOGENETIC CHANGES IN LYMPHOMAS AND LEUKEMIAS\u2014cont\u2019d\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_191.png", "summary": "The page discusses common cytogenetic changes in chronic leukemias, mastocytosis, and acute myeloid leukemia, including fusion genes, mutations, and their frequencies.", "questions": [ "What are some common cytogenetic changes found in chronic leukemias and mastocytosis?", "What is the significance of the FLT3 mutations in acute myeloid leukemia?", "How do NPM1 mutations impact the prognosis of AML patients?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 192, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n174\nTUMOR TYPE\nCYTOGENETIC \nCHANGES\nMOLECULAR EVENTS\nFREQUENCY\nCOMMENTS\nAcute Myeloid Leukemia\nAML (M1, M2, or M4)\nt(6;9)(p23;q34)\nDEK-CAN fusion\n1% of all AML\nPoor prognosis.\nFLT3 ITDs\n90% of this \nAML type\nAML with t(8;21) \n(M2)\nt(8;21)(q22;q22)\nAML1(RUNX1)-ETO \nfusion\n5-12% of AML\n30% of cases of AML with karyotypic \nabnormalities and maturation in \nneutrophilic lineage.\nUsually younger patients, good \n\u00adprognosis\nc-KIT mutations\n~50% of this \nAML type\nResponse to imatiniba untested.\nOther RUNX1 fusion\nToxic exposure.\nAcute promyelo\u00ad\ncytic leukemia \n(M3, M3v.)\nt(15;17)(q22;\nq11-12)\nPML-RARA fusion\n5-8% of AML \n(95-100% of \nAPML)\nAbnormal promyelocytes predominate. \nUsually occurs in adults in mid life. \nTreatment with all trans-retinoic \nacid acts to differentiate the cells. \n\u00adFavorable prognosis.\nt(11;17)(q23;p21)\nPLZF-RARA fusion\nt(5;17)(q34;q12)\nNPM1-RARA fusion\nt(11;17)(p13;q21)\nNUMA-RARA fusion\nFLT3 ITDs\n32% of APML\nAML with inv(16) or \nt(16;16)\ninv (16)(p13)(q22)\nt(16;16)(p13;q22)\ndel(16q)\nOther rare variants \nor cryptic translo\u00ad\ncations\nCBFB-MYH11 fusion\n10-12% of \nAML (100% \nof M4EO)\nMonocytic and granulocytic \n\u00addifferentiation and abnormal \n\u00adeosinophils in the marrow. \u00adUsually \nyounger patients. Favorable \n\u00adprognosis.\nc-KIT mutations\n~50% of this \nAML type\nResponse to imatiniba untested.\nAML with 11q23 \nabnormalities\n11q23 \n\u00adabnormalities\nMLL fusion with \n\u00adnumerous different \npartners (86)\n5-6% of AML\nUsually associated with monocytic \nfeatures. Occurs in infants \nand in patients after therapy \nwith topoisomerase II inhibitors. \n\u00adIntermediate prognosis.\nAML and MDS, \ntherapy related\n5q-/7q-/12p-/20q-\nOccurs after alkylating agents and/or \nradiation, usually 5 to 6 years after \ntreatment. Poor prognosis.\nt(9;11), t(11;19), \nt(6;11)\nMLL balanced \n\u00adtranslocations\nOccurs after DNA-topoisomerase II \ninhibitors, usually 3 years after \ntreatment. Long-term prognosis \nunknown.\nt(21q22)\nOther RUNX1 fusion\nTABLE 7\u201348.\u2003\nCOMMON CYTOGENETIC CHANGES IN LYMPHOMAS AND LEUKEMIAS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_192.png", "summary": "The page provides information on common cytogenetic changes in various types of acute myeloid leukemia (AML) and their associated molecular events and frequencies.", "questions": [ "What are some of the cytogenetic changes and molecular events associated with AML with favorable prognosis?", "What are the implications of c-KIT mutations in AML?", "How do therapy-related AML and MDS differ from de novo AML in terms of cytogenetic changes and prognosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 193, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n175\nTUMOR TYPE\nCYTOGENETIC \nCHANGES\nMOLECULAR EVENTS\nFREQUENCY\nCOMMENTS\nB Cell\nB \u00adlymphoblastic \nleukemia/\u00ad lym\u00ad\nphoma (ALL)\nt(9;22)(q34;q11.2)\nBCR-ABL fusion\n(usually p190 [esp. in \nchildren], but also \np210 protein)\n5% of \n\u00adchildhood \nALL, 20-\n25% of \nadult ALL\nPhiladelphia chromosome.\nPoor prognosis.\nt with 11q23\nMLL rearrangements\nPoor prognosis. Usually infants.\nt(12;21)(p13;q22)\nETV6(TEL)-AML1 fusion\n> 50% of \nchildhood \nALL or \nhyperdip\u00ad\nloid\nGood prognosis. This \u00adtranslocation \nis not detected by standard \n\u00adcytogenetics.\nDetected by FISH.\nt(1;19)(q23;p13.3)\nPBX1-E2A fusion\n5-6%\nPre-B-ALL; most common \u00adtranslocation \nin childhood. Unfavorable but \n\u00admodified by therapy.\nHypodiploid\nPoor prognosis.\nHyperdiploid >50\nGood prognosis (= DNA Index 1.16 to \n1.6).\nt(5;14)(q31;q32)\nIL3-IGH fusion\nPoor prognosis.\nt(8;14)(q24;q32)\nMYC-IGH fusion\nGood prognosis.\nt(2;8)(p12;q24)\nIGK-MYC fusion\nGood prognosis.\nt(8;22)(q24;q11)\nMYC-IGL fusion\nGood prognosis.\nt(17;19)(q21;p13)\nHLF-E2A fusion\nPoor prognosis.\nt(4;11)(q21;q23)\nMLL-AF4 fusion\nPoor prognosis.\nALL, therapy related\nSimilar to therapy-related AML.\nSmall lymphocytic \nlymphoma/CLL\ntrisomy 12\n16%\nUsually do not have IgVH mutations.\nAggressive clinical course.\ndel(11q22-23)\nATM deletion\n18%\nPoor prognosis.\nDetected by FISH.\ndel(13q14)\nD13S319 deletion\n55%\nUsually do have IgVH mutations.\nLong term survival.\nDetected by FISH.\nTABLE 7\u201348.\u2003\nCOMMON CYTOGENETIC CHANGES IN LYMPHOMAS AND LEUKEMIAS\u2014cont\u2019d\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_193.png", "summary": "This page provides a list of common cytogenetic changes in lymphomas and leukemias, along with associated tumor types, molecular events, and frequencies.", "questions": [ "What are the different types of cytogenetic changes associated with B cell lymphoblastic leukemia/lymphoma?", "How do different cytogenetic changes impact the prognosis of patients with small lymphocytic lymphoma/CLL?", "What is the significance of detecting certain cytogenetic changes using FISH in these malignancies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 194, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n176\nTUMOR TYPE\nCYTOGENETIC \nCHANGES\nMOLECULAR EVENTS\nFREQUENCY\nCOMMENTS\nB Cell\ndel(17p)\nP53 deletion\n7%\nWorse prognosis.\nDetected by FISH.\nIgVH not mutated\n40-50%\nWorse prognosis (< 8 year median \nsurvival).\nIgVH (mutated, \n> 2% \u00addifference in \n\u00adnucleotide sequence)\nZAP70\n50-60%\nBetter prognosis (median survival > 24 \nyears).\nLymphoplasma\u00ad\ncytic lymphoma \n(Waldenstr\u00f6m \nmacroglobulin\u00ad\nemia)\n6q deletion\n50% if in bone \nmarrow\nDetected by FISH. Not specific for LPL.\nMantle cell \n\u00adlymphoma\nt(11;14)(q13;q32)\nCCND1-IGH fusion\nATM point mutations\n>95%\nOverexpression of cyclin D1 detected \nby IHC.\nMarginal zone \n\u00adlymphoma \n(MALT)\n+3\n60%\nt(1;14)(p21;q32)\nBCL10-IGH fusion\nt(11;18)(q21;q21)\nAPI2-MALT1 fusion\n25-50%\nt(11;14)(q21;q32)\nMALT1-IGH fusion\nSplenic\ndel(7q21)\nFollicular lymphoma\nt(14;18)(q32;q21)\nIGH-BCL-2 fusion\n70-95%\nt(2;18)(p12;q21)\nIGK-BCL-2 fusion\nRare\nBurkitt lymphoma \nand Burkitt-like \nlymphoma\nt(8;14)(q24;q32)\nMYC-IGH fusion\n85%\nt(2;8)(p12;q24)\nMYC-IGK fusion\nRare\nt(8;22)(q24;q11)\nMYC-IGL fusion\nRare\nt(8q24)\nOther MYC fusion\nMediastinal (thymic) \nlarge B-cell \n\u00adlymphoma\n9p+\nREL amplification\nDiffuse large B-cell \nlymphoma\nt(3q27)\nBCL6 translocations with \nmany partners\n30%\nBCL6 is detected by IHC in most cases, \nBCL2 in some cases.\nt(14;18)(q32;q21)\ntrisomy 18\nBCL2-IGH fusion\n20-30%\nTABLE 7\u201348.\u2003\nCOMMON CYTOGENETIC CHANGES IN LYMPHOMAS AND LEUKEMIZAS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_194.png", "summary": "The page provides information on common cytogenetic changes in various types of lymphomas and leukemias, including specific chromosomal abnormalities and molecular events associated with different tumor types.", "questions": [ "How do cytogenetic changes impact the prognosis of different types of lymphomas?", "What are the specific molecular events associated with B cell lymphomas?", "How are cytogenetic changes detected in these types of cancers?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 195, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n177\nTUMOR TYPE\nCYTOGENETIC \nCHANGES\nMOLECULAR EVENTS\nFREQUENCY\nCOMMENTS\nB Cell\nHairy cell leukemia\nNo consistent changes.\nHodgkin lymphoma\nNo consistent changes.\nPrimary effusion \nlymphoma\nNo consistent changes.\nPlasmacytoma/\nmyeloma\nt(11;14)(q13;q32)\nCCND1-IGH fusion\nBest prognosis.\nt(6;14)(p21;q32)\nCCND3-IGH fusion\nt(4;14)(p16;q32)\nFGF23-IGH fusion\nAdverse prognosis.\nt(14;16)(q32;q23)\nIGH-MAF fusion\nAdverse prognosis.\nMonosomy 13/13q-\n15-40%\nT Cell\nPrecursor lympho\u00ad\nblastic leukemia/\nlymphoblastic \nlymphoma\nTranslocations \ninvolving TCR \nalpha, beta, delta, \nand gamma and \npartner genes \nMYC, TAL1, \nRBTN1, RBTN2, \nHOX11, and LCK\n30%\ndel(1)\nTAL1 (small deletion)\n25%\nAdolescents.\nt(1;14)\nTAL1-TCRdelta fusion\n>30%\nAdolescents.\nt(5;14)\nHOX11L2-TCRdelta \nfusion\nYoung children.\ndel(9p)\nCDKN2A deletion\nT-cell \n\u00adprolymphocytic \nleukemia\ninv(14)(q11;q32)\nTCR\u03b1/\u03b2-TCL1 & TCL1b \nfusion\n80%\nt(14;14)(q11;q32)\nTCR\u03b1/\u03b2-TCL1 & TCL1b \nfusion\n10%\nt(7;14)(q35;q32.1)\nTCR\u03b2-TCL 1A fusion\n70-80%\nChrom 8 \n\u00adabnormalities\nAdult T-cell \n\u00adlymphoma/\nleukemia\nNo consistent changes.\nTABLE 7\u201348.\u2003\nCOMMON CYTOGENETIC CHANGES IN LYMPHOMAS AND LEUKEMIAS\u2014cont\u2019d\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_195.png", "summary": "The page outlines common cytogenetic changes in various types of lymphomas and leukemias, including specific translocations and deletions associated with different tumor types.", "questions": [ "What are the cytogenetic changes associated with B cell plasmacytoma/myeloma and how do they impact prognosis?", "What translocations are commonly seen in T cell precursor lymphoblastic leukemia/lymphoblastic lymphoma and what are their frequencies?", "Are there any consistent cytogenetic changes identified in adult T-cell lymphoma/leukemia?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 196, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n178\nTUMOR TYPE\nCYTOGENETIC \nCHANGES\nMOLECULAR EVENTS\nFREQUENCY\nCOMMENTS\nT Cell\nMycosis \u00adfungoides \nand Sezary \n\u00adsyndrome\nNo consistent changes.\nPeripheral T-cell \nlymphoma, \nNOS\nNo consistent changes.\nHepatosplenic T-cell \nlymphoma\ni(7q)(q10)\n100%\nPanniculitis-like \nT-cell lymphoma\nNo consistent changes.\nAngioimmunoblas\u00ad\ntic lymphoma\nTrisomy 3, trisomy \n5, + X\nEnteropathy-type \nT-cell \nlymphoma\nNo consistent changes.\nAnaplastic large \ncell lymphoma \n(CD30+)\nt(2;5)(p23;q35)\nNPM1-ALK fusion pro\u00ad\ntein (p80)\n70-80%\nALK detected by IHC in nucleus, \n\u00adnucleolus, and cytoplasm.\nt(2p23)\nSeveral ALK fusions\nALK detected by IHC in cytoplasm.\nExtranodal NK/T-cell \nlymphoma, nasal \ntype\nNo consistent changes.\nBlastic NK-cell \n\u00adlymphoma\nNo consistent changes.\naImatinib mesylate (STI571, Gleevec, Glivec) is a small molecule tyrosine kinase inhibitor that may be used for the treatment of tumors overexpressing tyrosine kinases:\nBcr-Abl tyrosine kinase: CML, ALL (Ph+)\nKIT tyrosine kinase: GIST, systemic mastocytosis, some types of AML\nPDGFR kinase: CMML, chronic eosinophilic leukemia, rare cases of GIST\nThe KIT protein is encoded by the c-kit proto-oncogene and is a transmembrane receptor protein with tyrosine kinase activity. Mutations may render KIT independent of its \nligand, SCF (stem cell factor). Mutated proteins may or may not respond to therapy with Imatinib. Wild-type KIT and KIT with mutations in the juxtamembrane domain (the \nintracellular segment between the transmembrane and tyrosine kinase domains) are found in GIST\u2019s and are sensitive to imatinib. Other tumor types are associated with \nmutations in the enzymatic domain and the altered protein is generally not sensitive to imatinib.\nFor additional information on specific genes, see Online Mendelian Inheritance in Man (OMIM; www.ncbi.nlm.nih.gov).\nTABLE 7\u201348.\u2003\nCOMMON CYTOGENETIC CHANGES IN LYMPHOMAS AND LEUKEMIAS\u2014cont\u2019d\nTumors and Diseases Associated with Germline \nMutations (Tables 7-49 and 7-50)\nThe following features are suggestive of hereditary suscep\u00ad\ntibility to cancer:\n\t\u2022\t \u0007Two or more close relatives on the same side of the fam\u00ad\nily with cancer\n\t\u2022\t \u0007Evidence of autosomal dominant transmission\n\t\u2022\t \u0007Early development of cancer in the patient and relatives \n(in general, <50 years of age)\n\t\u2022\t \u0007Multiple primary cancers\n\t\u2022\t \u0007Multiple types of cancers\n\t\u2022\t \u0007Unusual pathologic features of tumors (Table 7-49)\n\t\u2022\t \u0007A constellation of tumors suggestive of a specific syn\u00ad\ndrome (Table 7-50)\nPathologists can aid in the detection of hereditary carcino\u00ad\nmas by being aware of the types and pathologic characteris\u00ad\ntics of carcinomas associated with these syndromes. Patients \nwith germline mutations are important to identify in order to:\n\t \u2022\t \u0007Screen patients for other common tumors or other \ncomponents of the disease\n\t \u2022\t \u0007Consider prophylactic surgery or preventive interventions\n\t \u2022\t \u0007Offer screening to family members at risk and genetic \ncounseling\nText continues on page 184.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_196.png", "summary": "The page discusses common cytogenetic changes in various types of lymphomas and leukemias, as well as the use of Imatinib mesylate in the treatment of tumors overexpressing tyrosine kinases.", "questions": [ "How do cytogenetic changes vary among different types of T-cell lymphomas?", "What are the implications of the ALK fusion proteins in anaplastic large cell lymphoma?", "How can pathologists aid in the detection of hereditary carcinomas and what are the suggested actions for patients with germline mutations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 197, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n179\nTABLE 7\u201349.\u2003 PATHOLOGIC FEATURES OF TUMORS AND DISEASES SUGGESTIVE OF A GERMLINE MUTATION\nTYPE OF TUMOR\n% OF CASES RELATED \nTO KNOWN GERMLINE \nMUTATIONS\nSYNDROMES/GENES \nINVOLVED\nCLUES FOR THE PATHOLOGIST\nAdrenocortical carci\u00ad\nnoma in children\n50% to 100%\nLi-Fraumeni, \n\u00adBeckwith-Wiedemann, \nMEN1\nUnusual occurrence in a child.\nAngiomyolipoma \nof kidney\n20%\nTuberous sclerosis\nPatients may be screened for other features of \ntuberous sclerosis.\nBasal cell carcinoma\nRare if solitary\nNevoid basal cell \n\u00adcarcinoma syndrome\nRisk of a mutation is increased if multiple or if \ntumor occurs at <30 years of age.\nBreast cancer, poorly \ndifferentiated, ER \nnegative*\n>25% if <35 years old, \n<10% if >35 years old\nBRCA1\nBRCA1 cancers are more likely to have \n\u00ad\u201cmedullary\u201d features, and be ER- PR- HER2/\nneu -. BRCA1 mutation more likely if patient \nhas a family history or has bilateral cancer.\nBreast cancer, male\n4% to 14%\nBRCA2\nCancers are of no specific type.\nColorectal carcinoma, \npoorly differentiated, \nmucinous, or with \nprominent lympho\u00ad\ncytic infiltrate\n\t ~ \u000710\u201315% overall, ~80% \nif patient is <40\nHNPCC\nHNPCC carcinomas are more likely \nright -sided (two-thirds), poorly \ndifferentiated (\u201cmedullary\u201d), mucinous, signet \nring, \u00adlymphocytic infiltrate.\nIHC for MSH2 and MLH1 can be used to detect \nmany, but not all, cases, but MLH1 may also \nbe absent in sporadic cases.\nGI neuroendocrine \ntumors:\nSomatostatinoma\nPPoma\nNon-functioning\nGastrinoma\nGlucagonoma\nVIPoma\nInsulinoma\nCarcinoid\n45%\n18-44%\n18-44%\n20-25%\n1-20%\n6%\n4-5%\nRare\nMEN1 mutations\nMEN1 mutations are also found in 15% to 70% \nof sporadic neuroendocrine tumors.\nHirschsprung \ndisease\n20-40%\nMEN2A (RET mutations \nin codons 609, 618, \n620)\nJuvenile \n\u00ad(hamartomatous) \npolyps\nRare if solitary\nJuvenile polyposis \n\u00adsyndrome\nSuspect JPS if there are >5 polyps, if present \nthroughout the GI tract, or if there is a family \nhistory of juvenile polyps.\nMedullary carcinoma \nof the thyroid\n25%\nMEN2A, MEN2B, familial \nmedullary carcinoma \n(RET mutations)\nMay be multiple and associated with C cell \nhyperplasia.\nCancers in occur in children in MEN2B and in \nyoung adults in MEN2A.\nMedulloblastoma\nRare (?)\nNevoid basal cell \n\u00adcarcinoma syndrome\nIf <3 years of age or of desmoplastic type, risk of \nmutation is increased.\nMyxoma, cardiac\n<5%\nCarney complex\nIncreased likelihood if multiple, right-sided, \nand/or recurrent and in young patients (<30).\nNeurofibromas\n~10% if solitary but >90% \nif plexiform\nNeurofibromatosis type 1\nIncreased risk if there are \u22652 neurofibromas or \none plexiform neurofibroma.\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_197.png", "summary": "The page discusses pathologic features of tumors and diseases suggestive of a germline mutation, including the types of tumors, percentage related to known germline mutations, syndromes/genes involved, and clues for the pathologist.", "questions": [ "How can pathologists use the information provided to identify potential germline mutations in patients?", "What are some specific characteristics of tumors that may indicate a higher likelihood of a germline mutation?", "How important is it for patients with these types of tumors to undergo genetic testing for germline mutations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 198, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n180\nTYPE OF TUMOR\n% OF CASES RELATED \nTO KNOWN GERMLINE \nMUTATIONS\nSYNDROMES/GENES \nINVOLVED\nCLUES FOR THE PATHOLOGIST\nOvarian carcinoma\nRare\nBRCA1, BRCA2\nIncreased risk if there is a history of breast cancer.\nBRCA1-associated carcinomas are more likely to \nbe serous in type.\nPheochromocytoma\n30% of all cases, 59% if \npatient is <18, 84% if \nbilateral\nMEN2A, MEN2B, VHL, \nIsolated familial pheo\u00ad\nchromocytoma\nMultiple tumors, hyperplasia of the medulla.\nPrimary \u00adpigmented \nnodular \n\u00adadrenocortical \n\u00addisease (PPNAD)\n>90%\nCarney complex (25% \nhave PPNAD)\nMay present with Cushing syndrome.\nMost are associated with germline mutations, \nbut patients may not have other manifesta\u00ad\ntions of the Carney complex.\nRetinoblastoma\n40% of all cases, 100% \nif bilateral or with a \n\u00adpositive family history\nRB mutations \n(13q14.1-q14.2)\nRhabdomyoma of \nheart in infants\n50%\nTuberous sclerosis\nSarcoma, children\n7-33%\nLi-Fraumeni, basal cell \nnevus syndrome, \nneurofibromatosis \ntype 1, pleuropul\u00ad\nmonary blastoma \nsyndrome\nSebaceous carcinoma\n~10% if ocular, 40% if \nabove the chin, 80% if \nelsewhere\nHNPCC\nIncreased likelihood if the tumor has cystic \ndegeneration or features of \u00adkeratoacanthoma.\nUsually due to germline MSH2 mutations.\nSchwannoma, \n\u00adpsammomatous \nmelanotic\n>50%\nCarney complex\nHigher likelihood if patient is young (<30 years) \nand/or multiple tumors present.\nSchwannoma, \n\u00advestibular\n5%\nNeurofibromatosis type 2\nRisk is increased if the patient is <30 or if there \nis bilateral involvement.\nSporadic cases almost all have somatic NF2 \nmutations.\nSertoli cell tumor, \nlarge-cell calcifying\n25-35%\nCarney complex, \n\u00adPeutz-Jeghers\nMost are bilateral and multifocal in young \npatients. Rarely malignant. Present in 30% of \nmales with Carney complex.\nTrichilemmoma, facial, \nmultiple\n~80%\nPTEN\nSporadic tumors also have loss of PTEN which \ncan be shown by IHC.\nWilms tumor\n10-15%\nGermline mutations in \nWT1 (11p13)\nNephrogenic rests are present and may be \nextensive.\n5% to 10% of cases associated with \ngermline mutations are multicentric or \nbilateral.\nAssociated with WAGR syndrome (Wilms tumor, \naniridia, GU anomalies, mental retardation) \nand Denys-Drash syndrome.\n*See Lakhani SR, et al, The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 \nin patients with mutations in BRCA1 and BRCA2. J Clin Oncol 20:2310-2318, 2002, for additional information relating pathologic characteristics to risk of a BRCA1 mutation.\nTABLE 7\u201349.\u2003 PATHOLOGIC FEATURES OF TUMORS AND DISEASES SUGGESTIVE OF A GERMLINE MUTATION\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_198.png", "summary": "The page discusses various types of tumors and diseases that are suggestive of a germline mutation, including ovarian carcinoma, pheochromocytoma, retinoblastoma, and Wilms tumor.", "questions": [ "What are some clues for the pathologist to consider when diagnosing ovarian carcinoma?", "What are the key syndromes and genes involved in pheochromocytoma?", "How are Sertoli cell tumors and Wilms tumors associated with germline mutations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 199, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n181\nTABLE 7\u201350.\u2003\nHEREDITARY SYNDROMES ASSOCIATED WITH MULTIPLE TUMORS\nSYNDROME\nGERMLINE MUTATIONS\nTUMORS (% OF PATIENTS \nDEVELOPING TUMOR)\nCOMMENTS\nBeckwith-Wiede\u00ad\nmann syndrome\n11p15 abnormalities \n(loss of methylation, \n\u00aduniparental disomy, \nmutations in CDKN1C)\nWilms tumor, neuroblastoma, hepato\u00ad\nblastoma, adrenocortical carcinoma, \nrhabdomyosarcoma\nMacrosomia, macroglossia, \nvisceromegaly, ear creases \nand pits, omphalocele, \n\u00adhypoglycemia.\nBloom syndrome\nBLM (RecQL3), 15q26.1\nAcute leukemia, lymphoma, gastrointes\u00ad\ntinal adenocarcinoma (20% of patients \ndevelop a malignancy)\nCharacteristic appear\u00ad\nance, \u00adcaf\u00e9-au-lait spots, \n\u00adtelangiectasias.\nCarcinomas do not have a specific \nappearance.\nBRCA1 and 2\nBRCA1 (17q21), BRCA2 \n(13q12.3)\nBreast (85%), ovary (BRCA1 63%, BRCA2 \n27%), prostate carcinoma, others\nBRCA1 breast cancers are more \noften poorly differentiated, \nhave medullary features, are \nER- PR- HER2/neu -, and \nhave p53 mutations. Ovarian \n\u00adcarcinomas are generally serous \n(90%), high grade, and bilateral. \nBRCA2 cancers do not have \nspecific pathologic features.\nCarney complex\nType 1 (CNC1) (30% of \npatients): PRKAR1A \n(17q23-24)\nType 2 (CNC2) (40% of \npatients): locus at 2p16\n30% of patients do \nnot have identified \n\u00admutations\nMyxomas (cardiac, cutaneous, breast), \n\u00adprimary pigmented nodular \n\u00adadrenocortical disease (25%), \u00adlarge-cell \ncalcifying Sertoli cell tumors (> 90% \nmales), multiple thyroid nodules or \ncarcinoma (75%), growth \u00adhormone \n\u00adproducing pituitary adenoma (10%), \npsammomatous melanotic schwannoma \n(10%), breast duct \u00adadenomas, \nosteochondromyxoma of bone\nPigmented skin lesions (lentigos, blue \nnevi (especially epithelioid blue nevus), \ncaf\u00e9-au-lait spots)\nThe skin lesions characteristically \ninvolve the vermillion border \nof the lip and the intercanthal \nportion of the eye.\nMyxomas of the heart can involve \nall chambers (sporadic tumors \nusually involve the left atrium) \nand frequently recur.\nCarney triad\nUnknown\nGastric gastrointestinal stromal tumor, \npulmonary chondroma, extra-adrenal \nparaganglioma\nAlso esophageal leiomyomas and \n\u00adadrenocortical tumors\nMost patients are young and \nfemale. Only 22% have all three \ntumors. Most family members \nare not affected.\nFamilial adenoma\u00ad\ntous poly\u00adposis \n(FAP; includ\u00ad\ning Gardner \n\u00adsyndrome and \nTurcot syndrome)\nAPC (5q21-22)\nColorectal carcinoma, upper GI carcinoma, \ndesmoid, Gardner fibroma, osteoma, \nthyroid, brain (1/3 to 2/3 are medullo\u00ad\nblastomas \u2013 Turcot syndrome)\nFamilial gastroin\u00ad\ntestinal stromal \ntumor syndrome\nKIT (4q12)\nPDGFRA\nGIST, often multiple (> 90% lifetime risk), \nhyperplasia of the interstitial cells of \nCajal\nGIST may occur at younger ages.\nFamilial \u00admedullary \nthyroid \n\u00adcarcinoma\nRET mutations in codons \n10, 11, 13, 14 (10q11.2)\nMedullary thyroid carcinoma\nCancers usually occur in adults.\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_199.png", "summary": "The page discusses hereditary syndromes associated with multiple tumors, detailing the germline mutations, tumors commonly seen, and specific characteristics of each syndrome.", "questions": [ "What are some common tumors associated with Beckwith-Wiedemann syndrome?", "How do BRCA1 and BRCA2 mutations differ in terms of breast and ovarian cancers?", "What are the key features and tumors associated with Carney complex?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 200, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n182\nSYNDROME\nGERMLINE MUTATIONS\nTUMORS (% OF PATIENTS \nDEVELOPING TUMOR)\nCOMMENTS\nHereditary diffuse \ngastric cancer \nsyndrome\nCDH1\n(e-cadherin) (16q22.1)\nSignet ring cell carcinoma of the \u00adstomach \n(67% men, 83% women), lobular \n\u00adcarcinoma of the breast (39% women)\n50% of sporadic signet ring cell \ncarcinomas have CDH1 somatic \nmutations and all show loss of \ne-cadherin by IHC.\nHereditary \nnon-polyposis \nsyndrome*\n(\u201cLynch \n\u00adsyndrome\u201d but \nfirst patients \nwere described \nby Warthin)\nMismatch repair genes: \nMSH2 (2p22-p21) (40%), \nMLH1 (3p21.3) (40%), \nMSH6 (2p16) (5 to 7%), \nPMS2 (7p22) (rare)\nColon carcinoma (80%), endometrial carci\u00ad\nnoma (20 to 60%), ovarian carcinoma \n(9 to 12%), stomach carcinoma (11 to \n19%), hepatobiliary tumors (2 to 7%), \ntransitional cell carcinoma (4 to 5% - \nesp ureter and renal pelvis), small bowel \ntumors (1 to 4%), lymphoma (rare)\nSebaceous skin tumors, \u00adadenomas, \n\u00adepitheliomas, carcinoma, \n\u00adkeratoacanthomas (Muir-Torre \u2013 \nusually MSH2)\nColon carcinomas are more likely \n(overall, 66%) to be on the \nright side, poorly differenti\u00ad\nated (\u201cmedullary\u201d), mucinous, \nsignet ring, or undifferentiated, \nwith a prominent lymphocytic \ninfiltrate.\nIHC can be used to detect the \nabsence of MSH2 (usually due \nto germline mutations) and \nMLH1 (can be due to \u00adgermline \nmutations, epigenetic changes \n(methylation), or less \u00adcommonly, \nsomatic mutations) in many \npatients. IHC is 92% \u00adsensitive for \nMSI and 100% specific.\nMSI testing is also used.\nJuvenile polyposis \nsyndrome\nMADH4 (or SMAD4) \n(18q21.10 (15%) or \nBMPR1A (10q22.3) \n(25%)\nHamartomatous (juvenile) polyps, GI \ncarcinomas\nLi-Fraumeni\np53 (17p13.1), rarely \nCHEK2 (22q12.1)\nSarcomas, breast cancer, leukemia, \n\u00adosteosarcomas, brain tumors, \n\u00adadrenocortical carcinoma, others\nMEN1\nMEN 1 (11q13)\nPituitary adenoma, pancreatic islet cell \ntumors, parathyroid adenomas, adreno\u00ad\ncortical tumors, carcinoids, lipomas\nMEN1 mutations also occur \nin 15 to 70% of sporadic \n\u00adneuroendocrine tumors.\nMEN2A\nRET\nexon 10 and 11 missense \nmutations (10q11.2)\nMedullary thyroid carcinoma (95%), \nhyperplasia of the parathyroids \n(15-30%), pheochromocytoma (50%), \nganglioneuromatosis of GI tract.\nSubsets of patients have Hirschsprung \n\u00addisease or cutaneous lichen amyloidosis\nSpecific mutations correlate \nwith age at development of \n\u00admedullary thyroid carcinoma.\nMEN2B\nRET\nmissense mutation in \nexon 16 (10q11.2)\nMedullary thyroid carcinoma (100%), \npheochromocytoma (50%)\nMucosal neuromas of lips and tongue,\nMarfanoid habitus, distinctive \nfacies.\nNevoid basal \ncell carcinoma \n\u00adsyndrome \u00ad(Gorlin \n\u00adsyndrome)\nPTCH (9q22.3)\nBasal cell carcinomas (90%), odontogenic \nkeratocysts (90%), cardiac or ovarian \nfibromas (20%), medulloblastoma in \nchildhood (5%)\nMacrocephaly, skeletal \u00adanomalies, \npalmar or plantar pits, \n\u00adcalcification of falx (90%).\nNeurofibromatosis \ntype 1\nNF1 (17q11.2)\nNeurofibromas (esp plexiform) (100%), \noptic gliomas, adrenal ganglioneuro\u00ad\nmas, pheochromocytoma (0.1 \u2013 6%), \nMPNST (10%), leukemia, ganglioneuro\u00ad\nmatosis of the GI tract\nCaf\u00e9-au-lait macules (95%), iris \nhamartomas (Lisch nodules), \naxillary freckling.\nTABLE 7\u201350.\u2003\nHEREDITARY SYNDROMES ASSOCIATED WITH MULTIPLE TUMORS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_200.png", "summary": "The page discusses various genetic syndromes associated with specific germline mutations and their correlation with different types of tumors.", "questions": [ "How do the specific germline mutations mentioned in the text contribute to the development of different types of tumors?", "What are some common characteristics or features of the tumors associated with the genetic syndromes described?", "How are these genetic syndromes diagnosed and managed in clinical practice?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 201, "text": "SPECIAL STUDIES\u2003 Cytogenetics\n183\nSYNDROME\nGERMLINE MUTATIONS\nTUMORS (% OF PATIENTS \nDEVELOPING TUMOR)\nCOMMENTS\nNeurofibromatosis \ntype 2\nNF2 (22q12.2)\nBilateral vestibular schwannomas (100%, \n40% have lobular pattern), schwanno\u00ad\nmas of other nerves, meningiomas \n(50%, often fibroblastic)\nPeutz-Jeghers \n(Hamartomatous \npolyp syndrome)\nLKBI/STK11 (19p13.3)\nColon, breast, stomach, pancreas, small \nbowel, thyroid, lung, uterus, sex cord \nstromal tumors, calcifying Sertoli cell \ntumors\nHamartomatous polyps of GI tract\nPerioral pigmentation.\nPheochomocytoma \nor paragangli\u00ad\noma, familial\nSDHB (1p36.1-p35) \nSDHD (11q23) \nSDHC (1q21) \n\u00ad(paraganglioma)\nPheochromocytoma, paraganglioma\nPatients are more commonly \nyoung (< 40), with multifocal \nadrenal tumors, or extra-adrenal \ndisease.\nSDHD is imprinted and only \n\u00adconfers susceptibility after \npaternal transmission.\nPTEN hamartoma \nsyndrome \n(including 80% \nof Cowden\u2019s syn\u00ad\ndrome, 50-60% \nof Bannayan-\nRIley-Ruvalcaba \nsyndrome)\nPTEN (10q23.31)\nBreast cancer (25 to 50%), thyroid \ncarcinoma (10% - especially \nfollicular), endometrial carcinoma \n(5 to 10%), hamartomatous polyps of \nGI tract\nMultiple facial trichilemmomas, acral \nkeratosis, oral papillomatous lesions, \nmucosal lesions\nMacrocephaly (megalencephaly, \n97th percentile), Lhermitte-\nDuclos disease.\nTuberous sclerosis\nTSC1 (9q34), \nTSC2 (16p13,3)\nSubependymal glial nodules (90%), \ncortical or subcortical tubers (70%), \nangiomyolipoma of kidney (70%), \nlymphangiomyomatosis of lung (1 to \n6%), rhabdomyoma of heart \n(47 to 67%)\nSkin lesions (100%, including \nmyomelanotic macules, multiple facial \nangiofibromas, shagreen patch, \nfibrous facial plaque, ungual \nfibroma)\nSeizures (80%), developmental \ndelay or retardation (50%).\nVon Hippel-Lindau \n(VHL)\nVHL (3p26-p25)\nHemangioblastomas (retinal, cerebellar, \nspinal cord) (80%), renal cell carcinoma \n(40%), renal cysts, pancreatic cysts, \npheochromocytoma, endolymphatic\n sac tumors (10%), epididymal cystad\u00ad\nenomas\n*MSI-H is found in 11% of sporadic colon carcinomas and has histologic features similar to patients with germline mutations. There is reduced response to 5-FU but better \nsurvival. >5 fold increased risk of metachronous cancers.\nFor additional information on most syndromes, see http://www.genetests.org/and Online Mendelian Inheritance in Man (OMIM; www.ncbi.nlm.nih.gov).\nTABLE 7\u201350.\u2003\nHEREDITARY SYNDROMES ASSOCIATED WITH MULTIPLE TUMORS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_201.png", "summary": "The page discusses various hereditary syndromes associated with multiple tumors, listing the specific genes involved and the types of tumors commonly seen in each syndrome.", "questions": [ "What are some common features shared by the hereditary syndromes mentioned on this page?", "How do the different germline mutations mentioned affect the types of tumors that develop in each syndrome?", "Is there a pattern in the age of onset or specific characteristics of the tumors seen in these hereditary syndromes?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 202, "text": "SPECIAL STUDIES\u2003 Specimen Radiography\n184\nAlthough the sporadic forms of cancers, in general, far \noutnumber cases associated with germline mutations, in \nsome cases the appearance or site of a carcinoma is highly \nsuggestive of a known syndrome and further investigation \nmay be warranted.\nANALYTICAL CYTOLOGY (FLOW CYTOMETRY)\nFlow cytometers analyze populations of thousands of dis\u00ad\nsaggregated cells as they pass by stationary detectors. Cell \nsize and cytoplasmic granularity can be measured as well as \nDNA content and the presence or absence of immunohis\u00ad\ntochemical markers added to the cell suspension. Newer \ntechniques can analyze three or more features simultane\u00ad\nously to divide cells into unique populations. DNA content \ncan be used to determine the number of cells in S-phase \n(a\u00a0 measure of proliferation\u00a0 - S-phase fraction). Because \ncells are not visualized by this technique, one must be sure \nto submit only lesional tissue.\nIndications for Ploidy and S-Phase Analysis.\u2002\n\t\u2022\t \u0007Hydatidiform moles \u2013 complete (diploid), partial (trip\u00ad\nloid)\n\t\u2022\t \u0007Some carcinomas \u2013 DNA ploidy and S-phase have been \nreported to be of prognostic significance for some car\u00ad\ncinomas (e.g., colon, breast, and prostate) but is not \nroutinely performed at all institutions or used by all \noncologists.\nIndications for Cell Surface Marker Analysis.\u2002\n\t\u2022\t \u0007Lymphomas and leukemias\nMethod for Submitting Tissue.\u2002 Single cell suspen\u00ad\nsions are necessary for analysis. For fresh tissues, cells must \nbe viable. Fresh tissue (approximately 0.3 to 0.5 cm3) is \nplaced in a specimen container and kept moist with HBSS. \nTissues can be held overnight in a refrigerator.\nFormalin-fixed paraffin-embedded sections may also \nbe used for DNA ploidy analysis by the Hedley method, \nalthough the results are not as satisfactory due to nuclear \nfragmentation.\nResults.\u2002 The results are usually incorporated into the \nfinal surgical pathology report.\nCYTOLOGIC PREPARATIONS FROM SURGICAL \nSPECIMENS\nCytologic preparations of surgical specimens often add \nadditional information.\n\t\u2022\t \u0007Intraoperative diagnosis: Touch preps or smears are \nespecially valuable for:\n\t \u2022\t \u0007Infectious cases (to avoid contamination of the cryo\u00ad\nstat and aerosolization of infectious agents)\n\t \u2022\t \u0007Neuropathology cases \u2013 for diagnosis and for the per\u00ad\nformance of cytogenetic (FISH) analysis.\n\t \u2022\t \u0007Tumors (for excellent cytologic detail, especially lym\u00ad\nphomas and papillary carcinomas of the thyroid)\n\t\u2022\t \u0007Special stains: Stains for microorganisms can be per\u00ad\nformed the same day on cytologic smears of specimens \nfrom critically ill patients. Do not submit air-dried \nsmears of infectious cases for staining as the unfixed \nmaterial may constitute a hazard to laboratory per\u00ad\nsonnel. Fat is dissolved during routine processing, \nbut can be demonstrated with fat stains on air dried \nslides.\n\t\u2022\t \u0007Genetic studies (FISH): In touch preparations nuclei \nare intact, unlike tissue sections in which only partial \nnuclei are present. This feature makes these prepara\u00ad\ntions superior for techniques such as FISH and image \nanalysis.\nComparing cytology preparations and the correspond\u00ad\ning surgical specimen is always a useful exercise in learning \nthe comparative morphology of these techniques.\nSPECIMEN RADIOGRAPHY\nSpecimen radiographs are often preferable over patient \nradiographs:\n\t\u2022\t \u0007A permanent record of the radiograph can be kept with \nthe case.\n\t\u2022\t \u0007A radiograph of the specimen may reveal more details \nof the underlying process (e.g., fewer structures may be \npresent to complicate the appearance).\n\t\u2022\t \u0007There may have been a significant time interval between \nthe patient radiograph and the surgical excision.\n\t\u2022\t \u0007The radiograph will often indicate important sites to \nexamine histologically (tumor invasion into a rib or \nmicrocalcifications in a breast biopsy).\n\t\u2022\t \u0007The specimen radiograph can confirm that the clinical \nlesion was removed.\nIndications.\u2002\n\t\u2022\t \u0007Tumors of bone and cartilage\n\t\u2022\t \u0007Tumors invading into bone\n\t\u2022\t \u0007Avascular necrosis\n\t\u2022\t \u0007All bioprosthetic heart valves (to document the degree \nof calcification)\n\t\u2022\t \u0007Breast biopsies or mastectomies performed for mammo\u00ad\ngraphic lesions that cannot be located grossly. Paraffin \nblocks of breast tissue can be radiographed if microcal\u00ad\ncifications were seen by specimen radiography but not \nin histologic sections and were not identified prior to \nprocessing. Clips placed after core needle biopsy are also \neasily identified.\nCalcifications can dissolve in formalin over several days. \nIf the demonstration of calcifications is important (e.g., \nmammographically detected calcifications) it is preferable \nto process the tissue within 1 to 2 days. If processing is to \nbe delayed, the tissue can be stored in ethanol.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_202.png", "summary": "The page discusses the use of special studies like specimen radiography, flow cytometry, and cytologic preparations from surgical specimens in pathology.", "questions": [ "How do flow cytometers analyze populations of cells?", "What are the indications for ploidy and S-phase analysis?", "Why are cytologic preparations valuable for intraoperative diagnosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 203, "text": "185\nSPECIAL STUDIES\u2003 Microbiological Culture and Smears\nMethod.\u2002 Radiographic equipment is available in radiol\u00ad\nogy departments and in some pathology departments. The \nspecimen may be placed on a piece of wax paper (to keep the \nsurfaces clean) lying on the film. Specimens can be radio\u00ad\ngraphed after decalcification (not all calcium is removed) \nbut best results are obtained on fresh undecalcified speci\u00ad\nmens. Lungs should not be inflated prior to radiography.\nIf the specimen is small, two exposures at different set\u00ad\ntings or at different angles may be useful. Lead sheets can \nbe used to allow two exposures on one piece of film.\nIf the film is too dark (overexposed), the exposure is too \nhigh and a lower setting should be tried. If the film is too \nlight (i.e., unexposed) the exposure is too low and a higher \nsetting is indicated.\nSpecial injection techniques with radiocontrast media are \navailable for unusual specimens (e.g., a recipient lung with \npulmonary hypertension, vascular ectasia of the bowel).\nOctreotide and Sentinel Nodes.\u2002 Labeled compounds are \nsometimes used to localize certain types of tumors (gener\u00ad\nally neuroendocrine) or sentinel lymph nodes. The patient \nis injected with the isotope prior to surgery and the sur\u00ad\ngeon uses a hand held probe to identify the labeled tissue. \nThe amount of radioactivity in the tissue is small and gen\u00ad\nerally does not pose a hazard to pathologists handling the \ntissue and does not need special disposal methods. How\u00ad\never, each pathology department should consult with their \nradiation safety department to ensure appropriate handling \nof such tissues. In some cases, if a gross lesion is not present \ncorresponding to the area of \u00adoctreotide uptake, specimens \ncan be imaged using a gamma camera.\nResults.\u2002 The radiographs are documented in the gross \ndescription and any information gained from the radio\u00ad\ngraph is incorporated into the surgical pathology report.\nTISSUE FOR RESEARCH \u2014 TUMOR BANK\nThe pathology department is a unique resource for \nresearchers who need human tissues. The pathologist plays \na key role as patient advocate and diagnostician in order to \nprovide appropriate human tissues for biologic research. \nMost hospitals have a policy that allows the release of \ntissue for research if it would otherwise be discarded. \nTherefore, tissue is never provided for research until all \nnecessary tissue has been taken for diagnosis. Tissue from \nprimary diagnostic breast biopsies and open lung biopsies \nwithout gross lesions must not be given away. It is in the \nbest interest of the patient that a pathologist evaluate the \nspecimen rather than have tissue given away by nonpathol\u00ad\nogists who are not aware of what is needed for diagnosis.\nIndications.\u2002 By request of researchers who have \nobtained permission from the hospital Institutional \nReview Board (IRB). Patients must provide specific con\u00ad\nsent. In some cases, all patient identification will need to \nbe removed from the specimen.\nMICROBIOLOGICAL CULTURE AND SMEARS\nThe investigation of infectious disease by culture is com\u00ad\nplementary to its investigation by histologic sections \n(Tables 7-51 to 7-53).\nTABLE 7\u201351.\u2003\nIDENTIFICATION OF INFECTIOUS DISEASES\nCULTURE\nHISTOLOGIC SECTIONS\nCan be performed on aspirates, swabs, fluids, or tissues.\nRequires surgical excision of tissues.\nCultures amplify the number of organisms present, \nallowing them to be recognized.\nOrganisms may be rare, or not seen in tissue sections.\nThe specific organism can be identified and tested for \ndrug susceptibility.\nCategories of organisms can be recognized but specific identification may \nnot be possible.\nSome organisms cannot be cultured.\nMany organisms can be identified that will not grow in culture or that \nrequire long culture times (e.g., TB).\nIt may be difficult to exclude contamination for \na \u00adpositive culture.\nMorphologic evidence of an inflammatory response provides evidence for \na clinical infection. The location of the infection may be of \u00addiagnostic \nimportance (e.g., cellulitis vs. necrotizing fasciitis or superficial \n\u00adcolonization of devitalized tissue vs. deep infections involving viable \ntissues).\nThe use of special studies, such as PCR and other molecular assays, may \nbe warranted if the tissue pattern of injury is indicative of a potential \norganism despite lack of culture evidence and/or lack of organisms \nseen on tissue sections.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_203.png", "summary": "The page discusses the use of radiographic equipment for imaging specimens, special injection techniques with radiocontrast media, and the importance of pathologists in providing appropriate human tissues for research.", "questions": [ "What are the best practices for radiographing specimens?", "How are labeled compounds used to localize tumors or sentinel lymph nodes?", "What is the role of the pathologist in providing human tissues for research?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 204, "text": "186\nSPECIAL STUDIES\u2003 Microbiological Culture and Smears\nTABLE 7-52.\u2003\nFUNGI: HISTOLOGIC APPEARANCE IN SURGICAL SPECIMENS\nHISTOLOGIC APPEARANCE OF FUNGUS\nSTAINS\nUSUAL SITES OF INFECTION \n(PATIENT GROUPS)\nTISSUE RESPONSE\nCANDIDA SPECIES (C. ALBICANS, 60%; C. TROPICALIS, C. PARAPSILOSIS, C. KRUSEI)\n3- to 4-\u03bcm round yeast forms\nTrue hyphae with acute angle \nbranching (5-10 \u03bcm)\nBudding yeast (single bud)\nExtracellular\nMSS (+)\nPAS (+)\nGram (+) (unlike \nmost other \nfungi)\nSkin/oral: superficial\nLarynx (thrush) (immunocom\u00ad\npromised; newborn)\nVagina (pregnancy; DM; anti\u00ad\nbiotic use)\nEsophagus (HIV; malignancy)\nInvasive/systemic: kidney, \nliver, lung, heart valves \n(immunocompromised)\nOral, vaginal, disseminated \n(immunocompromised; \nantibiotic therapy; elderly; \ndenture wearing)\nFungi on surface of \nepithelium, Cl, +/\u2212 \neosinophils\nUlcer, pseudomem\u00ad\nbrane, dirty necro\u00ad\nsis, PMNs, MP, GC, \noccasional GRAN\nAI\nCANDIDA GLABRATA (\u201cTORULOPSIS\u201d)\nSimilar to other Candida but \nno true hyphae\nOnly small yeast forms are \nusually present\nUrogenital tract (immuno\u00ad\ncompromised)\nBloodstream \n(\u00adimmunocompromised)\nSimilar to C. albicans\nHISTOPLASMA CAPSULATUM\n2- to 5-\u03bcm yeast forms\nUnequal budding\nOften intracellular in histio\u00ad\ncytes or PMNs (looks like \nleishmania but with no \nkinetoplast\u2014one dot only)\nVery rare short pseudohyphae\nGiemsa may give false impres\u00ad\nsion of a capsule\nMSS (+)\nPAS (+)\nMucicarmine (\u2212)\nFM (\u2212)\nGiemsa (+)\nLung (Mississippi and Ohio \nRiver valleys): usually an \nincidentally found fibro\u00ad\ncaseous nodule in lung, \nlymph node, liver, or spleen \n(patients are not immuno\u00ad\ncompromised)\nDisseminated (e.g., gastroin\u00ad\ntestinal, lung, lymph node) \n(immunocompromised)\nNEC GRAN or old \nresolved GRAN \nwith calcifications, \ndegenerate fungal \nforms\nPredominantly intra\u00ad\ncellular organisms, \nMP, GRAN, not AI\nIndications.\u2002\n\t\u2022\t \u0007Suspected infectious processes, either by clinical data or \nby frozen section\n\t\u2022\t \u0007Suspected sarcoid to exclude an infectious process\nMethod.\u2002 Tissue is kept as sterile as possible. Suture \nremoval kits are a convenient source of sterile scissors and \nforceps. Serially section the specimen to determine if there \nare focal lesions. Place representative sections in a sterile \nspecimen container making sure to retain a duplicate piece \nof tissue for histology. Label with the patient\u2019s name and \nunit number, patient\u2019s physician, type of specimen, collec\u00ad\ntion date, and time of collection (required for Joint com\u00ad\nmission accreditation).\nResults.\u2002 The results are generally reported by the micro\u00ad\nbiology laboratory. Communication with the microbiology \nlaboratory and staff is essential to correlate histologic results \nwith microbiology results from the same specimen.\nReports.\u2002 The results of culture of surgical specimens \nare usually reported in a separate report.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_204.png", "summary": "The page discusses the histologic appearance of various fungi in surgical specimens, including Candida species, Candida glabrata, and Histoplasma capsulatum. It also provides information on the usual sites of infection and tissue response.", "questions": [ "How can the histologic appearance of fungi in surgical specimens help in diagnosing infectious processes?", "What are the differences in tissue response between different Candida species?", "Why is it important to keep tissue sterile during the microbiological culture process?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 205, "text": "187\nSPECIAL STUDIES\u2003 Microbiological Culture and Smears\nHISTOLOGIC APPEARANCE OF FUNGUS\nSTAINS\nUSUAL SITES OF INFECTION \n(PATIENT GROUPS)\nTISSUE RESPONSE\nZYGOMYCETES (INCLUDING THE GENERA MUCOR, RHIZOPUS, RHIZOMUCOR, ABSIDIA, AND CUNNINGHAMELLA)\nLarge hyphae, irregular in \nwidth, infrequently septate \nhyphae, 6-50 \u03bcm\nRight angle branching\nBudlike or bulbous \n\u00adprojections\nNo yeast forms\nUsually seen without stains\nMSS (weak)\nPAS (weak)\nH&E (+)\nSkin (primary or hematog\u00ad\nenous) (DM)\nRhinocerebral (DM, leukemia, \ndialysis)\nLung (immunocompromised)\nGI or bladder\nInvasion of BVs with \ninfarction, hemor\u00ad\nrhage, perineural \ninvasion, little \nhost response or \nAI (all patients are \nimmunocompro\u00ad\nmised)\nASPERGILLUS SPP. (A. FUMIGATUS, 90%; A. FLAVUS, A. NIGER, A. TERREUS, A. NIDULANS)\nSeptate hyphae, 45-degree \nbranching, 3-8 \u03bcm, evenly \ncontoured\nFruiting bodies (pigmented) \nseen only in necrotic tissue \nwith air exposure (rarely in \ninvasive lesions)\nDilated and distorted hyphae \nare present in chronic \nlesions\nMSS (+)\nPAS (+)\nGram (weak)\nIHC and ISH \navailable\nNose/sinus:\nInvasive (immunocompro\u00ad\nmised)\nNoninvasive\nAllergic mucin\nBronchopulmonary:\nSuperficial (allergic broncho\u00ad\npulmonary aspergillosis)\nBronchocentric \n\u00adgranulomatosis\nAspergilloma: fungal ball in \npreexisting necrotic cavity \n(not immunocompromised)\nInvasive: target lesions \n(necrotic areas with periph\u00ad\neral hemorrhage) (immuno\u00ad\ncompromised)\nSkin: usually secondary to \nhematogenous spread\nUlceration, AI, fungi \nin viable tissue\nMat of fungal \nhyphae, little or no \ninflammation\nEosinophils and \nhyphae in mucin, \nCharcot-Leyden \ncrystals\nBronchiolitis or \nalveolitis, eosino\u00ad\nphils, mucoid \nimpaction with \nfragmented fungal \nhyphae\nCircumferential \nGRAN of small \nairways, mucin \nimpaction with \nfragmented fungal \nhyphae, eosino\u00ad\nphils\nLittle tissue \nresponse, Cl. \nConidiophores \n(fruiting bodies) \nmay be present if \nin contact with air. \nAspergillus niger \nis associated with \ncalcium oxalate \nproduction caus\u00ad\ning thrombosis \nand ischemic \nnecrosis\nInvasion of arteries \nwith thrombosis \nand infarction, \nmay be +/\u2212 host \nresponse; may \nresolve with GRAN\nMicroabscesses and \nNEC GRAN\nTABLE 7\u201352.\u2003\nFUNGI: HISTOLOGIC APPEARANCE IN SURGICAL SPECIMENS\u2014cont\u2019d\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_205.png", "summary": "The page discusses the histologic appearance and usual sites of infection for two types of fungi, Zygomycetes and Aspergillus spp.", "questions": [ "What are the distinguishing features of Zygomycetes in terms of hyphae structure and staining characteristics?", "What are the typical patient groups and sites of infection associated with Zygomycetes and Aspergillus spp.?", "What are the differences in histologic appearance between invasive and noninvasive forms of Aspergillus infections?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 206, "text": "188\nSPECIAL STUDIES\u2003 Microbiological Culture and Smears\nHISTOLOGIC APPEARANCE OF FUNGUS\nSTAINS\nUSUAL SITES OF INFECTION \n(PATIENT GROUPS)\nTISSUE RESPONSE\nCRYPTOCOCCUS NEOFORMANS\n2-15 \u03bcm, spherical or oval \nnarrow-based unequal \nbuds, prominent capsule \n(mucicarmine positive); \nvariable size and shape is \ncharacteristic\nSingle or multiple buds, rare \npseudohyphae. \nCapsule-deficient forms \n(mucicarmine negative) \nmay be present. However, \nFM is usually positive.\nPAS (+)\nGram (weak)\nMSS (+)\nFM (+)\nAB (+ capsule)\nMucicarmine \n(+\u00a0capsule)\nICH available\nLungs: symptomatic pneu\u00ad\nmonia that may affect \nboth lungs. Can also form \nresidual fibrocaseous \ngranulomas (rarely calcify).\nMeningoencephalitis (soap-\nbubble lesions): CSF (India \nink positive, but antigen \ntest is better) (immunocom\u00ad\npromised); the antigen test \ncross-reacts with Trichospo\u00ad\nron species.\nDisseminated (any organ) \n(immunocompromised)\nSolitary, well-circum\u00ad\nscribed focus of \nyeast forms sur\u00ad\nrounded by GRAN \nand GC\nFungi in Virchow-\nRobin space, little \nhost response\nLittle host response\nBLASTOMYCES DERMATITIDIS\n8-20 \u03bcm spheres with broad-\nbased budding\nDouble contour thick capsule\nOften in giant cells\nMultiple nuclei\nNo hyphae\nMSS (+)\nPAS (+)\nMucicarmine \n(+/\u2212)\nFM (\u2212)\nLung (Mississippi and Ohio \nRiver valleys) (residual nod\u00ad\nules are much rarer than for \nHistoplasma or Coccidioides \nspecies)\nSkin: fleshy fungating ulcers, \nmay be verrucous\nDisseminated (bones, GI, \nCNS, prostate, liver, spleen, \nkidney)\nUsually solitary focus \nof GRAN, rarely \ncalcified\nPseudoepithelioma\u00ad\ntous hyperplasia \nhyperkeratosis, \nmicroabscesses, \nAI (intraepithelial), \nGRAN\nDEMATIACEOUS FUNGI (BROWN PIGMENTED; >100 SPECIES)\n1.5- to 5-\u03bcm brown to black \nyeast \u201ccopper penny,\u201d may \nbe present in giant cells, \noften in pairs\nSclerotic bodies (septated \ncells) and septate hyphae\nH&E (+)\nMSS (+)\nPAS (+)\nChromoblastomycosis usually \ndue to traumatic introduc\u00ad\ntion of fungi by thorn or \nsplinter\nPhaeohyphomycosis (cutane\u00ad\nous phaeomycotic cyst) \nusually due to traumatic \nintroduction of fungi by \nthorn or splinter\nMycetoma (chronic tumor-\nlike lesion with draining \nsinuses)\nSystemic (cerebral)\u2014rare\nHyperkeratosis, \nmicroabscesses, \nPMNs, and GRAN; \nverrucous appear\u00ad\nance, sclerotic \nbodies present\nSubcutaneous cystic \ngranulomatous \nnodule, surface \nnot involved, \nhyphae usually \npresent\nGRAN, AI, hyaline \ngranules\nAbscesses\nDERMATOPHYTES (TRICHOPHYTON, MICROSPORUM, EPIDERMOPHYTON SPECIES)\nSeptate hyphae and yeast \nforms (\u201cspaghetti and \nmeatballs\u201d)\nMSS (+)\nPAS (+)\nFM (+)\nSkin (tinea corporis or \n\u201cringworm,\u201d \u2009tinea pedis or \nathlete\u2019s foot), hair (tinea \ncapitis), and nails (tinea \nunguium or onychomy\u00ad\ncosis)\nDisseminated (immunocom\u00ad\npromised)\u2014very rare\nChronic dermatitis \nand spongiosis, lit\u00ad\ntle host response, \nsuperficial fungal \nforms\nTABLE 7\u201352.\u2003\nFUNGI: HISTOLOGIC APPEARANCE IN SURGICAL SPECIMENS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_206.png", "summary": "This page discusses the histologic appearance and usual sites of infection for various fungi, including Cryptococcus neoformans, Blastomyces dermatitidis, Dematiaceous fungi, and Dermatophytes.", "questions": [ "How does the histologic appearance of Cryptococcus neoformans differ from Blastomyces dermatitidis?", "What are the typical sites of infection for Dematiaceous fungi?", "What are the common clinical presentations associated with Dermatophyte infections?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 207, "text": "189\nSPECIAL STUDIES\u2003 Microbiological Culture and Smears\nHISTOLOGIC APPEARANCE OF FUNGUS\nSTAINS\nUSUAL SITES OF INFECTION \n(PATIENT GROUPS)\nTISSUE RESPONSE\nPARACOCCIDIOIDES BRASILIENSIS (SOUTH AMERICAN BLASTOMYCOSIS)\n5- to 25-\u03bcm double-walled \nyeast forms that reproduce \nby gemmulation: 10- to \n60-\u03bcm \u201cship\u2019s wheel\u201d\nMSS (+)\nPAS (+)\nSkin ulceration (trauma with \nsoil, residency in South \nAmerica)\nUpper and lower respiratory \ntract\nDisseminated (lymph nodes, \nliver, spleen, gastrointesti\u00ad\nnal, genitourinary, bones, \nadrenal, CNS)\nUlcers or vegeta\u00ad\ntions, AI, GRAN, \neosinophils\nUlcers or vegeta\u00ad\ntions, AI, GRAN, \neosinophils, fol\u00ad\nlowed by fibrosis\nUlcers or vegeta\u00ad\ntions, AI, GRAN, \neosinophils\nSPOROTHRIX SCHENCKII\nRound or oval 2- to 6-\u03bcm \nyeast, often in GC\nUnequal narrow-based bud\u00ad\nding\nElongated cigar-shaped forms\nNo hyphae\nMSS (+)\nPAS (+)\nSkin (nodular lymphangitic \ncutaneous sporotrichosis): \nred papule that ulcerates \nand local lymphadenitis \n(farmers and gardeners, \nexposure to cats)\nExtracutaneous: bones and \njoints, lung\u2014very rare\nAI and NEC GRAN, \nhyperkeratosis, \npseudoepithelio\u00ad\nmatous hyperpla\u00ad\nsia, intraepithelial \nabscesses (looks \nlike blastomycosis)\nCavitary pneumoni\u00ad\ntis in one upper \nlobe\nCOCCIDIOIDES SPECIES (C. IMMITIS, C. POSADASII)\n20- to 200-\u03bcm nonbudding \nthick-walled spherules \ncontaining 2- to 5-\u03bcm \nendospores\nHyphae may rarely be found \nin pulmonary cavities\nMSS (+)\nPAS (+)\nMucicarmine (\u2212)\nFM (\u2212)\nLung (San Joaquin valley, \nSW and W): often seen \nas residual fibrocaseous \n\u00adnodules\u2014organisms may \nbe rare or absent\nSystemic (meninges, bone, \nadrenal CNS, liver) (immu\u00ad\nnocompromised, DM, \nelderly, pregnant)\nSingle focus, may \ncalcify, AI or GRAN \n(no GCs)\nGRAN: if spherules \nare unruptured\nAI: if spherules rup\u00ad\ntured and endo\u00ad\nspores released\nMay be hazardous to \nlaboratory work\u00ad\ners if cultured\nAB, Alcian blue; AI, acute inflammation; BV, blood vessel; CNS, central nervous system; CSF, cerebrospinal fluid; DM, diabetes mellitus; FM, Fontana Masson; GC, giant cell; \nGI,\u00a0gastrointestinal; GRAN, granulomas; IHC, immunohistochemical methods; ISH, in situ hybridization methods; MP, macrophage; MSS, silver stain (similar to GMS\u2014Grocott-\nGomori methenamine silver); NEC GRAN, necrotizing granulomas; PAS, periodic acid\u2013Schiff; PMNs, polymorphonuclear leukocytes; (+), positive; (-), negative.\nData from Lerone DH. Medically Important Fungi: A Guide to Identification, 4th ed. Washington, DC: ASM Press, 2004; and Chandler FW, Watts JC. Pathologic Diagnosis of \nFungal Infections. Chicago: ASCP Press, 1987.\nTABLE 7\u201352.\u2003\nFUNGI: HISTOLOGIC APPEARANCE IN SURGICAL SPECIMENS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_207.png", "summary": "This page discusses the histologic appearance and special studies for fungal infections caused by Paracoccidioides brasiliensis, Sporothrix schenckii, and Coccidioides species.", "questions": [ "What are the typical histologic features of Paracoccidioides brasiliensis infection?", "What are the usual sites of infection for Sporothrix schenckii?", "Why may Coccidioides species be hazardous to laboratory workers if cultured?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 208, "text": "190\nSPECIAL STUDIES\u2003 Microbiological Culture and Smears\nTABLE 7-53.\u2003 VIRUSES: HISTOLOGIC APPEARANCE AND ASSOCIATED NEOPLASMS\nHISTOLOGIC APPEARANCE \nOF VIRUS\nHOST REACTION\nCOMMON SITES \n(OR CELLS) OF \nINVOLVEMENT\nASSOCIATED \nNEOPLASMS/\nVALUE OF \nTESTING FOR \nVIRUS\nTESTS TO \nIDENTIFY VIRUS\nHERPES SIMPLEX VIRUS (HSV I AND II) (ds DNA)\nMultinucleated \nsquamous cells, \nhepatocytes, \npneumocytes, \nmicroglial cells, \nor placenta\nGlassy nuclei \nwith chromatin \ncompressed \nat nuclear \n\u00admembrane\nIntranuclear \neosinophilic \ninclusions with \na clear halo and \nthick nuclear \nmembrane \n(Cowdry A*)\nVesicles or ulcer\u00ad\nated surface \nwith CI and AI\nNecrosis of \norgans in \nneonates or \nimmunocom\u00ad\npromised \npatients\nSquamous mucosa of \nesophagus, cervix, \nor anus\nSkin\nLung\nTemporal lobe (diag\u00ad\nnosed by PCR of \nCSF)\nNo associated \nneoplasms\nIHC for viral \nproteins (does \nnot distinguish \ntypes I and II)\nISH/PCR\nVARICELLA-ZOSTER VIRUS (VZV, ds DNA)\nSimilar to HSV\nSimilar to HSV\nSkin: rarely biopsied\nLung\nNo associated \nneoplasms\nIHC (can distin\u00ad\nguish VZV from \nHSV)\nSMALLPOX VIRUS (ds DNA)\nEosinophilic \ncytoplasmic \ninclusions (Guar\u00ad\nnieri \u00adbodies), \nballooning \ndegeneration of \nepithelial cells\u2020\nMultilocular \nvesicles that \ncoalesce, \nperivascular \nlymphocytic \ninfiltrate, AI\nSkin\nGI tract\nAll organs in severe \nforms\nNo associated \nneoplasms\nIHC\nelectron micros\u00ad\ncopy: fluid from \nvesicles can be \nused to detect \nviral particles\nPCR\nReport immedi\u00ad\nately to the CDC!\nCYTOMEGALOVIRUS (CMV; ds DNA)\nEnlarged cells with \namphophilic \nintranuclear \n(with a sur\u00ad\nrounding halo) \nand basophilic \nintracytoplasmic \ninclusions\nUlcerated mucosa \nwith CI and AI\nEndothelial cells \nwith thrombo\u00ad\nsis and infarc\u00ad\ntion\nInterstitial pneu\u00ad\nmonitis\nEsophagus, colon, \nlung, adrenal, heart, \nliver, placenta\nNo associated \nneoplasms\nIHC (>40% of \nU.S. popula\u00ad\ntion is infected; \nsignificance of \n[+] in normal-\nappearing cells \nis unclear)\nISH/PCR", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_208.png", "summary": "The page provides information on the histologic appearance, host reactions, common sites of involvement, associated neoplasms, and testing methods for various viruses including Herpes Simplex Virus, Varicella-Zoster Virus, Smallpox Virus, and Cytomegalovirus.", "questions": [ "What are the common sites of involvement for Herpes Simplex Virus?", "How can Varicella-Zoster Virus be distinguished from Herpes Simplex Virus?", "What is the significance of a positive result for Cytomegalovirus in normal-appearing cells?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 209, "text": "191\nSPECIAL STUDIES\u2003 Microbiological Culture and Smears\nHISTOLOGIC APPEARANCE \nOF VIRUS\nHOST REACTION\nCOMMON SITES \n(OR CELLS) OF \nINVOLVEMENT\nASSOCIATED \nNEOPLASMS/\nVALUE OF \nTESTING FOR \nVIRUS\nTESTS TO \nIDENTIFY VIRUS\nHUMAN PAPILLOMAVIRUS (HPV, MORE THAN 200 TYPES; ds DNA)\nKoilocytosis \n\u00ad(irregular \nnuclear \n\u00adenlargement \nwith perinuclear \nclearing), \ndisrupted \nkeratohya\u00ad\nline granules, \nhyperkeratosis, \nparakeratosis\nSquamous \ncells with \nacanthosis, \npapillomatosis, \nand coarse \nclumped \nkeratohyaline \ngranules\nVerruca vulgaris: \nhands, oral cavity, \nlarynx (HPV 2), EV \n(HPV 5 and 8)\nVerruca plana: foot \n(HPV 5 and 8)\nCondyloma acumi\u00ad\nnatum: external \ngenitalia (HPV 6 \nand 11)\nCervix: LSIL, HSIL, can\u00ad\ncer (HPV 16 and 18)\nHead and neck cancer \n(especially tonsil) \n(HPV 16)\nSCC of cervix, \n\u00adtonsil, anogeni\u00ad\ntal, papillomas \nof skin and \nother sites, \ncervical adeno\u00ad\ncarcinoma\nValue of viral \ntesting: \n\u00adcervical cancer \n\u00adscreening\nMetastatic SCC: \nprobable pri\u00ad\nmary site\u2021\nHPV+ tonsillar \ncarcinomas \nhave a better \nprognosis\nISH/PCR\nIHC for p16 \n\u00ad(cellular protein \noverexpressed \nin >90% of \nHPV infections, \nespecially HPV \n16 and 18)\nEPSTEIN-BARR VIRUS (EBV; ds DNA)\nNo diagnostic \nfeatures\nInfected B cells \nmay have a \nplasmacytoid \nimmunoblastic \nappearance\nIn oral hairy \nleukoplakia, the \nepithelial cells \nhave a foamy \nballoon cell \nappearance\nLymphocytic \ninfiltrate, \nperipheral \n\u00adlymphocytosis\nB cells, oropharyngeal \nepithelial cells, gas\u00ad\ntric mucosa, smooth \nmuscle\nLymphomas,\u00a7 \nnasopharyn\u00ad\ngeal carcinoma, \nlymphoepithe\u00ad\nlioma-like gas\u00ad\ntric carcinoma, \nEBV-associated \nsmooth muscle \ntumors, IPFDT\nValue of viral \ntesting: \ndiagnosis of \nHD; diagnosis\nof nasopharyn\u00ad\ngeal carcinoma\nEBV+ gastric \ncarcinoma has \na better prog\u00ad\nnosis\nIHC for LMP-1 \n(nasopharyn\u00ad\ngeal carcino\u00ad\nmas, HD [not \nLP], transplant \nlymphomas, \nAIDS-related \nlymphomas, \nendemic Burkitt \nlymphoma) \nand EBNA 2 \n(transplant \nlymphomas, \nAIDS-related \nlymphomas)\nISH/PCR for EBER-1 \nand -2 RNA\nMOLLUSCUM CONTAGIOSUM (ds DNA)\nIntracytoplasmic \nmolluscum bod\u00ad\nies in squamous \ncells of granular \nlayer\nAcanthosis of skin\nSkin: umbilicated \nnodules\nNo associated \nneoplasms\nTABLE 7\u201353.\u2003 VIRUSES: HISTOLOGIC APPEARANCE AND ASSOCIATED NEOPLASMS\u2014cont\u2019d \nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_209.png", "summary": "The page discusses the histologic appearance, common sites of involvement, associated neoplasms, and value of testing for viruses such as Human Papillomavirus (HPV), Epstein-Barr Virus (EBV), and Molluscum Contagiosum.", "questions": [ "What are the common sites of involvement for Human Papillomavirus (HPV) and how do they manifest?", "What is the value of viral testing for cervical cancer screening?", "How can Epstein-Barr Virus (EBV) be identified and what are its associated neoplasms?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 210, "text": "192\nSPECIAL STUDIES\u2003 Microbiological Culture and Smears\nHISTOLOGIC APPEARANCE \nOF VIRUS\nHOST REACTION\nCOMMON SITES \n(OR CELLS) OF \nINVOLVEMENT\nASSOCIATED \nNEOPLASMS/\nVALUE OF \nTESTING FOR \nVIRUS\nTESTS TO \nIDENTIFY VIRUS\nADENOVIRUS (ds DNA)\nAlveolar lining \ncells and bron\u00ad\nchial epithelial \ncells with \ninclusions filling \nenlarged nuclei \n(\u201csmudge cells\u201d)\nNecrotizing bron\u00ad\nchiolitis and \npneumonia\nDiffuse alveolar \ndamage\nNo GCs\nLung and other organs\nNo associated \nneoplasms\nISH/PCR (rarely \nbiopsied; may \nbe cultured)\nPARVOVIRUS B19 (ss DNA)\nLarge glassy \nnucleus of \nnucleated red \nblood cells\nNone\nBone marrow, pla\u00ad\ncenta, fetus, and \nsites of EMH\nNo associated \nneoplasms\nISH/PCR\nRABIES VIRUS (ss RNA)\nNegri bodies: \ncytoplasmic \nround to oval or \nbullet-shaped \neosinophilic \ninclusions\nLittle inflamma\u00ad\ntion present\nNeurons or Purkinje \ncells\nNo associated \nneoplasms\nISH/PCR\nIHC\nMEASLES VIRUS (ss RNA)\nGC with eosino\u00ad\nphilic nuclear \nand cytoplasmic \ninclusions, War\u00ad\nthin-Finkeldey \ncells (multi\u00ad\nnucleated giant \ncells)\nGCs in tracheo\u00ad\nbronchial \nmucosa, \nalveoli, and \nlymphoid \ntissue\nLung: diffuse alveolar \ndamage\nBrain: subacute scle\u00ad\nrosing panencepha\u00ad\nlitis or measles \ninclusion body \nencephalitis\nNo associated \nneoplasms\nISH/PCR\n(rare in vaccinated \npopulations; \nrarely biopsied)\nRESPIRATORY SYNCYTIAL VIRUS (RSV; ss RNA)\nIntracytoplasmic \neosinophilic \ninclusions\nSyncytial GCs, \ndiffuse alveolar \ndamage, CI\nLung\nNo associated \nneoplasms\nRarely biopsied; \nclinical tests are \navailable\nMERKEL CELL POLYOMA VIRUS (MCV, MCPYV; ds DNA)\nNo specific fea\u00ad\ntures\nNo specific host \nresponse\nSkin\nMerkel cell carci\u00ad\nnoma\nClinical tests not \nyet available\nJC VIRUS, POLYOMAVIRUS (ds DNA)\nIntranuclear baso\u00ad\nphilic inclusions \nin oligoden\u00ad\ndroglia\nDemyelination \nwithout inflam\u00ad\nmation\nSubcortical white \nmatter (progressive \nmultifocal leukoen\u00ad\ncephalopathy)\nNo associated \nneoplasms\nIHC\nISH/PCR (can be \nperformed on \nCSF)\nTABLE 7\u201353.\u2003 VIRUSES: HISTOLOGIC APPEARANCE AND ASSOCIATED NEOPLASMS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_210.png", "summary": "This page provides information on the histologic appearance and common sites of involvement for various viruses, along with associated neoplasms and testing methods.", "questions": [ "What are some common histologic features of adenovirus infection?", "Which virus is associated with Merkel cell carcinoma?", "What testing methods are available for detecting JC virus?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 211, "text": "SPECIAL STUDIES\u2003 Microbiological Culture And Smears\n193\nHISTOLOGIC APPEARANCE \nOF VIRUS\nHOST REACTION\nCOMMON SITES \n(OR CELLS) OF \nINVOLVEMENT\nASSOCIATED \nNEOPLASMS/\nVALUE OF \nTESTING FOR \nVIRUS\nTESTS TO \nIDENTIFY VIRUS\nBK VIRUS, POLYOMAVIRUS (ds DNA)\nDecoy cells (tubu\u00ad\nlar or urothelial \ncells with inclu\u00ad\nsions) in urine\nNuclear enlarge\u00ad\nment in tubules \nin late phase of \ninfection\nPVAN\nTubular cell \nnecrosis, inter\u00ad\nstitial inflam\u00ad\nmation, fibrosis\nUrinary tract (trans\u00ad\nplanted kidneys)\nNo associated \nneoplasms\nIHC\nISH/PCR (can be \nused on urine or \nbladder wash\u00ad\nings)\nElectron micros\u00ad\ncopy\u2013specific \nintranuclear \ninclusions\nHEPATITIS B VIRUS (HBV; ds DNA)\nCells with ground-\nglass cytoplasm \ndisplacing the \nnucleus\nChronic active \nhepatitis, cir\u00ad\nrhosis\nApoptotic bodies\nHepatocytes\nHepatocellular \ncarcinoma\nIHC for core anti\u00ad\ngen (HBcAg) and \nsurface antigen \n(HbsAg)\nISH/PCR\nHEPATITIS C VIRUS (ss RNA)\nNo diagnostic \nfeatures\nChronic active \nhepatitis, \nsteatosis, \nintralobular \ninflammation, \nplasma cells, \ncirrhosis\nHepatocytes\nHepatocellular \ncarcinoma\nIHC\nISH/PCR\nKAPOSI SARCOMA\u2013ASSOCIATED HERPESVIRUS (KSHV, HUMAN HERPESVIRUS-8 [HHV-8]; ds DNA)\nNo diagnostic \nfeatures\nNone\nVascular endothelial \ncells, lymphocytes\nKaposi sarcoma, \nmulticentric \nCastleman \ndisease, HHV-\n8\u2013related \nlymphomas, \nprimary effu\u00ad\nsion lymphoma\nValue of testing \nfor virus: diag\u00ad\nnosis of Kaposi \nsarcoma\nISH/PCR\nNote: most primary \neffusion lym\u00ad\nphomas are also \nEBV+\nHUMAN T-CELL LEUKEMIA VIRUS (HTLV-1; ds DNA)\nLymphocytes with \ncondensed \nchromatin and \na convoluted \npolylobated \nnucleus (\u201cflower \ncells\u201d)\nNo specific reac\u00ad\ntion\nT cells\nAdult T-cell leu\u00ad\nkemia\nValue of test\u00ad\ning for virus: \ndiagnosis in \npatients sero\u00ad\nnegative for \nHTLV-1\nISH/PCR\nTABLE 7\u201353.\u2003 VIRUSES: HISTOLOGIC APPEARANCE AND ASSOCIATED NEOPLASMS\u2014cont\u2019d \nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_211.png", "summary": "The page discusses the histologic appearance, host reaction, common sites of involvement, associated neoplasms, and value of testing for various viruses including BK virus, Hepatitis B virus, Hepatitis C virus, Kaposi Sarcoma-associated herpesvirus, and Human T-cell leukemia virus.", "questions": [ "What are the common sites of involvement for BK virus?", "What are the histologic features associated with Hepatitis B virus infection?", "How is Kaposi Sarcoma-associated herpesvirus diagnosed?", "What is the value of testing for Human T-cell leukemia virus?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 212, "text": "194\nSPECIAL STUDIES\u2003 Microbiological Culture and Smears\nTABLE 7\u201353.\u2003 VIRUSES: HISTOLOGIC APPEARANCE AND ASSOCIATED NEOPLASMS\u2014cont\u2019d \nHISTOLOGIC APPEARANCE \nOF VIRUS\nHOST REACTION\nCOMMON SITES \n(OR CELLS) OF \nINVOLVEMENT\nASSOCIATED \nNEOPLASMS/\nVALUE OF \nTESTING FOR \nVIRUS\nTESTS TO \nIDENTIFY VIRUS\nHUMAN IMMUNODEFICIENCY VIRUS (HIV; ss RNA)\nNo specific \nchanges\nNo specific reac\u00ad\ntion\nCD4+ T cells\nImmunosuppres\u00ad\nsion increases \nrisk for other \nvirus-associ\u00ad\nated neo\u00ad\nplasms\nDiagnosis usually \nmade by serol\u00ad\nogy\n*Cowdry type B inclusions were described as smaller inclusions associated with polio. However, this finding has not been validated and is not currently used for diagnosis.\n\u2020Monkeypox has a similar appearance. Intracytoplasmic inclusions are characteristic of smallpox and are not seen in HSV or VZV infections. It may be difficult to distinguish \nsmallpox, HSV, and VZV by H&E alone (Nuovo GJ, Plaza JA, Magro C: Rapid diagnosis of smallpox infection and differentiation from its mimics. Diagn Mol Pathol 12:103-107, \n2003).\n\u2021The presence of HPV in metastatic carcinoma to a lymph node suggests a primary in the tonsil (if in the head and neck) or cervix (if abdominal).\n\u00a7Burkitt lymphoma, classic Hodgkin lymphoma (but not lymphocyte-predominant Hodgkin lymphoma), AIDS-associated B-cell lymphoma, plasmablastic lymphoma, post-\ntransplantation lymphoproliferative disorder, lymphomatoid granulomatosis, methotrexate-associated B-cell lymphoma, severe combined immunodeficiency\u2013associated \nB-cell lymphoma, Wiskott-Aldrich syndrome\u2013associated B-cell lymphoma, X-linked lymphoproliferative disorder\u2013associated B-cell lymphoma, EBV-positive diffuse large \nB-cell lymphoma of the elderly, peripheral T-cell lymphoma, extranodal NK/T-cell lymphoma, nasal type, virus-associated hemophagocytic syndrome T-cell lymphoma. \nAngioimmunoblastic T-cell lymphoma is associated with EBV+ B cells. However, the neoplastic T cells are negative for EBV.\nAI, acute inflammation; CI, chronic inflammation; CDC, Centers for Disease Control and Prevention; CSF, cerebrospinal fluid; ds, double-stranded; EBER, EBV-associated \nnonpolyadenylated early RNAs; EBNA 2, EBV nuclear antigen 2; EMH, extramedullary hematopoiesis; EV, epidermodysplasia verruciformis; GC, multinucleated giant cells; \nGI, gastrointestinal; HD, Hodgkin disease; HSIL, high-grade squamous intraepithelial lesion; IHC, immunohistochemistry uses antibodies to visualize either viral proteins \n(e.g., LMP-1 or HBcAg) or cellular proteins increased during infection (e.g., p16) on tissue sections; IPFDT, inflammatory pseudotumor-like follicular dendritic cell tumor; \nISH/PCR, viral nucleic acids are amplified by polymerase chain reaction (PCR) and either quantified or visualized on tissue sections (in situ hybridization); LMP-1, latent \nmembrane protein 1; LNA-1, latency-associated nuclear antigen (or LANA1); LP, lymphocyte predominant HD; LSIL, low-grade squamous intraepithelial lesion; PVAN, \npolyomavirus-associated nephropathy; SCC, squamous cell carcinoma; ss, single-stranded.\nData from Eyzaguirre E, Haque AK: Application of immunohistochemistry to infections. Arch Pathol Lab Med 132:424-431, 2008; McLaughlin-Drubin ME, Munger K: Viruses \nassociated with human cancer. Biochim Biophys Acta 1782:127-150, 2008; Nuovo GJ: The utility of in situ-based methodologies including in situ polymerase chain reaction \nfor the diagnosis and study of viral infections. Hum Pathol 38:1123-1136, 2007; Slifka MK, Hanifin JM: Smallpox: the basics. Dermatol Clin 22:263-274, 2004.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_212.png", "summary": "The page discusses the histologic appearance of viruses, host reactions, common sites of involvement, associated neoplasms, and the value of testing for viruses.", "questions": [ "How can the presence of HPV in metastatic carcinoma help determine the primary site of the cancer?", "What tests are typically used to diagnose Human Immunodeficiency Virus (HIV)?", "Why is it important to differentiate between smallpox, HSV, and VZV infections?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 213, "text": "195\nSPECIAL STUDIES\u2003 References\nREFERENCES\n\t\u2002 1.\t \u0007Werner M, Chott, Fabiano A, Battifora H. Effect of forma\u00ad\nlin fixation and processing on immunohistochemistry. Am J \nSurg Pathol 24:1016-1019, 2000.\n\t\u2002 2.\t \u0007Arber JM, Arber DA, Jenkins KA, Battifora H. Effect of \ndecalcification and fixation in paraffin-section immunohisto\u00ad\nchemistry. Applied Immunohistochem 4:241-248, 1996.\n\t\u2002 3.\t \u0007Fergenbaum JH, Garcia-Closas M, Hewitt SM, et al. Loss of \nantigenicity in stored sections of breast cancer tissue microar\u00ad\nrays. Cancer Epidemiol Biomarkers Prev 13:667-672, 2004.\n\t\u2002 4.\t \u0007Wester K, Wahlund E, Sunderstrom C, et al. Paraffin sec\u00ad\ntion storage and immunohistochemistry: effects of time, \ntemperature, fixation, and retrieval protocol with emphasis \non p53 protein and MIB1 antigen. Appl Immunohistochem \nMol Morphol 8:61-70, 2000.\n\t\u2002 5.\t \u0007Battifora H. Assessment of antigen damage in immunohisto\u00ad\nchemistry, the vimentin internal control. Am J Clin Pathol \n6:669-671, 1991.\n\t\u2002 6.\t \u0007Chu PG, Weiss LM. Keratin expression in human tissues \nand neoplasms. Histopathology 40:403-439, 2002.\n\t\u2002 7.\t \u0007Gyure KA, Morrison AC. Cytokeratin 7 and 20 expression \nin choroid plexus tumors: utility in differentiating these neo\u00ad\nplasms from metastatic carcinomas. Mod Pathol 13:638-643, \n2000.\n\t\u2002 8.\t \u0007Wang NP, Zee S, Zarbo RJ, et al. Coordinate expression of \ncytokeratins 7 and 20 defines unique subsets of carcinomas. \nAppl Immunohistochem 3:99-107, 1995.\n\t\u2002 9.\t \u0007Mierau GW, Berry PJ, Malott RL, et al. Appraisal of the \ncomparative utility of immunohistochemistry and electron \nmicroscopy in the diagnosis of childhood round cell tumors. \nUltrastruct Pathol 20:507-517, 1996.\n\t10.\t \u0007Varadhachary GR, Abbruzzese JL, Lenzi R. Diagnos\u00ad\ntic strategies for unknown primary cancer. Cancer 100:\n1776-1785, 2004.\n\t11.\t \u0007Harvey JM, et al. J Clin Oncol 17:1474-1481, 1999.\n\t12.\t \u0007Collins LC, Botero ML, Schnitt SJ. Bimodal frequency dis\u00ad\ntribution of estrogen receptor immunohistochemical stain\u00ad\ning results in breast cancer: an analysis of 825 cases. Am J \nClin Pathol 123:16-20, 2005.\n\t13.\t \u0007Wolff AC, et al. American Society of Clinical Oncology/\nCollege of American Pathologists Guideline Recommen\u00ad\ndations for Human Epidermal Growth Factor Receptor 2 \n\u00adTesting in Breast Cancer. Arch Pathol Lab Med 131:18-43, \n2007.\n\t14.\t \u0007Battifora H. Metastatic breast carcinoma to the stomach \nsimulating linitis plastica. Applied Immunohistochem 2:\n225-228, 1994.\n\t15.\t \u0007O\u2019Connell FP, Wang HH, Odze RD. Utility of immuno\u00ad\nhistochemistry in distinguishing primary adenocarcinomas \nfrom metastatic breast carcinomas in the gastrointestinal \ntract. Arch Pathol Lab Med 129:338-347, 2005.\n\t16.\t \u0007Corson JM. Pathology of mesothelioma. Thorac Surg Clin \nN Am 14:447-460, 2004.\n\t17.\t \u0007Kebbel A, Rocken C. Immunohistochemical classification \nof amyloid in surgical pathology revisited. Am J Surg Pathol \n30:673-683, 2006.\n\t18.\t \u0007Cao Y, Karsten U, Milqers J. Imnunohistochemical \n\u00adcharacterization of a panel of 56 antibodies with normal \nhuman small intestine, colon, and breast tissues. Tumor Biol \n19(Suppl\u00a01):88-99, 1998.\n\t19.\t \u0007Electron Microscopy of Tumors, Seminars in Diagnostic \nPathology, Volume 20: the entire February 2003 issue is \ndevoted to electron microscopy.\n\t20.\t \u0007Lerone DH. Medically Important Fungi, 4th edition: a guide \nto identification, ASM Press, 2004.\n\t21.\t \u0007Chandler FW, Watts JC. Pathologic Diagnosis of Fungal \nInfections. ASCP Press, 1987.\n\t22.\t \u0007Nuovo GJ, Plaza JA, Magro C. Rapid diagnosis of small\u00ad\npox infection and differentiation from its mimics. Diag Mol \nPathol 12:103-107, 2003.\n\t23.\t \u0007Eyzaguirre E, Haque AK. Application of immunohistochem\u00ad\nistry to infections. Arch Pathol Lab Med 132:424-431, 2008.\n\t24.\t \u0007McLaughlin-Drubin ME, Munger K. Viruses associated \nwith human cancer. Biochim Biophys Acta 1782:127-150, \n2008.\n\t25.\t \u0007Nuovo GJ. The utility of in situ-based methodologies includ\u00ad\ning in situ polymerase chain reaction for the diagnosis and \nstudy of viral infections,. Hum Pathol 38:1123-1136, 2007.\n\t26.\t \u0007Slifka MK, Hanifin JM. Smallpox: the basics. Dermatol Clin \n22:263-274, 2004.\ufeff", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_213.png", "summary": "The page lists references for various studies on the effects of fixation and processing on immunohistochemistry.", "questions": [ "What are some common factors that can affect immunohistochemistry results?", "How important is proper fixation and processing in immunohistochemistry?", "What are some key findings from the referenced studies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 214, "text": "196\n8\nSafety Precautions\nA pathology department can be a dangerous place to \nwork. Hazards include physical injury (scalpel cuts, needle \nsticks), infectious disease, radioactivity, and noxious chem\u00ad\nical fumes. Although we all take risks when we work with \nspecimens from patients, these risks can be minimized for \nboth ourselves and our coworkers by following the proce\u00ad\ndures outlined in this section.\nINFECTIOUS DISEASE: THE BAD NEWS\nThe incidence of infectious diseases, particularly those that \nare incurable or difficult to treat, is on the rise. In a study \nof patients undergoing major surgery in New York, 5.2% \nwere HCV positive, 1.4% HBV positive, and 1.6% HIV \npositive (or 6.7% with one or more of these viruses).1 Often, \nthe presence of infection is unknown or unreported to the \npathology department. Healthcare workers are at risk for \ncontracting these diseases by working with patients. The \nrisk is lower for pathology personnel, but exposure can \noccur by aerosolization of tissues, needlestick injury, scal\u00ad\npel wounds, and mucocutaneous exposure during the pro\u00ad\ncessing of pathology specimens (Box 8-1).\nOther types of infectious agents (e.g., other types of \nbacteria or fungi, Pneumocystis jiroveci, other viral agents) \nare also potential dangers, particularly to immunocompro\u00ad\nmised healthcare workers, but transmission is very rare and \nhas not yet been reported.\nINFECTIOUS DISEASE: THE GOOD NEWS\nThe actual incidence of transmission of infectious \nagents from unfixed surgical specimens to pathology \ndepartment personnel is extremely low. There are only \nthree reported cases, all involving conversions to posi\u00ad\ntive tuberculin skin tests after using an aerosolized gas \ncoolent to freeze a tissue block during an intraoperative \nconsultation.2,3 However, transmission of other types \nof infectious disease is theoretically possible and has \noccurred for HBV, HIV, and TB during the performance \nof autopsies.\nThe good news is that pathology personnel can take \naction to protect themselves: by educating themselves \nabout risks, taking physical precautions to protect them\u00ad\nselves and others, avoiding the use of hollow-bore needles, \nand making sure they are vaccinated for HBV (Table 8-1). \nPersonnel who are themselves immunocompromised must \nbe especially vigilant.\nHepatitis B Virus (HBV)\nThe CDC estimated that 18,000 healthcare workers whose \njobs entailed exposure to blood became infected with HBV \neach year prior to widespread vaccination. Of these, 200 \nto 300 died of complications of HBV infection. Prior \nto widespread vaccination, 25% to 30% of pathologists \nwere positive for HBV with their exposures likely due to \nthe performance of autopsies. However, the incidence of \nHBV infection has sharply declined with vaccination, and \nall pathology department workers who come into contact \nwith tissue should be vaccinated. OSHA bloodborne stan\u00ad\ndards require that employers offer the vaccine at no cost to \nall employees at risk.\nSeroconversion is 30% after a needle stick from \nHBeAg-positive blood and <6% after HBeAg-negative \nblood in nonvaccinated individuals. Mucocutaneous \nexposure can also occur.\nPostexposure prophylaxis with HBV hyperimmune \nglobulin and vaccine is suggested for nonvaccinated indi\u00ad\nviduals or in vaccinated persons with low antibody titers. \nTreatment provides about 75% protection from infection \nif instituted within a week.4,5\nHepatitis C Virus (HCV)\nThe seroprevalence in healthcare workers has ranged from \n0% to 1.7% in multiple studies. Occupational infections \nin pathology personnel have not been reported. Eighty \n\u00adpercent to 90% of infections will become chronic with risk \nfor the development of chronic hepatitis, cirrhosis (3% \nto 20% of patients), and hepatocellular carcinoma. HCV \nhas also been linked to cryoglobulinemia and many other \nimmune system\u2013related diseases.\nBOX 8\u20131.\u2003 \u0007Diseases that have been transmitted \nto healthcare workers\n \u2022 \u0007Hepatitis B, C, and A\n \u2022 \u0007Tuberculosis (including strains resistant to multiple drugs)\n \u2022 \u0007HIV\n \u2022 \u0007Syphilis\n \u2022 \u0007Creutzfeldt-Jakob disease\n \u2022 \u0007Coccidioides immitis (risk is primarily from cultures of the fungus \nin microbiology laboratories); if this infection is suspected all \nspecimens must be labeled appropriately\n \u2022 \u0007Also parvovirus, H. pylori, Cryptosporidium, scabies, pertussis", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_214.png", "summary": "Pathology department workers face various hazards such as physical injury, infectious diseases, radioactivity, and chemical fumes. While the risk of transmission of infectious agents from unfixed surgical specimens to personnel is low, precautions should still be taken to minimize exposure.", "questions": [ "What are some of the hazards faced by pathology department workers?", "What actions can pathology personnel take to protect themselves from infectious diseases?", "Why is it important for all pathology department workers to be vaccinated for HBV?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 215, "text": "197\nSAFETY PRECAUTIONS\u2003 Infectious Disease: the Good News\nThe risk is about 1.8% for HCV transmission after \na needle stick. Risk after skin or mucous membrane \nexposure is likely to be very low.\nPostexposure treatment has not been shown to be effec\u00ad\ntive. If there has been a potential exposure, the person \nshould be monitored for infection in order to start treat\u00ad\nment as early as possible.4-6\nHuman Immunodeficiency Virus (HIV)7-15\nAs of 2001, 57 healthcare workers had developed HIV \ninfection following documented occupational exposure and \nan additional 138 workers were considered possible cases. \nMost exposures (88%) were percutaneous involving hol\u00ad\nlow-bore needles, scalpels, and broken vials. 20% occurred \nduring the disposal of sharp objects. Mucous membrane \nand skin exposure were responsible in about 10% of cases. \nThe source in almost all cases was infected blood (86%). \nThe risk is increased with the volume of blood, the depth \nof the injury, and the viral titer of the patient (with an \nincreased risk with patients close to death).\nA pathologist was infected by HIV after a scalpel wound \nto the hand during an autopsy.10 Surgical specimens con\u00ad\ntaining blood could also potentially transmit the virus, if an \ninjury occurs. HIV can be cultured from cadavers hours to \ndays after death. The effect of fixation has not been studied \nbut would presumably lower or eliminate risk.\nApproximately 0.3% of persons will seroconvert \nafter a needle-stick exposure to HIV, 0.1% after muco\u00ad\ncutaneous exposure, and <0.1% after skin exposure.\nPostexposure treatment with antiviral agents can decrease \nthe risk of seroconversion by 81%. Treatment should be \nstarted as soon as possible, as it may be less effective after 2 \nto 3 days. Additional agents used in combination for prophy\u00ad\nlaxis may be more effective, as the source patients for occu\u00ad\npational cases have a high prevalence of drug-resistant HIV. \nThere have been 21 cases of healthcare personnel becoming \ninfected with HIV despite postexposure prophylaxis.\nTuberculosis\nThe risk of transmission of tuberculosis to autopsy per\u00ad\nsonnel during the performance of necropsies is well docu\u00ad\nmented. TB can be transmitted as an aerosol but also \npercutaneously.16 It must be kept in mind that many cases \nof TB are first diagnosed after death. Multiple individuals \nhad skin test conversions after the autopsy of an infected \nperson.17\nThe three cases of conversion to positive skin tests after \nfrozen sections previously mentioned were associated with \nuse of an aerosolized coolant. This method of cooling \nshould not be used.\nHealthcare workers also have a significant risk of con\u00ad\ntracting multiple-drug-resistant tuberculosis. Although \nhealthcare workers have been infected by drug-resistant \nTB, no fatal cases have been reported (yet!) if the worker \ndid not have an underlying immunodeficiency disorder.\nMycobacteria can survive in tissue fixed in formalin. Of \n138 autopsy cases with histologically documented acid-\nfast bacilli, 12 (8.7%) grew mycobacteria, including three \ncases of M. tuberculosis.18 Thus, even fixed tissue must be \nregarded as potentially infectious.\nSpecial respiratory protective devices are recommended \nfor personnel that may be exposed to tuberculosis.\nIf an exposed person does not develop a positive skin \ntest, no treatment is necessary. Converters and persons \nwho are immunocompromised should be treated.\nHospital workers are required to undergo yearly TB \ntesting.\nSevere Acute Respiratory Syndrome (SARS)\nSARS was first identified in China in late 2002. It is caused \nby SARS-associated coronavirus (SARS-CoV). Spread is \nvia respiratory droplets contacting the mucous membranes \nof a second person. Occupationally-acquired cases have \noccurred among healthcare workers. The risk to surgical \nTABLE 8\u20131.\u2003\nRISK OF EXPOSURE TO COMMON INFECTIOUS AGENTS\nAGENT\n% OF HOSPITAL \nPATIENTS\nRISK OF INFECTION \nAFTER PERCUTANEOUS \nINJURY*\nRISK AFTER \nMUCOCUTANEOUS \nEXPOSURE\nRISK OF \nENVIRONMENTAL \nEXPOSURE\nPOST-EXPOSURE \nPROPHYLAXIS \nAVAILABLE\nHIV\n~ 0.2 - 14%\n0.3%\n0.09%\nPossible, but very rare\nYES \u2212 effective\nHCV\n~ 2 - 5%\n1.8%\nRare\nYes, but rapidly degrades\nNO \u2013 not shown to \nbe effective\nHBV\n~ 2%\n30%\nYes, probably high\nOccurs, can be found in \ndried blood ~ 1 week\nYES \u2212 effective\nTB\n~ 10%\nYes \u2013 risk not quantified\nYes \u2013 risk not \n\u00adquantified\nYes\nNO \u2013 treatment ini\u00ad\ntiated only if skin \ntest converts\n*Percutaneous injury: needlestick injury (majority) or other penetrating injury with a sharp object (e.g., scalpel, broken glass).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_215.png", "summary": "The page discusses safety precautions for healthcare workers regarding infectious diseases such as HCV, HIV, and tuberculosis, including risks of transmission, postexposure treatment effectiveness, and preventive measures.", "questions": [ "What are the risks of HCV transmission after a needle stick versus skin or mucous membrane exposure?", "How effective is postexposure treatment for HIV and what factors can affect its efficacy?", "What are the risks and transmission methods of tuberculosis to healthcare workers, and how can it be prevented?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 216, "text": "198\nSAFETY PRECAUTIONS\u2003 Transmission of Tumors\npathology personnel is likely to be low, as most patients \nwill not undergo surgical procedures. However, autopsies \nmay be performed.\nThere are no reported cases of transferring SARS via \nthe handling of pathology specimens. However, as there \nis little experience with this virus, all cases from patients \nwith known or suspected SARS may best be handled as for \ncases of HBV. All tissue should be promptly fixed and the \ncryostat decontaminated if necessary.19\nCreutzfeldt-Jakob Disease\nThe only cases of infection in laboratory personnel from \nfixed tissue are due to Creutzfeldt-Jakob disease. As of \n1995, 24 healthcare workers had developed Creutzfeldt-\nJakob disease including two histotechnologists and one \npathologist. Infectious units are present in fixed and par\u00ad\naffin-embedded tissue for years. Any adult patient with a \nrapidly progressive dementia, myoclonus, and nonspecific \nneurologic findings should be considered as potentially \nhaving the disease.\nAny tissues from affected patients are potentially infec\u00ad\ntious. The virus is not inactivated by standard formalin \nfixation or boiling water. Tissues should be fixed in for\u00ad\nmalin for 24 hours, then in 95% formic acid for one hour \nfollowed by formalin fixation for one day.20,21\nBIOLOGIC TERRORISM\nHopefully, pathologists will not receive specimens from acts \nof biologic terrorism, but if such an event occurs, pathologists \ncan aid in recognizing the disease and the likely method of \ninfection (Table 8-2).22-31 The first anthrax case in 2001 was \nsuspected when typical organisms were seen on a Gram stain \nof CSF. The autopsy determined that the mode of exposure \nwas inhalational and this finding helped direct investigators \nto search for possible sources of airborne spores.\nIn the event of an actual or threatened bioterrorist \nattack, local health and law enforcement agencies should \nbe contacted and additional information can be found at \nwww.bt.cdc.gov/emcontact/index.asp or the CDC Emer\u00ad\ngency Response Hotline 770-488-7100.\nThe CDC recommends saving tissue from autopsies \n(and other specimens) from possible victims of biologic \nterrorism:\n\t\u2022\t \u0007Fixed tissue: Histologic examination for patterns of tis\u00ad\nsue damage and special stains for identification of organ\u00ad\nisms. IHC and DFA assays are available at the CDC and \nmost can be performed on fixed tissue.\n\t\u2022\t \u0007Blood, cerebrospinal fluid, tissue samples, or swabs for \nbacterial and viral culture. Mucosal swabs for cases of \npossible botulinum toxin inhalation.\n\t\u2022\t \u0007Serum for biologic and serologic assays\n\t\u2022\t \u0007Frozen tissue for PCR\n\t\u2022\t \u0007Fixed tissue (glutaraldehyde) for electron microscopy to \nidentify viral particles.\nLaboratory Response Network\nThe Laboratory Response Network (LRN) is a partner\u00ad\nship of local, state, and federal public health laboratories, \nand veterinary, food, and environmental laboratories, \nthe CDC, the Food and Drug Administration, the Envi\u00ad\nronmental Protection Agency, the US Army \u00adMedical \nResearch Institute of Infectious Diseases, and other \nDepartment of Defense laboratories (see www.bt.cdc.g\nov/lrn/biological.asp). The network functions to chan\u00ad\nnel specimens from sentinel laboratories to advanced \nlaboratories for confirmation and final identification of \npathogens. Specimens from suspected biologic terrorism-\nrelated cases can be submitted to the state public health \nlaboratory. Contact information for all state laboratories \nis included in the CDC guidebook listed in the resources. \nIf the suspected agent is smallpox, the state laboratory \nshould be notified as such specimens may be transported \ndirectly to the CDC.\nRisks to Pathology Personnel\nAll of the infectious agents listed in Table 8-2 could poten\u00ad\ntially be transmitted to personnel during the performance \nof an autopsy or by handling fresh tissue, except for botu\u00ad\nlinum toxin. Smallpox, tularemia, and viral hemorrhagic \nfevers have been transmitted to persons performing autop\u00ad\nsies. Biologic terrorism raises an additional risk of surface \ncontamination by the agent (e.g., powders used to transmit \nanthrax or botulinum toxin). Because of the incubation \nperiod, it is likely victims will have changed clothes and \nbathed and such contamination, in most cases, will likely \nbe minimal. Standard universal safety precautions should \nbe used for all and should be protective.\nCadavers of patients dying of B. anthracis, Y. pestis, or \nbotulinum toxin are unlikely to pose a threat to nonautopsy \npersonnel (e.g., funeral home workers). However, small\u00ad\npox virus and hemorrhagic fever viruses could be transmit\u00ad\nted and should only be handled with safety precautions. In \ngeneral, such bodies should not be embalmed as this might \nimpose increased risk.\nSending Specimens to Reference Laboratories\nDetailed descriptions for the packaging and shipping of \nspecimens to reference laboratories are available at the \nCDC website. In general, such specimens must have three \nlevels of containment and must be marked with an \u201cInfec\u00ad\ntious Substance\u201d label. The laboratory director of the state \nhealth department should be contacted before shipping a \nspecimen with a suspected biologic agent.\nTRANSMISSION OF TUMORS\nIn general, malignant tumors do not pose a risk to peo\u00ad\nple other than the patient. However, malignancies can be \ntransferred from a graft to organ transplant recipients.32", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_216.png", "summary": "The page discusses safety precautions related to the transmission of tumors, Creutzfeldt-Jakob disease, and biologic terrorism in pathology. It also mentions the Laboratory Response Network (LRN) as a partnership for public health laboratories.", "questions": [ "What are the recommended safety precautions for handling tissues from patients with known or suspected SARS?", "How can Creutzfeldt-Jakob disease be transmitted to laboratory personnel?", "What are the recommended actions for pathologists in the event of a bioterrorist attack?", "What is the purpose and function of the Laboratory Response Network (LRN)?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 217, "text": "199\nSAFETY PRECAUTIONS\u2003 Transmission of Tumors\nTABLE 8\u20132.\u2003\nAGENTS MOST LIKELY TO BE USED FOR BIOLOGIC TERRORISM (CATEGORY A AGENTS)\nAGENT \nMODE OF TRANSMISSION\nCLINICAL SYNDROME\nPATHOLOGIC FINDINGS\nAVAILABLE TESTSa/\nAPPEARANCE OF ORGANISM\nTREATMENT/PROPHYLAXIS\nSmallpox virus (variola major)\nInhalation \u2013 aerosols\nDirect contact with lesions or \ncontaminated surfaces\nPerson to person spread\nDiffuse rash (including palms and \nsoles): deep-seated, firm/hard, \nround well circumscribed vesicles \nor \u00adpustules, all in same stage of \ndevelopment\nHemorrhage into skin and GI tract\nEarly vesicles are multilocular \n(but coalesce in later stages), \nballooning degeneration of \nepithelial cells (not multinucle\u00ad\nated), eosinophilic intracytoplas\u00ad\nmic viral inclusions (Guarnieri \nbodies)\nIHC\nEM: fluid from vesicles can be \nused to detect viral particles\nPCR: viral DNA.\nVaccine availableb.\nRoutine vaccination in the \nUS ended in 1972. Persons \nwith remote vaccination \n\u00adprobably have some, but \nnot complete, immunity.\nBacillus anthracis (anthrax)\nDirect contact with spores (skin \nor ingestion)\nInhalation of spores\nNo person-to-person spread\nCutaneous \u2013 eschar with hemor\u00ad\nrhage, edema, necrosis, perivascu\u00ad\nlar infiltrate, vasculitis\nGastrointestinal \u2013 hemorrhagic \n\u00adenteritis, hemorrhagic lymphad\u00ad\nenitis, mucosal ulcers with necrosis \nin the terminal ileum and cecum, \nperitonitis\nInhalational - hemorrhagic mediasti\u00ad\nnitis, hemorrhagic lymphadenitis, \nhemorrhagic pleural effusion\nCNS \u2013 hemorrhagic meningitis\nSkin: edema, focal necrosis, \nvasculitis, acute inflammation, \nulceration. Organisms only rarely \nseen by H&E.\nLymph nodes: hemorrhage, \nnecrosis\nAfter antibiotic treatment, \n\u00adorganisms may only be visible \nby silver stains and IHC\nGram, silver stains: Large \nbroad (3 \u00d7 5 \u03bcm \u00d7 1 \u00d7 1.5 \n\u03bcm) encapsulated Gram pos \nbacilli with flattened ends in \nshort chains\nIndia ink: shows capsule in \nblood and CSF\nIHC \u2013 sensitive and specific\nDFA (but cannot be used on \nformalin fixed tissue)\nPCR: formalin or fresh tissue\nVaccine availableb\nAntibiotic prophylaxis \n\u00adavailable\nYersinia pestis (plague)\nFlea bites\nInhalation \u2013 aerosols\nPerson-to-person spread\nBubonic \u2013 acute lymphadenitis with \nsurrounding edema (a bubo is a \nlocal painful swelling)\nPneumonic \u2013 severe, hemorrhagic \nbronchopneumonia, often with \nfibrinous pleuritis, diffuse alveolar \ndamage (ARDS), sepsis with DIC\nCNS - meningitis\nLung: severe, confluent, \n\u00adhemorrhagic, necrotizing \nbronchopneumonia, often with \nfibrinous pleuritis\nLymph nodes: necrosis \u2013 preferred \nfor histologic examination and \nculture\nGram, silver, Giemsa stains: \nShort fat Gram neg bacilli\nIHC\nDFA\nVaccine available (but \ndoes not protect against \npneumonia)b\nAntibiotic prophylaxis \n\u00adavailable\nClostridium botulinum toxin \n(botulism)\nIngestion or inhalation of \npreformed neurotoxin\nNo person-to-person spread\nCNS \u2013 hyperemia and microthrombo\u00ad\nsis of small vessels associated with \n\u00adsymmetrical, descending pattern \nof weakness and paralysis of cra\u00ad\nnial nerves, limbs, and trunk\nNo specific findings for cases due \nto ingestion or inhalation of \npreformed toxin\nSwabs of mucosal surfaces or \nserum may be used for the botu\u00ad\nlinum toxin mouse bioassay\nSamples should be taken prior to \nthe use of antitoxin\nGram-positive bacteria \u2013 \n\u00adhowever organisms unlikely \nto be present in a terror \nattack\nAntitoxin available\ncontinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_217.png", "summary": "The page discusses safety precautions related to the transmission of tumors and lists agents most likely to be used for biologic terrorism, including smallpox virus, Bacillus anthracis, Yersinia pestis, and Clostridium botulinum toxin.", "questions": [ "What are the modes of transmission for the listed biologic terrorism agents?", "What are the clinical syndromes associated with each agent?", "What pathologic findings are characteristic of each agent?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 218, "text": "200\nSAFETY PRECAUTIONS\u2003 Transmission of Tumors\nAGENT \nMODE OF TRANSMISSION\nCLINICAL SYNDROME\nPATHOLOGIC FINDINGS\nAVAILABLE TESTSa/\nAPPEARANCE OF ORGANISM\nTREATMENT/PROPHYLAXIS\nFrancisella tularensis (tulare\u00ad\nmia)\nTick bite\nDirect contact with infected \nfluids or tissues\nIngestion of infected meat\nNo person-to-person spread\nUlceroglandular \u2013 skin ulcer with \nassociated suppurative lymphad\u00ad\nenitis\nGlandular \u2013 suppurative necrotizing \nlymphadenitis without associated \nskin ulcer\nOculoglandular \u2013 eyelid edema, \nacute conjunctivitis and edema, \nsmall conjunctival ulcers, regional \nlymphadenitis\nPharyngeal \u2013 exudative pharyngi\u00ad\ntis or tonsillitis with ulceration, \npharyngeal membrane formation, \nregional lymphadenitis\nTyphoidal \u2013 systemic involvement, \nDIC, focal necrosis of major organs\nPneumonic \u2013 acute inflammation, \ndiffuse alveolar damage\nUlcer with a nonspecific inflam\u00ad\nmatory infiltrate and a granulo\u00ad\nmatous reaction. In some cases, \nlarge necrotizing granulomas \nwith giant cells may be present.\nLymph nodes: extensive necrosis, \nirregular microabscesses and \nmultiple granulomas with \ncaseous necrosis.\nLung: necrotizing pneumonia with \nabundant fibrin, acute inflam\u00ad\nmation\nSmall encapsulated Gram-neg\u00ad\native coccobacilli - difficult to \nsee with histochemical stains\nIHC\nDFA\nAntibiotic prophylaxis \navailable\nHemorrhagic fever viruses, \nincluding:\n - \u0007Filoviruses (including \nEbola and Marburg \nviruses)\n - \u0007Arenaviruses (e.g., Lassa \nfever)\nClose personal contact with \ninfected person, blood, \n\u00adtissue, or body fluids\nDiffuse rash, massive hepatocellular \nnecrosis, extensive necrosis in \nother major organs, diffuse \nalveolar damage\nMassive hepatic necrosis with \nfilamentous viral inclusions in \nhepatocytes, extensive necrosis \nof other organs\nIHC\nEM: viral inclusions\nPCR\nNo specific treatment\nARDS: acute respiratory distress syndrome, DIC: disseminated intravascular coagulopathy, IHC: immunohistochemistry; DFA: direct fluorescent assay.\naIHC and DFA tests for each of these organisms are available at the CDC. Consult their website to determine how to decide if a specimen is appropriate for testing and how to send such a sample: call the CDC at 404-639-3133 or fax \nthe CDC at 404-639-3043, for more information.\nbVaccination is not currently recommended for individuals without a known exposure. Vaccination for smallpox may be considered for selected personnel who would be a first responder for the examination of the remains or speci\u00ad\nmens from patients dying of smallpox.\nTABLE 8\u20132.\u2003\nAGENTS MOST LIKELY TO BE USED FOR BIOLOGIC TERRORISM (CATEGORY A AGENTS)\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_218.png", "summary": "The page discusses safety precautions for transmission of tumors, including information on Francisella tularensis (tularemia) and hemorrhagic fever viruses. It covers modes of transmission, clinical syndromes, pathologic findings, available tests, and treatment/prophylaxis.", "questions": [ "What are the different clinical syndromes associated with Francisella tularensis (tularemia)?", "What are the pathologic findings in cases of tularemia?", "What are the modes of transmission for hemorrhagic fever viruses?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 219, "text": "201\nSAFETY PRECAUTIONS\u2003 Prevention of Injuries and Exposures\nBenign and malignant tumors can be transferred among \ndogs and wolves and among Tasmanian devils by contact. \nThe transfer of these tumors has been species-specific.\nThere has been one case of a sarcoma transferred to the \nhand of a nonimmunocompromised surgeon after a scalpel \ninjury.33 Thus, although the risk is extremely small, tumors \n(and all human tissue) must be handled with appropriate \nsafety precautions.\nGUIDELINES FOR PROCESSING SPECIMENS WITH \nKNOWN/PROBABLE INFECTIOUS DISEASE\nSpecimens from patients with infections not posing a risk \nto immunocompetent individuals (e.g., routine bacterial \nand fungal infections, opportunistic pathogens) can be \nprocessed as for other pathology specimens using univer\u00ad\nsal precautions. Specimens from patients with infections \n(or suspected infections) posing a greater risk to pathology \npersonnel (TB, HBV, HCV, HIV, Creutzfeldt-Jakob dis\u00ad\nease) must be handled with special precautions. All speci\u00ad\nmens must be fixed as soon as possible and stored in rigid \nleakproof containers. Gloves must always be worn when \nhandling specimens.\nFresh tissues are potentially infective and all specimens \nare placed in fixative as soon as possible. Formalin is effec\u00ad\ntive for inactivating viruses (including HIV and HBV) \nand will reduce the infectivity of mycobacteria. Proce\u00ad\ndures that could aerosolize an infectious agent (e.g., cut\u00ad\nting a specimen with a bone saw) should not be performed. \nCreutzfeldt-Jakob disease requires special procedures for \nhandling it safely (see specific section).\nSmall specimens (e.g., colon biopsies and open lung \nbiopsies) are usually of immediate diagnostic importance \nand can be processed as usual as long as the specimens fix \nin formalin for at least four to six hours.\nLarger specimens, if of no immediate diagnostic impor\u00ad\ntance (e.g., a placenta from a normal delivery or a colon \nresection for trauma) can be sectioned thinly and placed \nin an adequate volume of fixative (1:10 specimen/formalin \nfixative ratio) for 72 hours before submitting for histologic \nprocessing. If the specimen is of immediate diagnostic \nimportance, small sections can be cut for blocks and fixed \nas above before processing.\nPotentially infectious cases are not photographed in the \nfresh state. If it is an especially interesting case, pictures \nafter fixation may be taken if special precautions are used in \norder not to contaminate surfaces or the camera.\nFrozen sections on potentially infectious cases may be \nperformed but should be avoided if cytologic preparations \ncan be used or an intraoperative diagnosis is not necessary. \nFreezing does not inactivate infectious agents. If an infec\u00ad\ntious case is cut in a cryostat, the cryostat should be decon\u00ad\ntaminated. Pressurized sprays should not be used as this \ncan aerosolize infectious agents. Air-dried slides should be \nconsidered potentially infectious and are not saved or sub\u00ad\nmitted to the histology laboratory. Any smears submitted \nfor special stains must be fixed in methanol.\nPREVENTION OF INJURIES AND EXPOSURES\nPrevention of injuries and exposures is the goal of all \npathology personnel. The most common injury is to the \nnondominant hand. Most injuries and exposure to blood \nand other body fluids can be prevented if the following \nguidelines are followed:\n\t\u2022\t \u0007Gloves must be worn when handling fresh and fixed \ntissues. Two pairs of gloves are recommended for haz\u00ad\nardous specimens, as small tears in gloves are common. \nMetal mesh and Kevlar cloth type gloves can help pre\u00ad\nvent puncture injuries\n\t\u2022\t \u0007Latex gloves will protect against biohazards but not fixa\u00ad\ntives. Nitrile gloves will also provide protection from \nfixatives. Some individuals (5% to 10%) have or develop \nallergic reactions (usually dermatitis but sometimes \nasthma or anaphylaxis) to latex antigens.\n\t\u2022\t \u0007Do not touch objects in general use (door handles, tele\u00ad\nphone, computer, etc.) with contaminated gloves.\n\t\u2022\t \u0007Hands must always be washed after handling specimens \nand after leaving a specimen handling area because \ngloves are not completely leakproof.\n\t\u2022\t \u0007Protective clothing, including gloves, must be removed \nand disposed of properly before leaving the surgical cut\u00ad\nting or OR consultation rooms.\n\t\u2022\t \u0007Scrub suits or disposable jumpsuits are recommended if \nlarge bloody specimens need to be processed.\n\t\u2022\t \u0007Aprons must be worn when handling many specimens \n(e.g., at a cutting bench) or for handling large specimens.\n\t\u2022\t \u0007If lab coats are worn while working in the surgical cut\u00ad\nting room, they cannot be worn outside of this area.\n\t\u2022\t \u0007Any person using a scalpel blade, razor blade, or syringe \nneedle is responsible for disposing of it properly. Scal\u00ad\npel blades are removed from the handle with extreme \ncaution after gross blood and tissue have been removed. \nFrozen section blocks are not removed from the chuck \nwith a razor blade. Holding the stem for a few seconds \nwill melt the embedding medium sufficiently for removal \nwith a fingertip. Syringe needles are never recapped. \nAll blades, needles, and disposable scissors must be dis\u00ad\ncarded into impervious labeled sharps containers. Bro\u00ad\nken glass slides and coverslips must also be disposed into \ndesignated containers.\n\t\u2022\t \u0007Reusable but contaminated equipment should be decon\u00ad\ntaminated with bleach.\n\t\u2022\t \u0007All tissues are fixed as soon as possible. Unfixed speci\u00ad\nmens must be kept in leakproof containers and stored in \nan appropriate biohazard refrigerator or freezer.\n\t\u2022\t \u0007Always dispose of all blood and tissue fragments before \nleaving a worksite. All tissues, or nonreusable material \ncontaminated by any body fluid or tissue, must be disposed \nin labeled hazardous waste containers (containers with red \nbags and biohazard symbols). Urine, blood, and feces may \nbe disposed directly into the municipal sewerage system.\n\t\u2022\t \u0007Areas contaminated after handling a known infectious \ncase should be immediately cleaned with dilute bleach.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_219.png", "summary": "The page discusses safety precautions for handling specimens with known or probable infectious diseases, emphasizing the importance of proper handling to prevent exposure and transmission of diseases.", "questions": [ "What are some examples of infectious diseases that require special precautions when handling specimens?", "Why is it important to fix specimens in formalin as soon as possible?", "What are the guidelines for processing small specimens versus larger specimens with no immediate diagnostic importance?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 220, "text": "202\nSAFETY PRECAUTIONS\u2003 Radiation\n\t\u2022\t \u0007Eye protection should be worn when cutting into large \nspecimens. Cysts may feel deceptively solid when filled \nwith fluid. Such fluid may be under pressure and can \ntravel several feet when the cyst is opened (this has been \ndocumented by many pathologists!). Place near sink on a \nsurgical drape or blue barrier and make a small nick near \nthe bottom in order to let fluid slowly drain out of the \ncyst.\n\t\u2022\t \u0007Food or beverages must not be consumed, or brought \ninto, the cutting room or the OR consultation room. \nFoods cannot be stored in refrigerators used to store \nspecimens. Food or food containers (e.g., an empty cof\u00ad\nfee cup) cannot be disposed into containers in these areas \nas this may be used as evidence that food consumption is \noccurring in these areas. Evidence of food consumption is \nmonitored by OSHA and can be grounds for penalties or \nclosure.\nRADIATION34-39\nRadioactive substances are widely used in the evaluation \nof patients and may be present in tissues submitted to \npathology departments. In some cases, patients will have \nbeen injected with radioactive agents for the purpose of \nlocalizing and surgically removing a lesion (e.g., sentinel \nnodes, octreotide-positive lesions). In general, patients are \ninjected with small amounts (<5 millicuries) and typical \nhalf-lives are short (e.g., the half-life of 99mtechnetium used \nfor sentinel lymph nodes is 6 hours). Specimens should \nhave minimal residual radioactivity and can be generally \nhandled and disposed without special precautions. How\u00ad\never, radiation safety personnel should be consulted to \ndetermine the appropriate procedures for the techniques \nused in individual institutions.\nFederal law allows routine methods of solid medical \nwaste disposal for radioactive specimens after decay in \nstorage, which requires the lapse of 10 half-lives. Thus, \nspecimens containing technicium can be disposed using \nnormal methods 60 hours after the time of surgery.\nREFERENCES\n\t\u2002 1.\t \u0007Montecalvo MA, Lee MS, DePalma H, et al. Seroprevalence \nof human immunodeficiency virus-1, hepatitis B virus, and \nhepatitis C virus in patients having major surgery. Inf Con\u00ad\ntrol Hosp Epidem 16:627-632, 1995.\n\t\u2002 2.\t \u0007Tuberculosis infection associated with tissue processing. \nMMWR 30:73-74, 1981.\n\t\u2002 3.\t \u0007Duray PH, Flannery B, Brown S. Tuberculosis infection \nfrom preparation of frozen sections. NEJM 305:167, 1981.\n\t\u2002 4.\t \u0007CDC Hepatitis information line \u2013 888-443-7243 (www.cdc.\ngov/hepatitis).\n\t\u2002 5.\t \u0007Updated U.S. Public Health Service Guidelines for the Man\u00ad\nagement of Occupational Exposures to HBV, HCV, and \nHIV and Recommendations for Postexposure Prophylaxis \n(June 29, 2001) \u2013 http://www.cdc.gov/mmwr/preview/mmw\nrhtml/rr5011a1.htm.\n\t\u2002 6.\t \u0007NIH consensus statement on management of Hepatitis C: \n2002-htttp://consensus.nih.gov\n\t\u2002 7.\t \u0007Beltrami EM, Cheingsong R, Heneine WM, et al. Occu\u00ad\npational HIV Exposure Study Group. Infect Control Hosp \nEpidemiol 24:724-730, 2003.\n\t\u2002 8.\t \u0007Current Public Health Service guidelines for post-exposure \nprophylaxis \u2013 http://www.cdc.gov/mmwr/preview/mmwrht\nml/rr5011a1.htm\n\t\u2002 9.\t \u0007Do AN, Ciesielski CA, Metler RP, et al. Occupationally \nacquired human immunodeficiency virus (HIV) infection: \nnational case surveillance data during 20 years of the HIV \nepidemic in the United States. Infect Control Hosp Epide\u00ad\nmiol 24:86-96, 2003.\n\t10.\t \u0007Johnson MD, et al. Autopsy risk and acquisition of human \nimmunodeficiency virus infection. Arch Pathol Lab Med \n121:64-66, 1997; Johnson M, Working on a Miracle, \n\u00adBantam, USA, 1998.\n\t11.\t \u0007Gerberding JL. Occupational exposure to HIV in health care \nsettings. NEJM 348:826-833, 2003.\n\t12.\t \u0007National Clinician\u2019s Post-Exposure Prophylaxis \u00adHotline (PEP\u00ad\nline), University of California, San Francisco \u2013 San Francisco Gen\u00ad\neral Hospital \u2013 888-448-4911 (http://www.ucsf.edu/hivcntr).\n\t13.\t \u0007Needlestick! (an online decision-making support for cli\u00ad\nnicians), Emergency Medicine Center, UCLA School of \n\u00adMedicine \u2013 http://www.needlestick.mednet.ucla.edu.\n\t14.\t \u0007Nyberg M, et al. Isolation of human immunodeficiency virus \n(HIV) at autopsy one to six days postmortem. Am J Clin \nPathol 94:422-425, 1990.\n\t15.\t \u0007Paul SM. Recommendations for reducing the risk of \n\u00adoccupational HIV transmission, N J Med 100(9 Suppl):15-20, \n2003.\n\t16.\t \u0007Goette DK, Jacobson KW, Doty RD. Primary inocula\u00ad\ntion tuberculosis of the skin. Prosector\u2019s paronychia. Arch \n\u00adDermatol 114:567-569, 1978.\n\t17.\t \u0007Templeton GL, Illing LA, Young L, et al. The \nrisk for transmission of Mycobacterium tuberculosis at \nthe bedside and during autopsy. Ann Int Med 122:\n922-925, 1995.\n\t18.\t \u0007Gerston KF, Blumberg L, Tshabalala VA, et al. Viability \nof mycobacteria in formalin fixed lungs. Hum Pathol 35:\n571-575, 2004.\n\t19.\t \u0007National Institute for Occupational Safety and Health - http:\nwww.cdc.gov/niosh/topics/SARS.\n\t20.\t \u0007Brumbeck RA. Routine use of phenolized formalin on \nautopsy brain tissue. N Engl J Med 319:654, 1988.\n\t21.\t \u0007Brown P, Wolff A Gajdusek DC. A simple and effective \nmethod for inactivating virus activity in formalin-fixed \n\u00adtissue samples from patients with Creutzfeldt-Jakob disease. \n\u00adNeurology 40:887-890, 1990.\n\t22.\t \u0007Burgess TH, Steele KE, Schoneboom BA, Grieder FB. Clin\u00ad\nicopathologic features of viral agents of potential use by bio\u00ad\nterrorists. Clin Lab Med 21:475-493, 2001.\n\t23.\t \u0007Caya JG, Agni R, Miller JE. Clostridium botulinum and the \nclinical laboratorian. A detailed review of botulism, includ\u00ad\ning biologic warfare ramifications of botulinum toxin. Arch \nPathol Lab Med 128:653-662, 2004.\n\t24.\t \u0007CDC Bioterrorism webpage: http://www.bt.cdc.gov.\n\t25.\t \u0007Firmani MA, Broussard, Molecular diagnostic techniques for \nuse in response to bioterrorism. Expert Rev Mol Digan 3:\n605-615, 2003.\n\t26.\t \u0007Guarner J, Jernigan JA, Shieh WJ, et al. and the Inhala\u00ad\ntion Anthrax Working Group. Pathology and pathogenesis \nof bioterrorism-related inhalational anthrax. Am J Pathol \n163:701-709, 2003.\n\t27.\t \u0007Medical examiners, coroners, and biologic terrorism. A\u00a0guide\u00ad\nbook for surveillance and case management. \u00adMorbidity and \nMortality Weekly Report, supplement vol. 53(No. RR-8), \n2004.\n\t28.\t \u0007Nelson A, Wilson ML. Biothreat agents and pathology labo\u00ad\nratories. Sem Diag Pathol 24:209-216, 2007.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_220.png", "summary": "The page discusses safety precautions related to radiation exposure in the pathology lab, including the need for eye protection when cutting into specimens and restrictions on food consumption in certain areas. It also mentions the handling and disposal of radioactive specimens.", "questions": [ "What are the risks associated with cutting into large specimens without eye protection?", "Why is it important to restrict food consumption in certain areas of the lab?", "What are the guidelines for handling and disposing of radioactive specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 221, "text": "203\nSAFETY PRECAUTIONS\u2003 Radiation\n\t29.\t \u0007Robinson-Dunn B. The microbiology laboratory\u2019s role in \nresponse to bioterrorism. Arch Pathol Lab Med 126:2910294, \n2002.\n\t30.\t \u0007Rollins SE, Rollins SM, Ryan ET. Yersinia pestis and the \nplague. Am J Clin Pathol 119(Suppl):S78-S85, 2003.\n\t31.\t \u0007Wun-Ju Shieh, Guarner J, Paddock C, et al. the Anthrax \nBioterroism Investigation Team. The critical role of pathol\u00ad\nogy in the investigation of bioterrorism-related cutaneous \nanthrax. Am J Pathol 163:1901-1910, 2003.\n\t32.\t \u0007Loh E, Couch FJ, Hendricksen C, et al. \u00adDevelopment \nof donor-derived prostate cancer in a recipient fol\u00ad\nlowing orthotopic heart transplantation. JAMA 277:\n133-137, 1997.\n\t33.\t \u0007G\u00e4rtner H-V, Seidl C, Luckenbach C, et al. Genetic \u00adanalysis \nof a sarcoma accidentally transplanted from a patient to a sur\u00ad\ngeon. N Eng J Med 335:1494-1496, 1996.\n\t34.\t \u0007de Kanter AY, Arends PP, Eggermont AM, Wiggers T. \nRadiation protection for the sentinel node procedure in \nbreast cancer. Eur J Surg Oncol 29:396-399, 2003.\n\t35.\t \u0007Fitzgibbons PL, LiVolsi VA, for the Surgical Committee of \nthe College of American Pathologists and the Association of \nDirectors of Anatomic Surgical Pathology. Recommenda\u00ad\ntions for handling radioactive specimens obtained by sentinel \nlymphadenectomy. Am J Surg Pathol 24:1549-1551, 2000.\n\t36.\t \u0007Klausen TL, Chakera AH, Friis E, et al. Radiation doses to \nstaff involved in sentinel node operations for breast cancer. \nClin Physiol Funct Imaging 25:196-202, 2005. (Radiation \nlevels to the hands of pathologists was below the detection \nlimit in 17 cases.).\n\t37.\t \u0007Law M, Chow LWC, Kwong A, Lam CK. Sentinel lymph \nnode technique for breast cancer: radiation safety issues. Sem \nOncol 31:298-303, 2004.\n\t38.\t \u0007Morton R, Horton PW, Peet DJ, Kissin MW. Quantitative \nassessment of the radiation hazards and risks in sentinel node \nprocedures. Br J Radiol 76:117-122, 2003.\n\t39.\t \u0007Stratmann SL, McCarty TM, Kuhn JA. Radiation safety with \nbreast sentinel node biopsy. Am J Surg 178:454-457, 1999.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_221.png", "summary": "This page discusses safety precautions related to radiation exposure in the context of surgical pathology procedures, specifically focusing on sentinel node operations for breast cancer.", "questions": [ "What are some specific recommendations for handling radioactive specimens obtained by sentinel lymphadenectomy?", "How do radiation doses to staff involved in sentinel node operations for breast cancer compare to safety limits?", "What are the key radiation safety issues associated with the sentinel lymph node technique for breast cancer?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 222, "text": "204\n9\nMicroscopy and Photography\nA pathologist without a microscope is like a surgeon with\u00ad\nout a scalpel or a dermatologist without steroid cream \u2014 \nall are tools essential to our practice of medicine. Although \nit is not necessary to have an advanced degree in optics, it is \nimportant to understand the basics of microscope use, spe\u00ad\ncial techniques useful to the pathologist, and optical prop\u00ad\nerties of biologic and synthetic materials present in clinical \nspecimens. These topics are covered in the sections below.\nOPTIMAL OPTICS\nOptimal image formation occurs when the image is in \nfocus and the illumination is appropriately adjusted. First, \nthe eyepieces should be adjusted for width (by sliding them \nback and forth) in order to form a single image. Secondly, \neach eye is closed in turn individually to adjust the focus of \neach eyepiece. Many people have subtle differences between \ntheir two eyes. Finally, the illumination is adjusted to ensure \nthat the light is bright, evenly dispersed, glare free, and that \ngood image contrast is achieved. This procedure is termed \n\u201cKoehler illumination\u201d after the person who first deter\u00ad\nmined the optimal settings (Boxes 9-1 and 9-2; Fig. 9-1).\nUsing this technique, the microscope is now optimally \nadjusted for one objective. Other objectives will require \nreadjustment and in practical terms usually a compromise \nposition is used that is adequate for all of the objectives. \nA reasonable solution is to center the field diaphragm for \na 40\u00d7 objective and maintain its opening for a 10\u00d7 field. \nThe substage condenser should be slightly below the level \nwhere dust is brought into focus under 10\u00d7. As objectives \nare changed, only the aperture diaphragm need be changed \nto optimize contrast.\nIf the light intensity needs to be adjusted, it is accom\u00ad\nplished by using the transformer, not by changing the posi\u00ad\ntion of the condenser or diaphragm.\nContrast can be increased by closing the aperture dia\u00ad\nphragm below 60% or by lowering the substage condenser. \nHowever, resolution and sharpness are reduced. This \nmaneuver may be useful if looking for refractile material \n(see section below).\nOIL IMMERSION MICROSCOPY\nOil immersion lenses (usually 100\u00d7) can achieve higher \nmagnifications than dry lenses. Because the refractive \nindex of oil is higher than that of air, light rays coming \nfrom the slide are bent to a greater degree and thus an oil \n\u00adobjective can capture more of these light rays, which results \nin greater resolution.\nThere are two major uses in surgical pathology for oil \nimmersion magnification:\n 1.\t \u0007Hematologic specimens (due to the generally small size \nof the cells and the importance of subtle nuclear and \ncytoplasmic features for characterization)\n 2.\t \u0007Small microorganisms (e.g., acid-fast bacilli or micro\u00ad\nsporidia).\nThere is virtually no other use for oil immersion lenses. \nThe use of oil should be avoided outside of the applica\u00ad\ntions cited above due to the frequent contamination of the \nmicroscope and other objectives with oil if great care is not \nused.\nOnly immersion oil designed for microscopic use should \nbe employed. Lint-free tissues or lens paper should always \nbe available to wipe away any excess oil before it drips into \nthe microscope or onto other surfaces (Box 9-3).\nBOX 9\u20131.\u2003 Definitions\n \u2022 \u0007Field diaphragm: Source of light at the base of the microscope. \nAdjusted by moving the circular ring around it.\n \u2022 \u0007Substage condenser: Located just below the stage. It can be \nmoved up and down and centered with two screws.\n \u2022 \u0007Aperture iris diaphragm: Located in the substage condenser. \nAdjusted by using a rotating ring on the front of the condenser.\nBOX 9\u20132.\u2003 \u0007Adjusting a microscope for Koehler \n\u00adillumination\n 1. \u0007Open the aperture diaphragm and the field diaphragm \n\u00adcompletely. Using a 20\u00d7 objective, focus on a slide on the \nstage.\n 2. \u0007Close the field diaphragm almost completely. Raise the \n\u00adcondenser until the edges of the diaphragm are sharply \nfocused (the condenser is usually at about its highest \n\u00adposition).\n 3. \u0007Use the centering screws on the substage condenser to \ncenter the image of the field diaphragm. Slowly open the field \n\u00addiaphragm until it just disappears from view.\n 4. \u0007Remove one eyepiece objective and look into the tube. Open \nand close the aperture diaphragm until only 66% to 77% \nof the back lens is illuminated (see Fig. 9-1). This prevents \n\u00adunnecessary light from entering that will create glare.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_222.png", "summary": "The page discusses the importance of optimal optics in microscopy, including adjusting the eyepieces, illumination, and using oil immersion lenses for higher magnification.", "questions": [ "Why is it important to adjust the eyepieces and illumination for optimal image formation in microscopy?", "What is the significance of using oil immersion lenses in surgical pathology?", "What are the major uses of oil immersion magnification mentioned in the text?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 223, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Optical Properties\n205\nDo not attempt to view a slide with a high power \ndry objective while there is oil on the slide! If it is nec\u00ad\nessary to scan a slide, place a 4\u00d7 objective adjacent to the \noil objective. One can safely alternate between these two \nobjectives without contaminating the 4\u00d7 objective with oil. \nIt is very difficult to clean oil off a dry objective (see the \nsection on cleaning objective below).\nOPTICAL PROPERTIES\nThe optical properties of microscopic objects reveal clues \nabout their structure and identity (Table 9-1).\n\u201cRefractile\u201d Objects\nThese objects have a refractive index different than that of \nnormal tissue. Refractility can be highlighted by increasing \nthe contrast (i.e., by lowering the condenser or closing the \naperture diaphragm). Refractile objects look brighter and \nshinier than tissues. This material is usually foreign (e.g., \nsuture material) but can be endogenous. \u201cDoubly refractile\u201d \nis sometimes used to describe objects that are polarizable.\n\u201cPolarizable\u201d Objects\nPolarized light is light oriented in one specific plane and \nis produced by using two crossed polarizing filters. Most \ntissues are isotropic and do not change the quality of light \npassing through them. They appear dark under polarized \nlight as very little light passes through the filters in any \ngiven plane.\n\u201cPolarizable,\u201d \u201cbirefringent,\u201d or \u201canisotropic\u201d are terms \nused to describe substances that change the direction and \nspeed of the light passing through them. Polarized light \npassing through such an object is deviated in a particular \nplane or planes and can pass through a second polarizing \nfilter at an angle to the first. A \u201cpolarizable\u201d object appears \nbright in comparison to the surrounding dark nonpo\u00ad\nlarizable tissue. Some substances can reflect light at two \ndifferent wavelengths (e.g., the \u201cdichroic birefringence\u201d \nof amyloid). Many of these polarizable substances have \nregular repeating structures (e.g., crystalline) and may be \nbiologic (e.g., amyloid or collagen) or synthetic (e.g., poly\u00ad\nethylene).\nPolarizing Objects\nSome microscopes have built-in high-quality polarizers. \nPolarizing material may also be purchased as sheets and has \nthe advantage in being transportable. It is available from \nEdmund Scientific Company (101 East Gloucester Pike, \nBarrington, NJ 08007-1380, [609] 573-6879; TECH\u00ad\nSUP@EDSCI.COM or www.edsci.com). However, polar\u00ad\nizing material varies greatly in quality. Tissues (especially \nwith suspected amyloid) should be observed using the \nhigher quality built-in polarizers before it is determined \nthat polarizable material is not present.\nWhen the polarizer and the analyzer are at ninety \ndegrees to each other, no light can pass through and the \nfield is dark (Box 9-4). As the angle between the filters is \nchanged by rotating the polarizer, substances that prefer\u00ad\nentially reflect light in a specific direction (i.e., polarizable \nmaterials) allow light to pass through the analyzer and will \nappear bright.\nThe determination of \u201cpositive\u201d and \u201cnegative\u201d bire\u00ad\nfringence requires using a compensating first order red \nfilter under polarized light and can be used to distinguish \nuric acid crystals from CPPD crystals. However, this \n\u00addetermination is best performed on crystals in solution and \ncannot be reliably performed on fixed tissue.\nFULL\nCONE\n90%\n80%\n77%\n66%\nFigure 9\u20131.\u2002 Aperture size.\nBOX 9\u20133.\u2003 Using an oil immersion lens\n 1. \u0007Focus the microscope using the highest magnification avail\u00ad\nable with a dry objective. It is helpful to identify and mark the \narea(s) of the slide to be examined under oil with ink to avoid \nthe need to scan the slide after oil is applied.\n 2. \u0007Swing this objective away (in the direction to bring the oil \nobjective into place) and place a small amount of oil on the \nslide.\n 3. \u0007Swing the oil objective into place, making sure that the space \nbetween the objective and the slide is filled with oil. The slide \nmay now be observed.\n 4. \u0007After viewing, again swing the oil objective partially away from \nthe slide.\n 5. \u0007Immediately wipe the objective with lens paper to prevent oil \nfrom dripping onto the microscope.\n 6. \u0007Remove the slide and wipe off excess oil with lens paper. The \nslide may then be cleaned with a small amount of xylene. \nPeripheral blood smears are often viewed under oil without \nusing a coverslip. The oil can be wiped directly off the slide.\nBOX 9\u20134.\u2003 Definitions\n \u2022 \u0007Polarizer: The polarizing disk below the condenser.\n \u2022 \u0007Analyzer: The polarizing disk above the specimen (laid on top \nof the slide or built into microscope above the objectives).\nText continues on p.213", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_223.png", "summary": "The page discusses the optical properties of microscopic objects, including refractile, polarizable, and polarizing objects.", "questions": [ "How can refractile objects be highlighted to distinguish them from normal tissue?", "What is the significance of polarized light in identifying certain substances?", "How can the quality of polarizing material affect the observation of tissues?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 224, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\t\n15\n206\nTABLE 9\u20131.\u2003\nOPTICAL PROPERTIES OF COMMONLY SEEN NONCELLULAR MATERIAL\nTYPE\nPOLARIZATION\nREFRACTILE\nLOCATIONS \nUSUALLY SEEN\nAPPEARANCE/STAINS\nCOMMENTS\nHISTOLOGIC \nAPPEARANCE\nEndogenous Material\nAmyloid\nYes\nYes/no\nBone marrow (multiple \nmyeloma), medullary \ncarcinoma of the thy\u00ad\nroid, periarticular tissue \nin dialysis patients, \nmany other sites\nAcellular homogeneous \npink material, some\u00ad\ntimes with giant cells. \nCongo red +: orange/\nred without polarization \nand apple green with \npolarization\nImmunoperoxidase studies can be \nused to identify specific types of \namyloid:\n \u2022 \u0007Multiple myeloma \u2013 lambda and \nkappa chains\n \u2022 \u0007Medullary carcinoma of the thyroid \n\u2013 calcitonin\n \u2022 \u0007Dialysis-related amyloidosis \u2013 \u03b22 \nmicroglobulin\nEM can also be used to recognize \namyloid\nBile\nNo\nNo\nLiver \u2014 hepatocytes or \nintracanicular\nDark green\u2013brown glob\u00ad\nules (intra- or extracel\u00ad\nlular). PAS positive\nMay be helpful for recognition of HCC\nBone and \n\u00adcollagen\nYes\nNo\nJoints and connective \ntissue\nNormal bone \u2013 polarization \nshows regular osteoid \nseams (not seen in \nwoven bone).\nType I collagen is polariz\u00ad\nable. Type III collagen \n(reticulin) is not polariz\u00ad\nable.\nBone and collagen overstained with \nCongo red will also be apple green \nafter polarization. The background \nmust not show staining.\nTrichrome stains and reticulin stains \ncan be used to identify collagen.\nNodular sclerosing Hodgkin disease is \nassociated with polarizable collagen.\nCalcium \u00adoxalate\nYes\nYes\nApocrine cysts of the \nbreast, benign thyroid \nfollicles, giant cells in \nsarcoidosis\nFlat rhomboid (sometimes \nneedle shaped) colorless \nor pale yellow crystals. \nCan be difficult to see \nwithout polarization.\nCan be the source of mammographic \ncalcifications in breast biopsies.\nAlso present in congenital hyperoxal\u00ad\nuria.\nCalcium \n\u00adphosphate\nNo\nNo\nBenign and malignant \nbreast lesions, areas of \nchronic inflammation \nor necrosis, deposition \non collagen (e.g., heart \nvalves), pulmonary blue \nbodies\nPurple granular material.\nCalcium stain +.\nMost common source of mammo\u00ad\ngraphic calcifications", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_224.png", "summary": "The page discusses the optical properties of commonly seen noncellular materials in microscopy and photography, including amyloid, bile, bone and collagen, calcium oxalate, and calcium phosphate.", "questions": [ "What are some specific locations where amyloid is usually seen?", "How can immunoperoxidase studies be used to identify specific types of amyloid?", "What are some common sources of calcium oxalate crystals in the body?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 225, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\t\n15\n207\nContinued\nCalcium pyro\u00ad\nphosphate \ndihydrate \ncrystals \n(\u201cpseudogout\u201d \nor chondro\u00ad\ncalcinosis)\nYes\nYes\nLarge joints in periarticu\u00ad\nlar tissues (uncommon \nin small joints of foot or \nhand)\nBlue to purple short rhom\u00ad\nboid crystals (but may be \nneedle shaped)\nThe crystals are water soluble and \nrequire anaqueous processing for \nbest demonstration\nCharcot-Leyden \ncrystals\nNo\nYes\nSites of eosinophil accu\u00ad\nmulation (e.g., chronic \nsinusitis, parasitic infec\u00ad\ntions, asthma)\nBright-red, needle-like \ncrystals\nCorpora \namylacea\nNo\nNo\nProstate, brain, lung\nExtracellular laminated \nlight pink spherical \nstructures\nIncidence increases with age\nGamna-Gandy \nnodules\nNo\nYes/no\nSpleen, lymph nodes, \nthymus gland, thyroid, \ncardiac myxomas\nGranulomas consisting of \nhemosiderin, calcium, \nforeign body giant cells, \nand ovoid or bamboo-\nshaped structures\n\u201cSiderotic granulomas\u201d found in sites \nof prior hemorrhage\nCan mimic fungal mycelia or parasite \neggs\nHamazaki-\nWesenberg \nbodies\nNo\nYes\nAreas of prior hemor\u00ad\nrhage, lymph nodes \n(sinusoids)\nSmall round to ovoid \nbrown bodies that may \nappear to be budding\nCan mimic pigmented fungal forms or \nbacteria.2\nHemosiderin\nNo\nYes\nAny area of hemorrhage\nLiver in hemochromatosis \nand hemosiderosis\nCoarse granular brown \nintra- and extracellular \ngranules. Iron stain +.\nA complex of iron and ferritin\nUseful in distinguishing prior bleeding \nfrom intraoperative bleeding\nLiesegang rings\nNo\nNo\nAny area of old hemor\u00ad\nrhage\nRound extracellular \nconcentric laminated or \nfibrillated concretions of \nprecipitated proteins\nMay be mistaken for the Giant Kidney \nWorm or fungal organisms3", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_225.png", "summary": "The page discusses various types of crystals and structures that can be found in different tissues, including calcium pyrophosphate crystals, Charcot-Leyden crystals, Corpora amylacea, Gamna-Gandy nodules, Hamazaki-Wesenberg bodies, Hemosiderin, and Liesegang rings.", "questions": [ "What are the characteristics of calcium pyrophosphate crystals?", "Where can Charcot-Leyden crystals be found and what do they look like?", "How can Gamna-Gandy nodules be distinguished from other structures?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 226, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\t\n15\n208\nLipids\nNo/Yes\nNo\nPolarizable lipids may be \npresent in xanthomas, \nhistiocytosis X, and other \ndermatopathologic enti\u00ad\nties, and fat necrosis sec\u00ad\nondary to pancreatitis. \nCholesterol crystals are \noften seen as empty \nclefts in areas of cell \ninjury.\nNeedle-shaped clear \ncrystals of varying size, \nplate-like structures, or \nintracellular rounded \nstructures. Oil red O +. \nSudan black +.\nMust have special processing or \nfrozen sections to avoid loss during \nprocessing\nAlso present in metabolic storage \ndiseases such as Gaucher, Niemann-\nPick, and Wolman diseases\nFat necrosis4\nLipofuscin \n(oxidized lipid \nprecursors)\nNo\nNo\nSites of atrophy or chronic \ninjury\nFine yellow-brown gran\u00ad\nules to coarse granules \nresembling hemosiderin. \nPAS +.\nOchrocytes are histiocytes containing \nlipofuscin\nMalaria pigment \n(haemozoin, \nhematin)\nYes\nNo\nMacrophages and eryth\u00ad\nrocytes\nBrown to black granules \ninside macrophages\nPresent in malaria and schistosomal \ninfections or severe hemolytic \nanemia\nFormalin pigment can resemble \nmalaria pigment\nMelanin\nNo\nNo\nNormal melanocytes \nin basal epithelium, \npigmented malignant \nmelanomas\nFine brown or black gran\u00ad\nules but can sometimes \nresemble hemosiderin. \nFontana Masson +.\nMichaelis-\u00ad\nGutmann \nbody\nNo\nNo\nMalakoplakia\nConcentric targetoid bod\u00ad\nies (\u201cowl-eye\u201d), intra- and \nextracellular. Iron stain +, \nvon Kossa +, PAS +.\nThese bodies may form due to defec\u00ad\ntive phagocytosis of bacteria \u2013 most \npatients have a chronic coliform \ninfection\nProstatic crystal\u00ad\nloids\nNo\nYes\nProstate carcinomas\nBright eosinophilic angu\u00ad\nlated crystals in lumens \nof adenocarcinomas\nAlways associated with cancer \u2013 if pres\u00ad\nent on a core needle biopsy, addi\u00ad\ntional levels should be \u00adexamined\nSimilar crystals are rarely seen in DCIS \nof the breast\nTABLE 9\u20131.\u2003\nOPTICAL PROPERTIES OF COMMONLY SEEN NONCELLULAR MATERIAL\u2014cont\u2019d\nTYPE\nPOLARIZATION\nREFRACTILE\nLOCATIONS \nUSUALLY SEEN\nAPPEARANCE/STAINS\nCOMMENTS\nHISTOLOGIC \nAPPEARANCE\nEndogenous Material", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_226.png", "summary": "The page discusses various noncellular materials commonly seen in histology, such as lipids, lipofuscin, melanin, and other pigments, with details on their appearance and staining characteristics.", "questions": [ "What are some examples of conditions where polarizable lipids may be present?", "How can fat necrosis be differentiated from other lipid-containing entities?", "What staining techniques are commonly used to identify melanin in histological samples?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 227, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\t\n15\n209\nContinued\nPsammoma \nbody\nNo\nNo\nPapillary carcinoma of the \nthyroid, ovarian carci\u00ad\nnoma, breast, others\nLaminated concentric rings \nof calcium phosphate\nVery specific in the thyroid for papillary \ncarcinoma\nReinke crystals\nNo\nYes\nLeydig cells of the testis, \nhilus cells of ovary, and \ntheir tumors\nRod-shaped eosinophilic \ncrystals. Masson\u2019s tri\u00ad\nchrome + (magenta).\nSchaumann \nbodies\nNo\nNo\nLymph nodes in sarcoid\u00ad\nosis\nConcentric basophilic rings\nThe other two types of inclusions in \nsarcoidosis are calcium oxalate and \nasteroid bodies (spider-shaped \ninclusions). These findings are not \nspecific for sarcoid.\nSpironolactone \nbodies\nNo\nNo\nAdrenal adenomas \nassociated with Conn \nsyndrome\nConcentric laminated \neosinophilic inclusions \n(2 to 12 microns) in cyto\u00ad\nplasm. PAS +.\nFound in tumors in patients with Conn \nsyndrome, treated with spironolac\u00ad\ntone\nIHC can identify aldosterone in the \nbodies\nUric acid \u00adcrystals \n(gout)\nYes\nYes\nPeriarticular tissues \naround joints, other \nareas of connective \ntissue\nLong needle-shaped crys\u00ad\ntals (sheaves of wheat) \nare characteristic but \nmay be fractured and \nappear to be smaller \ncrystals\nRequires anaqueous processing for \npreservation.\nIn routine H&E sections only needle-\nshaped holes may be seen where \nthe crystals are dissolved. The crys\u00ad\ntals may be seen in routinely fixed \ntissue if the tissue is unstained.\nIatrogenic Material\nBarium sulfate\nNo/yes\nYes\nIn GI tract after radiologic \nexamination, in perito\u00ad\nneum after perforation, \nwithin bone cement\nGolden refractile granular \nmaterial. May be intra- or \nextracellular.\nRarely incites an inflammatory reaction\nCotton fibers\nYes\nYes\nAround surgical sites\nHollow discoid fibers, pres\u00ad\nent intra- or extracel\u00ad\nlularly", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_227.png", "summary": "The page discusses various microscopic findings in pathology, including Psammoma bodies, Reinke crystals, Schaumann bodies, Spironolactone bodies, and Uric acid crystals.", "questions": [ "What are some specific locations where Psammoma bodies are commonly found?", "How can Spironolactone bodies be identified in tumors associated with Conn syndrome?", "What are the characteristic features of Uric acid crystals in tissue samples?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 228, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\t\n15\n210\nCornstarch\nYes\nNo\nIn surgical sites\n3 to 20 micron spheres. \nMaltese cross appear\u00ad\nance after polarization. \nPAS+, MSS+.\nUsed to lubricate surgical gloves. How\u00ad\never, cornstarch may be avoided \nas it can incite a granulomatous \nresponse.\nFormalin \n\u00adpigment\nNo\nYes\nMost commonly seen in \nbloody tissues\nBrown or black finely \ngranular extracellular \ndeposits\nDue to a reaction between formic acid \nand heme during fixation. Can be \navoided by using buffered formalin.\nCan be mistaken for malaria pigment.\nGelfoam\nNo/yes\nNo/yes\nWithin vascular spaces of \nhemangiomas or other \nvascular lesions, some\u00ad\ntimes used to mark breast \ncore needle biopsy sites\nIrregular fenestrated bluish \nor clear material\nElastic stains may help in identification5\nGold\nYes\nNo\nSkin, lymph nodes, organs \nof patients treated with \ngold for RA\nSmall intracellular black \nparticles in histiocytes\nGold in intramammary LNs can mimic \nmammographic calcifications\nPolarization can be helpful for identi\u00ad\nfication6\nGraft material \n\u2013 Gore-Tex or \nDacron\nYes\nYes\nGrafts\nNumerous uniform round \nfilaments with small \nblack granules\nIndia ink (tattoo \npigment)\nNo\nNo\nInjected into the site of \nbiopsied colonic polyps\nBlack granular pigment in \nstroma or within histio\u00ad\ncytes\nMay be useful to document the site of \na previously biopsied polyp that has \nbeen completely removed\nMelanosis coli\nNo\nNo\nLamina propria of the \ncolon\nFine brown to black gran\u00ad\nules in macrophages. \nPAS +, silver stain +.\nAssociated with anthracene-derived \nbowel cathartics. Can cause grossly \npigmented colonic mucosa.\nMercuric \n\u00adchloride\nYes/no\nNo\nTissues fixed in mercury-\ncontaining fixatives\nDark brown granular \nextracellular deposits \nthroughout the tissues\nShould be removed by proper tissue \nprocessing\nTABLE 9\u20131.\u2003\nOPTICAL PROPERTIES OF COMMONLY SEEN NONCELLULAR MATERIAL\u2014cont\u2019d\nTYPE\nPOLARIZATION\nREFRACTILE\nLOCATIONS \nUSUALLY SEEN\nAPPEARANCE/STAINS\nCOMMENTS\nHISTOLOGIC \nAPPEARANCE\nIatrogenic Material", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_228.png", "summary": "The page discusses various noncellular materials commonly seen in surgical pathology, their optical properties, locations, appearances, and stains.", "questions": [ "How can cornstarch incite a granulomatous response in the body?", "What is the significance of formalin pigment in histological samples?", "How can gold in intramammary lymph nodes mimic mammographic calcifications?", "What are the potential implications of using India ink as a tattoo pigment in biopsied colonic polyps?", "How is melanosis coli associated with anthracene-derived bowel cathartics?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 229, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\t\n15\n211\nContinued\nMetal\nNo\nNo\nTissue around prosthetic \njoints\nSmall black irregular angu\u00ad\nlated or needle-shaped \nfragments that may be \nintra- or extracellular\nMinocycline\nNo\nNo\nThyroid, atheromatous \nplaques, substantia \nnigra\nBlack granular pigment\nFound in patients treated with mino\u00ad\ncycline\nMyospherulosis\nNo\nNo\nNasal cavity and paranasal \nsinuses\nSac-like structures with \nouter lipid surrounding \nendobodies (red blood \ncells)\nDue to packing with a petroleum-\nbased ointment\nCan be mistaken for protothecosis or \nfungi\nPolyethylene\nYes\nYes\nTissue around prosthetic \njoints\nLarge fragments, filaments, \nshards, or small intracel\u00ad\nlular fragments. Often \nwith a giant cell reaction. \nOil red O +.\nPolymethyl\u00ad\nmethacry\u00ad\nlate (bone \ncement)\nNo\nNo\nTissue around prosthetic \njoints\nRound to oval holes sur\u00ad\nrounded by a giant cell \nreaction\nDisolves in xylene. Barium sulfate may \nbe present within the bone cement.\nSilicone\nNo\nYes\nIn tissue around implants, \nrarely in draining lymph \nnodes\nSilicone may be removed \nduring processing and \nappear as empty holes \nwith residual refractile \nmaterial around the \nedge\nIntracellular silicone appears like mul\u00ad\ntiple vacuoles in histiocytes that can \nbe mistaken for lipoblasts\nOther organic oils can have the same \nappearance\nSodium polysty\u00ad\nrene sulfonate \n(Kayexalate)\nNo\nYes\nGastrointestinal tract\nIrregular eosinophilic crys\u00ad\ntals present in the lumen \nor within ulcers. PAS + \nand AFB +.\nMay cause necrosis of bowel wall.7\nSutures\nSurgical gut\nYes\nNo\nPrior biopsy sites (often \nseen in breast)\nOvoid deeply eosinophilic \nmonofilament often \nsurrounded by a chronic \ninflammatory response \nand giant cells\nNuclei may be spindle shaped (due \nto sterilization by cautery) and the \nsuture may develop jagged edges \nduring resorption. Gut sutures may \nbe mistaken for metaplastic bone.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_229.png", "summary": "The page discusses various types of foreign bodies commonly encountered in surgical pathology, including metal, minocycline, myospherulosis, polyethylene, polymethylmethacrylate, silicone, sodium polystyrene sulfonate, and sutures.", "questions": [ "How can myospherulosis be distinguished from protothecosis or fungi?", "What are the characteristics of foreign body reactions associated with polyethylene and polymethylmethacrylate?", "How can intracellular silicone be differentiated from lipoblasts?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 230, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\t\n15\n212\nOther sutures\nYes\nYes\nSurgical sites\nMay be monofilament \nor polyfilament. Often \ncolorless\nAbsorbable sutures may be sur\u00ad\nrounded by chronic inflammation\nTalc\nYes\nYes\nPleura after talc pleurode\u00ad\nsis, granulomas in \nIVDAs\nIrregular clear to yellow \ncrystalline material\nThorotrast\nNo\nNo\nLiver and spleen\nCoarse light brown or gray \ngranules in histiocytes \nor stroma \u2013 similar to the \nappearance of hemo\u00ad\nsiderin\nThis radiocontrast agent is no longer \nused as it is associated with cir\u00ad\nrhosis, HCC, bile duct carcinoma, \nand angiosarcomas of the liver and \nspleen. It has a half-life of 400 years.\nEnvironmental Material\nAnthracotic pig\u00ad\nment (\u00adcarbon)\nNo\nNo\nLymph nodes of the respi\u00ad\nratory tract\nBlack granular deposits in \nmacrophages\nAsbestos fibers\nNo/yes\nNo\nLung\nThin fibers encrusted with \nbeaded protein and iron \n(ferruginous bodies)\nSpecific identification requires spec\u00ad\ntroscopic analysis. Similar bodies \ncan be seen with aluminum silicate, \nfiberglass, or lung elastin.\nQuantification and identification of \nfibers can be performed by energy \ndispersive x-ray analysis.\nInsects (flies and \nticks)\nYes\nYes\nSkin and subcutaneous \ntissue\nVariable\nSilica\nYes\nNo\nLymph nodes of the respi\u00ad\nratory tract, silicotic \nnodules\nMinute polarizable material \nin histiocytes and fibrotic \nnodules\nMay be seen in workers exposed to \nsilica\nLung disease is often complicated by \nsuperimposed infections\nPlant material\nYes\nYes\nColonic rupture, lung (if \naspirated)\nCell walls are readily identi\u00ad\nfiable by polarization\nCan be useful to document colonic \n\u00adrupture\nThis table lists the most common findings for these materials. However, materials can be altered by in vivo responses, fixation conditions, and staining.\nEnergy dispersive x-ray analysis (EDAX), as well as other methods, can be used to identify small deposits of elements in tissue specimens. Other types of spectroscopy can be used as well.\nSee references 8 to 14.\nTABLE 9\u20131.\u2003\nOPTICAL PROPERTIES OF COMMONLY SEEN NONCELLULAR MATERIAL\u2014cont\u2019d\nTYPE\nPOLARIZATION\nREFRACTILE\nLOCATIONS \nUSUALLY SEEN\nAPPEARANCE/STAINS\nCOMMENTS\nHISTOLOGIC \nAPPEARANCE\nIatrogenic Material", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_230.png", "summary": "The page discusses the microscopy and photography of various noncellular materials commonly seen in surgical pathology, including sutures, talc, thorotrast, environmental materials, insects, silica, and plant material.", "questions": [ "How can the appearance of absorbable sutures surrounded by chronic inflammation impact diagnosis?", "What are the potential health risks associated with the use of thorotrast as a radiocontrast agent?", "How can energy dispersive x-ray analysis be utilized in the identification of fibers such as asbestos or silica in tissue specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 231, "text": "213\nMICROSCOPY AND PHOTOGRAPHY\u2003 Measuring with the Microscope\nSubstances may be neither refractile or polarizable \n(most tissues and cells), refractile but not polarizable (e.g., \nhemosiderin), polarizable but not (or poorly) refractile \n(e.g., amyloid), or both (e.g., suture material). Amyloid \ncan be identified by the apple-green color seen under \n\u00adpolarization.1\nMEASURING WITH THE MICROSCOPE\nIn some instances it is necessary to accurately measure \nmicroscopic sizes. For example:\n\t\u2022\t \u0007Depth of invasion of malignant melanomas\n\t\u2022\t \u0007Depth of invasion of cervical carcinomas\n\t\u2022\t \u0007Fuhrman nuclear grading\n\t\u2022\t \u0007Standardization of microscopic field size for counting \nmitoses (breast carcinoma grading, sarcoma grading)\n\t\u2022\t \u0007Size of lymph node metastases (isolated tumor cells vs. \nmicrometastasis vs. macrometastasis)\nDifferent methods are available depending upon the \nneed for accuracy, the size of the object to be measured, \nand the equipment available (Table 9-2).\nEstimation from Known Field Diameters\nThe field diameters on a microscope can be used to rapidly \ngauge the size of an object. The field diameter must also \nbe known in order to use some types of grading systems, \nas the number of mitoses scored must be standardized to \na given area.\nThe size of a microscope field will be affected by:\n\t\u2022\t \u0007The brand of the microscope.\n\t\u2022\t \u0007The eyepiece magnification and the objective magnifi\u00ad\ncation.\n\t\u2022\t \u0007The distance between the eyepiece and the objective. \nThe distance may be lengthened by additional heads \nadded to the microscope and built-in polarizing lenses.\nThe size of a microscope field can be determined by:\n\t\u2022\t \u0007Carefully marking two edges of the field on a glass slide \nand measuring with a ruler.\n\t\u2022\t \u0007Using the Vernier scale (see below). The edge of a cov\u00ad\nerslip is a convenient landmark that can be moved across \nthe field.\n\t\u2022\t \u0007Using a stage micrometer to measure a high power field \ndirectly (most micrometers are too small to measure the \nother fields). The size of the other fields can be calcu\u00ad\nlated with the following formula (Box 9-5):\nEyepiece magnification \u00d7 objective magnification \n\u00d7 field diameter = a constant\nOnce the field sizes are known (and conveniently posted \non the microscope) the size of objects can be estimated by \ndetermining the relative size to the microscopic fields (typ\u00ad\nically ranging between 0.05 and 1 cm). If grading systems \nusing the number of mitoses per HPF are employed, it is \nuseful to make a table of equivalent mitotic counts for the \nsize of the HPF the system is based on (see Table 15-4). \nUnfortunately, many different sizes of HPFs are used. The \narea of a HPF on a microscope can be calculated once the \nradius (equal to half the diameter) of the field is known:\nArea of HPF = 3.1415 \u00d7 radius2\nSize can also be estimated by comparison to cells with \nrelatively constant sizes:\n\t\u2022\t \u0007A lobe of a neutrophil nucleus: 2 \u03bcm\n\t\u2022\t \u0007Nucleus of a small lymphocyte: 5 to 6 \u03bcm\n\t\u2022\t \u0007A red blood cell: 7 \u03bcm\n\t\u2022\t \u0007A histiocyte nucleus: 10 \u03bcm\nDirect Measurement on Slides\nThis is the most convenient method for objects measuring \nseveral millimeters in size. The borders to be measured are \ncarefully marked by ink and an accurate ruler used to make \na direct measurement. Small breast carcinomas can often \nbe measured using this method as the gross measurements \nmay underestimate or overestimate the extent of the inva\u00ad\nsive carcinoma.\nThere are some coverslip films that are permanently \nmarked by ink. Marking on such slides should be minimized.\nTABLE 9\u20132.\u2003\nMETHODS OF MEASURING\nMETHOD\nAPPROXIMATE ACCURACY\nEstimation from known \nfield diameters\n1-2 mm\nDirect measurement on the \nslide\n1-2 mm\nVernier scale on movable \nstage\n0.1 mm\nOcular reticle (graticule)\n0.01 mm (10 \u03bcm)\nBOX 9\u20135.\u2003 Calculation of field diameter\nA microscope has 10\u00d7 eyepieces. The size of the field for the 2\u00d7 \nobjective is measured with a ruler as 0.8 cm. Using the formula \nthe value of the constant for this microscope can be calculated:\n10 (eyepiece magnification) \u00d7 2 (objective magnification) \n\u00d7 0.8 cm (field diameter) = 16 cm (a constant)\nThe field size for the 10\u00d7 objective can be calculated using the \nformula:\n10 (eyepiece magnification) \u00d7 10 (objective magnification) \n\u00d7 X (field diameter) = 16 cm (a constant)\nOr\nX (field diameter) = 16 cm/10 (eyepiece magnification) \n\u00d7 10 (objective magnification) = 0.16 cm", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_231.png", "summary": "The page discusses the importance of accurately measuring microscopic sizes using a microscope for various purposes in pathology, such as grading tumors and estimating the size of objects.", "questions": [ "How can field diameters on a microscope be used to gauge the size of an object?", "What factors can affect the size of a microscope field?", "Why is it important to standardize the number of mitoses scored to a given area in grading systems?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 232, "text": "214\nMICROSCOPY AND PHOTOGRAPHY\u2003 Cleaning and Care of the Microscope and Glass Slides\nVernier Scale\nThe Vernier scale is found on the edge of most microscope \nstages and is used to measure the movement of the stage \n(Box 9-6). Because the movement of the stage is measured \ndirectly, the eyepiece and objective magnifications are \nirrelevant to the measurement.\nThere are usually two sets of scales corresponding to X \nand Y axes.\nThe use of the Vernier scale is clearly described and \nillustrated by Warren, et al.15 (Box 9-7). Its use in measur\u00ad\ning objects not aligned in the X and Y axis is described by \nClark and Kung.16 This method can be more reproducible \nthan other measuring techniques.17\nOcular Reticle\nThe most precise measurements may be made using a scale \nmounted in an eyepiece objective that has been calibrated. \nThe disadvantage of this method compared to other meth\u00ad\nods is that two special pieces of equipment are required:\n \n1.\t \u0007Reticle: A reticle (graticule) has either a line scale \nor grid inscribed on the surface of a disc (either glass \nor plastic). It is used in conjunction with a focusing \nobjective. The scale distances are arbitrary and must \nbe calibrated for each microscope.\n \n2.\t \u0007Stage micrometer: This is a glass slide with a very \naccurate scale of known size etched into its surface. \nTypically the scale is 1 mm in length divided into \n100 equal divisions (1 mm = 1000 \u03bcm, thus each divi\u00ad\nsion equals 10 \u03bcm). \nReticles cost from $30 to $90, focusing eyepieces from \n$70 to $130, and stage micrometers from $100 to $200. \nAfter a reticle is calibrated for a microscope, the stage \nmicrometer is no longer needed. Most measurements \n(with the exception of the thickness of melanomas) can be \nmade using the diameter of microscopic fields. Therefore, \none reticle and stage micrometer can suffice for an entire \ndepartment (Boxes 9-8 and 9-9).\nReticles and stage micrometers are available from \nEdmund Scientific Company (101 East Gloucester Pike, \nBarrington, NJ 08007-1380, (609) 573-6879; \u00adTECHSUP@\nEDSCI.COM or www.edsci.com).\nCLEANING AND CARE OF THE MICROSCOPE \nAND GLASS SLIDES\nThe Microscope\nThe best method to keep a microscope clean is to prevent \nit from getting dirty by employing a cover when not in use \nand avoiding the use of immersion oil. However, inevitably \nmicroscopes will gather dust or oil on the objectives. Only \nlens paper should be used to touch the objectives. Other \ntypes of paper may be too coarse or may be dusty and will \nscratch the lens. Fingers contain oils that may damage the \ncoatings. If wiping the objective does not remove the dirt, \na small amount of xylene or other cleaning solution applied \nto piece of lens paper may be used. Do not place cleaning \nsolution directly onto the objective as it may seep inside of \nthe objective. Xylene should be wiped away immediately as \nit will damage the adhesives used to construct the objec\u00ad\ntive. Do not use alcohol, as this substance will damage the \nobjective.\nBOX 9\u20136.\u2003 Definitions\n \u2022 \u0007Rule scale: Located on the stage and divided into millimeters.\n \u2022 \u0007Vernier scale: Adjacent to the rule scale but fixed in position. It \nis divided into 10 divisions, each measuring 0.9 mm.\nBOX 9\u20137.\u2003 Measuring with the Vernier scale\n 1. \u0007The first reading is taken as the number of millimeters on the \nrule scale immediately before the \u201c0\u201d on the Vernier scale.\n 2. \u0007The decimal place is read off the Vernier scale and is the \nnumber at which there is perfect alignment between the two \nscales.\n 3. \u0007To measure an object, a reading is taken with the object at the \nedge of the field of view. The stage is then moved over the length \nof the object and a second reading is taken. The first number is \nsubtracted from the second number to determine the distance \nthe stage has moved.\nBOX 9\u20138.\u2003 \u0007Calibrating a reticle and measuring \nobjects\n 1. \u0007The measuring reticle is placed in one eyepiece in the \n\u00admicroscope. If possible, it is most convenient to have a \n\u00adfocusing objective with the reticle permanently installed.\n 2. \u0007The stage micrometer is viewed through the objective. The \ndistance between the lines on the reticle is measured.\n 3. \u0007This is repeated for all the objectives on the microscope.\n 4. \u0007A table giving the calibration of the markings on the reticle \nis made and kept with each microscope. It is also useful to \ninclude the diameter of each microscope field.\nBOX 9\u20139.\u2003 \u0007Measuring microscopic objects using \na reticle\n 1. \u0007The measuring reticle is placed in one eyepiece in the \n\u00admicroscope.\n 2. \u0007The calibration line is placed over the object or distance to be \nmeasured.\n 3. \u0007The object or distance is measured by determining the \n\u00adnumber of units spanned on the calibration line. This number \ncan then be converted to microns or millimeters using the \ntable prepared for the microscope.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_232.png", "summary": "The page discusses the use of Vernier scale and ocular reticle for precise measurements in microscopy, as well as cleaning and care tips for microscopes and glass slides.", "questions": [ "What are the advantages of using a Vernier scale in microscopy?", "How do reticles and stage micrometers contribute to precise measurements?", "What are the recommended cleaning methods for microscopes and glass slides?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 233, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\n215\nGlass Slides\nThe day a microscope slide is made, the mounting media \nwill still be wet. It takes six to seven days to dry and the \nmounting media will not be completely dry for one to \ntwo months. Therefore, special care must be taken when \ncleaning the coverslip as it is easily moved and may dam\u00ad\nage the underlying tissue. The corner of the coverslip \nshould be held with the tip of the finger to prevent dis\u00ad\nlodging it. Slides should not be filed until the following \nday for the same reason. An adhesive footplate on the end \nopposite the label can help prevent them from sticking \ntogether.\nMicroscope slides often become soiled due to handling. \nSmears and oil can be cleaned using a small amount of \nxylene on a lint free tissue. Excess dried mounting media \ncan be gently scraped off on the side of the microscope \nstage. Peripheral blood smears often do not have a cover\u00ad\nslip. Oil can be gently wiped off the surface.\nSometimes slides will be received with air bubbles caught \nunder the coverslip. As a temporary measure, before the \nmounting media has dried, a small amount of xylene can \nbe introduced under the coverslip to allow viewing of the \ntissue. However, these slides should be re-coverslipped to \navoid permanent damage to the tissue by drying.\nIf one wishes to notate findings on a glass slide it is con\u00ad\nvenient to write them on a small adhesive footplate on the \nopposite end of the slide from the label. These footplates \nare easily replaced, unlike the surgical number label, and \nalso serve to protect the slide when filed.\nIf a slide cannot be focused, the slide may be upside \ndown on the stage. Rarely a coverslip will be placed on \nthe wrong side or two coverslips may be present.\nPHOTOGRAPHY\nOne of the most important roles of a pathologist is as an \neducator. Most doctors, including surgeons, never have the \nopportunity to directly see the disease processes that they \ndiagnose and treat. Photography is an excellent means to \nconvey to clinicians the pathology of disease. For example, \nthe stellate appearance of a mass on a mammogram or the \nirregular feel of a breast mass on physical exam can be cor\u00ad\nrelated with the irregular margins of a breast carcinoma \nin a gross specimen. The underlying histologic finding \nof infiltration of fibroadipose tissue by the carcinoma can \nthen be appreciated.\nPhotomicroscopy\nPhotomicrographs are invaluable additions to teaching \nconferences and publications. Most photographs are now \ntaken with the digital cameras and are then manipulated in \nPhotoshop.\nSlide Selection.\u2002 The tissue should be well cut and \nstained without wrinkles or bubbles. Any ink present on \nthe \u00adcoverslip should be removed. The slide and coverslip \nshould be wiped clean of dust and oils before photography.\nMagnification.\u2002 For the novice, it is often tempting to \ntake photographs of the same image at each available mag\u00ad\nnification. However, the maximum amount of information \nis usually obtained with one lower power picture to show \nthe general location and architecture of the tissue and one \nhigher power picture to show the specific important patho\u00ad\nlogic features. If you find yourself repeatedly saying at con\u00ad\nference \u201c. . . and here is another picture of X,\u201d then you are \ntaking too many photographs! Each image should reveal \nanother feature of the tumor or pathologic process.\nAdding Text to Photographs.\u2002 Simple additions (e.g., let\u00ad\nters indicating the type of immunoperoxidase stain repre\u00ad\nsented), text, arrows, or graphics can greatly enhance the \ninformation provided by the microscopic image.\nModifications of Digital Images.\u2002 Images can be markedly \nimproved with a few of the tools available in imaging pro\u00ad\ncessing programs:\n\t\u2022\t \u0007Focus (\u201cunsharp mask\u201d) \u2013 but overuse will lead to pixil\u00ad\nlated pictures.\n\t\u2022\t \u0007Color \u2013 background color can be corrected to white.\n\t\u2022\t \u0007Cropping \u2013 use to remove unnecessary peripheral areas.\n\t\u2022\t \u0007Rips in the tissue, uneven staining, ink spots, and other \ndistracting marks \u2013 remove or copy over using erasing \nand cloning tools.\nPhotography of Gross Specimens (Box 9-10)\nMost specimens are photographed best prior to fixa\u00ad\ntion.18,19 Blood, bile, and fecal material should be gently \nrinsed off the specimen using saline. Immersion in 80% \nethanol for 15 to 30 minutes will restore some of the origi\u00ad\nnal color to the specimen.\nSome specimens are better demonstrated after fixation \nin an inflated state, such as lung, bladder, or colon resec\u00ad\ntions for diverticulosis.\nBOX 9\u201310.\u2003 \u0007Specimens in which photography may \nbe helpful\n \u2022 \u0007Surgical resections of tumors\n \u2022 \u0007Colon resections for IBD\n \u2022 \u0007Artificial heart valves and intact native valves\n \u2022 \u0007Transplant lungs, kidneys, and hearts\n \u2022 \u0007Possible medicolegal cases (e.g., amputations due to trauma, \nexplanted permanent silicone implants, bullets)\n \u2022 \u0007Pertinent negative specimens (e.g., a resection for a tumor if the \ntumor was not present on pathologic examination)\n \u2022 \u0007Unusual specimens or specimens with examples of classic \npathology (e.g., a classic porcelain gallbladder, Paget\u2019s disease \nof the nipple, rare grossly-evident prostate carcinomas)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_233.png", "summary": "The page discusses the process of preparing and cleaning microscope slides, as well as the importance of photography in pathology for education and documentation.", "questions": [ "How long does it take for the mounting media on a microscope slide to completely dry?", "What are some common issues that may arise with microscope slides and coverslips?", "Why is photography considered an important tool in pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 234, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\n216\nDissection.\u2002 Most pathologic lesions are best demon\u00ad\nstrated after partial dissection of the specimen. Think \nabout how best to demonstrate the lesion before start\u00ad\ning dissection. However, do not alter the specimen in a \nway that will impair the final diagnosis. Cross-sections of \ntumors offer much more information about tumor appear\u00ad\nance and relationships with normal structures. Examples:\n\t \u2022\t \u0007Colon carcinoma: A cross-section can reveal residual \nvillous adenoma at the edge of the tumor as well as \ntumor invasion into and through the muscularis pro\u00ad\npria.\n\t \u2022\t \u0007Whipple specimen: A photograph of a section taken \nthrough the plane of the common bile duct, the pan\u00ad\ncreatic duct, and the ampulla of Vater will reveal the \nappearance of the tumor and its relationship (obstruc\u00ad\ntion, invasion, dilation) to these structures. \nPhotographing Under Saline.\u2002 Saline supports delicate tis\u00ad\nsues and can be very helpful in bringing out fine textures. \nSections of lungs (e.g., severe emphysema) or papillary \nstructures (e.g., villous adenomas, PVNS, placental villi) \ncan be demonstrated best under saline. Transillumination \nthrough saline on a light box often gives the best demon\u00ad\nstration of a delicate floating structure.\nProbes and Arrows.\u2002 In some cases the informational \nvalue of a picture will be enhanced if certain features are \nemphasized. For example, a Whipple resection may be \nphotographed with a probe in the ampulla of Vater to \ndemonstrate the relationship of the tumor to the ampulla \nor a probe can be used to indicate the site of a colon per\u00ad\nforation. Small arrows may be cut out of white cardboard \nand used to indicate subtle features. Some specimens may \nneed to be propped open (e.g., laryngectomies) to show the \nimportant lesions. The handle of a Q-tip (with the tip cut \noff) can be used. Avoid including hands in the picture. If \nsomething needs to be held, grasp it with a hemostat.\nComposition of the Photograph\nLabel.\u2002 A label with the surgical pathology number and a \nruler are always included.\nPlace the ruler/label in an anatomically appropriate \norientation (e.g., with the upper pole of the kidney at the \nupper part of the photograph) so that it will be legible \nwhen the picture is displayed.\nOrient the ruler/label with the edge of the photograph. \nDo not place ruler/labels diagonally as they will be more \ndifficult to read and crop if necessary. The ruler should be \ncloser to the specimen than the label in order to be able to \ncrop the label but leave the ruler if the photograph is used \nfor publication.\nDo not allow the ruler/label to touch or overlap the \nspecimen. If the specimen will fill the entire field, take one \nlower magnification picture first to include the ruler/label, \nor take one picture with the label over the specimen first, \nand then remove it to take the remaining photographs.\nAlways keep the label clean. It is generally best to pre\u00ad\npare the label first, before handling the specimen, or to \nchange gloves before making the label. The label can be \nattached to a clean glass microscope slide in order to han\u00ad\ndle it without soiling it.\nThe ruler/label and the lesion of interest should be in \nthe same plane of focus. Use blocks or specimen cassettes \nto elevate the ruler/label to the appropriate height.\nSpecimen Placement.\u2002 Most \nspecimens \nphotograph \nwell on a dark background. For some specimens that are \nvery dark (e.g., a metastatic melanoma or a thyroid after \n\u00adminocycline therapy), it may be more appropriate to \nselect a light-colored background (e.g., a clean blue pad \nor drape).\nPlace the specimen in an anatomically reasonable \nposition if possible. Avoid confusing ways of showing \nspecimens. For example, if a kidney has been bivalved, \nphotograph only half of the specimen. Orient the speci\u00ad\nmen so that it will fill the frame of the photograph.\nUse as high a magnification as possible without leaving \nout important features of the specimen. It is often useful \nto take both a low magnification and a high magnifica\u00ad\ntion view. For example, clinicians can better understand \na Whipple specimen if the photograph includes the stom\u00ad\nach, duodenum, and pancreas. A second closeup photo\u00ad\ngraph can be taken showing the relationship of the tumor \nto the ampulla.\nREFERENCES\n\t\u2002 1.\t \u0007Howie AJ, et al. Physical basis of colors seen in Congo red-\nstained amyloid in polarized light. Lab Inv 88:232, 2008.\n\t\u2002 2.\t \u0007Ro JY, et al. Yellow-brown (Hamazaki-Wesenberg) bodies \nmimicking fungal yeasts. Arch Pathol Lab Med 111:555-559, \n1987.\n\t\u2002 3.\t \u0007Tuur SM, et al. Liesegang rings in tissue. Am J Surg Pathol \n11:598-605, 1987.\n\t\u2002 4.\t \u0007Keen CE, Buk SJA, Brady K, Levison DA. Fat necrosis pre\u00ad\nsenting as obscure abdominal mass: Birefringent saponified \nfatty acid crystalloids as a clue to diagnosis. J Clin Pathol \n47:1028-1031, 1994.\n\t\u2002 5.\t \u0007Kepes JJ, Yarde WL. Visualization of injected embolic mate\u00ad\nrial (polyvinyl alcohol) in paraffin sections with Verhoeff-\nVan Gieson elastica stain. Am J Surg Pathol 19:709-711, \n1995.\n\t\u2002 6.\t \u0007Al-Talib RK, Wright DH, Theaker JM. Orange-red bire\u00ad\nfringence of gold particles in paraffin wax embedded sec\u00ad\ntions: an aid to the diagnosis of chrysiasis. Histopathology \n24:176-178, 1994.\n\t\u2002 7.\t \u0007Rashid A, Hamilton SR. Necrosis of the gastrointestinal tract \nin uremic patients as a result of sodium polystyrene sulfonate \n(Kayexalate) in sorbitol. Am J Surg Pathol 21:60-69, 1997.\n\t\u2002 8.\t \u0007Donath K, LaaB M, Gunzl H-J. The histopathology of \ndifferent foreign-body reactions in oral soft tissue and \nbone tissue. Virchows Archiv A Pathol Anat 420:131-137, \n1992.\n\t\u2002 9.\t \u0007Fechner RE, Nichols GE. Iatrogenic lesions. In Silver\u00ad\nberg SG, DeLellis RA, Frable WJ, et al (eds): Silver\u00ad\nberg\u2019s Principles and Practice of Surgical Pathology and \nCytopathology, fourth edition, Churchill \u00adLivingstone, \n2005.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_234.png", "summary": "The page discusses the importance of microscopy and photography in demonstrating pathologic lesions, including the use of dissection, saline, probes, arrows, and proper composition of photographs.", "questions": [ "How can partial dissection of specimens help in demonstrating pathologic lesions?", "What are some examples of how cross-sections of tumors provide more information about tumor appearance and relationships with normal structures?", "Why is it important to include a label with the surgical pathology number and ruler in photographs of specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 235, "text": "MICROSCOPY AND PHOTOGRAPHY\u2003 Photography\n217\n\t10.\t \u0007Forest M, Tomeno B, Vanel D. Pathology of bone and joints \nafter surgery. In Orthopedic Surgical Pathology, Churchill \nLivingstone, 1998, pp 739-759.\n\t11.\t \u0007Johnson FB. Crystals in pathologic specimens. In Sommers \nSC, ed: Pathology Annual. New York, Appleton-Century-\nCrofts, 1972, pp 321-348.\n\t12.\t \u0007Walley VM, Stinson WA, Upton RT, Santerre JP, Mussiv\u00ad\nand T, Masters RG, Ghadially FN. Foreign materials found \nin the cardiovascular system after instrumentation or surgery \n(including a guide to their light microscopic identification). \nCardiovasc Pathol 2:157-185, 1993.\n\t13.\t \u0007Wallington EA. Artifacts in tissue sections. Med Lab Sci\u00ad\nences 36:3-61, 1979.\n\t14.\t \u0007Yeh I-T, Brooks JSJ, Pietra GG. Atlas of Microscopic Arti\u00ad\nfacts and Foreign Materials. Baltimore, Williams & Wilkins, \n1997.\n\t15.\t \u0007Warren BI, Davies JD. Pierre Vernier\u2019s invention: a \nneglected tool of our trade. Histopathol 18:361-362, 1991.\n\t16.\t \u0007Clark SP, Kung ITM. Measurement of Breslow depth [let\u00ad\nter]. J Pathol 165:269-270, 1991.\n\t17.\t \u0007Calder CJ, Campbell AP, Plastow SR. Measurement tech\u00ad\nniques for melanoma: a statistical comparison. J Clin Pathol \n43:922-923, 1990.\n\t18.\t \u0007Uthman ED, An introduction to photography in general\u2026 \nand gross specimen photography in particular (http://web2.\nairmail.net/uthman/gross_photo.html)\n\t19.\t \u0007Walsh S, Mirza T, Smith G, Hyde N: Impact of colour \ndigital photography on pathologists\u2019 orientation of resected \nspecimens a prospective pilot study. Br J Oral Maxillofacial \nSurg, 2008 (epub).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_235.png", "summary": "The page discusses various aspects of microscopy and photography in pathology, including the identification of foreign materials in tissue sections and the impact of color digital photography on pathologists.", "questions": [ "How can foreign materials found in tissue sections be identified under light microscopy?", "What is the significance of color digital photography in pathology?", "How do Breslow depth measurement and melanoma measurement techniques compare statistically?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 236, "text": "218\n10\nApproaching Perfection: \nAvoiding Errors in Surgical \nPathology\nStart out with the conviction that absolute truth is hard \nto reach in matters relating to our fellow creatures, healthy \nor diseased, that slips in observation are inevitable even with \nthe best-trained faculties, that errors in judgment must occur \nin the practice of an art which consists largely in balancing \nprobabilities.\nSir William Osler1\nShow me a pathologist who has never made a mistake, and I\u2019ll \nshow you a liar or someone who has never looked down the end \nof a microscope.\nA respected professor of pathology2\nThe standard of care is not perfection.\nA malpractice defense attorney\nWhen error is mentioned in medicine, the immediate \npresumption is that a physician failed to provide good care \ndue to either negligence or ignorance. The thought of \nbeing responsible for such an error strikes dread into the \nheart of all pathologists. However, within the broad spec\u00ad\ntrum of possible medical errors, errors due to negligence \nor ignorance are rare. Other types of errors are much more \ncommon and most of these can be minimized by under\u00ad\nstanding how they occur and designing systems to detect \nand prevent them.\nThe Institute of Medicine issued a report on medi\u00ad\ncal error and patient safety on November 29, 1999.3 The \nreport states that the current error rate is unacceptable \nand mandates a 50% reduction within 5 years. Both CAP \nand JCAHO have issued patient safety goals for surgical \npathology.4 Some changes have taken place at the regula\u00ad\ntory and governmental level, but the most important steps \nwill occur at the institutional and individual practitioner \nlevel.5-16\nDr. Ronald Sirota has described the \u201cculture of safety\u201d \nthat creates an environment that prioritizes patient safety \nand error reduction (Table 10-1).3\nTABLE 10\u20131.\u2003 THE CULTURE OF SAFETY\nA TYPICAL MEDICAL SYSTEM\nA BETTER MEDICAL SYSTEM\nPatient safety and error reduction are important, but may not be \ngiven as much attention as other organizational goals.\nPatient safety and error reduction are top organizational \n\u00adpriorities.\nAssumes that the system is perfect and that pathologists never \nmake mistakes.\nAssumes that mistakes are inevitable.\nSystems (e.g., procedures, computer programs) are not designed \nto prevent and detect errors.\nSystems are designed to prevent and detect all types of error.\nAll errors are considered to be the result of individual incompe\u00ad\ntence.\nRecognizes that there are many types of error. Only a small num\u00ad\nber are due to incompetence. Most are due to system failures.\nCreates strong incentives to not find errors or to conceal them.\nCreates strong incentives to find and correct errors. Errors are \nopenly reported and discussed.\nError detection results in shame and derision.\nUses each error as an opportunity to improve the system and to \neducate others in error prevention.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_236.png", "summary": "The text discusses the inevitability of errors in surgical pathology and emphasizes the importance of understanding and minimizing errors through a culture of safety.", "questions": [ "How does the text address the issue of errors in surgical pathology?", "What are some key points mentioned in the Institute of Medicine report on medical error and patient safety?", "How does the 'culture of safety' described by Dr. Ronald Sirota differ from a typical medical system?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 237, "text": "219\nAPPROACHING PERFECTION: AVOIDING ERRORS IN SURGICAL PATHOLOGY\u2003 Sources of Error\nSOURCES OF ERROR\nErrors can occur before specimens arrive in the pathol\u00ad\nogy department, during pathologic evaluation, or after the \nreport leaves the pathology department.\nPre-pathology errors:\n\t\u2022\t \u0007Failure to provide appropriate patient and specimen \nidentification.\n\t\u2022\t \u0007Failure to provide relevant clinical history.\n\t\u2022\t \u0007Failure to provide tissue in a timely and appropriate \nmanner to perform necessary pathology examination.\n\t\u2022\t \u0007Failure to transport the specimen to the pathology \n\u00adlaboratory.\nPathology errors:\n\t\u2022\t \u0007Loss of specimen.\n\t\u2022\t \u0007Errors in accessioning specimens.\n\t\u2022\t \u0007Errors in gross sampling of tissue.\n\t\u2022\t \u0007Failure to preserve tissue in appropriate fixatives or for \nspecial studies necessary for diagnosis.\n\t\u2022\t \u0007Failure to make the correct diagnosis or significant \nomissions to the pathology report.\n\t\u2022\t \u0007Failure to provide a completed pathology report without \ntypographical errors.\n\t\u2022\t \u0007Billing errors - usually due to failure to document \n\u00adbillable procedures in the report.\nPost-pathology errors:\n\t\u2022\t \u0007Failure of the pathology report to be available to \u00adtreating \nclinicians.\n\t\u2022\t \u0007Failure of the clinician to understand the report.\n\t\u2022\t \u0007Failure to inform clinicians directly of significant changes \nin diagnosis in addendums.\nPre-Pathology Errors\nBoth CAP and the JCAHO have issued guidelines for \nthe submission of specimens for pathologic examination. \nA Q-probes study revealed that 6% of specimens failed to \nmeet these standards.17 Errors constituted the following:\n\t \u2022\t \u0007Discrepant or missing information: 77.0%\n\t \u2022\t \u0007Specimen not appropriately identified: 9.6%\n\t \u2022\t \u0007Specimen handling: 3.6%\nIf a specimen is received without appropriate documen\u00ad\ntation, the submitting clinician must be contacted before \naccessioning the case.\nPathology Errors\nSpecimen identification\nSpecimens must be correctly identified by the clinician \nsubmitting the specimen. This identification should be \nconfirmed by the following:\n\t\n1.\t \u0007The tissue must correspond to the site biopsied. If \nit does not, identify the problem as clinician error \n(e.g., \u00adendometrial curettings are actually colonic \nmucosa) or \u00adpathology error (mixed-up specimens or \nextraneous tissue).\n\t\n2.\t \u0007Correlate the pathologic findings with the clinical \nsetting. If discordant, consider the possibility of a \nmisidentified specimen.\nClinicians often provide information that aids in detect\u00ad\ning such errors. If a clinician questions a diagnosis, the pos\u00ad\nsibility of an error should be addressed. In rare cases, it may \nbe appropriate to identify the specimen by tissue typing.\nGross examination\nAdvances in disease detection have resulted in the removal \nof increasingly smaller tumors or in situ disease that may \nbe difficult to find on gross examination.\nSmall specimens that are completely examined micro\u00ad\nscopically rarely present a problem. However, large resec\u00ad\ntions, particularly after preoperative therapy, can be \nproblematic. One study investigated the incidence of errors \nin breast pathology.18 The investigators found that failure to \nadequately examine specimens grossly were responsible for \nmajor discrepancies in 5% of cases and minor discrepancies in \n6% of cases, including missed cancers, missed metastatic car\u00ad\ncinoma to lymph nodes, and undetected skin invasion. The \nmajority (83%) of the major discrepancies occurred in mas\u00ad\ntectomy specimens. In \u00adcontrast, review of the original glass \nslides revealed major discrepancies in only 1.5% of cases and \nminor discrepancies in 6%. Errors due to suboptimal gross \nexamination may be reduced by the following procedures:\n\t\n1.\t \u0007Provide increased supervision for first year residents \nor new pathology assistants for large complicated \nspecimens. Most major discrepancies occur with less \nexperienced prosectors.\n\t\n2.\t \u0007Utilize additional techniques to find lesions when \nnecessary. For example, specimen radiography may \nbe necessary to localize small mammographic lesions \nin mastectomies when the diagnosis was made by \nneedle biopsy.\n\t\n3.\t \u0007Reexamine specimens grossly after microscopic \nevaluation if the following occurs:\n\t\n\u2022\t \u0007Prior diagnostic findings not confirmed (e.g., FNA \nsuspicious for papillary carcinoma but no carci\u00ad\nnoma found in the thyroid on initial sampling).\n\t\n\u2022\t \u0007Fewer lymph nodes than expected found.\n\t\n\u2022\t \u0007Prior biopsy or tumor site not identified.\n\t\n\u2022\t \u0007Radiologic findings not found. Radiographic reex\u00ad\namination of the specimen can be helpful.\nMicroscopic examination\nThe major reasons for differences in diagnosis among \npathologists in the microscopic examination of specimens \ninclude the following:\n\t\n1.\t \u0007Failure to see an area of a slide or an entire slide.\n\t\n\u2022\t \u0007Slides should be scanned on low power first to \nidentify all tissue fragments.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_237.png", "summary": "Errors in surgical pathology can occur at various stages, including before specimens arrive, during evaluation, and after the report leaves the pathology department. Pre-pathology errors include failures in providing appropriate identification and clinical history, while pathology errors can involve specimen loss, errors in diagnosis, and preservation issues.", "questions": [ "How can pre-pathology errors be minimized in the process of specimen submission?", "What are some common errors that can occur during the pathology evaluation of specimens?", "How important is it for clinicians to provide accurate information to aid in detecting errors in surgical pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 238, "text": "220\nAPPROACHING PERFECTION: AVOIDING ERRORS IN SURGICAL PATHOLOGY\u2003 Sources of Error\n\t\n\u2022\t \u0007If there are many fragments on the slide, it can \nbe helpful to mark a line around all the fragments \n(to facilitate screening the entire circled area) or \nto make a line interconnecting all the fragments \n(e.g., multiple lymph node sections).\n\t\n\u2022\t \u0007Avoid distractions during sign-out. Some patholo\u00ad\ngists mark each slide as it is examined or reverse \nexamined slides in the tray.\n\t\n2.\t \u0007Failure to recognize a diagnostic entity. This is what \nmost pathologists think of as an \u201cerror\u201d although \nthis is only a small portion of the total number of \nerrors possible. Pathologists do need to establish \nan adequate knowledge base and to know their \n\u00adlimitations. One should resist the temptation to \nmake a rare diagnosis with which one has little \nfamiliarity and should have a low threshold to seek \nconsultation with colleagues or acknowledged \nexperts. This type of error is rare, occurring in \n<1% of cases.\n\t\n3.\t \u0007Imprecise or ambiguous terms, or terminology \nwithout universally agreed upon definitions. Two \npathologists can see the same entity but render dif\u00ad\nferent diagnoses based on different opinions or use \nof terms (e.g., \u201cpositive\u201d or \u201cnegative\u201d to describe \nthe same result of an immunohistochemical study). \nEfforts to generate uniform diagnostic criteria and \nchecklists should reduce this variability.\n\t\n4.\t \u0007Diagnostically difficult cases. Although there will \nbe little variation in the diagnosis of some lesions \n(e.g., invasive colon carcinoma), other lesions can be \nvery difficult to classify. Differences in opinion for \nsuch lesions do not, in general, constitute an error \non the part of a pathologist who may disagree with \nanother pathologist. Unfortunately, it is often dif\u00ad\nficult for non-pathologists to understand that there \ncan be a differential diagnosis for pathologic lesions. \nSuch cases may benefit by obtaining and document\u00ad\ning opinions from more than one pathologist in the \nfinal report.\nPathology reporting\n\t\n1.\t \u0007Typographical errors. This is probably the most \ncommon type of error. Pathologists must be vigi\u00ad\nlant in detecting such errors, as they can sometimes \nchange a final diagnosis. Computer systems with \nspell checkers can be helpful, but will not find many \nerrors in meaning. Synoptic reports aid in typing \nreports and reducing spelling errors, but are difficult \nto proofread.\n\t\n2.\t \u0007Errors of omission: Failure to provide information \nrequired for the treatment of patients can adversely \naffect patient care. To some extent, this is dependent \non the information desired by the clinicians in each \ninstitution.\nThere are published recommendations for cancer \nreporting from the Association of Directors of Surgical \nPathology (ADASP; see www.adasp.org) and the College \nof American Pathologists (CAP; see www.cap.org). As of \nJanuary 1, 2004, the American College of Surgeons Com\u00ad\nmission on Cancer (ACS CoC) requires the reporting of \nall scientifically validated or regularly used data elements \nof the CAP checklists in reports of cancer-directed surgical \nresection specimens (not including cytologic specimens, \ndiagnostic biopsies, and palliative resection specimens) \nfrom CoC-approved cancer centers.\nPost-Pathology Errors\nThese errors consist of failure of the pathology informa\u00ad\ntion provided in a report to reach the relevant \u00adclinicians.\nUnexpected diagnosis\nClinicians may not see a pathology report on a routine \nspecimen until the patient is next seen for follow-up. If this \nappointment is delayed or does not occur, an important \nunexpected diagnosis may be overlooked. Examples would \ninclude finding carcinoma in a hernia sac, endocarditis in \na heart valve, and multiple myeloma in bone marrow from \na joint replacement. In such cases, it is recommended to \ncontact the clinician directly as well as to send the final \nreport.\nChanges in diagnosis after a case has been signed out\nInformation added in addendums can be easily lost or \noverlooked unless the original report specifically states \nthat an addendum will be added. If important information \nneeds to be added to a report at a later date, it is advis\u00ad\nable to contact the clinician directly. Problems can be \n\u00adminimized:\n\t\n1.\t \u0007Avoid putting important information in an adden\u00ad\ndum. If additional important diagnostic tests are \nbeing performed or consultation is sought, then it \nmay be preferable to hold the report until all infor\u00ad\nmation is available to render a final diagnosis.\n\t\n2.\t \u0007The original report can state that an addendum will \nbe added if it is known additional information will be \navailable later.\n\t\n3.\t \u0007An amended report should be identified on the first \npage of the report. If the addendum is added to the \nend of the report, the clinician may not realize that \nadditional information has been added.\nAmending a report (i.e., unsigning a report and chang\u00ad\ning or adding information) must be carefully documented. \nThe content of the original report must be preserved and \nthe specific changes documented. This option should only \nbe used for very significant changes in the diagnosis that \ncould alter patient care.\nFailure of the clinician to understand the diagnosis\nA recent study showed that surgeons misunderstood pathol\u00ad\nogy reports 30% of the time.19 Although the presence or \nabsence of carcinoma was well understood, problems arose", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_238.png", "summary": "The page discusses various sources of errors in surgical pathology, including failure to recognize diagnostic entities, imprecise terminology, diagnostically difficult cases, typographical errors, and errors of omission.", "questions": [ "How can pathologists avoid distractions during sign-out?", "What are some strategies for reducing variability in diagnostic criteria and terminology?", "Why is it important to obtain and document opinions from more than one pathologist for diagnostically difficult cases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 239, "text": "APPROACHING PERFECTION: AVOIDING ERRORS IN SURGICAL PATHOLOGY\u2003 Redundant Systems\n221\nwhen surgeons had to interpret histologic descriptions. \nSuch problems can be minimized:\n\t\n1.\t \u0007Provide specific, well-understood diagnostic terms \nwhenever possible.\n\t\n2.\t \u0007Standardize terminology within a department. Sign-\nout checklists can help in providing all important \ninformation in a format familiar to clinicians.\n\t\n3.\t \u0007Provide additional explanatory information in the \nreport if possible (e.g., information on grading or \nclassification systems).\n\t\n4.\t \u0007Provide AJCC classifications when possible for \nmalignant tumors.\n\t\n5.\t \u0007Avoid providing misleading information. For exam\u00ad\nple, clinicians may not understand that a specimen \nheading is not a diagnosis. If a specimen has been \nlabeled \u201cLeft thigh sarcoma\u201d but the lesion is not \na sarcoma, it is advisable not to include the word \n\u201c\u00adsarcoma\u201d in the heading for the final diagnosis. The \nspecimen heading can be documented in the gross \ndescription for medicolegal purposes.\n\t\n6.\t \u0007Include important information from the gross exami\u00ad\nnation in the final diagnosis. For example, the final \ndetermination of tumor size should be based a final \nassessment of both the gross and microscopic appear\u00ad\nance and should be recorded in the final \u00addiagnosis.\nSimilarly, the gross description should be edited after \nthe microscopic examination to remove mislead\u00ad\ning information. For example, if the gross descrip\u00ad\ntion states that a lymph node is grossly involved by \ntumor, but this later turns out to be false, this could \npotentially lead to confusion or the presumption \nthat the pathologist has made an error.\n\t\n7.\t \u0007Prioritize important information. The most impor\u00ad\ntant diagnosis should be stated first. A malignant \ndiagnosis may be overlooked if placed within a para\u00ad\ngraph describing benign findings.\nTEN WAYS TO AVOID PERSONAL ERRORS\n\t 1.\t \u0007Avoid signing out when tired, stressed, or ill. Have a \nlow threshold for setting aside difficult, unusual, or \nclinically important cases (e.g., a diagnostic biopsy prior \nto a major resection). Reflecting on a case a few hours \nlater or the next day can provide important insights.\nA rapid incorrect diagnosis is never better than a delayed \ncorrect diagnosis.\n\t 2.\t \u0007Know your limitations and have a low threshold for \nseeking opinions from your colleagues.\n\t 3.\t \u0007Require that all cases are logically consistent. If a \ncase does not make sense to you (e.g., a surgeon has \nresected a completely normal length of bowel) there is \nlikely missing clinical history (e.g., a subtle lesion has \nbeen missed during grossing or the surgeon resected \nthe wrong length of bowel).\n\t 4.\t \u0007Accept the fact that some lesions defy diagnostic cer\u00ad\ntainty. A number of studies have shown that some \nlesions cannot be consistently classified, even by a \npanel of experts under ideal conditions. For such cases, \na consensus opinion from a group of pathologists or an \n\u201cexpert\u201d opinion may be helpful.\n\t 5.\t \u0007Establish error-reduction systems and make sure \ncoworkers are aware of the reason for the system. \nExplain the importance of \u201credundant\u201d systems to \nthose using them (see later section).\n\t 6.\t \u0007Simplify tasks as much as possible for routine \u00adspecimens:\n\t\n\u2022\t \u0007Written procedures\n\t\n\u2022\t \u0007Checklists\n\t\n\u2022\t \u0007Synoptic reporting\nSave creativity for the rare unusual case.\n\t 7.\t \u0007Be responsive when clinicians question a pathology \nreport, as this is an effective method of detecting and \nrectifying errors.\n\t 8.\t \u0007Demand \nsufficient \nclinical \ninformation \nwhen \n\u00adappropriate. On the other hand, remain appropriately \nskeptical of the information you do receive, as it may \nbe incorrect or incomplete.\nClinical information is both our best friend and our worst enemy.\nRonald Sirota, MD\n\t 9.\t \u0007Be aware of common pitfalls that other pathologists \nhave fallen into, in order to avoid them yourself (see \nthe later section).\n\t10.\t\u0007Be appropriately grateful when someone discovers \none of your errors, especially if patient harm has been \navoided. Refrain from gloating over or reviling col\u00ad\nleagues when you discover they have made a mistake.\nREDUNDANT SYSTEMS\nRedundancy, or requiring that more than one person per\u00ad\nform the same task, can be an effective means of reducing \nerror. For example, one person makes up cassettes with the \nappropriate specimen number and a second person checks \nthe number on the cassette before using it for a specimen. \nOr, there may be a departmental requirement that some \npathologic diagnoses are reviewed by two pathologists.\nIf each person makes one mistake out of 100 specimens, \nthen the chance that both will make the mistake on the \nsame specimen is only one in 10,000.\nHowever, it is human nature to minimize the amount of \nwork one needs to do. If someone knows that another person \nis also performing the task, he or she is often less vigilant \nabout performing it. Therefore, the error rate can increase \nfor both people. The overall error rate may not only fail to be \ndecreased, but may actually increase in a redundant system.\nTherefore, when redundant systems are in place, every\u00ad\none must be aware of how the system works and why they \nmust not rely on someone else to check for mistakes. Each \nperson must take responsibility for any error made rather \nthan blaming a single person. Almost every error is due to \nmore than one person making multiple errors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_239.png", "summary": "The page discusses strategies to avoid errors in surgical pathology, including providing specific diagnostic terms, standardizing terminology, and prioritizing important information.", "questions": [ "How can providing specific diagnostic terms help minimize errors in surgical pathology?", "Why is it important to standardize terminology within a department?", "What are the potential consequences of not prioritizing important information in a pathology report?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 240, "text": "APPROACHING PERFECTION: AVOIDING ERRORS IN SURGICAL PATHOLOGY\u2003 Frequent Diagnostic Pitfalls\n222\nFREQUENT DIAGNOSTIC PITFALLS\nThere are some diagnostic situations that pose frequent \nproblems for pathologists. Knowledge of these problem \nareas can help avoid them.\nDermatopathology Specimens\nMisdiagnosis of melanoma is the most common claim filed \nagainst pathologists in surgical pathology.\n\t\u2022\t \u0007Making a diagnosis of melanoma (or failing to make the \ndiagnosis) on an inappropriate small or shave biopsy: \nClinicians should be educated about appropriate biop\u00ad\nsies of pigmented lesions.\n\t\u2022\t \u0007Melanomas vs. Spitz nevi.\n\t\u2022\t \u0007Failure to recognize desmoplastic melanoma: this diag\u00ad\nnosis may be difficult as this type of melanoma may not \nbe immunoreactive for typical melanoma markers.\n\t\u2022\t \u0007Metastatic melanoma vs. a primary sarcoma or carci\u00ad\nnoma: markers for melanoma are helpful.\n\t\u2022\t \u0007Metastatic melanoma to a lymph node vs. lymphoma: \nthis differential diagnosis is easily resolved with immu\u00ad\nnohistochemical markers.\nBreast Specimens\nThese specimens are the second most common source of \nmalpractice claims.\n\t\u2022\t \u0007Sclerosing adenosis vs. invasive carcinoma: This differ\u00ad\nential is made more difficult when the sclerosing adeno\u00ad\nsis is involved by apocrine metaplasia, LCIS, or DCIS. \nSmooth muscle alpha actin or P63 will show myoepithe\u00ad\nlial cells in sclerosing adenosis. This is a frequent dif\u00ad\nficult diagnosis in needle biopsies.\n\t\u2022\t \u0007Metastatic lobular carcinoma: The cells can be quite \nsmall and infiltrate in a diffuse pattern without a stromal \nresponse. A high index of suspicion and keratin studies \nmay be necessary for diagnosis.\n\t\u2022\t \u0007Low grade DCIS vs. hyperplasia: Some of these lesions \ndefy accurate classification. Micropapillary DCIS is \noften overlooked. Suspect carcinoma when cells of a \nsimilar appearance are seen in multiple ductal spaces.\n\t\u2022\t \u0007Freezing artifact in small lesions: Small lesions should \nnever be entirely frozen. In general, frozen section \nshould be avoided for any lesion less than 1 cm in size \nor if the pathologist thinks diagnosis would be compro\u00ad\nmised by freezing the lesion.\nPulmonary Specmens\n\t\u2022\t \u0007Crushed blue cells: Transbronchial biopsies may con\u00ad\ntain crushed blue cells. The diagnosis of small cell carci\u00ad\nnoma may be made without considering the possibility \nof carcinoid tumor or lymphocytes. If it is small cell car\u00ad\ncinoma, mitoses or tumor necrosis should be present. \nImmunoperoxidase studies can be used to distinguish \nlymphocytes from small cell carcinoma.\n\t\u2022\t \u0007Desmoplastic mesothelioma vs. reactive pleuritis: This \ncan be a difficult differential diagnosis, particularly when \nthe biopsy is small or the tumor is paucicellular. Repeat \nbiopsies may be necessary. Cytogenetics on pleural fluid \ncan be helpful if abnormal.\nGenitourinary Specimens\n\t\u2022\t \u0007Atrophy vs. prostate carcinoma: IHC for basal cells can \nbe helpful (see Chapter 7).\n\t\u2022\t \u0007Basal cell hyperplasia vs. PIN: IHC for basal cells can be \nhelpful (see Chapter 7).\n\t\u2022\t \u0007Urothelial carcinoma in prostatic ducts vs. PIN: IHC \ncan be helpful (see Chapter 7).\n\t\u2022\t \u0007Seminal vesicle vs. prostate carcinoma: The seminal \nvesicle can contain enlarged \u201cmonster cells.\u201d However, \nsurrounding cells will appear normal in appearance. The \nseminal vesicle has a characteristic papillary appearance \nand often has a golden-yellow cytoplasmic pigment. \nThe cells of the seminal vesicle are PSA-negative.\n\t\u2022\t \u0007Metastatic renal cell carcinoma: The cells can often be \nquite bland and mistaken for histiocytes. Metastases can \noccur decades after the original diagnosis and can occur \nin unusual sites (e.g., the eyelid).\nGastrointestinal Specimens\nThere are two types of pathologists. Those that have missed \nsignet ring cell carcinoma and those that will someday miss \nsignet ring carcinoma.\nAnonymous Pathologist\n\t\u2022\t \u0007Signet ring cell carcinoma: The cells can be very bland \nand infiltrate in the lamina propria without disrupting \nthe surrounding architecture. A high index of suspi\u00ad\ncion is necessary for all gastric biopsies. Mucin stains \nor IHC studies for keratin can be helpful. For women, \nmetastatic lobular carcinoma of the breast should also be \nconsidered.\n\t\u2022\t \u0007Pancreatic carcinoma vs. pancreatitis: This is a difficult \ndiagnosis on small specimens and on frozen section. \nSpecific criteria for diagnosis have been published and \nare helpful in these situations (see Chapter 6).\n\t\u2022\t \u0007Carcinoma or pseudoinvasion in polyps: Glands can \nbecome entrapped in the stalk of a polyp and can be \n\u00addifficult to distiguish from invasion. Invasive carci\u00ad\nnoma in a polyp should be considered as a possibility \nin small biopsies, particularly from the rectum. Inap\u00ad\npropriate surgery may be avoided by good communi\u00ad\ncation among the pathologist, the endoscopist, and the \nsurgeon.\nSoft Tissue Specimens\n\t\u2022\t \u0007Mistaking metastatic melanoma or carcinoma for sar\u00ad\ncoma: A good clinical history and immunoperoxidase \nstudies are often necessary for appropriate diagnosis.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_240.png", "summary": "The page discusses frequent diagnostic pitfalls in surgical pathology, focusing on common errors in dermatopathology, breast specimens, pulmonary specimens, and genitourinary specimens.", "questions": [ "How can clinicians be educated about appropriate biopsies of pigmented lesions to avoid misdiagnosis of melanoma?", "What are some challenges in distinguishing between sclerosing adenosis and invasive carcinoma in breast specimens?", "What techniques can be used to distinguish between small cell carcinoma and other possibilities in pulmonary specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 241, "text": "223\nAPPROACHING PERFECTION: AVOIDING ERRORS IN SURGICAL PATHOLOGY\u2003 When an Error Is Detected\n\t\u2022\t \u0007Nodular fasciitis: These lesions can have markedly atyp\u00ad\nical cells and look very alarming. A good clinical history \n(a rapidly growing mass, usually in a young adult) and a \nfamiliarity with this entity are helpful.\n\t\u2022\t \u0007Diffuse-type giant cell tumor (previously known as pig\u00ad\nmented villonodular synovitis) can be mistaken for a sar\u00ad\ncoma, particularly if extraarticular.\n\t\u2022\t \u0007Failure to recognize monophasic synovial sarcoma.\n\t\u2022\t \u0007Papillary endothelial hyperplasia (Masson lesion) vs. \nangiosarcoma: Organizing thrombi can closely mimic an \nangiosarcoma. There is often a history of prior trauma \nand the lesion may be within a vessel or have a well cir\u00ad\ncumscribed border. There is no endothelial multilayering.\nGynecologic Specimens\n\t\u2022\t \u0007Metastatic carcinoma vs. primary ovarian carcinoma: \nIHC studies can be helpful (see Chapter 7).\nNeuropathology\n\t\u2022\t \u0007Pituitary adenoma vs. multiple myeloma: On smears, \nplasma cells can closely resemble the cells of an \n\u00adadenoma.20\nHematopathology Specimens\n\t\u2022\t \u0007Lymphoma only partially involving a lymph node: This \ntype of missed diagnosis usually occurs in lymph nodes \ntaken out as part of a larger resection.\n\t\u2022\t \u0007Failure to diagnosis lymphoma in extranodal locations \n(e.g., skin, nasal cavity, mediastinum, stomach).\n\t\u2022\t \u0007Anaplastic lymphomas: These lymphomas can partially \ninvolve a lymph node and can closely mimic a metastatic \ncarcinoma. They are occasionally EMA positive and \nLCA negative. However, keratins are virtually always \nnegative.\nHead and Neck Pathology\n\t\u2022\t \u0007Squamous cell carcinoma vs. radiation changes \u2013 this \ncan be particularly difficult when the radiation changes \ninvolve small glands or ducts.\n\t\u2022\t \u0007Follicular variant of papillary carcinoma: Nuclear fea\u00ad\ntures of papillary carcinoma are present, but may be focal.\n\t\u2022\t \u0007Pseudoepitheliomatous hyperplasia over a granular cell \ntumor mistaken for squamous cell carcinoma.\n\t\u2022\t \u0007Necrotizing sialometaplasia vs. squamous cell carcinoma.\n\t\u2022\t \u0007Metastatic squamous cell carcinoma to a cervical lymph \nnode vs. a branchial cleft cyst.\nBone Specimens\n\t\u2022\t \u0007Routine rib specimens: The most common missed diag\u00ad\nnoses are multiple myeloma or chronic lymphocytic leu\u00ad\nkemia. However, the latter diagnosis is usually known \nto the clinicians because of the patient\u2019s peripheral \nblood count. In rare cases, unsuspected cases of multiple \nmyeloma may be detected in incidental specimens.\nWHEN AN ERROR IS DETECTED\nIf an error is detected, the report must be corrected and the \nclinicians notified.\nAn original report that has been issued should not be \naltered or deleted, as this report is part of the patient\u2019s med\u00ad\nical record. Minor errors can be corrected in an addendum. \nIf a major error has occurred then it may be advisable to add \na heading over the original diagnosis stating that a change \nin diagnosis has been made and directing the reader to the \ncorrected diagnosis. If an amended report is issued (i.e., the \noriginal report is unsigned and changed), the original diag\u00ad\nnosis must be preserved and the changes fully documented.\nThe circumstances and procedures leading to the error \nshould be reviewed to determine how the error occurred \nand whether the system can be improved. In general, it is \nfound that at least two people have made an error before \nan incorrect pathology report is released. For example, \none person makes an error, but a second person fails to \ndetect it. These occurrences should be viewed as excel\u00ad\nlent opportunities to discover ways to improve procedures \nand to educate pathology personnel on the importance of \n\u00adfollowing the procedures in place to prevent errors.\nREFERENCES\n\t\u2002 1.\t \u0007Stone MJ. The wisdom of Sir William Osler. Am J Cardiol \n75:269-276, 1995.\n\t\u2002 2.\t \u0007Wolber R, Chercover D. Am J Surg Pathol 27:1020-1024, \n2003: [letter to the editor].\n\t\u2002 3.\t \u0007Sirota RL. The Institute of Medicine\u2019s Report on Medical \nError. Arch Pathol Lab Med 124:1674-1678, 2000.\n\t\u2002 4.\t \u00072007 laboratory services national patient safety goals \u2013 \nhttp://www.jointcommission.org/PatientSafety/National\nPatientSafetyGoals/07_lab_npsgs.htm and CAP laboratory \npatient safety plan \u2013 http://cap.org).\n\t\u2002 5.\t \u0007Cooper K. Errors and error rates in surgical pathology. An \nAssociation of Directors of Anatomic and Surgical Pathology \nSurvey. Arch Pathol Lab Med 130:607-609, 2006.\n\t\u2002 6.\t \u0007Foucar E. Error in anatomic pathology. Am J Clin Pathol \n116(Suppl):S34-S46, 2001.\n\t\u2002 7.\t \u0007Foucar E. Error identification, A surgical pathology dilemma. \nAm J Surg Pathol 22:1-5, 1998.\n\t\u2002 8.\t \u0007Foucar E. Do pathologists play dice? Uncertainty and early \nhistopathological diagnosis of common malignancies. Histo\u00ad\npathology 31:495-502, 1997.\n\t\u2002 9.\t \u0007Goldstein NS. Diagnostic errors in surgical pathology. Clin \nLab Med 19:743-756, 1999.\n\t10.\t \u0007Hollensead SC, Lockwood WB, Elin RJ. Errors in pathol\u00ad\nogy and laboratory medicine: consequences and prevention. \nJ Surg Oncol 88:161-181, 2004.\n\t11.\t \u0007Makary MA, Epstein J, Pronovost PJ, et al. Surgical specimen \nidentification errors: a newmeasure of quality in surgical care. \nSurgery 141:450-455, 2007.\n\t12.\t \u0007Nakleh RE. Patient safety and error reduction in surgical \npathology, Arch Pathol Lab Med 132:181-185, 2008.\n\t13.\t \u0007Raab SS, Nakhleh RE, Ruby SG. Patient safety in anatomic \npathology: measuring discrepancy frequencies and causes, \nArch Pathol Lab Med 129:459-466, 2005.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_241.png", "summary": "The page discusses common errors in surgical pathology, including misdiagnoses and potential pitfalls in various specimen types. It emphasizes the importance of correcting errors and notifying clinicians.", "questions": [ "How can a pathologist differentiate between nodular fasciitis and other lesions with atypical cells?", "What are some key considerations when distinguishing between metastatic carcinoma and primary ovarian carcinoma?", "What steps should be taken if a major error is detected in a pathology report?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 242, "text": "224\nAPPROACHING PERFECTION: AVOIDING ERRORS IN SURGICAL PATHOLOGY\u2003 When an Error Is Detected\n\t14.\t \u0007Raab SS, Grzybicki DM. Measuring quality in anatomic \npathology. Clin Lab Med 28:245-259, 2008.\n\t15.\t \u0007Renshaw AA. Measuring and reporting errors in surgical \npathology. Lessons from gynecologic cytology. Am J Clin \nPathol 115:338-341, 2001.\n\t16.\t \u0007Troxel DB. Error in surgical pathology. Am J Surg Pathol \n28:1092-1095, 2004.There are also many other excellent \narticles by Dr. Troxel analyzing errors revealed by malprac\u00ad\ntice claims.\n\t17.\t \u0007Nakhleh RE, Zarbo RJ. Surgical pathology specimen iden\u00ad\ntification and accessioning. A College of American Patholo\u00ad\ngists Q-Probes study of 1,004,115 cases from 417 institutions. \nArch Pathol Lab Med 120:227-233, 1996.\n\t18.\t \u0007Wiley EL, Keh P. Diagnostic discrepancies in breast speci\u00ad\nmens subjected to gross reexamination. Am J Surg Pathol \n23:876-879, 1999.\n\t19.\t \u0007Powsner SM, Costa J, Homer RJ. Clinicians are from Mars \nand pathologists are from Venus. Arch Pathol Lab Med \n124:1040-1046, 2000.\n\t20.\t \u0007Folkerth RD. Smears and frozen sections in the intraopera\u00ad\ntive diagnosis of CNS lesions. Neurosurg Clin N Am 5:1-8, \n1994. Contains tables of differential diagnosis of similar-\nappearing lesions.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_242.png", "summary": "The page discusses various articles and studies related to measuring and reporting errors in surgical pathology, as well as diagnostic discrepancies in breast specimens and intraoperative diagnosis of CNS lesions.", "questions": [ "What are some common errors in surgical pathology that have been analyzed in the articles mentioned?", "How do clinicians and pathologists differ in their approach to diagnosing patients?", "What were the findings of the Q-Probes study on surgical pathology specimen identification and accessioning?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 243, "text": "2\nPart\nINTRODUCTION\nPart Two is a guide to the gross description, dissection, and processing of commonly received pathology \nspecimens. The following protocols have been found useful for most specimens. However, the optimal \nprocedure will vary according to specific issues associated with individual cases, institutional practices, \nand personal preferences of pathologists and \u00adclinicians.\nFormat\nEach section starts with a brief description of typical specimens and the commonly diagnosed disease \nprocesses.\n\u201cRelevant clinical history\u201d lists the most important clinical information specific for the organ site \nthat should be provided to the pathologist in order for a full evaluation of the specimen. Clinical history \nis required by JCAHO when a specimen is accepted for examination by pathologists (see also Chapter 1, \nRequests for Pathologic Evaluation). Important history for all specimens includes:\n\u2022\t The clinical indication for the procedure\n\u2022\t Any unusual features of the clinical presentation\n\u2022\t The organs/tissues resected or biopsied (including location and number of lesions present)\n\u2022\t \u0007Gross appearance of the organ/tissue/lesion sampled as observed by the surgeon, if unusual or unex\u00ad\npected\n\u2022\t Prior surgery or biopsies and the pathologic diagnoses\n\u2022\t Prior malignancies (type, location, stage)\n\u2022\t \u0007Prior treatment (radiation therapy, chemotherapy, or drugs that can alter the histologic appearance of \ntissues or increase susceptibility to infection)\n\u2022\t \u0007Immune system status (known immunosuppression or conditions that could result in immunosuppres\u00ad\nsion)\n\u2022\t Current or recent pregnancy\n\u201cProcessing the specimen\u201d outlines the step by step description, dissection, and sampling of speci\u00ad\nmens in order to document all diagnostic and prognostic features.\n\u201cSpecial studies\u201d lists tests beyond those applied to formalin fixed tissue that might be helpful for \nsome types of specimens.\n\u201cGross differential diagnosis\u201d describes the appearances of the most common tumors and disease \nprocesses. Illustrations are provided for the most common tumors and lesions.\n\u201cMicroscopic sections\u201d lists the types of tissue to be submitted and guidelines for the number of \ncassettes to submit. \n\u201cSample dictations\u201d are provided as examples of gross descriptions for common specimens.\n\u201cPathologic prognostic/diagnostic features sign-out checklist\u201d gives the major features of tumors \nthat are used for diagnosis, prognosis, staging, correlation with clinical and radiologic findings, and \ntreatment decision making. These lists are a guide to information that should be included in the final \npathology report. The lists incorporate the published recommendations of the Association of Directors \nof Surgical Pathology (ADASP) (see www.adasp.org) and the College of American Pathologists (CAP) \n(see www.cap.org), as well as the recommendations from other groups, when available. As of January \n1, 2004, the American College of Surgeons Commission on Cancer (ACS CoC) requires the report\u00ad\ning of all scientifically validated or regularly used data elements of the CAP checklists in reports of \ncancer-directed \u00adsurgical resection specimens (not including cytologic specimens, diagnostic biopsies, and", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_243.png", "summary": "Part Two of the manual provides a guide to the gross description, dissection, and processing of pathology specimens, including protocols for handling different types of specimens and relevant clinical history requirements.", "questions": [ "What are the key components of the 'relevant clinical history' that should be provided to the pathologist?", "Why is it important to document all diagnostic and prognostic features during the processing of specimens?", "What are some examples of special studies that may be listed for certain types of specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 244, "text": "226\n\u00adpalliative \u00adresection specimens) from CoC-approved cancer centers. These items are underscored in the \nchecklists provided in this manual.\n\u201cAJCC classifications\u201d are provided from the AJCC Cancer Staging Manual, seventh edition, 2009. \nThe AJCC sixth edition should be used to classify tumors diagnosed from Jan 1, 2003 through 2009. The \nseventh edition should be used after Jan 1, 2010. Other classification systems used for staging are also \nprovided.\nThe AJCC classification pertains to characteristics of a single tumor as determined at presentation, \nprior to treatment. The classification system uses suffixes and prefixes to indicate other situations:\nm: Indicates the presence of multiple tumors in a single site (e.g., T2 [m] N1 MX).\ny: Indicates the classification of a tumor during or following therapy (e.g.. ypT1 N0 MX).\nr: Indicates a recurrent tumor after a disease-free interval.\na: Indicates the classification at autopsy.\n\u201cGrading systems\u201d are provided for some specimens. Not all are universally accepted or used. Alter\u00ad\nnative grading systems are provided for some types of tumors. \nOther types of information useful for the preparation of the final surgical pathology report are pro\u00ad\nvided (e.g., Rosen criteria for lymphovascular invasion for breast cancer, evaluation of salivary gland \nbiopsies for Sj\u00f6gren\u2019s syndrome, and endometrial dating).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_244.png", "summary": "The page provides information on AJCC classifications for tumor staging, including the use of suffixes and prefixes to indicate different situations. It also discusses grading systems and other types of information useful for preparing surgical pathology reports.", "questions": [ "How are AJCC classifications used in tumor staging?", "What do the suffixes and prefixes in the AJCC classification system indicate?", "Why are alternative grading systems provided for some types of tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 245, "text": "227\n11\nAdrenal Gland\nAdrenal glands may be resected en bloc as part of a radical nephrectomy, to remove a clinically evident \ntumor (usually a functional cortical adenoma or a pheochromocytoma), or to investigate an incidental \nmass seen on CT scan (usually adenomas, rarely carcinomas). Cortical carcinomas, primary or secondary \nhyperplasia, and other benign lesions (e.g., myelolipomas, ganglioneuromas) are less common. Biopsies \nare usually fine needle aspirations to confirm the diagnosis of metastatic carcinoma.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nPROCESSING THE SPECIMEN\n \n1.\t \u0007If a mass is present, or if the surrounding soft tissue is abnormal (e.g., grossly involved by tumor), \nink the outer surface.\n \n2.\t \u0007Serially section through the specimen at 2 to 3 mm intervals. If no masses are present and signifi\u00ad\ncant amounts of peri-adrenal soft tissue are present, the soft tissue is dissected away and the exact \nweight and size of the gland measured. Weight is an important feature in assessing hyperplastic \nglands as well as tumors.\n \n\t\n\u0007Normal glands weigh from 4 to 6 grams.\n \n\t\n\u0007If a mass is present with only a small amount of peri-adrenal soft tissue, the entire specimen \nmay be weighed. If large amounts of soft tissue are present, take sections demonstrating mar\u00ad\ngins and possible soft tissue invasion. Non-involved soft tissue may then be removed before \nweighing.\nTABLE 11\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR ADRENAL SPECIMENS\nClinical indication for the procedure\nClinical symptoms of \u00adfunctional tumors:\nAdrenocortical tumors\nCushing syndrome- increased cortisol (central obesity, \nstriae, hypertension)\nConn syndrome \u2013 increased aldosterone (hypokalemia, \nhypertension)\nHypoglycemia\nCombined excess syndromes\nPheochromocytomas/\u00adparagangliomas \u2013 elevated \n\u00adcatecholamine levels (episodic hypertension, rare \n\u00adCushing syndrome)\nRadiologic findings (e.g., \u00adincidental mass or found on \u00adstudies \nfor non-specific \u00adsymptoms of weight loss or malaise)\nFamily or personal history of other endocrine tumors \n(see Table 7-50)\nAny unusual features of the clinical presentation\nOrgans resected or \u00adbiopsied (including \u00adlocation an \nthe number of lesions present)\nGross appearance of the organ/tissue/lesion \nsampled as observed by the surgeon, if unusual\nPrior surgery or \u00adbiopsies and the pathologic \u00addiagnoses\nPrior malignancies (type, location, stage)\nPrior treatment (radiation therapy, chemotherapy, \nor drug use)\nImmune system status\nCurrent or recent \u00adpregnancy", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_245.png", "summary": "Adrenal glands may be resected for various reasons including tumors, investigations of incidental masses, and biopsies for metastatic carcinoma. Processing the specimen involves inking the outer surface, serially sectioning, and measuring weight.", "questions": [ "What are the common clinical indications for resecting adrenal glands?", "How is the processing of adrenal gland specimens typically conducted?", "Why is weight measurement important in assessing hyperplastic glands and tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 246, "text": "ADRENAL GLAND\u2003 Gross Differential Diagnosis\n228\n \n3.\t \u0007Describe any lesions present including size, capsule (benign lesions are usually well-encapsulated, \nmalignant lesions may lack a capsule or invade into soft tissue), color (similar to normal cortex \nvs. brown, yellow/white, or red/brown), and relationship to normal adrenal gland (adenomas and \ncarcinomas arise from the cortex, pheochromocytomas arise from the medulla).\n \n4.\t \u0007Describe the non-lesional portion of the gland (color; golden yellow cortex, inner band of reddish \nzona reticularis, with a central pearly gray medulla), average thickness of gland (normal is 0.7 cm), \nand the presence or absence of nodularity.\n \n5.\t \u0007Carefully section through any adjacent soft tissue to search for additional tumor nodules or lymph \nnodes.\nSPECIAL STUDIES\nCytogenetics.\u2002 Many adrenal tumors are associated with germline mutations (e.g., 50% to 100% \nof adrenocortical carcinomas in children are associated with Li-Fraumeni syndrome and 30% of pheo\u00ad\nchromocytomas are associated with MEN or other syndromes; see Table 7-50). Cytogenetic changes in \nsporadic cortical tumors have been associated with clinical behavior and may be helpful for their evalu\u00ad\nation (see Table 7-47). Cytogenetic studies are also important for pediatric adrenal tumors (see below).\nChromaffin Reaction.\u2002 Ninety percent of pheochromocytomas can be diagnosed grossly by a positive \nchromaffin reaction. Fresh tumor tissue placed in chromate solutions turns a mahogany brown or black. \nZenker\u2019s fixative can be used, but is not as sensitive as it also contains acetic acid. A solution of potassium \ndichromate without acetic acid is preferable. Potassium iodide 10%, (which turns the tumors purple or \nmagenta) may be used but may be less sensitive than potassium dichromate.\nPediatric Adrenal Tumors.\u2002 Adrenal tumors in children are more likely to be neuroblastomas, gan\u00ad\nglioneuroblastomas, and ganglioneuromas, although cortical tumors and pheochromocytomas also occur. \nAs treatment decisions for neuroblastomas are based on biologic and morphologic variables, the patholo\u00ad\ngist plays a crucial role in managing the tissue allocation for these cases. In general, tissue should be placed \nin sterile culture medium for cytogenetic studies, snap-frozen in liquid nitrogen for molecular biology \nstudies, saved as air-dried touch preparations for in situ hybridization, and placed in fixative for EM.1,2\nGROSS DIFFERENTIAL DIAGNOSIS\nNormal Glands\u2002 are flat ovoid structures with a reticulated surface (Fig. 11-1A). On cross section the \ncortex is a distinctive bright canary yellow color. Lesions of this color at other sites usually correspond to \nadrenal rests. The zona reticularis is a narrow inner reddish-brown band. The central medulla has a more \nhomogeneous appearance and is a pearly gray color.\nHyperplastic Glands\u2002 show either diffuse (usually secondary hyperplasia due to increased ACTH) \nor nodular enlargement (usually primary hyperplasia) and commonly weigh more than 6 grams (Fig. \n11-1B). Multiple nodules may be present and are rarely encapsulated. There may be a dominant nodule \nbut the entire cortex should be increased in size.\nPrimary Pigmented Nodular Adrenocortical Disease (PPNAD)\u2002 is associated with Carney com\u00ad\nplex in over 90% of patients. Multiple black, brown, and/or red nodules involve the cortex of both glands. \nThe remaining adrenal may be small, normal, or enlarged. Most patients also have Cushing syndrome.\nAdenomas\u2002 are usually solitary and relatively small (less than 5 cm or 50 grams) and arise from the \ncortex (Fig. 11-1C). Most have a homogeneous bright-yellow parenchyma (like cortex) with a well-\ncircumscribed border. Larger lesions may have areas of necrosis or hemorrhage. Rarely adenomas will \nappear dark or black due to the presence of a pigment thought to be either lipofuscin or neuromelanin. \nThese dark adenomas are usually non-functioning.\n\t \u2022\t \u0007Cushing syndrome: Adenomas are bright yellow and of moderate size. They cause suppression of \nACTH by autonomously producing cortisol resulting in atrophy of the surrounding normal adrenal \n(as well as the contralateral gland). The cortex should measure less than 0.2 cm in thickness and \nthere may be fibrous thickening of the capsule.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_246.png", "summary": "The page discusses the gross differential diagnosis of adrenal gland lesions, including descriptions of lesions, non-lesional portions, special studies like cytogenetics and chromaffin reaction, and pediatric adrenal tumors.", "questions": [ "What are the key features to look for when describing lesions in the adrenal gland?", "How are cytogenetic studies important in evaluating adrenal tumors?", "What are the common types of adrenal tumors found in children?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 247, "text": "ADRENAL GLAND\u2003 Gross Differential Diagnosis\n229\n\t \u2022\t \u0007Conn syndrome: Adenomas are often smaller (<2 cm) and paler in color than those associated with \nCushing syndrome. The normal gland is not suppressed and should be normal in size.\n\t \u2022\t \u0007Adenomas associated with virilization or feminization: Often large (>1000 grams) and tan/white \nto brown.\n\t \u2022\t \u0007\u201cIncidentalomas\u201d: Adenomas found incidentally due to radiologic imaging of the adrenal glands \nfor another reason. These lesions are usually nonfunctioning and may be present in 0.6% to 1.3% of \npatients. Less than 1% of these lesions will be adrenal carcinomas. Large lesions or lesions showing \ngrowth over time are usually resected.\nAdrenal Carcinomas\u2002 are usually much larger (i.e., over 100 grams and 10 to 20 cm) than adenomas, \nbut can be small. The tumors may be bright yellow but often have a variegated appearance with areas of \nnecrosis and hemorrhage. A capsule is sometimes present but is often invaded by tumor with extension \ninto adjacent tissues. Vascular invasion is common along with thrombosis or tumor embolism. Half are \nfunctional and may cause atrophy of the surrounding cortex.\nPheochromocytomas\u2002 are yellow/white to red/brown and arise from the medulla (Fig. 11-1D). \nSmall tumors tend to be unencapsulated whereas larger tumors usually have a capsule. Larger or malig\u00ad\nnant tumors may have areas of necrosis, hemorrhage, and cystic degeneration. Most are 5 to 8 cm in size \nand weigh 70 to 100 grams. The surrounding cortex may be compressed.\nPheochromocytomas associated with hereditary syndromes (about 30% of total), are associated with \nmedullary hyperplasia in the adjacent gland; multiple nodules may be present. Adrenal medullary hyper\u00ad\nplasia is usually associated with MEN IIa and IIb syndromes and consists of diffuse or nodular expansion \nof the medulla of both adrenal glands. A nodule >1 cm is classified as a pheochromocytoma.\n\t\u2022\t \u000710% rule: 10% bilateral, 10% extra-adrenal, 10% in children, 10% malignant.\nNeuroblastomas\u2002 are the most common adrenal tumors in children. The tumors are soft and hemor\u00ad\nrhagic and may be cystic. Necrosis may be present and the tumor may invade into surrounding tissues. \nGanglioneuroblastomas and ganglioneuromas are firmer, white to tan, and often have areas with calcifi\u00ad\ncation. Focal areas typical of neuroblastoma should be sought and sampled in such tumors.\nMetastatic Tumors\u2002 are usually firm and white and appear to invade or destroy the adjacent adrenal. \nMultiple \u00adnodules may be present. Adrenal glands with metastasis from a distant site (usually lung, \nbreast, or melanoma) would be unusual surgical specimens, as the diagnosis can often be made by FNA. \nA\nB\nC\nD\nNormal\nHyperplasia\nCortical adenoma\n(arising from cortex)\nPheochromocytoma\n(arising from medulla)\nFigure 11\u20131.\u2002 Gross pathology of the adrenal gland.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_247.png", "summary": "The page discusses the gross differential diagnosis of adrenal gland tumors, including adenomas, adrenal carcinomas, pheochromocytomas, neuroblastomas, and metastatic tumors.", "questions": [ "How do adenomas associated with virilization or feminization differ in size and color compared to those associated with Conn syndrome?", "What are the characteristics of adrenal carcinomas in terms of size, appearance, and invasion?", "What distinguishes pheochromocytomas associated with hereditary syndromes from typical pheochromocytomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 248, "text": "230\nADRENAL GLAND\u2003 Pathologic Prognostic/Diagnostic Features Sign-out Checklist for Adrenal Tumors\n\u00adHowever, if the adrenal gland is removed during a radical nephrectomy, the gland may harbor metastatic \nrenal cell carcinoma (see Table 7-31).\nMyelolipomas\u2002 are soft, fleshy, circumscribed masses that resemble adipose tissue with focal red \nor fibrous areas. The mass compresses the adjacent gland. About 20% are associated with tuberous \n\u00adsclerosis.\nBenign Cysts\u2002 are usually unilocular and small and are filled with serous or serosanguinous fluid. Hem\u00ad\norrhagic cysts may be filled with clotted blood. Most probably arise from blood vessels or lymphatics.\nAny lesion not corresponding to the above descriptions may be an unusual benign or malignant tumor \n(e.g., primary lymphomas of the adrenal, ganglioneuromas, etc.). Such lesions should be carefully docu\u00ad\nmented and tissue may be taken for special studies (e.g., frozen tissue, EM, cytogenetics).\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Lesions:\n\t\u2022\t \u0007Small lesion (i.e., <2 cm): entire lesion including the capsule and relationship to adjacent adrenal \ngland.\n\t\u2022\t \u0007Large lesion (i.e., >2 cm): Three cassettes plus an additional cassette for each 1 cm of greatest \ndimension. Include the capsule and sample all areas that have different gross features (e.g., unusual \ncolor, necrosis, hemorrhage). Include relationship to the adjacent gland.\n\t\u2022\t \u0007Normal gland: If no gross lesions are present, and were not suspected clinically, submit one represen\u00ad\ntative section of the gland. If lesions are present, submit two sections of the junction of the nonlesional \ngland and the lesion.\n\t\u2022\t \u0007Margins: If the tumor is infiltrating into soft tissue, submit perpendicular margins.\n\t\u2022\t \u0007Lymph nodes: Serial section and submit (see Chapter 27).\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cright adrenal\u201d is an adrenalectomy \nspecimen (10 \u00d7 4 \u00d7 2 cm) completely surrounded by yellow/white unremarkable adipose tissue varying \nin thickness from 0.5 to 2.0 cm. There is a 20 gram 3 \u00d7 3 \u00d7 2 cm ovoid well-circumscribed bright-yellow \ntumor mass arising from the cortex of the adrenal, which is firm and lacks necrosis or hemorrhage. The \ntumor appears to compress the adjacent cortex, which is homogeneous and atrophic in appearance and \nmeasures 0.2 cm in thickness. The gray medulla is a narrow band and unremarkable. A single small \n(0.3 cm) lymph node is found in the adjacent soft tissue.\nCassette #1-4: Tumor including soft tissue margins, 4 frags, ESS.\nCassette #5: Remainder of tumor (ESS) and adjacent normal adrenal, 1 frag, RSS.\nCassette #6: Representative normal adrenal, 1 frag, RSS.\nCassette #7: Lymph node, 1 frag, ESS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR ADRENAL TUMORS\n\t\u2022\t \u0007Specimen: Unfixed, fixed in formalin\n\t\u2022\t \u0007Procedure: Total adrenalectomy, partial adrenalectomy, needle biopsy\n\t\u2022\t \u0007Specimen Integrity: Intact, fragmented. Laparoscopic removal may result in fragmentation.\n\t\u2022\t \u0007Specimen Size: Greatest dimension (optional: other dimensions). Adrenal cortical tumors over 6.5 cm \nin size are more likely to be malignant.\n\t\u2022\t \u0007Specimen Lasterality: Right, left\n\t\u2022\t \u0007Tumor Size: Greatest dimension (optional: other dimensions). Most cortical tumors over 5 cm will be \nmalignant.\n\t\u2022\t \u0007Tumor Gland Weight: In grams. Most benign cortical tumors weigh <50 g and most malignant \ntumors weigh > 100 g. The weight includes the tumor and the gland.\n\t\u2022\t \u0007Tumor Description: Hemorrhagic, necrotic, invasive (capsule, vessels, extra-adrenal) Hemorrhage \nand necrosis are unusual in benign lesions. Lesions with zonal necrosis are more likely to be malignant.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_248.png", "summary": "The page discusses various pathologic features of adrenal tumors, including myelolipomas, benign cysts, and other unusual benign or malignant tumors. It also provides guidelines for microscopic sections and sample dictation for adrenalectomy specimens.", "questions": [ "What are the typical characteristics of myelolipomas and benign cysts found in the adrenal gland?", "Why is it important to carefully document and study unusual benign or malignant tumors in the adrenal gland?", "What are the recommended guidelines for submitting microscopic sections of adrenal tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 249, "text": "231\nADRENAL GLAND\u2003 Pathologic Prognostic/Diagnostic Features Sign-out Checklist for Adrenal Tumors\n\t\u2022\t \u0007Histologic Type: Cortical adenoma, cortical carcinoma, pheochromocytoma, neuroblastoma, gan\u00ad\nglioneuroblastoma, ganglioneuroma, myelolipoma, other rare types. The WHO classification is rec\u00ad\nommended.\n\t \u2022\t \u0007It is not always possible to determine whether a cortical or medullary tumor is benign or malignant \nin the absence of distant metastases. However, histologic features can be used to divide tumors into \nlow- and high-risk groups (see later).\n\t \u2022\t \u0007The Shimada classification system is used for pediatric neuroblastic tumors (see Fig. 11-2)\n\t\u2022\t \u0007Margins: Uninvolved, involved (specify site, extent of involvement)\n\t\u2022\t \u0007Treatment Effect: No prior treatment, no effect identified, treatment effect present\n\t\u2022\t \u0007Lymph-Vascular Invasion: Present or not identified\n\t\u2022\t \u0007Perineural Invasion: Present or not identified\n\t\u2022\t \u0007Fuhrman Nuclear Grade: For carcinomas (see under renal carcinomas for criteria)\n\t\u2022\t \u0007Mitotic Rate: Number of mitoses per 10 HPF. For adrenocortical carcinomas, >20 mitoses per \n10 HPF is associated with a shorter disease-free survival (14 months) as compared with <20 mitoses \n(58 mo). A mitosis-karyorrhexis index is used for neuroblastic tumors.\n\t\u2022\t \u0007Additional Pathologic Findings: Degenerative changes (calcifications, hemorrhage, cystic change)\n\t\u2022\t \u0007Nonlesional Adrenal: Normal, atrophic, hyperplastic (cortex vs medulla)\n\t\u2022\t \u0007Ancillary Studies: Immunoperoxidase studies, histochemical stains, electron microscopy, cytogenetic \nstudies, molecular studies\n\t\u2022\t \u0007Regional Lymph Node Metastasis: Absent, present (number of nodes involved, number of nodes \nexamined)\n\t\u2022\t \u0007Lymph Nodes, Extranodal Extension: Present, not identified\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the \nM category is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 11-2). M0 \nis conferred after clinical assessment; there is no pMO category.\nTABLE 11-2.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF ADRENAL CORTICAL CARCINOMA\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nTumor 5 cm or less in greatest dimension, no extra-adrenal invasion\nT2\nTumor greater than 5 cm, no extra-adrenal invasion\nT3\nTumor of any size with local invasion, but not invading adjacent organs*\nT4\nTumor of any size with invasion of adjacent organs*\n* Note: Adjacent organs include kidney, diaphragm, great vessels, pancreas, spleen, and liver.\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional node metastasis\nN1\nMetastasis in regional lymph nodes\nDISTANT METASTASIS\nM0\nNo distant metastasis (clinically)\nM1\nDistant metastasis\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American joint Committee on Cancer (AJCC), \nChicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_249.png", "summary": "This page provides a checklist for evaluating adrenal tumors, including histologic types, margins, treatment effects, invasion status, grading criteria, metastasis classifications, and AJCC staging for adrenal cortical carcinoma.", "questions": [ "How do histologic features help in categorizing adrenal tumors into low- and high-risk groups?", "What is the significance of the Fuhrman Nuclear Grade in adrenal carcinomas?", "How is the AJCC classification system utilized in staging adrenal cortical carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 250, "text": "232\nADRENAL GLAND\u2003 Criteria for Malignant Clinical Behavior for Cortical Lesions in Pediatric Tumors (<20 Years of Age)\nTHE AGE-LINKED SHIMADA CLASSIFICATION OF CHILDHOOD NEUROBLASTOMA AND GANGLIONEUROBLASTOMA\nThe Shimada classification (Fig. 11-2) uses specific morphologic features (i.e., stroma, differentiation, \nmitosis-karyorrhexis index, nodularity, and calcification), age, stage, and nMYC status to evaluate pedi\u00ad\natric neuroblastic tumors. The character of the stroma is important for prognosis.1,2,12,13\nWEISS CRITERIA FOR MALIGNANCY FOR CORTICAL LESIONS IN ADULTS (>20 YEARS)\nFewer than 10% of cortical tumors will behave in a malignant fashion. No single or group of features is \nable to separate benign from malignant lesions. However, the criteria in Table 11-3 can be used to clas\u00ad\nsify cortical lesions into high and low risk lesions.3-5\nCRITERIA FOR MALIGNANT CLINICAL BEHAVIOR FOR CORTICAL LESIONS IN PEDIATRIC TUMORS (<20 YEARS OF AGE)6\n \n1.\t \u0007Tumor weight >400 g\n \n2.\t \u0007Tumor size >10.5 cm\n \n3.\t \u0007Extension into periadrenal soft tissue and/or adjacent organs\n \n4.\t \u0007Invasion into vena cava\n \n5.\t \u0007Venous invasion\n \n6.\t \u0007Capsular invasion\n \n7.\t \u0007Presence of tumor necrosis\n \n8.\t \u0007>15 mitoses per 20 HPF (400\u00d7)\n \n9.\t \u0007Presence of atypical mitotic figures\nSome tumors that would be classified as malignant by adult tumor criteria behave in a benign fashion \nin children.\n\t\u2022\t \u00070-2 criteria: benign long-term clinical outcome\n\t\u2022\t \u00073 criteria: indeterminate for malignancy (17% are malignant)\n\t\u2022\t \u0007>3 criteria: poor clinical outcome (64% are malignant)\nNodular\nPoor prognosis group\nUnfavorable stroma-rich\nUnfavorable stroma-poor\n>5y/o\n<1.5y/o\n<100\n<200\n1.5 \u2013 5y/o\nDiff.\n>100\n>200\nUndiff.\nStroma\nStroma-rich\ntumors\nN\nO\nD\nU\nL\nE\nS\nStroma-poor\ntumors\nA\nG\nE\nM\nK\nI\nM\nK\nI\nAbsent\nWell differentiated\nIntermixed\nPresent\nFigure 11\u20132.\u2002 The age-linked Shimada classification of childhood neuroblastoma and ganglioneuroblastoma.\nAn important factor is determination of the character of the stroma. Unfavorable stroma-rich and stroma-poor \n\u00adcategories are seen. MKI is mitosis-karyorrhexis index. (Reproduced with permission from Shimada H, Chatten J, Newton \nWA Jr, et al. J Natl Cancer Institute 73:405\u2013416, 1984.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_250.png", "summary": "The page discusses criteria for malignant clinical behavior for cortical lesions in pediatric tumors and adults, using specific morphologic features, age, and other factors to evaluate neuroblastic tumors.", "questions": [ "How do the Shimada classification and Weiss criteria differ in evaluating malignant behavior in cortical lesions?", "What are some key factors that contribute to the prognosis of pediatric neuroblastic tumors?", "Why is determination of the character of the stroma important in assessing the malignancy of tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 251, "text": "233\nADRENAL GLAND\u2003 Features Associated with Malignancy in Pheochromocytomas\nFEATURES ASSOCIATED WITH MALIGNANCY IN PHEOCHROMOCYTOMAS7\u20139\nFive to 15% of pheochromocytomas will behave in a clinically malignant fashion, but it is impossible to \npredict this group based on any single histologic feature. Even tumors with capsular invasion, vascular \ninvasion, and invasion into adjacent soft tissue may be surgically curable.\nTwo more recent systems (PASS [Table 11-4] and KIMURA [Table 11-5]) are controversial. \nMost pathologists do not currently employ any formal scoring system in routine practice, for reasons \nincluding the lack of prospective validation and uncertainty as to how to recognize some of the scored \nparameters.\nThe systems are described only for the purpose to elucidate some of the features described in malig\u00ad\nnant tumors. However, both systems await further studies and confirmation.\nBoth were developed to help predict the tumors most likely to behave in a clinically malignant \nfashion. The PASS system, however, has not shown to be reproducible and the criteria listed can be \neasily misinterpreted. Thus far, no validation studies have been performed assessing the robustness \nof this system, especially in correlating morphological parameters with tumor proliferative index, as \nassessed by MIB-1/Ki-67 staining, which has been most consistently correlated with malignancy in \nindependent studies.\nTABLE 11\u20133.\u2003 WEISS CRITERIA FOR MALIGNANCY FOR CORTICAL LESIONS IN ADULTS \n(>20 YEARS OF AGE)\nCRITERION\nDESCRIPTION\n1. Nuclear grade III or IV\nUse Fuhrman nuclear grade\n2. Mitotic rate >5/50 HPF\n\u00d740 objective on a Zeiss microscope. Mitoses are evaluated by counting 10 ran\u00ad\ndom HPFs in the area of greatest numbers of mitotic figures on the 5 slides \nwith the greatest number of mitoses (or if fewer slides, increase the number \nof HPFs per slide). Apoptotic and crushed cells are excluded.\n3. Atypical mitotic figures\nAtypical mitoses definitely have an abnormal distribution of chromosomes or \nan excessive number of mitotic spindles.\n4. Eosinophilic tumor cell \n\u00adcytoplasm (75%)\n\u2264 25% clear or vacuolated cells resembling the normal zona fasciculata\n5. Diffuse architecture (33%)\n> one-third of the tumor forms patternless sheets of cells. Trabecular, cordonal, \ncolumnar, alveolar, or nesting patterns are not considered diffuse.\n6. Necrosis\nMust occur in confluent nests of cells.\n7. Venous invasion\nA vein must be an endothelial-lined vessel with smooth muscle as a component \nof the wall. Free tumor cells floating in a vessel lumen are not included.\n8. Sinusoidal invasion\nA sinusoid is an endothelial-lined vessel in the adrenal gland with little \n\u00adsupportive tissues.\n9. Capsular invasion\nNest or cords of tumor extend into or through the capsule with a corresponding \nstromal reaction.\nCriteria 2, 3, and 7 were seen only in malignant tumors. >95% of malignant tumors had three or more of these criteria (most have 4), whereas \n>95% of benign lesions have two or fewer.\nTumors \u226550 grams behaved in a malignant fashion 91% of the time. Tumors \u22656.5 cm were malignant 92% of the time. Aldosterone-secreting \ntumors are always benign. These criteria do not accurately predict the clinical behavior of oncocytic adrenocortical tumors, as many have nuclear \natypia and a diffuse growth pattern. However, the presence of necrosis, invasion, and mitoses do correlate with malignancy in this tumor type.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_251.png", "summary": "Features associated with malignancy in pheochromocytomas are difficult to predict based on histologic features alone. Two scoring systems, PASS and KIMURA, have been developed but lack validation and reproducibility.", "questions": [ "How accurate are the PASS and KIMURA scoring systems in predicting malignancy in pheochromocytomas?", "What are the key histologic features associated with malignancy in pheochromocytomas according to the Weiss criteria?", "Why do most pathologists not currently employ formal scoring systems like PASS and KIMURA in routine practice?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 252, "text": "234\nADRENAL GLAND\u2003 Features Associated with Malignancy in Pheochromocytomas\nTABLE 11\u20134.\u2003\nPHEOCHROMOCYTOMA OF THE ADRENAL GLAND SCALED SCORE (PASS)\nFEATURE\nDESCRIPTION\nSCORE\nLarge nests or diffuse growth \n(>10% of tumor volume)\nA large nest is 3 to 4 times the size of a zellballen or the nor\u00ad\nmal size of the medullary paraganglia nests.\n2\nCentral (middle of large nests) or \nconfluent tumor necrosis\nDoes not include degenerative change (cyst formation, \n\u00adhemorrhage, hemosiderin-laden macrophages, and fibrosis)\n2\nHigh cellularity\nMany cells with a high nuclear-to-cytoplasmic ratio\n2\nCellular monotony\n2\nTumor cell spindling (even if focal)\n2\nMitotic figures >3/10 HPF\n\u00d740 with a \u00d710 objective using an Olympus BX40 microscope\n2\nAtypical mitotic figure(s)\nAbnormal chromosome spread, tripolar or quadripolar forms, \ncircular forms, or indescribably bizarre\n2\nExtension into adipose tissue\n2\nVascular invasion (either lymphatic \nor blood vessel)\nDirect extension into the vessel lumen, intravascular attached \ntumor thrombi, and/or tumor nests covered by endothe\u00ad\nlium identified in a capsular or extracapsular vessel\nTumors involving vessels within the tumor are not included\n1\nCapsular invasion\n1\nProfound nuclear pleomorphism\nGreatly enlarged nuclear size, irregular shape, and bizarre \nforms\n1\nNuclear hyperchromasia\nComplete opacification and heavy nuclear chromatin \n\u00addeposition\n1\nTotal\n20\nBenign tumors did not show invasion into adipose tissue, central confluent necrosis, or atypical mitotic figures. \n\u00adSustentacular cells (identified by S100) were present in the primary tumors as well as in metastases. Although \nmalignant tumors tend to be larger and weigh more, these features are not reliable for determining clinical \n\u00adbehavior.\nThe tumor is evaluated for each feature and a total score generated.\nPASS SCORE\nCLINICAL BEHAVIOR\n<4\nAll clinically benign\n\u22654\n66% clinically malignant", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_252.png", "summary": "The page discusses features associated with malignancy in pheochromocytomas of the adrenal gland, including criteria for scoring malignancy and predicting clinical behavior.", "questions": [ "What are the specific features evaluated in pheochromocytomas to determine malignancy?", "How is the malignancy of pheochromocytomas assessed using the PASS scoring system?", "What is the clinical significance of the PASS score in predicting the behavior of pheochromocytomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 253, "text": "235\nADRENAL GLAND\u2003 Features Associated with Malignancy in Pheochromocytomas\nREFERENCES\n\t\u2002 1.\t \u0007Shimada H, Ambros IM, Dehner LP, et al. Terminology and morphologic criteria of neuroblastic tumors: rec\u00ad\nommendations by the International Neuroblastoma Pathology Committee. Cancer 86:349-365, 1999.\n\t\u2002 2.\t \u0007Jarzembowski JA, et al: CAP Protocol for neuroblastoma at www.cap.org.\n\t\u2002 3.\t \u0007Weiss LM, Medeiros LJ, Vickery AL. Pathologic features of prognostic significance in adrenal cortical carci\u00ad\nnoma. Am J Surg Path 13:202-206, 1989.\n\t\u2002 4.\t \u0007Medeiros LJ, Weiss LM. New developments in the pathologic diagnosis of adrenal cortical neoplasms. Am J \nClin Pathol 97:73-83, 1992.\n\t\u2002 5.\t \u0007Aubert S, Wacreneir A, Leroy X, et al: Weiss system revisited. A clinicopathologic and immunohistochemical \nstudy of 49 adrenocortical tumors. AJSP 26:1612-1619, 2002.\n\t\u2002 6.\t \u0007Wieneke JA, Thompson LDR, Heffess CS. Adrenal cortical neoplasms in the pediatric population: A clinico\u00ad\npathologic and immunophenotype analysis of 83 patients. Am J Surg Pathol 27:867-881, 2003.\n\t\u2002 7.\t \u0007Medeiros LJ, Weiss LM. Adrenal gland: Tumors and tumor-like lesions. In Weidner N (ed): The Difficult \nDiagnosis in Surgical Pathology, pgs 377-407, Philadelphia, WB Saunders, 1996.\n\t\u2002 8.\t \u0007Kimura N, Watanabe T, Noshiro T, et al. Histological grading of adrenal and extra-adrenal pheochromocytomas \nand relationship to prognosis: a clinicopathological analysis of 116 adrenal pheochromocytomas and 30 extra-\nadrenal sympathetic paragangliomas including 38 malignant tumors. Endocr Pathol 16:23-32, 2005.\n\t\u2002 9.\t \u0007Thompson LDR. Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) to separate benign from \nmalignant neoplasms. A clinicopathologic and immunophenotype study of 100 cases,. AJSP 26:551-566, \n2002.\n\t10.\t \u0007Henley DJ, van Heerden JA, Grant CS, et al. Adrenal cortical carcinoma: a continuing challenge. Surgery \n94:926-931, 1983.\nTABLE 11\u20135.\u2003\nSCORING SCALE FOR PHEOCHROMOCYTOMAS AND EXTRA-ADRENAL \nSYMPATHETIC PARAGANGLIOMAS (KIMURA)\nFEATURE\nSCORE\nHistologic pattern\n\u2003 Uniform cell nests\n0\n\u2003 Large and irregular nests\n1\n\u2003 Pseudorosettes (even if focal)\n1\nCellularity\n\u2003 Low (<150 cells/mm2)\n0\n\u2003 Moderate (150 to 250 cells/mm2)\n1\n\u2003 High (>250 cells/mm2)\n2\nNecrosis (confluent or central in large nests)\n2\nVascular or capsular invasion\n1\nKi-67 immunoreactivity\n\u2003 >1% or 20 cells per medium-power field\n1\n\u2003 >3% or 50 cells per medium-power field\n2\nCatecholamine phenotype\n\u2003 Adrenergic\n0\n\u2003 Noradrenergic or \u201cnonfunctional\u201d\n1\nTotal\n10\nMetastases were reported in 13% of tumors with scores 1-2, 63% with 3-6, and 100% with 7-10. In addition, 5-year survivals of patients in the three \ngroups were reported to be 92%, 69% and 0, respectively (Kimura).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_253.png", "summary": "The page discusses features associated with malignancy in pheochromocytomas, including a scoring scale for determining the likelihood of metastases and survival rates based on the score.", "questions": [ "How is the scoring scale for pheochromocytomas and extra-adrenal sympathetic paragangliomas used to predict metastases and survival rates?", "What are the key histologic patterns and cellular characteristics that contribute to the scoring scale for pheochromocytomas?", "What are the implications of the reported 5-year survival rates for patients with different scores on the scoring scale?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 254, "text": "236\nADRENAL GLAND\u2003 Features Associated with Malignancy in Pheochromocytomas\n\t11.\t \u0007Lack E. Tumors of the Adrenal Gland and Extra-Adrenal Paraganglia, AFIP Fascicle No. 19, Third Series. \nWashington DC, American Registry of Pathology, 1997.\n\t12.\t \u0007Shimada H, Ambros IM, Dehner LP, et al: The International Neuroblastoma Pathology Classification (the \nShimada System), Cancer 86:364-372, 1999.\n\t13.\t \u0007Shimada H, Chatten J, Newton WA Jr, et al: Histopathologic prognostic factors in neuroblastic tumors: defini\u00ad\ntion of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomass. J Natl Cancer Inst \n73:405-416, 1984.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_254.png", "summary": "This page discusses features associated with malignancy in pheochromocytomas, referencing various pathology classification systems.", "questions": [ "What are the key features of malignancy in pheochromocytomas?", "How do the referenced pathology classification systems contribute to understanding pheochromocytomas?", "Are there specific treatment implications based on the features associated with malignancy in pheochromocytomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 255, "text": "237\n12\nAmputations and Large \nResections\nThe most common reasons for amputations are peripheral vascular disease, trauma, and occasionally \ntumors. Some amputation specimens may be requested by the patient (e.g., some religions require burial \nof the limb).\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nGENERAL GROSS DESCRIPTION\nThe description of all amputations includes the following:\n\t\u2022\t \u0007Structures present:\n\t \u2022\t \u0007Left lower leg below-the-knee amputation, right foot, left index finger, etc.\nTABLE 12\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR AMPUTATION SPECIMENS\nClinical indication for the procedure\nJoint disease (e.g., gout or rheumatoid arthritis)\nAny unusual features of the clinical presentation\nReason for the \u00adamputation (e.g., vascular disease \n\u00adassociated with \u00addiabetes, avascular necrosis, \n\u00admalignancy, \u00adpathologic fracture, \u00adtraumatic \u00adamputation)\nOrgans resected or \u00adbiopsied (including location \nand \u00adnumber of lesions present)\nPrior malignancy (e.g., \u00adprimary bone tumor, metastases to \nbone, or tumors such as lymphoma that involve bone \nmarrow)\nGross appearance of the organ/tissue/lesions \nsampled as observed by the surgeon, if unusual\nPrior treatment (e.g., \u00advascular grafts, treatment of \n\u00admalignant tumors)\nPrior surgery or biopsies and the pathologic \n\u00addiagnoses\nRadiologic findings (e.g., incidental mass or found on stud\u00ad\nies for \u00adnonspecific symptoms of weight loss or malaise)\nPrior malignancies (type, \u00adlocation, stage)\nPrior treatment (radiation \u00adtherapy, chemotherapy, \ndrug use that can change the \u00adhistologic appear\u00ad\nance of \u00adtissues)\nImmune system status\nCurrent or recent pregnancy", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_255.png", "summary": "Amputations are commonly performed for peripheral vascular disease, trauma, and tumors, with some patients requesting the amputated limb for burial purposes.", "questions": [ "What are the most common reasons for amputations?", "Why might a patient request their amputated limb?", "What clinical history is relevant for amputation specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 256, "text": "AMPUTATIONS AND LARGE RESECTIONS\u2003 Digits \u2212 Non-tumor\n238\n\t \u2022\t \u0007Dimensions of each structure (e.g., upper leg, lower leg, foot) including length and maximum \n\u00adcircumference of limbs.\n\t\u2022\t \u0007Type of procedure: Disarticulation (cartilage-covered joint surface present) vs. amputation (exposed \nbone surface present)\n\t\u2022\t \u0007Type of resection margin: Smooth (surgical) or irregular (traumatic) resection margin.\n\t\u2022\t \u0007Soft tissue at resection margin: Condition (e.g., grossly viable vs. necrotic or ulcerated). Distance of \nskin and soft tissue from bony resection margin.\n\t\u2022\t \u0007Skin: Color, lesions (ulcers, areas of discoloration, \u00adbruising, gangrene) or identifying marks (e.g., scars, \n\u00adtattoos).\n\t\u2022\t \u0007Lesions: Bone fractures, blood vessels (atherosclerosis, thrombosis), osteomyelitis, tumor (if present), \nprevious amputation sites.\n\t\u2022\t \u0007Prior surgical procedures: Amputations, vascular grafts, etc.\n\t\u2022\t \u0007Decalcification: Decalcification must be documented as this procedure can alter the histologic appear\u00ad\nance and immunogenicity of tissues and is required for appropriate billing.\nTRAUMATIC AMPUTATIONS\nTraumatic amputations may involve litigation and the pathologic examination may become legal evi\u00ad\ndence. It is helpful to photograph such specimens for documentation. Process as described for amputa\u00ad\ntions for vascular insufficiency. The presence and extent of peripheral vascular disease may be of clinical \nvalue if present.\nDIGITS \u2212 NON-TUMOR\nFingers and toes are usually removed due to vascular insufficiency (toes) or trauma (usually fingers).\n\t\n1.\t \u0007Describe including the features listed above.\n\t\n2.\t \u0007Submit one section of soft tissue margin and an additional section of any skin lesions.\n\t\n3.\t \u0007Fix entire specimen overnight.\n\t\n4.\t \u0007Decalcify the following day.\n\t\n5.\t \u0007When the bone is sufficiently decalcified, take one section of bone at the resection margin \nand one additional section of bone if there is a question of osteomyelitis (e.g., bone below a deep \nulcer bed).\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Skin and soft tissue: One section of margin and additional section(s) to evaluate any skin \nlesions.\n\t \u2022\t \u0007Bone: One section of the resection margin. Additional section(s) of bone beneath deep ulcers if \nthere is a question of osteomyelitis.\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201ctoes\u201d are two digits amputated \nthrough the first metatarsal bone with a smooth resection margin and measuring 2 \u00d7 2 \u00d7 1.5 cm and 1.5\u00a0\u00d7 \n1.5 \u00d7 1 cm. The larger digit has a deep ulcer on the plantar surface (1 \u00d7 1 cm) that grossly appears to \nextend to the underlying bone. The skin of the smaller digit has a purple/black color, but no ulceration is \npresent. The nails are unremarkable. The resection margins consist of unremarkable bone and soft tissue. \nThe bone is fixed and decalcified prior to \u00adsubmission.\nCassette #1: Larger digit, ulcer, 1 frag, RSS.\nCassette #2: Larger digit, skin at margin, 1 frag, RSS.\nCassette #3: Larger digit, bone below ulcer, 1 frag, RSS.\nCassette #4: Larger digit, bone at margin, 1 frag, RSS.\nCassette #5: Smaller digit, representative skin and soft tissue at tip, 1 frag, RSS.\nCassette #6: Smaller digit, skin at margin, 1 frag, RSS.\nCassette #7: Smaller digit, bone at margin, 1 frag, RSS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_256.png", "summary": "The page discusses the process and considerations for amputations and large resections, specifically focusing on non-tumor cases involving digits.", "questions": [ "What are the key features to describe in a specimen involving digits?", "What is the significance of submitting specific sections of soft tissue margin and skin lesions?", "Why is decalcification necessary for appropriate billing and how does it affect the histologic appearance of tissues?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 257, "text": "239\nAMPUTATIONS AND LARGE RESECTIONS\u2003 Lower Extremity \u2212 Non-tumor\nLOWER EXTREMITY \u2212 NON-TUMOR\nVascular Insufficiency\nVascular insufficiency is the most common reason for amputations. Often there will be prior amputations \n(e.g., several toes) and skin lesions (ulcers or frank gangrene). To document the disease process, dissect \nand examine the vessels of the leg.\nDissection of the Vessels of the Lower Extremity\nSee Figure 12-1.\n\t\n1.\t \u0007Make a skin incision that starts just behind the medial malleolus and extends proximally in an \noblique manner to reach the posterior aspect of the leg, and thence straight upwards to the line of \nresection.\n\t\n2.\t \u0007Identify the posterior tibial neurovascular bundle behind the medial malleolus. Sever the distal \nends and proceed to strip the vessels upwards, dissecting the muscle and subcutaneous tissue away \nfrom the vessels. Stop when the junction of the posterior tibial and popliteal arteries is reached at \nthe interosseous membrane between the tibia and fibula.\n\t\n3.\t \u0007Return to the ankle region and extend the original incision distally and then laterally to traverse the \ndorsum of the foot just distal to the ankle. Reflect the skin flap to expose the anterior compartment \nof the leg.\n\t\n4.\t \u0007Identify the anterior tibial neurovascular bundle at the ankle (the anterior tibial artery becomes \nthe dorsalis pedis artery and traverses the dorsum of the foot at this site). Sever the distal ends and \nreflect proximally as for the posterior tibial. When the interosseous membrane is reached, dissect \nbluntly around the vessel to free it. Then return to the posterior aspect of the leg and pull the \nanterior tibial vessels through the interosseous membrane.\n\t\n5.\t \u0007Complete the removal of the vessels by continuing the reflection of the popliteal artery to the lines \nof resection.\nUsually the vessels will be densely calcified and will require decalcification before cutting.\nPROCESSING THE SPECIMEN\n\t\n1.\t \u0007Record the measurements and features described in the first section.\n\t\n2.\t \u0007Dissect out the anterior and posterior vessels and any grafts, if present (see above). If vein grafts are \npresent, describe their anatomic relationships to other vessels, the status of the anastomosis (intact, \npatent, obstructed) and the presence or absence of thrombi.\n\t\n3.\t \u0007Take skin and soft tissue sections from the margin and from any lesions present. Take a cross \nsection of the soft tissue of one of the grossly normal toes to look for small vessel disease. \nBone sections need not be taken if there are no gross lesions. If there is a suspicion of bone \ninvolvement (osteomyelitis), that section of bone is resected with the bone saw for fixation and \ndecalcification.\nThe metatarsal-phalangeal joint of the great toe is dissected open and examined for evidence \nof joint disease (see in Chapter 14, \u201cSynovium,\u201d for gross differential diagnosis of joint disease).\nThe marrow can be removed from the cut section of the bone and prepared as for a rib marrow \nsqueeze if there is a clinical suspicion of disease involving the marrow.\n\t\n4.\t \u0007Fix the tissue sections and blood vessels in small formalin containers with appropriate labels (e.g., \n\u201canterior vessels and margin,\u201d \u201cposterior vessels and skin lesion\u201d). The remainder of the specimen \nis kept unfixed but refrigerated.\n\t\n5.\t \u0007The following day the soft tissue is submitted for processing (one cassette of margin, cassette[s] of \nlesion[s], cassette of soft tissue of toe). The vessels are decalcified.\n\t\n6.\t \u0007The next day the vessels and grafts are serially sectioned. Record the location and extent of occlu\u00ad\nsions (calcified plaque, thrombosis). Submit multiple cross sections in two separate cassettes from \nthe anterior and from the posterior vessels of the areas of greatest occlusion. If a graft is present, \nsubmit areas of obstruction and the vein-artery anastomotic site.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_257.png", "summary": "Vascular insufficiency is the most common reason for amputations in the lower extremity. Dissection and examination of the vessels of the leg are essential to document the disease process.", "questions": [ "What are the common signs of vascular insufficiency that may lead to amputations?", "What is the significance of dissecting and examining the vessels of the leg in cases of vascular insufficiency?", "How do vein grafts and thrombi play a role in the processing of the specimen in cases of vascular insufficiency?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 258, "text": "240\nAMPUTATIONS AND LARGE RESECTIONS\u2003 Lower Extremity \u2013 Non-tumor\nA\nB\nAnterior\nPosterior\nInterosseous\nmembrane\nAnterior tibial\nartery\nPosterior \ntibial\nartery\nAnterior\ntibial\nartery\nLateral\nmalleolus\nMedial malleolus\nInterosseous \nmembrane\nPopliteal\nartery\nAnterior tibial\nartery\nPosterior tibial artery\nTibialis anterior\nmuscle\nPeroneus brevis\nmuscle\nGastrocnemius\nmuscle\nSoleus muscle\nPeroneal artery\nTibia\nFibula\nTibialis posterior\nmuscle\nFigure 12\u20131.\u2002 Dissection of the lower extremity.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_258.png", "summary": "This page discusses amputations and large resections of the lower extremity in non-tumor cases, with a diagram showing the dissection of the lower extremity.", "questions": [ "What are the main arteries and muscles involved in the lower extremity dissection?", "How are amputations and large resections different in tumor versus non-tumor cases?", "What are the potential complications associated with these types of procedures?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 259, "text": "241\nAMPUTATIONS AND LARGE RESECTIONS\u2003 Amputations or Large Resections for Tumor\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Skin and soft tissue: One section of margin and additional section(s) to evaluate any skin lesions.\n\t \u2022\t \u0007Cross section of toe: One cross section (to evaluate small vessel disease).\n\t \u2022\t \u0007Bone: Only submit section(s) of bone if there is a question of osteomyelitis or if bony lesions are \npresent. The margin need not be submitted.\n\t \u2022\t \u0007Vessels and grafts: Submit one cassette each of anterior and posterior vessels showing area(s) of \ngreatest occlusion. Submit area of greatest occlusion of grafts and the vein-artery anastomotic site.\n\t \u2022\t \u0007Bone marrow: Only submitted if there is a clinical suspicion of disease affecting the bone marrow.\n\t \u2022\t \u0007Joint: Only submitted if there is clinical suspicion or gross evidence of disease affecting the joints \n(e.g., gout).\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cleg\u201d is a right lower extremity \namputated through the tibia and fibula with a smooth resection margin (length of leg 37 cm; circumfer\u00ad\nence of calf 40 cm; foot 26 \u00d7 9 cm). The fourth and fifth digits have been previously amputated. The skin \nis diffusely mottled purple and red. There are ulcerations present on the lateral aspect of the foot (3 \u00d7 1 \ncm) and on the plantar surface of the great toe (1 \u00d7 1 cm). The anterior vessels are diffusely calcified with \nluminal obstructions of up to 80%. The posterior vessels are diffusely calcified with luminal obstructions \nof up to 50%. The metatarsal-phalangeal joint of the great toe consists of smooth glistening white car\u00ad\ntilage and is grossly unremarkable. The bone and soft tissue at the resection margin are unremarkable. \nA cross section of the third digit is fixed and decalcified prior to submission.\nCassette #1: Skin, ulcers, 2 frags, RSS.\nCassette #2: Skin and soft tissue at margin, 1 frag, RSS.\nCassette #3: Cross section of third digit, 1 frag, RSS.\nCassette #4: Anterior vessels, 1 frag, RSS.\nCassette #5: Posterior vessels, 1 frag, RSS.\nAMPUTATIONS OR LARGE RESECTIONS FOR TUMOR\nLarge tumor resections are unusual and usually involve either tumors of bone or cartilage or soft tissue \ntumors involving major neurovascular bundles.1-4 See in Chapter 14, \u201cBone Resections for Tumors\u201d and \nChapter 32 for additional information about these specimens.\nIf bone is present, radiographs of the specimen are helpful to document the bony structures present \nand to identify areas of destruction of normal bone or abnormal bone formation for sampling. Tumors \ninvolving bone may require sectioning (either longitudinal or cross sections) with an electric hand-saw or \na band saw. If the distal limb is not involved, separating this part of the specimen may simplify dissection \nand fixation.\nDiagrams are often useful to document complex specimens and can be used to designate the location \nof tissue blocks. Polaroid photographs and photocopies have also been used for this purpose.1\nDescribe the specimen as outlined above in the general section. Identify the muscles, nerves, and \narteries present at the margin of the specimen and the sites of any prior biopsies. The best way to process \nthe specimen will depend on the type and location of the tumor. Tumors involving nerve bundles may be \nbest demonstrated by partial dissection of nerve trunks.\nDescribe the tumor, including size, appearance (color, necrosis, bone formation, cartilage formation), \nlocation (tissue compartment), relationship to surrounding structures (bone, vessels, nerves, muscle), \ncenter of tumor (epiphysis, metaphysis, diaphysis, intramedullary, periosteal), erosion of cortex, exten\u00ad\nsion into soft tissue (compression or true invasion), extension through epiphyseal plate, extension into or \nacross joint space, vascular involvement, skip metastases, distance from each margin.\nAfter all soft tissue sections have been removed, tumors involving bone can be decalcified after fixa\u00ad\ntion. Over-decalcification resulting in loss of histologic detail should be avoided by periodically checking \nthe specimen to minimize exposure. Bone dust may create histologic artifacts (i.e., bone fragments within \nthe marrow space). To avoid this, small sections of bone should be decalcified, the decalcified tissue \nthinly sectioned with a scalpel, and the tissue sections embedded so that the surface away from that cut \nby the saw is used to prepare tissue for slides.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_259.png", "summary": "This page provides guidelines for the microscopic evaluation of sections from amputations or large resections for tumors, including skin, soft tissue, bone, vessels, grafts, bone marrow, and joints.", "questions": [ "What are the specific sections that should be submitted for evaluation in cases of amputations or large resections for tumors?", "How are bone specimens handled differently depending on the presence of osteomyelitis or bony lesions?", "What are the indications for submitting sections of bone marrow or joints in these cases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 260, "text": "242\nAMPUTATIONS AND LARGE RESECTIONS\u2003 Amputations or Large Resections for Tumor\nAll margins, usually perpendicular, must be evaluated including soft tissue, blood vessels, nerves, and \nbone. Bone margins can be removed with a bone saw and decalcified separately.\nSPECIAL STUDIES\n\t \u2022\t \u0007Untreated tumors: Most amputations are performed for sarcomas, bone tumors, or other unusual \ntumors. It is often helpful to save tumor for rapid formalin fixation, electron microscopy, snap freez\u00ad\ning, and cytogenetics.\n\t \u2022\t \u0007Treated tumors: If the tumor has been previously diagnosed and special studies performed, and the \npatient has received preoperative chemotherapy and/or radiation therapy, the tumor may be largely \nnecrotic and additional studies may not be possible. However, a complete cross-section of the tumor \n(using multiple cassettes with locations indicated on a diagram) may be helpful to evaluate the extent \nof necrosis in response to treatment for osteosarcoma and Ewing sarcoma (see Chapter 14).\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Tumor: At least one section per cm including areas of intratumoral heterogeneity, relationship to \nadjacent normal structures, and relationship to margins. A diagram with a section code is usually \nneeded.\n\t \u2022\t \u0007Margins: All margins including soft tissue and bone are sampled using perpendicular sections.\n\t \u2022\t \u0007Normal structures: Representative sections of normal structures (e.g., blood vessels, major nerve \nbundles).\n\t \u2022\t \u0007Lymph nodes: Submit all lymph nodes found (see Chapter 27).\nREFERENCES\n\t\u2002 1.\t \u0007Olson DR. Specimen photocopying for surgical pathology reports. Am J Clin Pathol 70:94-95, 1978.\n\t\u2002 2.\t \u0007Barnes L, Johnson JT. Pathologic and Clinical Consideration in the Evaluation of Major Head and Neck Speci\u00ad\nmens Resected for Cancer, Path Ann (Part 1) 21:173-250, 1986 and Path Ann (Part 2), 21:83-110, 1986. (Head \nand neck.).\n\t\u2002 3.\t \u0007Weatherby RP, Krishnan KU. Practical aspects of handling orthopedic specimens in the surgical pathology \nlaboratory, Path Annual, 17. part 2:1-31, 1982. (Bone resections with tumors.).\n\t\u2002 4.\t \u0007Patterson K. The pathologic handling of skeletal tumors. Am J Clin Pathol 109(Suppl 1):S53-S66, 1998.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_260.png", "summary": "When performing amputations or large resections for tumors, it is important to evaluate all margins including soft tissue, blood vessels, nerves, and bone. Special studies may be necessary depending on whether the tumor is untreated or has been previously treated.", "questions": [ "What are some special studies that may be helpful when evaluating untreated tumors?", "How should margins be sampled when evaluating tumors?", "Why is it important to submit all lymph nodes found during the evaluation process?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 261, "text": "243\n13\nSmall Biopsies\nSmall biopsies are minute tissue fragments either taken by pinching and tearing tissue (e.g., endomyo\u00ad\ncardial, gastrointestinal, bladder, synovium, larynx, or lung) or with a core needle biopsy (e.g., liver, \nkidney, bone marrow, prostate, and breast) for a wide variety of reasons (e.g., malignancy, infection, \n\u00adinflammatory diseases, radiologic lesions, transplant rejection). The tissue is usually unidentifiable as to \nanatomic site.\nBiopsies of the small bowel, breast, heart, liver, bladder, lung (transbronchial), colon, synovium, brain, \nstomach, temporal artery, bone marrow, kidney, and skin have additional processing protocols in their \nrespective chapters.\nBecause there is limited tissue, the initial sections of the block must be made so as to conserve \ntissue for necessary studies. For example, if the biopsy is of a suspected malignancy, it is often helpful \nto order unstained slides suitable for immunoperoxidase studies when the first H&Es are cut.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nPROCESSING THE SPECIMEN\n\t1.\t \u0007Record:\n\t \u2022\t \u0007Number of fragments (if many, give an estimate, not \u201cmany\u201d or \u201cnumerous\u201d)\n\t \u2022\t \u0007Aggregate dimensions\n\t \u2022\t \u0007Greatest dimension of largest fragment. If there are only a few fragments (e.g., two to three), the \ndimensions of each one may be given.\nTABLE 13\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR SMALL BIOPSIES\nClinical indication for the procedure\nType of biopsy (e.g. needle, forceps, wedge, \ncurettage, punch)\nAny unusual features of the clinical presentation\nOrgans resected or biopsied (including location and number \nof lesions present)\nNumber of biopsies or fragments\nGross appearance of the organ/tissue/lesions sampled as \nobserved by the surgeon, if unusual\nAppearance of the clinical lesion\nPrior surgery or biopsies and the pathologic diagnoses\nPrior malignancies (type, location, stage)\nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic appearance of tissues)\nImmune system status\nCurrent or recent pregnancy", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_261.png", "summary": "Small biopsies are minute tissue fragments taken for various reasons from different anatomical sites, with additional processing protocols for specific organs. Careful handling is necessary due to limited tissue availability.", "questions": [ "What are the different types of small biopsies mentioned in the text?", "Why is it important to conserve tissue in small biopsies?", "How can prior clinical history impact the processing and interpretation of small biopsy specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 262, "text": "244\nSMALL BIOPSIES\u2003 Processing the Specimen\nAt sign-out it is important to correlate the number of fragments on the slide with the number of tissue \nfragments received to ensure that all tissue fragments are represented microscopically.\nCheck the sides and lid of the container, as well as any gauze or tissue paper, for small fragments that \nmay be attached. Every piece of tissue is important because sometimes a diagnosis can be made on only \na few cells!\nOn the other hand, small specimens are particularly susceptible to cross contamination from other \nspecimens. The work area must be kept fastidiously clean and all \u00addissecting tools cleaned between cases.\nSpecimens may be submitted on gauze; this can introduce artifacts into tissues that look like perpen\u00ad\ndicular empty hatchmarks under the microscope, corresponding to the weave of the cloth.\n\t2.\t \u0007Record the shape of the fragments \u2013 needle cores or small irregular fragments.\n\t3.\t \u0007Record the color and consistency of the fragments.\n\t \u2022\t \u0007White, firm \u2013 usual appearance of tissue\n\t \u2022\t \u0007Yellow, soft \u2013 adipose tissue, may fragment and not be seen well on slides\n\t \u2022\t \u0007Red, friable \u2013 usually blood clot, may not survive processing\n\t \u2022\t \u0007Brown, hard \u2013 may be foreign matter (e.g., seeds) sometimes present in colon biopsies\nThese features can be used to distinguish tissue fragments from non-tissue material in order to cor\u00ad\nrelate with the number of tissue fragments on the final slides.\n\t4.\t \u0007Small biopsy specimens should not be cut or inked. If the specimen is large enough to orient (e.g., \ncolon polyps, skin, or temporal arteries), see the specific section concerning this type of biopsy.\n\t5.\t \u0007All small biopsies must be supported within the cassette to prevent tissue loss during processing. All \nfragments are submitted. Small fragments may be dipped in eosin to make them more visible.\n\t \u2022\t \u0007Lens paper can be used for very small specimens or cell blocks. The paper must be thin enough for \nformalin to penetrate easily. Cut each sheet of lens paper into four 2\u201d \u00d7 3\u201d pieces. Wet the paper \nwith formalin. Tissue sticks to dry paper and this causes fragmentation and artifacts. Place the speci\u00ad\nmen or specimens in the center of the paper. The tissue should not overlap. Needle biopsies should \nbe aligned in a row. If necessary, use more than one cassette for large and/or numerous biopsies. \nFold the paper in thirds over the tissue (Fig. 13-1). Fold over the ends. Overfolded specimens may \nbe difficult to unfold for tissue embedding and underfolding may result in the paper opening during \nprocessing with loss of the specimen. A sponge can be placed in the cassette with the paper packet \nto keep the specimens flat and aligned.\nFold in thirds over the cores\nSmall biopsies\nPlace the packet in a cassette\nAdd lid and place in formalin\nFold over the ends\nFigure 13\u20131.\u2002 Preparation of small biopsies for pathology.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_262.png", "summary": "When processing small biopsy specimens, it is important to ensure all tissue fragments are represented microscopically and to prevent cross contamination. Various features such as color and consistency can help distinguish tissue fragments from non-tissue material.", "questions": [ "How can the number of tissue fragments on the slide be correlated with the number of tissue fragments received?", "What are some potential artifacts that may be introduced when specimens are submitted on gauze?", "Why should small biopsy specimens not be cut or inked?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 263, "text": "SMALL BIOPSIES\u2003 Sample Dictations\n245\n\t \u2022\t \u0007Nylon specimen bags can be used in the same manner as lens paper. Make sure the fragments are \nnear the bottom of the bag. Fold two times and place in a cassette. Specimen bags can also be used \nfor cell blocks. The cell suspension is poured through the bag. The filtered formalin should be col\u00ad\nlected in a clean specimen cup in order to retrieve specimens in case of spillage.\n\t \u2022\t \u0007Sponges hold the tissue flat and aid in embedding the tissue in the same plane. However, sponges \ncan create artifacts within the tissue (i.e., angulated \u201choles\u201d within the tissue). They cannot be used \nfor cell blocks. Wrapping the tissue in paper before placing between sponges may minimize tissue \ndistortion.\n\t \u2022\t \u0007Most types of biopsies have standard numbers of levels and special stains (see Chapter 3). Non-\nroutine small biopsies (i.e., none of those listed above) may be from tumors at unusual locations \nor unusual disease processes. Additional levels and unstained slides should be considered for \nthese specimens according to the clinical history, in order to conserve tissue when the block \nis first cut.\nSAMPLE DICTATIONS\nExample 1.\u2002 Received in formalin labeled with the patient\u2019s name, unit number, and \u201cheart biopsies\u201d \nare five fragments of soft tissue, each measuring approximately 0.4 \u00d7 0.3 \u00d7 0.3 cm. Three of the fragments \nare brown, one is white, and one is friable and red/brown.\nCassette #1: five frags, ESS\nExample 2.\u2002 Received in formalin labeled with the patient\u2019s name, unit number, and \u201cPNBX left\u201d are \nthree white/tan needle biopsies measuring 0.1 cm in diameter and 0.7, 0.5, and 0.3 cm in length.\nCassette #1: three frags, ESS.\nExample 3.\u2002 The specimen consists of three parts, all received in formalin labeled with the patient\u2019s \nname and unit number.\nThe first part is labeled \u201cTransverse \u201d and consists of a single fragment of tan soft tissue (0.4 \u00d7 0.4 \u00d7 \n0.4 cm).\nCassette #1: one frag, ESS. \nThe second part is labeled \u201cSigmoid\u201d and consists of two fragments of white/tan soft tissue, each \napproximately 0.3 \u00d7 0.3 \u00d7 0.3 cm.\nCassette #2: two frags, ESS. \nThe third part is labeled \u201cRectum\u201d and consists of three fragments of white/tan soft tissue, each \napproximately 0.4 \u00d7 0.3 \u00d7 0.2 cm and one fragment of friable tan/brown material measuring 0.2 \u00d7 0.2 \u00d7 \n0.2 cm.\nCassette #3: four frags, ESS.\nExample 4.\u2002 Received in formalin labeled with the patient\u2019s name, unit number, and \u201cBladder tumor\u201d \nare approximately 20 fragments of soft tan/white tissue with a micropapillary architecture, measuring in \naggregate 0.7 \u00d7 0.7 \u00d7 0.3 cm, the largest fragment measuring 0.4 \u00d7 0.4 \u00d7 0.4 cm.\nCassette #1: mult frags, ESS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_263.png", "summary": "The page provides guidance on handling small biopsies, including the use of specimen bags, sponges, and considerations for non-routine specimens. Sample dictations for various types of biopsies are also included.", "questions": [ "What are the advantages and disadvantages of using specimen bags for small biopsies?", "How can tissue distortion be minimized when using sponges for embedding tissue?", "Why is it important to consider additional levels and unstained slides for non-routine small biopsies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 264, "text": "246\n14\nBone and Joints\nBones are common surgical specimens that may be submitted after reconstructive or joint replacement \nsurgery, as part of a larger soft tissue resection, to diagnose metabolic bone disease, or after resection of \ntumors primary to bone.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nTOTAL JOINT ARTHROPLASTY (HIPS AND KNEES)\nBone, cartilage, and adjacent soft tissues are removed during artificial joint replacements, usually per\u00ad\nformed to treat degenerative joint disease, but also performed in patients with rheumatoid arthritis, \nosteonecrosis, traumatic fractures, and pathologic fractures.\nClinically important unsuspected diseases may be found in \u201croutine\u201d specimens for degenerative joint \ndisease (e.g., hemochromatosis, rheumatoid arthritis, gout, tumors, infection, osteonecrosis, Gaucher \ndisease, and others). However, the incidence of such findings is small, ranging from <1% to 8% in dif\u00ad\nferent studies.1-7\nTABLE 14\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR BONE AND JOINT SPECIMENS\nClinical indication for the procedure\nReason for the procedure (e.g., degenerative joint disease, \nfailed joint replacement, fracture, infection, malignancy, \nosteonecrosis, evaluation of metabolic bone disease)\nAny unusual features of the clinical presentation\nOrgans resected or biopsied (including location \nand number of lesions present)\nGross appearance of the organ/tissue/lesions \nsampled as observed by the surgeon, if unusual\nJoint disease (e.g., gout, rheumatoid arthritis)\nPrior surgery or biopsies and the pathologic \n\u00addiagnoses\nHistory of Paget disease of bone, bone infarction, or \n\u00adosteomyelitis\nPrior malignancies (type, location,\n stage)\nFamily history of Ollier disease, Mafucci syndrome, \n\u00adRothmund-Thomsom syndrome, etc.\nPrior treatment (radiation therapy, \nchemotherapy, drug use that can change the \nhistologic appearance of tissues)\nImmune system status\nCurrent or recent pregnancy", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_264.png", "summary": "Bone and joint specimens are commonly submitted for diagnosis after reconstructive or joint replacement surgery, soft tissue resections, or to diagnose metabolic bone disease or tumors primary to bone.", "questions": [ "What are some clinically important diseases that may be found in 'routine' specimens for degenerative joint disease?", "What is the range of incidence for finding clinically important diseases in bone and joint specimens?", "What are some relevant clinical history factors to consider for bone and joint specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 265, "text": "247\nBONE AND JOINTS\u2003 Total Joint Arthroplasty (Hips and Knees)\nThe method of examining well-defined \u201croutine\u201d specimens (defined by therapeutic procedures for \ndegenerative joint disease in patients without a history of malignancy [or risk factors for malignancy such \nas prior radiation], infection, or immunocompromise, and with normal gross findings) should be made \njointly among pathologists and clinicians and, in accordance with Joint Commission standards,8 should \nbe part of a written hospital or laboratory policy (see also \u201cGross Examination\u201d). Alternatives are gross \nexamination by the surgeon, gross examination by both surgeon and pathologist, or gross and micro\u00ad\nscopic examination by the pathologist. Even if not all specimens are examined microscopically, this is \nalways an option that can be requested by the surgeon.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Describe the number of fragments of bone (estimate if many), size in aggregate, range of sizes. \nDescribe any recognizable portions of bone: femoral head (see next section), tibial plateau, femoral \ncondyles.\n 2.\t \u0007Describe articular surface including color (usually white, black if ochronosis, brown/green if hemo\u00ad\nchromatosis), crystalline deposits (both gout and chondrocalcinosis will produce chalky white depos\u00ad\nits), erosions or pits, or eburnation (= bone that is markedly thickened and smooth [like ivory] due \nto complete loss of the overlying cartilage - do not mistake eburnated bone for cartilage!). Describe \nsubchondral cysts or osteophytes if present.\n 3.\t \u0007Describe the number of fragments of soft tissue (estimate if many), size in aggregate, range of sizes.\n 4.\t \u0007Describe the color and consistency of the soft tissue:\n\t\n\u2022\t \u0007Normal = white/tan, delicate, villous\n\t\n\u2022\t \u0007Hemochromatosis = brown/green\n\t\n\u2022\t \u0007\u03b22 microglobulin amyloidosis = tan/yellow, firm, and homogenous\n\t\n\u2022\t \u0007Giant cell tumor, diffuse type (pigmented villonodular synovitis or PVNS) = red/brown and shaggy \n(delicate villi with small nodules may be appreciated if the tissue is floated in saline). Necrotic foci \nmay appear yellow due to the presence of histiocytes.\n\t\n\u2022\t \u0007Gout or chondrocalcinosis = chalk white crystalline material. See the separate section on \u201cSynovium\u201d \nfor a more complete description and special processing of unusual specimens.\n 5.\t \u0007The bone is separated from the soft tissue. Submit one section of soft tissue including synovium if \npossible. Normal synovium will look like a thin delicate membrane. Fix the bone overnight in forma\u00ad\nlin and decalcify the following day. All decalcification procedures must be documented in the gross \ndescription.\n 6.\t \u0007Serially section through the decalcified bone to find the best diagnostic areas. One fragment of bone \nshould include the junction of normal and abnormal cartilage and the other fragment should be from \nthe periphery to include exostosis and/or pannus. The sections should be about 2 \u00d7 1 cm in size with \nthe short axis perpendicular to the cartilage surface including 5 to 10 mm of subchondral bone.\nIf osteonecrosis is suspected, the entire specimen must be serially sectioned to look for the characteristic \ngross findings (see below). Submit sections to document the interface of normal and abnormal bone. \nRadiography of the specimen may be helpful to identify the area of necrotic bone.\nSPECIAL STUDIES\nCrystal Disease.\u2002 Chalky white deposits in soft tissue may be due to urate crystals (gout) or calcium \npyrophosphate dihydrate crystals (= calcium pyrophosphate dihydrate deposition disease [CPPD] = \npseudogout = chondrocalcinosis). Tissue must be saved in absolute (100%) alcohol because these \ncrystals are soluble in aqueous solutions. The tissue must be hand processed and stained with an \nanaqueous Wright stain. Crystals can also be visualized in tissue smears, frozen sections, or unstained \nsections.\nCrystals sometimes survive routine processing in aqueous solutions but are lost in the final staining \nsteps. Look for preserved crystals in tissue folds if present. An unstained slide may also be requested and \nexamined under polarized light after deparaffinizing.\nCrystals can also be examined directly by smearing the unfixed crystals on a slide, or by suspending in \nabsolute alcohol as necessary (remember that they will dissolve in water). If the crystals are viewed using \na compensating first-order red filter under polarized light, uric acid can usually be distinguished from \nCPPD crystals. The crystals are aligned parallel to the line on the compensating filter. If not available in \nthe pathology department, most rheumatologists will have such a microscope available for examination", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_265.png", "summary": "The page provides guidelines for examining routine specimens from total joint arthroplasty procedures, including descriptions of bone and soft tissue features.", "questions": [ "What are the different options for examining routine specimens from total joint arthroplasty?", "How should the articular surface be described during the examination?", "What are the specific features to look for when describing the soft tissue in these specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 266, "text": "248\nBONE AND JOINTS\u2003 Total Joint Arthroplasty (Hips and Knees)\nof synovial fluids. Crystals will polarize in properly fixed and stained histologic sections, but positive and \nnegative birefringence cannot be reliably performed on fixed tissue (see Chapter 9 for a description of \npolarization).9,10\n\t \u2022\t \u0007Uric acid: needle shaped, strong negative birefringence, bright yellow\n\t \u2022\t \u0007CPPD crystals: rhomboid, weakly positive birefringence, less bright and blue\nCalcium oxalate crystals can be seen in bone, articular cartilage, and bone marrow in patients with \nprimary (familial) oxalosis or secondary oxalosis (usually due to chronic renal failure). The crystals are \nneedle shaped in radially arranged clusters and are both refractile and polarizable. They can dissolve in \nformalin, but only after several days. The type of crystal can be identified by chemical analysis, x-ray dif\u00ad\nfraction, or electron diffraction.\nMetastasis.\u2002 Determine from the clinical history whether there is a known primary malignancy. If \nnot, additional studies may be warranted (e.g., snap freezing, EM, or immunohistochemistry). Remove \nas much soft tissue as possible to avoid exposing potential tumor to decalcification.\nGROSS DIFFERENTIAL DIAGNOSIS\nDegenerative Joint Disease.\u2002 The cartilage surface shows fibrillation and loss over the center of the \nfemoral head or over the tibial plateau. The exposed bone becomes thickened and smoothly polished \n(\u201ceburnated\u201d or \u201clike ivory\u201d) and can be mistaken for a cartilage surface. Fractures through articular bone \nresult in subchondral cysts and collapse of the bone. The femoral head is often flattened and misshapen. \nOsteophytes commonly form around the edge of the articular surface. The soft tissue is relatively unaf\u00ad\nfected and may be fibrotic.\nRheumatoid Arthritis.\u2002 Patients usually undergo arthroplasty after significant secondary degenera\u00ad\ntive changes have occurred. Thus, most will show the changes of degenerative joint disease and features \nof rheumatoid arthritis may be subtle or absent. Findings characteristic of rheumatoid arthritis include an \nedematous hyperplastic synovium with growth over the cartilage surface to form a pannus.\nGout or CPPD.\u2002 Chalky white crystalline deposits are present in soft tissue, cartilage, and sometimes \nerode bone. The synovium becomes fibrotic, thickened, and hyperplastic and forms a pannus overlying \ncartilage. It is usually not possible to distinguish gout from chondrocalcinosis grossly in mid-sized joints \nin which both are common. However, CPPD crystals may preferentially be found within the cartilage and \nuric acid crystals in periarticular soft tissue. Gout is much more common in small joints of the foot and \nhand. Neither commonly affects the hip. Usually joint replacement is performed after significant secondary \ndegenerative changes have occurred (see above). Crystals should be saved in alcohol (see \u201cSpecial Studies\u201d).\nOsteonecrosis (Aseptic Necrosis, Avascular Necrosis).\u2002 Osteonecrosis of bone is a common cause \nof joint disease (approximately 10% of joint replacements) and is often bilateral. Patients are younger \nthan the typical patient with degenerative joint disease (averaging 55 vs. 67 years) and often have pre\u00ad\ndisposing conditions such as steroid use, sickle cell disease, or alcoholism. The pathogenesis is poorly \nunderstood but is thought to result from ischemic infarction of subchondral bone.\nThere is a characteristic wedge-shaped area of pale yellow necrotic bone below the cartilage sur\u00ad\nface. A band of hyperemia is often present below this area. Usually the overlying cartilage will have \nseparated away from the bone. The infarcted bone may collapse with distortion of the cartilage and \nresultant degenerative changes. Radiographs of bone slices can be helpful to look for areas of abnormal \nmineralization.\nMetastatic Disease.\u2002 A joint replacement is sometimes performed to repair a known or suspected \npathologic fracture, generally within the femur. The metastatic tumor may be subtle and only apparent \nafter histologic examination of numerous sections. The bone destruction observed radiologically is usu\u00ad\nally due to soluble factors produced by the tumor cells and not replacement of bone marrow by tumor \nper se. Therefore, in such cases histologic sampling of the fracture site is necessary to evaluate the pres\u00ad\nence of tumor. If a pathologic fracture is strongly suspected either clinically or grossly, and the primary \nsite is unknown, consider taking tissue for special studies (e.g., snap freezing, EM). If \u00adpossible, separate \nsoft tissue and submit separately as decalcification adversely affects some antigens (e.g., ER and PR).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_266.png", "summary": "The page discusses the identification of crystals in synovial fluids and tissues, as well as differential diagnoses for conditions affecting bones and joints.", "questions": [ "How are different types of crystals identified in synovial fluids and tissues?", "What are the key differences in gross findings between Degenerative Joint Disease, Rheumatoid Arthritis, Gout or CPPD, and Osteonecrosis?", "What additional studies may be needed to determine metastasis in cases without a known primary malignancy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 267, "text": "249\nBONE AND JOINTS\u2003 Total Joint Arthroplasty (Hips and Knees)\nMICROSCOPIC SECTIONS\n\t\n\u2022\t \u0007Soft tissue: One section including any grossly recognizable synovium. If a metastatic deposit is \nsuspected, submit as much soft material from the possible tumor and/or fracture site as possible that \nwill not need decalcification.\n\t\n\u2022\t \u0007Bone: One section including the junction of normal and abnormal cartilage and one from the \nperiphery.\nIf osteonecrosis is known or suspected, submit one to two sections of necrotic bone including interface \nwith normal bone and the area below the detached cartilage.\n\t\n\u2022\t \u0007Crystals: If crystals are present, submit one section fixed in absolute alcohol for special anaqueous \nprocessing. Order 1 H&E, 1 anaqueous Wright stain, and one unstained slide.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cleft total knee\u201d are multiple \nfragments of bone (in aggregate 5 \u00d7 5 \u00d7 3 cm, largest 2 \u00d7 1 \u00d7 1 cm) and soft tissue (4 \u00d7 3 \u00d7 2 cm, largest \n3.5 \u00d7 2 \u00d7 1 cm). The bone fragments include recognizable portions of the tibial plateau and femoral con\u00ad\ndyles. The articular surface is markedly roughened with areas of cartilage loss and eburnation of the bony \nsurface. The soft tissue is tan/pink and includes fragments of meniscus. The bone is fixed and decalcified.\nCassette #1: bone with articular surface, 4 frags, RSS.\nCassette #2: soft tissue, 3 frags, RSS.\nSpecimens with Intact Femoral Heads\n 1.\t \u0007The femoral head is cut into thirds, parallel to the long axis, with the bone saw. The central section \nmust be thin, approximately 0.5 cm in width.\n 2.\t \u0007Describe the femoral head including dimensions, shape (flattened, round), cartilage surface (smooth \nand glistening, erosions, pits, eburnation of bone surface, fibrillation of cartilage, pannus formation), \ndetachment of cartilage (as in osteonecrosis), presence of exostoses. Describe the quality of the bone \n(osteoporotic, sclerotic, pale as in osteonecrosis) and subchondral cysts.\n 3.\t \u0007Describe the resection margin including surface (flat and smooth if surgical, jagged and with medul\u00ad\nlary hemorrhage if fracture), quality of adjacent bone (osteoporotic, sclerotic, or soft \u2013 may indicate \nmetastatic tumor). If the fracture site is grossly or clinically suspicious for a pathologic fracture, save as \nmuch soft tissue from this site as possible in a cassette without bone (to avoid tissue alterations associ\u00ad\nated with decalcification) and consider taking tissue for special studies (see above).\n 4.\t \u0007Describe soft tissue (see description above) and submit one cassette including synovium if possible.\n 5.\t \u0007Fix the femoral head in formalin overnight and decalcify the following day.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Soft tissue: One section including any grossly recognizable synovium.\n\t \u2022\t \u0007Bone: One section including the junction of normal and abnormal cartilage and one from the \nperiphery.\n\t \u2022\t \u0007Fracture site: Two representative sections in one cassette from the fracture site. If sufficient soft \ntissue (i.e., possible tumor) is present, submit an additional cassette of nondecalcified tissue.\nSAMPLE DICTATION - HIP REPLACEMENT FOR DEGENERATIVE JOINT DISEASE\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cleft hip\u201d is a 5 \u00d7 5 \u00d7 4 cm flattened \nfemoral head and attached neck with a smooth resection margin. The articular surface is covered by \nirregularly surfaced cartilage with areas of cartilage loss and eburnation of the underlying bone. Multiple \nperipheral osteophytes are present. The bone is fixed and then decalcified. Also received are multiple \nfragments of pink/tan fibrous tissue measuring in aggregate 3 \u00d7 3 \u00d7 2 cm.\nCassette #1: Joint surface, 4 frags, RSS.\nCassette #2: Soft tissue, 3 frags, RSS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_267.png", "summary": "This page provides detailed instructions on the microscopic sections to be taken during total joint arthroplasty for hips and knees, including soft tissue, bone, and crystals.", "questions": [ "What specific sections should be included in the microscopic examination of soft tissue during total joint arthroplasty?", "How should the femoral head be prepared and described in the specimen with intact femoral heads?", "Why is it important to save soft tissue from a suspicious fracture site during total joint arthroplasty?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 268, "text": "250\nBONE AND JOINTS\u2003 Total Joint Arthroplasty (Hips and Knees)\nSAMPLE DICTATION - HIP REPLACEMENT AFTER FRACTURE\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cright hip\u201d is a 5 \u00d7 5 \u00d7 3 cm round \nfemoral head with a smooth white cartilage surface. The femoral neck resection margin is irregular and hemor\u00ad\nrhagic. There are multiple smaller fragments of irregular bone measuring in aggregate 3 \u00d7 3 \u00d7 1 cm. There are \nno areas of soft tissue within the bone. The bone trabeculae are markedly thinned. The bone is fixed and then \ndecalcified. Also received are multiple fragments of pink/tan fibrous tissue measuring in aggregate 3 \u00d7 3 \u00d7 2 cm.\nCassette #1: Fracture site, 2 frags, RSS.\nCassette #2: Joint surface, 2 frags, RSS.\nCassette #3: Soft tissue, 3 frags, RSS.\nSAMPLE DICTATION - HIP REPLACEMENT FOR AVASCULAR NECROSIS\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cright hip\u201d is a 4.5 \u00d7 4 \u00d7 4 cm deformed \nflattened femoral head with a smooth resection margin. There is a wedge-shaped area of pale yellow bone \nimmediately beneath the cartilage surface measuring 2 \u00d7 2 \u00d7 1 cm with a red/brown border. The overlying \ncartilage is intact but has pulled away from this area leaving a gap. The sliced section is radiographed. The \nbone is fixed and then decalcified. The remainder of the cartilage surface is smooth and unremarkable. Also \nreceived are multiple fragments of pink/tan fibrous tissue measuring in aggregate 3 \u00d7 2 \u00d7 2 cm.\nCassettes #1 - 2: Area of probable necrosis, 4 frags, RSS.\nCassette #3: Joint surface, 2 frags, RSS.\nCassette #4: Soft tissue, 3 frags, RSS.\nRevision Total Joint Arthroplasty\nAbout 5% of prosthetic joints fail, either from mechanical loosening or due to infection. It may be difficult \nto clinically distinguish between these two possibilities as the presentation may be similar and false positive \nand negative culture results are possible. Prosthetic joints that have failed mechanically may be removed \nand replaced in the same procedure. If infection is present, drainage or removal of the prosthesis may be \nindicated and replacement may be delayed until after treatment. The most common acute pathogens are \nS. epidermidis and S. aureus with gram-negative bacilli being more common in later infections. A frozen \nsection evaluation of periarticular soft tissue may be requested if infection is suspected (see Chapter 6).\nPROCESSING THE SPECIMEN\n \n1.\t \u0007The specimen usually consists of small fragments of bone, fibrous soft tissue, and, often, fragments \nof bone cement. Bone cement is usually light brown, homogeneous in appearance, hard, and may \nbe difficult to distinguish from bone. The soft tissue may be gray or black due to metallic debris.\n \n2.\t \u0007Describe the number of fragments of bone (estimate if many), size in aggregate, range of sizes. \nHowever, bone may not be present.\n \n3.\t \u0007Describe the number of fragments of soft tissue (estimate if many), size in aggregate, range of sizes, \ncolor, presence of necrosis. If infection is suspected clinically or by gross examination, and cultures \nhave not yet been sent, send tissue for bacterial culture.\n \n4.\t \u0007The explanted prosthesis is described including number of parts, hip or joint prosthesis, identifica\u00ad\ntion markings (e.g., serial numbers, brand names), and the presence of any marked abnormalities \n(e.g., broken metal components, erosions, ridges, or pits in the articular surfaces).\n \n5.\t \u0007The bone is separated from the soft tissue. Submit one section of soft tissue, including synovium, \nif possible. Fix the bone overnight in formalin and decalcify the following day. All decalcification \nprocedures must be documented in the gross description.\nGROSS DIFFERENTIAL DIAGNOSIS\nDetritic Synovitis.\u2002 Occasionally, there will be an exuberant papillary proliferation of synovium with \nhemosiderin deposition in response to foreign material that grossly mimics pigmented villonodular syno\u00ad\nvitis (PVNS or giant cell tumor, diffuse type). However, unlike PVNS, there will be a history of an", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_268.png", "summary": "The page discusses dictations for hip replacement after fracture and for avascular necrosis, as well as the process for revision total joint arthroplasty.", "questions": [ "How can you distinguish between mechanical loosening and infection in failed prosthetic joints?", "What are the common pathogens associated with infections in prosthetic joints?", "How is periarticular soft tissue evaluated for infection suspicion?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 269, "text": "251\nBONE AND JOINTS\u2003 Curettings and Needle Biopsies, Bone Tumors\n\u00adartificial joint, foreign material is present, and the process is usually superficial and does not extend \ndeeply into soft tissue.\nForeign Material from Implants.\u2002 Numerous types of foreign material derived from the implant \ncan be found around failed prostheses and include bone cement (with barium to make the material radi\u00ad\nopaque), metal fragments, polyethylene, methylmethacrylate, silicone, and ceramic (see \u201cNoncellular \nMaterial in Histologic Sections\u201d). The tissue may be black due to deposits of oxidized metal.\nInfection.\u2002 The soft tissue from infected joints may be necrotic and purulent. Cultures should be sent \neither by the surgeon or the pathologist. Some infections may not be apparent grossly.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Soft tissue: One section including any grossly recognizable synovium.\n\t \u2022\t \u0007Bone: One section.\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cleft hip\u201d are multiple fragments \nof soft tissue and bone. There are five bone fragments, measuring in aggregate 3 \u00d7 2 \u00d7 2 cm. No articular \nsurfaces are present. The bone is fixed and decalcified prior to submission. There are approximately 20 \nfragments of tan/white fibrous soft tissue without recognizable synovium.\nAlso received is a joint prosthesis consisting of an acetabular component consisting of a white pros\u00ad\nthetic socket (6 \u00d7 6 \u00d7 4 cm) inscribed with \u201cABDC\u201d and femoral component consisting of a metallic ball \nattached to a stem (15 \u00d7 3 \u00d7 2 cm). A fragment of brown bone cement with a smooth outer surface is also \npresent (4 \u00d7 2 \u00d7 2 cm).\nCassette #1: Bone, 4 frags, RSS.\nCassette #2: Soft tissue, 3 frags, RSS.\nCORE BIOPSY FOR ASEPTIC (AVASCULAR) NECROSIS\nCores of bone may be submitted from patients with clinical and radiologic osteonecrosis. These cores \nare taken through the femoral head and into the area of necrosis in order to promote revascularization \n(\u201cdecompression\u201d), and are generally used for treatment and not diagnosis. There should be an area of \nosteonecrosis at one edge of the biopsy. These core biopsies are fixed in formalin and then gently decalci\u00ad\nfied. If the specimen will not fit in a cassette in entirety, section the specimen longitudinally.\nBIOPSY, METABOLIC BONE DISEASE\nNeedle or core bone biopsies are sometimes submitted from patients with metabolic bone disease (osteo\u00ad\nmalacia, osteoporosis, hyperparathyroidism, effects of long-term hemodialysis, etc) with a request for \nmetabolic bone \u00adstudies.\nThe evaluation of metabolic disease requires sectioning of nondecalcified bone, special stains, and \nmorphometry. These techniques are generally performed by a specialty laboratory. The specialty labora\u00ad\ntory will provide instructions for the fixation and transportation of these specimens.\nCURETTINGS AND NEEDLE BIOPSIES, BONE TUMORS\nBiopsies of bone lesions are occasionally performed for both benign and malignant lesions. See Chatper \n6 for a description of how bone biopsies are processed for frozen sections. See Chapter 12 and below for \nlarger specimens.\nPROCESSING THE SPECIMEN\n \n1.\t \u0007Determine the type of specimen: needle biopsy or curettings. Grossly examine for the presence of \nbone and soft tissue. Most cases have at least small foci of soft, non-calcified non-necrotic tissue \nthat can be taken for special studies. However, if a definitive diagnosis of lesional tissue has not", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_269.png", "summary": "The page discusses the presence of foreign material from implants, infections in joints, and procedures for core biopsies related to bone diseases.", "questions": [ "What types of foreign materials can be found around failed prostheses?", "How are core biopsies used in the treatment of osteonecrosis?", "What techniques are used for evaluating metabolic bone diseases in needle or core bone biopsies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 270, "text": "252\nBONE AND JOINTS\u2003 Bone Resections for Tumors\nbeen made intraoperatively, most of the tissue should be reserved for routine sections and tissue \nshould not be taken for studies that will preclude examination of the tissue (e.g., cytogenetics). \nThe clinical and radiologic differential diagnosis is helpful in guiding apportionment of tissue.\n \n2.\t \u0007Fix the specimen in formalin for 2 to 4 hours depending on size.\n \n3.\t \u0007After fixation, the bone is gently decalcified for 4 to 12 hours. In unusual cases including larger \npieces of bone, it may be necessary to fix overnight, decalcify during the day (with periodic checks \nto see if the bone is soft), wash, fix again overnight, and decalcify again (up to four daily cycles) for \noptimal specimen preparation.\nSPECIAL STUDIES\nMost of these tumors are unusual and will warrant special studies. After lesional tissue has been taken for \nfomalin fixation, additional tissue can be taken for snap freezing, EM, and/or Zenker\u2019s fixation (which \ndecalcifies while preserving cytologic detail).\nIf definite lesional tissue is present, then tissue can be submitted for cytogenetics. For example, \nEwing\u2019s/PNET has a characteristic t(11;22) and extraskeletal myxoid chondrosarcoma has a characteris\u00ad\ntic t(9;22) (see Table 7-47). If no definitive lesional tissue is present, then all tissue should be examined \nhistologically.\nGROSS DIFFERENTIAL DIAGNOSIS\nIn general, gross examination of these small fragmented specimens is not helpful.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Tumor: Entire specimen up to 10 cassettes. If little tissue is available (e.g., only one cassette is sub\u00ad\nmitted), three levels are ordered.\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cfemur lesion\u201d are multiple \nirregular fragments of tan/brown tissue with minute areas of irregular bone, measuring in aggregate \n1 \u00d7 1 \u00d7 0.5 cm (the largest fragment measuring 0.4 cm in size). Frozen section examination is per\u00ad\nformed on a representative section. Tissue is apportioned for snap freezing, electron microscopy, and \ncytogenetics. The remainder of the tissue is fixed in Zenker\u2019s fixative or fixed in formalin and then \ndecalcified.\nCassette 1: Frozen section remnant, 1 frag, ESS.\nCassette 2: Tissue fixed in Zenker\u2019s, 3 frags, ESS.\nCassettes 3 - 9: Remainder of specimen in formalin and decalcified, mult frags, ESS.\nBONE RESECTIONS FOR TUMORS\nBone resections may be performed for either benign (enchondromas, osteochondromas, osteoid osteo\u00ad\nmas, bone cysts, fibrous dysplasia, giant cell tumors) or malignant (most chondrosarcomas, some osteo\u00ad\nsarcomas) lesions.11-13 The radiologic features of bone lesions are very helpful, and sometimes necessary, \nto distinguish benign from malignant tumors.\nPROCESSING THE SPECIMEN\n \n1.\t \u0007Determine the type of specimen (e.g., above-knee amputation, hip disarticulation, etc.). See the \nsection on Chapter 12 for additional information.\nGive the dimensions of each structure present including length and maximum circumference of limbs.\n \n2.\t \u0007Radiograph the intact specimen. The radiograph provides diagnostic information and is helpful to \nguide the specimen dissection.\n \n3.\t \u0007Incise the soft tissue in a plane that will demonstrate the greatest extent of the tumor. A band \nsaw can be used to bisect the specimen. Gently brush away bone dust under running water and", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_270.png", "summary": "Bone resections for tumors involve specific steps such as fixation, decalcification, and special studies. Lesional tissue can be taken for various additional studies, including cytogenetics.", "questions": [ "What are the steps involved in processing a bone resection specimen for tumors?", "Why is it important to reserve tissue for special studies like cytogenetics?", "How can the gross examination of small fragmented specimens be helpful in determining the diagnosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 271, "text": "253\nBONE AND JOINTS\u2003 Bone Resections for Tumors\n\u00adphotograph the specimen. It is useful at this point to make a diagram of the specimen to indicate \nwhere sections will be taken. For large specimens, an additional 0.5 cm parallel cut through bone \nshould be made to produce a relatively thin cut section of the tumor. This section is also photo\u00ad\ngraphed if it yields additional information.\n \n4.\t \u0007Describe the tumor including:\n \n\u2022\t \u0007Size \u2013 three dimensions\n \n\u2022\t \u0007Appearance \u2013 color, bone formation and/or cartilage formation\n \n\u2022\t \u0007Necrosis \u2013 % of tumor (areas that appear necrotic may be myxoid or edematous)\n \n\u2022\t \u0007Location \u2013 tissue compartment, region of bone (epiphysis, metaphysis, diaphysis, intramedul\u00ad\nlary, periosteal)\n \n\u2022\t \u0007Relationship to surrounding structures (bone, vessels, nerves, muscle)\n \n\u2022\t \u0007Erosion of cortex\n \n\u2022\t \u0007Extension into soft tissue (compression or true invasion)\n \n\u2022\t \u0007Extension through epiphyseal plate\n \n\u2022\t \u0007Extension into or across joint space\n \n\u2022\t \u0007Vascular involvement\n \n\u2022\t \u0007Skip metastases\n \n\u2022\t \u0007Distance from each margin.\n \n5.\t \u0007Take soft tissue sections of margins, representative structures (e.g., vessels and nerves), and any \nareas of noncalcified tumor showing relationships to soft tissues. Tumor can be taken for special \nstudies if not previously performed. Carefully search for lymph nodes and submit. Identify the \nprior biopsy site and sample this area to evaluate for soft tissue implants.\n \n6.\t \u0007Fix the entire specimen in formalin. After overnight fixation, gently decalcify the sections with \nbone. The specimen must be checked every few hours in order to avoid overdecalcification which \nwill adversely affect histologic examination.\n \n7.\t \u0007Sections are taken to show the tumor, relationship to adjacent normal bone, invasion of contiguous \nstructures (e.g., cortex, soft tissue, joint space), and margins. The location of sections taken is indi\u00ad\ncated on a diagram of the specimen. All areas of different radiologic appearance are sampled and \ncorrelated with the radiograph. For osteosarcomas and Ewing\u2019s sarcoma the extent of post therapy \ntumor necrosis is important to determine. An entire cross-section of these tumors is mapped out \nand submitted for histologic examination.\nBone dust can create artifacts that may be difficult to interpret. Orient the sections so that the por\u00ad\ntion cut by the histology laboratory will be opposite the side cut by the saw (e.g., ink one side and \nindicate the appropriate side to be sectioned).\nSPECIAL STUDIES\nMany of these tumors will be pretreated with radiation, chemotherapy, or both and will be predom\u00ad\ninantly necrotic. Special studies in general are not performed on such tumors. Cases with untreated \ntumors should have tissue sent for cytogenetic studies. Refer to Chapter 13.\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Figure 14-1.\nEwing\u2019s Sarcoma/PNET.\u2002 These tumors are generally treated with radiation and chemotherapy \nand not resected. Therefore, they will usually be diagnosed in biopsy specimens (see previous section). \nGrossly, the tumors are grayish white with indistinct borders and may have hemorrhage, cystic degenera\u00ad\ntion and necrosis. The adjacent bone is usually destroyed.\nOsteoid Osteoma.\u2002 The lesion is usually present in the cortex of a long bone and is less than 2 cm in \nsize. Grossly, it may look like a bright red or pink nodule. Radiographs of the specimen can be helpful to \ndemonstrate the characteristic central lucent zone with a rim of surrounding dense bone.\nFibrous Dysplasia.\u2002 A fusiform expansion of the bone, with thinning of the cortex and replacement \nof the bone by firm white/gray gritty tissue. Cysts and cartilage may be present in the lesion. There may \nbe a fracture site through the lesion.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_271.png", "summary": "The page discusses the process of bone resections for tumors, including specimen preparation, tumor description, soft tissue sections, fixation, and special studies.", "questions": [ "What are the key factors to consider when describing a tumor during bone resections?", "Why is it important to take soft tissue sections of margins and representative structures?", "What precautions should be taken during the decalcification process to avoid overdecalcification?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 272, "text": "254\nBONE AND JOINTS\u2003 Bone Resections for Tumors\nAneurysmal Bone Cyst.\u2002 A multiloculated cystic lesion, with cysts lined by soft brown fibrous tissue. \nThe cysts may contain blood clots. The telangiectatic variant of osteosarcoma can mimic an aneurysmal \nbone cyst radiologically and clinically. Extensive sampling may be necessary to exclude this diagnosis.\nOsteochondroma.\u2002 A mushroom shaped subperiosteal projection or exostosis from the bone surface, \nusually juxta-articular. The bone merges with cortical bone and the medullary cavities are in continuity. \nThe bone is covered by a thick cartilage cap.\nOsteosarcoma.\u2002 A destructive bone-forming tumor that often invades through the cortex and may \ninvade into adjacent soft tissue. Lytic areas may be present. The tumor replaces the normal marrow space \nwith firm tissue. Bone and/or cartilage may be present within the tumor mass.\nChondrosarcoma.\u2002 Usually appears as a lobulated grayish white or blue tumor mass that often is \ncalcified. The tumor may invade into or through normal bone. Areas of necrosis may be present.\nEnchondroma.\u2002 An intramedullary cartilagenous neoplasm consisting of multiple lobules of cartilage \nwithin bone.\nGiant Cell Tumor.\u2002 A well-defined lesion within the marrow space consisting of homogeneous tan/\npink tissue. Hemorrhage and necrosis may be present.\nTumors after Treatment.\u2002 Treated tumors may be predominantly necrotic or can be replaced by \ndense fibrous tissue. It may be difficult to find diagnostic areas.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Tumor: At least 1 section per cm showing relationship to cortex, medulla, adjacent joint, soft tissue.\nOsteosarcomas and Ewing sarcoma cases that have been previously treated are blocked out in a com\u00ad\nplete cross section in order to evaluate the extent of necrosis. The location of blocks of tissue \nshould be recorded on a diagram. Additional blocks are taken perpendicular to the cross section \n 1. Ewing\u2019s sarcoma, lymphoma,\n \nmyeloma\n 2. Osseofibrous dysplasia,\n \nadamantinoma\n 3. Osteroid osteoma\n 4. Fibrous dysplasia\n 5. Chondromyxoid fibroma\n 6. Nonossifying fibroma\n 7. Bone cyst, osteoblastoma\n 8. Osteochondroma\n 9. Osteosarcoma\n10. Enchondroma, chondrosarcoma\n11. Giant cell tumor\n12. Chondroblastoma\n1\n2\n3\n4\n5\n6\n7\n8\n9\n10\n11\n12\nMETAPHYSIS\nDIAPHYSIS\nEPIPHYSIS\nFigure 14\u20131.\u2002 Most frequent locations of common osseous lesions.\u2002 (From Fechner RE, Mills SE: AFIP Atlast of Tumor \nPathology: Tumors of the Bones and Joints, 3rd series, fascicle 8. Washington, DC, Armed Forces Institute of Pathology, \n1993.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_272.png", "summary": "This page discusses various bone tumors and lesions, including aneurysmal bone cyst, osteochondroma, osteosarcoma, chondrosarcoma, enchondroma, and giant cell tumor.", "questions": [ "How can the telangiectatic variant of osteosarcoma mimic an aneurysmal bone cyst?", "What are the key characteristics of osteosarcoma and chondrosarcoma?", "Why is it important to extensively sample an aneurysmal bone cyst to exclude the diagnosis of telangiectatic osteosarcoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 273, "text": "255\nBONE AND JOINTS\u2003 Bone Resections for Tumors\nto determine the extent of tumor in three dimensions. Blocks of tissue are also taken from areas \nthat may be less susceptible to chemotherapy: soft tissue extension, tumor/nodal tissue interface, \ncortex, subcortical marrow, pericartilaginous regions, and areas surrounding hemorrhagic necrosis \nand ligaments.\nOther types of tumors do not need to be mapped in such detail. At least one section per cm should be \ntaken including all unusual appearing areas and satellite lesions.\n\t \u2022\t \u0007Margins: Usually will include both soft tissue and bone.\n\t \u2022\t \u0007Normal structures: Representative sections of all normal structures (e.g., major vessels, major \nnerve trunks).\n\t \u2022\t \u0007Lymph nodes: Submit all lymph nodes found (see Chapter 27).\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name, unit number, and \u201cleft distal femur\u201d is an above-the-knee \namputation with disarticulation of the knee (12 \u00d7 9 \u00d7 7 cm). The distal femur is 12 cm in length and surrounded \nby skeletal muscle. Centered within the metaphysis is a tan/yellow tumor (7.8 \u00d7 7 \u00d7 7 cm) that occupies the \nmajority of the medullary cavity. The tumor appears to be entirely viable without gross areas of necrosis \nor hemorrhage. The tumor invades through the cortex medially, laterally, anteriorly, and posteriorly, and \nextends into soft tissue medially to form a soft tissue mass (2 \u00d7 1.8 \u00d7 0.4 cm). The tumor does not grossly \ninvolve the joint space. The tumor is located 3.5 cm from the proximal surgical resection margin, 0.4\u00a0cm \nfrom the posterior and lateral margins, and 0.1 cm from the anterior and medial margins. The tumor is 1 cm \nfrom the distal resection margin which consists of the grossly unremarkable cartilage surface of the distal \nfemur. There is an attached skin ellipse over the anterior/medial portion of the specimen, measuring 9.3 \n\u00d7 1.1 cm, with a centrally located well-healed surgical scar measuring 7.5 cm. There is a hemorrhagic \nbiopsy cavity (1 \u00d7 1 \u00d7 0.6 cm) located 4.5 cm deep to the skin surface and adjacent to the tumor. The \nfemoral artery and accompanying nerves and vein are not present. The specimen is radiographed. A dia\u00ad\ngram is prepared with the location of sections marked. Sections containing bone are fixed and decalcified \nprior to submission.\nCassettes 1-15: Complete cross section of tumor including relationship to cortex, submitted from \nproximal to distal, 15 frags, RSS.\nCassette 16: Tumor and medial margin including soft tissue extension, 1 frag, RSS.\nCassette 17: Tumor and lateral margin, 1 frag, RSS.\nCassette 18: Tumor and posterior margin, 1 frag, RSS.\nCassette 19: Tumor and anterior margin, 1 frag, RSS.\nCassette 20: Bone at proximal margin, 1 frag, RSS.\nCassette 21: Bone and cartilage at distal margin, 1 frag, RSS.\nCassette 22: Soft tissue at proximal margin, 1 frag, RSS.\nCassette 23: Soft tissue at proximal margin, 1 frag, RSS.\nCassette 24: Skin with scar, 1 frag, RSS.\nCassette 25: Biopsy site, 1 frag, RSS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR BONE TUMORS\n\t\u2022\t \u0007Specimen: Bone involved\n\t\u2022\t \u0007Procedure: Core needle biopsy, curettage, excisional biopsy, intralesional resection, marginal resec\u00ad\ntion, segmental/wide resection, radical resection\n\t\u2022\t \u0007Tumor Location(s):\n\t\u2022\t \u0007Epiphysis (articular cartilage to epiphyseal plate) or apophysis (a process on certain bones)\n\t\u2022\t \u0007Metaphysis (epiphyseal plate to diaphysis)\n\t\u2022\t \u0007Diaphysis (end of proximal metaphysis to beginning of distal metaphysis)\n\t\u2022\t \u0007Cortical\n\t\u2022\t \u0007Medullary cavity\n\t\u2022\t \u0007Surface\n\t\u2022\t \u0007Tumor involves joint\n\t\u2022\t \u0007Tumor extension into soft tissue", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_273.png", "summary": "This page discusses the process of bone resections for tumors, including the importance of mapping tumor extent in three dimensions and the need to include representative sections of normal structures.", "questions": [ "Why is it important to map the extent of tumors in three dimensions?", "What are the key areas that should be sampled during bone resections for tumors?", "Why is it necessary to include representative sections of normal structures in the specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 274, "text": "256\nBONE AND JOINTS\u2003 Bone Resections for Tumors\n\t\u2022\t \u0007Tumor Size: Greatest dimension (other dimensions optional), multifocal tumor/discontinuous tumor \nat primary site (skip metastasis)\n\t\u2022\t \u0007Histologic Type: The most important feature. Usually the diagnosis will have been established before \ndefinitive resection. The WHO Classification of bone tumors should be used.\n\t\u2022\t \u0007Mitotic Rate: Number of mitoses per 10 HPF (1 HPF = 0.1734 mm2) The most proliferative area \nshould be counted.\n\t\u2022\t \u0007Necrosis: Not identified, present (extent: %)\n\t\u2022\t \u0007Histologic Grade: See Tables 14-2 to 14-6 for grades of common bone tumors.\n\t\u2022\t \u0007Margins:\n\t\n\u2022\t \u0007Bone, soft tissue, marrow, involvement and distance of tumor from margin\n\t\n\u2022\t \u0007Neurovascular bundle at the margin: involved or not involved\n\t\n\u2022\t \u0007Intralesional margin = positive margin\n\t\n\u2022\t \u0007Marginal margin = < 2 cm of normal tissue at margin; less if the margin is fascia\n\t\n\u2022\t \u0007Wide margin = > 2 cm of normal tissue at margins, less if bounded by fascia\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present (present in 3% to 13% of osseous sarcomas)\n\t\u2022\t \u0007Cystic Change: Identified, not identified\nTABLE 14-2.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF BONE TUMORS\nGrade\nGX\nGrade cannot be assessed.\nG1\nWell differentiated, low grade\nG2\nModerately differentiated, low grade\nG3\nPoorly differentiated\nG4\nUndifferentiated\nNote: Ewing\u2019s sarcoma is classified as G4.\nTumor\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nTumor 8 cm or less in greatest dimension\nT2\nTumor more than 8 cm in greatest dimension\nT3\nDiscontinuous tumors in the primary bone site\nRegional Lymph \nNodes\nNX\nRegional Iymph nodes cannot be assessed.\nN0\nNo regional node metastasis\nN1\nRegional node metastasis\nNote: Because of the rarity of lymph node involvement in bone sarcomas, the designation NX may not be \nappropriate, and cases should be considered N0 unless clinical node involvement is clearly evident.\nDistant \nMetastasis\nM0\nNo distant metastasis\nM1\nDistant metastasis\nM1a\nLung\nM1b\nOther distant sites\nThis system is used for all primary malignant tumors of bone except lymphoma and multiple myeloma.\nNote: Primary malignant lymphoma and multiple myeloma are not included.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-\u00adVerlag, 2009. Used with the permission of the American Joint \nCommittee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_274.png", "summary": "This page provides guidelines for evaluating bone resections for tumors, including factors such as tumor size, histologic type, mitotic rate, margins, lymph-vascular invasion, and cystic change.", "questions": [ "How is the mitotic rate determined and why is it important?", "What are the different types of margins mentioned and how do they impact the prognosis?", "What is the significance of lymph-vascular invasion in osseous sarcomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 275, "text": "257\nBONE AND JOINTS\u2003 Bone Resections for Tumors\n\t\u2022\t \u0007Hemorrhage: Identified, not identified\n\t\u2022\t \u0007Radiographic Findings: Correlate with radiographic images\n\t\u2022\t \u0007Treatment Effect: No prior treatment, not identified, present. Report proportion of tumor that is \nnecrotic or replaced by fibrous or granulation tissue (Tables 14\u20135 and 14\u20136 for osteosarcoma and \nEwing sarcoma).\n\t\u2022\t \u0007Ancillary Studies (if performed): Immunohistochemistry, cytogenetics, molecular studies\n\t\u2022\t \u0007Regional Lymph Node Metastasis: Absent, present (number of nodes involved, number of nodes \nexamined)\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\nTABLE 14\u20133.\u2003\nBONE TUMORS \u2013 GRADE\nGrade 1 (low grade)\nLow-grade central osteosarcoma\nParosteal osteosarcoma\nAdamantinoma\nGrade 2\nPeriosteal osteosarcoma\nGrade 3 (high grade)\nVariable grade\nMalignant giant cell tumor\nEwing sarcoma/PNET\nMesenchymal chondrosarcoma\nDedifferentiated chondrosarcoma\nConventional osteosarcoma\nTelangiectactic osteosarcoma\nSmall cell osteosarcoma\nSecondary osteosarcoma\nHigh-grade surface osteosarcoma\nDedifferentiated chordoma\nConventional chondrosarcoma of bone (grades 1 to 3)\nSoft-tissue type sarcomas (e.g., leiomyosarcoma)\nSee CAP protocol for tumors of bone (www.cap.org).\nTABLE 14\u20134.\u2003\nCHONDROSARCOMA \u2013 GRADE\nCellularity\nNuclear Atypia\nMitoses\nOther Features\nGrade 1 (low grade)\nHypocellular\nMinimal\nMinimal\nAppearance similar \nto enchondroma\nGrade 2 \n(intermediate grade)\nMore cellular\nMore atypia, greater \nhyperchromasia, \nincreased nuclear size\nMinimal\nMay have extensive \nmyxoid stroma\nGrade 3 (high grade)\nHypercellular\nPleomorphic nuclei\nProminent\nSee CAP protocol for tumors of bone (www.cap.org).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_275.png", "summary": "This page discusses bone resections for tumors, including considerations for hemorrhage, radiographic findings, treatment effects, ancillary studies, lymph node and distant metastasis, and tumor grading.", "questions": [ "What are the different treatment effects that can be observed in bone resections for tumors?", "How are regional lymph node metastasis and distant metastasis assessed in these cases?", "What are the different grades of bone tumors and chondrosarcoma mentioned in the tables?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 276, "text": "258\nBONE AND JOINTS\u2003 Incidental Ribs\n\t\u2022\t \u0007AJCC Classification: T, N, and M categories should be provided, when possible. M0 is conferred \nafter clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nINCIDENTAL RIBS\nPortions of ribs are often removed to perform thoracotomies or nephrectomies. The rib is usually 2 to \n5 cm long and is rarely of diagnostic importance. The most important missed histologic diagnosis on \nincidental ribs is multiple myeloma. The patients often survive for long periods of time, may have proce\u00ad\ndures performed not related to the disease (unlike, for example, acute leukemia), and the disease may not \nhave been diagnosed clinically. Plasma cell dyscrasias can be diagnosed even on suboptimally fixed and \ndecalcified tissue. Involvement by chronic lymphocytic leukemia is also occasionally found, but is usually \nclinically evident due to a high peripheral white blood count.\nSPECIMEN PROCESSING\nRibs resected from patients without malignant disease and without other clinical indication for exami\u00ad\nnation (e.g., a known hematologic disorder) do not necessarily require histologic examination. There are \ntwo methods for examining all other specimens.\nDecalcification Method.\u2002 This method should be used for all patients with a history of lymphoma \nor other hematologic disorder (treat as a diagnostic bone marrow biopsy; see Chapter 27); a history of a \nmalignancy that frequently metastasizes to bone marrow (e.g., small cell lung carcinomas); or ribs with \ngrossly evident or clinically suspected lesions.\n \n1.\t \u0007The rib is described (measurements, color, gross identification as portion of rib) and fixed in for\u00ad\nmalin. Cartilage may be present at one end if near the costochondral junction. It will be homoge\u00ad\nneously pale white, will cut easily with a razor blade, and will not be visible on x-ray.\nTABLE 14\u20136.\u2003\nEWING SARCOMA \u2013 HISTOLOGIC RESPONSE GRADE TO TREATMENT\nGrade I\nMacroscopic viable tumor\nGrade II\nMicroscopic viable tumor\nGrade III\nNo viable tumor\nSee CAP protocol for tumors of bone (www.cap.org).\nTABLE 14\u20135.\u2003\nOSTEOSARCOMA \u2013 HISTOLOGIC RESPONSE GRADE TO TREATMENT\nI\nNo effect identified\nIIA\nSome necrosis, more than 50% viable tumor remaining\nIIB\n3% to 50% viable tumor remaining\nIII\nScattered foci, <3% viable tumor remaining*\nIV\nNo viable tumor noted\n*In some systems, 90% or 95% is used rather than 97%, which is the current standard of the Children\u2019s Oncology Group. Tumors that have 90% to \n97% necrosis have a better prognosis.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_276.png", "summary": "The page discusses the incidental removal of ribs during surgical procedures and the importance of histologic examination for detecting conditions like multiple myeloma and chronic lymphocytic leukemia.", "questions": [ "What are the key considerations for histologic examination of ribs removed incidentally during surgical procedures?", "Why is multiple myeloma considered the most important missed histologic diagnosis on incidental ribs?", "How do plasma cell dyscrasias and involvement by chronic lymphocytic leukemia present on suboptimally fixed and decalcified tissue?", "What are the different histologic response grades for Ewing sarcoma and osteosarcoma to treatment?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 277, "text": "BONE AND JOINTS\u2003 Synovium\n259\n \n2.\t \u0007If a gross lesion is present that is suspicious for metastatic disease, the specimen is radiographed, \nserially sectioned, and any soft tissue (i.e., potential tumor) removed prior to decalcification.\n \n3.\t \u0007The remainder of the bone is gently decalcified. Grossly normal bones can be submitted as mul\u00ad\ntiple sections in one cassette. If gross or radiographic lesions are present, submit them in a separate \ncassette. Do not submit grossly benign cartilage.\nRib Squeeze Method.\u2002 The disadvantage of this method is that metastatic tumors and lymphomas \nmay not be easily expressed from the bone marrow due to accompanying marrow fibrosis. However, \noften bone marrow involvement will have been investigated clinically before surgery is performed and \nthe finding of malignancy in incidental ribs is very rare.\nThe advantage of this method is that it provides better histologic preservation of the bone marrow \nelements and does not delay the rib in processing. Thus, this is the preferred method with the exceptions \nnoted above.\n \n1.\t \u0007The rib is described as above.\n \n2.\t \u0007The specimen must be fresh and unfixed. Use a bone saw to cut a portion about 2 cm in length \nwith marrow present at both ends of the specimen. Use pliers to squeeze until marrow is expressed \nfrom both ends. Collect the marrow in formalin. If very little marrow can be expressed, the bone \nshould be fixed and decalcified as described above. The remainder of the rib is cut longitudinally \nand examined for gross lesions. Submit any lesions seen. Document in the gross description that \nthe bone was not decalcified.\n \n3.\t \u0007The marrow should be wrapped in paper or placed in a specimen bag and submitted in one \u00adcassette.\nMENISCUS\nMenisci are usually removed because of traumatic tears that interfere with articular movement. Occa\u00ad\nsionally joint mice (= loose bodies) may be removed during the same type of procedure. These are frag\u00ad\nments of free cartilage in the joint space and often become ossified. The meniscus can also be affected by \nCPPD and ochronosis (see gross differential diagnosis under \u201cSynovium\u201d).\nPROCESSING THE SPECIMEN\n \n1.\t \u0007Describe the specimen including size, color (normally white and glistening), texture (smooth, fib\u00ad\nrillated), and presence or absence of tears.\n \n2.\t \u0007If chalky white deposits are present, a portion of the specimen is processed in absolute ethanol to \npreserve crystals (see also \u201cSynovium\u201d).\n \n3.\t \u0007Submit representative sections in one cassette.\nSYNOVIUM\nSynovium may be biopsied for diagnostic purposes (e.g., inflammatory arthritis) or removed for the treat\u00ad\nment of disease (e.g., pigmented villonodular synovitis [giant cell tumor, diffuse type] or dialysis-related \namyloidosis).\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the aggregate dimensions, size range, and approximate number of fragments.\nDescribe the color and consistency of the synovium (see descriptions under \u201cGross Differential \n\u00adDiagnosis\u201d).\nIf infection is suspected and fresh tissue is received, confirm that cultures have been taken. If not, send \nsterile tissue to microbiology.\n 2.\t \u0007Submit up to two cassettes and order one level (H&E). Order special studies as indicated below for \nspecific cases. If the specimen is a small biopsy, submit all the tissue and order three levels.\nSPECIAL STUDIES\n\t \u2022\t \u0007Crystal disease: Chalky white deposits may be present in synovium and representative sections \nmust be fixed in absolute alcohol. See \u201cTotal Joint Arthroplasty - Special Studies.\u201d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_277.png", "summary": "This page discusses the processing of bone and joint specimens, including the rib squeeze method for bone marrow evaluation and the removal of menisci for traumatic tears.", "questions": [ "What is the advantage of using the rib squeeze method for bone marrow evaluation?", "Why are menisci usually removed from joints?", "What information should be recorded when processing synovium specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 278, "text": "BONE AND JOINTS\u2003 Intervertebral Disc Material\n260\n\t \u2022\t \u0007Amyloidosis: All tissue can be fixed in formalin. Amyloid can be diagnosed using a Congo red stain \nand polarized light. Immunohistochemistry can be used to identify the type of amyloid present. \nDialysis related amyloidosis of joints is due to \u03b22 microglobulin.\n\t \u2022\t \u0007Infection: Fresh sterile tissue may be sent for culture.\nGROSS DIFFERENTIAL DIAGNOSIS\nNormal Synovium.\u2002 Normal synovium is glistening white with delicate villous projections.\nGout or CPPD.\u2002 Chalky white or crystalline deposits are present and must be fixed in absolute alcohol. \nSee \u201cTotal Joint Arthroplasty - Special Studies\u201d for information on how to process.\nGiant Cell Tumor, Diffuse Type (Pigmented Villonodular Synovitis, PVNS).\u2002 The synovium is \na rusty red color due to extensive hemosiderin deposition. Coarse villi with occasional attached nodules \nare present. These areas become more apparent when floated in saline and can be photographed well in \nthis manner. There may be an abundance of tissue with areas of fibrosis. Necrotic foci may appear \nyellow due to the presence of histiocytes.\nDetritic Synovitis.\u2002 Changes occurring around an artificial joint, which can appear very similar to \nPVNS (see \u201cRevision Total Joint Arthroplasty\u201d).\nDialysis-Related Amyloidosis.\u2002 There are characteristic yellow/tan plaques that may be superficial, \nrun along tendons, or form large homogeneous nodules.\nSynovial Chrondromatosis.\u2002 Multiple small nodules of cartilage are present within the synovial tis\u00ad\nsue. The cartilage may need to be decalcified.\nHemochromatosis.\u2002 The synovium can become hyperplastic and brown in color due to dense hemo\u00ad\nsiderin deposition. The appearance can mimic PVNS, but nodules are not present. The cartilage takes \non a characteristic greenish-black appearance.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Synovium: Up to two cassettes. If the biopsy is small (only enough tissue for one cassette), order \nthree levels.\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name, unit number, and \u201csynovium right knee\u201d are multiple \nfragments of reddish brown soft tissue measuring in aggregate 5 \u00d7 4 \u00d7 1 cm. Delicate villous projections \nand small nodules are present.\nCassettes 1 and 2: mult frags, RSS.\nCARPAL TUNNEL RELEASE (TENOSYNOVIUM)\nMost patients present with idiopathic carpal tunnel syndrome, and only a small fraction of these patients \nwill show evidence of amyloid on microscopic examination. However, in renal dialysis patients carpal \ntunnel syndrome is very common and \u03b22 microglobulin amyloidosis is often present.\nThese specimens consist of synovium and soft tissue from around the tendons and nerves of the carpal \ntunnel that are removed during a carpal tunnel release procedure. The specimens may be processed in \nthe same manner as synovium, but are examined with one level.\nINTERVERTEBRAL DISC MATERIAL\nThese specimens are derived from operations on herniated discs and will consist of small fragments of \nbone, nucleus pulposus, annulus fibrosus, and ligamentum flavum. The specimen is fixed, decalcified, and \none representative section is submitted.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_278.png", "summary": "The page discusses various pathologies related to bone and joints, including amyloidosis, infection, gout, giant cell tumor, dialysis-related amyloidosis, synovial chrondromatosis, and hemochromatosis.", "questions": [ "How can amyloidosis be diagnosed using histological techniques?", "What are the differences in appearance between Gout or CPPD and Giant Cell Tumor, Diffuse Type?", "What are the characteristic features of Dialysis-Related Amyloidosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 279, "text": "BONE AND JOINTS\u2003 Intervertebral Disc Material\n261\nThe likelihood of finding a clinically significant unsuspected finding in a patient without a history of \nmalignancy and/or suspected infection is very low (<1%).14-18 However, if the patient has a significant \nhistory or an unusual presentation, important pathologic findings are reported in over half of cases. If an \nadequate clinical history is provided, it may not be necessary to examine all such specimens histologically. \nSee \u201cGross Specimens\u201d for a discussion of this issue.\nSpecial cases:\n\t \u2022\t \u0007Metastatic disease: Any soft tissue is dissected away and submitted without decalcification. If the \nprimary site is unknown, and there is sufficient tissue, then consideration should be given to saving \ntissue for special studies (e.g., frozen tissue or EM).\n\t \u2022\t \u0007Infection: Any soft tissue is dissected away and submitted without decalcification. If there is suf\u00ad\nficient tissue, consideration should be given to sending tissue for cultures. Special stains may be \nhelpful. Aspergillus can invade into cartilage without an inflammatory response and may not be \ndetectable without fungal stains.\nREFERENCES\n\t\u2002 1.\t \u0007Billings SD, Wurtz LD, Tejada E, Henley JD. Occult sarcoma of the femoral head in patients undergoing total \nhip arthroplasty. J Bone Joint Surg 82-A:1536-1539, 2000.\n\t\u2002 2.\t \u0007Campbell ML, Gregory AM, Mauerhan DR. Collection of surgical specimens in total joint arthroplasty. Is rou\u00ad\ntine pathology cost effective? J Arthroplasty 12:60, 1997.\n\t\u2002 3.\t \u0007Clark CR, Bauer T. Routine pathological examination of operative specimens from primary total hip and total \nknee replacement: another look [Editorial]. J Bone Joint Surg 82-A:1529-1530, 2000.\n\t\u2002 4.\t \u0007DiCarlo EF, Bullough PG, Steiner G, et al. Pathological examination of the femoral head (FH). Mod Pathol \n7(Abstract 16):6A, 1994.\n\t\u2002 5.\t \u0007Kocher MS, Erens G, Thornhill TS, Ready JE. Cost and effectiveness of routine pathological examination \nof operative specimens obtained during primary total hip and knee replacement in patients with osteoarthritis. \nJ Bone Joint Surg 82-A, 1531-1535.\n\t\u2002 6.\t \u0007Meding JB, Ritter MA, Jones NL, et al. Determining the necessity for routine pathologic examinations in \nuncomplicated total hip and total knee arthroplasties. J Arthroplasty 15:69-71, 2000.\n\t\u2002 7.\t \u0007Palmer SH, Gibbons CL, Athanasou NA. The pathology of bone allograft. J Bone Joint Surg Br 81:333-335, 1999.\n\t\u2002 8.\t \u0007JCAHO Standard QC.2.10, Comprehensive Accreditation Manual for Laboratory and Point-of-Care Testing, 2009.\n\t\u2002 9.\t \u0007Shidham V, Chivukula M, Basir Z, Shidham G. Evaluation of crystals in formalin-fixed, paraffin-embedded \n\u00adtissue sections for the differential diagnosis of pseudogout, gout, and tumoral calcinosis. Mod Pathol 14:\n806-810, 2001.\n\t10.\t \u0007Yamakawa K, Iwasaki H, Masuda I, et al. The utility of alizarin red s staining in calcium pyrophosphate dihy\u00ad\ndrate crystal deposition disease. J Rheumatol 30:1032-1035, 2003.\n\t11.\t \u0007Unni KK, Inwards CY, Bridge JA, et al. Tumors of the Bones and Joints, AFIP Atlas of Tumor Pathology 4th \nSeries. Fascicle 2, 2005.\n\t12.\t \u0007Weatherby RP, Unni KK. Practical aspects of handling orthopedic specimens in the surgical pathology labora\u00ad\ntory, Path Ann, 17. part 2:1-31, 1982.\n\t13.\t \u0007Patterson K. The pathologic handling of skeletal tumors. Am J Clin Pathol 109(Suppl 1):S53-S66, 1998.\n\t14.\t \u0007Daftari TK, Levine J, Fischgrund JS, Herkowitz HN. Is pathology examination of disc specimens necessary after \nroutine anterior cervical discectomy and fusion? Spine 21:2156, 1996.\n\t15.\t \u0007Grzybicki DM, Callaghan EJ, Raab SS. Cost-benefit value of microscopic examination of intervertebral discs. \nJ Neurosurg 89:378-381, 1998.\n\t16.\t \u0007Hasselblatt M, Maintz D, Goll T, et al. Frequency of unexpected and important histopathological findings in \nroutine intervertebral disc surgery. J Neurosurg Spine 4:20-23, 2006.\n\t17.\t \u0007Reddy P, Williams R, Willis B, Nanda A. Pathological evaluation of intervertebral disc tissue specimens \nafter routine cervical and lumbar decompression. A cost-benefit analysis retrospective study. Surg Neurol 56:\n252-255, 2001.\n\t18.\t \u0007Wu AS, Fourney DR. Histopathological examination of intervertebral disc specimens: a cost-benefit analysis. \nCan J Neurol Sci. 34:451-455, 2007.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_279.png", "summary": "The likelihood of finding clinically significant findings in intervertebral disc material is low in patients without a history of malignancy or suspected infection, but increases in cases with significant history or unusual presentation.", "questions": [ "What are some special considerations for examining specimens with metastatic disease or infection?", "How can special stains be helpful in detecting certain pathologic findings?", "What is the significance of the references listed at the end of the text?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 280, "text": "262\n15\nBreast\nBreast biopsies are common surgical specimens for the evaluation of palpable masses, radiologic lesions, \nor nipple discharge, to search for possible cancer. Clinically significant non-malignant diseases of the \nbreast are rare. Surgery for malignant disease may include portions of the breast (e.g., lumpectomies or \nquadrantectomies) or the entire breast (mastectomy). Less commonly, breasts are removed for prophy\u00ad\nlactic (simple mastectomy) or cosmetic/functional reasons (reduction mammoplasty or gynecomastia).\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nLARGE CORE NEEDLE BIOPSIES\nLarge core needle biopsies may be performed for palpable masses (Tru-Cut) without radiologic guid\u00ad\nance, under ultrasound guidance to sample masses, mammographically directed (\u201cstereotactic\u201d) for either \ncalcifications or mammographic densities, or using MRI to detect enhancing lesions.\nSPECIMEN PROCESSING\n 1.\t \u0007Describe the number of cores, color, and size.\n 2.\t \u0007All tissue cores are wrapped in paper on a flat surface aligned in parallel (see Chapter 13 for details \nconcerning this method). A sponge can be used in the cassette to hold the biopsies flat. Order three \nlevels.\nTABLE 15\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR BREAST BIOPSIES\nOrgan/tissue resected or biopsied\nType of lesion biopsied (e.g., palpable mass, mammo\u00ad\ngraphic lesion [density, calcifications, or architectural \ndistortion], or nipple discharge). If the lesion is mam\u00ad\nmographic, a specimen radiograph with interpreta\u00ad\ntion may be required in order to fully evaluate the \nspecimen.\nPurpose of the procedure\nGross appearance of the organ/tissue/lesion sampled\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\nCurrent pregnancy or lactation\nPrior surgery/biopsies - results\nDrug use that could change the appearance of the \nbreast (e.g., oral contraceptives or other hormonal \ntherapy)\nPrior malignancy\nPrior treatment (radiation therapy, \u00adchemotherapy, \ndrug use that can change the histologic appear\u00ad\nance of tissues)\nPrior personal or family history of breast carcinoma\nCollagen vascular disease\nHistory of radiation therapy or neoadjuvant \n\u00adchemotherapy.\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_280.png", "summary": "Breast biopsies are common for evaluating masses, lesions, or nipple discharge for possible cancer. Surgery may involve partial or complete breast removal for malignant disease or other reasons.", "questions": [ "What are the different types of breast surgeries mentioned in the text?", "What are the different methods mentioned for performing large core needle biopsies?", "What clinical history is considered relevant for all breast specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 281, "text": "BREAST\u2003 Excisional Biopsies\n263\nSPECIAL STUDIES CALCIFICATIONS\nCalcifications.\u2002 If malignancy is present in a breast biopsy for radiologically suspicious calcifications, \nthe carcinoma will either be at the site of the calcifications or within 1 cm in over 95% of cases.\nRadiologic calcifications associated with malignancy are numerous, clustered (or in a linear array), \nand small. On mammography, or in specimen radiography, the calcifications occupy a three dimensional \nspace. Although an object must approximately 100 microns in size to be imaged in these studies, many of \nthe \u201ccalcifications\u201d present are likely due to many overlapping small crystals.\nHistologic sections reduce the tissue to essentially two dimensions. Many more calcifications are visu\u00ad\nalized that are either too small to be detected radiographically, or that would not be in a suspicious clus\u00ad\ntered configuration. Therefore, it is usually difficult, or impossible, to definitively identify a radiologic \ncluster of calcifications by the size, quantity, or distribution of calcifications on a histologic section. Thus \nit is imperative that the pathologist identifies the tissue grossly that contains the radiographic finding.\nRadiologists should document calcifications in the cores by specimen radiography. It is preferable for \nthe cores to be wrapped in lens paper and placed in a cassette immediately after biopsy to minimize the \nlikelihood that the calcifications will be lost during fixation and processing. Different cassettes may be \nused for different lesions or cores with or without calcifications.\nIt is useful to have the histology laboratory make shallower initial levels of cores containing calcifica\u00ad\ntions to make sure all tissue present is adequately sampled.\n\t \u2022\t \u0007Calcium phosphate crystals are purple in color and do not polarize. They are commonly seen in \nassociation with cysts, sclerosing adenosis, and in hyalinized fibroadenomas, as well as in DCIS and \ninvasive carcinomas.\n\t \u2022\t \u0007Calcium oxalate crystals are rhomboidal refractile pale-yellow or clear crystals usually found in \napocrine cysts and are easily seen under polarized light. They are sometimes seen in stroma adjacent \nto cysts, with or without a giant cell reaction. When the crystals are numerous in large cysts, they are \nreferred to as \u201cmilk of calcium\u201d by radiologists as they line the bottom of cysts in a tea-cup shape in \nthe medial-lateral-oblique view and change in spatial orientation (flatten) in the cranial-caudal view. \nCalcium oxalate crystals have not been associated with carcinomas.\nIf calcifications are not found, deeper sections are obtained of the blocks with radiologic calcifica\u00ad\ntions. In some cases it may be useful to radiograph the paraffin blocks to localize the calcifications (see in \nChapter 7, \u201c\u00adSpecimen Radiography\u201d). It can be helpful to radiograph the blocks flat and on edge to \ndetermine the depth of the calcifications in the block for the histotechnologist.\nRadiographic \u201ccalcifications\u201d can rarely be due to surgical debris (at an old biopsy site) that may not \nbe evident histologically. Evidence of an old biopsy site should be present. Material that looks like calci\u00ad\nfications can also be due to gold in macrophages after injections for rheumatoid arthritis or from foreign \nmaterial after traumatic injuries. Calcifications can also dissolve if left in formalin for over 24 hours.1 \nSmall biopsies should be processed expeditiously or stored in alcohol if processing will be delayed.\nHormone Receptors and HER2/neu.\u2002 Hormone receptor and HER2/neu status can be deter\u00ad\u00ad\nmined on carcinomas by immunohistochemistry (see \u201cExcisional Biopsies\u201d).\nINCISIONAL BIOPSIES\nIncisional biopsies are unusual specimens that are almost always performed to evaluate unresectable \ninvasive carcinomas. Often the purpose of the biopsy is to confirm the clinical diagnosis and to obtain \nhormone receptor and HER2/neu status.\nThe specimen usually consists of a single small fragment, or multiple small fragments, of tissue. The \nentire specimen is submitted. The tissue need not be inked if clearly labeled as an incisional biopsy.\nEXCISIONAL BIOPSIES\nExcisional biopsies are defined as procedures intended for the primary evaluation of a breast lesion with \ncomplete removal of the lesion. If there has been a prior diagnosis of malignancy (e.g., by core biopsy), \nthe intent of the procedure is to obtain adequate margins. The processing of an excisional biopsy will vary \ndepending on the type of lesion resected.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_281.png", "summary": "In breast biopsies with radiologically suspicious calcifications, malignancy is typically found at the site of the calcifications or within 1 cm in over 95% of cases. Histologic sections may not definitively identify radiologic clusters of calcifications, so it is important for pathologists to grossly identify the tissue containing the radiographic findings.", "questions": [ "How accurate is the correlation between radiologic calcifications and the presence of malignancy in breast biopsies?", "What are the characteristics of calcium phosphate crystals and where are they commonly seen?", "Why is it important for radiologists to document calcifications in the cores by specimen radiography?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 282, "text": "BREAST\u2003 Excisional Biopsies\n264\nAll biopsies must be inked in order to evaluate margins. Fragmented biopsies are inked because the \nlesion may be located in only one of the fragments.\nOrientation\nSome surgeons attempt to minimize cosmetic deformities by only resecting specific positive margins \nif malignancy is found. In such cases, it is necessary to identify each of six possible margins (superior, \ninferior, medial, lateral, anterior, posterior) and to evaluate them separately. This can be accomplished \nif the surgeon provides at least two orienting sutures perpendicular to each other (e.g., \u201csuperior\u201d and \n\u201clateral\u201d). Orientation can be maintained by taking and labeling sections in relation to the sutures, or by \ninking each margin with a different color. It is helpful to develop a standard method of inking margins \nto be used for all specimens.\nThe posterior margin always corresponds to the deep margin closest to the chest wall. The superficial \n(skin) margin is usually anterior but can correspond to any of the other margins depending on the loca\u00ad\ntion of the biopsy within the breast.\nExcisional Biopsies for Palpable Masses\nA primary biopsy performed without wire localization (see \u201cExcisional Biopsies for Mammographic \nLesions with Wire Localization\u201d) or a history of nipple discharge (see \u201cDuct Dissections\u201d) is usually to \nexcise a palpable mass. Invasive carcinoma will be found in about 20% of the specimens (average size \n2 cm), DCIS alone in less than 5%, and fibroadenomas in about 20%. The remainder of the specimens \nwill have a wide variety of benign lesions or other (very rare) malignant lesions.\nSPECIMEN PROCESSING\n 1.\t \u0007Record total dimensions and note any orienting sutures. Record the orientation of the dimensions \n(i.e., distance from medial to lateral, anterior to posterior, and inferior to superior).\n\t \u2022\t \u0007Ink all fragments. Blot the surface dry and change gloves if necessary to avoid introducing ink into \nthe interior of the specimen.\n\t \u2022\t \u0007Unoriented specimens can be inked entirely in black. Oriented specimens may be inked using col\u00ad\nored inks to identify specific margins. If there is any ambiguity about specimen orientation (e.g., a \nsuture has fallen off), contact the surgeon before proceeding.\n\t \u2022\t \u0007Serially section the specimen.\n 2.\t \u0007Describe lesions including size (accurate to nearest mm for staging), consistency (rubbery and bulg\u00ad\ning, soft, firm, hard), growth pattern (well-circumscribed, stellate, invasive, poorly-circumscribed), \nnecrosis, and distance from margins. If there are multiple lesions, describe their relationship to each \nother and the distance between lesions.\n\t \u2022\t \u0007Sample all gross lesions. For lesions suspicious for malignancy, four to five cassettes of the lesion \nare adequate. For fibroadenomas, or other grossly benign lesions, one section per 1 cm (two per \ncassette) of greatest dimension is adequate. If there are multiple lesions, submit a section of tissue in \nbetween the two lesions.\n\t \u2022\t \u0007If a gross lesion is not evident, make sure the biopsy was performed for a palpable mass. Most masses \npalpable to the surgeon will be grossly evident to the pathologist. Occasionally, surgeons will biopsy \nvaguely denser areas of breast tissue without a discrete mass. In such cases, submit at least 10 cas\u00ad\nsettes selecting out the most fibrous areas and avoiding pure adipose tissue. If carcinoma in situ \nor atypical hyperplasia is found in this tissue, then the entire specimen is submitted for histologic \nexamination.2\n\t \u2022\t \u0007Never take tissue for special studies or research unless a definitive diagnosis of invasive carcinoma \nhas been established.\n 3.\t \u0007Submit perpendicular sections of the closest approach of suspicious lesions to all margins of oriented \nspecimens. Up to twelve cassettes (corresponding to two sections from each of the six margins) may be \nsubmitted if malignancy is known or highly suspected. Often margins are included in the same cassette \nwith a section of the lesion.\n 4.\t \u0007If there is additional fibrous parenchyma not included in the cassettes with the lesion or margin, sub\u00ad\nmit at least one cassette. If skin is present submit one section.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_282.png", "summary": "Excisional breast biopsies must be inked to evaluate margins, with orientation and specific margin identification crucial for accurate evaluation. Specimens for palpable masses may reveal invasive carcinoma, DCIS, fibroadenomas, or other benign lesions.", "questions": [ "How is the orientation of excisional breast biopsies maintained?", "What are the common findings in specimens from excisional biopsies for palpable masses?", "Why is it important to ink all fragments of excisional breast biopsies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 283, "text": "BREAST\u2003 Excisional Biopsies\n265\nMost specimens can be submitted in ten cassettes or less. If the entire specimen is not submitted, the \ngross description should include a statement estimating the percentage of the lesion and total specimen \nsubmitted for histologic examination.\nIf there is a prior diagnosis of DCIS, it is preferable to submit the entire specimen in sequence (e.g., \nfrom medial to lateral) in order to determine the extent of the DCIS, the status of margins, and to exclude \nany areas of invasive carcinoma.\nSPECIAL STUDIES\nEstrogen and Progesterone Receptors.\u2002 This information is used for prognosis for patients \nwith invasive breast cancer and to determine if a patient would benefit from hormonal therapy (see in \nChapter 7, \u201cEstrogen and Progesterone Receptor Evaluation,\u201d and Tables 7-12, 7-13 and 7-14).\nHormone receptor antigenicity can be diminished or eliminated by some fixatives (e.g., Bouin\u2019s fixa\u00ad\ntive), over- or underfixation in formalin, or decalcification. Thus, these conditions should be avoided if \nhormone receptors may need to be determined. Delayed fixation or heat (e.g., by surgical cautery) can \nalso result in degradation of receptor proteins. If negative results are obtained (e.g., in both the carci\u00ad\nnoma and in normal tissue), and the specimen was not optimally fixed in formalin, this should be noted \nas a possible cause of false negative results.\nHER2/neu (c-erb B2).\u2002 Overexpression can be determined either by IHC or by FISH on formalin-\nfixed tissue, as about 95% of carcinomas with protein overexpression also have gene amplification (see \nTables 7-15 and 7-16). Rare cancers will overexpress HER2 due to other mechanisms.\nFlow Cytometric Analysis.\u2002 Flow cytometry may be used to determine DNA content and S phase \nfraction (SPF). Abnormal DNA content and high SPF are poor prognostic factors. These studies are best \nperformed on fresh tissue, but can also be performed on formalin-fixed tissue. See Chapter 7, \u201cAnalytical \nCytology,\u201d for more information.\nTissue for Research.\u2002 Tissue can only be removed for research if a diagnosis of invasive carcinoma \nhas been firmly established. In all other cases, it may be necessary to examine all the breast tissue micro\u00ad\nscopically.\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Figure 15-1.\nInvasive Carcinoma.\u2002 Invasive carcinoma usually appears as a very hard white mass with irregular or \nstellate borders. The consistency when cut through is gritty (like a water chestnut). Pale yellow streaks in \nthe tumor are usually due to elastosis in the desmoplastic response, not to necrosis. Some invasive tumors \nare well-circumscribed (e.g., medullary or mucinous carcinomas) and may be firm or soft. Occasionally \nthey are mistaken for fibroadenomas. However, these tumors will not bulge or have clefts and may have \nareas of necrosis. Mucinous carcinoma may have a gelatinous appearance.\nThe size of invasive carcinomas is difficult to determine visually, as the borders often blend into the \nsurrounding fibrous tissue. Size is better determined by palpation. The edges of the carcinoma usually \nform a shelf that can be pinched between the fingers and this defines the extent of the desmoplastic \nresponse around the carcinoma.\nLess commonly, lobular carcinomas, as well as some ductal carcinomas, may have a diffusely infiltrat\u00ad\ning pattern and may be subtle (consisting of diffusely firm white tissue) or occult on gross examination. \nThe size of such tumors can only be estimated using both gross and microscopic appearances.\nInflammatory Carcinoma.\u2002 This is a diagnosis based on both clinical and pathologic features. The \npatient presents with diffuse erythema and edema involving the breast and skin. The carcinoma often has \na diffusely invasive pattern with little or no desmoplasia and typically there is not a palpable mass. The \nskin changes correlate with tumor in dermal lymphatics; true inflammation is not present. The erythema \nand edema are not apparent in the excised breast. Mastectomy is often performed only after the patient \nhas responded to chemotherapy.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_283.png", "summary": "Excisional biopsies of breast specimens should be submitted in ten cassettes or less, with a gross description indicating the percentage of the lesion and total specimen submitted. Special studies like hormone receptor evaluation and HER2/neu testing are crucial for prognosis and treatment decisions.", "questions": [ "How many cassettes should breast specimens be submitted in for excisional biopsies?", "Why is it important to submit the entire specimen in sequence if there is a prior diagnosis of DCIS?", "What are some factors that can affect hormone receptor antigenicity in breast tissue?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 284, "text": "BREAST\u2003 Excisional Biopsies\n266\nMetastatic Carcinoma to a Lymph Node with an Occult \u00adPrimary.\u2002 This is a rare presentation for \nbreast cancer. If all radiologic studies are negative, including MRI, it is unlikely that the primary will be \nfound by gross or microscopic examination of the mastectomy. Prognosis is governed by the number of \ninvolved lymph nodes and is not altered whether or not the primary carcinoma is identified.\nDuctal Carcinoma in Situ (DCIS).\u2002 DCIS is most often occult on gross examination due to the lack of \na surrounding desmoplastic response. The one exception is comedo type DCIS, which is often associated \nwith periductal fibrosis and can have pinpoint areas of necrosis (\u201ccomedone-like\u201d), which are extruded when \nthe tissue is gently squeezed. The grossly involved area may be an ill-defined area of firm gray/white tissue.\nPapillary carcinoma in situ may appear as a well-circumscribed mass with a fine papillary surface when \nit involves a large duct.\nPaget Disease of the Nipple.\u2002 Paget disease of the nipple is a result of DCIS spreading from a ductal \nsystem into the skin of the breast. The normal squamous barrier is disrupted and extracellular fluid seeps \nonto the surface, resulting in a scale crust. This crust is removed by cleaning the skin prior to surgery \nand involved nipples usually have a normal gross appearance in the specimen. The malignant cells rarely \nextend beyond the nipple and areola within the skin.\nFibroadenomas (FAs).\u2002 FAs are the most common benign mass-forming lesions of the breast and \nusually occur in women under 40 years of age. The characteristic appearance is of an ovoid or smoothly-\nlobulated mass with a rubbery, firm consistency. Clefts are often grossly apparent due to stromal over\u00ad\ngrowth surrounded by epithelial lining cells. FAs are firmer than the surrounding tissue and appear to \nstand up from it and bulge outward. FAs may infarct during pregnancy and appear poorly circumscribed \nwith areas of necrosis and hemorrhage. There are numerous other benign lesions that are grossly similar \n(e.g., hamartomas, adenosis lesions, sclerosing lobular hyperplasia, pseudoangiomatous stromal hyper\u00ad\nplasia, fibrous tumors). Well-circumscribed carcinomas should be suspected in women >50 years of age \nand when the lesion is not grossly typical for FA (e.g., flat or depressed instead of bulging).\nA\nB\nC\nD\nDuctal carcinoma\nMedullary carcinoma\nFibroadenoma\nPhyllodes tumor\nWell circumscribed\nFigure 15-1.\u2002 Gross appearance of breast lesions.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_284.png", "summary": "The page discusses various types of breast lesions, including metastatic carcinoma, DCIS, Paget disease, and fibroadenomas, highlighting their gross appearances and clinical implications.", "questions": [ "How does the presence of necrosis in comedo type DCIS affect its gross appearance?", "What is the significance of Paget disease of the nipple in relation to breast cancer progression?", "How can fibroadenomas be distinguished from other benign breast lesions based on their gross appearance?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 285, "text": "BREAST\u2003 Excisional Biopsies\n267\nPhyllodes Tumors.\u2002 These may grossly resemble FAs. Phyllodes tumors are usually larger, may have \nareas of necrosis and hemorrhage, and may be less well circumscribed due to invasion into the surround\u00ad\ning stroma. Most large biphasic stromal lesions (either FAs or phyllodes tumors) will have \u201cleaf-like\u201d \nprotruberances due to areas of stromal overgrowth. Phyllodes tumors are rare and usually present at an \nolder age than FAs.\nFibrocystic Changes.\u2002 Fibrocystic changes \u00adoccasionally form palpable masses. A single unilocular \ncyst is \u00adgenerally aspirated and not excised. However, recurrent cysts or cysts that fail to disappear after \naspiration (e.g., due to debris within the cyst) may be excised. Tissue may be \u00addiffusely firm due to small \ncysts and fibrosis resulting from chronic inflammation. A discrete mass is usually not present.\nRadial Sclerosing Lesions (Radial Scars).\u2002 These lesions consist of a central hyalinized nidus with \nradiating arms consisting of epithelial hyperplasia. These lesions are rarely palpable. However, they may \npresent as spiculated mammographic densities closely mimicking invasive carcinomas. The center of the \nlesion is usually small in relation to the long arms as opposed to invasive carcinomas that have a more \nsolid center and shorter spiculations. Grossly, radial sclerosing lesions may look stellate but are often \nsoft except for the small firm nidus. Frozen sections should be avoided as the center of the lesion is easily \nmistaken for an invasive carcinoma and examination of the intact lesion is helpful for diagnosis.\nBiopsy Sites.\u2002 Most biopsy sites will form irregular firm (but not hard) areas of fibrosis with streaks \nof yellow (fat necrosis). Core needle biopsy sites may be quite subtle and can heal in less than a month. \nSome radiologists use systems that insert gel beads and a clip into the biopsy site. The gel beads will \nlook like ovoid white hard masses that may pop out of the biopsy site. The beads will be absorbed \nover time.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Mass: Four to five cassettes of possible carcinomas or one section per cm for other grossly identifi\u00ad\nable masses.\nIn the absence of a discrete mass, at least 10 cassettes of fibrous tissue are submitted.\nIf a diagnosis of DCIS has been made on core needle biopsy, it is preferable to completely submit \nthe specimen in sequence.\n\t \u2022\t \u0007Margins: At least twelve perpendicular sections representing each of the six margins for oriented \nspecimens suspicious for carcinomas (two cassettes per margin).\n\t \u2022\t \u0007Normal tissue: At least one cassette of representative fibrous tissue if not present in the slides \nabove.\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cleft breast mass\u201d is a 6 (medial \nto lateral) \u00d7 4 (inferior to superior) \u00d7 3 (anterior to posterior) cm breast biopsy with two sutures - the \nlong designated \u201clateral\u201d and the short designated \u201csuperior.\u201d There is a 2.3 \u00d7 2.0 \u00d7 1.5 cm very hard \nwhite stellate mass that is grossly within 0.1 cm of the medial resection margin. The mass is 1 cm from \nthe superior margin, 1.5 cm from the inferior margin, 4 cm from the lateral margin, 1.5 cm from the \nposterior margin, and 0.8 cm from the anterior margin. The remainder of the breast tissue consists of \ngrossly unremarkable adipose tissue. The entire tumor and 80% of the entire specimen are submitted for \nhistologic examination. The specimen is inked for the evaluation of margins: posterior = black; anterior = \nblue; superior = red; inferior = green; lateral = yellow; medial = orange. Sections of margins are submitted \nfor microscopic examination.\nCassettes #1-2: Tumor and medial margin, 2 frags, ESS.\nCassettes #3-4: Tumor and anterior margin, 4 frags, ESS.\nCassettes #5-6: Remainder of tumor, 2 frags, ESS.\nCassettes #7-8: Superior margin, 2 frags, RSS.\nCassettes #9-10: Inferior margin, 2 frags, RSS.\nCassettes #10-11: Lateral margin, 2 frags, RSS.\nCassettes #12-13: Posterior margin, 2 frags, RSS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_285.png", "summary": "The page discusses various types of breast excisional biopsies, including phyllodes tumors, fibrocystic changes, and radial sclerosing lesions.", "questions": [ "How do phyllodes tumors differ from fibroadenomas?", "What are the characteristics of radial sclerosing lesions?", "What is the recommended approach for biopsy sites healing after core needle biopsies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 286, "text": "BREAST\u2003 Excisional Biopsies\n268\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR TUMORS\nSee section after \u201cMastectomies.\u201d\nExcisional Biopsies for Mammographic Lesions with Wire Localization\nMammographic (nonpalpable) lesions are biopsied by placing a wire in the breast at the site of the mam\u00ad\nmographic abnormality. After excision, the biopsy is sent to mammography for a specimen radiograph \nand a radiologist confirms the presence of the lesion. The pathologist should receive a copy of the speci\u00ad\nmen radiograph as well as the interpretation by the radiologist. It is helpful to have the radiologist circle \nlesions (e.g., faint calcifications) that are not readily apparent.\nBiopsies performed for mammographic densities will reveal invasive carcinomas in 20% to 30% of \ncases (average size 1 cm), DCIS alone in less than 5%, and fibroadenomas in 20% to 30%. The types of \nmass-forming lesions are similar to those forming palpable masses but are smaller in size.\nBiopsies performed for mammographic calcifications without a mass will reveal invasive carcinomas \nin less than 10% of cases (average size less than 1 cm), DCIS alone in 20% to 30%, and fibroadenomas \nin 5% to 10%.\nBiopsies for architectural distortion are less common and may either correspond to irregular involu\u00ad\ntion, DCIS, or diffusely invasive carcinomas such as invasive lobular carcinoma.\nBiopsies for MRI-detected areas of enhancement are performed for lesions that cannot be identified \nby mammography or US (otherwise these modalities would be used to identify the lesion). A specimen \nradiograph may be performed, but usually does not show the targeted lesion (although other incidental \nfindings such as \u00adcalcifications may be present). The specimen should be completely \u00adsubmitted, if possible.\nIn general, women who undergo MRI are at high risk for carcinoma either because they have current or \nprior breast carcinoma or because they have a germ line mutation. Around one third of these biopsies will \nreveal carcinoma.3 Two thirds are small invasive carcinomas and one third DCIS.\nWide excisions after a core needle diagnosis of malignancy are processed similarly to diagnostic exci\u00ad\nsional biopsies, as the lesion is still within the specimen and will be marked with a wire. More extensive \nsampling (usually submission of the entire specimen) is indicated if a diagnosis of DCIS or ADH has \nalready been established. Important prognostic factors for DCIS are the size of the lesion and distance \nfrom the margins (preferably at least 1 cm). In order to optimally evaluate these features, it is usu\u00ad\nally preferable to submit the entire specimen in consecutive order with oriented margins. If this would \nrequire more than 20 blocks, it may be appropriate to examine initial sections before submitting addi\u00ad\ntional tissue.\nSPECIMEN PROCESSING FOR MAMMOGRAPHIC DENSITIES\nThese specimens usually contain the same types of lesions present in biopsies for palpable masses with \nthe exception that the lesions are smaller. They may be processed in a similar fashion if the lesion is \ngrossly evident. Lesions that cannot be identified grossly will require radiologic \u00adguidance.\n \n1.\t \u0007Examine the specimen radiograph and the radiologist\u2019s report, and determine what type of mam\u00ad\nmographic lesion is present (irregular, well-\u00adcircumscribed, ill-defined) and its location within the \nspecimen using the shape of the specimen and the wire as guides. Larger masses can often be \n\u00adpalpated.\nIt is helpful to identify and label the four margins \u00adidentified on the specimen radiograph in order \nto compare radiographic distance from margins to microscopic findings.\nThe specimen can be inked one color if not oriented or multiple colors if oriented.\nThe specimen can be bisected along the plane of the wire. In the majority of cases, a gross lesion \nwill be identified corresponding to the radiologic density and the specimen can be processed as for \npalpable masses.\nIn rare cases, if no gross lesion can be identified, it is important to identify the tissue in the \narea of the radiologic density. It is usually difficult or impossible to find a subtle mass lesion by \nradiographing the specimen again once the specimen has been sliced. If the site of the radiographic \nlesion cannot be identified, all fibrous tissue should be processed.\nNever take tissue for special studies or research unless a definitive diagnosis of invasive carci\u00ad\nnoma has been established.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_286.png", "summary": "Excisional biopsies for mammographic lesions with wire localization are commonly performed, revealing a variety of lesions including invasive carcinomas, DCIS, and fibroadenomas.", "questions": [ "What are the common findings in biopsies performed for mammographic densities?", "What are the differences in findings between biopsies performed for mammographic calcifications with and without a mass?", "Why is it important to submit the entire specimen in consecutive order with oriented margins for optimal evaluation of DCIS?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 287, "text": "BREAST\u2003 Excisional Biopsies\n269\n \n2.\t \u0007If the specimen is oriented, oriented margins should be submitted if the lesion is suspicious for \nmalignancy. Up to two cassettes per margin (12 total) may be submitted.\n \n3.\t \u0007If the entire specimen is not submitted, the gross description should make a statement estimating \nthe percentage of the specimen submitted.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Mass: Four to five cassettes of possible invasive carcinomas or one section per cm for other grossly \nevident masses.\nIf a diagnosis of DCIS has been made, it is preferable to submit the entire specimen in sequence.\nIn the absence of an identified mass, all fibrous breast tissue is submitted.\n\t \u2022\t \u0007Margins: Up to 12 perpendicular sections representing each of the six margins for oriented speci\u00ad\nmens suspicious for carcinoma or known to have carcinoma.\n\t \u2022\t \u0007Normal tissue: At least one cassette of representative fibrous tissue if not present in the slides above.\nSPECIMEN PROCESSING FOR MAMMOGRAPHIC CALCIFICATIONS OR PRIOR NEEDLE DIAGNOSES OF DCIS OR ADH\nExcisions for mammographic calcifications have the highest probability of revealing DCIS (20% to 30%). \nCarcinomas are almost always at or very near the area of the calcifications.4 The lesions are usually not \ngrossly evident and the specimen usually consists of benign-appearing breast tissue.\n \n1.\t \u0007Examine the specimen radiograph and the radiologist\u2019s report and determine the location of the \ncalcifications or clip within the specimen. \u00adCalcifications most likely to be associated with DCIS \nare small, numerous, clustered, and may be linear or branching. If a core has been performed and \nhas removed most of the calcifications, the radiologists will have placed a small clip at the biopsy \nsite. Large (\u201c\u00adpopcorn\u201d) calcifications are not normally biopsied, but may be present incidental to \nanother mammographic lesion.\n \u2022\t \u0007The specimen can be inked one color if not oriented or multiple colors if oriented.\n \u2022\t \u0007It is helpful to identify and label the four margins identified on the specimen radiograph in order \nto compare radiographic distance from margins to microscopic findings.\n \u2022\t \u0007The specimen may be bisected along the plane of the wire. In the majority of cases, no gross \nlesion will be present. If a gross lesion is present correlating with the radiologic calcifications \n(e.g., a small hyalinized fibroadenoma with calcifications, a biopsy site, gel beads corresponding \nto a core site), the specimen may be processed as for palpable masses.\n \u2022\t \u0007If there is no gross lesion, and the site of the calcifications cannot be identified (e.g., because the \nwire had fallen out of the specimen), then the sliced tissue should be re-radiographed. Small speci\u00ad\nmens (e.g., submitted in <10 cassettes) may be submitted in entirety without additional radiography.\n \u2022\t \u0007Low suspicion lesion: The tissue containing the calcifications is completely submitted along \nwith adjacent tissue on either side. The remaining slices may be placed in designated cassettes to \nmaintain orientation, but need not be submitted if the tissue appears grossly benign. The loca\u00ad\ntion of this tissue can be marked on the sliced specimen radiograph. If the blocks of the mam\u00ad\nmographic calcifications reveal atypical hyperplasia or DCIS, all additional fibrous tissue should \nbe examined microscopically.\n \u2022\t \u0007High suspicion lesion or prior diagnosis of DCIS or ADH by core needle biopsy: Com\u00ad\npletely submit all the tissue containing the mammographic calcifications, all fibrous tissue, and \nat least two representative sections of each margin. It preferable to submit the sections in order \n(e.g., from medial to lateral) to be able to determine the extent of the DCIS.\n \u2022\t \u0007Never take tissue for special studies or research unless a firm diagnosis of invasive carcinoma has \nbeen established.\n \n2.\t \u0007If the entire specimen is not submitted, the gross description should make a statement estimating \nthe percentage of the specimen submitted.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Calcifications: All tissue containing the radiologic calcifications and adjacent tissue. Indicate which \nblocks contain tissue with calcifications. If DCIS or ADH has been diagnosed previously, it is prefer\u00ad\nable to submit all fibrous tissue.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_287.png", "summary": "The page provides guidelines for handling excisional biopsies of the breast, including submitting oriented margins, estimating the percentage of specimen submitted, and processing specimens for mammographic calcifications or prior needle diagnoses of DCIS or ADH.", "questions": [ "How many cassettes per margin can be submitted for oriented specimens suspicious for malignancy?", "What is the recommended approach for processing specimens with mammographic calcifications?", "Why is it important to examine the specimen radiograph and the radiologist's report before determining the location of calcifications?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 288, "text": "BREAST\u2003 Re-excisions\n270\n\t \u2022\t \u0007Margins: At least twelve cassettes of two perpendicular sections from each of the six margins for \noriented specimens with known or suspected carcinoma.\nSAMPLE DICTATION\nReceived labeled with the patient\u2019s name and unit number and \u201cright breast\u201d is a 5 (medial to lateral) \u00d7 3 \n(inferior to superior) \u00d7 2 (anterior to posterior) cm breast biopsy with a localization wire in place, a short \nsuture marking the superior margin, and a long suture marking the lateral margin. An accompanying \nspecimen radiograph demonstrates a tight cluster of calcifications in the central portion of the specimen, \nadjacent to the localization wire. The specimen is inked for the evaluation of margins: posterior = black; \nanterior = blue; superior = red; inferior = green; lateral = yellow; medial = orange. The tissue consists of \ndense fibrous parenchyma with multiple small blue dome cysts. A gross lesion at the site of the radiologic \ncalcifications is not seen. The specimen is re-radiographed and the area of calcifications identified. This \narea is 0.2 cm from the superior margin, 2 cm from the inferior margin, 1 cm from the posterior margin, \n0.5 cm from the anterior margin, 3 cm from the medial margin, and 2 cm from the lateral margin. Two \nsections of each margin are submitted for microscopic examination. The margins consist of unremark\u00ad\nable adipose tissue. 50% of the specimen is submitted including all fibrous tissue. The location of the \ntissue blocks is recorded on a specimen diagram.\nCassettes #1-2: Mammographic microcalcifications with superior margin, 2 frags, ESS.\nCassettes #3-4: Closest lateral margin, 1 frag, RSS.\nCassettes #5-6: Closest medial margin, 1 frag, RSS.\nCassettes #7-8: Closest anterior margin, 1 frag, RSS.\nCassettes #9-10: Closest inferior margin, 1 frag, RSS.\nCassettes #11-12: Closest posterior margin, 1 frag, RSS.\nCassettes #13-15: Remaining fibrous tissue, 5 frags, ESS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR TUMORS\nSee section after \u201cMastectomies.\u201d\nRE-EXCISIONS\nBreast re-excision is a general term for larger excisions of an excisional biopsy site when malignancy has \nbeen found. Lumpectomies (used loosely because usually a \u201clump\u201d is no longer present) and quadran\u00ad\ntectomies (used to refer to a larger resection of an entire breast quadrant) are examples of this type of \nspecimen. Re-excisions often have a small ellipse of skin (containing the original biopsy scar) that may be \noriented with sutures of different lengths. The nipple will not be present. A biopsy cavity must be identi\u00ad\nfied. Separate axillary dissections or sentinel node biopsies are usually performed if invasive carcinoma \nwas diagnosed.\nIn the absence of gross lesions, the entire specimen would need to be submitted to reliably detect \nevery case of residual carcinoma of possible clinical significance. In one study, submitting one block \nper centimeter of maximal tissue dimension detected 88% of lesions of major clinical significance and \n81% of lesions with any clinical significance, and resulted in a 52% reduction in the number of blocks \n\u00adexamined.5 Submitting two blocks per centimeter resulted in the detection of 97% of lesions of major \nclinical significance and 95% of lesions with any clinical significance, and resulted in a 17% reduction in \nthe number of tissue blocks.\nThe amount of tissue appropriate to sample will also vary depending on the prior diagnosis. Almost \nall women with a history of invasive carcinoma will receive radiation to the breast, and the purpose of the \nmargin evaluation is to exclude relatively large areas of residual DCIS. Thus, such re-excisions may not \nneed to be sampled in entirety.\nAlthough many women with DCIS alone will also receive radiation to the breast, there may be a sub\u00ad\ngroup of women with widely clear margins that do not require radiation. Therefore, thorough margin \nevaluation of the re-excision specimen in these patients is more important for guiding patient manage\u00ad\nment. Even a small amount of DCIS at or near the margin would be treated with either additional sur\u00ad\ngery or radiation. In addition, if an area of invasion is found in the re-excision, the patient\u2019s prognosis \nchanges, and very likely her treatment as well.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_288.png", "summary": "The page discusses breast re-excisions, which are larger excisions of excisional biopsy sites when malignancy is found. It outlines the process of evaluating margins and submitting tissue for examination.", "questions": [ "What are the specific steps involved in evaluating margins for breast re-excisions?", "What are the different types of specimens that fall under the category of breast re-excisions?", "Why is it important to submit the entire specimen in the absence of gross lesions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 289, "text": "BREAST\u2003 Re-excisions\n271\n \n1.\t \u0007Record the total dimensions, size and color of skin ellipse, size and condition (well-healed, recent) \nof scar.\n \u2022\t \u0007Ink the entire specimen except for the skin. Different colors of ink can be used if this will help in \nidentifying margins.\n \u2022\t \u0007Serially section the specimen without cutting through the skin or any sutures. Carefully palpate \nthe specimen locating the biopsy cavity and any other lesions.\n \u2022\t \u0007Describe the size of the indurated area around the cavity, the diameter and contents of the cavity, \nthickness (range) of cavity wall, and the size of any areas suspicious for residual tumor. Describe \nthe nearest approach of the biopsy cavity and firm surrounding areas to the margins. Large \nspecimens should be fixed overnight in formalin with gauze between the sections.\n \n2.\t \u0007Submit up to four sections of the biopsy cavity, selecting areas that are most suspicious for residual \ncarcinoma close to the margins. More extensive sampling of suspicious areas around the biopsy \nsite and in the remaining breast is indicated for patients in whom only DCIS has been diagnosed. \nInvasive carcinoma may be difficult to detect due to the \u00adfibrosis of the prior biopsy cavity.\n \n3.\t \u0007Sample all margins, giving orientation if provided. Twelve cassettes (corresponding to two sections \nof each of the six margins) are usually adequate unless there are multiple suspicious areas. Cases of \nDCIS alone should be sampled more thoroughly or completely submitted if possible.\n \n4.\t \u0007Sample the skin to evaluate possible dermal lymphatic involvement or direct skin invasion.\n \n5.\t \u0007If the entire specimen is not submitted, give an \u00adestimate of the amount of tissue submitted for \n\u00adhistologic examination.\n \n6.\t \u0007If an axillary tail is submitted, see the section under \u201c\u00adAxillary Dissections\u201d below for instructions \non \u00adprocessing.\nOccasionally a wire localization will be performed in addition to a re-excision to remove a mammo\u00ad\ngraphic lesion close to a prior biopsy site. These specimens are processed in order to evaluate the radio\u00ad\nlogic lesion as well as the prior biopsy cavity.\nSPECIAL STUDIES\nSpecial studies are usually not indicated because the primary tumor has been removed. If gross tumor is \npresent, it would be prudent to determine whether studies have been performed on a prior specimen and \nconsider determining hormone receptor status and HER2/neu on fixed tissue.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Biopsy cavity: At least four cassettes including any areas suspicious for residual carcinoma.\n\t \u2022\t \u0007Margins: At least two sections of each margin. Take additional sections for specimens with only \nDCIS. It is preferable to submit the entire specimen, or all fibrous tissue, in these cases.\n\t \u2022\t \u0007Skin: One cassette.\nSAMPLE DICTATION\nThe specimen is received fresh in two parts labeled with the patient\u2019s name and unit number.\nThe first part labeled \u201c#1, right lumpectomy\u201d consists of a 10 (medial to lateral) \u00d7 9 (inferior to supe\u00ad\nrior) \u00d7 7 (anterior to posterior) cm re-excision specimen with a 4 \u00d7 1 cm white skin ellipse containing \na 3.5 cm well-healed surgical scar and two orienting sutures designated \u201cmedial\u201d and \u201csuperior.\u201d The \nspecimen is inked for the evaluation of margins: posterior = black; anterior = blue; superior = red; inferior \n= green; lateral = yellow; medial = orange. 2 cm deep to the skin there is a 3 \u00d7 3 \u00d7 2 cm biopsy cavity \nfilled with blood clot and surrounded by dense white tissue (approximately 1 cm in greatest thickness) \nand areas of fat necrosis. No areas grossly suspicious for invasive carcinoma are seen. The biopsy cavity \nis 0.5 cm from the deep margin, which is the closest margin. The remaining margins are at least two cm \nfrom the cavity and are taken as perpendicular sections for microscopic examination. The remainder of \nthe specimen consists of yellow/white \u00adadipose tissue. Approximately 70% of the specimen is submitted \nfor histologic examination.\nCassettes #1-4: Biopsy cavity, 4 frags, RSS.\nCassettes #5-6: Biopsy cavity and deep margin, 2 frags, RSS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_289.png", "summary": "The page provides detailed instructions on the proper handling and sampling of breast re-excision specimens, including the importance of thorough sampling of suspicious areas for residual carcinoma and proper evaluation of margins.", "questions": [ "What are the key steps involved in handling and sampling breast re-excision specimens?", "Why is it important to thoroughly sample suspicious areas for residual carcinoma?", "How should skin involvement be evaluated in breast re-excision specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 290, "text": "272\nBREAST\u2003 Mastectomies for Malignancy\nCassettes #7-8: Inferior margin, 2 frags, RSS.\nCassettes #9-10: Medial margin, 2 frags, RSS.\nCassettes #11-12: Superior margin, 2 frags, RSS.\nCassettes #13-14: Lateral margin, 2 frags, RSS.\nCassette #15: Skin, 3 frags, RSS.\nCassette #16: Representative fibrous tissue away from the biopsy cavity, 2 frags, RSS.\nThe second part labeled \u201c#2, axillary nodes\u201d consists of a 6 \u00d7 5 \u00d7 3 cm fragment of adipose tissue con\u00ad\ntaining twelve possible lymph nodes. The largest lymph node measures 1.2 cm in size and is firm tan/\nwhite with irregular borders.\nCassette #13: Largest lymph node, 3 frags, ESS.\nCassette #14: Three lymph nodes, 3 frags, ESS.\nCassettes #15 - 18: Two lymph nodes per cassette, inked blue or black, 8 frags, ESS.\nCassette #19: Possible small lymph nodes, 5 frags, ESS.\nSHAVE MARGINS\nShave margins consist of tissue take from a selected area of the primary biopsy cavity. These specimens \nare usually flattened pieces of tissue with one side marked with a suture as the new margin. It is preferable \nto mark these specimens with two colors of ink corresponding to the new margin and the side next to the \nbiopsy site (i.e., not marginal tissue). Sections are taken perpendicular to the new margin. At least one \nsection per 1 cm of length should be submitted. Additional sampling is indicated for women with DCIS \nalone (preferably the entire specimen unless it is quite large).\nMASTECTOMIES FOR MALIGNANCY\nA mastectomy attempts to remove all breast tissue. In some women, there may be ducts within subcuta\u00ad\nneous tissue of the chest wall which will not be removed. There are several types of mastectomy:\n\t\u2022\t \u0007Subcutaneous \u2013 does not remove skin or nipple (only performed in males for gynecomastia)\n\t\u2022\t \u0007Simple \u2013 removes the nipple with skin, but axillary lymph nodes are not intentionally removed (how\u00ad\never, a sentinel node biopsy may be performed)\n\t\u2022\t \u0007Prophylactic \u2013 a simple mastectomy in a woman at high risk for carcinoma\n\t\u2022\t \u0007Skin sparing \u2013 removes the nipple and areola with a \u00adnarrow rim of surrounding skin\n\t\u2022\t \u0007Modified radical \u2013 a simple mastectomy with an axillary dissection (Fig. 15-2)\n\t\u2022\t \u0007Radical \u2013 removes the pectoralis muscles (performed only in exceptional cases with chest wall invasion)\nMost women can be treated by breast conservation. Women undergoing mastectomy are more likely \nto have the following:\n\t\u2022\t \u0007Multiple cancers that cannot be resected in a single excision. If the cancers were diagnosed by core \nneedle biopsy, radiologic examination of the specimen may be necessary to find the known cancers.\n\t\u2022\t \u0007Locally advanced cancers, often with chest wall or skin invasion. Many of these women will have \nreceived preoperative therapy.\n\t\u2022\t \u0007Inflammatory cancer \u2013 most of these women will have received preoperative therapy.\n\t\u2022\t \u0007Metastatic carcinoma to a lymph node with an occult primary.\n\t\u2022\t \u0007Recurrent cancer in patients having previously been treated with radiation.\n\t\u2022\t \u0007Women at high risk for additional carcinomas (e.g., due to BRCA1 or BRCA2 mutations).\nThus, mastectomies tend to be complicated specimens. Unless a good history is provided (and \u201cbreast \ncancer\u201d does not constitute a good history!), it is usually necessary to review the medical record to deter\u00ad\nmine the number and type of lesions present, as well as whether or not any preoperative therapy has been \ngiven, prior to gross examination of the specimen. Additional important information can be derived from \nmastectomies after excision of an invasive carcinoma (e.g., increase in tumor size, deep margin involve\u00ad\nment, lymphatic invasion, skeletal muscle invasion, skin invasion) or DCIS (e.g., unsuspected areas of \ninvasion). Mastectomy specimens require meticulous gross examination as only a small proportion of \nthe specimen is examined microscopically. In one study, 83% of major diagnostic discrepancies in breast \nspecimens were due to inadequate sampling of tissue from mastectomies.6", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_290.png", "summary": "This page discusses the specimen processing and types of mastectomies performed for malignancy, including the different margins and lymph node evaluations.", "questions": [ "What are the different types of mastectomies mentioned on this page?", "How are shave margins prepared and processed in the laboratory?", "What are some indications for women to undergo mastectomy for malignancy according to the text?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 291, "text": "273\nBREAST\u2003 Mastectomies for Malignancy\nDifficult cases:\n\t\u2022\t \u0007Mastectomies after core needle biopsy are often problematic as it may be difficult to find the site of \nthe original lesion. If the biopsy was performed for a palpable mass or a mammographic density, most \nlesions can be found by careful gross examination. If the biopsy was performed for calcifications, it is \nhelpful to radiograph the specimen prior to sectioning to locate the area of calcifications and any clips \nplaced by the radiologist. Additional radiographs after sectioning of the specimen may be helpful to guide \nselection of tissue. Clips are difficult to see and can be displaced or lost after sectioning of the specimen.\n\t\u2022\t \u0007Mastectomies or excisions after preoperative \u00adtherapy can be problematic as the tumor bed may be \ndifficult to detect if there has been a marked response. The extent of residual carcinoma (viable or non\u00ad\nviable) is an important prognostic factor and must be documented. Women with a complete response \n(no residual invasive carcinoma) have a better prognosis than women with a partial or no response. The \ntumor bed must be identified and sampled.\nIf the carcinoma was originally palpable, the surgeon can indicate the site with a suture or a descrip\u00ad\ntion. If there were mammographic findings associated with the carcinoma (e.g., calcifications or a clip \nplaced prior to treatment), the specimen can be radiographed. Calcifications generally do not disappear \nafter treatment. Once the site of the prior carcinoma is identified, it is helpful to take a series of consecu\u00ad\ntive sections to sample the tumor bed (e.g., one tissue section per cm from medial to lateral in an area of \na previously palpable 5 cm carcinoma).\nProcessing the Specimen\u2002\n \n1.\t \u0007Describe:\n \u2022\t \u0007Weight: Entire specimen\n \u2022\t \u0007Dimensions: Total size of breast, size of axillary dissection\n \u2022\t \u0007Skin ellipse: Size, color, presence of skin retraction, presence of ulceration over tumors, \nskin lesions. Occasionally there will be red, oval-shaped marks that are often associated with \nAxillary tail\nScar\nUO\nUI\nLI\nLO\nNipple\nAreola\nLateral margin (Do not ink)\nDeep margin (Smooth fascial plane\nmay have small portion of\nattached muscle)\nFigure 15-2.\u2002 Modified radical mastectomy (left side).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_291.png", "summary": "Mastectomies for malignancy can be challenging in cases where the original lesion site is difficult to locate, especially after core needle biopsy or preoperative therapy.", "questions": [ "How can the site of the original lesion be found after a mastectomy following core needle biopsy?", "What are the challenges in detecting the tumor bed after preoperative therapy?", "Why is it important to document the extent of residual carcinoma in mastectomy specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 292, "text": "274\nBREAST\u2003 Mastectomies for Malignancy\n\u00addetachment of the overlying epidermis at the edges of the skin ellipse. These are clamp marks \nmade during the procedure that need not be sampled.\n \u2022\t \u0007Nipple: Size of nipple (i.e., the raised area where the ducts emerge, not the pigmented areola), \nsize of areola, retraction, inversion, irregular or crusted surface (may indicate Paget disease of \nthe nipple).\n \u2022\t \u0007Scar: Size and condition (well-healed, recent, sutured) of surgical incision or scar, location of \nincision (e.g., quadrant - most commonly upper outer) and distance from nipple. Scars are most \neasily found when the specimen is fresh. Semi-circular scars around the areola may be difficult \nto see. Scars can be distinguished from marks on the skin by making an incision and looking for \nthe area of underlying dermal fibrosis. A scar may be absent if the mastectomy was performed for \nprophylactic reasons, if the original diagnosis was made with a needle biopsy, or if a skin-sparing \nmastectomy is performed. If a scar or a biopsy cavity cannot be found and the reason for the \nmastectomy is unclear, the surgeon should be called.\n \u2022\t \u0007Deep margin: Usually consists of a smooth fascial plane overlying the pectoralis muscle. Areas of \nirregularity or attached portions of skeletal muscle are documented (size and location).\nIf the prior procedure was a core needle biopsy for a nonpalpable lesion, it may be useful to radiograph \nthe intact specimen before sectioning.\n \n2.\t \u0007Ink the deep fascial margin black, but not the lateral soft tissue margins. The adipose tissue not \nat the deep margin abuts subcutaneous tissue in the patient. Although breast ducts can some\u00ad\ntimes be present in subcutaneous tissue, this tissue is not generally considered to be a true mar\u00ad\ngin and a positive margin in this area is of unknown clinical significance. If this tissue is inked, it \nshould be in a different color than the deep fascial margin and reported separately as a skin flap \nmargin.\n \n3.\t \u0007Separate the axillary tail and fix in a separate container. If removing the tail will make the specimen \ndifficult to orient, cut a notch in the skin at the site of the tail. See the section on \u201cAxillary Dissec\u00ad\ntions\u201d for processing.\nLymph nodes MUST be searched for even in specimens designated \u201csimple mastectomies\u201d. Often \none or two low lymph nodes (but occasionally many more than this) are included; they are often \nthe most clinically important tissue to examine.\n \n4.\t \u0007Serially section the specimen at approximately 0.5 cm intervals but do not cut through the skin. \nCarefully palpate all sections and locate the biopsy cavity and any other suspicious lesions. This \nmust be done in the fresh state because formalin hardens tissues and small lesions may be missed.\nDescribe size, location (quadrant), and distance from the deep margin and skin of any lesions \nincluding the biopsy cavity. If tumor is present, also describe color, borders (infiltrating, well-\ncircumscribed, ill-defined), consistency (firm, hard), relationship, if any, to the biopsy cavity and \nnipple, and distance from skin, deep margin, and other margins (e.g., lateral) if involved.\nThe deep margin is always taken as a perpendicular margin because this is a true tissue plane \nand even a thin rim of tissue (e.g., less than 0.1 cm) would be considered a negative margin. Any \nskeletal muscle present is sampled to look for muscle invasion.\nIf multiple lesions are present, describe their relationship to each other (distance and direction) \nand submit a cassette of tissue in between the lesions.\nThe remainder of the non-lesional breast tissue is described (e.g., predominantly fatty, firm, \nwhite, cysts [size], gross calcifications, etc.).\nIf a grossly inapparent radiographic lesion is present (e.g., calcifications), it is usually useful to \nradiograph the sliced specimen to ensure that the lesion is sampled.\n \n5.\t \u0007Fix the specimen overnight in a large container filled with formalin. Gauze is used to separate the \nsections and is placed underneath the specimen.\n \n6.\t \u0007The following day, tissue blocks are taken from the mastectomy at the sites noted (see below).\nNipple: In the usual nipple examination, one perpendicular section is taken. This type of section will \nonly examine one to four of the main nipple ducts. If there is a reason to more thoroughly examine the \nnipple (e.g., the nipple is grossly abnormal or there is a clinical history of Paget disease) additional sec\u00ad\ntions may be taken (Fig. 15-3). The nipple is amputated in a plane parallel to the skin surface. A second, \ndeeper, section is taken in the same plane. This section will demonstrate all the major ducts as they \napproach the nipple. The more superficial section is serially sectioned perpendicular to the skin surface \nand all these slices submitted. These sections will demonstrate most of the nipple ducts as they empty \nonto the skin surface.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_292.png", "summary": "The page discusses important considerations for examining mastectomy specimens for malignancy, including evaluating the nipple, scar, deep margin, and lymph nodes.", "questions": [ "Why is it important to evaluate the size and condition of the nipple and scar during examination of mastectomy specimens?", "What steps should be taken to ensure accurate evaluation of the deep margin in mastectomy specimens?", "Why is it necessary to search for lymph nodes even in 'simple mastectomy' specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 293, "text": "275\nBREAST\u2003 Mastectomies for Malignancy\nPerpendicular sections\nEn face section\nAmputate the nipple\nFigure 15-3.\u2002 Nipple sectioning diagrams.\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cMRM \u2013 left\u201d is an 850 gram left \nmodified radical mastectomy specimen (15 \u00d7 10 \u00d7 5.5 cm) with a white/tan skin ellipse (14 \u00d7 7 cm) and \nan attached axillary tail (7 \u00d7 6 \u00d7 3 cm). There is a 3.4 cm well-healed surgical scar in the upper outer \nquadrant, 2 cm from the unremarkable 0.5 cm nipple. One cm deep to this scar is a firm white area \n(4.5 \u00d7 4.0 \u00d7 2.0 cm) containing a recent biopsy cavity (3.0 cm in diameter) filled with organizing red/\ntan clot, 1.5 cm from the deep margin, which is a smooth fascial plane without skeletal muscle present. \nThe wall of the cavity is firm and white to yellow, ranging from 0.5 to 1 cm in thickness, without gross \ntumor present. The remainder of the breast parenchyma is predominantly white and firm with small \ncysts measuring up to 0.3 cm in greatest dimension. There are fifteen tan lymph nodes in the axillary \ntail, the largest measuring 0.8 cm in greatest dimension. Lymph nodes placed in the same cassette are \ndifferentially inked.\nCassettes #1-4: Biopsy cavity, 4 frags, RSS.\nCassette #5: Deep margin of biopsy cavity, perpendicular section, 1 frag, RSS.\nCassette #6: Skin with scar, 2 frags, RSS.\nCassette #7: Upper outer quadrant, 1 frag, RSS.\nCassette #8: Upper inner quadrant, 1 frag, RSS.\nCassette #9: Lower outer quadrant, 1 frag, RSS.\nCassette #10: Lower inner quadrant, 1 frag, RSS.\nCassette #11: Nipple, 1 frag, RSS.\nCassettes #12-16: Lymph nodes, 3 per cassette, 15 frags, ESS.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Biopsy cavity: At least four sections. More sampling is indicated in cases of DCIS alone (to look for \nfoci of invasion), fewer for cases of known large invasive carcinomas.\n\t \u2022\t \u0007Invasive carcinomas: Residual tumor may be present if the prior procedure was an incisional biopsy \nor a core needle biopsy. Four to five cassettes of tumor including the relationship to skin and deep \nmargin should be submitted.\n\t \u2022\t \u0007Radiologic lesions: Mastectomies may be performed after a prior diagnosis of DCIS or invasive \ncarcinoma by core needle biopsy. The calcifications, density, and/or clip should be located by radio\u00ad\ngraphing the specimen if not grossly evident. The entire area of involved tissue is submitted.\n\t \u2022\t \u0007Skin: One section of biopsy scar. Additional sections should be submitted of skin lesions, carcinoma \ninvolving skin, or if there was a clinical history of inflammatory carcinoma (i.e., carcinoma involving \ndermal lymphatics).\n\t \u2022\t \u0007Deep margin: One section if not grossly involved. Take at the biopsy cavity and near any other \ngross lesions. Always take as a perpendicular margin. Do not routinely sample other deep margins \n(e.g., from quadrants) unless grossly abnormal. Skeletal muscle at the deep margin is sampled using \nperpendicular \u00adsections.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_293.png", "summary": "This page discusses the handling and sectioning of mastectomy specimens for malignancy, including specific instructions for sampling different areas of the breast and surrounding tissues.", "questions": [ "What is the significance of sampling different areas of the mastectomy specimen?", "How does the handling of specimens differ based on the type of carcinoma present?", "Why is it important to take perpendicular sections at the deep margin?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 294, "text": "BREAST\u2003 Axillary Dissections\n276\n\t \u2022\t \u0007Other margins: One perpendicular section may be taken if the biopsy site or a gross lesion \nis very close to a non-deep (subcutaneous tissue) margin. The clinical significance of such \nmargin involvement is unknown and such sections must be clearly distinguished from the deep \nmargin.\n\t \u2022\t \u0007Nipple: One section. Two sections (perpendicular and deep en face) if gross lesions are present or \nif there is a clinical history of Paget disease.\n\t \u2022\t \u0007Representative: One section from each quadrant (upper outer, upper inner, lower quadrants outer, \nlower inner). These sections should be away from any other lesions sampled (e.g., the biopsy cavity). \nIf they are not, this is noted in the gross description. They are taken of fibrous breast parenchyma \n(not adipose tissue).\n\t \u2022\t \u0007Lymph nodes: Each thinly sliced (0.2 to 0.3 cm) and entirely submitted. More than one lymph node \ncan be placed in one cassette if selectively inked in different colors.\nAXILLARY DISSECTIONS\nAxillary dissections are performed for the staging of women with invasive carcinoma. The number of \nlymph nodes with metastases is the most important prognostic factor for women with breast carcinoma. \nTreatment protocols may require a minimum number of examined lymph nodes for entry (typically 6 or \n10) to avoid enrolling women misclassified because of inadequate sampling.\nSee Chapter 27 for instructions on processing. All lymph nodes are thinly sliced and are completely \nsubmitted. The number of lymph nodes with metastases is important for prognosis and for treatment \nprotocols. In order to count the nodes, a single node should be placed in each cassette, or multiple lymph \nnodes may be placed in the same \u00adcassette if differentially inked to avoid mistaking fragments of the same \nlymph node as multiple nodes.\nRecord the total number of lymph nodes, the size of the largest lymph node, and the presence of any \nlymph nodes with areas suspicious for metastatic tumor (firm white lymph nodes or with irregular bor\u00ad\nders). If there is extensive extranodal extension with matting of lymph nodes, estimate the probable total \nnumber of lymph nodes involved.\nMost axillary dissections should yield between 10 and 20 lymph nodes. If fewer than 10 nodes are \nfound grossly, re-examine the specimen and submit any areas that may represent lymph nodes. Nodes \nlargely replaced by fat may be difficult to recognize but will have a firm rim of tissue around the fatty cen\u00ad\nter. If the specimen was not fixed in Bouin\u2019s originally, using this fixative later can help to identify nodes. \nFinally, the entire axillary tail may not have been identified on a mastectomy specimen and additional \nnodes in the lateral portion of the specimen should be sought.\nIf the mastectomy was performed for a diagnosis of extensive DCIS, some surgeons will perform a low \naxillary lymph node dissection. There may be fewer nodes in such specimens.\nAlthough simple mastectomies do not specifically remove axillary nodes, a few low nodes are some\u00ad\ntimes removed. Nodes should always be searched for in lateral tissue and their presence or absence \ndocumented.\nIf a portion of pectoralis minor muscle is attached, the level of the nodes can be determined. Level I \nnodes are inferior, Level II posterior, and Level III superior (these latter nodes often not resected because \nof the greater morbidity involved). The nodes are submitted in cassettes designated as to the levels and \nlabeled this way in the final report.\nSentinel node biopsy is a common procedure for breast carcinoma staging. See Chapter 27, \u201cSentinel \nNode\u201d for instructions on processing.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR BREAST CARCINOMAS\n\t\u2022\t \u0007Specimen: Partial breast, total breast\n\t\u2022\t \u0007Procedure: Needle core biopsy: U/S guided (masses), stereotactic (calcifications, density, archi\u00ad\ntectural distortion), or for palpable mass, incisional biopsy, excisional biopsy for palpable mass, \nexcisional biopsy for mammographic lesion (calcifications, density, architectural distortion), \nnipple duct excision, re-excision, simple mastectomy, skin-sparing mastectomy, modified radical \n\u00admastectomy\n\t\u2022\t \u0007Lymph Node Sampling: No lymph node sampling, sentinel lymph node(s) only, sentinel node with \naxillary dissection, axillary dissection\n\t\u2022\t \u0007Specimen Integrity: Single intact specimen, multiple designated specimens, fragmented specimen", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_294.png", "summary": "Axillary dissections are performed for staging women with invasive carcinoma, with the number of lymph nodes with metastases being a crucial prognostic factor. Proper processing and examination of lymph nodes is essential for accurate staging and treatment planning.", "questions": [ "What is the significance of examining lymph nodes in women with breast carcinoma?", "How should lymph nodes be processed and examined to avoid misclassification?", "What should be recorded during the examination of lymph nodes in axillary dissections?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 295, "text": "BREAST\u2003 Axillary Dissections\n277\n\t\u2022\t \u0007Specimen Size: Greatest dimension of the specimen should be provided, if the procedure is less than \na mastectomy. The size in three dimensions may also be given.\n\t\u2022\t \u0007Specimen Laterality: Right, left breast, unspecified.\n\t\u2022\t \u0007Tumor Site: Upper outer, lower outer, upper inner, lower inner, central, according to clock face, not \nspecified.\n\t\u2022\t \u0007Tumor Size: Invasive: Greatest dimension to nearest 1 mm based on gross and microscopic findings. \nDescribing as \u201csmall\u201d or \u201cmicroscopic\u201d is inadequate for staging (see below). If an exact size cannot \nbe given (e.g., due to fragmentation), an estimate or minimal size is clinically useful. Do not include \nadjacent areas of DCIS in the overall size.\nDCIS: The extent of DCIS refers to the volume of involved breast tissue. Although it is difficult or \nimpossible to give an exact size due to the elasticity of fatty breast tissue, an estimate is clinically useful \nto determine the likelihood of completely removing the DCIS by surgery and the likelihood of occult \nareas of invasion. Extent can be determined using multiple methods:\n\t\n(1)\t \u0007Area of breast tissue involved in a single slide. This method can only be used if DCIS is only \npresent on one slide. In other cases this method greatly underestimates extent.\n\t\n(2)\t \u0007Sequential serial sampling. If the entire specimen has been sectioned such that involved areas \ncan be mapped as to location, the extent of the DCIS can be determined.\n\t\n(3)\t \u0007Number of involved blocks. The number of blocks multiplied by 0.4 cm (or another number \nif the width of gross slices is known) will give an estimate of the extent.\n\t\n(4)\t \u0007Distance from margins. If opposing margins are positive or close, and the distance between \nmargins is known, this size can be used as extent.\nLCIS need not be quantified.\n\t\u2022\t \u0007Tumor Focality: Single focus of invasive carcinoma, multiple foci of invasive carcinoma.\nIf there are multiple invasive carcinomas, special studies should be performed on the largest focus. \nIf smaller carcinomas vary in histologic type or grade, it may be appropriate to also perform special \nstudies on additional carcinomas.\nThe aggregate size of grossly evident invasive carcinomas correlates better with the risk of lymph \nnode metastases than the size of the largest carcinoma. However, sizes should not be added together \nfor T classification. The presence of multiple invasive carcinomas is denoted by \u201cm\u201d or by giving the \nnumber of foci of invasion in parentheses.\n\t\u2022\t \u0007Skin: Not present, no skin invasion, direct invasion without skin ulceration, direct invasion with skin \nulceration, satellite foci of invasive carcinoma.\n\t\u2022 \u0007Nipple: Not involved, DCIS involves nipple epidermis (Paget disease of the nipple).\n\t\u2022 \u0007Skeletal Muscle: No skeletal muscle present, skeletal muscle present and free of carcinoma, carci\u00ad\nnoma invades into skeletal muscle, carcinoma invades into skeletal muscle and into the chest wall. \nInvasion into the pectoralis muscle alone is not considered chest wall invasion.\n\t\u2022\t \u0007DCIS: Not identified, present, architectural pattern.\n\t\u2022\t \u0007Extensive Intraductal Component (EIC): A carcinoma is EIC positive if DCIS is prominent within \nthe area of invasive carcinoma and is present outside the area of invasive carcinoma or if the carcinoma \nis primarily DCIS with only focal invasion.\n\t\t \u0007EIC-positive carcinomas are more likely to have residual carcinoma in the breast if margins are posi\u00ad\ntive or close compared with EIC-negative carcinomas.\n\t\u2022\t \u0007LCIS: Not identified, present.\n\t\u2022\t \u0007Histologic Type: Invasive carcinoma: ductal (no special type), lobular, mucinous, tubular, medullary, \nother rare types.\n\t\t \u0007DCIS, LCIS.\nIn situ carcinoma with microinvasion (foci of invasive carcinoma measuring less than 0.1 cm in size).\n\t\u2022\t \u0007Histologic Grade: Invasive carcinoma: Graded using the Nottingham Histologic Score (the Elston-\nEllis modification of the Scarff-Bloom-Richardson grading system; see Table 15-3 later).\n\t\t \u0007Grade all histologic subtypes of carcinoma. Necrosis is an additional poor prognostic indicator if \nextensive (\u22651 HPF).\nDCIS: Nuclear grade (low, intermediate, high), presence or absence of necrosis. Necrotic \nareas should contain ghost cells and karyorrhectic debris to distinguish necrosis from secretory \n\u00admaterial.\n\t\u2022\t \u0007Margins: The method of evaluating and reporting margins has not been standardized. If shave mar\u00ad\ngins (parallel to the margin) are taken by the pathologist, this must be specified. Perpendicular margins \nare recommended.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_295.png", "summary": "This page provides guidelines for reporting on breast axillary dissections, including specimen size, tumor site, tumor size, DCIS extent, tumor focality, skin and nipple involvement, and skeletal muscle invasion.", "questions": [ "How is the extent of DCIS determined in breast specimens?", "What special studies should be performed on multiple foci of invasive carcinoma?", "How does the aggregate size of grossly evident invasive carcinomas correlate with the risk of lymph node metastases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 296, "text": "BREAST\u2003 Axillary Dissections\n278\n\t \u2022\t \u0007Invasive carcinoma: Positive margins (= ink on tumor), give distance to closest margin. Describe \nextent of margin involvement (e.g., unifocal, multifocal, extensive, or give number of slides with \nmargin involvement). Give orientation of positive margins if the specimen was oriented.\n\t\t \u0007DCIS: Positive margins (= ink on tumor), give closest approach of DCIS to each margin if oriented. \nDescribe extent of margin involvement (e.g., unifocal, multifocal, extensive, or give number of slides \nwith margin involvement). Give orientation of positive margins if the specimen was oriented.\n\t\t \u0007LCIS: Margins are not given (recognized to be multifocal and bilateral).\n\t\u2022\t \u0007Treatment Effect: In the breast: If the patient has received preoperative therapy, the response to \ntreatment is a strong prognostic factor. Many different systems for evaluating response have been \ndeveloped (see Miller-Payne and RCB systems [Tables 15-6 and 15-7]).\n\u0007\t\t \u0007Complete response: No invasive carcinoma identified. However, make sure the prior tumor site has \nbeen identified and changes consistent with treated tumor are present (stromal fibrosis, chronic inflam\u00ad\nmation, often residual DCIS and/or calcifications).\n\t\t \u0007Partial response: Often not grossly identifiable, or only a vague firmer area is present at the tumor bed. \nMicroscopically, residual invasive carcinoma may consist of small islands of viable-appearing tumor \ncells within a larger area of fibrosis.\n\t\t \u0007No or minimal response: grossly evident tumor with little or no evidence of treatment effect.\n\t\t \u0007In the lymph nodes:\n\t\t \u0007The response in lymph node metastases is more important than the response in the breast. It is prefer\u00ad\nable to document a lymph node metastasis before treatment with FNA in order to leave the metastasis \nin place to be able to evaluate response. Small lymph node metastases after treatment have the small \nprognostic significance as larger metastases.\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present. Use criteria of Rosen (Box 15-1).\n\t\u2022\t \u0007Dermal Lymph-Vascular Invasion: No skin present, not identified, present.\n\t\t \u0007Dermal lymph-vascular invasion is a poor prognostic factor and is often associated with carcinomas \npresenting clinically as inflammatory carcinoma.\n\t\u2022\t \u0007Lymph Nodes: Number of nodes examined (intramammary nodes are included), number of sentinel \nnodes, number with metastases (tumor nodules in axillary fat without an indentifiable lymph node can \nbe counted as positive nodes).\n\t\t \u0007Size of largest metastasis, number of nodes with macrometastases, number of nodes with micrometas\u00ad\ntases, number of nodes with isolated tumor cells.\n\t\u2022\t \u0007Extranodal Extension: Not identified, present.\n\t\u2022\t \u0007Method of Evaluation of Lymph Nodes: H&E, multiple levels, immunohistochemical studies, RT-\nPCR.\n\t\u2022\t \u0007Perineural Invasion: Present or absent. This feature is of uncertain prognostic significance and is \noptional to report.\n\t\u2022\t \u0007Biopsy Cavity: Absent, present. This is important to document in specimens with a prior needle core \nbiopsy or excision. Include relationship to any residual tumor.\n\t\u2022\t \u0007Ancillary Studies: Hormone receptors and HER2/neu: Determined on all invasive carcinomas. Some \noncologists may request these studies for DCIS.\n\t\t \u0007Other prognostic tests may be requested by oncologists for specific cases.\n\t\u2022\t \u0007Additional Pathologic Findings: Relevant findings such as ADH, ALH, benign calcifications, radia\u00ad\ntion changes, etc.\nBOX 15\u20131.\u2003 \u0007Rosen criteria for lymphovascular \u00adinvasion (LVI)\n\t1.\t \u0007Lymphatic invasion must be diagnosed outside the border of the invasive carcinoma. The most common area to find \nLVI is within 0.1 cm of the edge of the carcinoma.\n\t2.\t \u0007The tumor emboli usually do not conform exactly to the \u00adcontours of the space in which they are found. In contrast, \ninvasive carcinoma with retraction artifact mimicking LVI will have exactly the same shape.\n\t3.\t \u0007Endothelial cell nuclei should be seen in the cells lining the space.\n\t4.\t \u0007Lymphatics are often found adjacent to blood vessels and often partially encircle a blood vessel.\nLVI may be seen in stroma between uninvolved lobules and can sometimes be mistaken for DCIS. Immunohistochemical \nstudies for vascular antigens have not been found to be superior to the histologic evaluation of LVI.\nAdapted from Rosen PP, Tumor emboli in intramammary \u00adlymphatics in breast carcinoma: Pathologic criteria for diagnosis and clinical significance, \nPathol Annu 18 pt 2:215-32, 1983.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_296.png", "summary": "This page discusses the evaluation of axillary dissections in breast pathology, including margin involvement in invasive carcinoma, DCIS, and LCIS, treatment effect, lymph node response, lymph-vascular invasion, dermal lymph-vascular invasion, lymph nodes evaluation, extranodal extension, method of lymph node evaluation, perineural invasion, and biopsy cavity presence.", "questions": [ "How is margin involvement described for invasive carcinoma, DCIS, and LCIS?", "What are the different responses to treatment in breast pathology?", "Why is lymph node response considered more important than breast response in evaluating treatment effect?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 297, "text": "BREAST\u2003 Axillary Dissections\n279\nContinued\nTABLE 15-2.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF BREAST CARCINOMAS\nTUMOR\nTX\nPrimary tumor cannot be assessed\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ\nTis (DCIS)\nDuctal carcinoma in situ\nTis (LCIS)\nLobular carcinoma in situ\nTis (Paget)\nPaget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ \n(DCIS and/or LCIS) in the underlying breast parenchyma. Carcinomas in the breast paren\u00ad\nchyma associated with Paget disease are categorized based on the size and \u00adcharacteristics \nof the parenchymal disease, although the presence of Paget disease should still be noted\nT1\nTumor \u2264 20 mm in greatest dimension\nT1mi\nTumor \u2264 1 mm in greatest dimension (microinvasion)\nT1a\nTumor > 1 mm but \u2264 0.5 cm in greatest dimension\nT1b\nTumor > 5 mm but \u2264 10 mm in greatest dimension\nT1c\nTumor > 10 mm but \u2264 20 mm in greatest dimension\nT2\nTumor > 20 mm but \u2264 50 mm\nT3\nTumor > 50 mm in greatest dimension\nT4\nTumor of any size with direct extension to the chest wall and/or to the skin (ulceration or \nskin nodules).\nNote: Invasion of the dermis alone does not qualify as T4.\nT4a\nExtension to the chest wall, not including only pectoralis muscle adherence/invasion\nT4b\nUlceration and/or ipsilateral satellite nodules and/or edema (including peau d\u2019orange) of \nthe skin, which do not meet the criteria for inflammatory carcinoma\nT4c\nBoth T4a and T4b\nT4d\nInflammatory carcinoma\nNote: Inflammatory carcinoma is restricted to cases with typical skin changes involving a third or more of the skin of the breast. Although the \nhistologic presence of invasive carcinoma invading dermal lymphatics is supportive of the diagnosis, it is not required, nor is dermal lymphatic \ninvasion without typical clinical findings sufficient for a \u00addiagnosis of inflammatory breast cancer.\n\t\t \u0007Microcalcifications \n\t\t \u0007If the surgery was performed for radiologically suspicious calcifications, it is helpful to report whether \nor not the calcifications were formed by the carcinoma.\n\t\t \u0007Present in DCIS, present in invasive carcinoma, present in nonneoplastic tissue, present in both carci\u00ad\nnoma and benign tissue.\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the \nM category is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 15-2). M0 \nis conferred after clinical assessment; there is no pM0 category.\n\t \u2022\t \u0007Grading systems: see Tables 15-3 to 15-9.\n\t\t \u0007This checklist incorporates information form the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements \nare considered to be scientifically validated or regularly used data elements that must be present in \nreports of cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. \nThe specific details of reporting the elements may vary among institutions.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_297.png", "summary": "The page provides information on the AJCC classification of breast carcinomas, including tumor size categories, distant metastasis, AJCC classification, and grading systems.", "questions": [ "How are breast carcinomas classified based on tumor size?", "What is the significance of distant metastasis in pathologic examination?", "What are the grading systems mentioned in Tables 15-3 to 15-9?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 298, "text": "BREAST\u2003 Prophylactic Mastectomies\n280\nTABLE 15\u20132.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF BREAST CARCINOMAS\u2014cont\u2019d\nREGIONAL LYMPH NODES\nThe axillary node staging is simplified to the following categories in the absence of infor\u00ad\nmation about infraclavicular lymph nodes (level III axillary), internal mammary lymph \nnodes, and supraclavicular lymph nodes:\npNX\nRegional lymph nodes cannot be assessed (e.g., previously removed, or not removed for \npathologic study)\npN0\nNo regional lymph node metastasis identified histologically\npN0(i\u2013)\nNo regional lymph node metastases histologically, negative IHC\npN0(i+)\nMalignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC \nincluding ITC).\npN0(mol-)\nNo regional lymph node metastases histologically, negative molecular findings (RT-PCR)\npN0(mol+)\nPositive molecular findings (RT-PCR), but no regional lymph node metastases detected by \nhistology or IHC\npN1mi\nMicrometastasis (greater than 0.2 mm and/or more than 200 cells, but none greater than \n2.0\u00a0mm)\npN1a\nMetastases in 1 to 3 axillary lymph nodes, at least one metastasis greater than 2.0 mm\npN2a\nMetastases in 4 to 9 axillary lymph nodes (at least one tumor deposit greater than 2.0 mm)\npN3a\nMetastases in 10 or more axillary nodes (at least one tumor deposit greater than 2.0 mm)\nNote: Isolated tumor cell clusters (ITCs) are defined as small clusters of cells not greater than 0.2 mm, or single tumor cells, or a cluster of fewer \nthan 200 cells in a single histologic cross section. ITCs may be detected by routine histology or by immunohistochemical (IHC) methods. Nodes \ncontaining only ITCs are excluded form the total positive node count for purposes of N classification but should be included in the total number \nof nodes evaluated.\nThe node count includes intramammary lymph nodes.\nWhen the combination of sentinel and nonsentinel nodes removed is less than a standard low axillary dissection, (less than six nodes) the (sn) \nmodifier is used. If six or more nodes are evaluated, the modifier is not used.\nCancerous nodules in the axillary fat adjacent to the breast, without histologic evidence of residual lymph node tissue, are classified as regional \nlymph node metastases (\u2265N1).\nDISTANT METASTASES\nM0\nNo clinical or radiographic evidence of distant metastases\ncM0(i+)\nNo clinical or radiographic evidence of distant metastases, but deposits of molecularly or \nmicroscopically detected tumor cells in circulating blood, bone marrow, or other non\u00ad\nregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or \nsigns of metastases\nM1\nDistant detectable metastases as determined by classic clinical and radiographic means \nand/or histologically proven metastases larger than 0.2 mm\nFrom the AJCC Cancer Staging Manual, Seventh Edition, New York, Springer-Verlag, 2009. Used with the permission of the American Joint Com\u00ad\nmittee on Cancer (AJCC), Chicago, Illinois.\nPROPHYLACTIC MASTECTOMIES\nProphylactic mastectomies are simple mastectomies performed to reduce the risk of developing breast \ncancer. Unilateral procedures may be performed on women with contralateral carcinoma. Bilateral pro\u00ad\ncedures may be performed on women at high risk for developing invasive \u00adcarcinoma either due to a \ndiagnosis of LCIS or women with an inherited susceptibility to breast cancer (BRCA1 or BRCA2 car\u00ad\nriers). Clinically and radiologically occult invasive carcinomas are found in 3% to 15% of prophylactic \nmastectomies and are typically small (<1 cm).15-17\nIf there is a known palpable or radiographic abnormality, the examination should be directed towards \nfinding and examining this area.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_298.png", "summary": "The page discusses the AJCC classification of breast carcinomas based on regional lymph nodes and distant metastases, as well as the criteria for prophylactic mastectomies.", "questions": [ "What are the different categories for regional lymph node staging in breast carcinomas?", "How are isolated tumor cell clusters (ITCs) defined and treated in the classification?", "What is the significance of the (sn) modifier in the node count during axillary dissection?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 299, "text": "BREAST\u2003 Reduction Mammoplasty\n281\nIn the absence of a known abnormality, the breast is thinly sectioned and examined in the fresh state. All \nareas grossly suspicious for in situ or invasive carcinoma should be submitted. In the absence of grossly suspi\u00ad\ncious areas, one to two blocks of tissue per quadrant and one section of the nipple may be submitted for micro\u00ad\nscopic examination. Lymph nodes should not be present but should be searched for and submitted if present.\nREDUCTION MAMMOPLASTY\nReduction mammoplasties are almost always bilateral and consist of fragments of breast tissue with \nattached skin. The nipples are not present. The procedure is considered therapeutic if the specimen \nweighs over 300 grams (e.g., to relieve back pain) but cosmetic if the specimen weighs less than this. The \nweight is important to document, as some insurance policies will not pay for cosmetic surgery.\nIncidental carcinomas are found rarely (approximately 2 to 4 per 1000 cases). The two sides must be \nclearly labeled and designated tissue submitted separately from each side. If the side is not specified, the \nwoman may require bilateral mastectomies if an incidental carcinoma is found.\nTABLE 15-3.\u2003\nNOTTINGHAM COMBINED HISTOLOGIC GRADE (THE ELSTON-ELLIS \nMODIFICATION OF THE SCARFF - BLOOM - RICHARDSON GRADING SYSTEM) FOR INVASIVE \nBREAST CARCINOMAS\nFEATURE\nSCORE\nTubule formation\nMajority of tumor (> 75%)\n1\nModerate degree (10\u201375%)\n2\nLittle or none (< 10%)\nClear lumina must be present to be scored\n3\nNuclear pleomorphism\nSmall, regular uniform cells\nSize of normal cells, uniform chromatin\n1\nModerate increase in size and variability\nOpen, vesicular nuclei with visible nucleoli\n2\nMarked variation, especially large and bizarre nuclei\nVesicular with prominent, often multiple nucleoli\n3\nMitotic counts (count 10 HPFs;) (see Table 15-4)\n\u22643 mitoses per mm2\n1\n4\u20137 mitoses per mm2\n2\n\u22658 mitoses per mm2\n3\nAssess mitotic counts at the periphery of the tumor, in most mitotically active area. Only clearly identifiable mitotic \nfigures are counted\u2014do not include hyperchromatic, karyorrhectic, or apoptotic nuclei. Count at least 10 fields. The \nnumber of mitoses per 10 HPFs is used to determine the score. The size of a 40 field varies widely with microscope type \nand with modifications (e.g., multiheaded microscopes and built-in polarizers). The size of the field should be mea\u00ad\nsured with a stage micrometer and the mitotic counts adjusted. See Chapter 9 for information on measuring field sizes.\nOVERALL TUMOR GRADE\n3\u20135 points\nGrade I\nWell differentiated\n6\u20137 points\nGrade II\nModerately differentiated\n8\u20139 points\nGrade III\nPoorly differentiated\nNote: All tumors should be graded regardless of histologic type. Overall, approximately 20% of cancers should be \ngrade 1, 40% grade II, and 40% grade III. All tubular carcinomas are well differentiated and all medullary carcinomas \nare poorly differentiated. Other histologic types vary in grade.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_299.png", "summary": "Reduction mammoplasties are examined by thinly sectioning the breast and submitting suspicious areas for microscopic examination. The weight of the specimen determines if the procedure is considered therapeutic or cosmetic.", "questions": [ "How are reduction mammoplasties examined for potential abnormalities?", "Why is the weight of the specimen important in reduction mammoplasty procedures?", "What are the implications of finding an incidental carcinoma in a reduction mammoplasty specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 300, "text": "BREAST\u2003 Reduction Mammoplasty\n282\nTABLE 15-4.\u2003\nSCORING MITOTIC COUNTS\nFIELD DIAMETER (mm)\nAREA (mm2)\nNUMBER OF MITOSES PER 10 FIELDS CORRESPONDING TO:\nSCORE 1\nSCORE 2\nSCORE 3\n0.40\n0.125\nUp to 4\n5 to 9\n10 or more\n0.41\n0.132\nUp to 4\n5 to 9\n10 or more\n0.42\n0.139\nUp to 5\n6 to 9\n11 or more\n0.43\n0.145\nUp to 5\n6 to 10\n11 or more\n0.44\n0.152\nUp to 5\n6 to 11\n12 or more\n0.45\n0.159\nUp to 5\n6 to 11\n12 or more\n0.46\n0.166\nUp to 6\n7 to 12\n13 or more\n0.47\n0.173\nUp to 6\n7 to 12\n13 or more\n0.48\n0.181\nUp to 6\n7 to 13\n14 or more\n0.49\n0.189\nUp to 6\n7 to13\n14 or more\n0.50\n0.196\nUp to 7\n8 to 14\n15 or more\n0.51\n0.204\nUp to 7\n8 to 14\n15 or more\n0.52\n0.212\nUp to 7\n8 to 15\n16 or more\n0.53\n0.221\nUp to 8\n9 to 16\n17 or more\n0.54\n0.229\nUp to 8\n9 to 16\n17 or more\n0.55\n0.238\nUp to 8\n9 to 17\n18 or more\n0.56\n0.246\nUp to 8\n9 to 17\n18 or more\n0.57\n0.255\nUp to 9\n10 to 18\n19 or more\n0.58\n0.264\nUp to 9\n10 to 19\n20 or more\n0.59\n0.273\nUp to 9\n10 to 19\n20 or more\n0.60\n0.283\nUp to 10\n11 to 20\n21 or more\n0.61\n0.292\nUp to 10\n11 to 21\n22 or more\n0.62\n0.302\nUp to 11\n12 to 22\n23 or more\n0.63\n0.312\nUp to 11\n12 to 22\n23 or more\n0.64\n0.322\nUp to 11\n12 to 23\n24 or more\n0.65\n0.332\nUp to 12\n13 to 24\n25 or more\n0.66\n0.342\nUp to 12\n13 to 24\n25 or more\n0.67\n0.353\nUp to 12\n13 to 25\n26 or more\n0.68\n0.363\nUp to 13\n14 to 26\n27 or more\n0.69\n0.374\nUp to 13\n14 to 26\n27 or more\nAssess mitotic counts at the periphery of the tumor, in the most mitotically active area. Only clearly identifiable mitotic figures are counted \u2013 do not \ninclude hyperchromatic, karyorrhectic, or apoptotic nuclei. Count at least 10 fields. The number of mitoses per 10 HPFs is used to determine the \nscore. The size of a 40\u00d7 field varies widely with microscope type and with modifications (e.g., multiheaded microscopes and built-in polarizers). The \nsize of the field should be measured and the mitotic counts adjusted. See in Chapter 9, \u201cMeasuring with the Microscope,\u201d for information on measur\u00ad\ning field sizes. See the CAP protocol for the examination of specimens from patients with invasive carcinoma of the breast (www.cap.org).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_300.png", "summary": "This page provides a table for scoring mitotic counts in breast reduction mammoplasty specimens, based on the number of mitoses per 10 fields at different field diameters.", "questions": [ "How are mitotic counts scored in breast reduction mammoplasty specimens?", "What factors should be considered when assessing mitotic counts in these specimens?", "Why is it important to only count clearly identifiable mitotic figures and not other types of nuclei?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 301, "text": "BREAST\u2003 Reduction Mammoplasty\n283\nTABLE 15\u20135.\u2003\nNUCLEAR GRADE OF DUCTAL CARCINOMA IN SITU\nFEATURE\nLOW GRADE\nINTERMEDIATE GRADE\nHIGH GRADE\nPleomorphism\nMonomorphic\nIntermediate\nMarked\nSize\n1.5 to 2 \u00d7 the size of a normal \nRBC or duct epithelial cell \nnucleus\nIntermediate\n>2.5 \u00d7 the size of a normal \nRBC or duct epithelial cell \nnucleus\nChromatin\nDiffuse, finely dispersed\nIntermediate\nVesicular with irregular \n\u00adchromatin\nNucleoli\nOnly occasional\nIntermediate\nProminent, often multiple\nMitoses\nOnly occasional\nIntermediate\nMay be frequent\nOrientation\nPolarized towards luminal \nspaces\nIntermediate\nUsually not polarized toward \nluminal space\nTABLE 15\u20136.\u2003 THE MILLER-PAYNE GRADING SYSTEM FOR RESPONSE TO CHEMOTHERAPY\nRESPONSE\nDEFINITION\nGrade 1\nNo change or some alteration to individual malignant cells but no reduction in overall \ncellularity.\nGrade 2\nA minor loss of tumor cells but overall \u00adcellularity still high; up to 30% loss.\nGrade 3\nBetween an estimated 30% and 90% \u00adreduction in tumor cells. \nGrade 4\nA marked disappearance of tumor cells such that only small clusters or widely \u00addispersed \nindividual cells remain; more than 90% loss of tumor cells. \nGrade 5\nNo malignant cells identifiable in sections from the site of the tumor. DCIS may be present.\nFrom Ogston KN, et al, A new histological grading system to assess response of breast carcinomas to primary chemotherapy: prognostic \nsignificance and survival, The Breast 12:320-327, 2003.\nThis system does not include lymph node metastases. The presence of lymph node metastases, and the response to treatment in metastases, \nis more important for prognosis than the response in the breast itself for women with positive lymph nodes.\nA unilateral reduction mammoplasty is occasionally performed in a woman who has had surgery for \ncarcinoma on the contralateral side to obtain a balanced cosmetic result. Additional sections should be \ntaken from such specimens because of the increased risk of carcinoma in these patients. Approximately \none third of these patients will have a contralateral carcinoma (in most cases DCIS or LCIS).\n \n1.\t \u0007Weigh the specimen. Measure the entire specimen in aggregate. Record the total number of frag\u00ad\nments, number of fragments with skin, skin color, and range of greatest dimension of fragments.\n \n2.\t \u0007Section and palpate each fragment for lesions.\n \n3.\t \u0007Submit two sections per side including breast parenchyma and skin. Any suspicious areas are \u00adsampled.\nAdditional sections are submitted if the patient has risk factors for breast carcinoma (e.g., a previous \nhistory of breast cancer or a strong family history). Be suspicious if one side is markedly different in size \nthan the other or if only one side is submitted. This may indicate that there has been a prior surgical \nprocedure performed for cancer.\nSAMPLE DICTATION\nThe specimen is received fresh in two parts, each labeled with the patient\u2019s name and unit number.\nThe first part labeled \u201cleft breast\u201d is a 350 gram specimen consisting of five fragments of breast paren\u00ad\nchyma with three of the fragments containing white/tan skin (in aggregate 25 \u00d7 10 \u00d7 10 cm; skin measuring \nup to 4 cm in size). A nipple is not present. The breast parenchyma consists of approximately 60% dense \nwhite tissue and the remainder yellow/white unremarkable adipose tissue. No gross lesions are present.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_301.png", "summary": "The page discusses nuclear grade of ductal carcinoma in situ, the Miller-Payne grading system for response to chemotherapy, and the importance of evaluating lymph node metastases for prognosis in breast cancer patients.", "questions": [ "How does the nuclear grade of ductal carcinoma in situ impact prognosis and treatment?", "What are the different grades in the Miller-Payne grading system for response to chemotherapy and how do they correlate with treatment outcomes?", "Why is evaluating lymph node metastases more important for prognosis in breast cancer patients with positive lymph nodes than the response in the breast itself?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 302, "text": "BREAST\u2003 Reduction Mammoplasty\n284\nTABLE 15\u20138.\u2003\nFIBROADENOMA AND GRADING OF PHYLLODES TUMORSa\nFEATURE\nFIBROADENOMA\nLOW GRADE \n(\u201cBENIGN\u201d)\nINTERMEDIATE \nGRADE \n(\u201cBORDERLINE\u201d)\nHIGH GRADE \n(\u201cMALIGNANT\u201d)\nStromal \u00adcellularity\nPaucicellular to mild\nMildly to moder\u00ad\nately cellular\nModerate to mark\u00ad\nedly cellular\nUsually highly \u00adcellular\nNuclear \n\u00adpleomorphism\nMinimal\nMinimal to mild\nMore evident\nMay be marked\nMitotic rateb\nUsually absent or \nvery rare\nUsually present but \ninfrequent (e.g., \n0 to 1/10 HPF)\nSlightly increased \n(e.g., 2 to 5/10 \nHPF)\nFrequently have a high \nmitotic rate \n(e.g., >5/10 HPF)\nStromal over\u00ad\ngrowth (absence \nof epithelium in \ncellular areas)\nAbsent (but may be \nhyalinized with \natrophic or absent \nepithelium)\nAbsent or focal\nOften present\nOften marked (may \nbe difficult to \ndistinguish from a \nsarcoma)\nBorders\nCircumscribed \n(fibroadenoma\u00ad\ntoid changes may \nbe ill-defined)\nUsually \n\u00adcircumscribed \nand pushing\nUsually has some \ninvasion into \nstroma\nUsually has marked \n\u00adinvasion into stroma\nHeterologous ele\u00ad\nments\nMay have benign \nlipomatous \nand osseous \n\u00admetaplasia\nMay have benign \n\u00adlipomatous \nand osseous \n\u00admetaplasia\nMay have benign \n\u00adlipomatous \nand osseous \n\u00admetaplasia\nMay have malignant \nstromal components \n(e.g., rhabdomyo-\u00ad\nsarcoma, \nliposarcoma, \n\u00adangiosarcoma)\naThere is no generally accepted grading system for phyllodes tumors. The WHO system uses a three category system (benign, borderline, and \n\u00admalignant) based on the features in the table.12\nbIn published series, mitotic rates have not been standardized for the size of the microscopic field.\nDue to the fact that rare \u201cbenign\u201d phyllodes tumors have been reported to have metastasized and resulted in the death of patients and because the \nmajority of \u201cmalignant\u201d or high-grade lesions are cured by local therapy, diagnostic terms implying clinical behavior should be used with caution.13 \nSome pathologists prefer to separate phyllodes into three grades (low, intermediate, and high).\nTABLE 15\u20137.\u2003\nRESIDUAL CANCER BURDEN (RCB) SYSTEM*\nThe following information is required to determine RCB:\n\t\u2022\t \u0007The size of the tumor bed in two dimensions.\n\t\u2022\t \u0007The overall cellularity of residual carcinoma (both invasive and DCIS) within the tumor bed, estimated as a percent.\n\t\u2022\t \u0007The percent of the carcinoma that is DCIS. The RCB value is based on only the residual invasive carcinoma.\n\t\u2022\t \u0007The number of positive lymph nodes.\n\t\u2022\t \u0007The size of the largest lymph node metastasis.\nThis information is entered into a weighted formula to calculate a continuous value \u2013 this can be performed at \nthe website given below. The values are divided into four classes:\nCLASS\nRESPONSE\nRCB 0\nPathologic complete response (no residual invasive \u00adcarcinoma or LN metastasis) \nRCB I\nMajor response \nRCB II\nMinor response \nRCB III\nNo or minimal response\nSee www.mdanderson.org/breastcancer_RCB for an online calculator.\nUnlike the Miller-Payne system, which compares changes in cellularity in the breast carcinoma, the RCB system evaluates the extent of residual \ncarcinoma in the breast and lymph nodes without regard to the cellularity of the pre-treatment carcinoma.\nIf positive nodes are removed prior to treatment, RCB cannot be determined, because the response of the metastasis to treatment is unknown.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_302.png", "summary": "The page discusses fibroadenoma and grading of phyllodes tumors, highlighting features such as stromal cellularity, nuclear pleomorphism, mitotic rate, stromal overgrowth, borders, and heterologous elements.", "questions": [ "What are the key differences between fibroadenoma and phyllodes tumors based on the grading system mentioned?", "How do pathologists approach the grading of phyllodes tumors, and why is caution advised when using diagnostic terms implying clinical behavior?", "What information is required to determine the Residual Cancer Burden (RCB) system, and how is it calculated?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 303, "text": "285\nBREAST\u2003 Duct Dissections/Nipple Biopsies\nCassettes #1-2: Breast parenchyma and skin, 4 frags, RSS.\nThe second part labeled \u201cright breast\u201d is a 375 gram specimen consisting of six fragments of breast \nparenchyma with three of the fragments bearing white/tan skin (in aggregate (27 \u00d7 11 \u00d7 10 cm; skin mea\u00ad\nsuring up to 5 cm in size). A nipple is not present. There is a 2 cm area of small simple cysts measuring \nup to 0.4 cm in size in the breast tissue. The remainder of the breast tissue consists of approximately 60% \ndense white tissue and the remainder unremarkable yellow/white adipose tissue.\nCassette #3-4: Breast parenchyma including area of cysts and skin, 5 frags, RSS.\nDUCT DISSECTIONS/NIPPLE BIOPSIES\nDuct dissections are usually performed to evaluate nipple discharge without a palpable mass. The \nmost common lesion found is a large duct papilloma, but occasionally papillary or micropapillary \nDCIS may be the cause of the discharge. A duct dissection specimen is usually small, and large ducts \nmay be grossly visible. Ducts look like flaccid white tubes approximately 0.2 to 0.3 cm in diam\u00ad\neter. Large papillomas may be evident grossly as lobulated outgrowths from the duct wall. Ink the \nouter portion of the specimen. If a ductal lesion is evident grossly, submit the ductal margin. Take \ncross-sections across the duct(s) and submit the entire specimen. Orient all sections if orientation is \n\u00adprovided.\nA nipple wedge excision (which includes skin) may be performed to treat a recurrent subareolar \nabscess.18 Skin should be identified grossly and placed in designated cassettes as it may be difficult to \ndistinguish skin from squamous metaplasia in tissue sections. If the lesion is recurrent, tissue may be sent \nfor aerobic and anaerobic bacterial cultures as secondary infections may occur.\nA nipple biopsy may be performed to evaluate possible Paget disease (see Table 7-18).\nSmall skin biopsies may be performed to evaluate possible inflammatory breast carcinoma. If carcinoma \nis not seen and another cause for the clinical appearance is not found (e.g., infection or an inflammatory \ndermatitis), inflammatory carcinoma is not excluded, as dermal lymphatic involvement by carcinoma in \nsuch cases can be very focal.\nTABLE 15\u20139.\u2003\nBREAST ANGIOSARCOMA - GRADE\nLOW\nINTERMEDIATE\nHIGH\nHistologic Features\nEndothelial tufting\nMinimal\nPresent\nProminent\nPapillary formations\nAbsent\nFocal\nPresent\nSolid and spindle cell foci\nAbsent\nAbsent or minimal\nPresent\nMitoses\nRare or absent\nPresent in papillary areas\nNumerous, even in \nlow-grade areas\nBlood lakes\nAbsent\nAbsent\nPresent\nNecrosis\nAbsent\nAbsent\nPresent\nClinical Features\n% of patients\n40%\n19%\n41%\nMedian age\n43\n34\n29\n5- and 10-year survival\n76%\n70%\n15%\nMedian DFS\n15 years\n12 years\n15 months\nBreast angiosarcomas in younger women are usually primary (and high grade) and in older women usually related to prior treatment for breast \ncarcinoma (s/p radiation therapy or, less often, therapy-related edema).\nModified from Rosen PP, Rosen\u2019s Breast Pathology, 2nd edition. Lippincott Williams & Wilkins, 2001. Other authors have not found grade to be an \nimportant prognostic factor.14", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_303.png", "summary": "The page discusses breast duct dissections and nipple biopsies, including the evaluation of nipple discharge and potential lesions found in duct specimens.", "questions": [ "What are the common lesions found in duct dissections for evaluating nipple discharge?", "How are large papillomas and ductal margins handled during duct dissections?", "What are the indications for performing a nipple wedge excision or biopsy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 304, "text": "BREAST\u2003 Breast Implants\n286\nBREAST IMPLANTS\nExplanted permanent implants should be well documented in the surgical pathology report due to the \nconcern over possible long-term complications. The Safe Medical Devices Act (SMDA) went into effect \nin August of 1993. This act requires that certain medical devices (including breast implants) used after \nthis date must be tracked by the manufacturer as well as by physicians and hospitals. \u00adCurrent information \nabout implants can be found at www.fda.gov/cdrh/breastimplants/.\nImplants are of two general types:\n 1.\t \u0007Tissue expanders are placed temporarily after a surgical procedure for malignancy. They are removed \nwithin days to weeks. These implants are almost always saline, have a textured surface, and a large \nport (a circular metallic disc) for changing the volume. These implants are unlikely to be involved in \nlitigation and do not need to be photographed unless they were removed due to a complication (most \nlikely infection).\n 2.\t \u0007Permanent implants are commonly placed for cosmetic reasons, are usually bilateral, and are filled \nwith either silicone or saline. These implants may be removed due to complications (rupture, calci\u00ad\nfication, capsular contracture, infection), systemic complaints attributed to the implant, or because \nof patient concerns over safety. Implants that are removed may be requested for litigation. All such \nimplants should be photographed.\nThe gross description includes:\n\t\u2022\t \u0007Size: Three dimensions\n\t\u2022\t \u0007Shape: Usually ovoid. If permanent folds or creases are present these are documented in the dictation \nand photographs taken.\n\t\u2022\t \u0007Surface appearance: Smooth or textured, presence or absence of calcifications and/or adherent tis\u00ad\nsue. A tacky (sticky) surface is usually indicative of silicone bleed through an intact shell. Implants with \nthicker shells or saline implants will have a dry smooth surface. The shell for both saline and silicone \nimplants is most commonly made of silicone polymers.\n\t\u2022\t \u0007Contents: Silicone is more viscous than saline. Saline will freeze if placed in a freezer whereas silicone \nwill not. However, this should not be done to distinguish the two because the shell may be damaged \nby freezing.\n\t\u2022\t \u0007Color of contents: Usually translucent or with a slight yellowish cast. If the contents are opaque, cloudy, \nor colored (e.g., red or brown) this is an unusual finding that may indicate infection or degradation.\n\t\u2022\t \u0007Single or double lumen: Some implants have an inner and outer chamber. One may be filled with \nsilicone and the other with saline.\n\t\u2022\t \u0007Presence of a patch: A Dacron patch was present on some of the earliest implants.\n\t\u2022\t \u0007Presence of a fill port: Some saline implants will have a large port (if intended for temporary use) or a \nsmall port (if intended for permanent use) that can be used to alter the total volume. Silicone implants \ndo not have a port.\n\t\u2022\t \u0007Gross evidence of leakage: A leaking saline implant will be completely collapsed and the surface will \nnot be sticky. A leaking silicone implant may be intact or \u00adcompletely ruptured. In the latter case the \nspecimen may consist of thick viscous sticky silicone gel with portions of the shell floating within it.\n\t\u2022\t \u0007Source of leakage: Tacky surface, pinpoint holes, or gross tears. Give the size of any tears present.\n\t\u2022\t \u0007Identifying marks: Most implants were not identified with the manufacturer\u2019s name. Some will have \na name, number, or design.\nTake three pictures (more if necessary) demonstrating identifying marks and gross abnormalities of \npermanent implants (not tissue expanders).\nSoft tissue removed with the implant is carefully examined for gross evidence of foreign material. \nEssentially all implants release small amounts of silicone (i.e., \u201cgel bleed\u201d), even if leakage is not apparent \ngrossly. Submit 1 to 2 cassettes and sample all tissue with grossly different appearances. Tumors may be \ndifficult to detect clinically and radiologically in the presence of implants and must be diligently searched \nfor in these specimens. Silicone granulomas can be very hard gritty nodular masses closely simulating the \ngross appearance and texture of carcinoma.\nSome older implants were covered with a polyurethane shell. This shell is textured and rapidly \nbecomes incorporated into the surrounding fibrous capsule. The capsular material may appear shiny if \nthis material is present.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_304.png", "summary": "The surgical pathology report for explanted breast implants should be well documented due to concerns over long-term complications. The Safe Medical Devices Act requires tracking of certain medical devices, including breast implants, since August 1993.", "questions": [ "What are the two general types of breast implants mentioned in the text?", "What information should be included in the gross description of breast implants?", "Why is it important to document the presence of a fill port in saline implants?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 305, "text": "BREAST\u2003 Gynecomastia\n287\nSAMPLE DICTATION\nThe specimen is received fresh, labeled with the patient\u2019s name and unit number, in four parts.\nThe first part labeled \u201cright implant\u201d consists of an ovoid implant with a smooth dry surface and \nviscous translucent contents (9 \u00d7 9 \u00d7 4 cm). No gross ruptures, adherent tissue, or identifying marks are \npresent. Photographs are taken.\nThe second part labeled \u201cright capsule\u201d consists of six fragments of tan/white fibrous tissue measur\u00ad\ning in aggregate 7 \u00d7 5 \u00d7 4 cm. Most of the fragments have a smooth surface and an opposite surface \nwhich is irregular and is comprised of yellow/tan soft tissue. The fibrous areas measure up to 0.8 cm in \nthickness.\nCassettes #1 and 2: four frags, RSS.\nThe third part, labeled \u201cleft implant, ruptured,\u201d consists of three portions of synthetic translucent \nmaterial measuring 9 \u00d7 9 \u00d7 0.3 cm, 9 \u00d7 7 \u00d7 0.3 cm, and 3 \u00d7 2 \u00d7 2 cm grossly consistent with the outer shell \nof a breast implant. No identifying marks are present. Associated with these fragments is viscous tacky \ntranslucent material measuring approximately 9 \u00d7 9 \u00d7 4 cm. Photographs are taken.\nThe fourth part, labeled \u201cleft capsule,\u201d consists of approximately fifteen fragments of tan/white soft \ntissue (in aggregate 6 \u00d7 5 \u00d7 5 cm). Two of the fragments have poorly circumscribed areas that are tan/\ngrey, gritty in consistency, and measure 0.8 cm in greatest dimension. Some of the remainder of the frag\u00ad\nments have a smooth surface and are grossly consistent with portions of the capsule.\nCassettes #3 and 4: gritty areas, four frags, ESS.\nCassettes #5 and 6: areas of capsule, RSS.\nGYNECOMASTIA\nThe specimens are usually subcutaneous mastectomies. The skin and nipple are not present. The speci\u00ad\nmen is weighed and measured. Serially section the specimen and carefully palpate for gross lesions. Two \nsections are submitted unless gross lesions are present. If a mastectomy is performed in a male for breast \ncarcinoma, it is processed as for a mastectomy in a female (see previous section).\nREFERENCES\n\t\u2002 1.\t \u0007Moritz JD, Luftner-Nagel S, Westerhof JP, et al. Microcalcifications in breast core biopsy specimens: disap\u00ad\npearance at radiography after storage in formaldehyde. Radiology 200:361-363, 1996.\n\t\u2002 2.\t \u0007Schnitt SJ, Wang HH. Histologic sampling of grossly benign breast biopsies. How much is enough? Am J Surg \nPath 13(6):505-512, 1989.\n\t\u2002 3.\t \u0007Carlson JW, Birdwell RL, Gombos EC, et al: MRI-directed, wire-localized breast excisions: incidence of malig\u00ad\nnancy and recommendations for pathologic evaluation. Hum Pathol 38:1754-1759, 2007.\n\t\u2002 4.\t \u0007Owings DV, Hann L, Schnitt SJ. How thoroughly should needle localization breast biopsies be sampled \nfor microscopic examination: A prospective mammographic/pathologic correlative study. Am J Surg Pathol 14:\n578-583, 1990.\n\t\u2002 5.\t \u0007Abraham SC, Fox K, Fraker D, \u00adet al. Sampling of grossly benign breast reexcisions. A multidisciplinary approach \nto assessing adequacy. Am J Surg Pathol 23:316-322, 1999.\n\t\u2002 6.\t \u0007Wiley EL, Keh P. Diagnostic discrepancies in breast specimens subjected to gross reexamination. Am J Surg \nPathol 23:876-879, 1999.\n\t\u2002 7.\t \u0007Andea AA, Bouwman D, Wallis T, Visscher DW. Correlation of tumor volume and surface area with lymph \nnode status in patients with multifocal/multicentric breast carcinoma. Cancer 100:20-27, 2004.\n\t\u2002 8.\t \u0007Singletary SE, Greene FL, Sobin LH. Classification of isolated tumor cells: Clarification of the 6th edition of the \nAmerican Joint Committee on Cancer staging manual. \u00adCancer 98:2740-2741, 2003.\n\t\u2002 9.\t \u0007Elston E, Ellis IO. Grading invasive carcinoma. In O\u2019Malley FP, Pindar SE, editors: Breast Pathology, New \nYork, Churchill \u00adLivingstone, 2006.\n\t10.\t \u0007Consensus conference on the classification of ductal carcinoma in situ. the Consensus Conference Commit\u00ad\ntee. Cancer 80:1798-1802, 1997.\n\t11.\t \u0007Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival \nafter neoadjuvant chemotherapy. J Clin Oncol 25:4414-4422, 2007.\n\t12.\t \u0007The World Health Organization: Tumours of the Breast and Female Genital Organs, pub. 2003.\n\t13.\t \u0007Reinfuss M, Mitus J, Duda K, et al. The treatment and prognosis of patients with phyllodes tumor of the breast. \nAn analysis of 170 cases. Cancer 77:910-916, 1996.\n\t14.\t \u0007Nascimento AF, Raut CP, Fletcher CD. Primary angiosarcoma of the breast: clinicopathologic analysis of 49 \ncases, suggesting that grade is not prognostic. Am J Surg Pathol 32:1896-1904, 2008.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_305.png", "summary": "The page describes the examination of breast specimens labeled as implants and capsules, with details of their measurements, characteristics, and processing.", "questions": [ "What are the key differences in the characteristics of the right implant and left implant specimens?", "How are the specimens processed and examined for gynecomastia?", "What significance do the gritty areas in the left capsule fragments hold in the diagnosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 306, "text": "288\nBREAST\u2003 References\n\t15.\t \u0007Isern AE, Loman N, Malina J, et al. \u00adHistopathologic findings and follow-up after prophylactic mastectomy and \nimmediate breast reconstruction in 100 women from families with hereditary breast cancer. EJSO 34:1148-\n1154, 2008.\n\t16.\t \u0007Khurana KK, Loosmann A, Numann PJ, Khan SA. \u00adProphylactic mastectomy. Pathologic findings in high-risk \npatients. Arch Pathol Lab Med 124:378-381, 2000.\n\t17.\t \u0007Leunen K, Drijkoningen M, Neven P, et al: Prophylactic mastectomy in familial breast carcinoma. What do the \npathologic findings learn us? Breast Cancer Res Treat 107:79-86, 2008.\n\t18.\t \u0007Mequid MM, Oler A, Numann PJ. Subareolar breast abscess: the penultimate stage of the mammary duct-\u00ad\nassociated inflammatory disease sequence. In Bland KI, Copeland EM III, editors: The Breast, Comprehensive \n\u00adManagement of Benign and Malignant Diseases, second \u00adedition, Saunders, 1998, p 109.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_306.png", "summary": "This page provides references to studies on histopathologic findings and follow-up after prophylactic mastectomy and immediate breast reconstruction in high-risk patients.", "questions": [ "What are some key findings from the referenced studies on prophylactic mastectomy?", "How do the histopathologic findings in high-risk patients impact treatment decisions?", "What are the implications of subareolar breast abscess as the penultimate stage of mammary duct-associated inflammatory disease?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 307, "text": "289\n16\nCardiovascular Specimens\nInformation gained by the gross examination of some cardiac tissues (e.g., valves and hearts) is often of \nconsiderable diagnostic importance; gross findings are often more critical than microscopic features in \nrendering a specific etiologic diagnosis.\nFor general information on diagnostic and technical considerations, see Silver1 and Schoen et al.2\nENDOMYOCARDIAL BIOPSIES\nBiopsies of the heart taken percutaneously by catheter \u00ad(typically from the right ventricle) are most often \nperformed to evaluate graft status in cardiac transplant patients or to evaluate cardiomyopathies. Rarely, \nan endomyocardial biopsy will be performed to diagnose an intracavitary or myocardial tumor.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Describe the specimen, including the number of fragments (carefully check lid and sides of container), \nsize, and color (myocardium = tan, scar = white, clot = red/brown).\n\t \u2022\t \u0007Transplant biopsies (evaluation for rejection): At least 3 or 4 fragments of \u226550% myocardium for \nlight microscopy.\n\t \u2022\t \u0007Cardiomyopathies: At least 3 or 4 fragments of \u226550% myocardium for light microscopy and, in \nsome cases, additional biopsies for EM and for freezing.\n 2.\t \u0007Wrap in lens paper and submit in one cassette. Three H&E stained sections are routinely cut \non all tissue received in formalin. Masson\u2019s trichrome, iron, or amyloid stains may be ordered if \n\u00adindicated.\nAdditional biopsies may be received for special \u00adstudies:\n\t \u2022\t \u0007Electron microscopy: Tissue is fixed in glutaraldehyde (Karnovsky\u2019s fixative).\n\t \u2022\t \u0007Immunofluorescence or freezing: Tissue is sent fresh on saline moistened gauze.\nSPECIAL STUDIES FOR SPECIFIC DISEASES\nAnthracycline (Adriamycin) Cardiotoxicity.\u2002 Semithin (plastic) sections prepared prior to electron \nmicroscopy are necessary for the evaluation of myocyte vacuolization and myofibrillar lysis.\nAmyloidosis.\u2002 All forms of amyloidosis are characterized by deposition of extracellular fibrils \n\u00adresulting from protein misfolding into an extended \u03b2-pleated sheet. The \u03b2-pleated sheet conformation \ncan be highlighted by Congo red staining, which shows apple-green birefringence under polarized \nlight; \u00adamyloid also has a distinct color pattern when stained with sulfated Alcian Blue (amyloid: sea-\nfoam green; myocytes: yellow; connective tissue: red-purple). The most common types affecting the \nheart are:\n\t \u2022\t \u0007Primary (AL) amyloid: immunoglobulin light chains\n\t \u2022\t \u0007Senile cardiac amyloid: transthyretin (or less commonly atrial natriuretic peptide)\n\t \u2022\t \u0007Hereditary amyloid: mutated transthyretin protein\n\t \u2022\t \u0007Chronic inflammation: SAA-type amyloid\nDetermining the type of amyloid protein deposited has become increasingly important for patient \n\u00adtreatment and prognosis.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_307.png", "summary": "Gross examination of cardiac tissues can provide crucial diagnostic information, often more important than microscopic features. Endomyocardial biopsies are commonly performed for evaluating graft status in cardiac transplant patients or cardiomyopathies.", "questions": [ "What are the key considerations for processing endomyocardial biopsy specimens?", "How are special studies used to evaluate specific diseases like Anthracycline Cardiotoxicity and Amyloidosis?", "Why is determining the type of amyloid protein deposited in the heart important for patient treatment and prognosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 308, "text": "CARDIOVASCULAR SPECIMENS\u2003 Endomyocardial Biopsies\n290\nTyping of amyloid deposition requires examination by immunofluorescence (IF) and immunohisto\u00ad\nchemistry. In addition to myocardial biopsy fragments submitted in formalin, an additional piece should \nbe submitted fresh for IF. Order summary for cases of amyloidosis:\n\t \u2022\t \u0007Histochemical stains: Sulfated alcian blue (SAB) and Trichrome\n\t \u2022\t \u0007Immunofluorescence: IgG, IgA, IgM, kappa, lambda, protein A (serum amyloid-associated protein), \nand albumin (negative control)\n\t \u2022\t \u0007Immunohistochemistry on formalin fixed tissue: Transthyretin.\nHemochromatosis and Hemosiderosis.\u2002 Iron deposition can be diagnosed using iron stains on fixed \ntissue.\nMetabolic Disease.\u2002 Frozen tissue may be useful for the evaluation of metabolic disease.\nMitochondrial Myopathies.\u2002 Electron microscopy is necessary for evaluation. However, the changes \nin the mitochondria are typically nonspecific.\nHypertrophic Cardiomyopathy.\u2002 This is more appropriately diagnosed by clinical imaging studies \n(e.g., echocardiography). Biopsy material will almost never reveal diagnosable myocyte disarray. Even if \ndisarray is present, it is not pathognomonic for hypertrophic \u00adcardiomyopathy.\nPATHOLOGIC FEATURES SIGN-OUT CHECKLIST\nNontransplant\u2002\n\t \u2022\t \u0007Site: Right ventricle\n\t \u2022\t \u0007Adequacy: At least 3 to 4 fragments of evaluable \u226550% myocardium\n\t \u2022\t \u0007Myocyte hypertrophy: Present or absent, mild, moderate, or severe\n\t \u2022\t \u0007Interstitial and/or perivascular fibrosis: Present or absent, mild, moderate, or severe\n\t \u2022\t \u0007Subendocardial myocyte vacuolization: \u00adPresent or absent, focal or diffuse (suggestive of chronic \n\u00adischemia)\n\t \u2022\t \u0007Replacement fibrosis: Present or absent (consistent with healed ischemic injury)\n\t \u2022\t \u0007Myocardial infarction: Present or absent, acute or organizing\n\t \u2022\t \u0007Scattered necrotic myocytes/inflammation: Present or absent (consistent with catecholamine \neffect)\n\t \u2022\t \u0007Endocardial thickening: Present or absent, focal or diffuse\n\t \u2022\t \u0007Active myocarditis: Present or absent, focal lymphocytic, diffuse lymphocytic, eosinophilic (hyper\u00ad\nsensitivity), giant cell, toxoplasma, CMV, granulomatous\n\t \u2022\t \u0007Mesothelial cells: Present or absent, indicates cardiac perforation\n\t \u2022\t \u0007Other: Amyloid, iron deposition, carcinoid plaque, anthracycline cardiotoxicity, old biopsy site, \ncontraction bands, thrombus\nTransplant\u2002\n\t \u2022\t \u0007Site: Right ventricle\n\t \u2022\t \u0007Adequacy: At least 3 or 4 fragments of evaluable \u226550% myocardium should be present\n\t \u2022\t \u0007Time since transplantation: Interval since operation\n\t \u2022\t \u0007Rejection: Give ISHLT grade (Table 16-1)3\n\t \u2022\t \u0007Coagulation necrosis: Present or absent, focal, multifocal, confluent\n\t \u2022\t \u0007Healing ischemic injury: Present or absent, focal, multifocal, confluent\n\t \u2022\t \u0007Subendocardial myocyte vacuolization: Present or absent, mild, moderate, or severe (suggestive \nof chronic ischemia)\n\t \u2022\t \u0007Endocardial infiltrate: Quilty lesions (A and B lesions are no longer distinguished)\n\t \u2022\t \u0007Mesothelial cells : Present or absent, indicates cardiac perforation\n\t \u2022\t \u0007Other: Old biopsy site, fat necrosis, foreign body giant cell reaction, dystrophic calcification", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_308.png", "summary": "The page discusses the typing of amyloid deposition, diagnosis of iron deposition, evaluation of metabolic disease, mitochondrial myopathies, and hypertrophic cardiomyopathy in cardiovascular specimens.", "questions": [ "How is amyloid deposition typed in endomyocardial biopsies?", "What methods are used to diagnose iron deposition?", "Why is frozen tissue useful for evaluating metabolic disease?", "What imaging studies are more appropriate for diagnosing hypertrophic cardiomyopathy?", "What are the key features to check for in the sign-out checklist for nontransplant and transplant specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 309, "text": "291\nCARDIOVASCULAR SPECIMENS\u2003 Native Mitral and Aortic Valves\nNATIVE MITRAL AND AORTIC VALVES\nCritical information relative to removed valves is obtained from the gross examination and dissection of \nthe valves. Although all specimens (excluding mechanical valves) are sectioned, histologic study is par\u00ad\nticularly valuable to address a specific question such as endocarditis. All prosthetic valves, intact native \nvalves, and any unusual lesions (e.g., vegetations or endocardial fibroelastomas) should be photographed, \nas close-up as possible. Document both acute and underlying chronic lesions. For more information see \nSchoen.4\nNative aortic valves are most frequently replaced due to calcific degeneration (valves with either two \nor three cusps). Mitral valves are replaced for rheumatic valve disease or because of myxomatous degen\u00ad\neration. In most cases, the most important diagnostic information is derived from the gross examination \nof the specimen.\nSPECIMEN EXAMINATION, DICTATION, AND PROCESSING\n 1.\t \u0007Examine grossly and determine type of valve (aortic or mitral).\n\t \u2022\t \u0007Leaflets or cusps: Number of recognizable leaflets (atrioventricular valves) or cusps (semilunar \nvalves), size, consistency (thickened, fibrotic, calcified, thinned, redundant [ballooned], perforated), \nadditional fragments. If an abnormality is present describe the distribution (focal or diffuse), surface \n(atrial or ventricular or both), and location (free edge or base).\n\t \u2022\t \u0007Commissures: Relationship to each other (fused, completely, partially).\n\t \u2022\t \u0007Chordae tendineae (tendinous cords): Length (shortened, elongated), status (intact, thickened, rup\u00ad\ntured, fused). Mitral valves, but not aortic valves, have cords.\n\t \u2022\t \u0007Papillary muscles: Dimensions, abnormalities (hypertrophied, elongated, scarred).\nTABLE 16\u20131.\u2003\n\u0007INTERNATIONAL SOCIETY FOR HEART AND LUNG TRANSPLANTATION (ISHLT) \nGRADING OF CARDIAC REJECTION\nLEVEL\nDIAGNOSIS\nAcute Cellular Rejection\n0R\nNo rejection\n1R, mild\nInterstitial and/or perivascular infiltrate with up to 1 focus of myocyte damage\n2R, moderate\nTwo or more foci of infiltrate with associated myocyte damage\n3R, severe\nDiffuse infiltrate with multifocal myocyte damage +/- edema, +/- hemorrhage \n+/\u2013 vasculitis\nAcute Antibody-Mediated Rejection (AMR)*\nAMR 0\nNegative for acute antibody-mediated rejection\nNo histologic or immunopathologic features of AMR\nAMR 1\nPositive for AMR\nHistologic features of AMR\nPositive immunofluorescence or immunoperoxidase staining for AMR (positive \nCD68, C4d)\n*Acute antibody-mediated rejection (AMR) remains controversial with a highly varied incidence between transplant centers and no consensus on its \nrecognition and diagnosis either by histopathologic or immunologic testing. If there is suspicion of AMR, either clinically or by proposed histologic \ncriteria, biopsies may be analyzed by immunofluorescence or immunohistochemistry for (1) immunoglobulin (IgG, IgM, and/or IgA) plus comple\u00ad\nment deposition (C3d, C4d, and/or C1q) in capillaries, (2) CD68 staining of macrophages within capillaries, and/or (3) C4d staining of capillaries. \nTreatment of patients with AMR typically requires the presence of hemodynamic compromise and the presence of circulating HLA antibodies in \naddition to positive biopsy findings.\nNote: \u201cR\u201d indicates the 2004 revision.\nAdapted from Stewart S, Winters GL, Fishbein MC, et al: Revision of the 1990 working formulation for the standardization of nomenclature in the \ndiagnosis of heart rejection. The Journal of Heart and Lung Transplantation 24(11):1710-1720, 2005.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_309.png", "summary": "The examination and dissection of native mitral and aortic valves provide critical information for diagnosis, with histologic study being particularly valuable for addressing specific questions like endocarditis. Gross examination of the specimen is key for diagnostic information.", "questions": [ "How is the diagnosis of acute antibody-mediated rejection (AMR) defined and what are the controversies surrounding it?", "What are the key aspects to examine during the gross examination of native mitral and aortic valves?", "Why is histologic study important for addressing specific questions like endocarditis in valve specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 310, "text": "292\nCARDIOVASCULAR SPECIMENS\u2003 Native Mitral and Aortic Valves\n\t \u2022\t \u0007Vegetations: Color, size, location, consistency (firm, friable), presence or absence of destruction of \nunderlying tissue.\n\t \u2022\t \u0007Endocarditis is a life-threatening disease and any indication that acute endocarditis is present should \nbe immediately brought to the attention of the clinician. Order Gram and MSS if there is any \n\u00adpossibility of endocarditis, either from clinical information or after gross or histologic examination.\n 2.\t \u0007Submit one cassette with representative sections taken from the free edge to the annulus. It may be \nnecessary to decalcify some specimens.\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Figures 16-1, 16-2, and 16-3 and Tables 16-2 and 16-3.\nDegenerative Calcific Aortic Valve Stenosis.\u2002 Calcific deposits are present within the cusps, primarily \nat the base (attachment margin). The free cuspal edges are usually not involved. The cusps may be heavily \nfibrosed and thickened but are not fused. Congenital bicuspid valves are predisposed to degenerative calci\u00ad\nfication. Usually one of the cusps is larger with a midline raphe resulting from the incomplete separation of \ntwo cusps. Less frequently the cusps may be of equal size. The raphe is often the site of extensive calcification.\nMitral Annular Calcification.\u2002 Calcifications occur in the annulus of the mitral valve. The chordae \nare uninvolved.\nMyxomatous Degeneration of the Mitral Valve.\u2002 The leaflet is enlarged, thickened and redundant. \nThe cords may be elongated and thinned and sometimes ruptured.\nAortic Post-inflammatory Scarring (Rheumatic Type).\u2002 The cusps are fused at the commissures. \nThere is diffuse thickening and calcification is rather evenly distributed and includes the free cuspal \nedges. The mitral valve is virtually always involved as well.\nMitral Post-inflammatory Scarring (Rheumatic Type).\u2002 The leaflets are thickened and there is \ncommissural fusion and shortening. The cords are thickened and fused. Calcification is often present.\nEndocarditis.\u2002 In acute bacterial endocarditis, large friable vegetations are found on the valves and \nmay be single or multiple. They may extend onto the chordae. There is often perforation or erosion of \nthe underlying valve. The vegetations of nonbacterial thrombotic endocarditis (NBTE) are small, bland, \nand typically attached at the line of closure on the flow surfaces of the valve. Systemic lupus may be \nassociated with small bland vegetations that can be located on both surfaces of the valve or on the cords \n(Libman-Sacks endocarditis).\nSAMPLE DICTATION FOR CALCIFIC DEGENERATION OF THE AORTIC VALVE\nThe specimen, received fresh, labeled with the patient\u2019s name, unit number, and \u201caortic valve,\u201d consists \nof three semilunar valve cusps, measuring 2.5, 2.6, and 2.3 cm along the free edges and 1.0 cm from \nfree edge to base. The outflow surfaces of all three cusps contain numerous irregular yellow/tan calcific \ndeposits up to 1.0 cm. There is no evidence of commissural fusion. No vegetations are present. The \nspecimen is fixed and decalcified prior to processing.\nMicro 1: Aortic valve cusp, 3 frags, RSS.\nSAMPLE DICTATION FOR MYXOMATOUS DEGENERATION OF THE MITRAL VALVE\nThe specimen, received fresh, labeled with the patient\u2019s name, unit number, and \u201cmitral valve leaflet,\u201d \nconsists of an atrioventricular valve leaflet measuring 4.0 cm along the free edge and 1.4 cm from free \nedge to base. There is diffuse myxomatous thickening of the leaflet which appears billowing and redun\u00ad\ndant. The chordae are thin and elongated and there is rupture of one chorda.\nMicro 1: Mitral valve leaflet, 3 frags, RSS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_310.png", "summary": "The page discusses various cardiovascular specimens, focusing on native mitral and aortic valves. It provides information on different pathologies such as degenerative calcific aortic valve stenosis, mitral annular calcification, myxomatous degeneration of the mitral valve, and post-inflammatory scarring in both aortic and mitral valves.", "questions": [ "What are the key features to look for in vegetations on native mitral and aortic valves?", "How can acute endocarditis be identified and what steps should be taken if suspected?", "What are the differences in presentation between degenerative calcific aortic valve stenosis, mitral annular calcification, myxomatous degeneration of the mitral valve, and post-inflammatory scarring in aortic and mitral valves?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 311, "text": "293\nCARDIOVASCULAR SPECIMENS\u2003 Native Mitral and Aortic Valves\nNormal aortic valve\nAorta\nAorta\nR\nN\nN\nL\nLeft cusp\nAnterior\nmitral\nleaflet\n(AMVL)\nSlightly dilated aorta\nMitral\nannular Ca#\nCa#\nFocal cuspal\nfibrous thickening\nPosterior\nPosterior\nPosterior\nleaflet\nLeft\natrium\nLeft\nventricle\nPapillary\nmuscle\nChordae\ntendineae\nRuptured\nchordae\nIncreased annulus\nlength, leaflet area\nand buckling\nVegetation\nAnterior\nCalcific deposits\nRaphe\nRaphe\nValve or\ncommissure\nExtensive\nfibrous\nthickening\nMild\nCa#\nCommissural fusion\nDiffusely\nthickened\nAMVL \u00b1 Ca#\nCentral leak\nDilated ascending aorta\nTaut margins\nof closure\nFocal fibrous\nthickening\nA\nP\nP\nA\nVegetation\nVegetation\nIndentation\nPerforation\nPerforation\nLoss of\ncuspal\ntissue\nCongenitally bicuspid\nInfective endocarditis (active or healed) (tricuspid)\nInfective endocarditis (active or healed) (bicuspid)\nRheumatic (with or without commissural fusion)\nSystemic hypertension (chronic, severe)\nRHD\nIE\nNBTE\nLSE\nNormal mitral valve\nInfective endocarditis (active or healed)\nFloppy (mitral valve prolapse) \nRheumatic\nAnnular calcium\nDiffusely thickened mitral\nvalve also present\nAnnulus \nDiffuse fibrous thickening\nFocal chordal\nthickening\nAnnular calcific\ndeposits\nproducing\nleaflet\nprotrusion\ntoward left\natrium\nA\nB\nR\nL\nPerforation or indentation\nDegenerative\nVentricular\ndiastole\nFigure 16\u20131.\u2002 A, B, Evaluation of operatively excised cardiac valves: etiologic determination of valvular heart disease. RHD, \nrheumatic heart disease; IE, infective endocarditis; NBTE, nonbacterial thrombotic endocarditis; LSE, Libman-Sacks endocardi\u00ad\ntis.\u2002 (A modified from Waller BF, et al: Cardiol Clin 2:687, 1984. B modified from Schoen FJ: The heart. In Cotran RS, Kumar V, Robbins \nSL [eds]: Robbins Pathologic Basis of Disease, 5th ed., Philadelphia, W.B. Saunders, 1994, p. 554.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_311.png", "summary": "The page discusses the evaluation of operatively excised cardiac valves, including findings such as normal and abnormal features, calcific deposits, fibrous thickening, and indications of various heart diseases.", "questions": [ "What are some common abnormalities found in the native mitral and aortic valves?", "How can the presence of calcific deposits impact the function of the valves?", "What are the potential implications of findings such as vegetations, perforations, and chordal thickening on valve function?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 312, "text": "294\nCARDIOVASCULAR SPECIMENS\u2003 Native Mitral and Aortic Valves\nSAMPLE DICTATION FOR RHEUMATIC MITRAL VALVE\nThe specimen, received fresh, labeled with the patient\u2019s name, unit number, and \u201cmitral valve leaflet,\u201d \nconsists of an atrioventricular valve leaflet measuring 3.5 cm along the free edge and 1.5 cm from free \nedge to base. The leaflet is diffusely thickened to 0.4 cm and fibrotic. The surface of the leaflet is white/\ntan and smooth without vegetations or perforations. Focal calcific deposits are located toward the annu\u00ad\nlus. The attached chordae are thickened, measuring up to 1.8 cm in length and 0.2 cm in thickness, and \nare focally fused.\nMicro 1: Mitral valve leaflet, 3 frags, RSS.\nAORTIC VALVE DISEASE\nDiffusely fibrotic,\nthickened cusps\nBicuspid valve\nwith calcification\nNodular calcification, cuspal bases\n1 cusp\nCongenital\nunicuspid with\ncalcification\nDegenerative\ncalcification\nFree edge\nfibrosis;\ncommissural\nfusion\nRheumatic heart\ndisease\nOther cuspal\nabnormality\nCusps\nnormal\nAortic disease\n(probable)\nFocal fibrosis;\ncuspal destruction;\nvegetations\nEndocarditis,\nhealed or\nactive\nOther\n2 cusps\n3 cusps\nFigure 16\u20132.\u2002 Overview of major diagnostic considerations in aortic valve disease.\u2002 (From Schoen FJ: Evaluation of \nsurgically removed natural and prosthetic heart valves. In Virmani R, Fenoglio JJ [eds]: Cardiovascular Pathology. \nPhiladelphia, W.B. Saunders, 1991, p. 404.)\nMITRAL VALVE DISEASE\nDiffusely fibrotic,\nthickened leaflets\nHeavily calcified\ncut edge\nCalcification of\nmitral annulus\nRheumatic\nheart disease\nCuspal redundancy,\nhooding; thinned\nelongated cordae\nMyxomatous\nmitral valve\nEndocarditis,\nhealed or active\nCommissural fusion;\nthickened, shortened\ncordae\nFunctional regurgitation\nor ischemic heart disease\nNormal or thinned\nleaflets\nFocally fibrotic or\nperforated, destroyed\nleaflets; vegetations\nFigure 16\u20133.\u2002 Overview of major diagnostic considerations in mitral valve disease.\u2002 From Schoen FJ: Evaluation \nof surgically removed natural and prosthetic heart valves. In Virmani R, Fenoglio JJ [eds]: Cardiovascular Pathology. \n\u00adPhiladelphia, W.B. Saunders, 1991, p. 404.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_312.png", "summary": "The page discusses specimens of native mitral and aortic valves, detailing the characteristics of rheumatic mitral valve and aortic valve disease.", "questions": [ "What are the key features of rheumatic mitral valve disease described in the specimen?", "What are the major diagnostic considerations in aortic valve disease according to the text?", "How do the characteristics of mitral valve disease differ from those of aortic valve disease?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 313, "text": "CARDIOVASCULAR SPECIMENS\u2003 Prosthetic Heart Valves\n295\nPATHOLOGIC FEATURES SIGN-OUT CHECKLIST\n\t\u2022\t \u0007Type of valve: Aortic, pulmonary, mitral, tricuspid\n\t\u2022\t \u0007Disease process: Calcific degeneration; congenital bicuspid aortic valve; myxomatous degeneration; \n\u00adpost-inflammatory scarring, rheumatic type; endocarditis\n\t\u2022\t \u0007Papillary muscle: Infarcted or scarred\n\t\u2022\t \u0007Vegetations: Present or absent, type\nPROSTHETIC HEART VALVES\nA good reference for the examination of prosthetic heart valves is Schoen.5\nPROCESSING THE SPECIMEN\n 1.\t \u0007Identify the type of prosthesis by using Figures 16-4, 16-5, 16-6, and 16-7 and Table 16-4. Mea\u00ad\nsure the external diameter of the outside sewing ring. The type of valve is included in the diagnosis. \n\u00adCommonly used valves are either Hancock or Carpentier-Edwards porcine bioprostheses, bovine \npericardial bioprostheses, or St. Jude bileaflet (all carbon) valves.\n 2.\t \u0007Describe any tissue overgrowth of the sewing ring.\n 3.\t \u0007For mechanical valves, also describe any asymmetry, notches, or cracks of any of the components. \nDescribe any impairment in motion of the components.\nTABLE 16\u20132.\u2003\n\u0007GROSS MORPHOLOGIC ASSESSMENT OF ABNORMAL CARDIAC VALVULAR \nFUNCTION\nPATHOLOGIC FEATURE\nSTENOTIC VALVE\nPURELY REGURGITANT VALVE\nFor All Valves\nValve weight\nIncreased\nNormal, or slightly increased or decreased\nFibrous thickening\nDiffuse\nDiffuse, focal, or none\nCalcific deposits\nNone to heavy\nMinimal (if any)\nTissue loss (perforation, indentation)\nNone\nMay be present\nVegetations\nMinimal\nMay be present\nCommissural fusion\nMay be present\nMinimal (if any)\nAnnular circumference\nNormal\nNormal or increased\nFor Aortic Valves\nNumber of cusps\nOne to three\nTwo or three\nFor Mitral (or Tricuspid) Valves\nAbnormal papillary muscles\nNo\nMay be present\nChordae tendineae\nFusion\nUsually present\nAbsent\nElongation\nAbsent\nMay be present\nShortening\nUsually present\nMay be present\nRupture\nAbsent\nMay be present\nFrom Schoen FJ, Surgical pathology of removed natural and prosthetic cardiac valves, Hum Pathol 18:558, 1987.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_313.png", "summary": "This page provides information on the examination of prosthetic heart valves, including identifying the type of valve, describing tissue overgrowth, and assessing mechanical valve components.", "questions": [ "What are the common types of prosthetic heart valves mentioned in the text?", "How can the type of prosthesis be identified during examination?", "What are some key differences in the gross morphologic assessment of abnormal cardiac valvular function between stenotic and purely regurgitant valves?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 314, "text": "CARDIOVASCULAR SPECIMENS\u2003 Prosthetic Heart Valves\n296\n 4.\t \u0007For tissue valves, describe any tears or perforations of the cusps and/or any impairment of cusp motion.\n 5.\t \u0007Describe tissue overgrowth, vegetations including color, site (surface of valve, sewing ring), size, con\u00ad\nsistency (firm, friable), presence or absence of destruction of underlying material.\n 6.\t \u0007Describe any calcific deposits and their location.\n 7.\t \u0007Photograph all valves. Radiograph tissue valves, but not mechanical valves, to evaluate the degree of \ncalcification. Calcification is graded on a scale from 0 to 4 using the specimen radiograph.\n 8.\t \u0007Submit a portion of bioprosthetic valve cusps for histologic examination.\nIMPORTANT: Submit tissue on the sewing ring adjacent to all valve prostheses, as infection of the sew\u00ad\ning ring annulus may be the only manifestation of endocarditis in mechanical valves, and also occurs in bio\u00ad\nprosthetic valves. In cases of suspected endocarditis, Gram and fungal (methenamine silver) stains are ordered.\nSAMPLE DICTATION FOR MECHANICAL VALVES\nThe specimen, received fresh, labeled with the patient\u2019s name, unit number, and \u201caortic valve,\u201d consists \nof a St. Jude bileaflet tilting-disc prosthesis with an external sewing ring diameter of 21 mm. The pros\u00ad\nthesis is intact. There is focal tissue overgrowth of the sewing ring. The leaflets move freely and open \nand close completely. No thrombi or vegetations are present. Also present in the same container are \nmultiple detached fragments of tan soft tissue measuring in aggregate 3.0 \u00d7 2.5 cm. The specimen is \nphotographed.\nMicro 1: Tissue from sewing ring and detached tissue fragments, mult frags, ESS.\nTABLE 16\u20133.\u2003\nETIOLOGIC ASSESSMENT OF VALVULAR HEART DISEASE\nSENILE \nDEGENERATION\nMYXOMATOUS \nDEGENERATION\nRHEUMATIC\nINFECTIVE\nSECONDARY\nGross Features\nLeaflet/cuspal \n\u00adthickening\n0\n0/+\n+\n0\n0\nCalcification\n+\n0\n0/+\n0\n0\nCommissural/ chordal \nfusion\n0\n0\n+\n0\n0\nLeaflet/cuspal redun\u00ad\ndancy\n0\n+\n0\n0\n0\nLeaflet/cuspal defects\n0\n0\n0\n+\n0\nChordal rupture\n0\n0/+\n0\n0/+\n0\nHistologic Features\nPreservation of lay\u00ad\nered \u00adarchitecture\n+\n+\n0\n0/+\n+\nGAG accumulation in \nspongiosa\n0\n+\n0\n0\n0/+\nThinned fibrosa\n0\n+\n0\n0\n0\nNeovascularization\n0\n0\n0/+\n0/+\n0\nSuperficial \u00adfibrosis \nonly\n0/+\n0/+\n0\n0/+\n0/+\n0, absent; +, present; 0/+, present in some cases; GAG, glycosaminoglycan.\nFrom Schoen FJ, Surgical pathology of removed natural and prosthetic cardiac valves, Hum Pathol 18:558, 1987.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_314.png", "summary": "The page discusses the examination of prosthetic heart valves, including descriptions of tears, tissue overgrowth, calcific deposits, and the importance of submitting tissue for histologic examination.", "questions": [ "How is calcification graded on a scale from 0 to 4 using the specimen radiograph?", "Why is it important to submit tissue on the sewing ring adjacent to all valve prostheses?", "What are the key gross and histologic features used in the etiologic assessment of valvular heart disease?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 315, "text": "CARDIOVASCULAR SPECIMENS\u2003 Prosthetic Heart Valves\n297\nSAMPLE DICTATION FOR BIOPROSTHETIC VALVES\nThe specimen, received fresh, labeled with the patient\u2019s name, unit number, and \u201cmitral valve,\u201d consists \nof a bioprosthetic valve with an external sewing ring diameter of 31 mm. The valve cusps are moderately \nstiffened and there is focal commissural calcification. One of the cusps contains a single 0.4 cm linear \ntear near the commissure involving the cuspal free edge. The remaining cusps are intact. No thrombi \nor vegetations are present. Also present in the same container are 6 detached irregular fragments of tan/\nyellow soft tissue, measuring in aggregate 2.0 \u00d7 1.5 cm. The specimen is photographed and \u00adradiographed.\nMicro 1: Valve cusp and detached fragments, mult frags, RSS.\nPATHOLOGIC FEATURES SIGN-OUT CHECKLIST\n\t \u2022\t \u0007Site: Aortic or mitral\n\t \u2022\t \u0007Type of valve: Use Figures 16-4 to 16-7 and Table 16-4 to identify the type of valve\n\t \u2022\t \u0007Calcifications: Grade 0 to 4+ using the specimen radiograph\n\t \u2022\t \u0007Cuspal tears: Present or absent, size\n\t \u2022\t \u0007Mechanical degeneration: Type, location\nA\nB\nC\nD\nE\nF\nG\nH\nI\nFigure 16\u20134.\u2002 Representative prosthetic heart valves. A, Starr-Edwards caged ball valve. B, Bj\u00f6rk-Shiley tilting disk valve. \nC, Medtronic-Hall tilting disk valve. D, St. Jude Medical tilting disk valve. E, CarboMedics (CPHV) bileaflet tilting disk valve. \nF, Hancock porcine aortic valve bioprosthesis. G, Ionescu-Shiley bovine pericardial bioprosthesis. H, Carpentier-Edwards \nbovine pericardial bioprosthesis. I, Medtronic Freestyle stentless porcine aortic valve prosthesis.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_315.png", "summary": "The page discusses a sample dictation for a bioprosthetic valve specimen, detailing the findings of a valve with stiffened cusps, commissural calcification, and a tear in one cusp.", "questions": [ "What are the key components of the sample dictation for a bioprosthetic valve specimen?", "How are calcifications graded in the pathologic features sign-out checklist?", "What are the different types of prosthetic heart valves shown in Figure 16-4?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 316, "text": "CARDIOVASCULAR SPECIMENS\u2003 Prosthetic Heart Valves\n298\nOBSERVATION\nStruts project\nvertically from\nsewing ring\nTwo long metal struts with sharply angled ends project at angle less than 90?;\n3 small metal feet project into orifice\u2013two act as hinges, third as stopper.\nStruts or feet project\nhorizontally into\nvalve orifice\nFour tiny metal struts with angled ends project\ninto orifice; thin, curvilinear black pyrolytic carbon-\ncoated disk pivots between them. Struts on inflow surface\nalso angle up from metal inner ring. Disk at angle of\n12? when prosthesis is closed. Sewing ring has 3 or 4\nblack marks on it for surgeon\u2019s orientation.\nNo obvious cage, 2 small feet in inner ring; disk Z-shaped\nin profile; occludes orifice by seating on both surfaces.\n2 roughly semicircular struts project horizontally into\nvalve orifice; pyrolytic carbon-coated disk may be\nmesa-shaped or convexoconcave in profile.\nSingle roughly semicircular strut projects horizontally\ninto valve orifice, opposed by single short metal projection\nwith bulbous end.\nSmall rounded metal strut and larger roughly S-shaped\nstrut project horizontally into orifice on opposite sides of\nring. Both project into central hole in black pyrolytic\ncarbon-coated disk. Two smaller metal pivots with angled\nends found in orifice at right angles to struts.\nProsthesis as described above, but all parts including\nsewing ring coated with black pyrolytic carbon. Sewing\nring has 2 or 3 black marks on it for surgeon\u2019s\norientation.\nVery large horizontal U-shaped metal strut with two\nhorizontal straight metal projections opposite each other.\nPyrolytic carbon-coated disk concavoconvex.\nThree straight metal struts project horizontally. Two small\nones with larger one, which has a bulbous end and is perpendicular\nto the other two. Pyrolytic carbon disk flat with well on one side.\nSingle linear horizontal metal strut is both tapered and\nnotched. Two small notches on luminal surface oppsite\neach other.\nTwo housings containing pivoting ends of disk project\nsmoothly and like hillocks from inflow surface. All parts of\nprosthesis (except sewing ring) coated with black pyrolytic\ncarbon. Disk at angle when prosthesis closed.\nComparable morphology to St. Jude prosthesis but disks\nhorizontal when prosthesis closed.\nNo obvious struts.\nTwo D-shaped disks\nocclude orifice\nCage\nCage\nopen\n4 struts; metal feet in orifice;\nblack disk biconical poppet;\neccentric sewing ring\nCooley-Cutter\nCross-Jones\nBeall 104\nBeall-Surgitool 105\nor 106\nKay-Shiley\nStarr-Edwards 6520\nKay-Suzuki\nHarken\nStarr-Edwards 6500\nLillehei-Kaster\nWada-Cutter\nBj\u00f6rk-Shiley\nBj\u00f6rk-Shiley\nMonostrut\nMedtronic-Hall\nOmniscience\nOmnicarbon\nUltracor\nBieer-Val\nJatene-Macchi\nSt. Jude Medical\nEdwards-Duromedics\n(formerly Hemex)\n3 struts; no feet in orifice; plastic\npoppet has metal ring in substance\nStruts, bars, and disk coated\nwith white plastic\nStruts, bars, and disk coated\nwith black pyrolytic carbon\nInner ring extends onto\noutflow surface; plastic disk\nhas metal ring in substance\nFour feet project into orifice\nopposite cage; plastic poppet\nNaked metal struts; plastic disk\nNaked metal struts; metal disk\nStruts and bars of naked metal;\nplastic disk; may have muscle guards\nMetal inner ring\nCloth-covered\ninner ring\n4 struts form\ntwo bars\n4 struts meet\nat apex of cage\nCage\nclosed\nTYPE OF PROSTHESIS\nFigure 16\u20135.\u2002 Key for identifying caged-disk and tilting prostheses.\u2002 (Modified from Silver MD, Wilson JG: Pathology of cardiovascular \n\u00adprostheses including coronary artery bypass and other vascular grafts. In Silver MD [ed]: Cardiovascular Pathology. New York, Churchill \n\u00adLivingstone, 1991.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_316.png", "summary": "The page describes various types of prosthetic heart valves, detailing the structure and components of each.", "questions": [ "What are the differences in structure between the various types of prosthetic heart valves mentioned?", "How do the different components of the prosthetic heart valves function in valve operation?", "What are the implications of the different coatings (black pyrolytic carbon, white plastic) on the struts, bars, and disks of the prosthetic heart valves?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 317, "text": "CARDIOVASCULAR SPECIMENS\u2003 Heart Transplants\n299\n\t \u2022\t \u0007Tissue degeneration: Present or absent\n\t \u2022\t \u0007Tissue overgrowth: Focal or extensive\n\t \u2022\t \u0007Overhanging suture: Present or absent\n\t \u2022\t \u0007Endocarditis: Present or absent\n\t \u2022\t \u0007Vegetations: Present or absent\n\t \u2022\t \u0007Cuspal perforation: Present or absent\nHEART TRANSPLANTS\nPatients receiving heart transplants are typically in end-stage cardiac failure due to ischemic heart disease or \nidiopathic cardiomyopathy. The specimen usually consists of both ventricles and atria amputated above the \nventricles. Occasionally small portions of the donor heart will also be received (e.g., auricular appendages).\nCAGED-BALL PROSTHESIS\nCage\nOpen\nDouble cage\nSingle cage\nFeet in valve orifice\nNaked\nmetal\nstruts\nCage has\nthree\nstruts\nMetal inner ring\nextends onto inflow\nsurface of sewing ring\nInner ring does not extend\nonto sewing ring\nInner ring does not extend\nonto surface\nCloth-covered\ninner ring\nMetal struts not\nwelded at apex\nof cage\nMetal struts\nwelded\nComposite strut\ncomposition\nComposite strut\ncomposition\nComposite (cloth and\nmetal studs)\ninner ring\nPlastic inner ring\nCloth-covered\ninner ring\nComposite inner ring\nMetal inner ring extends\nonto inflow surface\nPlastic (polyethylene) inner\nring; recent model has struts\ncoated with black pyrolytic\ncarbon\nCage has\nthree\nstruts\nCage has\nfour\nstruts\nCloth-\ncovered\nstruts\nNo feet\nin orifice\nNaked metal struts\nSmeloff-Sutter\n(formerly Smeloff-Cutter)\nMcGovern-Cromie\nBraunwald-Cutter\nStarr-Edwards 1000\nStarr-Edwards 1200\nStarr-Edwards 1260\nStarr-Edwards 6000\nStarr-Edwards 6120\nStarr-Edwards 2300\nStarr-Edwards 2310, 2320\nStarr-Edwards 2400\nStarr-Edwards 6300\nStarr-Edwards 6310, 6320\nStarr-Edwards 6400\nHarken\nSurgitool 200\nCage has\nfour\nstruts\nDebakey-Surgitool\nCloth-covered struts\nClosed\nOBSERVATION\nTYPE OF PROSTHESIS\nFigure 16\u20136.\u2002 Key for identifying caged-ball prostheses.\u2002 (Modified from Silver MD, Wilson JG: Pathology of cardiovascular prostheses \nincluding coronary artery bypass and other vascular grafts. In Silver MD [ed]: Cardiovascular Pathology. New York, Churchill Livingstone, 1991.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_317.png", "summary": "This page discusses cardiovascular specimens from heart transplants, including tissue degeneration, overgrowth, endocarditis, and other related features.", "questions": [ "What are the common reasons for patients receiving heart transplants?", "What are the key components of a caged-ball prosthesis?", "How are different types of caged-ball prostheses identified?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 318, "text": "CARDIOVASCULAR SPECIMENS\u2003 Heart Transplants\n300\nTABLE 16\u20134.\u2003\nPATHOLOGIC ANALYSIS OF BIOPROSTHETIC VALVES\nGROSS EXAMINATION\nHISTOLOGY\nRADIOGRAPHY\nIdentification (e.g., porcine aortic \u00ad[Hancock or \n\u00adCarpentier-Edwards], pericardial \u00ad[Pericardial])\nIdentification\nVegetations\nVegetations/organisms\nThrombi\nThrombi\nParavalvular leak\nHost cell \u00adinteractions\nTissue overgrowth\n\u00adEndothelialization\nCuspal stiffness\nPannus \u00adovergrowth\nCuspal hematomas\nDegeneration\nCalcification\nCalcification\nDegree\nMorphology\nLocation\nCalcification\nDegree\nLocalization\nCuspal fenestrations and tears\nCuspal abrasions\nCuspal stretching\nStrut relationships\nExtrinsic interference or damage\nTissue separation from strut\nBIOPROSTHESES\nRadiopaque\nbase ring\nAbsent\nNo radiopaque parts\nAngell-Shiley\nCarpentier-Edwards\nHancock\nIonescu-Shiley\nSerpiginous wire stent\nradiopaque\nNarrow, wirelike base ring;\nstent is radiolucent\nBase ring and stent integral,\nflattened and perforated\nPresent\nRadiologic finding\nProsthesis\nFigure 16\u20137.\u2002 Key for identifying bioprostheses.\u2002 (Modified from Silver MD, Wilson JG: Pathology of cardiovascular pros\u00ad\ntheses including coronary artery bypass and other vascular grafts. In Silver MD [ed]: Cardiovascular Pathology. New York, \nChurchill Livingstone, 1991.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_318.png", "summary": "This page discusses the pathologic analysis of bioprosthetic valves, including gross examination, histology, and radiography.", "questions": [ "What are some common findings during the gross examination of bioprosthetic valves?", "How do vegetations and thrombi play a role in the pathology of bioprosthetic valves?", "What are some key differences in the radiopacity of various bioprostheses?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 319, "text": "CARDIOVASCULAR SPECIMENS\u2003 Heart Transplants\n301\nPROCESSING THE SPECIMEN\n \u2002 1.\t \u0007Weigh the specimen. Normal weights for the entire heart are 270 to 360 gm for males and 250 to \n280 gm for females.\n \u2002 2.\t \u0007Describe the epicardial surface including pericardial fat (abundant, scant), petechiae, and adhesions.\n \u2002 3.\t \u0007In general, hearts are cut after fixation in a manner \u00addictated by the pathology to be demonstrated \n(Fig. 16-8).\n\t\n\u2022\t \u0007Hearts with dilated cardiomyopathy are cut longitudinally from base to apex, bivalving both ven\u00ad\ntricles and bisecting the tricuspid and mitral valves (\u201cfour-chamber\u201d cut).\n\t\n\u2022\t \u0007Hearts with ischemic heart disease are typically cut transversely at approximately 1 to 2 cm inter\u00ad\nvals beginning at the apex to the level of the mitral valve (\u201cserially sectioned\u201d). The base of the \nheart may be cut longitudinally or opened according to the lines of flow.\n \u2002 4.\t \u0007Describe each ventricle separately including hypertrophy or dilatation, fibrosis (endocardial, epicardial, \ntransmural, location and degree), infarcts (old or recent, size, location, transmural or subendocardial), \ntrabeculation, papillary muscles (hypertrophied, thinned, scarred, infarcted), presence of mural throm\u00ad\nbus. Measure the wall thickness of both ventricles. Normal thickness of the left ventricle is 0.9 to 1.5 cm \nand the right ventricle 0.25 to 0.3 cm. The diagrams provided may facilitate documentation of findings.\n \u2002 5.\t \u0007Describe atria if there are any endocardial lesions.\n \u2002 6.\t \u0007Describe any valve lesions as in section above (native or prosthetic).\n \u2002 7.\t \u0007Atherosclerotic coronary arteries are dissected from the heart, fixed and decalcified, and sectioned \ntransversely at 3 to 5 mm intervals. Soft, unobstructed coronary arteries may be carefully cut in \ntransverse sections on the fixed heart at 3 mm intervals. Describe the arteries including dominance \n(right or left), percent of luminal compromise, location, recent thrombi or plaque hemorrhage, \nand the locations of these lesions.\n \u2002 8.\t \u0007Describe any bypass grafts including type (saphenous vein, left internal mammary), location of graft to \nnative vessel, and patency. Remove the junction of the graft and native vessel as a block of tissue from \nthe epicardial surface. Serially section perpendicular to the vessels to look for luminal \u00adobstructions.\n \u2002 9.\t \u0007Describe any devices or parts thereof, including pacer wires, AICD wires, annuloplasty rings, Alfieri \nstitches, VAD cannulae, etc.\n 10.\t \u0007Submit sections according to the list below.\nAS\nRA\nTV\nLA\nAML\nPML\nANT\nANT\nANT\nAML\nPML\nPOS\nPOS\nPOS\nVS\nVS\nRV\nRV\nRV\nLV\nLV\nLV\nINF\nLAT\nLAT\nVS\nA\nB\nPM\nSeptum Primum\nAS \n= atrial septum\nRA \n= right atrium\nLA \n= left atrium\nTV \n= tricuspid valve\nVS \n= ventricular septum\nAML \n= anterior mitral leaflet\nPML \n= posterior mitral leaflet\nPM \n= papillary muscle\nLat RV = lateral right ventricle\nAnt RV = anterior right ventricle\nAnt VS = anterior ventricular septum\nPost VS = posterior ventricular septum\nPost RV = posterior ventricular septum\nAnt LV = anterior left ventricle\nLat LV = lateral left ventricle\nPost (inf) LV = posterior (inferior) left ventricle\nFossa Ovalis\nFigure 16\u20138.\u2002 Cardiac anatomy. A, Longitudinal cut. B, Transverse cut.\u2002 (A from Virmani R, Ursell PC, Fenoglio JJ: \n\u00adExamination of the heart. In Varmani R, Atkinson JB, Fenoglio JJ [eds]: Cardiovascular Pathology. Philadelphia, W.B. \n\u00adSaunders, 1991, p. 9.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_319.png", "summary": "This page outlines the processing and examination of heart transplant specimens, including specific techniques for different cardiac conditions and detailed descriptions of various cardiac structures.", "questions": [ "How do the processing techniques differ for hearts with dilated cardiomyopathy versus hearts with ischemic heart disease?", "What specific details should be included when describing each ventricle separately?", "Why is it important to describe atria and valve lesions in heart transplant specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 320, "text": "CARDIOVASCULAR SPECIMENS\u2003 Heart Transplants\n302\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Left ventricular free wall: Two sections (apex and base) in one cassette.\n\t\u2022\t \u0007Right ventricular free wall: Two sections (apex and base) in one cassette\n\t\u2022\t \u0007Septum: Two sections (apex and base) in one cassette\n\t\u2022\t \u0007Native coronary arteries: Up to four cassettes if abnormalities are present in the left main (LMA), \nleft anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) including \nareas of obstruction.\n\t\u2022\t \u0007Bypass grafts: One cassette of each graft.\n\t\u2022\t \u0007Other lesions: Representative sections\nGROSS DIFFERENTIAL DIAGNOSIS\nIschemic Heart Disease.\u2002 By the time a patient comes to cardiac transplantation, there is usually \nextensive damage present. There may be fibrous scars and pericardial adhesions due to previous healed \ninfarcts. Aneurysms may be present. The vessels usually are involved by extensive atherosclerosis and \nbypass grafts are often present.\nIdiopathic Dilated Cardiomyopathy.\u2002 The heart is usually enlarged (two to three times the normal \nweight) and all four chambers are enlarged. The ventricular wall thickness can be thin, thick, or normal, \ndepending on the balance of hypertrophy and dilatation. There may be small patchy subendocardial \nfibrous scars in the left ventricle. Endocardial plaques may be present. Mural thrombi are commonly \nfound near the apex of the ventricles. The valves and coronary arteries are generally normal.\nSAMPLE DICTATION FOR IDIOPATHIC DILATED CARDIOMYOPATHY\nThe specimen, received fresh, labeled with the patient\u2019s name and unit number, consists of a heart weigh\u00ad\ning 650 grams. The atria have been severed approximately 3 cm above the ventricles. The epicardial \nsurface is smooth and glistening without adhesions. The major epicardial coronary arteries arise in their \nusual configuration in a right dominant system and show no gross atherosclerosis. Sectioning the heart \nlongitudinally reveals severe biventricular dilatation and hypertrophy. There is patchy fibrous thickening \nof the endocardium. No mural thrombi are present. The valves are grossly of normal configuration. The \nleft ventricular myocardium is 1.3 cm in thickness; the right ventricular myocardium is 0.3 cm in thick\u00ad\nness. There is no evidence of myocardial discoloration or necrosis.\nMicro 1: Left ventricle, base and apex, 2 frags, 1 cass.\nMicro 2: Interventricular septum, base and apex, 2 frags, RSS.\nMicro 3: Right ventricle, base and apex, 2 frags, RSS.\nSAMPLE DICTATION FOR ATHEROSCLEROTIC CORONARY ARTERY AND ISCHEMIC HEART DISEASE WITH BYPASS GRAFTS\nThe specimen, received fresh, labeled with the patient\u2019s name, unit number, and \u201cheart,\u201d consists of a \nheart weighing 485 grams. The atria have been severed approximately 3 cm above the ventricles. The \n\u00adepicardial surface contains dense fibrous adhesions which are most extensive over the base of the heart. \nWithin these adhesions, segments of bypass grafts inserting into the left anterior descending, circum\u00ad\nflex, and right coro\u00adnary arteries are identified. The graft to the left anterior descending artery is totally \noccluded by thrombus. The graft to the circumflex has a circumferentially thickened wall but remains \npatent. The graft to the right coronary artery is widely patent. Examination of the native epicardial coro\u00ad\nnary arteries reveals a right dominant system with severe, diffuse atherosclerosis. The left main coronary \nartery is approximately 50% occluded by atheromatous plaque. The left anterior descending coronary \nartery is 100% occluded by atheromatous plaque. The left circumflex and right coronary arteries are each \napproximately 70% occluded by atheromatous plaque. There are no acute plaque changes. Sectioning \nthe heart transversely reveals biventricular dilation with aneurysmal dilatation to 4 cm of the anterior \nleft ventricle at the apex. The anterior left ventricular myocardium is replaced by dense white transmu\u00ad\nral fibrous scarring and measures 0.3 cm in thickness. The lateral, posterior, and septal walls contain \nfocal areas of fibrous scarring up to 1 cm. The endocardium of the anterior wall is thickened, measuring \n0.2\u00a0cm. No mural thrombus is present. The right ventricular myocardium measures 0.3 cm and shows no", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_320.png", "summary": "This page provides details on the microscopic sections and gross differential diagnosis for heart transplant specimens, specifically focusing on ischemic heart disease and idiopathic dilated cardiomyopathy.", "questions": [ "What are the specific sections included in the microscopic examination of heart transplant specimens?", "How does the gross differential diagnosis differentiate between Ischemic Heart Disease and Idiopathic Dilated Cardiomyopathy?", "What are the key findings in the sample dictation for Idiopathic Dilated Cardiomyopathy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 321, "text": "CARDIOVASCULAR SPECIMENS\u2003 Ventricular Assist Devices\n303\nevidence of scarring or necrosis. The valves are grossly of normal configuration. The coronary arteries \nare removed from the specimen and decalcified prior to processing.\nMicro 1: Left ventricle anterior, 1 frag, RSS.\nMicro 2: Left ventricle lateral, 1 frag, RSS.\nMicro 3: Left ventricle posterior, 1 frag, RSS.\nMicro 4: Interventricular septum, 1 frag, RSS.\nMicro 5: Right ventricle, 2 frags, RSS.\nMicro 6: Left main coronary artery, 3 frags, RSS.\nMicro 7: Left anterior descending coronary artery, 3 frags, RSS.\nMicro 8: Left circumflex coronary artery, 3 frags, RSS.\nMicro 9: Right coronary artery, 3 frags, RSS.\nMicro 10: Bypass graft to left anterior descending, 3 frags, RSS.\nMicro 11: Bypass graft to left circumflex, 3 frags, RSS.\nMicro 12: Bypass graft to right coronary artery, 3 frags, RSS.\nPATHOLOGIC FEATURES SIGN-OUT CHECKLIST\n\t \u2022\t \u0007Size: Weight in grams\n\t \u2022\t \u0007Hypertrophy: Present or absent, degree (mild, moderate, or severe), gross or microscopic\n\t \u2022\t \u0007Dilatation: Present or absent, degree (mild, moderate, or severe)\n\t \u2022\t \u0007Asymmetric septal hypertrophy: Present or absent\n\t \u2022\t \u0007Atrial septal defect: Present or absent, size\n\t \u2022\t \u0007Ventricular septal defect: Present or absent, size\n\t \u2022\t \u0007Foramen ovale: Describe if patent\n\t \u2022\t \u0007Previous interventional sites: If present, describe (e.g., stents, annuloplasty rings present)\n\t \u2022\t \u0007Myocardial infarcts: Acute, remote, location, size, extent (transmural)\n\t \u2022\t \u0007Aneurysm: Location, size\n\t \u2022\t \u0007Mural thrombus: Location, size\n\t \u2022\t \u0007Subendocardial myocyte vacuolization: Focal or diffuse (suggestive of chronic ischemia)\n\t \u2022\t \u0007Replacement fibrosis: Focal or diffuse\n\t \u2022\t \u0007Myofiber disarray: Present or absent in septum\n\t \u2022\t \u0007Endocardial fibrosis: Present or absent, degree (focal, multifocal, diffuse)\n\t \u2022\t \u0007Endocarditis: Present or absent\n\t \u2022\t \u0007Myocarditis: Present (lymphocytic, eosinophilic, giant cell/granulomatous) or absent\n\t \u2022\t \u0007Pericardium: Fibrous or fibrinous pericarditis\n\t \u2022\t \u0007Coronary arteries: Atherosclerosis, location, degree (% occlusion), thrombosis, acute plaque change\n\t \u2022\t \u0007Bypass grafts: Present or absent, location, intimal hyperplasia (% luminal narrowing)\n\t \u2022\t \u0007Valves: Report as for native or prosthetic valves as appropriate\n\t \u2022\t \u0007Devices: Pacemaker wire, defibrillator patches, ventricular assist device\nVENTRICULAR ASSIST DEVICES\nVentricular assist devices (VADs) may be used to provide mechanical support as a bridge to transplanta\u00ad\ntion, and are sometimes received with an explanted heart. Either the entire device or parts of the device \nattached to the heart may be received. Often the device is removed several days after the heart transplant.\nVADs can totally replace ventricular function for extended periods and may be inserted into the left \nventricle (LVAD), right ventricle (RVAD), or both ventricles (BiVAD). The device is connected from the \natrium or ventricle to the pump via the inflow (inflow to the pump) cannula and from the pump to the \naorta or pulmonary artery via the outflow (outflow from the pump) cannula. Prosthetic valves are present \nwithin the metal connectors of both cannulae.\nTwo types of VADs are the Thoratec HeartMate (Fig. 16-9A), Abiomed, and Thoratec (Fig. 16-9B). \nThe HeartMate is inserted into the left ventricular apex (resulting in a specimen consisting of an apical \ncore of ventricle) and is powered either pneumatically or electrically. It can only be used in the left ven\u00ad\ntricle and is typically considered not removable once inserted. The Abiomed and Thoratec devices may \nbe used to augment either (or both) ventricles. They may be inserted with their inflow cannulae in the \natria and, therefore, can be removed should cardiac function of the native heart recover.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_321.png", "summary": "The page discusses the examination of cardiovascular specimens, specifically ventricular assist devices (VADs), which are used to provide mechanical support as a bridge to transplantation.", "questions": [ "What are the different types of ventricular assist devices (VADs) mentioned in the text?", "How are ventricular assist devices (VADs) connected to the heart and pump?", "What pathologic features are checked for in the sign-out checklist for ventricular assist devices (VADs)?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 322, "text": "304\nCARDIOVASCULAR SPECIMENS\u2003 Atrial or Ventricular Myocardium\nGoldstein,6 Hunt,7 and Schoen8 provide a more detailed discussion of pathologic analysis and device \ncomplications.\nSAMPLE DICTATION (ESSENTIALLY DESCRIBING THE DEVICE IN THE ORDER THAT BLOOD PASSES THROUGH THE \nCOMPONENTS)\nThe specimen is received fresh, in one part, labeled with the patient\u2019s name, medical record number and \nthe description \u201cLVAD.\u201d The specimen consists of a Thoratec HeartMate left ventricular assist device \nwith the serial number \u201cVAD 12345\u201d inscribed on the pump. The bioprosthetic inflow valve within the \ninflow cannula has a single 4 mm tear in one cusp. The inflow valve and cannula are otherwise unremark\u00ad\nable. The pump itself is unremarkable with no thrombi or vegetations within. Attached to the pump is \na 25 cm segment of driveline with scant attached soft tissue. The bioprosthetic outflow valve within the \noutflow cannula is unremarkable with no vegetations, tears, thrombi or apparent calcification. The out\u00ad\nflow graft to the aorta is unremarkable. The specimen has been photographed. No microscopic sections \nare submitted.\nATRIAL OR VENTRICULAR MYOCARDIUM\nPortions of the heart may be removed during open heart surgery (e.g., repair of ventricular aneurysms, \nhypertrophic cardiomyopathy septal resection, Maze procedures to treat atrial fibrillation, or removal of \natrial myxomas). An apical core may be removed during insertion of a cardiac assist device. Describe the \nspecimen including size, variations in the thickness of the wall, presence of scarring (transmural or not \ntransmural), necrotic tissue, calcification, or mural thrombus (organized or not organized), hemorrhage, \ncolor and thickness of epicardium, color and thickness of endocardium.\nUsually 2 to 3 sections in one cassette are sufficient. For hypertrophic cardiomyopathy, submit 2 to \n3 cassettes and order Masson\u2019s trichrome and H&E stains. For atrial myxomas, submit 2 to 3 cassettes.\nOutflow\nA\nB\nAorta\nAorta\nRight\natrium\nPulmonary\nartery\nLeft\nventricle\nInflow\nOutflow\nRVAD\nLVAD\nPercutaneous\ndrive lines\nLeft\nventricle\nBlood\npump\nPercutaneous\ndrive line\nInflow\nFigure 16\u20139.\u2002 A, The HeartMate implantable pneumatic left ventricular assist system. B, The Thoratec ventricular \nassist system in the biventricular support configuration. RVAD, right ventricular assist device; LVAD, left ventricu\u00ad\nlar assist device.\u2002 (From Hunt SA, Frazier OH: Mechanical circulatory support and cardiac transplantation. Circulation \n97:2079-2090, 1998.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_322.png", "summary": "The page discusses the examination of atrial or ventricular myocardium specimens, including descriptions of devices like the Thoratec HeartMate left ventricular assist device.", "questions": [ "What are some common procedures that may involve the removal of portions of the heart?", "What specific details should be included in the description of atrial or ventricular myocardium specimens?", "How many sections are usually sufficient for examination in one cassette?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 323, "text": "CARDIOVASCULAR SPECIMENS\u2003 Blood Vessels\n305\nBLOOD VESSELS\nTypical specimens include endarterectomies of the carotid bifurcation, abdominal aortic aneurysm \nrepairs, revision of vascular grafts, and varicose veins. Temporal artery biopsies are performed for the \ndiagnosis of arteritis.\nAorta (With or Without Dissection)\nAn aortic dissection results in a medial hematoma that usually has an associated intimal flap entrance \nsite and often has either an intimal reentrant or adventitial rupture site. These specimens may be labeled \n\u201cascending aortic aneurysm\u201d or \u201cthoracic aortic aneurysm.\u201d Specimens taken during aortic aneurysm \nrepair consist of the inner media only or both inner and outer media. Increasingly, fragments of aorta \nare also submitted from aortic valve replacements or from bypass cannula sites and may be of diagnostic \nimportance.\nIn cases of dissections, sections are taken from areas of medial separation. Representative sections \n(three to four in one cassette) are also taken of grossly normal tissue. It is important to characterize the \nlocation of any dissection, its age, medial flaps, the presence of prior dissection, and underlying vessel \nwall pathology as the etiology of the dissection. Request that the histology laboratory carefully orient \nthe specimens on edge, to ensure that the entire wall thickness may be assessed. The signout diagnosis \nshould include a statement regarding the presence or absence of acute aortitis, dissection and/or other \npathologic lesions.\nAbdominal Aortic Aneurysm\nDuring the surgical repair the aneurysm is opened, the clot removed, and the graft sewn inside the aorta. \nThe aorta is then closed around the graft. The specimen usually consists of laminated thrombus, with \nor without calcified plaque. It is relatively unusual to receive portions of the aortic wall. Portions of the \nwall can usually be identified because they have more consistency (i.e., they are less \u201cflaky\u201d and friable) \nthan thrombus.\nThe thrombus is serially sectioned grossly (to look for the rare mycotic [infected] aneurysm, or tumor \nmetastasis \u2013 these diseases do occur!). Describe overall dimensions, color, consistency (rubbery), and \npresence of calcifications. Several representative sections of thrombus in one cassette are adequate. If \naortic wall is present, additional sections are submitted.\nAtherectomy Specimens\nTechniques are now available for the removal of atherosclerotic plaque via a catheter in the cardiac \ncatheterization laboratory. The most widely used method, rotational atherectomy, uses a catheter with \na cylindrical cutting blade at its end. This procedure results in multiple strips of fibrous and calcified \nplaque that defy anatomic orientation. These pieces are submitted in their entirety.\nEndarterectomy Specimens\nThese specimens consist of the luminal plaque with portions of the intima and media attached. The \nadventitia is not removed. Often the specimen retains the shape of the bifurcation. Open the specimen \n(if intact) longitudinally. Describe the shape (\u201cY-shaped fragment consistent with carotid bifurcation\u201d), \ncolor, size, presence of calcifications, degree of stenosis, and the presence of acute plaque change. One \nsection is adequate. Most specimens require decalcification.\nSmall Vascular Segments\nPortions of vessels are resected due to atherosclerotic occlusion or aneurysm, vasculitis, or fibromuscular \ndysplasia. For some non-aortic arterial aneurysms and small vascular segments, the best approach to sec\u00ad\ntioning may be longitudinal (for example, in fibromuscular dysplasia, the variable thickness of the media \nis best demonstrated by longitudinal, not transverse, sectioning).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_323.png", "summary": "The page discusses various cardiovascular specimens including blood vessels such as aorta, abdominal aortic aneurysm, atherectomy specimens, and endarterectomy specimens.", "questions": [ "What are the typical specimens included in cardiovascular specimens of blood vessels?", "What is the significance of performing temporal artery biopsies?", "What is the process involved in surgical repair of an abdominal aortic aneurysm?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 324, "text": "CARDIOVASCULAR SPECIMENS\u2003 Blood Vessels\n306\nVascular Grafts\nGrafts are generally removed due to thrombosis, fibrous obstruction, or infection. Cultures may \nbe requested (order bacteria [aerobic and anaerobic], fungi, and AFB cultures). Describe dimensions \n(length, diameter), integrity (any holes or tears), color (usually white and not discolored), type of graft \n(e.g., saphenous vein, Gore-Tex, Dacron, see below), and soft tissue present in the lumen.\nGore-Tex (expanded polytetrafluoroethylene) is smooth-surfaced and homogeneous, and is about 0.5 \nmm thick. It does not appear woven or corrugated. In contrast, Dacron polyester is a fabric with a grossly \nvisible weave; it has a rough surface and it is corrugated. Tissue grafts are usually derived from large veins \nand are easily distinguished from synthetic material.\nAny soft tissue is submitted for histologic examination, as infection is frequently occult. The graft is \nalso submitted. Saphenous vein and Gore-Tex grafts cut easily with a scalpel blade and are easily sec\u00ad\ntioned for slides. Dacron grafts are difficult to section with a scalpel and will feel \u201cgritty\u201d to the blade. \nWhen Dacron graft material is submitted it is helpful to notify the histology laboratory as it will likely be \ndifficult to cut with a microtome. A Gram stain is ordered on any grafts with a clinical history of infection \nor with a request to rule out infection.\nCoronary Bypass Grafts\nSaphenous vein or internal mammary artery grafts may occasionally be removed during a second coro\u00ad\nnary artery bypass operation. Describe length, average diameter, presence of atherosclerosis or intimal \nhyperplasia, acute plaque change, thrombus, presence and extent of occlusions. One cassette per graft \ncontaining multiple cross-sections of the specimen is usually sufficient.\nVaricose Veins\nVaricose veins are flaccid veins from the lower extremities. They are often inverted during removal. \nDescribe length, average diameter, and unusual features (such as obvious thrombus, tortuosity, thicken\u00ad\ning of wall, or nodularities). One transverse section is sufficient.\nTemporal Arteries\nTemporal arteries are biopsied (approximately 1 cm in length) to evaluate patients for temporal \n(giant cell) arteritis. Describe the dimensions (length and diameter), color, and any additional soft \ntissue. Do not cut the specimen! Orientation is very important for proper evaluation and cannot \nbe accomplished with small cross-sections. Wrap the entire specimen in lens paper. The specimen \nshould be cut into cross sections by the histotechnologist after processing, and just before embedding. \nThe histologic findings may be scored (Table 16-5).\nTABLE 16\u20135.\u2003\nSCORING SYSTEM FOR TEMPORAL ARTERITIS\nSCORE\nHISTOLOGIC FEATURES\nPositive\nInflammatory infiltrate with giant cells\nProbable\nLymphohistiocytic infiltrate involving the arterial wall transmurally or constituting 25% or \nmore of the arterial wall without giant cells, or evidence of healed arteritis (transmural \nfibrosis).\nHealed arteritis\nDisruption of the elastica for at least a third of the circumference of the vessel with trans\u00ad\nmural fibrosis.\nNegative\nNo inflammatory infiltrate or giant cells or evidence of healed arteritis.\nAdapted from Robb-Nicholson C, et al, Diagnostic value of the history and examination in giant cell arteritis: A clinical pathological study of 81 \ntemporal artery biopsies, J Rheumatol 15:1793-6, 1988.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_324.png", "summary": "The page discusses the examination of cardiovascular specimens, including vascular grafts, coronary bypass grafts, varicose veins, and temporal arteries, detailing the dimensions, characteristics, and necessary procedures for each type of specimen.", "questions": [ "What are the common reasons for removing vascular grafts?", "What are the distinguishing features between Gore-Tex and Dacron grafts?", "Why is orientation important when evaluating temporal arteries for giant cell arteritis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 325, "text": "CARDIOVASCULAR SPECIMENS\u2003 References\n307\nREFERENCES\n\t1.\u2002 \u0007Silver MD, Gotlieb AI, Schoen FJ (eds), Cardiovascular Pathology, 3rd ed, Philadelphia, W.B. Saunders, 2001\n\t2.\u2002 \u0007Schoen FJ. Blood vessels, and The heart chapters. In Kumar V, Abbas A, Aster J, Fausto N (eds), Robbins \n& Cotran Pathologic Basis of Disease, 8th ed, Philadelphia, W.B. Saunders, 2009, pp. 511-554 and pp 555-618.\n\t3.\u2002 \u0007Stewart S, Winters GL, Fishbein MC, et al: Revision of the 1990 Working Formulation for the Standardization \nof Nomenclature in the Diagnosis of Heart Rejection. J Heart Lung Transplantation 24:1710-1720, 2005.\n\t4.\u2002 \u0007Schoen FJ. Surgical pathology of removed natural and prosthetic cardiac valves. Hum Pathol 18:558, 1987.\n\t5.\u2002 \u0007Schoen FJ. Approach to the analysis of cardiac valve prostheses as surgical pathology or autopsy specimens.\n Cardiovasc Pathol 4:241-255, 1995.\n\t6.\u2002 \u0007Goldstein, et al. Implantable left ventricular assist devices. N Engl J Med 339:1522, 1998.\n\t7.\u2002 \u0007Hunt SA, et al: Mechanical circulatory support and cardiac transplantation. Circulation 97:2079, 1998.\n\t8.\u2002 \u0007Schoen FJ, et al: Ventricular assist device (VAD) pathology analysis: Guidelines for clinical studies. J Appl \nBiomat 1:49, 1990.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_325.png", "summary": "This page provides references related to cardiovascular pathology, including books, journal articles, and guidelines.", "questions": [ "What are the key resources mentioned for studying cardiovascular pathology?", "How do the references on heart rejection and cardiac valve prostheses contribute to the field?", "What specific guidelines are provided for analyzing ventricular assist device pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 326, "text": "308\n17\nCytology Specimens\nCytologic specimens are obtained by minimally invasive methods:\n\t\u2022\t \u0007Brushings and scrapes: bronchial brushings, GI \u00adbrushings, Pap tests\n\t\u2022\t \u0007Washings: bronchial washings, bronchoalveolar lavage, peritoneal washings\n\t\u2022\t \u0007Aspirations: fine needle aspiration (FNA) of mass lesions, body cavity effusions (e.g., CSF or pleural \neffusions)\n\t\u2022\t \u0007Sputum\n\t\u2022\t \u0007Urine\nCytologic preparations can also be made after surgical excision (e.g., touch preparations). Cytologic \nspecimens have the following advantages over excisional specimens or large core biopsies:\n\t\u2022\t \u0007Minimal or no morbidity to patient.\n\t\u2022\t \u0007Excellent cytologic preservation (e.g., crush and cautery artifacts are absent).\n\t\u2022\t \u0007Large areas can be sampled.\n\t\u2022\t \u0007Cells and nuclei are intact; this is an advantage for certain studies such as FISH.\n\t\u2022\t \u0007Specimen acquisition, preparation, and examination can be performed in a short period of time.\nCELL BLOCKS\nCells suspended in fluid solution may be used to make smears, cytospins, Thin-Preps, or cell blocks. The \ncell block is the leftover sediment fixed in formalin, embedded in paraffin, and sectioned like a tissue biopsy. \nCell blocks can provide multiple sections of the same group of cells to be used for histochemical stains and/\nor immunoperoxidase studies.\nPROCESSING THE SPECIMEN FLUIDS\n 1.\t \u0007Record the volume and color of the fluid and the size of any particulate matter in the specimen. \nRemove any clots, wrap in lens paper, and submit as cell blocks.\n 2.\t \u0007Centrifuge 80 mL (in two 50 mL tubes) for 20 minutes at maximum speed. If the sediment is scanty, \ndecant the fluid, refill the tubes with more specimen fluid, and recentrifuge.\n 3.\t \u0007Decant the fluid, being careful not to lose any of the pellet or particulate matter. Make about 4 smears \non previously labeled glass slides. Use a wooden applicator or spatula to transfer a small portion of the \npellet to one end of the slide. Use a second slide to make a smear. Immediately fix in 95% alcohol.\n 4.\t \u0007Transfer the pellet and wrap it in lens paper. Alternatively, the pellet may be resuspended in a small \namount of fluid and poured through a nylon specimen bag. Do this over a clean specimen cup, in \norder to be able to retrieve any spilled fluid. Order one H&E stain as well as other special stains as \nindicated.\n 5.\t \u0007If the quantity of fluid is small and appears clear or yields essentially no sediment, the specimen may \nrequire processing by the cytospin method.\nBronchoalveolar lavage is a method in which small quantities of fluid are introduced into the bronchial tree \nvia a fiberoptic bronchoscope and then aspirated for analysis of cells and secretions from the distal airways. It is \na useful method to recover pathogenic organisms (Pneumocystis, fungi, bacteria, mycobacteria, and CMV) from", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_326.png", "summary": "Cytology specimens can be obtained through minimally invasive methods such as brushings, washings, aspirations, sputum, and urine. Cell blocks can be created from cells suspended in fluid solution for further analysis.", "questions": [ "What are the advantages of cytologic specimens over excisional specimens or large core biopsies?", "How are cell blocks created from cells suspended in fluid solution?", "What is bronchoalveolar lavage and how is it used in the analysis of cells and secretions from the distal airways?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 327, "text": "309\nCYTOLOGY SPECIMENS\u2003 Storage of Cytology Specimens\nimmunocompromised patients. These cases are treated as potentially infectious. Masks, gloves, and aprons \nshould be worn. The specimen should be handled gently to avoid aerosolization of organisms. All instruments \nand surfaces should be cleaned with bleach.\nFine Needle Aspirations.\u2002 The following equipment should be assembled in a kit:\n\t\u2022\t \u0007Blank slides\n\t\u2022\t \u0007Pencil\n\t\u2022\t \u0007Spray fixative\n\t\u2022\t \u0007A 50 mL Falcon tube with normal saline (\u201cnormosol\u201d = 0.9% saline) \u2013 store in refrigerator when not \nin use\n\t\u2022\t \u0007Empty container or tube holder\n\t\u2022\t \u0007Slide tray\nAfter the FNA is performed the specimen is prepared as follows:\n 1.\t \u0007Take the needle and syringe and express a small drop on each of two slides (using a stylet if the mate\u00ad\nrial is stuck in the needle). Stand the needle/syringe in the Falcon tube.\n 2.\t \u0007Immediately take one slide with material and spread the drop with a blank spreader slide GENTLY \nbut quickly.\n 3.\t \u0007Spray fix these two slides IMMEDIATELY or they will air dry within seconds, rendering the nuclear \ndetail less distinct and difficult to interpret.\n 4.\t \u0007Take the other slide with a drop of material and spread it with yet another blank spreader slide, but \nallow these two to thoroughly air dry. Cytoplasmic and extracellular material are seen well in air-dried \nslides.\n 5.\t \u0007Rinse the needle/syringe into the Falcon tube, backwashing 2 to 3 times.\nThe needle rinsings (in saline) may be critical for special studies (e.g., flow cytometry, Thin-Preps, \ncell blocks).\n\t\u2022\t \u0007Lymphoma: The specimen may be sent for flow cytometry. \n\t\u2022\t \u0007Infection: If an infectious process is suspected, notify the radiologist, who will usually take a separate \naspiration for multiple cultures.\n\t\u2022\t \u0007Cell block: The remainder of the specimen can be used to prepare a cell block. \nThe slides may be stained with DiffQuik or PAP stains if the adequacy of the specimen is to be \nassessed or a \u00addiagnosis is to be made at the time of the procedure.\nSTORAGE OF CYTOLOGY SPECIMENS\nCytology specimens obtained at night or during the weekend may need to be stored before processing. \nMost fluids are reasonably preserved for 48 to 72 hours in a refrigerator without fixation, especially \npleural fluids. Other fluids (urine, cerebrospinal fluid) may deteriorate after 24 hours, even if refriger\u00ad\nated. This can be prevented by adding an equal volume of 50% ethanol (final concentration 25%) to the \nfluid and refrigerating. Note that adding ethanol precludes the preparation of air-dried slides, which are \nespecially useful in the evaluation of lymphoma and leukemia.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_327.png", "summary": "The page discusses the storage of cytology specimens, particularly in relation to fine needle aspirations, emphasizing the importance of proper handling and preservation methods.", "questions": [ "What equipment is recommended to be assembled for fine needle aspirations?", "How should cytology specimens be prepared after a fine needle aspiration is performed?", "What special studies may the needle rinsings from a fine needle aspiration be critical for?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 328, "text": "310\n18\nDermatopathology\nOf all organ systems, the skin has the greatest number of lesions described, perhaps because the skin is subject \nto a wide variety of environmental exposures and no special procedures are necessary to visualize its surface.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nGENERAL CONSIDERATIONS\nThe ability to clearly visualize the entire epidermis in a perpendicular section is important for diagnosis, \nand at times for prognosis (e.g., malignant melanoma). \u00adTherefore, try to maintain vertical orientation \nat all times in sections. Any specimen that is labeled \u201cexcision,\u201d regardless of the type of specimen, must \nhave the margins evaluated by inking and submission of appropriate sections. Diagrams are used for any \ndifficult or complicated specimens.\nNever cut through small vesicular lesions in any type of specimen. The overlying tissue layer is important \nfor diagnosis, but is fragile and easily detached and lost. Cut the specimen so as to leave the vesicle intact or \nsubmit small specimens whole and request that the histotechnologists bisect the specimen after processing.\nSKIN - SPECIAL STUDIES\nOccasionally fresh or frozen specimens (usually punch biopsies) will be submitted for special studies for \nthe evaluation of specific disease:\n\t \u2022\t \u0007Immunofluorescence: lupus erythematosus, bullous pemphigoid, or pemphigus\n\t \u2022\t \u0007Immunofluorescence on frozen tissue: leukemias and lymphomas\nTABLE 18\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR \nDERMATOPATHOLOGY SPECIMENS\nOrgan/tissue resected or biopsied\nSite, duration, and appearance of the lesion \n(especially for incisional biopsies)\nPurpose of the procedure\nGross appearance of the organ/tissue/lesion sampled\nSystemic diseases that affect the skin\nAny unusual features of the clinical presentation\nClinical differential diagnosis\nAny unusual features of the gross appearance\nFamily history (see Table 7-50)\nPrior surgery/biopsies \u2013 results\nPrevious similar lesions\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic appearance of tissues)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_328.png", "summary": "The skin is subject to a wide variety of environmental exposures, leading to a large number of described lesions. Maintaining a vertical orientation in sections is crucial for diagnosis and prognosis.", "questions": [ "How does the ability to visualize the entire epidermis impact diagnosis and prognosis?", "Why is it important to maintain a vertical orientation in sections?", "What are some special studies that may be performed on skin specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 329, "text": "DERMATOPATHOLOGY\u2003 Skin Shave Biopsies\n311\n\t \u2022\t \u0007Electron microscopy: epidermolysis bullosa, other blistering diseases, some melanomas (e.g., S100 \nnegative tumors), unusual tumors, amyloid\nSKIN PUNCH BIOPSIES\nPunch biopsies are performed to completely excise small lesions, to sample large lesions, or to evaluate \nan inflammatory process or a systemic disease (e.g., pustular psoriasis). Punches can be 2, 3, 4, 5, 6, 8, or \n10 mm in diameter.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Describe the type of specimen (\u201cpunch biopsy\u201d) including diameter and depth and skin color. Describe \nany lesions including size, type (macular, papular, vesicular, plaque), borders (well-circumscribed, irregu\u00ad\nlar), color (brown, black, variegated), shape (verrucous, lobulated), and distance from the closest margin.\n\t\nInk all punch biopsies.\n 2.\t \u0007Punch biopsies 3 mm or less are submitted uncut in their entirety (Fig. 18-1). These specimens can be \nbisected by the histology laboratory.\n\t\n\t\n\u0007Punch biopsies greater than 4 mm are bisected or trisected, depending on size. If there is a discrete \nlesion, cut in a plane to demonstrate the closest margin. If the lesion is very small (i.e., leveling the \nblock might remove the lesional tissue), cut the punch biopsy on either side of the lesion. Do not sec\u00ad\ntion through vesicles or blisters \u2013 submit whole and request sectioning by the laboratory.\n 3.\t \u0007Request three levels.\nSAMPLE DICTATION\nReceived in formalin labeled with the patient\u2019s name and unit number and \u201c5 mm punch, left leg\u201d is a 5 \nmm in diameter by 5 mm (depth) punch biopsy with tan/white skin. There is a flat homogeneously brown \nlesion with slightly irregular margins, 0.3 \u00d7 0.3 cm, on the skin surface. The lesion is less than 0.1 cm \nfrom the nearest margin, but does not grossly involve the margin.\nCassette: bisected, 2 frags, ESS.\nSKIN SHAVE BIOPSIES\nShave biopsies are usually performed to remove nonmalignant lesions (e.g., seborrheic keratoses, actinic \nkeratoses, or fibroepithelial polyps) or for diagnosis of basal cell carcinomas. Shave biopsies of pigmented \nlesions should be strongly discouraged and interpreted with caution. The diagnosis of melanoma may be \ndifficult in such a specimen due to limited sampling and the depth of invasion may be impossible to assess. \nSpecimens are inked if designated \u201cexcisions.\u201d\nDo not bisect specimens with vesicles or blisters\nInk if labeled \u201cexcision\u201d\n\u001f 3 mm\nSubmit uncut\n\u001e 3 mm\nBisect or trisect through closest margin\nFigure 18\u20131.\u2002 Punch biopsy of the skin.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_329.png", "summary": "The page discusses skin punch and shave biopsies, including the processing of specimens and the importance of proper handling for accurate diagnosis.", "questions": [ "What are the different reasons for performing skin punch biopsies?", "Why is it important to bisect or trisect punch biopsies greater than 4 mm?", "What are the implications of not bisecting shave biopsies of pigmented lesions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 330, "text": "DERMATOPATHOLOGY\u2003 Skin Ellipses\n312\nPROCESSING THE SPECIMEN\n 1.\t \u0007Describe the specimen type (\u201cshave biopsy\u201d), the dimensions (including depth) and the surface appear\u00ad\nance. The specimen is usually oval and relatively flat. The edges may curl due to retraction of the der\u00ad\nmis. Ink the base to aid in orientation during embedding.\n\t\n\t\n\u0007Specimens greater than 3 to 4 mm in diameter may be bi- or trisected. Try to maintain the verti\u00ad\ncal orientation in sections by making one or more cuts perpendicular to the surface at 2 to 3 mm \nintervals.\n 2.\t \u0007Submit in entirety and order three levels. Indicate that the fragments should be embedded on edge.\nSKIN CURETTINGS\nSkin scrapings (curettings) of seborrheic or actinic keratosis or basal cell carcinoma may be performed.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Describe the specimen, including number of fragments (or estimate), color, and size in aggregate.\n 2.\t \u0007Submit entirely using a nylon specimen bag or lens paper to wrap the fragments. Check the sides of \nthe container and lid for small pieces. Orientation is usually not possible. Margins cannot be evaluated \ndue to the specimen fragmentation.\n 3.\t \u0007Order three levels.\nSKIN ELLIPSES\nThese specimens are excisions of malignant tumors (squamous cell carcinoma or basal cell carcinoma), \ntypical or atypical melanocytic nevi (and to rule out melanoma), or large benign lesions (e.g., epithelial \ninclusion cysts). Occasionally, ellipses are submitted for the evaluation of panniculitis or large vessel \nvasculitis.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the dimensions (length, width, and depth) and describe the skin color.\n\t\n\t\n\u0007Describe any lesions including color, borders, ulceration, shape, and distance from margins. Describe \nany scars from prior biopsies (length, recent or well-healed).\n 2.\t \u0007If an orienting suture is present, use the clinical designation or (lacking this) designate it 12 o\u2019clock. \nUse two different colors of ink to mark the two longitudinal halves of the specimen and dictate the \nlocation of the inks (e.g., \u201cthe 12 o\u2019clock margin is inked green and the 6 o\u2019clock margin is inked \nblue\u201d). Green and blue inks are reccommended as these colors are easier for the histotechnologists to \nsee during embedding and sectioning the tissue (Fig. 18-2).\nSerially section the entire specimen along the short axis at 2 to 3 mm intervals.\n\u0007Submit the most distal sections (\u201ctips\u201d) as two of the margins in two cassettes. If the ellipse is small \nand unoriented, both tips can be placed in one cassette. Each tip is taken as a 0.1 to 0.2 cm en face \nmargin.\n\u0007Submit the remainder of the specimen in one or more cassettes.\nA simple diagram showing orientation and sections is very helpful in interpreting the sections histo\u00ad\nlogically. This is especially true for large or irregularly shaped skin excisions.\n\u0007For pigmented lesions, the initial cut is made through the thickest or darkest portion of the lesion \n(most likely area to have deep invasion). Describe the gross depth of invasion or involvement of \nsubcutaneous tissues.\n 3.\t \u0007Very large ellipses (several centimeters) are usually \u00adre-excisions. The central scar is serially sectioned \nand representative sections taken including the deep margin. Representative sections are taken of the \n3, 6, 9, and 12 o\u2019clock margins.\n 4.\t \u0007The following levels are ordered:\n \u2022\t \u0007Non-pigmented lesions and re-excisions: One level on all blocks\n \u2022\t \u0007Pigmented lesions:\n\t \u2022\t \u0007Three levels on the block with the lesion\n\t \u2022\t \u0007One level on other blocks (e.g., tips without lesion)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_330.png", "summary": "The page provides guidelines for processing skin ellipses, including recording dimensions, describing lesions, and submitting sections for evaluation.", "questions": [ "How should the dimensions of skin ellipses be recorded?", "What is the significance of using two different colors of ink to mark the longitudinal halves of the specimen?", "Why are the most distal sections ('tips') of the specimen submitted separately in cassettes?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 331, "text": "DERMATOPATHOLOGY\u2003 Skin Ellipses\n313\nGROSS DIFFERENTIAL DIAGNOSIS\nSeborrheic Keratosis.\u2002 This is a rounded, raised, lesion sharply demarcated from any surrounding \nskin with a \u201cstuck on\u201d appearance. The color is usually dark brown, black, or gray and has a dirty appear\u00ad\nance due to the presence of horn cysts containing keratinous debris.\nEpidermal Inclusion Cyst.\u2002 These cysts are often received in multiple fragments. The wall of the cyst \nis thin (1 to 2 mm) and has a smooth inner lining. The cyst is filled with white or yellow friable, often \nmalodorous, material corresponding to keratinaceous debris. Some are due to \u00adtraumatic or iatrogenic \nintroduction of keratinizing epithelium into deep soft tissues. If located near the nipple, the lesion may \nbe in a lactiferous sinus (squamous metaplasia of lactiferous ducts or recurrent subareolar abscess).\nFibroepithelial Polyp (Acrochordon).\u2002 A flesh colored papule often designated \u201cskin tag\u201d by the clinician.\nBasal Cell Carcinoma.\u2002 Translucent papule or plaque with a yellow or pearly hue. Central ulceration \nwith a rolled border is common in larger lesions. The outer margin tends to be sharply demarcated from \nthe surrounding skin.\nSquamous Cell Carcinoma.\u2002 A raised irregular flesh colored lesion that is often centrally ulcerated.\nNevus.\u2002 A pigmented or flesh-colored flat or raised lesion. Dysplastic nevi have some of the character\u00ad\nistics of melanoma such as an irregular shape and some variation in pigmentation.\nMalignant Melanoma.\u2002 The most common appearance is as a pigmented lesion with irregular or \nnotched borders. The pigmentation is often variable and may be very dark. Nodules or ulcers within the \nlesion are usually indicative of invasion.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Small ellipses (<2 cm): The lesion is entirely submitted in the first cassette(s). Submit tips in one \ncassette (if unoriented) or in two cassettes (if oriented).\n\t \u2022\t \u0007Larger ellipses (>2 cm): Representative sections of the lesion and margins submitted. Re-excisions \nmust have the margins carefully evaluated.\nSkin surface\nTips are two margins\nDeep surface\nInk in two different\ncolors (not red)\nSerial section the\nremainder of ellipse\nFigure 18\u20132.\u2002 Skin ellipses.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_331.png", "summary": "The page discusses different skin lesions and their gross differential diagnosis, including seborrheic keratosis, epidermal inclusion cyst, fibroepithelial polyp, basal cell carcinoma, squamous cell carcinoma, nevus, and malignant melanoma.", "questions": [ "How can one differentiate between seborrheic keratosis and basal cell carcinoma based on their appearance?", "What are the characteristics of an epidermal inclusion cyst and how is it different from other skin lesions?", "What are the key features of a malignant melanoma and how is it diagnosed?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 332, "text": "314\nDERMATOPATHOLOGY\u2003 Skin Ellipses\nSAMPLE DICTATION\nReceived in formalin labeled with the patient\u2019s name, unit number, and \u201cright shoulder\u201d is a 2.5 \u00d7 1 \u00d7 0.8 cm \n(depth) skin ellipse with tan/brown skin and an orienting suture at one tip (designated by the surgeon as \n12 o\u2019clock). There is a variegated brown and black lesion (1 \u00d7 0.8 cm) with markedly irregular borders \nwith notching located in the center of the ellipse. Within the lesion there is a raised black nodule (0.3 \n\u00d7 0.3 cm) that grossly appears to extend through the epidermis into the dermis and is 0.2 cm from the \ndeep resection margin. The closest margin is the 3 o\u2019clock margin, which is 0.1 cm from the lesion. The \n3 o\u2019clock margin is inked black and the 9 o\u2019clock margin is inked blue.\nCassette #1: 12 o\u2019clock margin, 1 frag, ESS.\nCassette #2: 6 o\u2019clock margin, 1 frag, ESS.\nCassette #3: Cross sections from 3 to 9 o\u2019clock, 4 frags, ESS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR SKIN CARCINOMAS\n\t\u2022\t \u0007Procedure: Punch biopsy, shave biopsy, curettings, excisional biopsy (ellipse)\n\t\u2022\t \u0007Tumor Site: Specify, if known\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Histologic Type: Squamous cell (subtypes: acantholytic, adenosquamous, basaloid, spindle cell (sar\u00ad\ncomatoid), pseudovascular, undifferentiated (lymphoepithelioma), verrucous), basal cell, adenocarci\u00ad\nnomas of sweat and sebaceous glands\n\t\u2022\t \u0007Histologic Grade: Well, moderate, poor, or undifferentiated (Table 18-2)\n\t\u2022\t \u0007Maximum Tumor Thickness: Thickness in millimeters\n\t\u2022\t \u0007Anatomic Level: Clark level (I to V)\n\t\u2022\t \u0007Margins: Radial (\u201cperipheral\u201d or non-deep): uninvolved (optional: distance form closest margin), \ninvolved (specify location if possible). Specify if carcinoma in situ or invasive carcinoma at margin.\n\t \u2022\t \u0007Deep: Uninvolved (optional: distance form closest margin), involved (specify location if possible)\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Lymph Nodes: Number of nodes, number of nodes with metastases\n\t \u2022\t \u0007Optional: Size of largest metastatic deposit\n\t\u2022\t \u0007Extranodal Extension: Not identified, present\n\t\u2022\t \u0007Tumor Features: Inflammatory response, association with actinic keratosis, association with human \npapilloma virus (HPV), association with Bowen disease\n\t\u2022\t \u0007Adjacent Epithelium: Dysplasia, grade (mild, moderate, severe/CIS), extent (focal, multifocal, exten\u00ad\nsive), proximity to invasive carcinoma (adjacent or distant)\nTABLE 18\u20132.\u2003\nHISTOLOGIC GRADE \u2013 SQUAMOUS CELL CARCINOMA\nGrade 1\nWell differentiated tumors are characterized by squamous epithelium that frequently shows easily \nrecognizable and often abundant keratinization. Intercellular bridges are readily apparent. There \nis minimal pleomorphism, and mitotic figures are mainly basally located.\nGrade 2\nModerately differentiated tumors show more structural disorganization in which squamous epithe\u00ad\nlial derivation is less obvious. Nuclear and cytoplasmic pleomorphism are more pronounced, and \nmitotic figures may be numerous. Keratin formation is typically limited to keratin pearls, horn \ncysts, and scattered individually keratinized cells.\nGrade 3\nIn poorly differentiated tumors it may be difficult to establish squamous differentiation, usually by \nidentification of rare intercellular bridges or small foci of keratinization.\nGrade 4\nUsed to denote anaplastic or undifferentiated tumors.\nFrom Protocol for the Examination of Specimens from Patients with Squamous Cell Carcinoma of the Skin (www.cap.org).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_332.png", "summary": "The sample dictation describes a skin ellipse specimen with a variegated brown and black lesion, including a raised black nodule. The pathology checklist for skin carcinomas includes various prognostic/diagnostic features to consider.", "questions": [ "What are the key features of the skin ellipse specimen described in the sample dictation?", "What information is included in the pathologic prognostic/diagnostic features checklist for skin carcinomas?", "How does the histologic grade of squamous cell carcinoma differ between well-differentiated and moderately differentiated tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 333, "text": "315\nDERMATOPATHOLOGY\u2003 Skin Ellipses\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 18-3). M0 \nis conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined \u00adelements \nTABLE 18\u20133.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF CUTANEOUS SQUAMOUS CELL \nCARCINOMA AND OTHER CUTANEOUS CARCINOMAS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ\nT1\nTumor 2 cm or less in greatest dimension with less than two high-risk features*\nT2\nTumor greater than 2 cm in greatest dimension or Tumor any size with two or more high-risk features*\nT3\nTumor with invasion of maxilla, mandible, orbit, or temporal bone\nT4\nTumor with invasion of skeleton (axial or appendicular) or perneural invasion of skull base\n*HIGH-RISK FEATURES FOR THE PRIMARY TUMOR (T) STAGING\nDepth/invasion\n> 2 mm thickness Clark level \u2265 IV\nPerineural invasion\nAnatomic location\nPrimary site ear\nPrimary site non-hair-bearing lip\nDifferentiation\nPoorly differentiated or undifferentiated\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in a single ipsilateral lymph node, 3 cm or less in greater dimension.\nN2\nMetastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest \n\u00addimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in \nbilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension.\n\u2003 N2a\nMetastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension.\n\u2003 N2b\nMetastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension.\n\u2003 N2c\nMetastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension.\nN3\nMetastasis in a lymph node, more than 6 cm in greatest dimension\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: Used for squamous cell and basal cell carcinomas of the skin and adenocarcinomas developing from sweat or sebaceous glands. The classifica\u00ad\ntion is not used for carcinomas of the eyelid, melanomas, or Merkel cell carcinomas.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-\u00adVerlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_333.png", "summary": "The page discusses the presence of distant metastasis in skin ellipses and provides information on the AJCC classification for cutaneous squamous cell carcinoma and other cutaneous carcinomas.", "questions": [ "What is the significance of distant metastasis in skin ellipses?", "How are T, N, and M classifications determined for cutaneous squamous cell carcinoma?", "What are the high-risk features for the primary tumor staging?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 334, "text": "316\nDERMATOPATHOLOGY\u2003 Skin Ellipses\nare considered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR MELANOMA OF THE SKIN\n\t\u2022\t \u0007Procedure: Punch biopsy, shave biopsy, excisional biopsy, re-excision, lymphadenectomy (sentinel or \nregional nodes)\n\t\u2022\t \u0007Specimen Laterality: Right, left, midline\n\t\u2022\t \u0007Tumor Site: Specify (if known)\n\t\u2022\t \u0007Tumor Size: Greatest dimension (optional: additional dimensions), if gross tumor is present\n\t\u2022\t \u0007Macroscopic Satellite Nodules: Not identified, present (specify)\n\t \u2022\t \u0007Distance from primary tumor\n\t\u2022\t \u0007Macroscopic Pigmentation: Not identified, present, diffuse, present, patchy/focal, indeterminate\n\t\u2022\t \u0007Histologic Type: Lentigo maligna, superficial spreading, nodular, acral lentiginous, desmoplastic, \nothers\n\t\u2022\t \u0007Maximal Tumor Thickness: Measure in millimeters\n\u0007Prognosis is primarily related to the depth of invasion measured vertically in millimeters from the \ngranular cell layer of the epidermis (or the base of the ulcer, if ulcerated) to the deepest point of tumor \npenetration, excluding tumor surrounding skin appendages (see Breslow A, Thickness, cross-sectional \nareas, and depth of invasion in the prognosis of cutaneous melanoma, Ann Surg 172:902-908, 1970, \nTable 18-4). If satellite lesions are used in this measurement, this should be recorded. An ocular \nmicrometer should be used for \u00admeasurements.\n\t\u2022\t \u0007Anatomic Level: Clark level (I to V; Table 18-5)\n\t\u2022\t \u0007Ulceration: Not identified, present\n\t \u2022\t \u0007Post traumatic ulceration (e.g., due to prior surgery) should be distinguished from ulceration due to \ninvasion by tumor when possible. The width of the ulcerated area should be reported.\n\t \u2022\t \u0007Ulceration includes the following features:\n\t \u2022\t \u0007Full-thickness epidermal defect (including absence of stratum corneum and basement membrane)\n\t \u2022\t \u0007Reactive changes (fibrin deposition, neutrophils)\n\t \u2022\t \u0007Surrounding epidermis is thinned or may show reactive hyperplasia\n\t\u2022\t \u0007Margins: Peripheral and deep: Involved or free, positive = ink on tumor. The distance to the closest \nmargins should be given. Specify whether melanoma in situ or invasive melanoma.\n\t\u2022\t \u0007Mitotic Index: Mitoses per mm2 < 1 mitotic figure per mm2 or \u2265 1 mitotic figure per mm2 is used for \nAJCC classification.\nTABLE 18\u20134.\u2003\nBRESLOW DEPTH OF INVASION\nNonulcerated lesions\nMeasure from the top of the granular layer to the deepest point of invasion\nUlcerated lesions\nMeasure from the ulcer base overlying the deepest point of invasion\nDifficult cases\nMelanocytes in junctional nests (i.e., not invasive into stroma) are not included in the \n\u00admeasurement. This includes junctional involvement of skin appendages.\nMicroscopic satellite lesions in reticular dermis are sometimes used in measurements. \nIt is usually preferable to measure a contiguous area of invasion from the surface. If \nsatellite lesions are used, this can be described in the report.\nIf there is marked epidermal hyperplasia (resulting in a thickened granular layer), then \nthe measurement may overestimate the thickness of the melanoma. This situation \ncan be described in the report.\nLesions with tangential sectioning or curetted lesions cannot have the depth mea\u00ad\nsured accurately.\nMeasurements should be performed with an ocular reticule.\nAdapted from Breslow A: Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172:902-908, \n1970.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_334.png", "summary": "The page provides a checklist for reporting pathologic prognostic/diagnostic features for melanoma of the skin, including details on specimen type, tumor characteristics, thickness measurement, ulceration, margins, and mitotic index.", "questions": [ "How is the prognosis of melanoma primarily related to?", "What are the key elements to include in the reporting of melanoma of the skin?", "How should ulceration be distinguished and reported in melanoma specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 335, "text": "317\nDERMATOPATHOLOGY\u2003 Skin Ellipses\n\t \u2022\t \u0007Assessed in the vertical growth phase (not the intraepidermal component). The area with the great\u00ad\nest number of mitoses should be counted first, and then the surrounding area, until a 1 mm2 area has \nbeen counted. The size of a microscopic field depends on the microscope (see \u201cMeasuring with the \nMicroscope\u201d).\n\t\u2022\t \u0007Microsatellitosis: Not identified, present. Defined as tumor cell nests greater than 0.05 mm in size in \nthe reticular dermis, panniculus, or vessels beneath the principal invasive tumor but separated from it \nby at least 0.3 mm of normal tissue.\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Tumor Infiltrating Lymphocytes (TILs): Not identified, non-brisk, brisk\n\t \u2022\t \u0007TILs absent: no lymphocytes present, or present but do not infiltrate tumor\n\t \u2022\t \u0007TILs non-brisk: lymphocytes infiltrate melanoma only focally or not along the entire base of the \nvertical growth phase\n\t \u2022\t \u0007TILs brisk: lymphocytes diffusely infiltrate the entire base of the vertical growth phase or the entire \ninvasive component of the melanoma.\n\t\u2022\t \u0007Tumor Regression: Not identified, present involving < 75%, present involving 75% or more of \nlesion\n\t \u2022\t \u0007Partial or complete obliteration of melanoma by host response (fibrosis, telangiectasia, lymphocytes, \nand melanophagocytosis)\n\t\u2022\t \u0007Growth Phase: Radial growth phase: Present or not identified, type (lentigo maligna, acral-\u00adlentiginous, \nsuperficial spreading). The tumor is generally of uniform cytologic appearance and is wider than it is \ndeep.\n\t \u2022\t \u0007Vertical growth phase: Present or not identified, type (epithelioid, spindle, or mixed). Expansile \nnests of tumor cells are present in the papillary and/or reticular dermis.\n\t\u2022\t \u0007Lymph Nodes: Number of nodes examined, number of sentinel nodes, number of nodes with metas\u00ad\ntases\n\t \u2022\t \u0007Extranodal invasion not identified or present\nTABLE 18\u20135.\u2003\nCLARK LEVEL\nLevel I\nMelanoma confined to the epidermis and epidermal appendages\nLevel II\nExtension into the papillary dermis by single cells, and sometimes small clusters of cells, with, at \nmost, only a few cells extending to the interface between the papillary and reticular dermis\nLevel III\nExtension of tumor cells throughout the papillary dermis, filling it and impinging upon the \nreticular dermis but not invading it\nLevel IV\nInvasion of the reticular dermis\nLevel V\nInvasion of the subcutaneous fat\nAdapted from Clark WH Jr, From L, Bernardino EH, et al: Histogenesis and biologic behavior of primary human malignant melanoma of the skin. \nCancer Res 29:705-727, 1969.\nTABLE 18\u20136.\u2003\nIMMUNOHISTOCHEMICAL MELANOMA MARKERS\nTYPE OF CELL IN THE LYMPH NODE\nS100\nMART-1\nMetastatic melanoma\nPOS\nHigh*\nNevus cells\nPOS\nPOS\nDendritic cells\nPOS\nneg\nNerves, ganglion cells\nPOS\nneg\n*About 20% of metastatic melanomas are negative for HMB45 and MART-1.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_335.png", "summary": "This page discusses the assessment of skin ellipses in the vertical growth phase of melanoma, including factors such as microsatellitosis, lymph-vascular invasion, perineural invasion, tumor infiltrating lymphocytes, tumor regression, growth phase, and lymph node involvement.", "questions": [ "What is the significance of microsatellitosis in melanoma assessment?", "How do tumor infiltrating lymphocytes impact the prognosis of melanoma?", "What are the different growth phases of melanoma and how do they differ?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 336, "text": "318\nDERMATOPATHOLOGY\u2003 Skin Ellipses\nTABLE 18\u20137.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF MELANOMA OF THE SKIN\nTUMOR\nTX\nPrimary tumor cannot be assessed. (e.g., curettaged or severely regressed melanoma)\nT0\nNo evidence of primary tumor\nTis\nMelanoma in situ\nT1\nMelanomas 1.0 mm or less in thickness with or without ulceration\n\u2003 T1a\n\u2264 1.0 mm in thickness, without ulceration, and mitosis < 1/mm2\n\u2003 T1b\n\u2264 1.0 mm in thickness, with ulceration, or mitoses \u2265 1/mm2\nT2\nMelanomas 1.01 to 2.0 mm in thickness with or without ulceration\n\u2003 T2a\n1.01 to 2.0 mm in thickness without ulceration\n\u2003 T2b\n1.01 to 2.0 mm in thickness with ulceration\nT3\nMelanomas 2.01 to 4.0 mm in thickness with or without ulceration\n\u2003 T3a\n2.01 to 4.0 mm in thickness without ulceration\n\u2003 T3b\n2.01 to 4.0 mm in thickness with ulceration\nT4\nMelanomas more than 4.0 mm in thickness with or without ulceration\n\u2003 T4a\n> 4.0 mm in thickness without ulceration\n\u2003 T4b\n> 4.0 mm in thickness with ulceration\nREGIONAL LYMPH NODES\nNX\nPatients in whom regional lymph nodes cannot be assessed (e.g., previously removed for \nanother reason)\nN0\nNo regional metastasis detected\nN1\nMetastasis in one lymph node\n\u2003 N1a\nClinically occult (microscopic) metastasis\n\u2003 N1b\nClinically apparent (macroscopic) metastasis\nN2\nMetastasis in two to three regional nodes or intralymphatic regional metastasis without nodal \nmetastases\n\u2003 N2a\nClinically occult (microscopic) metastasis\n\u2003 N2b\nClinically apparent (macroscopic) metastasis\n\u2003 N2c\nSatellite or in-transit metastasis without nodal metastasis\nN3\nMetastasis in four or more nodes, or matted nodes, or in transit metastasis/satellites with \nmetastatic nodes.\nMicrometastases are diagnosed after sentinel node biopsy and completion lymphadenectomy (if performed). A micrometastasis is a pathologically \ndocumented metastasis (of any size) in a node detected by clinical or radiologic examination. Metastases detected only by immunohistochemical \nstudies (i.e., not present on H&E slides) should be confirmed by at least one melanoma-associated marker (e.g., HMB-45, Melan-A/MART-1) in addi\u00ad\ntion to less specific markers such as S100 or tyrosinase.\nMacrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis \nexhibits extracapsular extension.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_336.png", "summary": "This page outlines the AJCC (7th edition) classification of melanoma of the skin based on tumor thickness and ulceration status, as well as regional lymph node involvement.", "questions": [ "How is melanoma thickness categorized in the AJCC classification?", "What are the different categories for regional lymph node metastasis in melanoma?", "How are micrometastases and macrometastases defined in melanoma staging?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 337, "text": "DERMATOPATHOLOGY\u2003 Large Skin Excisions\n319\nLocation of metastatic tumor in sentinel node: subcapsular, intramedullary, or subcapsular and intra\u00ad\nmedullary.\nSentinel nodes may be examined by mutliple H&E levels and immunoperoxidase studies; a standard \nprotocol for all institutions has not been established. Typically, three H&E levels and one to three \nimmunohistochemical studies on intervening levels are examined. S100 is sensitive but other markers \nare more specific (Table 18-6). The significance of small metastases (< 0.2 cm) is unknown but is cur\u00ad\nrently being investigated.\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Tables 18-7 and \n18-8). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nLARGE SKIN EXCISIONS\nLarge resections are usually carried out after the lesion has been biopsied and a diagnosis made.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the dimensions (length, width, depth), skin color, lesions, scars (presence of a prior biopsy scar), \nand deep margin (soft tissue, fascia, muscle). Describe the closest approach of the lesion to a margin.\n 2.\t \u0007Ink all margins, excluding skin surfaces. All sections taken must be thin to allow for adequate fixation \nof the fatty subcutaneous tissue.\n 3.\t \u0007There is usually an orienting suture with a designated \u201co\u2019clock.\u201d If there are no orienting sutures, try \nto pick an identifiable area to designate 12 o\u2019clock. Document in the gross description that the speci\u00ad\nmen is unoriented and the o\u2019clock designations are arbitrarily assigned. Take four perpendicular sec\u00ad\ntions of the margin at 12 o\u2019clock, 3 o\u2019clock, 6 o\u2019clock, and 9 o\u2019clock but including the closest approach \nof tumor to the margin(s). This is adequate unless the lesion is grossly at or near the margin. More \nsections are taken in these areas.\nDefinitions:\nSatellite metastases: Defined arbitrarily as grossly visible cutaneous and/or subcutaneous metastases occurring \nwithin 2 cm of the primary melanoma.\nMicrosatellite metastases: Microscopic and discontinuous cutaneous and/or subcutaneous metastases found \non pathologic examination adjacent to a primary melanoma.\nIn transit metastases: Defined arbitrarily as clinically evident cutaneous and/or subcutaneous metastases identi\u00ad\nfied at a distance greater than 2 cm from the primary melanoma in the region between the primary and the \nfirst echelon of regional lymph nodes.\nDISTANT METASTASIS\nM0\nNo detectable evidence of distant metastasis\nM1\nDistant metastasis\n\u2003 M1a\nMetastasis to skin, subcutaneous tissue, or distant lymph nodes, LDH is normal\n\u2003 M1b\nLung metastases, LDH is normal\n\u2003 M1c\nAll other visceral metastases, LDH is normal or Any distant metastasis, LDH is elevated\nNote: This classification is not used for melanomas of sites other than skin (e.g., ocular, mucosal, urethral, etc.).\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \u00ad\nCommittee on Cancer (AJCC), Chicago, Illinois.\nTABLE 18\u20137.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF MELANOMA OF THE SKIN\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_337.png", "summary": "The text discusses the location of metastatic tumors in sentinel nodes, the examination process for sentinel nodes, the significance of small metastases, distant metastasis, AJCC classification, and processing large skin excisions.", "questions": [ "What are the different methods used to examine sentinel nodes?", "What is the significance of small metastases (< 0.2 cm)?", "How are large skin excisions processed and what information should be recorded during the process?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 338, "text": "DERMATOPATHOLOGY\u2003 Large Skin Excisions\n320\n\u0007Even the smallest ellipses must be cross-sectioned perpendicular to the scar (i.e., do not bisect longi\u00ad\ntudinally) in order to evaluate the closest (lateral) margins.\n 4.\t \u0007Block out the lesion or the biopsy scar and submit the entire lesion or biopsy site. If these sections do \nnot include the deep margin, separate sections of the deep margin should be submitted.\n 5.\t \u0007Carefully section through soft tissue looking for lymph nodes. Submit all lymph nodes found.\n 6.\t \u0007Draw a diagram of the specimen that includes the location of all sections taken and a key to the cor\u00ad\nresponding cassettes in which they are submitted. This is particularly important for irregularly shaped \nspecimens.\nTABLE 18\u20138.\u2003\nAJCC (7TH EDITION) CLASSIFICATION \u2013 MERKEL CELL CARCINOMA\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor (e.g., nodal/metastatic presentation without associated primary)\nTis\nIn situ primary tumor\nT1\nLess than or equal to 2 cm maximum tumor dimension\nT2\nGreater than 2 cm but not more than 5 cm maximum tumor dimension\nT3\nOver 5 cm maximum tumor dimension\nT4\nPrimary tumor invades bone, muscle, fascia, or cartilage\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed\nN0\nNo regional lymph node metastasis\ncN0\nNodes negative by clinical exam* (no pathologic node exam performed)\npN0\nNodes negative by pathologic exam\nN1\nMetastasis in regional lymph node(s)\n\u2003 N1a\nMicrometastasis\n\u2003 N1b\nMacrometastasis\nN2\nIn transit metastasis\n* Clinical detection of nodal disease may be via inspection, palpation, and/or imaging.\nMicrometastases are diagnosed after sentinel or elective lymphadenectomy. A micrometastasis is a pathologically documented metastasis \n(of any size) in a node not detected by clinical or radiologic examination.\nMacrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or needle biopsy.\nIn transit metastasis: a tumor distinct from the primary lesion and located either (1) between the primary lesion and the draining regional lymph \nnodes or (2) distal to the primary lesion.\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nMetastasis beyond regional lymph nodes\n\u2003 M1a\nMetastasis to skin, subcutaneous tissues, or distant lymph nodes\n\u2003 M1b\nMetastasis to lung\n\u2003 M1c\nMetastasis to all other visceral sites\nThis system does not include Merkel Cell carcinoma of the eyelid.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \nCommittee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_338.png", "summary": "The page discusses the proper handling and evaluation of large skin excisions in dermatopathology, emphasizing the importance of cross-sectioning perpendicular to the scar, submitting the entire lesion or biopsy site, and carefully examining lymph nodes.", "questions": [ "Why is it important to cross-section perpendicular to the scar in evaluating skin excisions?", "What steps should be taken when submitting the entire lesion or biopsy site?", "How are micrometastases and macrometastases defined in the context of regional lymph node involvement?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 339, "text": "321\nLIP EXCISIONS\nSquamous cell carcinoma is the most common neoplasm of the lip. The specimens are more complicated \nbecause there is often both a mucosal and skin surface (Fig. 18-3). There are three margins: the side \nmargins (lateral and medial) margins and a deep margin.\nPROCESSING THE SPECIMEN\u2002\n 1.\t \u0007Describe the specimen including overall dimensions and dimensions of mucosal and skin surfaces.\n 2.\t \u0007Describe any lesions including size, color, quality (exophytic, verrucous, polypoid, ulcerated), and \nlocation (with respect to skin, mucosa, and vermilion border, and distance from margins).\n 3.\t \u0007Ink the lateral, medial, and deep surgical margins.\n 4.\t \u0007Serially section the specimen. Note the depth of invasion of the tumor. Submit sections demonstrat\u00ad\ning the tumor and its deepest extent, relationship to skin and mucosa, and relationship to all margins.\n 5.\t \u0007Draw a diagram showing the location of the lesion and a key to the location of tissue sections and the \ncorresponding cassettes.\nFORESKIN\nThe foreskins of newborn infants are generally not submitted for histologic examination unless there are \ngross abnormalities. Circumcisions of older males are performed in two age groups:\n\t \u2022\t \u0007Young adults (18 to 25 years old): Usually performed for phimosis due to a subtle anatomic defect \n(e.g., minimal hypospadias). The only histologic finding is slight nonspecific chronic balanitis.\n\t \u2022\t \u0007Older men (>50): A specific inflammatory or neoplastic lesion is usually found. Common lesions are \ncondylomas, balanitis xerotica obliterans (lichen sclerosus), balanitis circumscripta plasmacellularis \n(Zoon\u2019s balanitis), squamous cell carcinoma in situ, and invasive squamous cell carcinomas. If no \nlesions are detected on the initial sections, and the clinical history is not provided, call the clinician \nto find out the reason for the circumcision.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Measure length, width, and thickness. The specimen usually consists of a rectangle of tissue including \nskin and mucosa on the surface with underlying loose areolar tissue. It is usually not possible to orient \nthe specimen as to proximal and distal margins.\n 2.\t \u0007Examine the surface carefully for any epidermal lesions. If any are present, describe size, appearance \n(verrucous, papillary, ulcerated), depth of invasion, and distance from the nearest cut edge. Ink mar\u00ad\ngins if a focal lesion is present.\nDERMATOPATHOLOGY\u2003 Foreskin\nMucosa\nMucosa\nMinor salivary\nglands\nSkin\nMuscle\nDermal\nappendages\nSkin\nVermillion\nborder\nVermillion\nborder\nFigure 18\u20133.\u2002 Lip resection.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_339.png", "summary": "Squamous cell carcinoma is the most common neoplasm of the lip, presenting challenges in specimen processing due to the presence of both mucosal and skin surfaces.", "questions": [ "What are the three margins that need to be considered in lip excisions?", "How should the specimen be processed to accurately assess the depth of invasion of the tumor?", "Why are foreskins of newborn infants generally not submitted for histologic examination?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 340, "text": "322\nDERMATOPATHOLOGY\u2003 Fingernails and Toenails\nDescribe the uninvolved skin including color, texture (rugose, atrophic, thickened).\n 3.\t \u0007The specimen is sectioned longitudinally including both skin and mucosa. One cassette with rep\u00ad\nresentative sections is adequate if there are no gross lesions and the foreskin is removed in the clinical \ncontext of phimosis. Additional cassettes are submitted to document all lesions and adjacent margins.\nFINGERNAILS AND TOENAILS\nClippings\nToenail clippings may be sent for the evaluation of fungal infection. Inform the histology laboratory that \nthe specimen consists of a nail as these specimens are usually very difficult to section and may require \nspecial techniques for softening.1,2 Order a PAS stain (for fungi).\nNail bed biopsies are usually submitted for the evaluation of pigmented lesions. Do not order a PAS \nstain on these specimens.\nTumor\nSubungual melanomas occur in all ethnic groups but are proportionately more common in persons of \ncolor. These lesions may present as linear pigmented streaks of the nail, if the melanoma cells involve \nthe nail matrix. Specimens consisting of only the nail (and not the matrix) will not be diagnostic because \nmelanocytes are not present. The appropriate specimen is a punch biopsy of the nail matrix. If a nail is \nreceived with a pigmented area, it is submitted for microscopic examination for evaluation of an atypical \nmelanocytic lesion or melanoma.\nREFERENCES\n\t1.\t \u0007Lewin K, et al: Softening techniques for nail biopsies. Arch Dermatol 107:223-224, 1973.\n\t2.\t \u0007Shapiro L. Softening hard keratin in specimens for microscopic sections. Am J Clin Pathol 54:773-774, 1970.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_340.png", "summary": "The page discusses the evaluation of fingernails and toenails in dermatopathology, including the description of uninvolved skin, sending clippings for fungal infection evaluation, and the importance of proper specimen collection for subungual melanomas.", "questions": [ "What special considerations should be made when sending toenail clippings for evaluation?", "Why is it important to submit nail bed biopsies for the evaluation of pigmented lesions?", "How can subungual melanomas present and what is the appropriate specimen for diagnosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 341, "text": "323\n19\nGastrointestinal Specimens \n(Including Hepatobiliary \nand Pancreatic Specimens)\nSpecimens from the gastrointestinal tract are common. Endoscopic biopsies are often performed to \nevaluate patients with symptoms (bleeding, diarrhea, malabsorption), to look for pathogens, as well as to \nevaluate mass lesions (polyps and tumors). Resections are commonly performed for tumors but are also \nperformed for inflammatory bowel disease, diverticulosis, and ischemic bowel.\nESOPHAGUS\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nBiopsies\nBiopsies are commonly performed for evaluation of heartburn (e.g., due to reflux or ulcers in immuno\u00ad\ncompromised patients), for the evaluation of dysphagia (usually \u00adsecondary to strictures or tumors), or \nsurveillance for dysplasia in patients known to have Barrett\u2019s esophagus. Small biopsies are submitted as \ndescribed in Chapter 13.\nTABLE 19\u20131.\u2003\nRELEVANT CLINICAL HISTORY \u2013 ESOPHAGUS\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR ESOPHAGEAL SPECIMENS\nOrgan/tissue resected or biopsied\nGross appearance of lesions (e.g., raised masses, ulcers, \nstrictures)\nPurpose of the procedure\nGross appearance of the organ/tissue/lesion \nsampled\nLocation of biopsies in the esophagus\nAny unusual features of the clinical \npresentation\n\u2192 for example, a history of reflux or lye ingestion\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\n\u2192 for example, a history of Barrett\u2019s esophagus\nPrior malignancy\nPrior treatment (radiation therapy, \nchemotherapy, drug use that can change \nthe histologic appearance of tissues)\nCompromised immune system\n\u2192 for example, thrush, HIV, bone marrow transplant", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_341.png", "summary": "This page discusses gastrointestinal specimens, including hepatobiliary and pancreatic specimens. It covers the common reasons for endoscopic biopsies and resections in patients with symptoms or mass lesions.", "questions": [ "What are some common symptoms that lead to endoscopic biopsies of the gastrointestinal tract?", "What are the different purposes for which resections are commonly performed in gastrointestinal specimens?", "How does the clinical history play a role in the evaluation of esophageal specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 342, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Esophagus\n324\nEsophagectomies\nThe esophagus is usually removed with the proximal stomach for severe dysplasia or for adenocarcinoma \narising in a background of Barrett\u2019s esophagus. Patients with squamous cell carcinomas are often treated \nwith chemotherapy and radiation therapy prior to resection.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Stapled margins are removed by cutting away the staple line (as close as possible to the staples) with a \npair of scissors. Locate the lesion by gently palpating the GE junction with one finger in the lumen. \nOpen the specimen longitudinally. Avoid cutting across any palpable lesions.\n 2.\t \u0007Record the length, circumference, and wall thickness of the esophagus and of the stomach. Record the \nsize of any lesions and the distance to distal and proximal margins.\n 3.\t \u0007Ink the proximal and distal margins and the deep margin underneath the tumor. Pin out on a board. If \nthe tumor is large, make one to three longitudinal cuts into the tumor to aid in fixation. The specimen \nis fixed in formalin overnight.\nDescribe the lesion and/or area of ulceration (if no gross tumor is present after preoperative therapy) \nincluding size, color, tumor configuration (exophytic or polypoid, ulcerated, or infiltrative), depth \nof invasion, location (including relationship to squamo-columnar junction), percent of circumfer\u00ad\nence involved, luminal diameter at the site of the tumor, and proximal dilatation.\nThe distance from the margins (distal, proximal, and deep) should be measured as soon as possible on \nthe fresh specimen as considerable retraction occurs after excision.\nThe squamo-columnar junction (Z line) is the intersection of glandular and squamous mucosa. The \nGE junction is defined as the junction of the tubular esophagus and the sack-shaped stomach, irre\u00ad\nspective of the type of mucosa present. In normal individuals, this point usually corresponds to the \nproximal extent of the gastric folds. Any proximal displacement of the Z line above the GE junction \nis indicative of columnar-line (Barrett\u2019s) esophagus.\n 4.\t \u0007Describe uninvolved mucosa.\n\t \u2022\t \u0007Normal esophagus (squamous): glistening smooth white mucosa.\n\t \u2022\t \u0007Normal stomach (glandular): velvety pink/red mucosa with rugal folds.\n\t \u2022\t \u0007Barrett\u2019s mucosa (glandular): pale pink, finely granular, and may be patchy.\n 5.\t \u0007The adventitial soft tissue away from the tumor can be stripped and placed in Bouin\u2019s to aid in identi\u00ad\nfying lymph nodes. Nodes are virtually always present and may be located very close to the esophagus \nor stomach. Even small areas of attached adipose tissue need to be searched for lymph nodes.\n 6.\t \u0007Submit sections after fixing the specimen overnight. Section through the fat and submit all lymph nodes.\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Figure 19-1.\nAdenocarcinomas\u2002 of the esophagus are usually present at or just above the GE junction and have a \ngross appearance similar to colonic adenocarcinomas. The main tumor is often tan/pink, polypoid, and \nmay have an ulcerated \u00adcenter. These tumors often tunnel underneath the proximal noninvolved squa\u00ad\nmous mucosa and may be present at the proximal or distal margins in the \u00adsubmucosa. This is of great \nimportance when evaluating margins \u00adintraoperatively. A section that includes the full thickness of the \nesophageal or gastric wall should be taken.\nOccasionally gastric tumors arising in the proximal stomach may be removed using a similar proce\u00ad\ndure. Note the location of the center of the tumor in relation to the GE junction to help discriminate \nbetween esophageal and gastric origin.\nBarrett\u2019s Mucosa\u2002 is pale pink, finely granular, and may be patchy. It is distinct from the normal \nesophageal squamous mucosa, which is white, smooth, and glistening. Barrett\u2019s mucosa is found extend\u00ad\ning proximally from the GE junction. It is often seen in association with esophageal adenocarcinomas, \nalthough the tumor may have obliterated the precursor lesion.\nSquamous Cell Carcinomas\u2002 can occur at any level of the esophagus. These tumors may be exo\u00ad\nphytic (intraluminal), ulcerating, or present as a diffuse thickening with narrowing of the lumen. In most", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_342.png", "summary": "Esophagectomies are performed for severe dysplasia or adenocarcinoma in Barrett's esophagus, with squamous cell carcinomas often treated with chemotherapy and radiation therapy prior to resection.", "questions": [ "What are the key steps in processing esophagectomy specimens?", "How is the squamo-columnar junction defined and its significance in Barrett's esophagus?", "Why is it important to describe uninvolved mucosa in esophagectomy specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 343, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Esophagus\n325\nA\nB\nC\nD\nNormal\nBarrett's esophagus\nAdenocarcinoma\nSquamous cell carcinoma\nGE junction\nBarrett's mucosa\nEsophagus\nStomach\nTumor within Barrett's mucosa\nTumor anywhere in\nesophagus\nZ-line\nZ-line\nZ-line\nZ-line\nFigure 19\u20131.\u2002 Esophagectomy specimens.\ncases, preoperative radiation therapy will have been given. The residual tumor may be difficult to appre\u00ad\nciate grossly and may consist of areas of shallow ulceration or irregular/granular appearing squamous \nmucosa. Intraoperatively the margins should be evaluated for carcinoma in situ in the squamous mucosa.\nTumors After Treatment.\u2002 The main tumor mass may be absent with only a shallow ulceration present \nat its former site. Post-radiation changes may be present including fibrosis and esophageal mucosal erosions.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_343.png", "summary": "This page discusses esophagectomy specimens, including findings such as Barrett's esophagus, adenocarcinoma, and squamous cell carcinoma.", "questions": [ "How is Barrett's esophagus different from other esophageal conditions mentioned?", "What are the implications of preoperative radiation therapy on the evaluation of esophagectomy specimens?", "How do post-radiation changes affect the interpretation of esophageal mucosal specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 344, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Esophagus\n326\nLeiomyomas\u2002 of the esophagus almost always arise from the muscularis propria and only rarely from \nthe muscularis mucosae. The tumors are well circumscribed, pink to white, and have a whorled appear\u00ad\nance, similar to uterine leiomyomas. Most are present within the wall, but some may project into the \nlumen as a polypoid mass. GISTs are less common than leiomyomas in the esophagus, but are more \ncommon at other sites in the GI tract.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Tumor: Four or fewer sections including maximal depth of invasion, relationship to esophagus and \nstomach. Longitudinal sections are usually best.\n\t\n\u2022\t \u0007If no gross tumor is present, block out the ulcerated/fibrosed area and submit four sections.\n\t \u2022\t \u0007Margins: Up to three sections of proximal, distal, and deep margins. The deep margin can usually \nalso be one of the tumor blocks. Use en face (not perpendicular) sections of the proximal margins \nunless tumor and margin can be included in multiple perpendicular sections.\n\t \u2022\t \u0007Esophagus and stomach: Document normal esophageal and gastric mucosa if not included in \n\u00admargins.\n\t \u2022\t \u0007Other lesions: Submit sections of all other gross lesions including a representative area of Barrett\u2019s \nmucosa.\n\t \u2022\t \u0007Lymph nodes: Submit all lymph nodes found (see Chapter 27).\nNote: LYMPH NODES ARE ALWAYS PRESENT. They may be very close to the esophageal wall. \nALL attached adipose tissue must be searched for nodes.\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cesophagus\u201d is an esophagectomy \nand partial gastrectomy specimen consisting of esophagus (15 cm in length \u00d7 4 cm in circumference) \nand stomach (5 cm in length \u00d7 12 cm in circumference). There is a 3.5 \u00d7 3 cm tan/pink, firm, centrally-\nulcerated tumor mass arising just proximal to, and partially involving, the gastroesophageal junction. The \ntumor invades into and focally through the muscularis propria into adjacent soft tissue. Tumor is present \n0.1 cm from the deep margin which is inked. The tumor is 12 cm from the proximal margin and 5 cm \nfrom the distal margin. The esophageal mucosa adjacent to the tumor is tan/pink and finely granular \nand extends to within 5 cm of the proximal resection margin. The remainder of the mucosal surfaces are \nunremarkable. Five lymph nodes are found in the surrounding soft tissue, the largest measuring 1 cm in \ngreatest dimension. This node is very firm and white. The specimen is photographed.\nCassettes #1-2: Tumor and deepest extent of invasion and deep margin, 2 frags, ESS.\nCassette #3: Tumor and adjacent esophageal mucosa, 1 frag, RSS.\nCassette #4: Tumor and adjacent gastric mucosa, 1 frag, RSS.\nCassette #5: Proximal margin, en face, 1 frag, RSS.\nCassette #6: Distal margin, en face, 1 frag, RSS.\nCassette #7: Abnormal esophageal mucosa, 1 frag, RSS.\nCassette #8: Largest lymph node, 3 frags, ESS.\nCassette #9: Four lymph nodes, 4 frags, ESS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR ESOPHAGEAL CARCINOMAS\n\t\u2022\t \u0007Specimen: Esophagus, proximal stomach\n\t\u2022\t \u0007Procedure: Endoscopic resection, esophagectomy, esophagogastrectomy, other\n\t\u2022\t \u0007Tumor Site: Center of tumor and extent of tumor: GE junction, stomach, location in esophagus\n\t\u2022\t \u0007Relationship of Tumor to Esophagogastric Junction: Entirely within tubular esophagus, tumor \nmidpoint in the distal esophagus and involves GE junction, tumor midpoint at the GE junction, tumor \nmidpoint in the proximal stomach or cardia and involves the GE junction\n\t \u2022\t \u0007Give the distance of the tumor center from the GE junction, if applicable.\n\t\u2022\t \u0007Carcinomas with the epicenter within the proximal 5 cm of the stomach (cardia) that extend into the \nGE junction are classified as esophageal carcinomas for AJCC staging. Carcinomas within the proxi\u00ad\nmal 5 cm of the stomach that do not extend into the GE junction, or carcinomas with the epicenter \ngreater than 5 cm from the GE junction are classified as gastric carcinomas.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_344.png", "summary": "Leiomyomas of the esophagus arise from the muscularis propria and have a whorled appearance, while GISTs are less common but found at other GI tract sites.", "questions": [ "What is the typical appearance of leiomyomas in the esophagus?", "How do GISTs in the esophagus compare to leiomyomas?", "Why is it important to document normal esophageal and gastric mucosa in the specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 345, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Esophagus\n327\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions are optional). Provide the greatest longi\u00ad\ntudinal dimension, the distance of the midpoint of the tumor from the GE junction, and the relative \nproportions of the tumor in the esophagus and in the stomach.\n\t\u2022\t \u0007Histologic Type: Adenocarcinoma (including mucinous [> 50% mucinous], signet ring cell [>50% \nsignet ring cells] types), squamous cell carcinoma (including verrucous, spindle cell, and basaloid \ntypes), adenosquamous carcinoma, small cell carcinoma, undifferentiated carcinoma, other rare types. \nThe WHO Classification is recommended.\n\t\u2022\t \u0007Histologic Grade: Well, moderately, or poorly differentiated, or undifferentiated (Tables 19-2 and \n19-3)\n\t\u2022\t \u0007Microscopic Tumor: High-grade dysplasia (carcinoma in situ) (Tis), invasion into lamina propria \n(T1a), invasion into muscularis mucosae (T1a), invasion into submucosa (T1b), invasion into muscu\u00ad\nlaris propria (T2), invasion through muscularis propria into the periesophageal soft tissue (adventitia) \n(T3), invasion into adjacent structures (T4)\n\t\u2022\t \u0007Margins: Proximal, distal, and circumferential (radial or adventitial margin; soft tissue at deepest \nextent of tumor), involved or not involved, distance from closest margin, centimeters of involvement, \ntype of mucosa at margin. Margins are also evaluated for the presence of dysplasia and/or Barrett \nmucosa.\n\t\u2022\t \u0007Treatment Effect: No prior treatment, no residual tumor (complete response, grade 0), marked \nresponse (grade 1, minimal residual cancer as single cells or small groups of cells), moderate response \n(grade 2, residual cancer outgrown by fibrosis), no definite response (poor or no response, grade 3 as \nextensive residual cancer)\n\t \u2022\t \u0007Pools of acellular mucin should not be interpreted as residual carcinoma.\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Regional Lymph Nodes: The total number and location of nodes examined should be specified, \nwhen possible.\n\t \u2022\t \u0007The nodes around the stomach and esophagus are considered regional nodes.\n\t \u2022\t \u0007Mediastinal nodes are regional nodes for the intrathoracic esophagus.\n\t \u2022\t \u0007Cervical and supraclavicular nodes are regional nodes for the cervical esophagus.\nTABLE 19-2.\u2003\nGRADING SYSTEM FOR ESOPHAGEAL ADENOCARCINOMAS\nGrade X\nGrade cannot be assessed.\nGrade 1\nWell differentiated (> 95% gland forming, includes tubular)\nGrade 2\nModerately differentiated (50% to 95% of tumor composed of glands)\nGrade 3\nPoorly differentiated (< 49% of tumor composed of glands, includes signet ring cell carcinomas)\nGrade 4\nUndifferentiated (cannot be categorized as squamous cell carcinoma or adenocarcinoma) \n(includes small cell carcinoma)\nThe tumor is given the grade of the least differentiated part. Mucoepidermoid carcinomas and adenoid cystic carcinomas are not usually graded. \nFor the purpose of AJCC staging, grade X carcinomas are grouped as grade 1\u00a0carcinomas and grade 4 carcinomas are staged as grade 3 squamous \ncell carcinomas.\nTABLE 19-3.\u2003\nGRADING SYSTEM FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMAS\nGrade X\nGrade cannot be assessed.\nGrade 1\nWell differentiated\nGrade 2\nModerately differentiated\nGrade 3\nPoorly differentiated\nGrade 4\nUndifferentiated (cannot be categorized as squamous cell carcinoma or adenocarcinoma)\nThe tumor is given the grade of the least differentiated part. For the purpose of AJCC staging, grade X carcinomas are grouped as grade 1 carcino\u00ad\nmas and grade 4 carcinomas are staged as grade 3 squamous cell carcinomas.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_345.png", "summary": "The page provides detailed information on the assessment and classification of esophageal tumors, including tumor size, histologic type, grade, microscopic features, margins, treatment effect, lymphovascular invasion, perineural invasion, and regional lymph nodes.", "questions": [ "How is the histologic type of esophageal tumors classified and what are the recommended types?", "What are the different grades used to assess esophageal adenocarcinomas and how are they determined?", "Why are pools of acellular mucin not interpreted as residual carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 346, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Esophagus\n328\n\t \u2022\t \u0007Number of positive lymph nodes\n\t \u2022\t \u0007Presence or absence of extranodal extension\n\t\u2022\t \u0007Additional Pathologic Findings: Barrett esophagus (intestinal metaplasia), dysplasia (low grade, high \ngrade), esophagitis (type), gastritis (type), Helicobacter pylori, ulceration, granulomas\n\t\u2022\t \u0007Ancillary Studies: If performed.\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 19-4). M0 \nis conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/\u2009\u2009) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nTABLE 19-4.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF ESOPHAGEAL CARCINOMAS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nHigh-grade dysplasia*\nT1\nTumor invades lamina propria, muscularis mucosae, or submucosa\nT1a\nTumor invades lamina propria or muscularis mucosae\nT1b\nTumor invades submucosa\nT2\nTumor invades muscularis propria\nT3\nTumor invades adventitia\nT4\nTumor invades adjacent structures\nT4a\nResectable tumor invading pleura, pericardium, or diaphragm\nT4b\nUnresectable tumor invading other adjacent structures, such as aorta, vertebral body, \ntrachea, etc.\n*High-grade dysplasia includes all noninvasive neoplastic epithelia that were formerly called carcinoma in situ, a diagnosis that is no longer used for \ncolumnar mucosae anywhere in the gastrointestinal tract.\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in 1-2 regional lymph nodes\nN2\nMetastasis in 3-6 regional lymph nodes\nN3\nMetastasis in seven or more regional lymph nodes\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: This classification includes squamous cell carcinomas and adenocarcinomas but not well-differentiated neuroendocrine tumors (carcinoid \ntumors), lymphomas, or sarcomas. \nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_346.png", "summary": "This page provides guidelines for reporting on esophageal cancer specimens, including information on lymph node involvement, ancillary studies, distant metastasis, and AJCC classification.", "questions": [ "What are the key elements that must be included in reports of cancer-directed surgical resection specimens from ACS CoC-approved cancer programs?", "How is the AJCC classification of esophageal carcinomas determined?", "What are the different categories for regional lymph node metastasis in esophageal cancer?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 347, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Stomach\n329\nSTOMACH\nThe stomach is commonly affected by inflammatory processes (i.e., gastritis) as well as primary malignant \ntumors.\nRELEVANT CLINICAL HISTORY\nSee Table 19-5.\nBiopsy\nBiopsies can be processed as described in Chapter 13. Special stains (e.g., Alcian Yellow, Diff Quik, \nGiemsa, or Steiner) may be used to evaluate the biopsy for Helicobacter pylori.\nIf lymphoma is suspected, an unfixed biopsy specimen may be submitted. This tissue may be frozen \nfor use for hematopathology markers.\nGastrectomy\nStomachs are resected for primary tumors (carcinoma or lymphoma, rarely partial resections for a gas\u00ad\ntrointestinal stromal tumor), less commonly for benign ulcers, and as part of larger resections (esophago\u00ad\ngastrectomies or \u00adWhipple procedures).\nGastrectomies may be total, but usually are partial. Look carefully at the margins to determine whether \nduodenal or esophageal mucosa is present.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Examine the outer surface of the specimen for evidence of tumor invasion through the wall and \ndescribe the serosa (color, glistening, dull, indurated, retracted, nodules). Carefully ink the proximal \nand distal resection margins without getting ink on the mucosa. Once the specimen is opened, the \nmucosal edges tend to curl under, and it is sometimes difficult to identify the resection margins. The \nink can help with this identification.\n 2.\t \u0007Very gently palpate the mucosa and wall to locate the lesion. The mucosa is very delicate and should \nbe touched as little as possible. Open the stomach along the greater curvature, unless a lesion is pres\u00ad\nent at that site. Record the length of the greater curvature, lesser curvature, proximal resection margin \n(circumference - look for esophageal mucosa), distal resection margin (circumference - look for duo\u00ad\ndenal mucosa), and the thickness of the wall. Cassettes can be clipped to the edges of the margins to \nhelp in identify them after the stomach is opened.\nTABLE 19\u20135.\u2003\nRELEVANT CLINICAL HISTORY \u2013 STOMACH (IN ADDITION TO AGE AND GENDER)\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR STOMACH SPECIMENS\nOrgan/tissue resected or biopsied\nGastritis (Helicobacter pylori or atrophic gastritis)\nPurpose of the procedure\nGross appearance of the organ/tissue/lesion sampled\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\n\u2192 Gastric surgery (e.g., Billroth)\nPrior malignancy\n\u2192 History of gastric dysplasia, location of biopsy\nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic appearance of tissues)\nImmunocompromise", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_347.png", "summary": "The stomach is commonly affected by inflammatory processes and primary malignant tumors. Biopsies and gastrectomies are common procedures for evaluating and treating stomach conditions.", "questions": [ "What special stains are commonly used to evaluate stomach biopsies for Helicobacter pylori?", "What are the common reasons for performing a gastrectomy?", "How should the specimen be processed to identify resection margins during a gastrectomy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 348, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Stomach\n330\n 3.\t \u0007Identify mucosal lesions and describe:\n\t \u2022\t \u0007Size (including depth of invasion) \u2013 Ink the deep margin of any lesions and make several cuts to \nevaluate the depth of penetration into the wall.\n\t \u2022\t \u0007Color\n\t \u2022\t \u0007Shape (ulcerating, polypoid, diffuse, exophytic)\n\t \u2022\t \u0007Consistency (hard, firm, soft)\n\t \u2022\t \u0007Margins of ulcers (irregular, rolled, puckered)\n\t \u2022\t \u0007Location (cardia, fundus, antrum, greater or lesser curvature, anterior or posterior wall)\n\t \u2022\t \u0007Perforation of wall\n\t \u2022\t \u0007Relationship to resection margins \u2013 The distance to margins should be measured on the fresh speci\u00ad\nmen as soon as possible after resection, as considerable contraction of the specimen can occur.\n\t \u2022\t \u0007Relationship to the visceral peritoneum \u2013 Tumor penetration of the visceral peritoneum (grossly \ncorresponding to tumor present at the surface of the perigastric adipose tissue) is classified as T3, \nwhereas tumor that invades into perigastric soft tissue (e.g., greater omentum) but not through vis\u00ad\nceral peritoneum is classified as T2.\nIf the nature of the lesion (i.e., carcinoma vs. lymphoma) has not been established (e.g., by previ\u00ad\nous biopsy) and is not evident from the gross examination, a frozen section or cytologic preparation \n(e.g., a touch preparation) may be useful to aid in apportioning tissue (e.g., saving tissue for hemato\u00ad\nlogic studies if lymphoma is suspected).\nDescribe the uninvolved mucosa including color, texture (glistening, hemorrhagic, granular, flat\u00ad\ntened, fibrotic, constricted), and the preservation or absence of rugal folds.\n 4.\t \u0007Remove the adventitial soft tissue except at the deep margin of lesions and place in Bouin\u2019s fixative, if \ndesired, to better visualize lymph nodes.\n 5.\t \u0007Pin out the stomach and fix overnight in formalin. The following day, submit microscopic sections of \nstomach and lesions. Section through soft tissue and submit all lymph nodes. Describe including size \nof largest node, evidence of metastasis (white, hard).\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Figure 19-2.\nBenign Ulcers tend to be sharply delineated with converging mucosal folds. The edges are usually \nflat or only slightly heaped up. About 10% of ulcers thought to be clinically benign are shown to be \nmalignant after pathologic examination. Malignancy is more common in ulcers over 2 cm in size.\nGastric Carcinomas of Intestinal Type are similar in appearance to colonic adenocarcinomas and \nusually arise in the antrum. The edges are usually heaped up and serpiginous with a central ulcer bed. \nPolypoid and villous architecture may be present. Nodularity around the edge of an ulcer or an exo\u00ad\nphytic component are more common in carcinomas. However, some tumors may be ulcerating and lack a \nheaped up border. Radial mucosal folds are usually absent. Intestinal-type carcinomas are associated with \nchronic atrophic gastritis that causes marked thinning and flattening of the surrounding mucosa. This \ntype of carcinoma is more common in males than females.\nDiffuse Type (Signet Ring Cell Carcinomas) are usually located in the prepyloric region or body of \nthe stomach and can have minimal or absent superficial mucosal involvement. The only sign of an early \nlesion may be subtle mucosal effacement or erosion, which may be better appreciated in a fixed, pinned-\nout specimen. In advanced lesions the wall of the stomach is markedly thickened due to the infiltrative \nnature of the malignant cells (termed \u201clinitis plastica\u201d) but the muscularis propria can still be identified \nand appears thickened and hypertrophic. It may be difficult to determine the extent of the tumor grossly. \nThere is a similar incidence in males and females.\nLymphomas can have a gross appearance very similar to signet ring cell carcinomas, with little or \nno mucosal involvement (i.e., ulceration). Although they also commonly present in the distal stomach, \nthey rarely involve the pyloric region. The gross appearance may resemble hypertrophied mucosal folds \nor may appear to be a large mass, sometimes with perforation. The wall may appear diffusely thickened \n(linitis plastica).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_348.png", "summary": "This page provides guidelines for identifying and describing mucosal lesions in stomach specimens, including details on size, color, shape, consistency, margins, location, and relationship to surrounding structures.", "questions": [ "How can the depth of invasion of mucosal lesions in stomach specimens be evaluated?", "What are the key characteristics to describe when examining uninvolved mucosa in stomach specimens?", "What are the differences in appearance between benign ulcers and malignant ulcers in stomach specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 349, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Stomach\n331\nGastrointestinal Stromal Tumors (GISTs).\u2002 arise from the specialized interstitial cells of Cajal in the \nmuscularis propria. Some protrude into the lumen with ulceration of the overlying mucosa. Others pro\u00ad\ntrude out on the serosal side. The cut surface is tan and lacks the whorled appearance of smooth muscle \ntumors. Most (60% to 70%) arise in the stomach with fewer in small intestine (30% to 40%), colon or \nrectum (5%), or esophagus (5%). The risk of malignant behavior is related to location (gastric tumors \nare less likely to behave in a malignant fashion), size, and mitotic rate (see Chapter 32 for a table with \nclassification). Leiomyomas are uncommon in the stomach (<10%).\nA\nB\nC\nGastric ulcer\nIntestinal type adenocarcinoma\nSignet-ring cell carcinoma (linitis plastica)\nGastric wall markedly\nthickened\nConverging mucosal\nfolds\nMarkedly heaped-up\nulcer edge\nSlightly heaped up\nulcer edge\nSubmucosa\nMuscularis\npropria\nMucosa\nSubmucosa\nMuscularis\npropria\nMucosa\nSubmucosa\nMuscularis\npropria\nMucosa\nFigure 19\u20132.\u2002 Gross appearances of stomach lesions.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_349.png", "summary": "Gastrointestinal Stromal Tumors (GISTs) arise from the specialized interstitial cells of Cajal in the muscularis propria of the stomach, with varying protrusions and appearances. Most GISTs occur in the stomach, with different risk factors for malignant behavior.", "questions": [ "What are the key characteristics of Gastrointestinal Stromal Tumors (GISTs) in the stomach?", "How do the risk factors for malignant behavior differ based on the location of GISTs?", "What is the significance of the whorled appearance of smooth muscle tumors in comparison to GISTs?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 350, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Stomach\n332\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Lesion: Four or fewer sections including deepest penetration of wall and radial sections of ulcers.\n\t \u2022\t \u0007Margins: Representative proximal margin, distal margin, and deep margin (three sections). If \nesophagus is included, take an en face (not transverse) section of that margin. Take stomach margin \nen face if the tumor is far from this margin. Take sections perpendicular to the margin (and through \nthe tumor if possible) if the tumor is close to the margin.\n\t \u2022\t \u0007Stomach: Representative sections of cardia, fundus, and antrum if not included in other sections.\n\t \u2022\t \u0007Lymph nodes: Submit all lymph nodes.\nSAMPLE GROSS DESCRIPTION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201cstomach\u201d is a 20 (greater curvature) \n\u00d7 15 (lesser curvature) \u00d7 15 (circumference of proximal margin) \u00d7 5 cm (circumference of distal margin) \ntotal gastrectomy specimen with attached portion of duodenum (1.5 cm in length \u00d7 5 cm in circumfer\u00ad\nence). The maximal wall thickness is 1.2 cm. There is a 3 \u00d7 2.5 cm firm tan/pink polypoid tumor with \ncentral ulceration located on the lesser curvature, which is 5 cm from the proximal margin and 7 cm from \nthe distal margin. The tumor grossly invades through the muscularis propria into perigastric soft tissue, \nbut is 0.2 cm from the deep (serosal) inked margin. The remainder of the mucosal surface is unremark\u00ad\nable. The gastric wall is not thickened away from the tumor (average thickness 0.5 cm). There is a small \namount of attached adipose tissue (approximately 10 \u00d7 1 \u00d7 1 cm). A single hard white lymph node mea\u00ad\nsuring 1 cm in greatest dimension is present. Five additional small lymph nodes, the largest measuring \n0.3 cm in greatest dimension are present.\nCassettes #1-2: Deepest invasion by tumor and deep margin, 2 frags, RSS.\nCassettes #3-4: Tumor and adjacent mucosa, 2 frags, RSS.\nCassette #5: Proximal margin, en face, cardia, 1 frag, RSS.\nCassette #6: Distal margin, en face, duodenum, 1 frag, RSS.\nCassette #7: Fundus, 1 frag, RSS.\nCassette #8: Antrum, 1 frag, RSS.\nCassette #9: Large lymph node, 2 frags, ESS.\nCassettes #10-11: Five lymph nodes, 5 frags, ESS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR STOMACH CARCINOMAS\n\t\u2022\t \u0007Specimen: Stomach, portion of stomach, distal esophagus, proximal duodenum\n\t\u2022\t \u0007Procedure: Endoscopic resection, partial gastrectomy (proximal or distal), total gastrectomy, other\n\t\u2022\t \u0007Tumor Site: Fundus (anterior or posterior wall), body (anterior or posterior wall, greater or lesser \ncurvature), antrum (anterior or posterior wall, greater or lesser curvature)\n\t \u2022\t \u0007Carcinomas involving the GE junction and with an epicenter > 5 cm from the GE junction are clas\u00ad\nsified as gastric carcinomas.\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Histologic Type: Adenocarcinoma (intestinal or diffuse type), papillary adenocarcinoma, tubular ade\u00ad\nnocarcinoma, signet ring cell carcinoma (>50% signet ring cells), mucinous adenocarcinoma (>50% \nmucinous), carcinoma in situ (or high grade/severe dysplasia), other rare types\n\t\u2022\t \u0007Histologic Grade: Well, moderate, poor, undifferentiated (Tables 19-6 and 19-7)\n\t\u2022\t \u0007Microscopic Extent of Tumor: High-grade dysplasia, carcinoma in situ (Tis), invasion into lamina \npropria or muscularis mucosae (T1a), invasion into submucosa (T1b), invasion into muscularis propria \n(T2), invasion into subserosal connective tissue without invasion of visceral peritoneum or adjacent \nstructures (T3), invasion of serosa (visceral peritoneum [T4a]), invasion of adjacent structures (T4b).\n\t\u2022\t \u0007Margins: Proximal, distal, radial (omental; lesser or greater), deep (if endoscopic), distance from clos\u00ad\nest margin, invasive or in situ carcinoma or adenoma\n\t\u2022\t \u0007Treatment Effect: No prior treatment, no residual carcinoma (complete response, grade 0), marked \nresponse (minimal residual cancer, grade 1), moderate response (grade 2), no definite response identi\u00ad\nfied (poor or no response, grade 3)\n\t \u2022\t \u0007Acellular pools of mucin should not be interpreted as residual carcinoma.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_350.png", "summary": "This page provides guidelines for handling gastrointestinal specimens, specifically focusing on stomach specimens, including lesion sections, margins, lymph nodes, and gross descriptions.", "questions": [ "What are the key sections that need to be included in the microscopic examination of stomach specimens?", "How should margins be approached when dealing with stomach specimens?", "What are the important considerations for handling lymph nodes in stomach specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 351, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Stomach\n333\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Regional Lymph Nodes: Number of positive nodes and total number of nodes examined.\n\t \u2022\t \u0007At least 15 lymph nodes should be examined.\n\t\u2022\t \u0007Tumor Configuration: Exophytic (polypoid), infiltrative, ulcerating, ulcerating and infiltrative, dif\u00ad\nfusely infiltrative (linitis plastica)\n\t\u2022\t \u0007Additional Pathologic Findings: Intestinal metaplasia, dysplasia, gastritis (Helicobacter pylori-type, \natrophic, autoimmune, other), polyps (types, size)\n\t\u2022\t \u0007Ancillary Studies: If performed\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 19-8). M0 \nis conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/\u2009\u2009) and the ADASP (see www.adasp.org\u2009). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nTABLE 19\u20137.\u2003\nGASTRIC ADENOCARCINOMA \u2013 CAP RECOMMENDED GRADING SYSTEM\nGrade 1\nWell differentiated (>95% of tumor composed of glands)\nGrade 2\nModerately differentiated (50 - 95% of tumor composed of glands)\nGrade 3\nPoorly differentiated (<49% of tumor composed of glands)\nGrade 4\nUndifferentiated (cannot be determined to be squamous cell carcinoma or adenocarcinoma)\nTubular carcinomas are not usually graded but would correspond to grade 1.\nSignet ring cell carcinomas are not typically graded but would correspond to grade 3.\nSmall cell carcinomas and undifferentiated carcinomas are not typically graded but would correspond to grade 4.\nModified from the CAP stomach protocol, revised October 2009. Available at www.cap.org.\nTABLE 19\u20136.\u2003\nGASTRIC ADENOCARCINOMA \u2013 GRADE\nFEATURE\nWELL (1)\nMODERATE (2)\nPOOR (3)\nUNDIFFERENTIATED (4)\nGland for\u00ad\nmation\nWell developed\nLess well developed, \ncribriform or \nacinar patterns\nPoor gland formation, \nloss of cell cohesion, \nsmall clusters of cells\nNo gland formation, solid \nsheets of cells\nStroma\nDesmoplasia \npresent but less \npronounced\nDesmoplasia \npresent but less \npronounced\nDesmoplastic\nDesmoplastic\nCell types\nWell differenti\u00ad\nated, special\u00ad\nized types may \nbe present\nSome differentiation\nMinimal differen\u00ad\ntiation. Most signet \nring cell carcinomas \nbelong in this group\nNo differentiation\nSee reference 2.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_351.png", "summary": "This page provides detailed information on the pathology assessment of gastric adenocarcinoma specimens, including lymphovascular invasion, perineural invasion, regional lymph nodes, tumor configuration, additional pathologic findings, ancillary studies, distant metastasis, and AJCC classification.", "questions": [ "What are the key elements that should be included in reports of cancer-directed surgical resection specimens from ACS CoC-approved cancer programs?", "How is gastric adenocarcinoma graded according to the CAP recommended grading system?", "What are the differences in features between well-differentiated, moderately differentiated, poorly differentiated, and undifferentiated gastric adenocarcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 352, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Small Intestine\n334\nTABLE 19-8.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF STOMACH CARCINOMAS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ: intraepithelial tumor without invasion of the lamina propria\nT1\nTumor invades lamina propria, muscularis mucosae, or submucosa\nT1a\nTumor invades lamina propria or muscularis mucosae\nT1b\nTumor invades submucosa\nT2\nTumor invades muscularis propria*\nT3\nTumor penetrates subserosal connective tissue without invasion of visceral perito\u00ad\nneum or adjacent structures\u2020\u2021\nT4\nTumor invades serosa (visceral peritoneum) or adjacent structures\u2020,\u2021\nT4a\nTumor invades serosa (visceral peritoneum)\nT4b\nTumor invades adjacent structures\n*A tumor may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omen\u00ad\ntum, without perforation of the visceral peritoneum covering these structures. In this case, the tumor is classified as T3. If there is perforation of the \nvisceral peritoneum covering the gastric ligaments or the omentum, the tumor should be classified as T4.\n\u2020The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, \nsmall intestine, and retroperitoneum.\n\u2021Intramural extension to the duodenum or esophagus is classified by the depth of the greater invasion in any of these sites, including the stomach.\nREGIONAL LYMPH NODES\nNX\nRegional lymph node(s) cannot be assessed.\nN0\nNo regional lymph node metastasis*\nN1\nMetastasis in 1-2 regional lymph node(s)\nN2\nMetastasis in 3-6 regional lymph nodes\nN3\nMetastasis in 7 or more regional lymph nodes\nN3a\nMetastasis in 7-15 regional lymph nodes\nN3b\nMetastasis in 16 or more regional lymph nodes\n*A designation of pN0 should be used if all examined lymph nodes are negative, regardless of the total number removed and examined.\nRegional lymph nodes are perigastric lymph nodes found along the greater or lesser curvatures; along the left gastric, common hepatic, splenic, or \nceliac arteries; or in the greater or lesser omentum. Involvement of other intra-abdominal lymph nodes, such as the hepatoduodenal, retropancre\u00ad\natic, mesenteric, and para-aortic, is classified as distant metastasis.\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nThe AJCC classification applies only to carcinomas, and should not be used for carcinoid tumors (low-grade neuroendocrine tumors), lymphomas, \nor sarcomas. \nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.\nSMALL INTESTINE\nThe small intestine is subject to immunologic disease (e.g., sprue or Crohn disease), infectious disease \n(e.g., Giardia, Cryptosporidia, or rarely Isospora), ischemia, and neoplasms (carcinoids, lymphomas, ampul\u00ad\nlary adenomas, adenocarcinomas, and leiomyosarcomas).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_352.png", "summary": "This page provides the AJCC classification of stomach carcinomas, outlining the primary tumor stages, regional lymph node involvement, and distant metastasis criteria.", "questions": [ "How does the AJCC classification system help in staging stomach carcinomas?", "What are the different stages of regional lymph node metastasis according to the AJCC classification?", "Why is the AJCC classification not applicable to carcinoid tumors, lymphomas, or sarcomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 353, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Small Intestine\n335\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 19-9.\nBiopsy\nBiopsies are usually performed to evaluate patients with malabsorption and, less commonly, for neoplasms.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Specimens submitted in formalin can be processed like other small biopsies (see Chapter 13).\n 2.\t \u0007Some specimens may be submitted in Hollendes, which is possibly a better fixative for histologic \ndetail. The biopsies are on mesh to preserve orientation. The biopsies must fix in Hollendes for two \nto four hours.\n 3.\t \u0007Each biopsy and its attached mesh are wrapped together in lens paper. Submit each biopsy in a separate \ncassette in order for each one to be oriented by the \u00adhistotechnologist. Tissue fixed in Hollendes must be \nwashed in water for at least 3 hours, and up to overnight. Transfer to formalin and submit after washing.\nResection\nThe small bowel is usually resected as part of a larger resection (Whipple, right colectomy), for inflam\u00ad\nmatory bowel disease (e.g., Crohn disease), or for ischemic bowel (e.g., due to a volvulus). Resection for \nprimary tumors is unusual. Although carcinoid is the most common neoplasm, lymphoma, adenomas, \nadenocarcinoma, and gastrointestinal stromal tumor are occasionally seen.\nResections for tumors can be processed in the same manner as colon resections. If the resection is for \nCrohn disease, follow the guidelines for examination of the specimen and microscopic sections in the \n\u201cColon\u201d section.\nIf the small intestine has been resected due to ischemia, sample the margins, the ischemic portion, and \nvessels found in the mesentery to look for vascular lesions such as atherosclerosis, thrombi, or vasculitis.\nGROSS DIFFERENTIAL DIAGNOSIS\nMost tumors of the small intestine will have the same gross appearance as that seen with colonic lesions.\nCarcinoid tumors are most commonly found in the appendix, but the second most common site is ileum. \nThe tumor grossly appears to be an intramural or submucosal very firm mass with a solid yellow appearance. \nThe overlying mucosa may be intact or focally ulcerated. There is prominent desmoplasia that causes the mus\u00ad\ncularis to buckle or kink, which can lead to obstruction. Tumors in the stomach and ileum may be multicentric.\nTABLE 19\u20139.\u2003\nRELEVANT CLINICAL HISTORY \u2013 SMALL INTESTINE\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR SMALL INTESTINE SPECIMENS\nOrgan/tissue resected or biopsied\nCeliac disease (or other cause of malabsorption)\nPurpose of the procedure\nInherited polyposis syndromes (including familial adeno\u00ad\nmatous polyposis, hereditary non-polyposis colon \ncancer, and Peutz-Jeghers syndrome, see Table 7-50)\nGross appearance of the organ/tissue/lesion sampled\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\nCrohn disease\nPrior surgery/biopsies - results\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, \ndrug use that can change the histologic appear\u00ad\nance of tissues)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_353.png", "summary": "Gastrointestinal specimens from the small intestine are typically biopsied for malabsorption or neoplasms, while resections are commonly done for inflammatory bowel disease or ischemic bowel. Carcinoid tumors are the most common neoplasm found in the small intestine.", "questions": [ "What are the common reasons for biopsying the small intestine?", "How should specimens submitted in Hollendes fixative be processed?", "What are the typical gross features of carcinoid tumors in the small intestine?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 354, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Meckel Diverticulum\n336\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR SMALL INTESTINE TUMORS\n\t\u2022\t \u0007Specimen: Duodenum, jejunum, ileum, other organs excised\n\t\u2022\t \u0007Procedure: Polypectomy, segmental resection, pancreaticoduodenectomy (Whipple resection), other\n\t\u2022\t \u0007Tumor Site: Duodenum, jejunum, ileum\n\t\u2022\t \u0007Tumor Configuration: Exophytic (polypoid), infiltrative, ulcerating\n\t\u2022\t \u0007Tumor Size: Greatest dimension (other dimensions optional)\n\t\u2022\t \u0007Macroscopic Tumor Perforation: Not identified, present\n\t\u2022\t \u0007Histologic Type: Carcinoid, adenoma, adenocarcinoma, signet ring cell carcinoma (>50% signet ring \ncells), mucinous adenocarcinoma (>50% mucinous), squamous cell carcinoma, all others rare\n\t\u2022\t \u0007Histologic Grade: Carcinomas: Well, moderately, poorly, undifferentiated (similar to stomach and \ncolorectal carcinomas; Table 19-10)\n\t\u2022\t \u0007Microscopic Tumor Extension: Carcinoma in situ (Tis), invasion into lamina propria (T1a), inva\u00ad\nsion into submucosa (T1b), invasion into muscularis propria (T2), invasion through muscularis propria \ninto subserosa or the nonperitonealized perimuscular tissue with extension of 2 cm or less (T3), perfo\u00ad\nration of the visceral peritoneum or direct invasion other organs or structures (T4)\n\t\u2022\t \u0007Margins: Proximal, distal, circumferential (radial), or mesenteric; distance to margin; specify invasive \nor in situ carcinoma or adenoma\n\t \u2022\t \u0007Pancreatic and bile duct margins for pancreaticoduodenectomy (Whipple resection)\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural invasion: Not identified, present\n\t\u2022\t \u0007Regional Lymph Nodes: Number of positive nodes and total number of nodes, with locations speci\u00ad\nfied when possible\n\t\u2022\t \u0007Additional Pathologic Findings: Adenoma(s), Crohn disease, celiac disease, polyps, epithelial dyspla\u00ad\nsia, ulcers, strictures\n\t \u2022\t \u0007If polyps are present, specify type, sessile or pedunculated, presence or absence of high-grade dys\u00ad\nplasia or adenocarcinoma.\n\t\u2022\t \u0007Ancillary Studies: Microsatellite instability (stable, low, high; specify testing method)\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (see Table \n19-11). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/\u2009\u2009) and the ADASP (see www.adasp.org\u2009). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nMECKEL DIVERTICULUM\nA Meckel diverticulum is persistence of a portion of the vitelline duct and always occurs on the antimes\u00ad\nenteric border of the small bowel. This is a \u201ctrue\u201d congenital diverticulum that has a complete muscular \nwall (unlike the acquired sigmoid diverticula of diverticulosis or the esophageal Zenker diverticulum: \nboth lack complete muscular walls). Ectopic tissue (gastric, pancreatic) may be found within the diver\u00ad\nticulum. Often a diverticulum is removed due to symptoms of acid production by ectopic gastric mucosa \ncausing ulceration or, rarely, because of intussusception or tumors.\nTABLE 19\u201310.\u2003\n\u0007HISTOLOGIC GRADE OF SMALL INTESTINE CARCINOMAS\nGrade 1\nWell differentiated (>95% of tumor composed of glands) with <5% of solid or cord-like growth patterns\nGrade 2\nModerately differentiated (50% to 95% of tumor composed of glands) with 5% to 50% solid or cord-\nlike growth patterns\nGrade 3\nPoorly differentiated (<50% of tumor composed of glands) with >50% of solid or cord-like growth patterns\nGrade 4\nUndifferentiated carcinoma and small cell \u00adcarcinoma", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_354.png", "summary": "The page provides a checklist for reporting on small intestine tumors, including details on tumor site, configuration, size, histologic type, grade, extension, margins, lymph-vascular invasion, and more.", "questions": [ "What are the different histologic types of small intestine tumors mentioned in the checklist?", "How is the AJCC classification used in the assessment of small intestine tumors?", "Why is it important to specify the presence or absence of lymph-vascular invasion and perineural invasion in the pathology report?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 355, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n337\nPROCESSING THE SPECIMEN\n 1.\t \u0007Orient the specimen. The specimen usually consists of a segmental resection of the ileum with a small \noutpouching from the wall, which is often the size and shape of an appendix. Record the dimensions \nof the ileum (length and circumference) and diverticulum (length and diameter). Examine the ileal \nmucosa for ulceration, erosion, or inflammation (sometimes seen with production of acid by ectopic \ngastric mucosa).\n 2.\t \u0007The diverticulum can be processed like an appendix. Cut off the tip and submit one of the longitu\u00ad\ndinal sections. Submit a second cassette with cross-sections of the middle portion. Look carefully for \nheterogeneous areas. Ectopic gastric mucosa or pancreatic parenchyma is often found.\n 3.\t \u0007Submit the two margins of the ileum and representative sections of any lesions present.\nCOLON\nThe most common surgical diseases of the colon are neoplasms (almost all are adenocarcinomas or ade\u00ad\nnomatous polyps), inflammatory bowel disease (both ulcerative colitis and Crohn disease), diverticulosis, \nand, rarely, hemorrhage from ectatic blood vessels.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 19-12.\nTABLE 19-11.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF SMALL INTESTINE CARCINOMAS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ\nT1a\nTumor invades lamina propria\nT1b\nTumor invades submucosa*\nT2\nTumor invades muscularis propria\nT3\nTumor invades through the muscularis propria into the subserosa or into the nonperitonealized \nperimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less*\nT4\nTumor perforates the visceral peritoneum or directly invades other organs or structures (includes \nother loops of small intestine, mesentery, or retroperitoneum more than 2 cm, and abdominal \nwall by way of serosa; for duodenum only, invasion of pancreas or bile duct).\n*The nonperitonealized perimuscular tissue is, for jejunum and ileum, part of the mesentery and, for duodenum in areas where serosa is lacking, \npart of the interface with the pancreas.\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in 1-3 regional lymph nodes\nN2\nMetastasis in four or more regional lymph nodes\nMETASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: This classification is not used for carcinoma arising at the ileocecal valve, carcinomas arising in Meckel diverticulum, carcinomas arising in the \nampulla of Vater, carcinoid tumors, sarcomas, or lymphomas. \nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_355.png", "summary": "The page discusses processing gastrointestinal specimens, specifically the colon, including segmental resection of the ileum with diverticulum. It also mentions common diseases of the colon and provides AJCC classification for small intestine carcinomas.", "questions": [ "What are the key steps involved in processing a gastrointestinal specimen from the colon?", "What are the most common surgical diseases of the colon mentioned in the text?", "Can you explain the significance of the AJCC classification for small intestine carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 356, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n338\nBiopsies\nMost biopsies can be processed as described in Chapter 13.\nSmall or large pedunculated polyps can be removed during colonoscopy. \u201cHot\u201d polypectomies refer \nto removal of polyps with a cauterizing wire that may allow identification of the surgical margin by the \npresence of a cautery artifact.\nPROCESSING THE SPECIMEN: POLYPS\n 1.\t \u0007Describe size, color, surface configuration (polypoid or villiform), and the base of the polyp (sessile, \nstalk: include length and width). Often the stalks (consisting of normal mucosa pulled out by the \npolyp) retract into the base and are difficult to see.\n 2.\t \u0007Always ink the base, if possible. The presence of cautery artifact is also a helpful landmark for the loca\u00ad\ntion of the margin (Fig. 19-3).\n\t \u2022\t \u0007Small polyps: Bisect the polyp along the vertical plane of the stalk to reveal the surgical margin, and \nsubmit both halves in one cassette. Order three levels on this section if the polyp is over 1 cm in size.\n\t \u2022\t \u0007Large polyps: If the head of the polyp is too wide to fit in a cassette, trim the sides away from the stalk. \nSubmit the sections of the stalk in a designated cassette and order three levels. The peripheral frag\u00ad\nments not containing the stalk are submitted in a separate cassette and can be examined in one level.\nSPECIAL STUDIES\nHirschsprung disease: Children with constipation may undergo endoscopic or open biopsy. Normal \nbowel has nerve fibers and ganglion cells in the submucosa and muscularis propria with thin nerve fibers \nextending to the musclaris mucosa. In Hirschsprung disease, ganglion cells will be absent from the sub\u00ad\nmucosal (and myenteric) plexuses. Frozen tissue may be used for acetylcholinesterase reactions to demon\u00ad\nstrate coarse, irregular nerve fibers that extend from the muscularis propria to the lamina propria. Similar \nfindings can be seen with neurofibromatosis, Crohn disease, and neuronal dysplasia (see Table 7-50).\nIdentification of Colon Segments\nLarge resections of colon are often submitted as specimens with nonspecific labels such as \u201ccolon\u201d or \nmisleading labels such as \u201csigmoid\u201d when the actual specimen is rectosigmoid. It is important to identify \nall the anatomical subdivisions of the resected bowel. This is especially important in distinguishing rectal \nfrom sigmoid carcinomas as they have different natural histories, prognostic features, and treatment. Use \nFigures 19\u20134, 19\u20135, Table 19-13, and the descriptions to identify specimens. Isolated portions of the \nascending, descending, and sigmoid colon cannot be distinguished by morphologic features.\nTABLE 19\u201312.\u2003\nRELEVANT CLINICAL HISTORY - COLON\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR COLON SPECIMENS\nOrgan/tissue resected or biopsied\nInflammatory bowel disease (type, history of dysplasia)\nPurpose of the procedure\nInherited polyposis syndromes (including familial \nadenomatous polyposis, hereditary non-polyposis \ncolon cancer, and Peutz-Jeghers syndrome, see \nTable 7-50)\nGross appearance of the organ/tissue/lesion sampled\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\n\u2192 pedunculated polyp or ulcerated mass\nPrior surgery/biopsies - results\nColonic bleeding\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic appearance of tissues)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_356.png", "summary": "The page provides guidelines for processing gastrointestinal specimens, specifically focusing on the removal and processing of colon polyps. It also discusses the importance of identifying colon segments in large resections.", "questions": [ "What are the key steps involved in processing colon polyps?", "How can the presence of cautery artifact be utilized in identifying surgical margins of polyps?", "Why is it important to accurately identify colon segments in large resections?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 357, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n339\nTYPICAL SPECIMENS\nRectosigmoid.\u2002 To preserve the anal sphincter, only a limited amount of rectum can be resected. The \ntumor is usually very close to the distal end of the specimen, adjacent to the anal sphincter. The transi\u00ad\ntion from the sigmoid to the rectum is marked by the fusion of the longitudinal taenia coli of the sigmoid \nto form the complete outer longitudinal muscle sheath of the rectum. However, it is easier to mark the \ntransition to the rectum by identifying the end of the mesentery and the peritoneal serosal surface. Spe\u00ad\ncifically, the rectum is covered by peritoneum on its anterior and lateral sides in the upper third, only \nthe anterior aspect in the middle third, and has no peritoneum over the lower third. The point at which \nthe peritoneal covering no longer completely surrounds the bowel segment is the rectosigmoid junction. \nIn the gross description and in the final report, state the location of the tumor within the specimen (i.e., \n\u201csigmoid,\u201d \u201crectal,\u201d or \u201crectosigmoid junction\u201d).\nThe distance to the closest, usually distal, margin is important to document. Immediate examination \nafter excision (before the colon contracts) is optimal. The length of this margin may be used to decide \nwhether post-surgical radiation therapy is required.\nRight Colectomy.\u2002 This specimen consists of terminal ileum (which may be very short, only 1 to 2 \ncm, but is invariably present), cecum (has a wider lumen than the remainder of the colon), appendix (may \nhave been removed by previous surgery), and a variable length of ascending colon. The ileocecal valve is \nused as a landmark for measurement of the lengths of the ileum and colon. The proximal portion of the \nascending colon may be retroperitoneal; the distal portion is on a mesentery. The transverse colon has a \nmesentery and is usually not included in the resection.\nTransverse Colon.\u2002 This is the only portion of the colon with omentum. The omentum is some\u00ad\ntimes submitted separately. The transverse colon is entirely intraperitoneal (i.e., surrounded by visceral \n\u00adperitoneum/serosa).\nSmall\nLarge\nTrim sides\nTrisect section with stalk\nBisect\nStalk section\nSide sections\nFigure 19\u20133.\u2002 Polypectomies.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_357.png", "summary": "The text provides detailed information on typical gastrointestinal specimens, including the rectosigmoid, right colectomy, and transverse colon, and emphasizes the importance of documenting tumor location and margin distance.", "questions": [ "How is the transition from the sigmoid to the rectum marked in a rectosigmoid specimen?", "Why is it important to document the location of the tumor within the specimen?", "What is the significance of the length of the closest margin in deciding post-surgical radiation therapy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 358, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n340\nA-P (Abdominoperineal) Resections.\u2002 This specimen consists of perianal skin, anus, and rectum, \nand may include sigmoid. This procedure is used to resect low tumors of the rectum and anal tumors \nlocated at or near the anal \u00adsphincter.\nThe anus is a complex structure that is usually 3 to 4 cm in length, and is demarcated by the proxi\u00ad\nmal and distal margins of the internal sphincter muscle.3 The luminal surface is marked proximally by \nlongitudinal folds (the rectal columns) that interface with distal folds (the anal columns) at the zone of \ntransition from colonic to anal mucosa (the pectinate or dentate line). Anal papillae are raised projections \nof anal mucosa that extend upward on the rectal columns. Between the rectal columns are depressions \ntermed rectal sinuses. The anal columns are linked circumferentially at the dentate line by transverse \nplicae, known as anal or semilunar valves that delineate the anal crypts. Although prominent in young \npersons, they may be indistinct or absent in adults.\nThere are many different definitions of what constitutes the anal canal. The surgical definition is the \none most widely accepted and is used by the AJCC. It is based on clinically identifiable landmarks that \nare difficult to define in surgical specimens. The start of the anal canal is defined as the point where the \nrectum enters the puborectalis sling at the apex of the anal sphincter complex, which can be palpated \nclinically as the anorectal ring. By this definition, the upper portion of the anal canal is lined by 1 to 2\u00a0cm \nof rectal-type glandular mucosa and transitional (cloacogenic) mucosa (if present) at the dentate line (anal \ntransition zone), and the lower portion by the non-keratinized squamous epithelium that extends to the \nperianal hair-bearing skin. On the anal papillae, the squamous and columnar mucosa interface directly.\nBowel Rings.\u2002 Separate specimen(s) of small rings of colon, sometimes on a plastic rod, may be \nreceived. These are the products of a stapler that creates the surgical anastomosis. These rings represent \nthe true margins of the specimen. Examine them for lesions and submit representative sections. Make \nsure that the submitted tissue does not contain staples or suture material.\nTotal Colectomy with Ileoanal Pull-Through Reconstruction (Performed for Ulcerative \nColitis or Familial Adenomatous Polyposis).\u2002 The specimen includes terminal ileum to rectum and \na \u00adsecond specimen designated \u201crectal mucosa.\u201d The subdivisions of the total colectomy specimen \n(ileum, cecum, colon, and rectum) are identified and described as above. To perform the pull-through, \nTransverse colon\nMesentery\nHaustra\nTaenia coli\nIleum\nCecum\nAppendix\nPeritoneal reflection\nAnus\nSquamocolumnar junction\nRectum\nOmentum\nEpiploic\nappendages\nDescending\ncolon\nAscending\ncolon\nFigure 19\u20134.\u2002 Gross anatomy of the colon.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_358.png", "summary": "The page discusses gastrointestinal specimens related to colon surgeries, including abdominoperineal resections and total colectomy with ileoanal pull-through reconstruction.", "questions": [ "What are the key components of an abdominoperineal resection specimen?", "How is the anal canal defined in surgical specimens?", "What is the significance of examining bowel rings in colon specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 359, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n341\nthe surgeon dissects the rectal mucosa off the internal anal sphincter along the plane of the submucosa, \ngenerating an unoriented and \u00adtraumatized collar of rectal tissue that is submitted as a separate speci\u00ad\nmen. The muscularis propria (i.e., the \u201csphincter\u201d) is not removed. One representative section of this \nlatter specimen is submitted.\nRectal Resections.\u2002 Small tumors of the rectum may be resected transanally without removing an \nentire circumferential segment, in order to preserve the sphincter. The specimens are usually small and \nA\nB\nD\nRight colectomy\n Lesion in cecum\nTransverse colectomy\n Lesion in center\nTerminal ileum\nAppendix\nLesion\nAbdominoperineal resection\n Lesion in rectum\nLevator ani\nmuscle\nExternal anal sphincter\nmuscle\nRectum\nC\nRectosigmoid\nLesion close to distal rectal margin\nLesion\nMesentery present\nLesion\nRectosigmoid junction\n(mesentery ends at rectum)\nFigure 19\u20135.\u2002 Common colon resections.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_359.png", "summary": "The page discusses the dissection of rectal mucosa during colon surgeries and the preservation of the sphincter in rectal resections.", "questions": [ "How is the rectal mucosa dissected during colon surgeries?", "Why is the preservation of the sphincter important in rectal resections?", "What are the different types of colon resections mentioned in the figure?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 360, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n342\nconsist of an ovoid \u00adfragment of mucosa, submucosa, and superficial muscularis propria consisting almost \nentirely of tumor with a 1 to 2 mm rim of uninvolved mucosa around the tumor. The normal mucosa may \ncurl under and may be difficult to see. Careful orientation, inking, fixation, and evaluation of all margins \nby taking perpendicular sections are very important to evaluate the completeness of the excision.\nPROCESSING RESECTION SPECIMENS\nSee sections below for specific instructions depending on the underlying disease process.\n 1.\t \u0007Identify and record the components of the colon present. Palpate the specimen to identify the location \nof mass lesions. If no mass lesions are present, open the specimen along the antimesenteric border \nusing blunt scissors. If a mass lesion is present, cut through an area of uninvolved mucosa and wall.\nFor some specimens, primarily with diverticular disease, inflation of the bowel segment with forma\u00ad\nlin is advantageous, followed by further dissection (see the section \u201cDiverticulosis\u201d).\nClean the lumen using saline. Record the dimensions of each of the components of the specimen \n(length and circumference) including length of mesentery and size of omentum if present. If a mass \nlesion or stricture is present, document any dilation of the lumen proximal to the lesion. Record the \nbowel wall thickness and any variation in thickness (e.g., tumor, stricture, or muscular hypertrophy \nassociated with diverticulosis).\n 2.\t \u0007Identify and describe any lesions (see special sections below). The distance of lesions (especially inva\u00ad\nsive carcinomas) from margins is noted.\nBowel segments may contract as much as 40% within 10 to 20 minutes of resection.4 Therefore, \nmargins are best measured as soon as possible after excision. The distal margin of rectal carcinomas is \ntypically short (due to the desire to avoid resecting the anal sphincter) and the length of this margin \nmay indicate the need for postoperative radiation therapy (e.g., if this margin is <2 cm in length).\n 3.\t \u0007Tumor cases: Identify all lymph nodes present. The fat can be stripped off the colon and placed in \nBouin\u2019s. HOWEVER, leave the fat at the deep margin of tumors intact and do not strip the fat in cases \nof diverticulosis (this maneuver will also remove the base of the diverticula). Soft tissue nodules in con\u00ad\ntinuity with the main tumor mass must be described as such and submitted in designated cassette(s). \nIf there is no histologic evidence of residual lymph node, such nodules are usually best interpreted as \ndirect spread of tumor. Well-circumscribed soft tissue nodules with a smooth outer contour that are \nseparate from the main tumor mass are classified as nodal metastasis, even in the absence of definitive \nnodal architecture.\nThe number of lymph nodes present will depend on the length of the specimen. At least twenty \nshould be present in an entire colectomy. In segmental resections, at least 12 (the minimum number \nconsidered necessary for accurate staging) are usually present (see Chapter 27, \u201cLymph Nodes for \nTABLE 19\u201313.\u2003\nGROSS FEATURES OF COLON SEGMENTS\nCOLON SEGMENTS\nSEROSA\nTAENIA COLI\nEPIPLOIC APPENDAGES\nMESENTERY\nOMENTUM\nIleum\nPresent\nAbsent\nAbsent\nPresent\nAbsent\nAppendix\nPresent\nPresent\nPresent or absent\nPresent\nAbsent\nCecum\nPresent\nPresent\nAbsent\nAbsent\nAbsent\nAscending colon\nPresent\nPresent\nPresent\nPresent or absent\nAbsent\nTransverse colon\nPresent\nPresent\nPresent\nPresent\nPresent\nDescending colon\nPresent\nPresent\nPresent\nPresent or absent\nAbsent\nSigmoid\nPresent\nPresent\nPresent\nPresent\nAbsent\nRectum\nAbsent\nAbsent\nAbsent\nAbsent\nAbsent\nAnus\nAbsent\nAbsent\nAbsent\nAbsent\nAbsent\nTaenia coli: Three longitudinal bands of muscle.\nHaustra: Sacculation of wall due to taenia coli.\nEpiploic appendages: Pouches of peritoneum filled with fat.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_360.png", "summary": "The page discusses the processing of gastrointestinal specimens, specifically the colon, emphasizing the importance of careful orientation, inking, fixation, and evaluation of margins to assess the completeness of excision.", "questions": [ "What are the key steps involved in processing resection specimens of the colon?", "Why is it important to identify and describe any lesions in the colon specimens?", "How does the presence of lymph nodes in colon specimens impact the diagnosis and staging of tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 361, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n343\nTumor Staging\u201d). If fewer than 12 nodes are identified, re-examine the tissue and submit any areas \nthat may \u00adrepresent small nodes. Lymph nodes in colon specimens tend to be small (<0.5 cm) even \nwhen involved by metastatic disease.\nThere may be prognostic significance if the metastases are present in proximal or distal lymph \nnodes with respect to the tumor. If the specimen can be oriented (e.g., right colectomy, rectosigmoid \ncolectomy, obstructing tumors with obvious proximal dilation of the bowel lumen, or as oriented by \nsurgeon), lymph nodes can be examined as separate groups. Strip the fat as above but keep proximal \nand distal soft tissue in separate containers. Identify lymph nodes in cassettes as \u201cdistal\u201d or \u201cproximal.\u201d\nNon-tumor cases: Abnormal lymph nodes (enlarged, hard) must be diligently sought after and \nsubmitted for examination. Occasionally tumors will be first discovered by \u00adunsuspected lymph node \nmetastases. However, it is not necessary to extensively search for and document at least 12 nodes. \nOnly one block of the largest nodes found may be submitted. However, if carcinoma is present after \nmicroscopic examination, all nodes should be retrieved and \u00adsubmitted.\n 4.\t \u0007Pin the colon out on a paraffin block. Float upside down in formalin overnight.\n 5.\t \u0007Submit sections including representative sections of all components present (e.g., ileum, appendix, \nascending colon, sigmoid, rectum) and all lesions (including polyps) present. Submit at least one repre\u00ad\nsentative block from grossly uninvolved colon mucosa (this can also serve as a margin if grossly \u00adnormal). \nSubmit sections of margins that are within 5 cm of the carcinoma. Grossly normal margins that are \nmore than 5 cm from the carcinoma need not be submitted. Submit all lymph nodes (see \u00adearlier).\nSPECIAL STUDIES\nHereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome): HNPCC is an \nautosomal-dominant disorder due to mutations in DNA repair genes, present in 0.1% of the popu\u00ad\nlation. There is an 80% lifetime risk for colorectal cancer and a 60% lifetime risk for endometrial \ncancer. HNPCC accounts for 2% to 5% of all colon carcinomas. Intensive surveillance and more \nextensive surgery can improve outcomes. Family members may be at risk and can be tested for the \ngene. 95% of HNPCC patients have germ-line mutations in two genes involved in mismatch DNA \nrepair: hMSH2 (human mutS homolog 2) and hMLH1 (human mutL homolog 1). Other mutations \nare in hPMS1, hPMS2, hMSH6, as well as others. These mutations result in high microsatellite \ninstability (MSI-H).\nClinical features typical of HNPCC:\n\t \u2022\t \u0007Young age (mean age 42 years compared to 65 for sporadic tumors), women > men\n\t \u2022\t \u0007Right sided carcinomas more common than left\n\t \u2022\t \u0007Multiple synchronous or metachronous tumors\n\t \u2022\t \u0007Extracolonic tumors: stomach, small bowel, biliary tract, pancreas, urothelium, kidney, ovarian, \nendometrial, brain tumors, sebaceous adenomas, and keratoacanthomas\n\t \u2022\t \u0007Better prognosis than sporadic carcinomas (fewer regional or distant metastases)\n\t \u2022\t \u0007Better response to anti-metabolic chemotherapy than to alkylating agents\nPathologic features typical of MSI-H (may vary with specific mutations):\n\t \u2022\t \u0007Large bulky tumors (often T3) with pushing borders.\n\t \u2022\t \u0007Prominent tumor-infiltrating lymphocytes (approximately 3 or more per HPF). These are distin\u00ad\nguished from Crohn-like peritumoral infiltrates consisting of lymphoid aggregates or follicles at the \nedge of the tumor.\n\t \u2022\t \u0007Medullary growth pattern.\n\t \u2022\t \u0007High-grade tumor cells with necrosis, mucin production, or signet ring cell features\n\t \u2022\t \u0007Diploid DNA content\n\t \u2022\t \u0007Absence of hMSH2, hMLH1, PMS2, MSH6 and other gene products confirmed by immunohisto\u00ad\nchemisty \u2013 PCR assays are also used to detect microsatellite instability. Approximately 10 to 20% \nof sporadic tumors have inactivation of the same genes by methylation of the promoter (most com\u00ad\nmonly in hMLH1). These carcinomas also have similar clinical, histologic, and prognostic features \nand can be identified by immunohistochemistry or PCR assays.\n\t \u2022\t \u0007MSI-H positive colon carcinomas often have reduced CK20 positivity compared to microsatellite \nstable (MSS) cases (Table 19-14).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_361.png", "summary": "The page discusses the examination of colon specimens, including the importance of identifying lymph nodes, submitting sections of all components present, and special studies related to hereditary non-polyposis colorectal cancer (HNPCC).", "questions": [ "How should abnormal lymph nodes be handled in non-tumor cases?", "What are the clinical features typical of HNPCC?", "What are the implications of identifying metastases in proximal or distal lymph nodes with respect to the tumor?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 362, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n344\nThe Revised Bethesda criteria developed to identify individuals with HNPCC recommend testing \ncolorectal carcinomas for microsatellite instability in the following cases:\n \n1.\t \u0007Colorectal carcinoma diagnosed in a patient younger than 50 years.\n \n2.\t \u0007Presence of synchronous, metachronous, or other HNPCC-associated tumors in patients of any age.\n \n3.\t \u0007Colorectal cancer with MSI-H pathologic features in a patient younger than 60 years.\n \n4.\t \u0007Colorectal cancer in one or more first-degree relatives with an HNPCC-related tumor, with one \nof the cancers being diagnosed at younger than 50 years.\n \n5.\t \u0007Colorectal cancer diagnosed in two or more first- or second-degree relatives with HNPCC-related \ntumors, regardless of age.\nGROSS DIFFERENTIAL DIAGNOSIS\nDiverticulosis of the descending colon and sigmoid is a common disease and is resected after multiple \nepisodes of diverticulitis (Fig. 19-6 and Box 19-1). The \u00admuscularis propria becomes markedly hypertro\u00ad\nphied (presumably due to long-term straining at stool) resulting in a thickened bowel wall and a narrowed \nlumen. The increased intraluminal pressure causes herniation of mucosa through weak points in the \nmuscularis propria adjacent to the penetrating vasculature on either side of each taenia coli. These are \nfalse diverticula because they lack a complete muscular coat. True diverticula (e.g., Meckel diverticulum \nor a solitary cecal diverticulum) have a complete muscle coat and are thought to be congenital in origin.\nThe best demonstration of diverticula requires inflating an intact specimen with formalin. Close off \nthe ends with hemostats or twine and fix overnight. Open along the antimesenteric side or hemisect. The \nfat should not be stripped from the specimen, as this will also remove the diverticula.\nA metal probe can be used to find the ostia of the diverticula. Count the number of diverticula or \nestimate the number if there are many. Sections of diverticula can be obtained by cutting in the plane \nFigure 19\u20136.\u2002 Cross-section of bowel showing diverticulosis.\nBOX 19\u20131.\u2003 Linguistic note\nThe plural form of diverticulum is \u201cdiverticula,\u201d not diverticuli or diverticulae as is commonly believed (look it up in your \ndictionary! Or see in Chapter 2, \u201cA Classical Interlude.\u201d).\nTABLE 19\u201314.\u2003\n\u0007MSI-H VERSUS MSS COLON CARCINOMA\nCYTOKERATIN PATTERN\nMSI-H\nMSS\nCK7\ue05d/CK20+\n55%\n77%\nCK7+/CK20+\n14%\n14%\nCK7\ue05d/CK20\ue05d\n27%\n9%\nCK7+/CK20\ue05d\n4%\n0%\nData from McGregor DK, et al: Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability, Am J Surg \nPathol 28:712, 2004.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_362.png", "summary": "The Revised Bethesda criteria recommend testing colorectal carcinomas for microsatellite instability in specific cases. Diverticulosis of the descending colon and sigmoid is a common disease with distinct characteristics.", "questions": [ "What are the criteria for testing colorectal carcinomas for microsatellite instability?", "What distinguishes false diverticula from true diverticula?", "How can diverticula be best demonstrated in a specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 363, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n345\nof the probe. Sample areas of interdiverticular mucosa (two to three sections) to look for superimposed \ndiverticulosis-associated colitis, inflammatory bowel disease or ischemia.\nIf the history is of diverticulitis or there is gross evidence of perforation (induration of pericolonic fat, \na serosal exudate, hemorrhage, pericolonic necrosis), the perforated diverticulum should be identified. \nProbe the diverticula in the most inflamed area and cut cross sections. A perforated diverticulum will \nshow effacement of the mucosa associated with necrosis and hemorrhage in the surrounding soft tissue. \nIf the wall of the diverticulum can be seen, then it is not perforated and it is just an adjacent diverticulum \nsurrounded by the inflammation. Submit sections of all diverticula that appear to be inflamed. Peritonitis \nwithout a documented site of perforation can be a medical emergency because the perforation is presum\u00ad\nably still within the patient.\nSolitary Cecal Diverticulum presents with symptoms of acute appendicitis. However, at surgery \nthe appendix appears normal and a pericecal abscess is found. Often a right colectomy is performed. A \nsolitary cecal diverticulum is thought to be congenital in origin (it is a true diverticulum with a complete \nmuscular wall), is usually located within a few centimeters of the ileocecal valve, and has a broad orifice \n(as opposed to the narrow orifices of diverticulosis).\nVascular Ectasia (Angiodysplasia)\u2002 This is a degenerative acquired lesion of older adults (>60 years) \nand usually presents as bleeding from the cecum or ascending colon. Clinical arteriography may reveal \nbleeding from an area of ectatic vessels, and embolization is sometimes attempted. The lesion consists of \nmultiple small (5 to 10 mm) areas of ectatic thin-walled vessels in the submucosa and mucosa that rupture \nand bleed. The pathogenesis is thought to be obstruction of veins passing through the muscularis propria \ndue to high wall tension in the right colon (Laplace\u2019s law predicts the highest wall tension in the area of \ngreatest bowel diameter).\nThe specimen is usually unrevealing grossly because bleeding has usually been controlled at the time \nof surgery. There may be small petechial hemorrhages or areas of congestion or, commonly, there are no \nmucosal lesions. The area most often affected is near the cecum and the first 10 cm of ascending colon. \nTake sections of any mucosal lesions. If no lesions are visible, on the outer surface of the specimen the \nmajor vessels tied off with sutures can be located. If sections near these vessels are examined, large dilated \nvessels traversing the muscularis propria are sometimes identified.5,6\nInflammatory Bowel Disease.\u2002 Segments of bowel may be removed in Crohn disease due to com\u00ad\nplications (e.g., strictures, fistulas), or a total colectomy may be performed for long-standing UC due to \nthe increased risk of carcinoma.\nUlcerative colitis and Crohn disease can be distinguished in resected segments of bowel by their gross \nfeatures (Table 19-15; Fig. 19-7). Typically, segments of large or small bowel involved by Crohn dis\u00ad\nease will not lie flat when opened due to the transmural inflammation and thickening of the bowel wall. \nMesenteric fat also surrounds a greater portion of the bowel circumference (\u201ccreeping substitution\u201d). In \ncontrast, since UC involves only the mucosa, the bowel will flatten out once opened, similar to normal \nnoninflamed bowel.\nThe pattern of mucosal involvement is an important feature to distinguish UC (which has continu\u00ad\nous involvement) from colonic Crohn disease (which can have discontinuous involvement). Sequential \nsections are taken at every 10 cm (including both normal and abnormal appearing mucosa) to deter\u00ad\nmine whether the involvement is continuous or patchy. Additional sections of any raised, \u00adpolypoid \nareas, or areas of flat mucosa with velvety, villiform, or granular areas are taken, as these gross find\u00ad\nings may indicate areas of dysplasia or early carcinoma. A mass lesion (mass, plaque-like region, \npolyp, or group of polyps) associated with microscopic dysplasia is associated with an increased \nrisk of \u00adcarcinoma \u00ad(dysplasia-associated lesion or mass = DALM). These lesions are described as to \nwhether they \u00adresemble an adenoma (which can possibly be treated with local excision) or do not \nresemble an adenoma (e.g., broad-based, irregular, associated with a stricture \u2013 may be best treated \nwith \u00adcolectomy).\nGross mucosal disease (aphthous ulcers) at or near (within 1 cm) of the surgical margins of resections \nfor Crohn disease is very useful in determining the likelihood of recurrence after surgery. Microscopic \ninvolvement alone (e.g., a single crypt abscess) does not predict recurrence. Gross ulcers present at or \nnear the margins predict a 100% probability of recurrence. Grossly nonulcerated margins have a 50% \nrisk of recurrence. However, the amount of normal tissue required for adequate margins is controversial \n(see in Chapter 6, \u201cEvaluation of Colon Specimens in the OR Consultation Room\u201d).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_363.png", "summary": "The text discusses various gastrointestinal specimens, including colon specimens, focusing on diverticulosis, vascular ectasia, and inflammatory bowel disease.", "questions": [ "What are the key features to look for in a perforated diverticulum during examination?", "How does a solitary cecal diverticulum differ from diverticulosis?", "What is the pathogenesis of vascular ectasia and how is it typically managed?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 364, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n346\nResections for UC are always \u201ccomplete\u201d (i.e., all colonic mucosa is removed leaving the proximal \nmargin in the small intestine). A section from the ileal mucosal margin, designated \u201cproximal mucosal \nmargin,\u201d is submitted.\nSpecimen integrity is better preserved if longitudinal, rather than transverse, sections are taken. Good \nperpendicular sections of the wall are taken after fixation to help determine wall thickness. The appendix \nis sampled if present.\nLymph nodes must be searched for and carefully evaluated because of the increased risk of carcinoma \nassociated with inflammatory bowel disease. These cancers can occur in young patients and may be dif\u00ad\nficult to detect by biopsy due to the extensive inflammatory changes of the mucosa.\nPolyposis Syndromes.\u2002 Affected patients may have tens to thousands of colonic polyps. Total colec\u00ad\ntomy is performed to prevent the development of colon carcinoma. The specimen is carefully examined \nto look for any lesions suspicious for invasion. All polyps greater than 1 cm in size are sampled. Rep\u00ad\nresentative samples from smaller polyps are taken as one section per quadrant (four sections for a total \ncolectomy). Lymph nodes are identified and abnormal nodes submitted for histologic examination.\nTABLE 19\u201315.\u2003\n\u0007GROSS FEATURES OF INFLAMMATORY BOWEL DISEASE IN COLONIC \nRESECTIONS\nGROSS FEATURES\nULCERATIVE COLITIS\nCROHN DISEASE\nDistribution\nStarts in rectum and spreads proximally. Dis\u00ad\ncontinuous cecal/appendiceal involvement \nis rarely present (~ 10%).\nFocal involvement with skip lesions; \nright > left.\nDepth of inflammation\nMucosal and submucosal\nMucosal, submucosal, or transmural\nMucosal lesions\nIrregular geographic ulcers. Adjacent mucosa \nis hyperemic with an inflammatory exu\u00ad\ndate. The mucosa may become atrophic.\nLinear serpiginous ulcers connected \nby transverse ulcers (= cobble\u00ad\nstoning*). The adjacent mucosa is \nrelatively normal in appearance.\nPseudopolyps\nMay be present.\nMay have mucosal bridges.\nMay be present.\nMay have mucosal bridges.\nBowel wall\nNot involved or may be fibrotic in late stages.\nMay be relatively normal or thickened \nand \u00adedematous.\nCreeping substitu\u00ad\ntion**\nAbsent\nOften present\nStrictures\nUsually absent\nOccasionally present\nInternal fistulas\nUsually absent\nMay be present\nFissuring\nUsually absent\nCommon, but may be absent.\nIleal Involvement\nPresent in <10% of patients (\u201cbackwash ileitis\u201d \nof distal 2 to 3 cm), with mild superficial \nactive mucosal inflammation only.\nPresent in 50% of patients, often \nstenotic.\nRectal involvement\nPresent in all patients, but may appear mini\u00ad\nmal due to prior enema therapy.\nPresent in 15% of patients.\nAnal involvement\nPresent in 5% to 10% of patients, may have a \nperianal fistula.\nPresent in 75% of patients; fissures, fis\u00ad\ntulas, and ulcerations are common.\nCarcinoma\nIncreased risk.\nIncreased risk.\n*The use of the term \u201ccobblestone appearance\u201d should be avoided because this term is imprecise and is used to describe different findings by \n\u00adclinicians, radiologists, and pathologists. Depending on the way it is used, it may be associated either with Crohn disease or with UC. Be descriptive \nin the gross dictation. If linear and transverse ulcers are present, describe them as such. If pseudopolyp formation is present (i.e., islands of normal \nmucosa surrounded by ulcerated areas) describe them accordingly.\n**Extension of fat onto antimesenteric surface.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_364.png", "summary": "The page discusses the handling and examination of gastrointestinal specimens, particularly in cases of ulcerative colitis and polyposis syndromes.", "questions": [ "How are specimens from patients with ulcerative colitis processed differently than those from patients with polyposis syndromes?", "Why is it important to carefully examine lymph nodes in cases of inflammatory bowel disease?", "What are the key differences in gross features between ulcerative colitis and Crohn disease?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 365, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n347\nTumors.\u2002 The description includes:\n\t \u2022\t \u0007Size\n\t \u2022\t \u0007Appearance: The typical colonic adenocarcinoma is firm, tan/pink, and has raised serpentine bor\u00ad\nders with an ulcerated center (Fig. 19-8). Mucinous tumors may produce lakes of gelatinous mucin \nwithin the tumor mass or bowel wall.\n\t \u2022\t \u0007Anatomic depth of invasion (e.g., into or through the muscularis propria).\n\t \u2022\t \u0007Location. If the specimen includes sigmoid colon and rectum, describe the location of the carcinoma \nwith respect to the mesentery (i.e., sigmoid, junction of sigmoid and rectum, or rectal).\nA\nB\nCrohn disease\nUlcerative colitis\nSerpiginous ulcers\nPseudopolyps\nSkip area\n(normal mucosa)\nSkip area\n(normal \nmucosa)\nThickened wall\nNormal wall thickness\nFigure 19\u20137.\u2002 Inflammatory bowel disease.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_365.png", "summary": "This page discusses the description of tumors in the colon, including size, appearance, depth of invasion, and location.", "questions": [ "What are the typical characteristics of a colonic adenocarcinoma?", "How do mucinous tumors differ in appearance from other types of colon tumors?", "Why is it important to describe the location of the carcinoma with respect to the mesentery?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 366, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n348\n\t \u2022\t \u0007Distance from margins including deep or serosal margin. The radial margin represents the adven\u00ad\ntitial (i.e., non-peritonealized) soft tissue margin closest to the deepest penetration of tumor. This \nmargin is significant for rectal carcinomas and for colon carcinomas penetrating into the mesentery. \nThis margin is not significant for colon carcinomas invading into adipose tissue on the antimesen\u00ad\nteric side of the bowel unless the carcinoma penetrates the visceral peritoneum. For segments of \ncolon that are completely surrounded by a peritonealized (serosal) surface (e.g., transverse colon), \nthe only circumferential/radial margin is the mesenteric resection margin.\n\t \u2022\t \u0007Distance from anatomical landmarks such as ileocecal valve, rectosigmoid junction, squamocolum\u00ad\nnar \u00adjunction)\n\t \u2022\t \u0007Percent of circumference occupied by tumor and minimal luminal diameter at the site of the tumor \n(if the lesion is obstructing, describe the dilation of the proximal colon)\n\t \u2022\t \u0007Presence or absence of perforation - there may be induration of surrounding fat, a purulent exudate, \nand adhesions to other serosal surfaces.\nWhile the specimen is fresh, ink the radial margin at the site of the tumor. The remainder of the fat \ncan be stripped and placed into Bouin\u2019s to aid in searching for lymph nodes. It may be useful to separate \nproximal from distal lymph nodes (see above).\nPrimary vs. Metastatic Carcinomas to the Colon.\u2002 The epicenter of a primary tumor is usually \nlocated in the mucosa and submucosa and the intraluminal component predominates. Sections from the \nedge of a primary tumor often reveal continuity with the remainder of the mucosa and association with a pre-\nexisting adenoma. The epicenter of metastatic tumors is usually in pericolonic fat (because the tumor origi\u00ad\nnates in a focus of lymphatic spread). The tumor may then invade through the muscularis propria and erode \nthrough the overlying mucosa. Metastatic carcinomas usually have the appearance of erupting upwards from \nbelow and may ulcerate the mucosal surface without an exophytic component. Findings consistent with a \npre-existing polyp are not present, although carcinomas can sometimes grow for a distance along the surface.\nRecurrent Colon Carcinoma.\u2002 Carcinomas occasionally recur at a prior colonic resection site. The \nmucosa heals without scarring and the anastomosis is not grossly evident on the surface. However, surgi\u00ad\ncal staples may be present and history will support the location of the carcinoma at the prior surgical site.\nFigure 19\u20138.\u2002 Gross appearance of colon carcinoma.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_366.png", "summary": "The page discusses important considerations for evaluating gastrointestinal specimens, specifically colon carcinomas, including distance from margins, anatomical landmarks, tumor characteristics, and distinguishing between primary and metastatic carcinomas.", "questions": [ "What is the significance of the radial margin in rectal and colon carcinomas?", "How can the presence or absence of perforation be identified in a colon carcinoma specimen?", "What are the differences in the epicenter and appearance of primary vs. metastatic carcinomas in the colon?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 367, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n349\nMelanosis Coli.\u2002 The colonic mucosa is dark brown in color due to accumulation of pigment in lam\u00ad\nina propria histiocytes. The right colon is involved more frequently than the left. This finding is second\u00ad\nary to chronic laxative ingestion and is generally an incidental finding.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Tumor: Four or fewer of the tumor, including relationship to adjacent mucosa (in-situ changes may \nreveal a pre-existing adenoma or exclude metastasis from another site), deepest extent of invasion, \nand any involvement of contiguous organs.\n\t \u2022\t \u0007Other lesions: Representative of all other lesions (e.g., polyps)\n\t \u2022\t \u0007Diverticula: One representative section. If resection was for diverticulitis, submit one section of the \nperforated diverticulum\n\t \u2022\t \u0007Inflammatory bowel: Sequential sections, every 10 cm, including all unusual, raised, or polypoid \ndisease lesions and areas of grossly normal-appearing mucosa.\n\t \u2022\t \u0007Lymph nodes: All lymph nodes from tumor cases (see Chapter 27). Submit nodes so that the total \nnumber of positive nodes can be determined (e.g., by inking with different colors). If proximal and \ndistal nodes have been separated, submit in separate identified cassettes. If cancer is not present, \nsubmit all abnormal lymph nodes.\n\t \u2022\t \u0007Surgical margins: Proximal and distal margins and the deep margin or serosal surface. The \nmargins may be taken en face if the tumor is far from the margin. If the tumor is close to the \nmargin, the section is taken perpendicular to the margin and through the tumor (if possible). \nIf the tumor is \u22655 cm from the margin, sections need not be submitted if the mucosal surface \nappears normal.\n\t \u2022\t \u0007Normal structures: Any normal components that have not been sampled in the sections already \n(for example, in a right colectomy the margins are usually a sample of normal colon and ileum but \none should also submit a section of the appendix).\nSAMPLE DICTATION FOR TUMORS\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201ccolon\u201d is a 35 cm in length seg\u00ad\nment of rectosigmoid colon which is 6 cm in circumference at the sigmoid margin and 3 cm in circumfer\u00ad\nence at the rectal margin. A 6 cm in length mesentery is present along the 32 proximal cm of the colon \nand is absent from the distal 3 cm. There is a 2.5 \u00d7 3 \u00d7 2 cm tan/pink centrally ulcerated tumor with \nserpiginous borders arising 1 cm distal to the rectosigmoid junction. The tumor invades into, but not \nthrough, the muscularis propria. The tumor spares only 0.5 cm of the colon circumference and the lumen \nis narrowed to approximately 0.5 cm in diameter. The proximal colon is markedly dilated. The tumor is \n1 cm from the distal margin and 32 cm from the proximal margin. The remainder of the mucosal surface \nis unremarkable. Ten firm lymph nodes are present in the pericolonic soft tissue, the largest measuring \n0.6 cm in greatest dimension.\nCassette #1-2: Tumor at area of deepest invasion and deep margin, 2 frags, ESS.\nCassette #3: Tumor and adjacent mucosa, 1 frag, RSS.\nCassette #4: Distal margin and tumor, perpendicular, 1 frag, RSS.\nCassette #5-9: Lymph nodes, two per cassette, 10 frags, ESS.\nSAMPLE DICTATION FOR DIVERTICULITIS\nThe specimen is received fresh in two parts, labeled with the patient\u2019s name and unit number.\nThe first part labeled \u201ccolon\u201d consists of a segment of colon (12 cm in length by 3 cm in circumfer\u00ad\nence with one stapled margin and one open margin). The bowel wall is markedly thickened and there are \nfive diverticula. The tip of one diverticulum is perforated and is surrounded by a green-yellow purulent \nexudate which also covers the adjacent serosal surface. There is a 0.4 cm pedunculated polyp which is 4 \ncm from the closest margin (stapled). Three lymph nodes are found in the pericolonic fat.\nCassette #1: Area of perforation, 1 frag, RSS.\nCassette #2: Nonperforated diverticulum, 1 frag, RSS.\nCassette #3: Polyp, 2 frags, ESS.\nCassette #4: Three lymph nodes (inked black, blue, and green), 5 frags, ESS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_367.png", "summary": "Melanosis Coli is a dark brown discoloration of the colonic mucosa due to pigment accumulation in histiocytes, often associated with chronic laxative use.", "questions": [ "What is the significance of melanosis coli in terms of patient health?", "How does the presence of melanosis coli impact the interpretation of other colonic lesions?", "What are the key considerations for sampling and examining gastrointestinal specimens for tumors?", "How does the dictation for tumors in the colon specimen provide important information for pathology analysis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 368, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n350\nThe second part labeled \u201crings\u201d consists of two ring-shaped sections of colonic mucosa with tan/\nbrown normally appearing mucosa. One ring is attached to a 5 cm green plastic rod.\nCassette #5: Representative mucosa from both rings, 2 frags, RSS.\nSAMPLE DICTATION FOR INFLAMMATORY BOWEL DISEASE\nThe specimen is received in two parts, labeled with the patient\u2019s name and unit number.\nThe first part labeled \u201ctotal colectomy\u201d consists of a total colectomy specimen extending from the \nterminal ileum (4 cm in length \u00d7 4 cm in circumference), cecum with appendix (appendix 5 cm in length \n\u00d7 0.8 cm in diameter), and colon (100 cm in length \u00d7 5 cm circumference). The mucosal surface over the \ndistal 50 cm is dusky red and has multiple ulcers and pseudopolyp formation. No skip lesions are seen \ngrossly. The remainder of the proximal mucosa is tan/brown and unremarkable. The bowel wall is thin \nand the distribution of the adipose tissue is normal. The ulcerations extend to the distal margin. Twenty \nlymph nodes are found in the pericolic fat, the largest measuring 0.8 cm in size.\nCassettes #1-10: Sequential sections of colon from distal to proximal, every 10 cm, 10 frags, RSS.\nCassette #11: Terminal ileum, margin, 1 frag, RSS.\nCassette #12: Appendix, 2 frags, RSS.\nCassette #13: Two largest lymph nodes (one inked in black), 4 frags, ESS.\nCassettes #14-19: Three lymph nodes per cassette, 18 frags, ESS.\nThe second part labeled \u201crectum\u201d consists of a mucosal segment measuring 10 cm in length by 4 cm \nin circumference. The mucosal surface is brown/red and irregular with effacement of the normal mucosal \nsurface. The mucosal changes extend throughout the length of the specimen. No muscularis propria is \npresent.\nCassette #20: Representative sections from one end, 2 frags, RSS.\nCassette #21: Representative sections from opposite end, 2 frags, RSS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR COLON AND RECTAL CARCINOMAS\n\t\u2022\t \u0007Specimen: Terminal ileum, cecum, appendix, ascending colon, transverse colon, descending colon, \nsigmoid colon, rectum, anus\n\t\u2022\t \u0007Procedure: Right hemicolectomy (terminal ileum, colon, and appendix), transverse colectomy, left \nhemicolectomy, sigmoidectomy, rectal/rectosigmoid colon (low anterior resection), total abdominal \ncolectomy, abdominoperineal resection (sigmoid colon, rectum, and anus), total proctocolectomy (ter\u00ad\nminal ileum, colon, appendix, and rectum), transanal disk excision\n\t\u2022\t \u0007Specimen Length: Give length of each segment of colon present in cms, if applicable\n\t\u2022\t \u0007Tumor Site: Ileocecal valve, cecum, right (ascending) colon, hepatic flexure, transverse colon, splenic \nflexure, left (descending) colon, sigmoid, rectosigmoid, rectum, anus\n\t\u2022\t \u0007Tumor Configuration: Exophytic (pedunculated or sessile), endophytic (ulcerative), diffusely infil\u00ad\ntrative (linitis plastica)\n\t\u2022\t \u0007Tumor Size: Greatest dimension in cm (other dimensions optional)\n\t\u2022\t \u0007Macroscopic Tumor Perforation: Not identified, present\n\t\u2022\t \u0007Macroscopic Intactness of Mesorectum: Not applicable, complete, near complete, incomplete; \nevaluates the completion of resection of rectal tumors (Box 19-2)\n\t\u2022\t \u0007Histologic Type: Adenoma, adenocarcinoma, signet ring cell carcinoma (>50% signet ring cells), \nmucinous (colloid) adenocarcinoma (>50% mucinous), undifferentiated (no gland formation), \nmedullary, small cell, squamous cell carcinoma, all others rare. The WHO Classification may be \nused.\n\t\u2022\t \u0007Histologic Grade: Low grade (well to moderately differentiated, \u226550% gland formation) or high \ngrade (poorly differentiated to undifferentiated, <50% gland formation) (see later)\n\t\u2022\t \u0007Histologic Features Suggestive of Microsatellite Instability\n\t\u2022\t \u0007Intratumoral Lymphocytic Response (tumor-infiltrating lymphocytes): None, mild to moderate \n(0 to 2 lymphocytes per HPF), marked (\u22653 lymphocytes per HPF)\n\t\u2022\t \u0007Peritumor Lymphocytic Response (Crohn-like response): None, mild to moderate, marked\n\t\u2022\t \u0007Tumor Subtype and Differentiation: Mucinous tumor component (specify percentage that is muci\u00ad\nnous), medullary tumor component, high histologic grade (poorly differentiated)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_368.png", "summary": "The page describes gastrointestinal specimens, specifically focusing on colon specimens from patients with inflammatory bowel disease. It details the macroscopic appearance of the specimens and the corresponding cassettes for processing.", "questions": [ "What are the key components of the colon specimen received for a patient with inflammatory bowel disease?", "How are the cassettes labeled and what sections are included in each for processing?", "What are the pathologic prognostic/diagnostic features checklist items for colon and rectal carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 369, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n351\n\t\u2022\t \u0007Microscopic Tumor Extension: Intraepithelial carcinoma (including invasion into lamina propria) \n(Tis), invasion into submucosa (T1), invasion into muscularis propria (T2), invasion through muscula\u00ad\nris propria into pericolorectal tissues (T3), penetration to surface of visceral peritoneum (T4a), direct \ninvasion or adherence to other organs or structures (T4b). A measurement of the depth of invasion is \nsometimes used for rectal carcinomas.\n\t \u2022\t \u0007Invasion into another segment of the colorectum by way of the serosa or mesocolon is classified \nas T4b. Invasion into another segment of colorectum by growth along the bowel wall (e.g., a cecal \ncarcinoma extending into the ileum) would not be sufficient for classification as T4.\n\t \u2022\t \u0007Perforation of visceral peritoneum is defined using the following criteria:\n \n(1)\t \u0007Tumor present at the serosal surface with inflammatory reaction, mesothelial hyperplasia, and/\nor erosion/ulceration\n \n(2)\t \u0007Free tumor cells on the serosal surface (in the peritoneum) with underlying ulceration of the \nvisceral peritoneum\n\t\u2022\t \u0007Margins: Proximal, distal, serosal, circumferential (radial) margin (for rectal carcinomas), mesenteric, \ndistance to margin. Anastomotic recurrences are rare if the distance is >5 cm. A distal margin less than \n2 cm for a rectal carcinoma may be an indication for radiation therapy.\n\t \u2022\t \u0007The distance of a rectal carcinoma from the radial margin may be important for rectal carcinomas.\n\t \u2022\t \u0007The margins for a noncircumferential transanal disk excision include all the sides of the specimen.\n\t \u2022\t \u0007Margins should be evaluated for adenomatous changes, intramucosal carcinoma, and invasive carci\u00ad\nnoma.\n\t \u2022\t \u0007Colon segments contract after excision. Distances to margins are best determined while the speci\u00ad\nmen is fresh, immediately after excision.\n\t \u2022\t \u0007The distance of a carcinoma from a nonperitonealized surface (the radial/circumferential or mes\u00ad\nenteric margin) predicts local recurrence if positive or <0.1 cm. This includes if carcinoma within a \nlymph node is close to this margin. This margin should be considered negative if >0.1 cm.\n\t\u2022\t \u0007Treatment Effect: No prior treatment, present. If present, give degree of response:\n\t \u2022\t \u0007Grade 0: No residual carcinoma\n\t \u2022\t \u0007Grade 1: Minimal residual carcinoma, moderate response\n\t \u2022\t \u0007Grade 2: Minimal response\n\t \u2022\t \u0007Grade 3: No definite response, poor response\n\t \u2022\t \u0007Note specific location of acellular mucin pools in wall and margins. These are not considered to be \nresidual carcinoma.\n\t \u2022\t \u0007Postchemotherapy inflammatory changes include fibrosis, obliterative vasculopathy, telangiectasia, \ncellular atypia, active inflammation, ulceration\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present, indeterminate\nBOX 19\u20132.\u2003 Evaluation of the mesorectal envelope\nComplete excision of the rectum and surrounding tissues decreases the risk of local recurrence. The extent of resection \ncan be determined by gross evaluation of the nonperitonealized surface of the specimen. The entire specimen is scored \naccording to the worst area.\nIncomplete\n\t\u2022\t \u0007Little bulk to the mesorectum\n\t\u2022\t \u0007Defects in the mesorectum down to the muscularis propria\n\t\u2022\t \u0007After transverse sectioning, the circumferential margin appears very irregular.\nNearly complete\n\t\u2022\t \u0007Moderate bulk to the mesorectum\n\t\u2022\t \u0007Irregularity of the mesorectal surface with defects > 0.5 cm, but none extending to the muscularis propria\n\t\u2022\t \u0007No areas of visibility of the muscularis propria except at the insertion site of the levator ani muscles\nComplete\n\t\u2022\t \u0007Intact bulky mesorectum with a smooth surface\n\t\u2022\t \u0007Only minor irregularities of the mesorectal surface\n\t\u2022\t \u0007No surface defects > 0.5 cm in depth\n\t\u2022\t \u0007No coning towards the distal margin of the specimen\n\t\u2022\t \u0007After transverse sectioning, the circumferential margin appears smooth\nFrom Hermanek P, Hermanek P, Hohenberger W, Klimpfinger M, Kockerling F, Papadopoulos T: The pathological assessment of \nmesorectal excision: implications for further treatment and quality management, Int J Colorectal Dis;18(4):335-41, 2003.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_369.png", "summary": "This page discusses the microscopic tumor extension, margins, treatment effect, and lymph-vascular invasion in gastrointestinal specimens, specifically focusing on colon specimens.", "questions": [ "How is the depth of invasion classified for rectal carcinomas?", "What are the criteria for defining perforation of visceral peritoneum?", "Why is it important to evaluate margins for adenomatous changes, intramucosal carcinoma, and invasive carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 370, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n352\n\t\u2022\t \u0007Perineural Invasion: Not identified, present, indeterminate\n\t\u2022\t \u0007Tumor Deposits: Not identified, present, indeterminate\n\t \u2022\t \u0007Carcinomas found away from the main tumor and not associated with a lymph node are likely \nsatellite tumors due to lymph-vascular invasion or perineural invasion. These are not counted as \nmetastases to lymph nodes but are considered \u201cdiscontinuous extramural extension.\u201d The number \nof tumor deposits should be recorded. If the lymph nodes are free of carcinoma, then this finding \nis reported as N1c.\n\t\u2022\t \u0007Type of Polyp (in which invasive carcinoma arose): Tubular adenoma, villous adenoma, tubulovil\u00ad\nlous adenoma, traditional serrated adenoma, sessile serrated adenoma, hamartomatous polyp\n\t\u2022\t \u0007Additional Pathologic Findings: Adenoma, chronic ulcerative proctocolitis, Crohn disease, dysplasia \narising in inflammatory bowel disease, other polyps\n\t\u2022\t \u0007Ancillary Studies: Microsatellite instability (immunohistochemistry, DNA studies), mutational analy\u00ad\nsis (BRAF V600E, KRAS)\n\t\u2022\t \u0007Regional Lymph Nodes: Number of positive nodes, number of nodes examined, presence of extra\u00ad\ncapsular invasion, specify location or \u201capical\u201d if designated by surgeon\n\t \u2022\t \u0007All nodes should be examined (preferably, at least 12). If fewer than 12 nodes are found, additional \ntechniques to identify lymph nodes and additional tissue sampling should be considered.\n\t \u2022\t \u0007Tumor nodules in pericolonic/perirectal fat without histologic evidence of residual lymph node tis\u00ad\nsue are classified as \u201ctumor deposits.\u201d\n\t\u2022\t \u0007Tumor border configuration\n\t \u2022\t \u0007Not assessed, pushing type (expansile, uniformly smooth), or irregular (infiltrative, streaming dis\u00ad\nsection), mixed (Box 19-3)\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Tables 19-16 \nand 19-17). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/\u2009\u2009) and the ADASP (see www.adasp.org\u2009). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR ANAL CARCINOMAS\n\t\u2022\t \u0007Specimen: Anus, anorectal junction, rectum, sigmoid\n\t\u2022\t \u0007Procedure: Abdominoperineal resection (sigmoid colon, rectum, anus), transanal disk excision\n\t\u2022\t \u0007Tumor Site: Anus, anorectal junction, rectum. Rectum, anal canal, relationship to squamocolumnar \njunction, anterior wall\n\t\u2022\t \u0007Tumor size: Greatest dimension (T1 \u2264 2 cm; T2 > 2 but \u2264 5 cm; T3 > 5 cm) (other dimensions \noptional)\n\t\u2022\t \u0007Specimen Length: Give length of anus, rectum, and colon present in centimeters.\nBOX 19\u20133.\u2003 Diagnostic criteria for an infiltrative border of colorectal carcinoma\nNaked eye examination of a microscopic slide of the tumor border\n\t\u2022\t \u0007Inability to define limits of invasive border of tumor and/or\n\t\u2022\t \u0007Inability to resolve host tissue from malignant tissue\nMicroscopic examination of the tumor border\n\t\u2022\t \u0007\u201cStreaming dissection\u201d of muscularis propria (dissection of tumor through the full thickness of the \nmuscularis propria without stromal response) and/or\n\t\u2022\t \u0007Dissection of mesenteric adipose tissue by small glands or irregular clusters of cords of cells and/\nor perineural invasion\nData from Jass J, Ajioka Y, Allen JP, Chan YF, Cohen RJ, Nixon JM, et al. Assessment of invasive growth pattern and lymphocytic \ninfiltration in colorectal cancer. Histopathology 28:543-548, 1996 and Jass JR: Lymphocytic infiltration and survival in rectal \ncancer, J Clin Pathol 39:585-589, 1986.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_370.png", "summary": "The page provides detailed information on the assessment and classification of gastrointestinal specimens, particularly focusing on colon cancer.", "questions": [ "What are the different types of polyps in which invasive carcinoma can arise?", "Why is it important to record the number of tumor deposits in colon cancer specimens?", "How is the presence of distant metastasis determined in colon cancer specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 371, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n353\nTABLE 19-16.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF COLON AND RECTAL CARCINOMAS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ: intraepithelial or invasion of lamina propria*\nT1\nTumor invades submucosa\nT2\nTumor invades muscularis propria\nT3\nTumor invades through the muscularis propria into pericolorectal tissues\nT4a\nTumor penetrates to the surface of the visceral peritoneum*\nT4b\nTumor directly invades or is adherent to other organs or structures\u2020,\u2021\n*Tis includes cancer cells confined within the glandular basement membrane (intraepithelial) or mucosal lamina propria (intramucosal) with no \nextension through the muscularis mucosae into the submucosa.\n\u2020Direct invasion in T4 includes invasion of other organs or other segments of the colorectum as a result of direct extension through the serosa, as \nconfirmed on microscopic examination (e.g., invasion of the sigmoid colon by a carcinoma of the cecum) or, for cancers in a retroperitoneal or sub\u00ad\nperitoneal location, direct invasion of other organs or structures by virtue of extension beyond the muscularis propria (i.e., respectively, a tumor \non the posterior wall of the descending colon invading the left kidney or lateral abdominal wall; or a mid or distal rectal cancer with invasion of \nprostate, seminal vesicles, cervix, or vagina).\n\u2021Tumor that is adherent to other organs or structures, grossly, is classified cT4b. However, if no tumor is present in the adhesion, microscopically, \nthe classification should be pT1-4a depending on the anatomical depth of wall invasion.\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis*\nN1\nMetastasis in 1-3 regional lymph node(s)\nN1a\nMetastasis in 1 regional lymph node\nN1b\nMetastasis in 2-3 regional lymph nodes\nN1c\nTumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal \ntissues without regional nodal metastasis\nN2\nMetastasis in 4 or more regional lymph nodes\nN2a\nMetastasis in 4-6 regional lymph nodes\nN2b\nMetastasis in 7 or more regional lymph nodes\nNote: A satellite peritumoral nodule in the pericolorectal adipose tissue of a primary carcinoma without histologic evidence of residual lymph \nnode in the nodule may represent discontinuous spread, venous invasion with extravascular spread (V1/2), or a totally replaced lymph node \n(N1/2). Replaced nodes should be counted separately as positive nodes in the N category, whereas discontinuous spread or venous invasion \nshould be classified and counted in the site-specific factor category of Tumor Deposits (TD).\n*Nodes with isolated tumor cells (single cells or small clusters of cells not more than 0.2 mm in greatest diameter) are classified as N0 (i+) and \nmicrometastases (> 0.2 mm but \u22642 mm) are classified as N1mi.\nRegional lymph nodes for the anatomic subsites of the colon and rectum are as follows:\nCecum: anterior cecal, posterior cecal, ileocolic, right colic\nAscending colon: ileocolic, right colic, middle colic\nHepatic flexure: middle colic, right colic\nTransverse colon: middle colic\nSplenic flexure: middle colic, left colic, inferior mesenteric\nDescending colon: left colic, inferior mesenteric, sigmoid\nSigmoid colon: inferior mesenteric, superior rectal sigmoidal, sigmoid mesenteric\nRectosigmoid: perirectal, left colic, sigmoid mesenteric, sigmoidal, inferior mesenteric, superior rectal, middle \nrectal", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_371.png", "summary": "This page provides the AJCC classification of colon and rectal carcinomas, detailing the primary tumor stages and regional lymph node metastasis stages.", "questions": [ "What are the different stages of primary tumor invasion in colon and rectal carcinomas according to the AJCC classification?", "How is regional lymph node metastasis classified in colon and rectal carcinomas?", "What is the significance of tumor deposits in the context of regional lymph node metastasis staging?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 372, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Colon\n354\nTABLE 19\u201316.\u2003\n\u0007AJCC (7TH EDITION) CLASSIFICATION OF COLON AND RECTAL \nCARCINOMAS\u2014cont\u2019d\nRectum: perirectal, sigmoid mesenteric, inferior mesenteric, lateral sacral, presacral, internal iliac, sacral prom\u00ad\nontory, superior rectal, middle rectal, inferior rectal\nMetastases to nonregional lymph nodes (e.g., external iliac, para-aortic) should be classified as distant metastases \n(M1).\nMETASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nM1a\nMetastasis confined to one organ or site (e.g., liver, lung, ovary, nonregional node)\nM1b\nMetastases in more than one organ/site or the peritoneum\nThis staging system should not be used for carcinoid tumors. Appendiceal tumors have separate staging systems. \nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Com\u00ad\nmittee on Cancer (AJCC), Chicago, Illinois. This list also incorporates recommendations for reporting from the AJCC (Compton C, Fenoglio-Preiser \nCM, Pettigrew N, Fielding LP, American Joint Committee on Cancer Prognostic Factors Consensus Conference, Colorectal Working Group, Cancer \n88:1739-1757, 2000).\nREGIONAL LYMPH NODES\nTABLE 19\u201317.\u2003\nAJCC GRADE\nGX\nGrade cannot be assessed\nG1\nWell differentiated\nG2\nModerately differentiated\nG3\nPoorly differentiated\nG4\nUndifferentiated\nThe AJCC recommends using a two-tiered system:\n\u2002 1.\u2002 Low grade (G1-G2)\n\u2002 2.\u2002 \u0007High grade (G3-G4)\nSome authors suggest that G4 lesions be identified separately because they may represent a small subgroup of carcinomas that are very \n\u00adaggressive.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \u00ad\nCommittee on Cancer (AJCC), Chicago, Illinois.\n\t\u2022\t \u0007Histologic Type: Squamous cell carcinoma, adenocarcinoma, mucinous adenocarcinoma, small cell \ncarcinoma, other rare types\n\t\u2022\t \u0007Histologic Grade: Well, moderately, poorly, or undifferentiated (Table 19-18)\n\t\u2022\t \u0007Microscopic Tumor Extension: In situ, invasion into lamina propria, invasion into muscularis \nmucosae, invasion into submucosa, invasion into sphincter muscle, invasion into muscularis pro\u00ad\npria, invasion into subserosa, invasion into perianal or perirectal soft tissue, invasion into adjacent \nstructures. A measurement of the depth of invasion may be used as a prognostic factor for rectal \ncarcinomas.\n\t\u2022\t \u0007Margins: Uninvolved (distance to closest margin), involved\n\t \u2022\t \u0007Specify proximal, distal, and radial (circumferential) margin.\n\t \u2022\t \u0007Specify if it is carcinoma in situ or invasive carcinoma at the margin.\n\t\u2022\t \u0007Treatment Effect: No prior treatment, prior treatment. If there was prior treatment, give degree \nof response:\n\t \u2022\t \u0007Grade 0: Complete response, no viable tumor cells\n\t \u2022\t \u0007Grade 1: Moderate response, single cells or small groups of tumor cells", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_372.png", "summary": "The page provides information on the AJCC classification of colon and rectal carcinomas, including metastasis, regional lymph nodes, histologic grade, and other relevant factors.", "questions": [ "What are the different categories of distant metastasis according to the AJCC classification?", "How does the AJCC recommend grading the histologic type of colon and rectal carcinomas?", "Why is it important to specify the margins and treatment effect in the pathology report?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 373, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Appendix\n355\n\t \u2022\t \u0007Grade 2: Minimal response, residual tumor outgrown by fibrosis\n\t \u2022\t \u0007Grade 3: No definite response, poor response, extensive residual tumor\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present, indeterminate\n\t\u2022\t \u0007Perineural Invasion: Not identified, present, indeterminate\n\t\u2022\t \u0007Tumor Configuration: Polypoid, exophytic, infiltrative, ulcerating, other\n\t\u2022\t \u0007Regional Lymph Nodes: Present or absent, number of nodes examined, number with metastases, \nlocation (perirectal, inguinal, internal iliac), size, presence of extracapsular invasion, specify location or \n\u201capical\u201d if designated by surgeon\n\t \u2022\t \u0007Carcinomas of the anal canal usually metastasize to the anorectal and perirectal nodes.\n\t \u2022\t \u0007Carcinomas of the anal margin metastasize to superficial inguinal nodes.\n\t\u2022\t \u0007Additional Findings: Condyloma acuminatum, Paget disease, dysplasia, Crohn disease\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (see Table \n19-19). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nAPPENDIX\nAppendices are generally removed due to acute appendicitis, occasionally \u201cincidentally\u201d during opera\u00ad\ntions for other reasons, and as part of a right colectomy.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record dimensions (length, diameter including range), color (tan/pink, gray/green), external surface \n(edematous, fibrinous exudate, hyperemia, purulence, perforations, hemorrhagic (may be seen in \nendometriosis).\nIf the mesoappendix is present, record dimensions, color, appearance (edema, fibrinous exudate, \n\u00adpurulence).\n 2.\t \u0007Make a longitudinal section of the tip, just long enough to fit into a cassette. The serosal side may be \ninked to orient the tip for embedding. The remainder of the appendix is sectioned at 3 mm intervals \n(Fig. 19-9).\nTABLE 19\u201318.\u2003\nHISTOLOGIC GRADE OF ANAL ADENOCARCINOMAS\nGrade X\nGrade cannot be assessed\nGrade 1\nWell differentiated (>95% of tumor composed of glands)\nGrade 2\nModerately differentiated (50% to 95% of tumor composed of glands)\nGrade 3\nPoorly differentiated (<49% of tumor composed of glands)\nGrade 4\nUndifferentiated\nSmall cell carcinomas and tumors with no differentiation or minimal \u00addifferentiation that is only present in rare small foci (classified as WHO \n\u00adundifferentiated \u00adcarcinomas) are categorized as grade 4.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_373.png", "summary": "The page provides information on grading, invasion, metastasis, and additional findings in gastrointestinal specimens, specifically focusing on anal carcinomas. It also outlines the AJCC classification and the importance of reporting specific elements in cancer-directed surgical resection specimens.", "questions": [ "What are the different grades used to assess anal adenocarcinomas?", "How do carcinomas of the anal canal and anal margin differ in terms of lymph node metastasis?", "Why is it important to include specific elements in reports of cancer-directed surgical resection specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 374, "text": "356\nGASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Appendix\nSx-xxx\nSx-xxx\nFigure 19\u20139.\u2002 Appendectomies.\nTABLE 19-19.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF ANAL CARCINOMAS*\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ (Bowen disease, high-grade squamous intraepithelial lesion [HSIL], anal \nintraepithelial neoplasia II-III [AIN II-III])\nT1\nTumor 2 cm or less in greatest dimension\nT2\nTumor more than 2 cm but not more than 5 cm in greatest dimension\nT3\nTumor more than 5 cm in greatest dimension\nT4\nTumor of any size with invasion of adjacent organ(s), e.g., vagina, urethra, bladder*\n*Direct invasion of the rectal wall, perirectal skin, subcutaneous tissue, or the sphincter muscle(s) is not classified as T4.\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in perirectal lymph node(s)\nN2\nMetastasis in unilateral internal iliac and/or inguinal lymph node(s)\nN3\nMetastasis in perirectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal \nlymph nodes\nRegional lymph nodes include perirectal (anorectal, perirectal, and lateral sacral), internal iliac (hypogastric), and inguinal (superficial and deep). \nAll other lymph node groups are considered distant metastasis.\nMETASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: Carcinomas arising at the junction of the hair-bearing skin and mucous membrane of the anal canal are staged as skin cancers. This clas\u00ad\nsification is only used for carcinomas. Melanomas, sarcomas, and carcinoid tumors are not included.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_374.png", "summary": "This page provides the AJCC classification of anal carcinomas, detailing the staging criteria for primary tumor, regional lymph nodes, and distant metastasis.", "questions": [ "What are the different stages of primary tumors in anal carcinomas according to the AJCC classification?", "How is regional lymph node metastasis classified in anal carcinomas?", "What is the significance of distant metastasis in the staging of anal carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 375, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Appendix\n357\n 3.\t \u0007Record the thickness of the wall, the diameter of the lumen (dilated, fibrosed, constricted), the condi\u00ad\ntion of the mucosa (glistening, ulcerated, hyperemic), and the contents of the lumen:\n\t \u2022\t \u0007Fecalith\n\t \u2022\t \u0007Foreign body (e.g., seeds, gallstone calculus)\n\t \u2022\t \u0007Purulence or blood (acute appendicitis)\n\t \u2022\t \u0007Parasites (Oxyuris vermicularis)\n\t \u2022\t \u0007Mucin \u2013 may be associated with a mucocele or a mucinous neoplasm (check for mucinous implants \non serosa)\n\t \u2022\t \u0007Fibrous obliteration\n 4.\t \u0007Submit one longitudinal section of the tip and two transverse sections (one near the resec\u00ad\ntion margin and one near the tip), including any abnormalities seen (perforations, ulcerations, \n\u00adserositis).\nIf there is mucin accumulation in the lumen (i.e., a possible cystadenoma or cystadenocarcinoma) or an \narea suspicious for tumor, submit the entire appendix and submit the resection margin in a separate cassette.\nIf the appendectomy was performed for appendicitis, and the appendix is grossly normal, the entire \nspecimen must be submitted.\nGROSS DIFFERENTIAL DIAGNOSIS\nAppendicitis is usually apparent as a purulent exudate on the serosal surface of the appendix, often \nwith a gross perforation. More subtle cases may appear edematous or may not be grossly apparent. \n\u00adSurgeons may be incorrect in up to 7% of cases of acute appendicitis (both false-positive and false-\u00ad\nnegative clinical diagnoses). Thus, histologic confirmation is useful for clinical management after \nappendectomy.\nNeuroendocrine Tumors (e.g., carcinoid, tubular or goblet cell carcinoid, crypt cell carcinoma) are \nusually found at the tip of the appendix. Carcinoids are found incidentally in one to six specimens out \nof 1000 appendectomies and are the most common appendiceal tumor. Small tumors are often difficult \nor impossible to see grossly because of their infiltrative growth pattern in the submucosa. The normal \narchitecture may be effaced. Large tumors may be firm, yellow to white, well circumscribed but not \nencapsulated, and usually look like a bulbous swelling of the tip.\nEndometriosis is not an uncommon finding in the appendix. Often the muscularis propria will appear \nto be markedly hypertrophied and areas of focal hemorrhage may be present.\nMucocele is seen as diffuse globular enlargement of the appendix which is filled with mucus. \u00adMucinous \ncystadenomas and mucinous cystadenocarcinomas have this same appearance.\nAdenocarcinoma of the appendix is rare and has the same gross appearance as a colonic adenocar\u00ad\ncinoma. Some tumors may perforate and present as acute appendicitis. These cases may be difficult to \ndistinguish from inflammation grossly.\nA Cecal Diverticulum (thought to be of congenital \u00adorigin) may present clinically as appendicitis. \nIntraoperatively, the surgeon finds a pericecal abscess with a normal appendix and a right colectomy is \nperformed. Search for the diverticulum in the proximal cecum with a metal probe \u2013 the probe will enter \nthe abscess cavity from the mucosal surface.\nSpecific Infections such as TB or Yersinia, are rarely causes of appendiceal inflammation but may be \nmore common in patients from outside the US. The gross appearance may be unremarkable or the same \nas for acute appendicitis.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cappendix,\u201d is a 5 cm in length \u00d7 \n0.9 cm in diameter appendix with attached mesoappendix (5 \u00d7 1 \u00d7 0.8 cm). There is a 0.3 cm in diameter \nperforation of the appendiceal wall, 1.5 cm from the tip. The serosal surface is dull and covered with \npurulent material. The mesoappendix is edematous, tan/brown, and has areas of focal hemorrhage. The", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_375.png", "summary": "The page discusses the examination and submission guidelines for gastrointestinal specimens, specifically focusing on the appendix. It highlights the importance of recording various characteristics and abnormalities, as well as differentiating between different pathologies such as appendicitis, neuroendocrine tumors, endometriosis, mucocele, and adenocarcinoma.", "questions": [ "What are the key characteristics that should be recorded when examining an appendix specimen?", "How can mucin accumulation in the lumen indicate potential pathologies like cystadenoma or cystadenocarcinoma?", "Why is histologic confirmation important in cases of acute appendicitis, even if the diagnosis is clinically suspected?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 376, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Appendix\n358\nmucosal surface is red/brown and ulcerated. There is a 0.5 \u00d7 0.5 \u00d7 0.5 cm brown friable fecalith in the \nlumen of the proximal appendix.\nCassette #1: longitudinal section of tip and proximal margin, 2 frags, RSS.\nCassette #2: cross sections including area of perforation, 4 frags, RSS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR APPENDICEAL CARCINOMAS\n\t\u2022\t \u0007Specimen: Appendix, cecum, right colon, terminal ileum\n\t\u2022\t \u0007Procedure: Appendectomy, right colectomy (terminal ileum, appendix, cecum, and ascending colon)\n\t\u2022\t \u0007Specimen Integrity: Intact, fragmented\n\t\u2022\t \u0007Specimen Length: Give length of each segment of colon and appendix in centimeters.\n\t\u2022\t \u0007Tumor Site: Proximal half of appendix (base involved or not involved), distal half of appendix, dif\u00ad\nfusely involving appendix\n\t\u2022\t \u0007Tumor Configuration: Ulcerative, polypoid, infiltrative\n\t\u2022\t \u0007Tumor Size: Greatest dimension (cm) (additional dimensions are optional)\n\t\u2022\t \u0007Histologic Type: Adenocarcinoma, signet ring cell carcinoma (> 50% signet ring cells), mucinous \n(colloid) adenocarcinoma (> 50% mucinous), undifferentiated (no gland formation), small cell carci\u00ad\nnoma, goblet cell carcinoid. The WHO Classification may be used.\n\t \u2022\t \u0007Note: The AJCC system for appendicial carcinomas is also used for goblet cell carcinoid tumors. \nThere is a separate system for carcinoid tumors.\n\t\u2022\t \u0007Histologic Grade: Well differentiated (> 95% gland formation; grade 1), moderately differentiated \n(50% to 95% gland formation; grade 2), poorly differentiated (5% to 50% gland formation; grade 3), \nundifferentiated (< 5% gland formation; grade 4)\n\t\u2022\t \u0007Microscopic Tumor Extension: Intraepithelial carcinoma (no invasion) (Tis), intramucosal car\u00ad\ncinoma (invasion into lamina propria) (Tis), invasion into submucosa (T1), invasion into muscu\u00ad\nlaris propria (T2), invasion through muscularis propria into the subserosa, or into mesoappendix, \nbut not to the serosal surface (T3), perforation of visceral peritoneum (including mucinous peri\u00ad\ntoneal tumor within the right lower quadrant) (T4a), direct invasion of other organs or structures \n(T4b).\n\t\u2022\t \u0007Regional Lymph Nodes: Number of positive nodes, number of nodes examined, presence of extra\u00ad\ncapsular invasion. Regional lymph nodes for the appendix are anterior cecal, posterior cecal, ileocolic, \nand right colic.\n\t\u2022\t \u0007Margins: Proximal margin, distal margin, circumferential (radial) margin, mesenteric, (give distance \nfrom mesenteric margin). If the distance is > 5 cm, histologic confirmation is not necessary.\n\t \u2022\t \u0007Margins should be evaluated for adenomatous changes and invasive carcinoma.\n\t\u2022\t \u0007Perforation of Bowel Wall: Present or absent, related to tumor or other process\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present, indeterminate\n\t\u2022\t \u0007Satellite Peritumoral Nodules: Not identified, present (give number)\n\t \u2022\t \u0007Irregular foci of carcinoma in periappendiceal adipose tissue are classified as \u201cdiscontinuous extra\u00ad\nmural extension\u201d and may be due to lymph-vascular invasion or perineural invasion. They are not \nclassified as lymph node metastases. If a focus of carcinoma has smooth borders and can be identified \nas a replaced lymph node, it is classified as a lymph node metastasis.\n\t\u2022\t \u0007Perineural Invasion: Not identified, present, indeterminate\n\t\u2022\t \u0007Additional Pathologic Findings: Inflammatory bowel disease (with or without dysplasia), appendici\u00ad\ntis, diverticulosis, carcinoid tumor (low-grade neuroendocrine tumor, if a carcinoma is also present), \nperforation (not due to tumor)\n\t\u2022\t \u0007Ancillary Studies: MSI testing, if performed. Only a few appendiceal carcinomas show MSI, and this \ntesting is not routinely recommended at this time.\n\t\u2022\t \u0007Distant Metastasis: Present, intraperitoneal metastasis beyond the right lower quadrant, including \npseudomyxoma peritonei, nonperitoneal metastasis. If distant metastasis is not present on pathologic \nexamination, the M category is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Tables 19-20 \nand 19-21). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_376.png", "summary": "The page provides information on the pathologic prognostic and diagnostic features checklist for appendiceal carcinomas, including specimen details, tumor characteristics, histologic grade, tumor extension, lymph node involvement, margins evaluation, and other relevant factors.", "questions": [ "What are the different histologic types of appendiceal carcinomas mentioned in the checklist?", "How is the AJCC system used for appendiceal carcinomas and goblet cell carcinoid tumors?", "What are the regional lymph nodes examined for appendiceal carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 377, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Hemorrhoids\n359\nTABLE 19-20.\u2003\n\u0007AJCC (7TH EDITION) CLASSIFICATION OF APPENDICEAL CARCINOMAS \n(INCLUDING GOBLET CELL CARCINOIDS)\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ: intraepithelial or invasion of lamina propria*\nT1\nTumor invades submucosa\nT2\nTumor invades muscularis propria\nT3\nTumor invades through the muscularis propria into subserosa or into mesoappendix\nT4a\nTumor penetrates visceral peritoneum, including mucinous peritoneal tumor within the right \nlower quadrant\nT4b\nTumor directly invades other organs or structures\u2020,\u2021\n*Tis includes cancer cells confined within the glandular basement membrane (intraepithelial) or lamina propria (intramucosal) with no extension \nthrough the muscularis mucosae into the submucosa.\n\u2020Direct invasion in T4 includes invasion of other segments of the colorectum, by way of the serosa, e.g., invasion of ileum.\n\u2021Tumor that is adherent to other organs or structures, grossly, is classified cT4b. However, if no tumor is present in the adhesion, microscopically, \nthe classification should be pT1-3 depending on the anatomical depth of wall invasion.\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in 1-3 regional lymph node(s)\nN2\nMetastasis in 4 or more regional lymph nodes\nNote: A satellite peritumoral nodule or tumor deposit (TD) in the periappendiceal adipose tissue of a primary carcinoma without histologic \nevidence of residual lymph node in the nodule may represent discontinuous spread (T3), venous invasion with extravascular spread (T3, V1/2), \nor a totally replaced lymph node (N1/2). Replaced nodes should be counted as positive nodes, whereas discontinuous spread or venous invasion \nshould be classified and counted in the site-specific factor (TD).\nMETASTASIS \nM0\nNo distant metastasis\nM1\nDistant metastasis\nM1a\nIntraperitoneal metastasis beyond the right lower quadrant, including pseudomyxoma \n\u00adperitonei\nM1b\nNonperitoneal metastasis\nCarcinoid tumors of the appendix have a separate staging system. However, goblet cell carcinoids are classified using the system for appendiceal \ncarcinomas. \nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.\nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nHEMORRHOIDS\nHemorrhoids are dilated veins of the hemorrhoidal plexus resected due to recurrent bleeding and \npain. The specimen consists of a local resection of anal mucosa and submucosa. Squamous cell car\u00ad\ncinomas, condylomata, tuberculosis, and nonspecific granulomas can sometimes be found inci\u00ad\ndentally in the adjacent anal tissue. Occasionally a fibroepithelial polyp will clinically mimic a \nhemorrhoid.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_377.png", "summary": "The page discusses the AJCC classification of appendiceal carcinomas, including goblet cell carcinoids, as well as the staging system for metastasis.", "questions": [ "What are the different stages of tumor invasion in appendiceal carcinomas according to the AJCC classification?", "How are regional lymph nodes classified in the staging of appendiceal carcinomas?", "What is the significance of the separate staging system for carcinoid tumors of the appendix?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 378, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Liver\n360\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record number of fragments and size of each one. Examine the anal mucosa carefully for any lesions. \nSerially section each fragment. Dilated vascular spaces with or without thrombosis can sometimes be \nseen grossly.\n 2.\t \u0007Submit one cassette of representative tissue. Submit additional cassettes to document any lesions seen.\nLIVER\nThe liver is involved by a wide variety of non-neoplastic, and less commonly, neoplastic dis\u00ad\neases. See Chapter 27 for processing of liver biopsies performed for staging of Hodgkin disease. \nBiopsies may be performed to evaluate a liver prior to transplantation. See Chapter 6 for more \ninformation.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 19-22.\nNeedle Biopsy\nNeedle biopsies are commonly used to assess liver diseases affecting hepatic function and are also used to \nevaluate liver masses (primary tumors or metastases). Scoring systems are available for chronic hepatitis \n(Table 19-23).\nTABLE 19-21.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF APPENDICEAL CARCINOID TUMORS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nTumor 2 cm or less in greatest dimension\nT1a\nTumor 1 cm or less in greatest dimension\nT1b\nTumor more than 1 cm but not more than 2 cm\nT2\nTumor more than 2 cm but not more than 4 cm or with extension to the cecum\nT3\nTumor more than 4 cm or with extension to the ileum\nT4\nTumor directly invades other adjacent organs or structures, e.g., abdominal wall and skeletal \nmuscle*\nNote: Tumor that is adherent to other organs or structures, grossly, is classified cT4. However, if no tumor is present in the adhesion, microscopi\u00ad\ncally, the tumor should be classified pT1-3 depending on the anatomical depth of wall invasion.\n*Penetration of the mesoappendix does not appear to be as important a prognostic factor as the size of the primary tumor and is not separately \ncategorized.\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nRegional lymph node metastasis\nMETASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Committee \non Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_378.png", "summary": "The page discusses processing liver specimens, including the importance of recording fragment details and examining for lesions. It also mentions the use of needle biopsies for assessing liver diseases and evaluating liver masses.", "questions": [ "What are the key steps involved in processing liver specimens?", "How are needle biopsies used in assessing liver diseases?", "What scoring systems are available for chronic hepatitis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 379, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Liver\n361\nPROCESSING THE SPECIMEN\n 1.\t \u0007Describe the specimen including color (tan/brown, white probably indicates capsular tissue or \ntumor), length, diameter, and whether the specimen appears fragmented (may indicate a cirrhotic \nliver).\n 2.\t \u0007Wrap in lens paper and submit in entirety. Trichrome, reticulin, and iron stains are often used in the \nevaluation.\nSPECIAL STUDIES\nHemochromatosis (Iron).\u2002 Iron stains show increased iron within hepatocytes. Fixed or unfixed tissue \nbiopsies may be used for quantitative iron assessment by a specialty laboratory.\nTABLE 19\u201323.\u2003\nGRADING AND STAGING OF LIVER SPECIMENS WITH CHRONIC VIRAL HEPATITIS\nSCORE\nGRADE OF NECROINFLAMMATORY ACTIVITY\nSTAGE OF FIBROSIS/CIRRHOSIS\nPortal Activity\nLobular Activity\n0\nNo portal inflammation\nNone\nNo fibrosis\n1\nPortal inflammation only, no/\nminimal piecemeal necrosis\nMinimal inflammation, no \nnecrosis\nEnlarged fibrotic portal tracts\n2\nMild piecemeal necrosis \n(some or all portal tracts)\nFocal hepatocyte necrosis\nPeriportal or portal to portal septa; \nno bridging\n3\nModerate piecemeal necrosis \n(all portal tracts)\nModerate, with multifocal \nnecrosis\nBridging fibrosis with architectural \ndistortion, no obvious cirrhosis\n4\nSevere piecemeal necrosis\nSevere with prominent diffuse \nnecrosis (may be bridging)\nCirrhosis\nGrade refers to the extent of current inflammation and can increase or decrease over time. The most severe degree of portal or lobular injury is graded.\nStage refers to the degree of fibrosis and is usually progressive over time; fibrosis may regress during antiviral therapy.\nSee references 7 and 8.\nTABLE 19\u201322.\u2003\nRELEVANT CLINICAL \u00adHISTORY \u2013 LIVER\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR LIVER SPECIMENS\nOrgan/tissue resected or biopsied\nViral hepatitis (A, B, or C)\nPurpose of the procedure\nHemochromatosis\nGross appearance of the organ/tissue/lesion sampled\nCirrhosis\nAny unusual features of the clinical presentation\nBile duct disease (e.g., liver fluke infection, obstruc\u00ad\ntion, jaundice)\nAny unusual features of the gross appearance\nLiver function tests, serum AFP\nPrior surgery/biopsies - results\nFamily history of liver tumors\nPrior malignancy\nPregnancy\nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic appearance of tissues)\n\u2192 drug use that can alter the histologic appearance \nof the liver\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_379.png", "summary": "The page focuses on processing and evaluating liver specimens, including special stains and studies. It also provides a grading and staging system for chronic viral hepatitis in liver specimens.", "questions": [ "How are liver specimens processed and evaluated?", "What special stains and studies are commonly used in the evaluation of liver specimens?", "Can you explain the grading and staging system for chronic viral hepatitis in liver specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 380, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Liver\n362\nWilson Disease (Copper).\u2002 Quantitative copper measurements may require that the specimen be \nacquired and handled with special equipment to avoid contamination of the specimen with trace metals. \nThe specialty laboratory should be contacted before processing such a specimen.\nSpecial stains for copper (rhodanine stain) or copper-associated protein (orcein stain) can be used to \nvisualize the abnormal copper stores within hepatocytes. These stains may also be positive in other dis\u00ad\neases, such as chronic biliary disorders.\nAcute Fatty Liver of Pregnancy, Reye\u2019s Syndrome, etc.\u2002 These diseases require the demonstration \nof microvesicular fat which is removed by routine processing. Oil Red O stains may be performed on fro\u00ad\nzen tissue sections that have been air dried (do not fix in methanol). EM can also be used. Because these \nare acutely ill patients and a timely diagnosis is clinically useful, a frozen section is generally preferable \nto EM studies.\nAlpha 1-Antitrypsin Deficiency.\u2002 PAS-positive, diastase-resistant, eosinophilic hyaline globules can \nbe seen in periportal hepatocytes in routinely fixed tissues.\nLymphoma.\u2002 Evaluation of the disease process using a cytologic preparation may be helpful \nbefore allocating tissue. If lymphoma is suspected, a portion of the tissue may be fixed in B5. The \nentire specimen should not be fixed in B5 because nonlymphoid markers may not be optimally pre\u00ad\nserved if (e.g., keratins). If a portion is frozen, histologic sections of the frozen tissue should always \nbe examined.\nLobectomy\nHepatocellular carcinomas may be treated with surgery but cholangiocarcinomas are rarely respectable. \nResections are more commonly performed for adenomas and focal nodular hyperplasia. An individual \nmetastasis from colon carcinoma also may be resected.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh and measure the specimen. Identify the cut surgical margins and the capsular surface. Assess \nthe overall appearance of the resected liver (e.g., normal homogeneous parenchyma with a smooth \ncapsule vs. the nodular and fibrotic appearance of a cirrhotic liver). Identify the vascular pedicle.\n 2.\t \u0007Section the specimen thinly at 0.5 cm to look for lesions.\n 3.\t \u0007Describe the size, location (with respect to the liver capsule and with respect to the surgical margins), \ncolor, and other gross features (central scar, hemorrhage, nodularity, bulging on cut section).\n 4.\t \u0007Describe the remainder of the liver parenchyma including color, presence of nodules (give range of \nsizes), congestion, fibrosis. Describe the appearance of the capsule (normal = thin, smooth and glisten\u00ad\ning; abnormal = thickened, nodular, adhesions, etc.).\nExamine major portal vein and hepatic vein structures for gross evidence of vascular invasion.\n 5.\t \u0007Take sections to demonstrate the lesion, nearby vasculature, cauterized margins, vascular margins, \nand uninvolved liver.\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Figure 19-10.\nFocal Nodular Hyperplasia (FNH).\u2002 Usually a solitary (but 20% are multiple) gray/white unencap\u00ad\nsulated nodule that may be located beneath the liver capsule. Most are <5 cm. On cut section there is a \nvery characteristic white depressed area of fibrosis with broad strands radiating out in a stellate configura\u00ad\ntion and prominent nodularity of the intervening parenchyma. The surrounding liver is most commonly \nnormal in appearance. An elastic stain on a section from the central scarred area helps to delineate the \nabnormal vasculature.\nAdenoma.\u2002 Usually a solitary, well-encapsulated mass with a homogeneous parenchyma that has a \nslightly different color from the adjacent normal parenchyma (yellow to tan/brown). Some can be quite \nlarge (up to 30 cm). They are usually located beneath the liver capsule, and some are pedunculated.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_380.png", "summary": "The page discusses the processing and evaluation of gastrointestinal specimens, specifically focusing on liver diseases such as Wilson Disease, Acute Fatty Liver of Pregnancy, and Alpha 1-Antitrypsin Deficiency.", "questions": [ "What special equipment and precautions are necessary for acquiring and handling specimens for quantitative copper measurements in Wilson Disease?", "How can abnormal copper stores within hepatocytes be visualized using special stains?", "Why is a frozen section generally preferable to electron microscopy studies in acutely ill patients with diseases like Acute Fatty Liver of Pregnancy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 381, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Liver\n363\nFocal nodular hyperplasia\nHepatic adenoma\nFibrolamellar carcinoma\nMicronodular cirrhosis\nHepatocellular carcinoma\nMetastatic colon carcinoma\nA\nB\nC\nD\nE\nF\nFigure 19\u201310.\u2002 Gross appearance of common liver lesions.\n\u00adHemorrhage and necrosis are common. Look carefully for gross vascular invasion or pale areas that \nwould suggest a well-differentiated carcinoma. The surrounding liver is usually normal in appearance. \nMost occur in young women and are related to oral contraceptive use.\nHepatocellular Carcinoma.\u2002 May consist of multiple nodules or a large infiltrating mass. Tumors are \nusually white/yellow with areas of punctate hemorrhage and necrosis, although bile-producing tumors \nmay be green. The surrounding liver parenchyma is often cirrhotic. Look for a \u201cnodule within a nodule\u201d. \nThis may represent an incipient carcinoma arising in a benign hyperplastic nodule.\nFibrolamellar carcinoma is an unusual variant but may be more likely to be resected because of its \nbetter prognosis. It usually presents as a single large mass that may have a capsule in a liver that is non-\ncirrhotic. The mass appears to be composed of smaller nodules (reminiscent of FNH).\nCholangiocarcinoma.\u2002 These carcinomas are often unresectable at presentation, so excisional speci\u00ad\nmens are very uncommon. Intrahepatic tumors are gray/white hard irregular masses.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_381.png", "summary": "The page discusses various common liver lesions including focal nodular hyperplasia, hepatocellular carcinoma, fibrolamellar carcinoma, and metastatic colon carcinoma. It also mentions the gross appearance of these lesions and their characteristics.", "questions": [ "What are some common liver lesions mentioned on this page?", "What is the typical appearance of hepatocellular carcinoma?", "Why are fibrolamellar carcinomas more likely to be resected?", "What is the significance of finding a 'nodule within a nodule' in hepatocellular carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 382, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Liver\n364\nExtrahepatic tumors may be nodular or flat and usually invade into the wall of the bile duct. Klatskin \n(hilar) tumors originate at the hepatic duct junction and spread along the biliary tree. The liver may be green \ndue to bile duct obstruction. The intrahepatic bile duct and distal extrahepatic bile duct margins must be \nevaluated.\nMetastatic Carcinoma.\u2002 Usually of colonic origin if resected. The tumor often appears as a circum\u00ad\nscribed necrotic mass with a central depression beneath the surface of the liver. Multiple lesions may be \npresent. The surrounding liver is usually normal in appearance. Margins are evaluated.\nPediatric Tumors.\u2002 Children are subject to a wider variety of liver lesions, including hepatoblasto\u00ad\nmas, infantile hemangioendothelioma, mesenchymal hamartomas, and undifferentiated \u201cembryonal\u201d \nsarcoma, as well as lesions also found in adults.9 At least one section per centimeter of greatest dimension \nof the tumor should be examined including all areas of differing appearance. Some tumors may have been \ntreated prior to resection with chemotherapy or embolization. Special studies are not needed for the \ndiagnosis of these tumors. However, since these tumors are rare, tissue should be saved for EM, frozen, \nand submitted for cytogenetic analysis if feasible.\n\t \u2022\t \u0007Hepatoblastoma: Essentially only occurs in infants. The tumor can be large (up to 25 cm) and is \nvariegated in appearance, with cysts, necrosis, and hemorrhage. The surrounding liver appears normal. \nTumor and normal tissue should be taken for snap-freezing and cytogenetic studies. There is a CAP \nprotocol for the reporting of hepatoblastomas in pediatric patients with details about processing speci\u00ad\nmens and reporting (see www.cap.org).\n\t \u2022\t \u0007Mesenchymal hamartoma: Presents in the first two years of life as a large circumscribed mass com\u00ad\nprised of multiple cystic spaces filled with clear fluid. Solid areas may be fibrous and white, myxoid, \nor resemble normal liver.\n\t \u2022\t \u0007Embryonal (undifferentiated) sarcoma: Most common between the ages of 6 and 10. The tumors \nare circumscribed and soft with a variegated solid and cystic appearance. Necrosis and hemorrhage \nmay be present.\nBile Duct Hamartomas (Meyenburg Complexes).\u2002 Usually multiple small (<0.5 cm) well-circum\u00ad\nscribed nodules on the surface of the liver. They are most commonly biopsied during laparotomy to \nexclude metastatic carcinoma. Bile may be present.\nBile Duct Adenomas (Peribiliary Gland Hamartomas).\u2002 Solitary lesions, usually <1 cm in size, \nlocated below the capsule. Like bile duct hamartomas, they are most commonly biopsied during lapa\u00ad\nrotomy to exclude carcinoma. They do not connect to the biliary system and do not contain bile.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Tumor: Four cassettes including relationship to liver capsule, capsule of tumor, relationship to \nother anatomic landmarks (e.g., large vessels).\n\t \u2022\t \u0007Margins: Representative sections of all margins at the closest approach of the tumor. Take vascular \nmargins if they can be identified.\n\t \u2022\t \u0007Uninvolved liver: Two cassettes of uninvolved liver parenchyma. Order reticulin, iron, and tri\u00ad\nchrome stains on one of the cassettes if diffuse liver disease is suspected clinically or grossly.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR LIVER TUMORS\n\t\u2022\t \u0007Specimen: Liver, gallbladder\n\t\u2022\t \u0007Procedure: Wedge resection, minor hepatectomy (three or more segments), major hepatectomy (less \nthan three segments), explanted liver\n\t\u2022\t \u0007Tumor Size: Size of greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Tumor Focality: Solitary (location), multiple (locations)\n\t\u2022\t \u0007Histologic Type: Hepatocellular carcinoma, cholangiocarcinoma, combined hepatocellular and chol\u00ad\nangiocarcinoma, fibrolamellar hepatocellular carcinoma, metastatic carcinoma, bile duct cystadeno\u00ad\ncarcinoma, other rare types. The WHO Classification is recommended.\n\t\u2022\t \u0007Histologic Grade: Well, moderately, poor, undifferentiated, or grades I to IV (Tables 19-24 and \n19-25)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_382.png", "summary": "The page discusses various types of liver tumors, including extrahepatic tumors, metastatic carcinoma, pediatric tumors, bile duct hamartomas, and bile duct adenomas.", "questions": [ "What are the characteristics of hepatoblastoma in infants?", "How are pediatric liver tumors different from those found in adults?", "What is the significance of evaluating the margins in liver tumor specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 383, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Liver\n365\nTABLE 19\u201324.\u2003\n\u0007GRADING OF HEPATOCELLULAR CARCINOMAS (EDMONDSON AND STEINER \nSYSTEM)\nCYTOPLASM\nNUCLEI\nN/C RATIO\nCOHESION\nCELL \nFUNCTION\nARCHITECTURE\nGrade I\nGranular and \nacidophilic\nSlightly \nabnormal\nNormal\nNormal\nBile fre\u00ad\nquent\nNormal\nGrade II\nGranular and \nacidophilic \nwith sharp \nand clear-cut \nborders\nLarger and \nmore \nhyper-\nchromatic\nHigher\nNormal\nBile fre\u00ad\nquent\nFrequent acini\nGrade III\nNot as granular \nand acidophilic\nLarger and \nmore \nhyper-\u00ad\nchromatic \nthan \nGrade\u00a0II\nHigher, \ntumor \ngiant \ncells \nmay be \npresent\nSome intra\u00ad\nvascular \nsingle \ncells\nBile less \nfrequent\nBreakup or \ndistortion of \nthe trabecular \npattern\nGrade IV\nVariable, often \nscanty, with \nfewer granules\nIntensely \nhyper-\u00ad\nchromatic\nVery high\nLack of \ncohe\u00ad\nsiveness\nRare acini \nwith bile\nTrabeculae dif\u00ad\nficult to find, \nspindle cells \nmay be present\nGrade I: Best reserved for those areas in Grade II hepatocellular carcinomas where the difference between the \ntumor cells and hyperplastic liver cells is so minor that a diagnosis of carcinoma rests upon the demonstration of \nmore aggressive growths in other parts of the neoplasm.\nGrade II: Cells show a marked resemblance to normal hepatic cells. Nuclei are larger and more hyperchromatic than \nnormal cells but the cytoplasm is abundant and acidophilic. The cell borders are often sharp and clear cut. Acini \nare frequent with lumina varying in size from tiny canaliculi to large thyroid-like spaces. The lumina are often \nfilled with bile or protein precipitate.\nGrade III: Nuclei are usually larger and more hyperchromatic than Grade II cells. The nuclei occupy a relatively \ngreater proportion of the cell (high N:C ratio). Cytoplasm is granular and acidophilic, but less so than Grade II \ntumors. Acini are less frequent and not as often filled with bile or protein precipitate. More single cells were seen \nin the intravascular growths than in Grade II. Tumor giant cells are the most numerous in this group.\nGrade IV: Nuclei are intensely hyperchromatic and occupy a high percentage of the cell volume. Cytoplasm is vari\u00ad\nable in amount, often scanty and contains fewer granules. The growth pattern is medullary in character, trabecu\u00ad\nlae difficult to find, and cell masses seem to lie loosely without cohesion in vascular channels. Only rare acini are \nseen. Spindle cell areas are present in some tumors. Short plump cell forms, resembling \u201coat cell\u201d carcinoma of \nthe lung seen in some.\nThis system is sometimes simplified to a three grade system with grades I and II equivalent to grade I, grade III \nequivalent to grade II, and grade IV equivalent to grade III. This modification should be stated if used.\nModified from Edmondson HA, Steiner PE, Primary carcinoma of the liver, a study of 100 cases among 48,900 necroscopies, Cancer 7:462-503, 1954.\nTABLE 19\u201325.\u2003\nGRADING SYSTEM FOR CHOLANGIOCARCINOMAS\nGrade 1\nWell differentiated (>95% of tumor composed of glands)\nGrade 2\nModerately differentiated (50% to 95% of tumor composed of glands)\nGrade 3\nPoorly differentiated (5% to 49% of tumor composed of glands)\nGrade 4\nUndifferentiated (<5% of tumor composed of glands)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_383.png", "summary": "The page discusses the grading systems for hepatocellular carcinomas and cholangiocarcinomas, providing detailed criteria for each grade.", "questions": [ "What are the key differences in the criteria for grading hepatocellular carcinomas between Grade I and Grade II?", "How does the presence of tumor giant cells differ in Grade III hepatocellular carcinomas compared to other grades?", "What modifications can be made to simplify the grading system for hepatocellular carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 384, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Gallbladder\n366\n\t\u2022\t \u0007Tumor Growth Pattern: For cholangiocarcinomas: mass-forming, periductal infiltrating, mixed \nmass-forming and periductal infiltrating\n\t\u2022\t \u0007Extent of Invasion: Hepatocellular carcinoma: Solitary tumor with no vascular invasion (T1), solitary \ntumor with vascular invasion or multiple tumors, none more than 5 cm (T2), multiple tumors more \nthan 5 cm or tumor involving a major branch of the portal or hepatic veins (T3), tumors with direct \ninvasion of adjacent organs other than the gallbladder or perforation of visceral peritoneum (T4).\nCholangiocarcinoma: Carcinoma in situ (Tis), solitary tumor without vascular invasion (T1), soli\u00ad\ntary tumor with vascular invasion (T2a), multiple tumors (T2b), tumor perforating the visceral peri\u00ad\ntoneum or involving the local extrahepatic structures by direct invasion (T3), tumor with periductal \ninvasion (T4). The periductal infiltrating pattern is a diffuse longitudinal growth pattern along the \nintrahepatic bile ducts on gross and microscopic examination.\n\t\u2022\t \u0007Regional Lymph Nodes: Absent (N0), present (N1), number of nodes examined, number with metastases\n\t\u2022\t \u0007Margins: Not involved or involved (distance from closest margin), bile duct margin (only for cholan\u00ad\ngiocarcinoma), invasive or in situ\n\t\u2022\t \u0007Tumor Necrosis: Present or absent (minimal, moderate, or extensive)\n\t\u2022\t \u0007Macroscopic Venous (Large Vessel) Invasion: Not identified, present. Portal vein or hepatic vein \ninvasion are important prognostic factors. Identify the vessel involved, if possible.\n\t\u2022\t \u0007Microscopic (Small Vessel) Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Additional Pathologic Findings: Cirrhosis/fibrosis, hepatitis (type and activity), steatosis, macrore\u00ad\ngenerative nodule, hepatocellular dysplasia (low-grade dysplastic nodule, high-grade dysplastic nod\u00ad\nule), ductal dysplasia, iron overload, primary sclerosing cholangitis, biliary stones\n\t \u2022\t \u0007The degree of fibrosis as defined by Ishak (Ishak K, Baptista A, Bianchi L, et al. Histologic grading \nand staging of chronic hepatitis. J Hepatol 22:696-699, 1995) is a prognostic factor for hepatocel\u00ad\nlular carcinomas.\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Tables 19-26 \nand 19-27). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/\u2009\u2009) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nGALLBLADDER\nGallbladders are commonly removed for chronic cholecystitis with cholelithiasis. Tumors are uncom\u00ad\nmon, and are usually associated with gallstones. Carcinoma may also be associated with an anomalous \ncholedochopancreatic junction or with chronic inflammatory bowel disease.\nLaparoscopic cholecystectomies are frequent procedures. It is sometimes necessary for the surgeon to \nfragment the gallstones within the intact gallbladder with forceps prior to removing it through the small \nlaparotomy incision. This can lead to a rather tattered appearance to the specimen. Gallbladders are \n\u00adoccasionally torn during this procedure, spilling the contents into the abdominal cavity. Note should be \nmade of whether the specimen is intact or if perforations and tears are present. The peritoneal cavity is \nnot well visualized as in open cholecystectomies. Therefore, be alert to serosal implants or inflammation \nthat could indicate clinically unsuspected disease outside of the gallbladder.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Describe the serosal appearance.\n\t \u2022\t \u0007Normal: smooth and glistening\n\t \u2022\t \u0007Adhesions and/or portion of attached liver: normally found at the attachment of the gallbladder \nto the liver capsule\n\t \u2022\t \u0007Inflammation: dull and irregular, subserosal fibrosis, fat necrosis (very firm yellow hemorrhagic \nsoft tissue, may indicate pancreatitis), fibrinous or purulent exudates.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_384.png", "summary": "The page provides detailed information on the evaluation of gastrointestinal specimens, specifically focusing on gallbladder tumors and their growth patterns, extent of invasion, lymph node involvement, margins, tumor necrosis, vascular invasion, perineural invasion, additional pathologic findings, distant metastasis, and AJCC classification.", "questions": [ "How does the extent of invasion in hepatocellular carcinoma differ from that in cholangiocarcinoma?", "What are the key prognostic factors related to venous invasion in gallbladder tumors?", "How is the degree of fibrosis defined and why is it considered a prognostic factor for hepatocellular carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 385, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Gallbladder\n367\n\t \u2022\t \u0007Tumor implants: firm tan/white nodules.\n\t \u2022\t \u0007Necrosis: blue-black discoloration (gangrene) associated with possible perforation\n\t \u2022\t \u0007Porcelain gallbladder: the wall may be markedly thickened in chronic cholecystitis. If there is \nextensive calcification the gallbladder may take on the appearance of \u201cporcelain\u201d (shiny hard and \nwhite).\n\t \u2022\t \u0007Intact or with perforations and tears or previously opened\nLook for lymph nodes, most commonly present near the cystic duct.\n 2.\t \u0007Open the gallbladder longitudinally, starting away from the cystic duct. The cystic duct is tortuous \nand need not be opened completely. Record the length, circumference and wall thickness. Describe \nthe mucosa.\n\t \u2022\t \u0007Normal: tan/green and velvety with a honeycomb pattern, thin pliable wall\n\t \u2022\t \u0007Cholesterolosis (\u201cstrawberry gallbladder\u201d): speckled yellow mucosa due to aggregates of foamy \nhistiocytes in the mucosa. This finding has no definite clinical significance.\n\t \u2022\t \u0007Inflammation: ulcerated, friable, flattened and white (atrophy), wall thickened and fibrotic or \nedematous. Acute acalculous cholecystitis (i.e., without gallstones) is a life-threatening disease of \nseverely ill or debilitated patients. Often transmural (gangrenous) necrosis is present which may be \napparent on examination of the serosa. The wall may be very thin and friable or markedly thickened \nby edema.\n\t \u2022\t \u0007Polyps: usually small and papillary, uncommon\n\t \u2022\t \u0007Carcinoma is rare and usually appears as a solid white mass infiltrating the wall or as an exophytic, \nsoft, fronded intraluminal tumor. Papillary carcinomas may have a more favorable prognosis. How\u00ad\never, infiltrating tumor may be obscured by superimposed inflammation and be occult grossly. The \nwall may be slightly thickened with effacement of the normal tissue planes. If present, describe and \nTABLE 19-26.\u2003\nAJCC (7th EDITION) CLASSIFICATION OF HEPATOCELLULAR CARCINOMA\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nSolitary tumor without vascular invasion\nT2\nSolitary tumor with vascular invasion or multiple tumors, none more than 5 cm\nT3a\nMultiple tumors more than 5 cm\nT3b\nSingle tumor or multiple tumors of any size involving a major branch of the portal vein or \nhepatic vein\nT4\nTumor(s) with direct invasion of adjacent organs other than the gallbladder or with perfora\u00ad\ntion of the visceral peritoneum\nVascular invasion includes radiologic or pathologic (gross or microscopic) involvement of vessels.\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nRegional lymph node metastasis\nA regional lymphadenectomy usually includes three or more lymph nodes. Regional lymph nodes include hilar, \nhepatoduodenal ligament, inferior phrenic, and caval lymph nodes.\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: This classification does not include intrahepatic bile duct tumors, sarcoma, or metastatic carcinomas.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_385.png", "summary": "The page discusses various findings in gallbladder specimens, including tumor implants, necrosis, porcelain gallbladder, and different pathological conditions like inflammation, polyps, and carcinoma.", "questions": [ "What are the different characteristics of a normal gallbladder mucosa?", "What are the clinical implications of cholesterolosis in the gallbladder?", "How does the appearance of gallbladder carcinoma differ from other gallbladder pathologies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 386, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Gallbladder\n368\ndocument invasion through the wall (including serosa and adjacent liver if present), and submit the \ncystic duct as a margin.\n 3.\t \u0007Record the number (estimate if there are many, not just \u201cseveral\u201d or \u201cmany\u201d), size in aggregate and \nrange of sizes, color, quality, and shape (ovoid or faceted - if faceted there must have been multiple \nstones) of any gallstones present.\n\t \u2022\t \u0007Cholesterol calculi: green/yellow/black, hard and crystalline\n\t \u2022\t \u0007Pigment calculi: black, soft and crumbly\nNote whether there are stones lodged in the isthmus or cystic duct.\nIf stones were fragmented during laparoscopy, the stones may appear to be \u201cgravel\u201d within the bile. Note \nwhether the luminal contents include bile (viscous green/black fluid) or clear watery mucin (suggests \ntotal obstruction resulting in hydrops or mucocele).\nGallstones are sometimes requested for return to the patient (see Chapter 2, \u201cReturning Specimens to \nPatients\u201d). In these cases place them in a sealed container, labeled with the patient\u2019s name. Do not release a \ncontainer filled with liquid formalin as the fixative is a biohazard. If the stones were placed in formalin, they \ncan be rinsed in water and then placed in an empty container. If chemical analysis is requested, see below.\n 4.\t \u0007Submit one cassette of gallbladder with sections demonstrating cross-sections of the fundus, neck \nwith serosa, and cystic duct. If a cystic duct lymph node is present a representative section should be \nsubmitted as well. Submit additional sections of gross lesions.\nGROSS DIFFERENTIAL DIAGNOSIS\nAdenocarcinomas.\u2002 These tumors are rare (6 to 15 per 1000 cholecystectomies) and many may be \ngrossly inapparent. Most have an infiltrating pattern and will appear as a diffuse homogeneous thickening \nof the wall that effaces the normal texture. About one third of tumors are exophytic and grow into the \nTABLE 19-27.\u2003\n\u0007AJCC (7TH EDITION) CLASSIFICATION OF TUMORS OF INTRAHEPATIC \nBILE DUCTS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ (intraductal tumor)\nT1\nSolitary tumor without vascular invasion\nT2a\nSolitary tumor with vascular invasion\nT2b\nMultiple tumors, with or without vascular invasion\nT3\nTumor perforating the visceral peritoneum or involving the local extra hepatic \nstructures by direct invasion\nT4\nTumor with periductal invasion\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nRegional lymph node metastasis\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis present\nNote: This classification includes combined hepatocellular and cholangiocarcinoma (mixed hepatocholangiocarcinoma). It does not include \nsarcomas or metastases to the liver. There are separate AJCC classification systems for perihilar (proximal) extrahepatic bile duct tumors and distal \nextrahepatic bile duct tumors.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_386.png", "summary": "The text discusses the examination of gallbladder specimens, including recording the presence of gallstones, submitting sections for analysis, and the gross differential diagnosis of adenocarcinomas.", "questions": [ "What are the characteristics of cholesterol and pigment gallstones?", "How should gallstones be handled if they are requested for return to the patient?", "What is the AJCC classification of tumors of intrahepatic bile ducts and what does it include?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 387, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Gallbladder\n369\nlumen as a mass as well as invade into the wall. In most cases, gallstones and fibrosis will also be present. \nPorcelain gallbladders are associated with an increased risk of carcinoma.\nMetastatic Carcinomas.\u2002 Metastatic carcinoma (usually to the serosal surface) is found in one to five \ncases per 1000. Rarely, a lymph node removed adjacent to the cystic duct will reveal metastatic carcinoma \nor a lymphoma.\nAcute Calculous or Acalculous Cholecystitis.\u2002 The gallbladder is enlarged and firm and bright \nred, green-black, or violaceous. The lumen may be filled with cloudy hemorrhagic or purulent fluid. The \nwall may be markedly thickened and edematous. In gangrenous cholecystitis, the entire gland is necrotic \nwith multiple perforations. The serosal surface is often covered with a fibrinous or purulent exudate.\nChronic Cholecystitis.\u2002 The wall may be thickened and fibrotic. The mucosa is usually preserved. \nSerosal adhesions may be present. If the wall is thickened with multiple calcifications it may give the \nappearance of a porcelain gallbladder. Xanthogranulomatous cholecystitis has the appearance of a small \nshrunken nodular gallbladder and can be mistaken for a malignancy.\nMucoceles can be mistaken for mucinous carcinomas. Muciphages may resemble signet ring cells in \nthe wall. However, these cells will not be immunoreactive for cytokeratin.\nInfections.\u2002 Gallbladders from patients with AIDS may show CMV, Cryptosporidium sp., or MAI. \nRarely, parasites may be found.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Grossly normal: Three sections (one from fundus, one from body, and one from neck). If carci\u00ad\nnoma in situ or invasive carcinoma is found, additional sections should be submitted.\n\t \u2022\t \u0007Tumors: Most lesions can be submitted in entirety including the deepest extent of invasion and \nrelationship to attached liver (if present). If a gross lesion is present, submit the cystic duct separately.\n\t \u2022\t \u0007Lymph node: If a lymph node is present, submit in its entirety.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cgallbladder,\u201d is a 6 \u00d7 4 \u00d7 0.5 cm \n(wall thickness) gallbladder with a green/tan velvety mucosa with focal ulcerations (largest 0.5 \u00d7 0.3 cm). \nThe wall is slightly thickened but pliable and the serosal surface is smooth and glistening. Within the \ngallbladder is green/black bile and approximately 20 hard yellow crystalline faceted gallstones (in aggre\u00ad\ngate 4 \u00d7 3 \u00d7 2 cm; largest 1.5 cm). One of the gallstones is lodged within the cystic duct.\nCassette: Sections of wall and cystic duct, 6 frags, RSS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR GALLBLADDER CARCINOMAS\n\t\u2022\t \u0007Specimen: Gallbladder, liver, extrahepatic bile duct\n\t\u2022\t \u0007Procedure: Laparoscopic or open cholecystectomy, radical cholecystectomy (resection of liver tissue \nand possible resection of lymph nodes)\n\t\u2022\t \u0007Tumor Site: Fundus, body, neck, cystic duct, indeterminate\n\t\u2022\t \u0007Peritoneal side of gallbladder, hepatic side of gallbladder\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Histologic Type: Carcinoma in situ, adenocarcinoma, papillary adenocarcinoma, adenocarci\u00ad\nnoma\u2014intestinal type, adenocarcinoma\u2014gastric type, mucinous adenocarcinoma (> 50% mucinous), \nadenosquamous carcinoma, small cell carcinoma, other rare types. The WHO Classification is recom\u00ad\nmended.\n\t\u2022\t \u0007Configuration: Exophytic (fungating/polypoid), endophytic (ulcerating), or diffusely infiltrating\n\t \u2022\t \u0007Papillary carcinomas (usually polypoid) have a favorable prognosis.\n\t\u2022\t \u0007Histologic Grade: Well, moderately, poor, undifferentiated (Table 19-28)\n\t \u2022\t \u0007Papillary adenocarcinoma and clear cell adenocarcinoma are usually not graded.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_387.png", "summary": "The text discusses various pathological conditions of the gallbladder, including acute and chronic cholecystitis, mucoceles, infections, and metastatic carcinomas.", "questions": [ "What are the characteristic features of acute calculous or acalculous cholecystitis?", "How can xanthogranulomatous cholecystitis be distinguished from malignancy?", "What are the potential infections that may be found in gallbladders from patients with AIDS?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 388, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n370\n\t\u2022\t \u0007Microscopic Tumor Extension: In situ (Tis), invasion into lamina propria (T1a), invasion into mus\u00ad\ncular layer (T1b), invasion into perimuscular connective tissue (no extension beyond serosa or into \nliver) (T2), perforates serosa (visceral peritoneum) and/or directly invades liver and/or one other organ \nor structure, such as the stomach, duodenum, colon, or pancreas, omentum, or extrahepatic bile ducts \n(T3), tumor invades the main portal vein or hepatic artery or invades two or more extrahepatic organs \nor structures (T4).\n\t\u2022\t \u0007Margins: Involved or not involved (distance from nearest margin), involved by invasive carcinoma or \nin situ carcinoma: cystic duct, liver parenchymal margin\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Regional Lymph Nodes: No regional lymph node metastasis (N0), metastasis to nodes along cystic \nduct, common bile duct, hepatic artery, and portal vein (N1), metastasis to periaortic, pericaval, supe\u00ad\nrior mesenteric artery, or celiac artery nodes (N2)\n\t \u2022\t \u0007Number of nodes examined, number of nodes involved\n\t\u2022\t \u0007Gallstones: Absent, present. If absent, the carcinoma may be associated with anatomic abnormalities \n(e.g., an anomalous choledochopancreatic junction) or inflammatory bowel disease\n\t\u2022\t \u0007Additional Pathologic Findings: Acute cholecystitis, chronic cholecystitis, metaplasia (squamous, \npyloric gland, intestinal), chronic inflammatory changes, dysplasia/adenoma, diffuse calcification (por\u00ad\ncelain gallbladder)\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 19-29). \nM0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/\u2009) and the ADASP (see www.adasp.org\u2009). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nChemical Analysis of Gallstones\nRarely, there may be a request from a clinician for chemical analysis of gallstones to determine choles\u00ad\nterol content. This is an expensive test and is only ordered by special request. In these cases the gallstones \nare placed in a separate dry sterile container and sent to a specialty laboratory.\nPANCREAS\nThe pancreas is most frequently biopsied or resected because of tumors or severe debilitating chronic \npancreatitis.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 19-30.\nTABLE 19\u201328.\u2003\nGRADING SYSTEM FOR GALLBLADDER ADENOCARCINOMAS\nGrade 1\nWell differentiated (>95% of tumor composed of glands)\nGrade 2\nModerately differentiated (50% to 95% of tumor composed of glands)\nGrade 3\nPoorly differentiated (<49% of tumor composed of glands [includes signet ring cell carcinomas])\nGrade 4\nUndifferentiated (small cell carcinomas, undifferentiated carcinomas)\nPapillary carcinomas and clear cell carcinomas are usually not graded.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_388.png", "summary": "The page provides detailed information on the microscopic tumor extension, margins, lymph-vascular invasion, perineural invasion, regional lymph nodes, gallstones, additional pathologic findings, distant metastasis, and AJCC classification of pancreatic specimens.", "questions": [ "What are the different categories of tumor extension mentioned for pancreatic specimens?", "How is the presence of gallstones related to carcinoma in the pancreas?", "Why is chemical analysis of gallstones rarely requested and what does it involve?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 389, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n371\nTABLE 19-29.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF GALLBLADDER TUMORS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ\nT1\nTumor invades lamina propria or muscular layer\nT1a\nTumor invades lamina propria\nT1b\nTumor invades muscular layer\nT2\nTumor invades perimuscular connective tissue; no extension beyond serosa or into liver\nT3\nTumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one \nother adjacent organ or structure, such as the stomach, duodenum, colon, or pancreas, omen\u00ad\ntum, or extrahepatic bile ducts\nT4\nTumor invades main portal vein or hepatic artery or invades two or more extrahepatic organs or \nstructures\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis to nodes along the cystic duct, common bile duct, hepatic artery, and/or portal vein\nN2\nMetastases to periaortic, pericaval, superior mesenteric artery, and/or celiac artery lymph nodes\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis (includes lymph nodes in peripancreatic nodes along the body and tail)\nNote: This classification does not include carcinoid tumors or sarcomas. Tumors of the extrahepatic bile ducts have separate AJCC classification \nsystems.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \n\u00adCommittee on Cancer (AJCC), Chicago, Illinois.\nTABLE 19\u201330.\u2003\nRELEVANT CLINICAL HISTORY \u2013 PANCREAS\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR PANCREATIC SPECIMENS\nOrgan/tissue resected or biopsied\nDiabetes mellitus\nPurpose of the procedure\nPancreatitis\nGross appearance of the organ/tissue/lesion sampled\nJaundice\nAny unusual features of the clinical presentation\nZollinger-Ellison syndrome\nAny unusual features of the gross appearance\nFamily or personal history of tumors or hyperplasia \nof other endocrine organs (i.e., MEN syndromes)\nPrior surgery/biopsies \u2013 results\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic appearance of tissues)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_389.png", "summary": "The page provides the AJCC classification of gallbladder tumors and relevant clinical history for pancreatic specimens.", "questions": [ "What are the different stages of gallbladder tumors according to the AJCC classification?", "What clinical history is considered relevant for pancreatic specimens?", "How does prior treatment, such as radiation therapy or chemotherapy, impact the histologic appearance of tissues?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 390, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n372\nBiopsy\nPancreatic biopsies may be transabdominal (usually fine needle biopsies), via ERCP (often brushings), or \nintraoperative needle or incisional biopsies. Small biopsies are processed as described in Chapter 13. Fro\u00ad\nzen sections of pancreatic biopsies can be very difficult to interpret (see Chapter 6).\nPancreatic Resections\nPancreatic adenocarcinomas of the body or tail usually present late (because they don\u2019t obstruct) with \nextension into peripancreatic tissue or metastases, and therefore are rarely resectable. Resectable tumors of \nthis region are more likely to be tumors of the ampullary region (presenting with obstruction), endocrine \ntumors, or unusual non-endocrine tumors (e.g., cystic lesions such as cystadenoma or cystadenocarci\u00ad\nnoma). Benign conditions (e.g., pancreatic pseudocyst) or chronic pancreatitis are resected less frequently.\nExamination of the lymph nodes as separate groups is important for staging and prognosis.10 About \nhalf of small ampullary and duodenal carcinomas will have metastases at surgery. These tumors com\u00ad\nmonly metastasize to a single location (most often the posterior or inferior lymph node groups), and \noften to a single lymph node.\nIn contrast, most tumors of the head of the pancreas metastasize to multiple lymph node groups and \noften to multiple lymph nodes within the group. The most common sites are posterior, superior, and \ninferior nodal groups.\nMetastases to gastric or splenic nodes are rare, probably due to the lack of lymphatic connections \nbetween these nodes and the pancreas. Therefore, metastases to these nodes indicate either a very aggres\u00ad\nsive tumor or a second primary site.\nDistal Pancreatectomy\nThe specimen usually consists of distal pancreas and attached spleen (Fig. 19-11), but may also include \ntransverse colon or stomach.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Orient the specimen (anterior, posterior, superior, inferior). Identify the pancreatic resection margin \nand the main pancreatic duct. Photographs are taken of the entire specimen, and of cross-sections \nwhen appropriate. Record the outer appearance including color (tan/yellow, white), consistency (firm, \nhard), texture (finely nodular, fibrous bands, architecture obscured by dense white infiltrate) noting \nwhether there are areas grossly suspicious for tumor.\nPancreatic tail\nPancreatic duct\nResection margin\nSpleen\nFigure 19\u201311.\u2002 Distal pancreatectomy.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_390.png", "summary": "The page discusses pancreatic biopsies, resections, and examination of lymph nodes in pancreatic specimens.", "questions": [ "What are the different methods of obtaining pancreatic biopsies?", "What types of tumors are more likely to be resectable in the pancreatic region?", "Why is examination of lymph nodes important in staging and prognosis of pancreatic tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 391, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n373\nInk the soft tissue margins around the pancreas. The proximal (pancreatic) resection margin may be \ntaken en face or perpendicular, depending on the distance of the tumor from the margin.\n 2.\t \u0007Serially section through the pancreas, perpendicular to the long axis. Describe any lesions, including \nsize, location (body or tail), color, borders (encapsulated, infiltrating), relationship to margins (pan\u00ad\ncreatic, anterior, retroperitoneal, superior, inferior).\n 3.\t \u0007Separate the spleen if not directly involved by tumor. Section thinly, looking for lesions (see Chapter \n27, \u201cSpleen\u201d). Evaluate the splenic vein (if present) for thrombosis or tumor.\n 4.\t \u0007Fix entire specimen in formalin overnight. Take microscopic sections the following day. Cystic \nlesions are carefully sectioned and sections of any thickened walls or solid areas taken. Most \nshould have the entire wall submitted. Take perpendicular sections of the closest approach of \ntumor to soft tissue margins (posterior, anterior, superior, and inferior) and place in labeled cas\u00ad\nsettes.\nAfter the tumor and margins have been sampled, the soft tissue is examined carefully for lymph nodes. \nThese are of great importance for prognosis (curative vs. palliative resection) and diagnosis (malignant \nvs. benign endocrine tumors). The peripancreatic nodes are described and submitted separately from \nthe splenic nodes. These are all regional nodes for tumors in the body and tail. The adipose tissue may \nbe carefully sectioned while attached to the specimen, or the adipose tissue can be removed and fixed \nin Bouin\u2019s overnight. Nodes adjacent to other structures (stomach, transverse colon) are submitted \nseparately because these are not considered regional nodes.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Tumor: Submit at least one cassette per cm of tumor including borders and relationship to unin\u00ad\nvolved pancreas. Cystic lesions are usually completely submitted unless >5 cm. In these cases one \nsection per cm is taken including the most irregular and nodular areas.\n\t \u2022\t \u0007Margins: Proximal pancreatic margin (usually the most important), submit en face. This section \nshould include the pancreatic duct. Soft tissue margins (perpendicular) around pancreas to evaluate \ninvasion into soft tissue and/or retroperitoneum\n\t \u2022\t \u0007Pancreatic duct: The duct margin is sampled in the en face margin section.\n\t \u2022\t \u0007Other structures: One section of spleen (if no lesions). Representative sections of any other struc\u00ad\ntures.\n\t \u2022\t \u0007Lymph nodes: Submit each lymph node. Describe as separate groups peripancreatic, splenic, and \nany other sites.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cpancreas,\u201d is the pancreatic tail \n(7 \u00d7 4 \u00d7 3 cm) and attached spleen (10 \u00d7 5 \u00d7 4 cm; 150 gm). Within the pancreas there is a 5 \u00d7 4 \u00d7 3 cm \nwell-circumscribed, fleshy, homogeneous, yellow/tan tumor mass. The tumor is 2 cm from the pancre\u00ad\natic resection margin, which is uninvolved. The outer margins of the specimen consist of yellow/white \nadipose tissue varying in thickness from 0.5 to 2.0 cm. The margins are grossly uninvolved by tumor. \nThe remainder of the pancreatic parenchyma is yellow/tan and grossly unremarkable. The spleen has a \ndark red/brown homogeneous parenchyma with slight prominence of the white pulp. Two lymph nodes \nare present in the perihilar soft tissue, the largest measuring 0.5 cm in greatest dimension. Two addi\u00ad\ntional lymph nodes are present in the posterior and inferior soft tissue surrounding the distal pancreas, \nthe largest measuring 0.4 cm in greatest dimension. A frozen section was performed on the pancreatic \nresection margin (en face). Tumor is saved for EM and snap freezing. The margins are inked and taken \nperpendicular to the specimen except as noted. Photographs are taken.\nCassette #1: Pancreatic resection margin, en face, FSR, 1 frag, ESS.\nCassette #2: Tumor and anterior margin, 1 frag, RSS.\nCassette #3: Tumor and superior margin, 1 frag, RSS.\nCassette #4: Tumor and posterior margin, 1 frag, RSS.\nCassette #5: Tumor and inferior margin, 1 frag, RSS.\nCassette #6: Tumor and adjacent pancreas, 1 frag, RSS.\nCassette #7: Spleen, 1 frag, RSS.\nCassette #8: Perihilar lymph nodes, 2 frags, ESS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_391.png", "summary": "The surgical pathology manual provides detailed instructions on handling gastrointestinal specimens, specifically focusing on the pancreas. It includes guidelines for margin assessment, sectioning, fixation, and evaluation of lymph nodes.", "questions": [ "What are the specific steps involved in margin assessment of pancreatic specimens?", "Why is it important to separate the spleen if not directly involved by tumor?", "How are lymph nodes evaluated and submitted for tumors in the body and tail of the pancreas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 392, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n374\nCassette #9: Inferior lymph node, 2 frags, ESS.\nCassette #10: Posterior lymph node, 2 frags, ESS.\nWhipple Procedure (Partial Gastrectomy, Duodenectomy, Partial Pancreatectomy)\nA Whipple procedure is performed for resection of tumors in the head of the pancreas or in the ampul\u00ad\nlary or periampullary region.\nThe specimen usually consists of distal stomach (although the pylorus may be spared), duodenum, \nhead of pancreas, and common bile duct remnant (Fig. 19-12). The gallbladder is usually submitted as a \nseparate specimen. The specimen is dissected carefully to determine the site of origin of the tumor (e.g., \nduodenal, ampullary, periampullary, bile duct, pancreatic duct, head of pancreas). Anatomic orientation \nmust be maintained at all times.\nPROCESSING THE SPECIMEN\n 1.\t \u0007While the specimen is unfixed and pliable, open the stomach along the greater curvature, across the \nanterior wall of the pylorus, and down the outer curvature of the duodenum. The distal portion of \nthe duodenal mucosa usually looks dusky because the blood supply to this portion is ligated earlier in \nthe operation. Record the dimensions of the stomach (proximal to distal, greater curvature and lesser \ncurvature, circumference, wall thickness), duodenum (length and circumference), pancreatic head \n(three dimensions), common bile duct (length and diameter), and margins (stapled vs. open, length, \n\u00addiameter).\nClean the mucosa with saline and look for mucosal lesions, especially around the ampulla. A probe in \nthe common bile duct extending to ampulla is helpful for orientation.\nIdentify the distal pancreatic resection margin. It will be the only pancreatic tissue visible (the remain\u00ad\nder being surrounded by a thin rim of soft tissue). Take two or more en face sections including the pan\u00ad\ncreatic duct if visible (more if suspicious for involvement by tumor) and place in labeled cassettes.\nAlternatively (particularly if the tumor appears close to the distal margin), this margin may be taken \n\u00adperpendicular to the resection margin after further dissection (see below).\nIdentify the uncinate process of the pancreas, which extends inferiorly from the pancreatic head. The \nposterior surface of this portion of the pancreas is not peritonealized as it lies directly on the \u00adsuperior \nPylorus\nStomach\nPancreas\nAmpulla\nHead of\npancreas\nPancreatic\nduct\nCommon bile\nduct\nCROSS-SECTION ALONG\nPLANE OF THE DUCTS\nMain\npancreatic\nduct\nCommon bile duct\nDuodenum\nAmpulla of\n Vater\nFigure 19\u201312.\u2002 Whipple procedure.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_392.png", "summary": "The Whipple procedure is a surgical resection performed for tumors in the head of the pancreas or periampullary region, involving removal of the distal stomach, duodenum, head of pancreas, and common bile duct remnant.", "questions": [ "What are the components of the specimen obtained during a Whipple procedure?", "How is the distal pancreatic resection margin identified and processed?", "Why is anatomic orientation important during the dissection of the Whipple procedure specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 393, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n375\nmesenteric vessels for a distance of approximately 3 to 4 cm. This pancreatic margin is sometimes \n\u00adspecifically designated by the surgeon, but is critical in all cases, since it represents a true surgical \u00admargin. \nCarcinomas may be closest to this margin as the surgeon must preserve the mesenteric vessels and is \nlimited in the amount of surrounding tissue that he or she can take. Ink the uncinate margin and the deep \nposterior soft tissue margin different colors.\n 2.\t \u0007Identify the common bile duct as it exits the pancreas and passes behind the proximal duodenum. The \nduct is often markedly dilated because the tumor is usually causing obstruction. Remove the proximal \nbile duct margin en face and place in a separate cassette. Gently place a probe in the duct and advance \nit until it exits through the ampulla of Vater. This is usually possible to do even if the duct is func\u00ad\ntionally obstructed. This must be done while the specimen is fresh and pliable. Ink the soft tissue and \nuncinate process margins of the pancreas, excluding the distal resection margin (to be able to identify \nit for orientation).\nIdentify the main pancreatic duct. This may be difficult and may require two or three serial sections \nstarting at the pancreatic margin to look for the duct as it enlarges proximally. If the duct is found, gently \nplace a probe in it and advance the probe to the ampulla if possible.\nIf a probe cannot be advanced through the bile duct or the pancreatic duct into the ampulla, find \nthe ampulla starting at the mucosal surface. It is usually more distal than it seems it should be and may \nappear like an edematous fold of mucosa. Note whether the duodenal mucosa appears grossly normal \nor abnormal in this region.\nIn about 8% of individuals the main pancreatic duct from the body and tail empties via the accessory \nduct of Santorini into an accessory papilla, usually located proximal to the ampulla of Vater. The uncinate \nhead only drains into the ampulla. Thus, there may be no communication between the main ampulla and \nthe main pancreatic duct.\n 3.\t \u0007Make a section along the plane of both pancreatic duct and bile duct probes or along the probe in the \ncommon bile duct. This bisects the ampulla. This gives the best demonstration of the relationship \nof the tumor to the ampulla, duodenal mucosa, common bile duct, pancreatic duct, and pancreatic \nparenchyma. If two parallel cuts are made on either side of this cut, the resulting sections are usually \nvery photogenic and demonstrate the tumor relationships well. An alternative method involves cut\u00ad\nting along the main pancreatic duct in the transverse (i.e., anterior to posterior) plane. This method \nillustrates the relationship of the tumor to the posterior margin and preserves the uncinate process in \nthe inferior half of the specimen.\nDescribe the tumor, including size, color, consistency, cysts, relationship to anatomic sites, distance from \nmargins, and obstruction of ducts.\nThe tumor may be grossly subtle, but is best identified as a lesion that partially effaces or blurs the normal \n\u00adlobular architecture of the pancreatic parenchyma, usually without gross scarring.\nDescribe the remainder of the pancreatic parenchyma, including color, fibrosis, nodularity, fat necrosis, \ncysts, ducts (determine if dilated), and calculi. Describe any anatomical variations of the merger of the \ncommon bile duct and pancreatic duct.\nOnly at this point is the specimen is fixed overnight (pinning out the stomach and duodenum) before \ntaking additional sections.\n 4.\t \u0007Lymph node involvement is the most important prognostic indicator. Carefully section through the \nsurrounding soft tissue to look for lymph nodes. The location of each lymph node found is recorded \n(i.e., anterior, inferior, posterior, superior pancreas, pyloric, stomach, distal duodenal, and splenic), as \nthis information is used in staging. Although little adipose tissue is present, several lymph nodes are \nalways present. Commonly, a lymph node is present near the common bile duct. Some lymph nodes \nmay be submitted by the surgeon as separate specimens.\n 5.\t \u0007If other specimens are submitted (commonly the gallbladder or spleen) they are examined as described \nin the separate sections. However, special attention is paid to looking for tumor involvement as well \nas identifying additional lymph nodes.\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Figure 19-13.\nAdenocarcinomas may be difficult to define grossly. The tumor may be an infiltrating white mass \nthat effaces the normal architecture and can resemble a chronically inflamed fibrotic pancreas. The distal \ncommon bile duct or pancreatic duct are frequently invaded at the head of the pancreas with \u00adobstruction", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_393.png", "summary": "The page provides detailed instructions on handling gastrointestinal specimens, specifically focusing on the pancreas, including identifying margins, ducts, and tumor relationships.", "questions": [ "What are the key considerations when identifying the common bile duct and main pancreatic duct during specimen handling?", "How does the presence of an accessory duct of Santorini impact the drainage of the pancreas?", "What are the benefits of making a section along the plane of both pancreatic duct and bile duct probes for demonstrating tumor relationships?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 394, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n376\nand proximal dilatation of the duct. Carcinomas involving the ampulla typically present earlier with \nsymptoms and are frequently small in size. In larger carcinomas, invasion into the retroperitoneum is \ncommon.\nEndocrine Tumors\u2002 tend to be well-circumscribed with a capsule and occur within the tail. May be \nfleshy, yellow, and homogeneous in appearance. Necrosis, cysts, and hemorrhage may be present. Save \ntissue for EM and snap freezing.\nSolid Pseudopapillary Tumor\u2002 is usually a well-circumscribed large mass arising anywhere in the \npancreas, comprised of single or multiple cystic spaces. Central necrosis is common. The inner wall \nmust be sectioned extensively to look for solid areas. This tumor is most common in young women \nand carries a relatively good prognosis.\nA\nB\nC\nD\nDuctal adenocarcinoma\nSubtle effacement of normal texture\nObstruction or narrowing of ducts\nMucinous cystadenocarcinoma\nMultiloculated, cystic mass\nMay find solid areas\nEndocrine tumor\nWell circumscribed with pseudocapsule\nHemorrhage, necrosis, and cystic areas common\nSolid pseudopapillary tumor\nWell-circumscribed encapsulated mass\nHemorrhage, necrosis, and cystic areas common\nPancreatic duct narrowed\nDistal pancreatic duct\nis distended\nSuperior\nmesenteric\nartery and\nvein \nSolid\nCystic\nHemorrhage \nCystic, necrotic\nFigure 19\u201313.\u2002 Differential diagnosis of pancreatic tumors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_394.png", "summary": "The page discusses various types of tumors in the pancreas, including endocrine tumors, solid pseudopapillary tumors, ductal adenocarcinoma, and mucinous cystadenocarcinoma.", "questions": [ "What are the common characteristics of endocrine tumors in the pancreas?", "How does a solid pseudopapillary tumor typically present and who is most commonly affected by it?", "What are the key features that differentiate ductal adenocarcinoma from mucinous cystadenocarcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 395, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n377\nMucinous Cystic Tumors of the Pancreas (Cystadenoma and Cystadenocarcinoma)\u2002 can be \nfound anywhere in the pancreas, but more commonly occur in the body or tail. The tumors are com\u00ad\nprised of mucin-\u00adcontaining cystic spaces, usually thin-walled. Look for solid areas or thickened walls with \npapillary excrescences; these areas are more likely to contain invasive tumor.\nSerous Cystic Neoplasms\u2002 are more uniform in appearance and are virtually always benign. These \ntumors only occasionally communicate with the normal ductal system. The tumors consist of a circum\u00ad\nscribed area of small cysts separated by thin septa and may have a central stellate scar.\nIntraductal Papillary Mucinous Neoplasms\u2002 are grossly similar to mucinous cystic tumors in that \nthey are comprised of mucin-containing spaces. However, these tumors are usually in continuity with the \nmain pancreatic duct and are more common in the head region.\nAcinar Cell Carcinoma\u2002 occurs anywhere in the pancreas and consists of multiple, soft, well-cir\u00ad\ncumscribed red/brown nodules separated by fibrous septa. Occasionally tumors can consist of multiple \ncysts.\nPancreatoblastoma\u2002 is the most common pancreatic tumor of childhood. The large, soft, encapsu\u00ad\nlated mass can occur at any site in the pancreas.\nChronic Pancreatitis\u2002 can result in a very hard, scarred pancreas that is difficult to distinguish from \nan invasive carcinoma. Calculi may be present within the pancreatic duct and pseudocysts may form in \nperipancreatic soft tissue.\nPseudocysts\u2002 are usually associated with pancreatitis and arise due to digestion of tissues by pancre\u00ad\natic enzymes. The cystic cavity is generally extrapancreatic but attached by fibrotic tissue. A portion of \nthe adjacent stomach may be included with the specimen. The cyst may be filled with blood and necrotic \nmaterial.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: Up to six blocks, including relationship to pancreas, ducts, ampulla, duodenal mucosa, and \nsurrounding soft tissue.\n\t\u2022\t \u0007Margins: Pancreatic resection margin (either perpendicular or en face), soft tissue around pancreas, \ncommon bile duct, stomach, duodenum. Only the posterior retroperitoneal soft tissue and the poste\u00ad\nrior (non-peritonealized) surface of the uncinate process are true margins being in continuity with the \npatient. The remaining soft tissue \u201cmargins\u201d evaluate tumor invasion outside of the pancreas and are \ntaken perpendicular to the tumor.\n\t\u2022\t \u0007Uninvolved pancreas: One to two cassettes including normal and abnormal-appearing areas.\n\t\u2022\t \u0007Ampulla: One cassette (if not previously submitted)\n\t\u2022\t \u0007Lymph nodes: Submit all lymph nodes as separate groups. Regional lymph nodes include the \n\u00adfollowing:\n\t \u2022\t \u0007Superior pancreatic nodes: superior to the head and body of the pancreas\n\t \u2022\t \u0007Anterior pancreatic nodes: anterior pancreaticoduodenal, pyloric, and proximal mesenteric\n\t \u2022\t \u0007Inferior pancreatic nodes: inferior to the head and body of the pancreas\n\t \u2022\t \u0007Posterior pancreatic nodes: posterior pancreaticoduodenal, common bile duct or pericholedochal, \nand proximal mesenteric\n\t \u2022\t \u0007Retroperitoneal nodes\n\t \u2022\t \u0007Lateral aortic nodes\n\t \u2022\t \u0007Hepatic artery nodes\n\t \u2022\t \u0007Superior mesenteric nodes\n\t \u2022\t \u0007Infrapyloric nodes (tumors of the head only)\n\t \u2022\t \u0007Subpyloric nodes (tumors of the head only)\n\t \u2022\t \u0007Celiac nodes (tumors of tne head only)\n\t \u2022\t \u0007Pancreaticolienal nodes (tumors of the body and tail only)\n\t \u2022\t \u0007Splenic nodes: hilum of spleen and tail of the pancreas (tumors of the body and tail only)\n Involvement of other nodal groups is considered distant metastasis", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_395.png", "summary": "The page discusses different types of pancreatic tumors, including mucinous cystic tumors, serous cystic neoplasms, intraductal papillary mucinous neoplasms, acinar cell carcinoma, pancreatoblastoma, and conditions like chronic pancreatitis and pseudocysts.", "questions": [ "What are the key differences between mucinous cystic tumors and serous cystic neoplasms?", "How can chronic pancreatitis be distinguished from invasive carcinoma?", "Why is it important to evaluate lymph nodes in pancreatic specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 396, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n378\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cWhipple,\u201d are the stomach (20 \ncm in length \u00d7 15 cm in circumference x 0.5 cm wall thickness), duodenum (30 cm in length \u00d7 4 cm in \ncircumference) and pancreatic head (5 \u00d7 4 \u00d7 4 cm (length)). There is a tan/white, 3 \u00d7 2 \u00d7 2 cm, diffusely \ninfiltrating tumor mass in the head of the pancreas which surrounds the main pancreatic duct and the \ncommon bile duct at their junction. The bile duct is patent but dilated to 0.7 cm in diameter. The pan\u00ad\ncreatic duct is obstructed by the tumor mass. The tumor is 1 cm from the ampulla of Vater and does not \ngrossly involve the duodenal muscularis or mucosa. The tumor is 2 cm from the distal pancreatic resec\u00ad\ntion margin which is grossly free of tumor. The lateral margins are composed of yellow/white adipose \ntissue ranging in thickness from 1 to 3 cm and are grossly free of tumor. The remainder of the pancreatic \nparenchyma is firm and nodular. The cystic duct remnant is 2 cm in length by 0.7 cm in diameter. There \nis an adjacent 1.1 cm fleshy lymph node. The gastric mucosa is unremarkable. Two lymph nodes are pres\u00ad\nent in the perigastric soft tissue (0.5 and 0.3 cm). The distal 20 cm of the duodenal mucosa has a dusky \nred/brown color. Three periduodenal lymph nodes are found, the largest measuring 0.6 cm. Three lymph \nnodes are found adjacent to the pancreas (one anterior and two inferior), the largest measuring 0.9 cm. \nThe margins are inked. Photographs are taken.\nCassettes #1-2: Pancreatic resection margin, en face, 2 frags, ESS.\nCassettes #3-4: Tumor and common bile duct, 2 frags, RSS.\nCassettes #5-6: Tumor and pancreatic duct, 2 frags, RSS.\nCassettes #7-8: Tumor and pancreatic parenchyma, 2 frags, RSS.\nCassette #9: Anterior margin, perpendicular, 1 frag, RSS.\nCassette #10: Superior margin, perpendicular, 1 frag, RSS.\nCassette #11: Posterior margin, perpendicular, 1 frag, RSS.\nCassette #12: Inferior margin, perpendicular, 1 frag, RSS.\nCassette #13: Gastric resection margin, en face, 1 frag, RSS.\nCassette #14: Duodenal resection margin, en face, 1 frag, RSS.\nCassette #15: Common bile duct margin, en face, 1 frag, RSS.\nCassette #16: Uninvolved pancreas, 2 frags, RSS.\nCassette #17: Ampulla, 1 frag, RSS.\nCassette #18: Common bile duct lymph node, 2 frags, ESS.\nCassette #19: Two perigastric lymph nodes, 2 frags, ESS.\nCassette #20: Three periduodenal lymph nodes, 3 frags, ESS.\nCassette #21: One anterior pancreatic node, 2 frags, ESS.\nCassette #22: Two inferior pancreatic nodes, 2 frags, ESS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR PANCREATIC TUMORS\n\t\u2022\t \u0007Specimen: Pancreas (head, body, or tail), duodenum, stomach, common bile duct, gallbladder, spleen, \nlarge vessels (portal vein, superior mesenteric vein)\n\t\u2022\t \u0007Procedure: Pancreaticoduodenectomy (Whipple procedure), distal partial pancreatectomy (body or \ntail), other organs included (spleen, gallbladder)\n\t\u2022\t \u0007Tumor Site: Ampulla, periampullary, head of pancreas (to the right of the left border of the superior \nmesenteric vein including the uncinate process), body of pancreas (between the left border of the \nsuperior mesenteric vein and the left border of the aorta), tail of pancreas (between the left border of \nthe aorta and the hilum of the spleen). Clinical information may be necessary to identify the location \nof some tumors.\n\t\u2022\t \u0007Tumor Size: Greatest dimension (other dimensions optional)\n\t \u2022\t \u0007For endocrine tumors, tumors \u2265 2.5 cm are correlated with aggressive biologic behavior (tumors < \n2.5 cm are almost always benign, tumors > 10 cm are highly likely to be malignant).\n\t\u2022\t \u0007Tumor Focality: For endocrine tumors: unifocal, multifocal (give number)\n\t\u2022\t \u0007Histologic Type: Pancreas, exocrine: Ductal adenocarcinoma, mucinous noncystic carcinoma, signet ring \ncell carcinoma (> 50% signet ring cells), adenosquamous carcinoma, undifferentiated (anaplastic) carcinoma, \nmixed ductal-endocrine carcinoma, serous cystadenocarcinoma, mucinous cystic neoplasm (noninvasive or \ninvasive), intraductal papillary-mucinous neoplasm (noninvasive or invasive), acinar cell carcinoma, acinar \ncell cystadenocarcinoma, mixed acinar-endocrine carcinoma solid pseudopapillary tumor, others", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_396.png", "summary": "The specimen received is from a Whipple procedure involving the stomach, duodenum, and pancreatic head, with a tumor mass present in the head of the pancreas.", "questions": [ "What are the dimensions and characteristics of the tumor mass in the pancreatic head?", "How are the main pancreatic duct and common bile duct affected by the tumor?", "What are the findings related to lymph nodes in the perigastric and periduodenal areas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 397, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n379\n\t \u2022\t \u0007Pancreas, endocrine: well-differentiated endocrine neoplasm, poorly differentiated endocrine carci\u00ad\nnoma (small cell carcinoma or large cell carcinoma), other. The WHO Classification may be used \n(well-differentiated endocrine tumor, benign behavior, well-differentiated endocrine tumor, uncer\u00ad\ntain behavior, poorly differentiated endocrine carcinoma (Tables 19-31 and 19-32)\n\t\u2022\t \u0007Functional Type: If an endocrine tumor is present, correlate with clinical syndrome and/or elevated \nserum levels of hormone product\n\t\u2022\t \u0007Mitotic Activity: Endocrine tumors: Not identified, present (< 2 mitoses/10 HPF), present \u2265 2 mito\u00ad\nses/10 HPF). If Ki-67 is performed, report < 2%, 3% to 20%, or > 20% positive cells.\n\t\u2022\t \u0007Tumor Necrosis: Endocrine tumors: Not identified, present\n\t\u2022\t \u0007Histologic Grade: Well, moderately, poorly, undifferentiated (for ductal carcinomas; Table 19-33)\n\t\u2022\t \u0007Microscopic Tumor Extension: Carcinoma in situ (Tis), limited to pancreas, \u2264 2 cm (T1), lim\u00ad\nited to pancreas, > 2 cm (T2), extension beyond pancreas but without involvement of the celiac axis \nor the superior mesenteric artery (T3), involvement of the celiac axis or the superior mesenteric \nartery (T4)\n\t \u2022\t \u0007Invasion of duodenum, ampulla of Vater, sphincter of Oddi, common bile duct, peripancreatic tis\u00ad\nsues (retroperitoneum, mesentery, mesocolon), stomach, spleen, colon, large vessels (portal vein, \nmesenteric vessels, common hepatic artery), mesentery, omentum\n\t\u2022\t \u0007Margins: Invasive carcinoma or in situ dysplasia or carcinoma:\n\t \u2022\t \u0007Involved or not involved (distance from closest margin), including common bile duct margin, pan\u00ad\ncreatic parenchymal margin including pancreatic duct margin, uncinate process margin (nonperito\u00ad\nnealized surface of the uncinate process), posterior (retroperitoneal) pancreas, duodenum, stomach, \nperipancreatic soft tissue margins (anterior, inferior, posterior, superior)\n\t \u2022\t \u0007Type of ductal epithelium at parenchymal margin (normal, mucinous metaplasia, dysplasia). The \nPanIN classification scheme should be used.\nTABLE 19\u201331.\u2003\nCLASSIFICATION OF PANCREATIC ENDOCRINE TUMORS\nTUMOR TYPE\nCLINICAL SYMPTOMS\nPancreatic Endocrine Tumor, Functional\nInsulinoma (insulin-\u00adsecreting)\nHypoglycemia, neuropsychiatric disorders\nGlucagonoma (\u00adglucagon-secreting)\nDiabetes, skin rash (necrolytic migratory erythema), stomatitis\nGastrinoma (gastrin-secreting)\nAbdominal pain, ulcer disease, diarrhea, gastrointestinal \n\u00adbleeding\nSomatostatinoma (somatostatin-secreting)\nDiabetes, steatorrhea, achlorhydria\nPP-oma (pancreatic polypeptide-secreting)\nClinically silent, elevated serum PP levels\nVIP-oma (vasoactive intestinal polypeptide \nsecreting, Verner-Morrison tumors)\nWatery diarrhea, hypokalemia, achlorhydria\nAdrenocorticotropic hormone secreting\nCushing syndrome: central obesity, muscle weakness, glucose \nintolerance, hypertension\nCarcinoid tumor (serotonin-producing)\nCarcinoid syndrome: flushing, diarrhea\nPancreatic Endocrine Tumor, Non-Functional\nPancreatic endocrine tumor, non-secretory\nMixed ductal-endocrine carcinoma\nMixed acinar-endocrine carcinoma\nHigh mitotic activity (>4 per 10 HPFs, 80% malignant), a high degree of pleomorphism, and tumor necrosis correlate with malignant potential. Larger \ntumor size (\u22652.5 cm) correlates with local invasion, vascular invasion, and metastasis.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_397.png", "summary": "This page provides information on the classification and evaluation of pancreatic endocrine tumors, including clinical symptoms associated with different tumor types.", "questions": [ "What are the different types of pancreatic endocrine tumors mentioned in the text?", "How is the histologic grade of endocrine tumors determined?", "What are the clinical symptoms associated with a VIP-oma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 398, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n380\n\t\u2022\t \u0007Treatment Effect: No prior treatment, prior treatment with: no residual tumor (complete response, \ngrade 0), marked response (minimal residual carcinoma, grade 1), moderate response (grade 2), no \ndefinite response (poor or no response, grade 3)\n\t \u2022\t \u0007Pools of acellular mucin should not be interpreted as residual carcinoma.\n\t \u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\nTABLE 19\u201332.\u2003 WHO CLASSIFICATION OF ENDOCRINE TUMORS OF THE PANCREAS\nWELL \nDIFFERENTIATED \nENDOCRINE TUMOR\nWELL \nDIFFERENTIATED \nENDOCRINE \nCARCINOMA\nPOORLY DIFFERENTIATED \nENDOCRINE CARCINOMA \nOR SMALL CELL CARCINOMA\nGrowth Pattern\nSmall solid nests, \ntrabeculae, gyriform \ncords, or pseudo\u00ad\nglandular structures\nSolid nests and sheets, \ntrabeculae, gyriform \ncords, or pseudoglan\u00ad\ndular structures\nLarge, ill-defined solid aggregates or \ndiffuse sheets of cells\nCytologic \n\u00adFeatures\nNo or minimal atypia\nMild to moderate \natypia, hyperchro\u00ad\nmatic nuclei, fairly \nprominent nucleoli\nHighly atypical, small to intermedi\u00ad\nate sized cells with high N:C ratio, \npoorly granular or agranular cyto\u00ad\nplasm\nLocal Extent\nUsually circumscribed, \ncan be ill-defined, \nconfined to pancreas\nMay invade local struc\u00ad\ntures\nUsually invades locally\nSize\n<2 cm\nMost >3 cm\nAny size\nNecrosis\nAbsent\nUsually absent\nOften present\nLymphovascular \nor perineural \ninvasion\nAbsent\nOften present\nUsually prominent\nMitoses (per 10 \nHPF)\n\u22642\n2 to 10\n>10\nKi-67 (% of cells)\n\u22642%\n>5%\n>15%\nP53\nFrequently present\nMetastases\nAbsent\nMay be present (regional \nlymph nodes or liver)\nOften present (liver and extra-\u00ad\nabdominal sites)\nMixed exocrine-endocrine carcinomas are tumors with an admixture of the two components; the biologic behavior is determined by that of the \nexocrine component.\nFrom Kloppel G, Solcia E, Longnecker DS, Capella C, Sobin LH: Histological Typing of Tumours of the Exocrine Pancreas (WHO World Health \nOrganization International Histological Classification of Tumours), 2nd ed. Springer, 2002.\nTABLE 19\u201333.\u2003\n\u0007GRADING SYSTEM FOR INFILTRATING DUCTAL CARCINOMAS \nOF THE PANCREAS\nGrade I\nWell differentiated (>95% of the tumor is composed of glands)\nGrade II\nModerately differentiated (50% to 95% of the tumor is composed of glands)\nGrade III\nPoorly differentiated (5% to 49% of the tumor is composed of glands)\nGrade IV\nUndifferentiated (<5% of the tumor is composed of glands)\nSee reference 11.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_398.png", "summary": "This page provides information on the treatment effect, lymph-vascular invasion, WHO classification of endocrine tumors of the pancreas, and grading system for infiltrating ductal carcinomas of the pancreas.", "questions": [ "What are the different treatment responses mentioned for pancreatic specimens?", "How does the presence of pools of acellular mucin impact the interpretation of residual carcinoma?", "What are the key differences in growth pattern, cytologic features, local extent, and other characteristics between well-differentiated endocrine tumors and poorly differentiated endocrine carcinomas of the pancreas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 399, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n381\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Tumor Configuration: Infiltrative, circumscribed (solid or cystic, partially or entirely circumscribed)\n\t\u2022\t \u0007Intraductal Lesions: Papillary hyperplasia, carcinoma in situ\n\t\u2022\t \u0007Regional Lymph Nodes: Metastases present or absent, number of metastases, number of nodes examined\n\t \u2022\t \u0007Regional vs. distant. Note: The definition of regional nodes depends on the location of the tumor.\n\t \u2022\t \u0007Gastric lymph nodes: distant for all\n\t \u2022\t \u0007Pyloric lymph nodes: regional for head, distant for body and tail\n\t \u2022\t \u0007Peripancreatic lymph nodes: regional for all. Divide into superior, inferior, anterior, and posterior \ngroups.\n\t \u2022\t \u0007Splenic lymph nodes: regional for body and tail, distant for head.\n\t\u2022\t \u0007Additional Pathologic Findings: Nonlesional pancreas\n\t \u2022\t \u0007Chronic pancreatitis, acute pancreatitis, fibrosis, pancreatic intraepithelial neoplasia, intraductal \npancreatic mucinous tumor, islet cell hyperplasia, adenomatosis\n\t \u2022\t \u0007Stomach and duodenum: Gastritis (chemical or Helicobacter pylori), duodenitis, peptic ulcer disease, \nampullitis\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (see Table \n19-34). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/\u2009\u2009) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nTABLE 19-34.\u2003\n\u0007AJCC (7TH EDITION) CLASSIFICATION OF EXOCRINE AND ENDOCRINE \nPANCREATIC TUMORS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ*\nT1\nTumor limited to the pancreas, 2 cm or less in greatest dimension\nT2\nTumor limited to the pancreas, more than 2 cm in greatest dimension\nT3\nTumor extends beyond the pancreas but without involvement of the celiac axis or the supe\u00ad\nrior mesenteric artery\nT4\nTumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor)\n* This also includes the PanInIII classification (severe ductal dysplasia/carcinoma in situ).\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nRegional lymph node metastasis\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nDistant metastasis includes seeding of the peritoneum (even if limited to the lesser sac region) and positive peritoneal cytology.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_399.png", "summary": "This page provides detailed information on the pathological findings in gastrointestinal specimens, specifically focusing on the pancreas, including tumor configuration, intraductal lesions, regional lymph nodes, additional pathologic findings, distant metastasis, and AJCC classification.", "questions": [ "What are the different types of intraductal lesions that can be identified in pancreatic specimens?", "How are regional lymph nodes classified in relation to pancreatic tumors?", "What is the significance of distant metastasis in pancreatic cancer staging?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 400, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n382\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR CARCINOMAS OF THE AMPULLA OF VATER\n\t\u2022\t \u0007Specimen: Ampulla of Vater, stomach, pancreas (head, body), duodenum, common bile duct, gall\u00ad\nbladder\n\t\u2022\t \u0007Procedure: Pancreatoduodenectomy (Whipple procedure), ampullectomy\n\t\u2022\t \u0007Tumor Site: Intra-ampullary, periampullary, papilla of Vater (junction of ampullary and duodenal \nmucosa), not specified\n\t\u2022\t \u0007Tumor Size: Greatest dimension (tumors < 2.5 cm have a 65% 5-year survival rate whereas tumors \n> 2.5 cm have a 20% 5-year survival rate).\n\t\u2022\t \u0007Histologic Type: Papillary adenocarcinoma, adenocarcinoma, intestinal type, mucinous adenocarci\u00ad\nnoma, clear cell adenocarcinoma, signet ring cell carcinoma (> 50% signet ring cells), adenosquamous \ncarcinoma, others\n\t\u2022\t \u0007Histologic Grade: Well, moderate, poorly, undifferentiated (Table 19-35)\n\t\u2022\t \u0007Microscopic Tumor Extension: Carcinoma in situ, tumor limited to ampulla of Vater or sphincter \nof Oddi, invasion of muscle of the sphincter of Oddi, invasion of duodenal wall, invasion into pancreas, \ninvasion into peripancreatic soft tissue or other adjacent organs or structures\n\t\u2022\t \u0007Margins: Involved or not involved, pancreatic margins, duodenal margins, distance to closest margin \nincluding common bile duct and pancreatic duct\n\t\u2022\t \u0007Intraductal Lesions: Papillary hyperplasia, carcinoma in situ\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural invasion: Not identified, present\n\t\u2022\t \u0007Regional Lymph Nodes: Regional lymph nodes include nodes superior, inferior, and posterior to the \nhead and body of pancreas, pyloric nodes, proximal mesenteric nodes, hepatic artery nodes, common \nbile duct nodes, infrapyloric nodes, subpyloric nodes, celiac nodes, superior mesenteric nodes, retro\u00ad\nperitoneal nodes, and lateral aortic nodes.\n\t \u2022\t \u0007Specify the number of nodes examined and the number with metastases\n\t\u2022\t \u0007Additional Pathologic Findings: Chronic pancreatitis, metaplasia, pancreatic intraepithelial neopla\u00ad\nsia, acute pancreatitis, fibrosis, islet cell hyperplasia\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 19-36). \nM0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nTABLE 19\u201335.\u2003\n\u0007GRADING SYSTEM FOR NON-PAPILLARY CARCINOMAS \nOF THE AMPULLA OF VATER\nGrade I\nWell differentiated (>95% of the tumor is composed of glands)\nGrade II\nModerately differentiated (50% to 95% of the tumor is composed of glands)\nGrade III\nPoorly differentiated (<49% of the tumor is composed of glands)\nGrade IV\nUndifferentiated carcinomas and small cell carcinoma (high-grade neuroendocrine carcino\u00ad\nmas in the WHO classification)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_400.png", "summary": "This page provides a checklist for pathologic prognostic and diagnostic features for carcinomas of the ampulla of Vater, including details on tumor site, size, histologic type, grade, extension, margins, lymphatic invasion, distant metastasis, and AJCC classification.", "questions": [ "What are the different histologic types of carcinomas of the ampulla of Vater?", "How does tumor size impact the 5-year survival rate for carcinomas of the ampulla of Vater?", "What are the regional lymph nodes included in the assessment for carcinomas of the ampulla of Vater?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 401, "text": "GASTROINTESTINAL SPECIMENS (INCLUDING HEPATOBILIARY AND PANCREATIC SPECIMENS)\u2003 Pancreas\n383\nREFERENCES\n\t\u2002 1.\t \u0007Lee RG, et al: Protocol for the examination of specimens removed from patients with esophageal carcinoma: \nA basis for checklists. Arch Pathol Lab Med 121:925-929, 1997.\n\t\u2002 2.\t \u0007Lewin KJ, Appelman HD. Tumors of the Esophagus and Stomach. AFIP Fascicle 18, Third Series 293, 1995.\n\t\u2002 3.\t \u0007Fenger C. Histology of the anal canal. Am J Surg Pathol 12:41-55, 1988.\n\t\u2002 4.\t \u0007Am J Clin Pathol 111:349-351, 1999.\n\t\u2002 5.\t \u0007Thelmo WL, Vetrano JA, Wibowo A, et al. Angiodysplasia of colon revisited: pathologic demonstration without \nthe use of intravascular injection technique. Hum Pathol 23:37-40, 1992.\n\u0007(A description of an alternative method for processing these specimens. The specimen is fixed inflated for three \nhours. The mucosa is carefully removed and passed through ethanol. Dilated vessels in the mucosa are visualized \ngrossly using transillumination.)\n\t\u2002 6.\t \u0007Mitsudo SM, et al: Vascular ectasias of the right colon in the elderly: A distinct pathologic entity. Human Path \n10:585, 1979.\n\t\u2002 7.\t \u0007Hytiroglou P, Thung SN, Gerber MA. Histological classification and quantitation of the severity of chronic \nhepatitis: keep it simple!. Seminars in Liver Disease 15:414-421, 1995.\n\t\u2002 8.\t \u0007Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 13:372-374, 1991.\n\t\u2002 9.\t \u0007Stocker JT. An approach to handling pediatric liver tumors. Am J Clin Pathol 109(Suppl 1):S67-S72, 1998.\n\t10.\t \u0007Cubilla AL, et al: Lymph node involvement of the head of the pancreas area. Cancer 41:880-887, 1978.\n\t11.\t \u0007Recommendations for reporting resected pancreatic neoplasms. Mod Pathol 11:500-504, 1998.\nTABLE 19-36.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF TUMORS OF THE AMPULLA OF VATER\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ\nT1\nTumor limited to the ampulla of Vater or sphincter of Oddi\nT2\nTumor invades duodenal wall\nT3\nTumor invades pancreas\nT4\nTumor invades peripancreatic soft tissues or other adjacent organs or structures other than \npancreas\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nRegional lymph node metastasis\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: This staging system is not used for carcinoid tumors or other neuroendocrine tumors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_401.png", "summary": "The page provides references and a description of an alternative method for processing gastrointestinal specimens, specifically the pancreas.", "questions": [ "What is the significance of fixing the specimen inflated for three hours?", "How does the alternative method for processing gastrointestinal specimens differ from traditional methods?", "Why is it important to visualize dilated vessels in the mucosa using transillumination?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 402, "text": "384\n20\nGenitourinary Specimens\nGenitourinary pathology includes specimens from the kidney, ureters, bladder, prostate, and testis. The \nkidney may be biopsied as part of the evaluation of renal function. Otherwise, genitourinary specimens \nare generally biopsied or excised for neoplastic disease.\nKIDNEY\nNeedle or Wedge Biopsies\n\u201cMedical\u201d renal biopsies are typically performed for evaluation of renal function or urinary abnormalities \nand are assessed in the context of the clinical presentation of the patient, with particular attention to the \nresults of serological tests and the urinalysis (see Table 20-1). Resectable kidney masses are rarely biop\u00ad\nsied because of the virtually diagnostic appearance of tumors on CT scan and the need for resection for \ntreatment. Unresectable tumors are usually diagnosed by FNA. Occasionally, biopsies will be performed \non kidneys with tumors that will be treated with cryotherapy, or before a kidney is used for transplanta\u00ad\ntion (see Chapter 6).\nRELEVANT CLINICAL HISTORY\nSee Table 20-1.\nTABLE 20\u20131.\u2003\nRELEVANT CLINICAL HISTORY \u2013 KIDNEY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR KIDNEY SPECIMENS\nOrgan/tissue resected or biopsied\nUrinalysis: presence and quantity of protein (spot \nurine protein to urine creatinine ratio, 24-hour \n\u00adquantification); blood; amount and type of casts \n(e.g., red blood cells, white blood cells, muddy brown).\nPurpose of the procedure\nRenal function tests (BUN and creatinine) and time \nframe of changes.\nGross appearance of the organ/tissue/lesion sampled\nSystemic conditions (e.g., connective tissue and \n\u00adautoimmune diseases, acute or chronic infections, \nhemoglobinopathies, hypertension, obesity, \u00addiabetes \nmellitus, anti-phospholipid syndrome, myeloma, \nvasculitis, HUS)\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nResults of serology (e.g., anti-GBM antibodies, ANCA, \nANA, C3, C4, cryoglobulins, hepatitis B and C)\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, \ndrug use that can change the histologic \n\u00adappearance of \u00adtissues)\nDrug use (analgesics, penicillamine, hydralazine, \n\u00adchemotherapeutic agents, antihypertensives, \nACE inhibitors, angiotensin receptor blockers)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_402.png", "summary": "Genitourinary pathology includes specimens from various organs such as the kidney, ureters, bladder, prostate, and testis, with kidney biopsies typically performed for evaluation of renal function or neoplastic disease.", "questions": [ "What are the common indications for performing kidney biopsies?", "How are resectable kidney masses typically diagnosed?", "What are some relevant clinical history factors to consider when evaluating kidney specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 403, "text": "GENITOURINARY SPECIMENS\u2003 Kidney\n385\nPROCESSING THE SPECIMEN\n 1.\t \u0007The biopsy is usually performed by a nephrologist in conjunction with a radiologist, under ultra\u00ad\nsound guidance. Occasionally, the radiologist may perform a percutaneous biopsy under CT guid\u00ad\nance, or a transjugular biopsy in the angiography suite. After each pass, the needle core biopsy \n(ideally 15-gauge) is examined unfixed under stereo-microscopy by the renal pathologist to assess \nthe adequacy of the specimen and to determine the need for additional biopsies. The consensus clas\u00ad\nsification for adequacy of a transplant biopsy recommends that there must be 10 or more glomeruli, \nand two arteries.1\n 2.\t \u0007Clean forceps must be used when allocating tissue for light microscopy, IF, and EM! \nMinute amounts of formalin or glutaraldehyde can destroy the antigenicity of the tissue \nallocated for IF, and glutaraldehyde can create problems in interpreting tissue for light \nmicroscopy.\nRepresentative cortex and, if available, medulla (for evaluation of casts), are allocated for IF by place\u00ad\nment in Zeus transport solution (Michel\u2019s solution).\nA few viable glomeruli are usually sufficient for placement in Karnovsky\u2019s glutaraldehyde/paraformal\u00ad\ndehyde fixative for EM.\n 3.\t \u0007The remaining tissue is fixed in formalin. Each core is separately wrapped in tissue paper and placed \nin a separate green cassette. Tissue sections are cut at 3 to 4 microns. Special stains are evaluated on \nall renal biopsies (H&E, PAS, Jones\u2019 silver methenamine, and AFOG trichrome.\nNephrectomy\nNephrectomies are commonly performed for tumors (usually renal cell carcinoma, rarely urothelial \n(transitional) cell carcinoma of the renal pelvis) or to remove nonfunctioning grafts. Native nonfunction\u00ad\ning kidneys are also sometimes removed. Partial nephrectomies are becoming more common to resect \ntumors if the other kidney is absent or nonfunctioning or if the primary tumor is small (e.g., a tumor \nfound incidentally on CT scan or ultrasound).\nThe examination of the non-neoplastic kidney is important for the recognition of other diseases that \nput the patient at risk for progressive renal failure.2,3\nTransplant Nephrectomy\nRenal grafts are transplanted to the pelvis with a short vascular pedicle connected to the inguinal \nvessels. The specimen usually consists simply of the kidney, without surrounding soft tissue, and ves\u00ad\nsels cut flush with the hilum. Transplant failure may be due to preexisting disease in the allograft, \nvascular insufficiency (e.g., thrombosis or plaque), rejection, or recurrence of the patient\u2019s original \nrenal disease.\nCompromised immune system\nBlood pressure\nEdema\nGlucose values and hemoglobin A1c\nCulture results\nSPEP and UPEP\nRadiographic findings (symmetry, obstruction, etc.)\nFor transplants: Duration of transplant, donor informa\u00ad\ntion (living, deceased, related, unrelated, \u201cexpanded \ncriteria\u201d, polyoma serology, history of prior trans\u00ad\nplants, results of prior transplant biopsies, relevant \ninterventions (e.g., changes in immunosuppressive \ntherapy), serum levels of immunosuppressive therapy.\nTABLE 20\u20131.\u2003\nRELEVANT CLINICAL HISTORY - KIDNEY\u2014cont\u2019d\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR KIDNEY SPECIMENS", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_403.png", "summary": "The page discusses the processing of kidney specimens for biopsy and nephrectomy procedures, emphasizing the importance of proper handling and allocation of tissue for different types of analysis.", "questions": [ "What are the key steps involved in processing a kidney biopsy specimen?", "Why is it important to use clean forceps when allocating tissue for different types of microscopy?", "What are some common reasons for performing nephrectomies and how are they different from transplant nephrectomies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 404, "text": "GENITOURINARY SPECIMENS\u2003 Kidney\n386\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh (normal is 125 to 170 gm for males and 115 to 155 gm for females) and record the measure\u00ad\nments of the kidney. Record the length and diameter of any vessels at the hilum. Look for patency of \nvessels (thrombosis, intimal proliferation, atherosclerotic plaques).\n 2.\t \u0007Describe the renal parenchyma including color (tan/red, gray/green), thickness of cortex, shape of \ncalyces and papillae (normal, blunted), state of pelvis and ureter, vessels, infarcts (size and location), \nhemorrhage, necrosis.\n 3.\t \u0007Submit four cassettes including cortex and medulla, hilar vessels, and focal lesions and request one \nH&E, PAS stain, Jones\u2019 silver methenamine, and trichrome (AFOG) on one block containing kidney \ncortex (see also below).\nIf the transplant has failed six months or more after transplantation, or if there is significant proteinuria, \nand recurrence of the patient\u2019s original disease is suspected, always save cortex for EM and immuno\u00ad\nfluorescence microscopy.\nNative Kidney Nephrectomy\nNonfunctioning kidneys may be removed due to hypertension refractive to medical therapy, persistent \npyelonephritis, severe renal protein loss, polycystic kidneys, or in patients with bilateral renal tumors. \nA native kidney may also be removed to provide a native ureter for the allograft.\nAcquired cystic kidney disease (ACKD) occurs in over 30% of patients with end-stage renal disease, \nand the incidence increases over time. Papillary hyperplasia is commonly present in the walls of the cysts \nand is thought to be a precursor lesion for carcinomas. Adenomas are frequently found in this population \n(about 25%) and are typically multiple and bilateral.\nRenal cell carcinomas develop in 5% to 10% of patients, and 70% to 80% of these patients will have \nACKD. Carcinomas are more likely to be multifocal (50%) and 25% of patients have bilateral tumors. \nAlthough many are small and incidental, some do metastasize, for an overall five-year survival rate of \n35%. Different types of tumor types are seen.4 About one third are \u201cACKD associated\u201d renal cell carci\u00ad\nnomas \u2013 well circumscribed and encapsulated, often with papillary areas, AMACR+, CK7-. 15% are clear \ncell papillary carcinomas (AMACR-), 18% papillary, and 8% chromophobe.\nThe incidence of urothelial carcinomas is increased in patients with analgesic-related renal failure.\nThe cortex is examined as for a diagnostic renal biopsy to identify the etiology of the renal failure.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh (normal is 125 to 170 gm for males and 115 to 155 gm for females) and record the measure\u00ad\nments of the kidney. Record the length and diameter of any vessels at the hilum. Look for patency of \nvessels (thrombosis, intimal proliferation, atherosclerotic plaques).\n 2.\t \u0007Describe the renal parenchyma including color (tan/red, gray/green), thickness of cortex, shape of \ncalyces and papillae (normal, blunted), state of pelvis and ureter, vessels, infarcts (size and location), \nhemorrhage, necrosis. The number and size of cysts are recorded.\nThe entire kidney is thinly sectioned and examined for solid lesions. The lining of cysts is examined \nfor any areas of thickening or irregularities.\nFresh normal cortical tissue may be saved for immunofluoresence (Zeus medium) and fixed for EM if \nthese studies might be requested.\n 3.\t \u0007Submit four cassettes including cortex and medulla and hilar vessels. Additional cassettes are submit\u00ad\nted to document any solid or cystic areas suspicious for carcinoma.\nLaparoscopic Nephrectomy with Morcellation\nLaparoscopic surgery offers numerous advantages for patients. However, in order to remove tissues and \norgans through a small skin incision, they must be morcellated (i.e., reduced to small fragments) and this \nprocedure introduces new challenges to pathologists. This procedure has been used for the removal of \nadrenal glands, kidneys, spleens, and prostate glands.\nIt may not be possible to determine the size, status of margins, and renal vein involvement for such \nspecimens. However, this information can also be determined from imaging studies and the decreased \nmorbidity to the patient may outweigh the loss of specific pathologic confirmation.\nA method has been described to allow inking of margins prior to morcellation.5 If gross tumor, vessels, \nand/or ureter are apparent, these specific structures can be selected for microscopic \u00adexamination.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_404.png", "summary": "The page discusses the processing and examination of kidney specimens, including the importance of weighing and measuring the kidney, describing the renal parenchyma, and submitting specific cassettes for testing.", "questions": [ "What are some common reasons for native kidney nephrectomy?", "What is the significance of acquired cystic kidney disease (ACKD) in patients with end-stage renal disease?", "What are the different types of renal cell carcinomas and their associated characteristics?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 405, "text": "GENITOURINARY SPECIMENS\u2003 Kidney\n387\nPathologic examination will be more problematic if there is a small mass and a prior diagnosis has \nnot been made. In most cases, fragments containing tumor are grossly identifiable. A model has been \ndescribed to estimate the amount of tissue that would need to be examined in order to find a tumor of \na given size in a specimen of a certain size with 95% certainty if gross tumor cannot be identified.6 For \nexample, to find a 4.5 cm tumor in a normal-sized kidney, approximately 11 cassettes of tissue would need \nto be examined. However, it could take over 100 cassettes to find a 1\u00a0cm tumor. Cytology washings from \nthe retrieval bag can also provide a diagnosis in the majority of patients.7\nRadical Nephrectomy\nRadical nephrectomies consist of the kidney, most of the ureter, renal vein and artery, perinephric fat, \nand surrounding Gerota\u2019s fascia. An adrenal gland may or may not be present.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the entire specimen and record its dimensions. Examine the hilum carefully and identify the \nureter, renal vein, and renal artery. The vessels will usually be tied off with sutures.\nTumor involvement of the renal vein is usually obvious and has the appearance of a smoothly \nsurfaced projection of tumor extending out from the hilum. There may be a \u201cplug\u201d of tumor in the \nlumen, or the tumor may invade into the vessel wall. It is useful to determine if vessel invasion was seen \non pre-operative radiologic studies in order to specifically document this finding.\nTake cross-sections of the margins (vein, artery, and ureter) and place in a labeled cassette.\nPalpate the hilar region for any lymph nodes and save in a labeled cassette. Typically lymph nodes \nare not found.\n 2.\t \u0007Inspect the outer portion of the specimen. The kidney is surrounded by perirenal fat. Surrounding \nthis fat, the kidney, and the adrenal gland is the renal fascia (\u201cGerota\u2019s fascia\u201d).\nIf there are areas suspicious for tumor at the margin (which is rarely seen as most tumors are limited \nto the renal parenchyma), ink these areas selectively.\nThe kidney is then bivalved with a single longitudinal cut.\nIf the section starts at the hilum, place a probe into the ureter. Cut along the probe to bisect the \nureter and extend the cut to divide the kidney. This method facilitates the complete evaluation of the \nurothelium in cases of urothelial (transitional) cell carcinoma.\nAlternatively, start at the side of the kidney opposite the hilum and bivalve the kidney, but do not \ncut completely through the hilum.\nDescribe all lesions including size, number (both RCC and TCC may be multifocal), location (with \nrespect to the upper and lower pole, cortex, pelvis), distance from margins (Gerota\u2019s fascia, vascular, \nureteral), involvement of calyceal or pelvic mucosa (open completely with scissors), gross invasion of \ncapsule, perirenal soft tissue,or hilar soft tissue, involvement of adjacent structures (renal vein, adre\u00ad\nnal). Make additional cuts as necessary to assess the parenchyma.\nDescribe the uninvolved renal parenchyma including color, thickness of the cortex, corticomedul\u00ad\nlary junction (well defined, effaced), shape of the papillae (blunted, necrotic), calyces, renal pelvis (dila\u00ad\ntion, petechiae, mucosa), presence of calculi, and types of cysts (simple are usually benign; complex \ncysts may represent tumor). Note any tan/yellow or white nodules in the cortex that might represent \na cortical \u201cadenoma\u201d or additional foci of tumor.\n 3.\t \u0007Fix the entire specimen in formalin overnight. Large tumors are partially sectioned with gauze used \nto wick formalin around the sections.\n 4.\t \u0007The following day sections of the tumor, margins, and kidney are taken. The adrenal gland may be \npresent at the upper pole. Free the gland from the surrounding fat and describe including color, size, \nnodularity (see Chapter 11). Section it carefully looking for evidence of tumor metastasis (nodules). If \nabnormal, weigh the gland and/or focal lesions.\n 5.\t \u0007Carefully section through the remainder of the fat looking for lymph nodes. Most nodes will be near \nthe renal hilum.\n 6.\t \u0007A portion of rib may be submitted with the nephrectomy specimen. See in Chapter 14, \u201cIncidental \nRibs,\u201d for instructions on processing.\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Figure 20-1.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_405.png", "summary": "Pathologic examination of kidney specimens can be challenging, especially with small masses. A model exists to estimate the amount of tissue needed to find a tumor of a certain size with certainty.", "questions": [ "How does the model described in the text help in estimating the amount of tissue needed to find a tumor?", "What role do cytology washings from the retrieval bag play in providing a diagnosis?", "What are the key components of a radical nephrectomy specimen and how are they processed?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 406, "text": "GENITOURINARY SPECIMENS\u2003 Kidney\n388\nRenal Cell Carcinoma.\u2002 The most common type is clear cell (conventional) carcinoma, but other \ntypes are also seen.\n\t\u2022\t \u0007Clear cell carcinomas are usually golden yellow to red, spongy to firm, and occur in discrete nodules \nwith pushing borders. Blood lakes are typical. Necrosis may be present. The tumor may appear brown \nif the cytoplasm is granular. Cysts may be absent or quite prominent. Most are in the upper pole. The \ntumor may bulge out beyond the contour of the renal capsule, but rarely invades into adipose tissue.\n\t\u2022\t \u0007Papillary carcinomas are brown (due to hemosiderin) and very soft and friable, and thus may appear \nto be necrotic (although they usually are not).\n\t\u2022\t \u0007Chromophobe carcinomas are usually well circumscribed and tan/brown in color, with possible focal \nnecrosis or hemorrhage.\nA\nB\nC\nClear cell carcinoma\nPapillary transitional cell carcinoma\nOncocytoma\nUreter\nPelvis\nCalyces\nMahogany brown,\nbulging\nPapillary fronds\nBright yellow\nHemorrhage\nFigure 20\u20131.\u2002 Renal lesions.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_406.png", "summary": "Renal cell carcinoma is the most common type of kidney cancer, with clear cell carcinoma being the predominant subtype. Other types include papillary and chromophobe carcinomas.", "questions": [ "How does clear cell carcinoma of the kidney typically present?", "What are the distinguishing features of papillary carcinoma?", "What is the appearance of chromophobe carcinoma?", "Are there any specific locations within the kidney where these different types of renal cell carcinomas are commonly found?", "How does the presence of necrosis or hemorrhage vary among the different types of renal cell carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 407, "text": "GENITOURINARY SPECIMENS\u2003 Kidney\n389\n\t\u2022\t \u0007Collecting duct carcinomas occur in the renal medulla and have a hard gray/white appearance. The \nborders are typically irregular, and necrosis is frequent.\n\t\u2022\t \u0007Sarcomatoid differentiation in tumors of all types appears as gray/white firm to fleshy masses. Hem\u00ad\norrhage and necrosis are common.\n\t\u2022\t \u0007Renal cell carcinoma in the setting of acquired cystic disease may be quite subtle and have the \nappearance of an irregular area or papillary projection within a cyst. Different tumor types are seen in \nthis setting (see \u201cNative Kidney Nephrectomy\u201d).\n Cytogenetic studies can be helpful to distinguish the different types of RCC (see Table 7-47). EM can \nbe helpful to distinguish chromophobe carcinomas from oncocytomas (see Table 7-46).\nUrothelial (Transitional) Cell Carcinoma is usually a tan/pink friable mass with a minute villous archi\u00ad\ntecture. There may be a rather small base, compared to the size of the tumor, attached to the renal pelvic \nurothelium. However, some tumors have a broad base and involve the majority of the urothelium of the \nrenal pelvis.\nRenal Cortical Adenomas are usually well circumscribed, unencapsulated gray or yellow tumors \npresent below the renal capsule. They are typically an incidental finding and are less than 2 cm in size. \nThey are sometimes associated with long-term hemodialysis or chronic pyelonephritis.\nMetanephric Adenomas are also well circumscribed but can range in size from 1 to 15 cm. The \ncolor is fleshy tan/yellow, and hemorrhage or necrosis may be present.\nOncocytomas are usually deep red/brown, soft, and well circumscribed, without areas of necrosis, \nand located in the cortex. Central \u201cscarring\u201d is present in about half of cases, especially in larger tumors.\nPediatric Tumors\u2002 The types of renal tumors occurring in children are quite different than those seen \nin adults, and include nephroblastoma (Wilms tumor), clear cell sarcoma, rhabdoid tumor, mesoblastic \nnephroma, lymphoma, neural tumors, renal cell carcinoma, and angiomyolipoma. The specimens may be \nprocessed as above, but additional sections should be taken to document the relationship of the tumor to \nthe normal kidney and to evaluate the relationship of the tumor to the capsule and the renal sinus. Normal-\nappearing cortex should also be sampled. Since these tumors tend to be more heterogeneous in appear\u00ad\nance, at least one section per centimeter of greatest tumor dimension should be taken including all areas \nof differing appearance. Some protocols require that the patient have negative lymph nodes. Therefore, all \nhilar tissue should be examined microscopically. Tissue should also be taken for special studies (Box 20-1).\n\t \u2022\t \u0007Nephroblastoma (Wilms tumor): This is the most common type of pediatric renal tumor (80% of \ntotal) and occurs in children from 1 to 6 years of age. Most are well circumscribed lobulated masses \nwith a variegated appearance from gray to pink. Extensive necrosis and hemorrhage are common. If \nthere are multiple nodules, each should be sampled. Cysts may be present. The tumor may invade \ninto the renal vein, ureter, or adipose tissue. Characteristic cytogenetic changes are present (see \nTable 7-47).\nBOX 20\u20131.\u2003 \u0007Special studies in pediatric renal tumors\n\t\u2022\t \u0007Snap-frozen: The National Wilms Tumor Study Protocols (see www.nwstg.org) require snap-frozen tissue from all \npediatric renal tumors and adjacent normal tissue (preferably 1 gram or a minimum of 100 mg in two or more vials \nalong with a separate portion of normal kidney in at least one vial). Nephrogenic rests may also be frozen. Adjacent \ntissue should be sampled for formalin fixation for histologic correlation.\n\t\u2022\t \u0007EM: EM may occasionally be of use.\n\t\u2022\t \u0007Touch preparations: Fixed in 95% alcohol. Can be used for some studies (e.g., FISH) if other tissue is not available.\n\t\u2022\t \u0007Flow cytometry: In some cases flow cytometric analysis of ploidy, S-phase fraction, or surface markers (i.e., for lym\u00ad\nphomas) may be requested.\n\t\u2022\t \u0007Cytogenetics: Cytogenetic studies may be useful for classification and prognosis:\n\t \u2022\t \u0007Cellular mesoblastic nephroma: t(12;15)\n\t \u2022\t \u0007Malignant rhabdoid tumor: 22q11.2 deletion\n\t \u2022\t \u0007Wilms tumor: del 11p13\nSee references 8 and 9.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_407.png", "summary": "The page discusses various types of kidney tumors, including collecting duct carcinomas, sarcomatoid differentiation, renal cell carcinoma, urothelial cell carcinoma, renal cortical adenomas, metanephric adenomas, oncocytomas, and pediatric tumors.", "questions": [ "What are the distinguishing features of collecting duct carcinomas in the kidney?", "How can cytogenetic studies help distinguish different types of renal cell carcinoma?", "What are the characteristics of nephroblastoma (Wilms tumor) and how does it differ from other pediatric renal tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 408, "text": "GENITOURINARY SPECIMENS\u2003 Kidney\n390\nThe weight of the kidney may be used as an eligibility factor for clinical protocols and must be deter\u00ad\nmined accurately.\nAt least one section per cm of tumor should be taken, as tumors can be quite heterogeneous. Most \nsections should be taken from the periphery to evaluate the relationship to the capsule, the renal \nsinus, the normal kidney, and possible vascular involvement.\nMore than one third of cases will be associated with nephrogenic rests (Table 20-2). These appear as \ngrossly pale areas. The presence of nephrogenic rests is associated with the probability of a syn\u00ad\ndrome and involvement of the contralateral kidney. Renal lobes are more easily seen in the kidneys \nof infants and children. Nephroblastomatosis is defined as multiple or diffusely distributed rests.\nThe renal sinus (the hilum of the kidney occupied by the renal pelvis, hilar vessels, and fat) should be \nwell-sampled, as tumors often involve vessels at this point. The renal cortex lacks a capsule here. The \ntumor often involves the renal vein as a tumor thrombus, and the vein may retract around a tumor \nthrombus. This should not be interpreted as a positive margin if the thrombus is not transected.\n\t\u2022\t \u0007Clear cell sarcoma: These make up 4% of renal tumors in children and occur in children between the \nages of 1 and 3 years. Thirty percent present with metastases to lymph nodes. The tumor is usually a \nlarge, well-circumscribed gray/white mass with pushing borders into the adjacent renal parenchyma. Focal \nnecrosis and hemorrhage may be present. Characteristic cytogenetic changes are present (see Table 7-47).\n\t\u2022\t \u0007Rhabdoid tumor: Most are well defined and fleshy in appearance with frequent necrosis and hemorrhage. \nThe renal pelvis is usually involved. Characteristic cytogenetic changes are present (see Table 7-47).\n\t\u2022\t \u0007Congenital mesoblastic nephroma: Rare tumors (2% of pediatric renal tumors) that occur in children \nfrom birth to age 2 (most patients are less than 3 months old). The tumor is an irregular gray/white to tan \nmass often of large size. Cysts, necrosis, or hemorrhage are unusual. These tumors can involve the renal \nvein and the vessels at the hilum; this is an important prognostic factor, and this area should be thoroughly \nsampled. Characteristic cytogenetic changes are present (see Table 7-47). There are two main types:\n\t \u2022\t \u0007Classic CMN (24% of cases) corresponds to infantile fibromatosis\n\t \u2022\t \u0007Cellular CMN (66% of cases) corresponds to infantile fibrosarcoma and have a t(12;15). All relapses \nare of this type or mixed.\n\t \u2022\t \u0007Mixed CMN (10%) have features of both histologic types.\n\t\u2022\t \u0007Lymphoma: A well-defined homogenous gray to white mass involving the cortex or medulla.\nCystic Kidney Disease.\u2002 Genetic (presenting at birth or as an adult), sporadic, and acquired (due to \nlong-term hemodialysis) forms occur. The location and size of the cysts vary among the different types \nof cystic renal disease. Because of the increased risk of RCC in acquired cystic disease, all cysts must be \ncarefully examined for mural nodules or papillary projections (Table 20-3).\nXanthogranulomatous Pyelonephritis.\u2002 Appears as single or multiple golden-yellow nodules in \nand around the pelvis and calyces. The nodules may rarely be found in the renal capsule or in adjacent \nfat. The gross appearance can mimic a renal cell carcinoma.\nTABLE 20\u20132.\u2003 TYPES OF NEPHROGENIC RESTS\nFEATURE\nPERILOBAR REST\nINTRALOBAR REST\nSite in renal lobe\nPeriphery (including subcortical)\nRandom; cortex,medulla, sinus\nMargins\nClearly demarcated\nPoorly demarcated\nRelation to nephrons\nNo nephrons within rest\nDispersed between nephrons\nComposition\nBlastemal or tubular; stroma scanty or \nsclerotic\nTubules, blastema, cysts; stroma usually \npredominates\nNumber\nUsually numerous\nOften single\nAssociations\nBeckwith-Wiedemann syndrome, Perl\u00ad\nman syndrome, and hemihypertrophy\nWAGR syndrome and Denys-Drash \nsyndrome\nModified from Mills SE (ed): Sternberg\u2019s Diagnostic Surgical Pathology, 4th ed., Philadelphia, Lippincott Williams & Wilkins, 2004.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_408.png", "summary": "The page discusses the importance of accurately determining the weight of the kidney for clinical protocols, the need to take multiple sections of tumors due to their heterogeneity, and the presence of nephrogenic rests in more than one third of cases.", "questions": [ "How is the weight of the kidney used as an eligibility factor for clinical protocols?", "Why is it important to take multiple sections of tumors from the periphery?", "What is the significance of nephrogenic rests in relation to syndromes and contralateral kidney involvement?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 409, "text": "GENITOURINARY SPECIMENS\u2003 Kidney\n391\nAngiomyolipoma.\u2002 The tumors are usually well-circumscribed. The radiologic appearance is often \ndiagnostic. The tumors are variegated due to the mixture of adipose tissue (yellow) and smooth muscle \n(gray/white). However, some tumors can consist almost entirely of smooth muscle and mimic a smooth \nmuscle neoplasm. The smooth muscle cells are positive for HMB-45 and other melanoma markers (see \nTable 7-9). The vascular component is often associated with hemorrhage. The tumor may be confined to \nthe kidney, or extend through the capsule. Rare cases may involve the renal vein or regional lymph nodes. \nThe gross appearance can closely mimic a RCC. About half the cases are associated with tuberous sclerosis, \nand these patients more commonly have multiple and bilateral tumors. These tumors can rarely be associ\u00ad\nated with RCC. Therefore, adequate sampling of non-fatty areas is necessary to evaluate this possibility.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: Three to four cassettes including portions of tumor with varying appearance, relationship \nto adjacent uninvolved tissue, invasion of adjacent structures (such as perinephric or perihilar fat). \nIf involvement of the renal vein is known or suspected, representative sections of the vein should be \nsubmitted.\n\t\u2022\t \u0007Margins: Radial margin in perirenal fat, vascular margins and ureteral margin (these latter three sec\u00ad\ntions can be submitted in the same cassette).\n\t\u2022\t \u0007Other lesions: Cysts, infarcts, adenomas, etc. One section of each.\n\t\u2022\t \u0007Normal kidney: At least one cassette of uninvolved kidney. If an underlying disease is suspected \nthat could affect the other kidney, tissue for EM or immunofluorescence and special stains may be \n\u00adindicated.\nTABLE 20\u20133.\u2003\nCYSTIC KIDNEY DISEASE\nDISEASE\nKIDNEY SIZE\nLOCATION \nOF CYSTS\nSIZE OF CYSTS\nCLINICAL CORRELATIONS\nInfantile \npolycystic \nkidney \ndisease\nMassively \nenlarged\nCortex and medulla, \n\u00adradially arranged \nand \u00adoriented \nperpendicular to \nrenal capsule\nSmall\nAutosomal recessive\nCan also affect liver (congenital \nhepatic fibrosis \u2013 Caroli disease)\nUsually fatal at birth\nMedullary \nsponge \nkidney\nNormal\nArise in collecting \nducts and found \nin medullary \npyramids and \nrenal \u00adpapillae\nSmall, <0.5 cm\nMost sporadic \u2013 rarely hereditary\nRarely progress to renal failure, \nassociated with urolithiasis\nMedullary cys\u00ad\ntic kidney \ndisease\nSmall, \n\u00adcontracted, \ngranular \nsurface\nCorticomedullary \njunction\nSmall, <2 cm\nAutosomal dominant\nTwo types \u2013 gout often develops in \ntype 2\nRenal failure develops from 30 to \n70 yrs\nNephro\u00ad\nnophthisis/ \nmedullary \ncystic kid\u00ad\nney disease\nSmall, con\u00ad\ntracted, \ngranular \nsurface\nCorticomedullary \njunction\nSmall, <2 cm\nAutosomal recessive\nFour types \u2013 renal failure develops \nfrom 1 to 19 yrs\n15% develop retinal disease\nAdult polycys\u00ad\ntic kidney \ndisease\nNormal to \nmarked \nincrease\nCortex and medulla\nSmall to very \nlarge (several \ncentimeters)\nAutosomal dominant\nLiver cysts may be present\nAbout half progress to renal failure \nin adulthood\nAcquired cys\u00ad\ntic disease\nSmall\nCortex\nVariable \u2013 small \nto very large\nOccurs after long term hemodialysis. \nThere is an increased risk of RCC", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_409.png", "summary": "Angiomyolipomas are well-circumscribed kidney tumors with a variegated appearance due to the mixture of adipose tissue and smooth muscle. Adequate sampling of non-fatty areas is necessary to evaluate the possibility of mimicking a smooth muscle neoplasm.", "questions": [ "How can angiomyolipomas be differentiated from smooth muscle neoplasms?", "What are the implications of angiomyolipomas being associated with tuberous sclerosis?", "Why is it important to sample non-fatty areas when evaluating angiomyolipomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 410, "text": "392\nGENITOURINARY SPECIMENS\u2003 Kidney\n\t\u2022\t \u0007Adrenal: At least one cassette demonstrating normal adrenal. Additional cassettes to demonstrate \nlesions.\n\t\u2022\t \u0007Lymph nodes: Submit all lymph nodes found.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name, unit number, and \u201ckidney,\u201d is a 333 gram left radical \nnephrectomy specimen including kidney (12 \u00d7 8 \u00d7 5.5 cm) and left adrenal gland (3.8 \u00d7 1.8 \u00d7 0.7 cm) \nand surrounding perirenal fat measuring in thickness from 2 to 3 cm. Extending from the renal pelvis is \na ureter (1 cm in length by 0.3 cm in diameter), renal vein (2.5 cm in length by 1 cm in diameter), and \nrenal artery (1 cm in diameter by 0.4 cm in \u00addiameter). In the upper pole is a circumscribed golden-yellow \ntumor mass with areas of hemorrhage (5 \u00d7 5 \u00d7 3 cm). The tumor protrudes into the renal vein for a dis\u00ad\ntance of 3.2 cm but is not present at the vein margin. The tumor pushes against the renal capsule but does \nnot appear to penetrate the capsule or invade into the perirenal fat. The remainder of the renal cortex is \ntan/brown with a well-defined cortical medullary junction. The pelvis and calyces are covered by smooth \nglistening mucosa. The adrenal gland consists of normal medulla and cortex without focal lesions. The \nadipose tissue is thinly sectioned and no lymph nodes are found.\nCassette #1: Tumor and capsule and perirenal fat, 1 frag, RSS.\nCassette #2: Tumor and adjacent normal kidney, 1 frag, RSS.\nCassette #3: Tumor and renal vein, 1 frag, RSS.\nCassette #4: Renal vein margin, 1 frag, ESS.\nCassette #5: Renal artery and ureter margins, 2 frags, ESS.\nCassette #6: Normal kidney, 1 frag, RSS.\nCassette #7: Representative sections of adrenal, 2 frags, RSS.\nPartial Nephrectomy\nA partial nephrectomy is performed for a radiologically indeterminate mass, tumor in a solitary kid\u00ad\nney (the contralateral nephrectomy may have been performed for prior tumor), or underlying disease \nexpected to affect renal function (e.g. diabetes). Process as above with the following exceptions:\n 1.\t \u0007Examine the cut surface of the kidney for areas suspicious for tumor. Ink this margin. Often, the \nsurgeon will indicate the resection margin using a surgical suture. Because orientation and evalua\u00ad\ntion of this margin is very important, contact the surgeon for orientation if necessary. Serially section \nthrough the specimen. Describe the distance of the tumor from the cut renal resection margin.\n 2.\t \u0007No major vessels or the ureter will be present.\n 3.\t \u0007Take multiple sections demonstrating the relationship of the tumor to the renal resection margin as \nwell as to the deep (perirenal fat) margin.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR RENAL TUMORS\n\t\u2022\t \u0007Specimen: Kidney, adrenal\n\t\u2022\t \u0007Procedure: Partial nephrectomy, radical nephrectomy\n\t\u2022\t \u0007Specimen Laterality: Right, left\n\t\u2022\t \u0007Tumor Site: Upper pole, middle pole, lower pole, hilum, medulla, cortex\n\t\u2022\t \u0007Tumor Size: Greatest dimension (4 cm, 7 cm, and 10 cm are used for staging), if multiple tumors, give \nthe size of the largest tumor\n\t\u2022\t \u0007Focality: Unifocal, multifocal\n\t\u2022\t \u0007Macroscopic and Microscopic Extent of Tumor: RCC: Limited to kidney, extension into peri\u00ad\nnephric tissues, extension beyond Gerota fascia, extension into adrenal (direct invasion is classified as \nT4, noncontiguous involvement is classified as M1), extension into major veins\n\t\n\u2022\t \u0007TCC: Into or through renal pelvis into parenchyma or invades into peripelvic fat\n\t\n\u2022\t \u0007Ureter: involvement of lamina propria, muscularis propria, periureteric soft tissue\n\t\u2022\t \u0007Histologic Type: Clear cell (conventional) renal cell carcinoma, multilocular clear cell renal cell car\u00ad\ncinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma, \nrenal medullary carcinoma, translocation carcinoma (Xp11 or others), urothelial (transitional) cell car\u00ad\ncinoma, oncocytoma, Wilms tumor, others", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_410.png", "summary": "The page discusses the handling and examination of kidney specimens, including partial and radical nephrectomy specimens, as well as the dictation of a left radical nephrectomy specimen.", "questions": [ "What are the key components included in a left radical nephrectomy specimen?", "What are the differences in processing a partial nephrectomy specimen compared to a radical nephrectomy specimen?", "What are the important factors to consider when examining renal tumors for prognostic/diagnostic purposes?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 411, "text": "393\nGENITOURINARY SPECIMENS\u2003 Kidney\n\t\u2022\t \u0007Sarcomatoid Features: RCC: Not identified, present (give percentage of sarcomatoid element)\n\t\u2022\t \u0007Tumor Necrosis: RCC: Not identified, present\n\t\u2022\t \u0007Histologic Grade: RCC: Fuhrman nuclear grade (Table 20-4)\n\t \u2022\t \u0007TCC: various systems (see \u201cBladder\u201d)\n\t\u2022\t \u0007Margins: Involved or not involved, renal vein, ureter, perinephric fat, Gerota fascial margin, renal \nparenchyma (for partial nephrectomies), renal capsular margin (for partial nephrectomies)\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present. This does not include the renal vein and its mus\u00ad\ncle containing segmental branches or the inferior vena cava. Involvement of these vessels is reported \nseparately.\n\t\u2022\t \u0007Regional Lymph Nodes: Metastases present or absent, number of involved nodes, number of nodes \nexamined, size of largest metastasis, extracapsular invasion\n\t\u2022\t \u0007Additional Pathologic Findings: Glomerular disease, tubulointerstitial disease, vascular disease, \ncysts, adenomas, inflammation\n\t \u2022\t \u0007For Wilms tumor: nephrogenic rests (intralobar or perilobar)\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Tables 20-5 and \n20-6). M0 is conferred after clinical assessment; there is no pM0 category.\nTABLE 20\u20134.\u2003\nFUHRMAN NUCLEAR GRADING SYSTEM FOR RENAL CELL CARCINOMA\nNUCLEI\nNUCLEOLI\nGrade I\nRound, uniform, measure 10 microns\nInconspicuous or absent\nGrade II\nSlightly irregular, measure 15 microns\nSmall\nGrade III\nVery irregular, measure 20 microns\nProminent, large\nGrade IV\nBizarre multilobated, chromatin clumping, \u2265 20 microns\nProminent\nModified from Fuhrman SA, et al, Prognostic significance of morphologic \u00adparameters in renal cell carcinoma. Am J Surg Pathol 6:655, 1982.\nTABLE 20\u20135.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF RENAL CELL CARCINOMAS\nTumor\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nTumor 7 cm or less in greatest dimension, limited to the kidney\nT1a\nTumor 4 cm or less in greatest dimension, limited to the kidney\nT1b\nTumor 10more than 4 cm but not more than 7 cm in greatest dimension limited to the kidney\nT2\nTumor more than 7 cm in greatest dimension limited to the kidney\nT2a\nTumor more than 7 cm but less than or equal to 10 cm in greatest dimension, limited to the kidney\nT2b\nTumor more than 10 cm, limited to the kidney\nT3\nTumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond \nGerota\u2019s fascia\nT3a\nTumor grossly extends into the renal vein or its segmental (muscle-containing) branches, or tumor invades \n\u00adperirenal and/or renal sinus fat but not beyond Gerota\u2019s fascia\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_411.png", "summary": "The page provides detailed information on various pathological features of kidney specimens, including sarcomatoid features, tumor necrosis, histologic grade, margins, lymph-vascular invasion, regional lymph nodes, additional pathologic findings, distant metastasis, and AJCC classification.", "questions": [ "What is the significance of sarcomatoid features in renal cell carcinoma?", "How is the Fuhrman nuclear grading system used to classify renal cell carcinoma?", "What are the key components of the AJCC classification for renal cell carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 412, "text": "TABLE 20\u20136.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF TUMORS OF THE RENAL PELVIS AND URETER\nTumor\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTa\nPapillary noninvasive carcinoma\nTis\nCarcinoma in situ\nT1\nTumor invades subepithelial connective tissue\nT2\nTumor invades the muscularis\nT3\n(For renal pelvis only) Tumor invades beyond muscularis into peripelvic fat or the renal parenchyma\nT3\n(For ureter only) Tumor invades beyond muscularis into periureteric fat\nT4\nTumor invades adjacent organs, or through the kidney into the perinephric fat\nRegional Lymph Nodes\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in a single lymph node \u2264 2 cm\nN2\nMetastasis in a single lymph node > 2 cm but \u2264 5 cm or in multiple lymph nodes \u2264 5 cm\nN3\nMetastasis in a lymph node > 5 cm\nNote: Regional lymph nodes for the renal pelvis are renal hilar, paracaval, aortic, and retroperitoneal. Regional lymph nodes for the ureter are renal hilar, iliac, paracaval, \nperiureteral, and pelvic. Laterality does not affect N classification.\nDistant Metastasis\nM0\nNo distant metastasis\nM1\nDistant metastasis\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Committee on Cancer (AJCC), \nChicago, Illinois.\nT3b\nTumor grossly extends into the vena cava below the diaphragm\nT3c\nTumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava\nT4\nTumor invades beyond Gerota\u2019s fascia (including contiguous extension into the ipsilateral adrenal gland)\nRegional Lymph Nodes\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in regional lymph node(s)\nNote: Regional lymph nodes include renal hilar, paracaval, aortic, and retroperitoneal. Laterality does not affect the N classification. If a lymph node dissection is performed, \nusually at least 8 would be included.\nDistant Metastasis\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: Sarcomas and adenomas are not included in this classification.\nThere is a separate staging system for pediatric Wilms tumors (see \u201cCancer Protocols and Checklists\u201d at www.cap.org).\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Committee on Cancer (AJCC), \nChicago, Illinois.\nTABLE 20\u20135.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF RENAL CELL CARCINOMAS\u2014cont\u2019d\nTumor", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_412.png", "summary": "This page provides the AJCC (7th edition) classification of tumors of the renal pelvis and ureter, including details on primary tumor assessment, regional lymph nodes, and distant metastasis.", "questions": [ "How does the classification of tumors in the renal pelvis differ from those in the ureter?", "What are the specific criteria for determining regional lymph node metastasis?", "Are there any exceptions or special considerations mentioned in the classification for certain types of tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 413, "text": "395\nGENITOURINARY SPECIMENS\u2003 Bladder\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nThere is a separate CAP Cancer Protocol for the reporting of pediatric Wilms tumor (see \u201cCancer \nProtocols and Checklists\u201d at www.cap.org).\nBLADDER\nUrothelial (transitional) cell carcinoma is the most common tumor of the bladder. Other tumors at this \nsite are rare (e.g., squamous cell carcinoma or adenocarcinoma).\nThe bladder muscularis mucosae is poorly defined (not unlike the gallbladder!) and incomplete. \nTherefore the term \u201csubmucosa\u201d is not used. Invasion is reported as being into the lamina propria or \ndeeper into the muscularis propria.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 20-7.\nBiopsies and Transurethral Resection of Bladder Tumors\nBladder biopsies are processed as small biopsies (see Chapter 13). Transurethral resections of bladder \ntumors (TURBT) sometimes result in specimens grossly recognizable as papillary tumors. Orient if pos\u00ad\nsible. However, the specimens generally cannot be oriented.\nOrder two levels on each small biopsy. Order one level on grossly recognizable tumor specimens.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR BLADDER TUMOR BIOPSIES\n\t\u2022\t \u0007Procedure: Biopsy, transurethral resection of bladder tumor (TURBT)\n\t\u2022\t \u0007Histologic Type: Urothelial (transitional) cell carcinoma, squamous cell carcinoma, adenocarcinoma, \nothers\n\t\u2022\t \u0007Associated Epithelial Lesions: Urothelial (transitional cell) papilloma, urothelial (transitional cell) \npapilloma, inverted type, papillary urothelial (transitional cell) neoplasm, low malignant potential\nTABLE 20\u20137.\u2003\nRELEVANT CLINICAL \u00adHISTORY \u2013 BLADDER\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR BLADDER SPECIMENS\nOrgan/tissue resected or biopsied\nRenal or bladder stones\nPurpose of the procedure\nRecent urinary tract infections\nGross appearance of the organ/tissue/lesion sampled\nRecent urinary tract procedures\nAny unusual features of the clinical presentation\nObstruction\nAny unusual features of the gross appearance\nInfections\nPrior surgery/biopsies \u2013 results\nHereditary non-polyposis colon cancer (HNPCC) \nsyndrome \u2013 can be associated with carcinomas of \nthe ureter\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, \ndrug use that can change the histologic appearance \nof tissues)\nSystemic or intravesical chemotherapy, immunother\u00ad\napy with BCG, or radiation\nAnalgesic nephropathy, with papillary necrosis \u2013 may \nincrease the risk of renal pelvic tumors\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_413.png", "summary": "The most common tumor of the bladder is urothelial (transitional) cell carcinoma, with other tumors such as squamous cell carcinoma or adenocarcinoma being rare. Bladder biopsies and transurethral resections of bladder tumors are processed differently.", "questions": [ "How are bladder biopsies processed differently from transurethral resections of bladder tumors?", "What are the specific histologic types and associated epithelial lesions that are reported in bladder tumor biopsies?", "What are some relevant clinical history factors to consider for bladder specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 414, "text": "396\nGENITOURINARY SPECIMENS\u2003 Bladder\n\t\u2022\t \u0007Histologic Grade: Urothelial carcinoma: Low-grade, high-grade (WHO 2004/International Society \nof Urologic Pathology Consensus Classification)\n\t \u2022\t \u0007Adenocarcinoma and squamous cell carcinoma: well differentiated, moderately differentiated, \npoorly differentiated\n\t\u2022\t \u0007Tumor Configuration: Papillary, solid/nodule, flat, ulcerated\n\t\u2022\t \u0007Muscularis Propria: Muscularis propria (detrusor muscle) not identified, muscularis propria (detrusor \nmuscle) present\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Microscopic Extent of Tumor: Noninvasive papillary carcinoma, flat carcinoma in situ, invasion \nof subepithelial connective tissue (lamina propria), invasion of muscularis propria (detrusor muscle), \nurothelial carcinoma in situ in prostatic urethra in prostatic chips, urothelial carcinoma in situ involv\u00ad\ning prostatic ducts and acini in prostatic chips, urothelial carcinoma invasive into prostatic stroma in \nprostatic chips\n\t\u2022\t \u0007Additional Pathologic Findings: Urothelial dysplasia (low-grade intraurothelial neoplasia), inflam\u00ad\nmation or regenerative changes, therapy-related changes, cautery artifact, cystitis cystica glandularis, \nkeratinizing squamous metaplasia, intestinal metaplasia\nThis list incorporates the recommendations in Gephardt GN, Baker PB, Interinstitutional comparison \nof bladder carcinoma surgical pathology report adequacy: A College of American Pathologists Q-probes \nstudy of 7234 bladder biopsies and curettings in 268 institutions. Arch Pathol Lab Med 119:681-685, \n1995; and the CAP Protocol for the Examination of Specimens from Patients with Carcinoma of the \nUrinary Bladder (see \u201cCancer Protocols and Checklists\u201d at www.cap.org).\nRadical or Partial Cystectomy\nThe bladder is usually resected because of biopsy-proven invasive urothelial (transitional) cell carcinoma. \nRarely, the bladder will be removed because of prostatic carcinoma invasive into the bladder or because \nof synchronous bladder and prostatic primary tumors. It is not uncommon to have the majority of the \ntumor removed by biopsy and have only minimal, or no, tumor present in the cystectomy specimen. It is \nalso common to find an incidental (clinically occult) prostate carcinoma.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record outer dimension of bladder, length and diameter of attached ureters. \nMales: The prostate is attached (Fig. 20-2). Record outer dimensions, seminal vesicles (dimensions), \nvasa deferentia (length and diameter). \nFemales: The anterior vaginal wall will be attached. Describe size (length, width, depth), color (usu\u00ad\nally white), any lesions.\nRecord the outer appearance of the specimen (e.g., any gross tumor present at the resection margin). \nUsually the margin consists of unremarkable adipose tissue. Palpate (but do not remove) this tissue, \nlooking for grossly involved lymph nodes. Usually lymph nodes will not be found.\n 2.\t \u0007Ink the prostate (if present) and any suspicious areas of the external bladder.\nBladders that arrive intact are inflated with formalin through the urethra and allowed to fix in an \nexpanded state overnight. It is very difficult to examine a contracted and highly folded bladder \nmucosa for small or multicentric tumors.\nHold the bladder neck upright with a hemostat. Fill the lumen with formalin. When the bladder is full, \nthe urethra can be plugged with a large cotton swab.\nIf the bladder has already been opened, the specimen is pinned out on a paraffin board for fixation \novernight.\n 3.\t \u0007Before opening the bladder, determine the location of the tumor by looking up prior biopsy speci\u00ad\nmens or radiology reports. Avoid cutting through the tumor when opening the bladder.\nIf the location is unknown, or if it is in the usual location near the trigone, open the bladder anteriorly \nthrough the urethra and extend the \u00adincision to the dome. A probe placed into the urethra is helpful \nto guide the knife.\n 4.\t \u0007Locate the site of the tumor. Avoid touching the mucosal surface because it is very delicate and is eas\u00ad\nily denuded. In some cases the luminal tumor will be very small or only a shallow ulceration from a \nprior biopsy will be present.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_414.png", "summary": "The page provides information on histologic grade, tumor configuration, muscularis propria, lymph-vascular invasion, microscopic extent of tumor, and additional pathologic findings in bladder specimens. It also discusses radical or partial cystectomy for bladder carcinoma.", "questions": [ "What are the different histologic grades of urothelial carcinoma mentioned?", "What are the various tumor configurations described for bladder specimens?", "Why is the bladder usually resected in cases of invasive urothelial cell carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 415, "text": "397\nGENITOURINARY SPECIMENS\u2003 Bladder\nInk the deep margin at the site of the tumor. Make parallel sections through the tumor.\nRecord the tumor\u2019s size, configuration (papillary, sessile, ulcerated, fungating, flat or plaque-like), \ncolor, consistency (firm, soft), depth of penetration of wall (submucosa, into or through muscularis \npropria, into perivesical soft tissue), location (dome, anterior, posterior, lateral wall, trigone), rela\u00ad\ntionship to ureteral orifices (obstructing, extending into ureter).\nSubmit up to four sections of tumor (more if the tumor is very large) including junction with unin\u00ad\nvolved mucosa, deepest extension through wall, and deep margin.\n 5.\t \u0007Describe the remainder of the bladder mucosa (smooth and glistening, hemorrhagic, edematous). If \nthere are any abnormal areas, describe location and appearance.\nSubmit representative sections of anterior wall, posterior wall, lateral wall, dome, and any abnormal \nareas.\n 6.\t \u0007The true ureteral margins are usually submitted separately and have often been examined by frozen \nsection. Additional margins from the specimen do not need to be submitted.\nThe entire length of the ureter is examined for additional foci of tumor. Either take multiple cross \nsections or open longitudinally. Submit any suspicious lesions.\n 7.\t \u0007Males: The prostate can be processed similar to radical prostatectomies (see the section on pros\u00ad\ntatectomies for details). The prostate is sectioned through the posterior surface in serial sections \nperpendicular to the prostatic urethra. Describe color (white, yellow), consistency (firm, hard), \nand any areas of necrosis or hemorrhage, and texture (nodular or effaced). The most common \nlocation of tumors is along the posterior wall. If no gross lesions are present, submit four sections \nfrom the posterior right lobe and four sections from the posterior left lobe. If lesion(s) are present, \nsubmit enough sections to document them as well as representative sections from the uninvolved \nprostate.\nThe bladder base is not a margin and is not submitted. However, if gross tumor is present take a sec\u00ad\ntion to document invasion into prostate.\nThe urethral margin (also the apex of the prostate) is best sampled with a perpendicular section \nthrough the urethra to try to assess urethral mucosa which may be retracted and not seen in an en \nface apical margin.\nSection the seminal vesicles perpendicular to the long axis. Submit one section of each at the junction \nwith the prostate.\n 8.\t \u0007Females: Submit one representative section of the vaginal mucosa and any gross lesions.\n 9.\t \u0007After all microscopic sections have been taken, the perivesical soft tissue is carefully sectioned to look \nfor lymph nodes. These nodes are found in only a small percentage of cases and more often in females \nthan in males.\nMale\nProstate\nTrigone\nFigure 20\u20132.\u2002 Cystectomy.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_415.png", "summary": "The page provides detailed instructions on processing genitourinary specimens, specifically focusing on bladder and prostate specimens.", "questions": [ "What specific information should be recorded when examining a bladder tumor?", "How should the prostate be processed for examination?", "Why are the ureteral margins usually submitted separately?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 416, "text": "398\nGENITOURINARY SPECIMENS\u2003 Bladder\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: Up to four cassettes including junction with normal mucosa, deepest point of invasion, deep \nmargin.\n\t\u2022\t \u0007Bladder mucosa: Up to six cassettes of representative sections of anterior wall, posterior wall, right \nand left lateral walls, if no gross tumor is present. If gross tumor is present, additional representative \nmucosa need not be sampled in that area.\n\t\u2022\t \u0007Ureters: Need not be submitted if margins have been evaluated in separate specimens. Up to four \ncassettes including left and right specimen margins, and all lesions.\n\t\u2022\t \u0007Prostate: Four cassettes of posterior right lobe and four cassettes of posterior left lobe.\n\t\u2022\t \u0007Urethral margin: One perpendicular section.\n\t\u2022\t \u0007Seminal vesicles: Two cassettes documenting left seminal vesicle and right seminal vesicle.\n\t\u2022\t \u0007Anterior vaginal wall: One cassette documenting normal mucosa and any lesions present.\n\t\u2022\t \u0007Lymph nodes: All lymph nodes present in perivesical soft tissue.\nSAMPLE DICTATION\nReceived fresh labeled \u201cBladder\u201d is a radical cystectomy specimen containing bladder (15 \u00d7 10 \u00d7 5 cm), \nprostate (5 \u00d7 4.5 \u00d7 4 cm) and right (7 cm in length \u00d7 0.8 cm in \u00addiameter) and left (6 cm in length \u00d7 0.8 cm \nin diameter) ureters. There is a soft tan/pink papillary tumor (3.0 \u00d7 2.0 \u00d7 1.5 cm) located at the base of \nthe posterior wall. The tumor extends into, but not through, the muscularis propria, and is 1.5 cm from \nthe deep margin.\nThere is a second soft tan/pink papillary tumor (1.2 \u00d7 0.8 \u00d7 0.7 cm) located in the dome of the \nbladder which is confined to the mucosal surface. This tumor is 8 cm from the previously described \ntumor.\nThe remainder of the bladder mucosa is edematous and congested; however, no other gross lesions \nare noted.\nThe right ureter is unremarkable. In the left ureter there is an area of mucosal irregularity (0.3 \u00d7 \n0.3 cm), which is 3 cm from the unremarkable surgical margin.\nThe prostate consists of diffusely firm white parenchyma with a whorled appearance. The right semi\u00ad\nnal vesicle (3 \u00d7 1.5 \u00d7 0.5 cm), left seminal vesicle (2.5 \u00d7 1.8 \u00d7 0.6 cm), right vas deferens (0.8 cm in length \u00d7 \n0.5 cm in diameter), and left vas deferens (0.6 cm in length \u00d7 0.6 cm in diameter) are unremarkable.\nThree fleshy tan lymph nodes are present in the perivesical soft tissue, the largest measuring 0.5 cm \nin greatest dimension.\nCassettes #1-2: deepest extent of invasion of large tumor including deep margin, 2 frags, ESS.\nCassettes #3-4: large tumor and adjacent mucosa, 2 frags, RSS.\nCassettes #5-6: small tumor including deep margin, 2 frags, ESS.\nCassette #7: anterior wall, 1 frag, RSS.\nCassette #8: right lateral wall, 1 frag, RSS.\nCassette #9: posterior wall, between the two tumors, 1 frag, RSS.\nCassette #10: left lateral wall, 1 frag, RSS.\nCassette #11: right ureter margin, 1 frag, ESS.\nCassette #12: left ureter margin, 1 frag, ESS.\nCassette #13: suspicious area in left ureter, 3 frags, ESS.\nCassette #14: right seminal vesicle, 2 frags, RSS.\nCassette #15: left seminal vesicle, 2 frags, RSS.\nCassette #16: urethral margin of prostate, perpendicular, 1 frag, RSS.\nCassettes #17-20: right lobe, 4 frags, RSS.\nCassettes #21-24: left lobe, 4 frags, RSS.\nCassette #25: three lymph nodes, 3 frags, ESS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR BLADDER TUMORS\n\t\u2022\t \u0007Specimen: Bladder, prostate, vaginal wall\n\t\u2022\t \u0007Procedure: Partial cystectomy, total cystectomy, radical cystectomy, radical cystoprostatectomy, \nanterior exenteration\n\t\u2022\t \u0007Tumor Site: Trigone, right lateral wall, left lateral wall, anterior wall, posterior wall, dome", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_416.png", "summary": "The page provides guidelines for the microscopic examination of genitourinary specimens, specifically the bladder, ureters, prostate, urethral margin, seminal vesicles, anterior vaginal wall, and lymph nodes.", "questions": [ "What are the specific guidelines for sampling bladder mucosa if no gross tumor is present?", "What are the recommended number of cassettes for sampling the ureters?", "How are the seminal vesicles documented in the specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 417, "text": "399\nGENITOURINARY SPECIMENS\u2003 Bladder\nTABLE 20\u20138.\u2003 \u0007WHO/INTERNATIONAL SOCIETY OF UROLOGICAL PATHOLOGY CONSENSUS CLASSIFICATION OF UROTHELIAL (TRANSITIONAL CELL) \nNEOPLASMS OF THE URINARY BLADDER (WHO 2004)\nARCHITECTURE\nCYTOLOGY\nPAPILLAE\nORGANIZATION OF \nCELLS\nNUCLEAR SIZE\nNUCLEAR SHAPE\nNUCLEAR \nCHROMATIN\nNUCLEOLI\nMITOSES\nUMBRELLA \nCELLS\nPapilloma\nDelicate\nIdentical to normal\nIdentical to \nnormal\nIdentical to normal\nFine\nAbsent\nAbsent\nUniformly \npresent\nPUNLUMPa\nDelicate, \n\u00adoccasionally \nfused\nPolarity identical to \nnormal; any thickness, \ncohesive\nMay be \n\u00aduniformly \nenlarged\nElongated, \n\u00adround-oval, \n\u00aduniform\nFine\nAbsent to incon\u00ad\nspicuous\nRare, basal\nPresent\nLow-grade \n\u00adpapillary \n\u00adcarcinoma\nFused, \n\u00adbranching, \ndelicate\nPredominantly ordered, \nyet minimal crowding \nand minimal loss of \npolarity; any thick\u00ad\nness; cohesive\nEnlarged with \nvariation in \nsize\nRound-oval; \nslight variation \nin shape and \ncontour\nMild \u00advariation \nwithin and \nbetween cells\nUsually \n\u00adinconspicuousb\nOccasional, \nat any \nlevel\nUsually \n\u00adpresent\nHigh-grade \n\u00adpapillary \n\u00adcarcinomac\nFused, \n\u00adbranching, \ndelicate\nPredominantly ordered \nwith frequent loss of \npolarity; any thick\u00ad\nness; often discohe\u00ad\nsive\nEnlarged with \nvariation in \nsize\nModerate-marked \npleomorphism\nModerate-\nmarked \nvariation both \nwithin and \nbetween cells \nwith hyper\u00ad\nchromasia\nMultiple \n\u00adprominent \nnucleoli may be \npresent\nUsually \nfrequent, \nat any \nlevel\nMay be absent\naPapillary urothelial neoplasm of low malignant potential. It is suggested that this diagnosis be accompanied by the following note: \u201cPatients with these tumors are at risk of developing new bladder tumors (\u201crecurrence\u201d), usually of a \nsimilar histology. However, occasionally these subsequent lesions manifest as urothelial carcinoma, such that follow-up of the patient is warranted.\u201d\nbIf present, small and regular and not accompanied by other features of high-grade carcinoma.\ncThe degree of nuclear anaplasia may be included in a note.\nFrom Epstein JI, Amin MB, Reuter VR, Mostofi FK, and the Bladder Consensus Conference Committee, The World Health Organization/International Society of Urological Pathology Consensus Classification of Urothelial (Transitional \nCell) Neoplasms of the Urinary Bladder, Am J Surg Pathol 22:1435-1448, 1998.\nDefinitions:\n\t\n\u2022\t\u0007Urothelial papilloma: Exophytic urothelial papilloma composed of a delicate fibrovascular core covered by urothelium indistinguishable from that of the normal urothelium.\n\t\n\u2022\t\u0007Inverted papilloma: Benign urothelial tumor that has an inverted growth pattern with normal to minimal cytologic atypia of the neoplastic cells.\n\t\n\u2022\t\u0007Papillary urothelial neoplasm of low malignant potential (PUNLMP) (former WHO Grade 1): A papillary urothelial tumor that resembles the exophytic urothelial papilloma, \nbut shows increased cellular proliferation exceeding the thickness of normal urothelium.\n\t\n\u2022\t\u0007Non-invasive low grade papillary urothelial carcinoma (former WHO Grade 2): A neoplasm of urothelium lining papillary fronds that shows an orderly appearance, but \n\u00adeasily recognizable variations in architecture and cytologic features.\n\t\n\u2022\t\u0007Non-invasive high grade papillary urothelial carcinoma (former WHO Grade 3): A neoplasm of urothelium lining papillary fronds that shows a predominant pattern of \n\u00addisorder with moderate to marked architectural and cytologic atypia.\n\t\n\u2022\t\u0007Urothelial carcinoma in situ: A non-papillary (i.e. flat) lesion in which the surface epithelium cells are cytologically malignant.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_417.png", "summary": "The page discusses the WHO/International Society of Urological Pathology consensus classification of urothelial neoplasms of the urinary bladder, focusing on the architectural and cytological characteristics of different types of bladder tumors.", "questions": [ "What are the key architectural and cytological differences between papilloma, low-grade papillary carcinoma, and high-grade papillary carcinoma?", "What is the significance of umbrella cells in the classification of bladder tumors?", "How does the presence of nucleoli and mitoses differ between low-grade and high-grade papillary carcinomas?", "What are the defining features of Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) and how does it differ from other bladder tumors?", "Why is follow-up of patients with Papillary Urothelial Neoplasm of Low Malignant Potential important?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 418, "text": "GENITOURINARY SPECIMENS\u2003 Ureter\n400\n\t \u2022\t \u0007Tumors at the dome or anterior surface of the bladder have a worse prognosis than those at the base. \nMost tumors occur near the trigone.\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Histologic Type: Urothelial (transitional cell) carcinoma, adenocarcinoma, squamous cell carcinoma, \nother rare types.\n\t\u2022\t \u0007Associated Epithelial Lesions: Urothelial (transitional cell) papilloma, urothelial (transitional cell) \npapilloma, inverted type, papillary urothelial (transitional cell) neoplasm, low malignant potential\n\t\u2022\t \u0007Histologic Grade: Urothelial carcinoma: Low-grade, high-grade (Table 20-8)\n\t \u2022\t \u0007Adenocarcinoma and squamous cell carcinoma: well differentiated, moderately differentiated, \npoorly differentiated\n\t\u2022\t \u0007Tumor Configuration: Papillary, solid/nodule, flat, ulcerated\n\t\u2022\t \u0007Microscopic Tumor Extension: Noninvasive papillary carcinoma (pTa), flat carcinoma in situ \n(pTis), tumor invades subepithelial connective tissue (lamina propria) (T1), tumor invades superficial \nmuscularis propria (inner half) (pT2a), tumor invades deep muscularis propria (outer half) (pT2b), \ntumor invades perivesical tissue microscopically (pT3a), tumor invades perivesical tissue (an extravesi\u00ad\ncal mass is present) (pT3b), tumor invades prostatic stroma, seminal vesicles, uterus, vagina (pT4a), \ntumor invades pelvic wall or abdominal wall (pT4b).\n\t \u2022\t \u0007Also specify whether the carcinoma invades rectum or ureter. Carcinoma in situ may involve the \nprostatic urethra, ducts, and acini.\n\t \u2022\t \u0007Distinguish invasion of muscularis mucosae from invasion of muscularis propria.\n\t \u2022\t \u0007Extent of invasion: focal or extensive; depth in millimeters; by level\u2014above, at, or below muscularis \nmucosae.\n\t \u2022\t \u0007The depth of invasion in muscularis propria should not be staged in TURBT specimens. Adipose \ntissue is sometimes present in the lamina propria and muscularis propria, and involvement does not \nnecessarily indicate extravesicular invasion.\n\t\u2022\t \u0007Margins: Uninvolved or involved, distance from closest margin, invasive carcinoma or in situ carci\u00ad\nnoma.\n\t \u2022\t \u0007Ureteral, urethral, soft tissue, invasion through to peritoneal surface\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Multiple Tumors: Multiple tumors are common and if present predict a greater likelihood of tumor \nat other sites (ureter, renal pelvis) and recurrence; pagetoid spread of carcinoma in situ in urethral \nmucosa.\n\t\u2022\t \u0007Regional Lymph Nodes: Number of nodes examined, number with metastases, size of metastasis. \nPelvic nodes are usually submitted separately. Nodes in the perivesical fat are also reported.\n\t\u2022\t \u0007Additional Pathologic Findings: Urothelial dysplasia (low-grade intraurothelial neoplasia), inflam\u00ad\nmation/regenerative changes, cystitis cystica glandularis, keratinizing squamous metaplasia, intestinal \nmetaplasia, granulomatous cystitis, ulceration, therapy related changes\n\t\u2022\t \u0007Prostate: Normal, hyperplasia, PIN, carcinoma (report as for prostatectomies), invasion by bladder \ncarcinoma\n\t\u2022\t \u0007Vaginal Wall: Normal, lesions\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 20-9). \nM0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nURETER\nUreters are rarely removed intentionally except as part of a radical cystectomy, radical nephrectomies for \nurothelial (transitional) cell carcinoma, or if there is a tumor present in the ureter. Almost all tumors of \nthe ureter will be transitional cell carcinomas and are sometimes associated with HNPCC. The uretero\u00ad\npelvic junction is sometimes resected to relieve obstruction (see section later).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_418.png", "summary": "The page discusses various aspects of tumors and lesions in the ureter, including tumor size, histologic type, grade, configuration, extension, invasion, margins, lymph-vascular invasion, multiple tumors, regional lymph nodes, and additional pathologic findings.", "questions": [ "What are the different histologic types of tumors that can occur in the ureter?", "How is the extent of tumor invasion in the ureter classified?", "Why are multiple tumors in the ureter considered significant in terms of predicting recurrence and spread to other sites?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 419, "text": "GENITOURINARY SPECIMENS\u2003 Ureter\n401\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the length and diameter (range if it varies). Palpate the specimen and determine if a lesion \nis present. The proximal and distal margins are taken as thin cross sections at either end of the \nspecimen.\n 2.\t \u0007Carefully open the ureter longitudinally with a small pair of scissors and avoid cutting into any lesions. \nExamine the mucosal surface for any lesions. Urothelial (transitional) cell carcinoma usually looks like \na soft tan/pink papillary mass on a stalk.\n 3.\t \u0007If a lesion is present, photograph the specimen. Ink the deep margin. Pin out on a paraffin board and \nfix overnight.\n 4.\t \u0007Section through the tumor looking for the deepest extent of invasion. If soft tissue is attached, look \nfor lymph nodes.\nTABLE 20\u20139.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF URINARY BLADDER CARCINOMAS\nTumor\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTa\nNoninvasive papillary carcinoma\nTis\nCarcinoma in situ: \u201cflat tumor\u201d\nT1\nTumor invades subepithelial connective tissue\nT2\nTumor invades muscularis propria\nT2a\nTumor invades superficial muscularis propria (inner half)\nT2b\nTumor invades deep muscularis propria (outer half)\nT3\nTumor invades perivesical tissue\nT3a\nMicroscopically\nT3b\nMacroscopically (extravesical mass)\nT4\nTumor invades any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall\nT4a\nTumor invades prostatic stroma, uterus, or vagina\nT4b\nTumor invades pelvic wall, abdominal wall\nRegional Lymph Nodes\nNX\nLymph nodes cannot be assessed.\nN0\nNo lymph node metastasis\nN1\nSingle regional lymph node metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph \nnode)\nN2\nMultiple regional lymph node metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph \nnode)\nN3\nLymph node metastasis to the common iliac lymph nodes\nRegional lymph nodes include both primary and secondary drainage regions. All other nodes above the aortic bifurcation are considered distant lymph nodes.\nDistant Metastasis\nM0\nNo distant metastasis\nM1\nDistant metastasis\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Committee on Cancer (AJCC), \nChicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_419.png", "summary": "This page provides guidelines for processing ureter specimens, including recording dimensions, identifying lesions, and sectioning through tumors to assess invasion.", "questions": [ "How can urothelial (transitional) cell carcinoma be identified on the mucosal surface of the ureter?", "What is the significance of photographing specimens with lesions and inking the deep margin?", "How does the AJCC classification system categorize urinary bladder carcinomas based on tumor invasion and lymph node involvement?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 420, "text": "GENITOURINARY SPECIMENS\u2003 Ureteropelvic Junction\n402\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: Up to four cassettes including greatest depth of invasion into the wall of the ureter and deep \nmargin.\n\t\u2022\t \u0007Margins: Proximal and distal mucosal margins.\n\t\u2022\t \u0007Ureter: Submit at least one cassette of uninvolved ureter to look for additional lesions.\n\t\u2022\t \u0007Lymph nodes: Submit all lymph nodes.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR URETERAL TUMORS\n\t\u2022\t \u0007Procedure: Ureterectomy, nephroureterectomy (partial or complete)\n\t\u2022\t \u0007Specimen Laterality: Right, left\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Histologic Type: Urothelial (transitional cell) carcinoma (papillary or nonpapillary), rarely adenocar\u00ad\ncinoma or squamous cell carcinoma. The WHO Classification is recommended.\n\t\u2022\t \u0007Associated Epithelial Lesions: Urothelial (transitional cell) papilloma, urothelial (transitional cell) \npapilloma, inverted type, papillary urothelial (transitional cell) neoplasm, low malignant potential\n\t\u2022\t \u0007Histologic Grade: Urothelial carcinoma: low grade, high grade (use the WHO/International Society \nof Urologic Pathology Classification)\n\t \u2022\t \u0007Adenocarcinoma or squamous cell carcinoma: well differentiated, moderately differentiated, poorly \ndifferentiated\n\t\u2022\t \u0007Tumor Configuration: Papillary, solid/nodule, ulcerated, flat\n\t\u2022\t \u0007Margins: Uninvolved, involved, invasive or in situ carcinoma, distance to closest margin.\n\t \u2022\t \u0007Ureteral, soft tissue margins\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Extent of Invasion: Papillary noninvasive carcinoma (pTa), carcinoma in situ (Tis), tumor invades \nsubepithelial connective tissue (lamina propria) (pT1), tumor invades the muscularis (pT2), tumor \ninvades beyond muscularis into periureteric fat (pT3), tumor invades adjacent organs (pT4)\n\t\u2022\t \u0007Multiple Tumors: Multiple tumors are common and if present predict a greater likelihood of tumor at \nother sites (ureter, renal pelvis) and recurrence; pagetoid spread of carcinoma in situ in urethral mucosa.\n\t\u2022\t \u0007Regional Lymph Nodes: Absent (N0), present in one node \u2264 2 cm in size (N1), present in one node \n> 2 cm but \u2264 5 cm, or multiple nodes, none > 5 cm (N2), or present in a lymph node > 5 cm (N3).\n\t \u2022\t \u0007Number of nodes examined, number with metastases, size of metastasis. Pelvic nodes are usually \nsubmitted separately.\n\t\u2022\t \u0007Additional Pathologic Findings: Urothelial carcinoma in situ, urothelial dysplasia (low-grade intrau\u00ad\nrothelial neoplasia), inflammation/regenerative changes, cystitis cystica glandularis, keratinizing squa\u00ad\nmous metaplasia, intestinal metaplasia, granulomatous cystitis, ulceration, therapy related changes.\n\t \u2022\t \u0007If kidney is present: glomerular disease, tubulointerstitial disease, vascular disease, inflammation\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (see Table 20-6). \nM0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nURETEROPELVIC JUNCTION\nPrimary causes of ureteropelvic junction obstruction are usually congenital in origin and may be due to \nmuscular bundle disarray or absence, increased collagen deposition, or abnormal anatomical location of \nthe renal pelvis. The diagnosis of these lesions is histologically problematic, does not affect the treatment \nor prognosis of the patient, and should not be attempted except on a research basis.\nIn adults, secondary causes of obstruction such as papillary urothelial (transitional) cell carcinoma \nor external compression by metastatic carcinoma, as well as lesions unrelated to the obstruction such as \nurothelial dysplasia, must be excluded.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_420.png", "summary": "This page provides guidelines for the microscopic examination of ureteropelvic junction specimens, including tumor evaluation, margins assessment, lymph node submission, and pathologic prognostic/diagnostic features for ureteral tumors.", "questions": [ "What are the key microscopic sections that should be included when examining ureteropelvic junction specimens?", "What are the important pathologic prognostic/diagnostic features to consider for ureteral tumors?", "How are regional lymph nodes classified in the evaluation of ureteral tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 421, "text": "GENITOURINARY SPECIMENS\u2003 Prostate\n403\nPROCESSING THE SPECIMEN\n 1.\t \u0007The specimen may be funnel-shaped if unopened. Describe the length, diameter at both ends, thick\u00ad\nness of wall, and the presence and size of any strictures. Open the specimen along the long axis.\nIf the specimen has been opened, it may look like a triangular fragment of mucosa. Describe the dimen\u00ad\nsions including the wall thickness.\n 2.\t \u0007Carefully examine the surface of the mucosa for any lesions or irregularities in texture. Examine the \nouter surface for any mass lesions, fibrosis.\n 3.\t \u0007Take sections along the long axis. Submit multiple sections in one cassette.\nCALCULI (KIDNEY AND BLADDER)\nKidney and bladder calculi are submitted for chemical analysis.\n\t \u2022\t \u0007Phosphate stones: gray to gray/white and may be hard or soft\n\t \u2022\t \u0007Urate stones: yellow or brown, hard, and round to oval\n\t \u2022\t \u0007Cystine stones: yellow, hard, smooth, and have a waxy appearance\n\t \u2022\t \u0007Oxalate stones: hard and may be either multilobated or spiculated.\nIf bleeding has occurred the stones may be black or dark brown.\nThe specimen is described including number, color, shape (round, multilobated, spiculated), consis\u00ad\ntency (soft, hard), and dimensions (in aggregate and range of sizes). Do not place in fixative!\nThe unfixed specimen may be sent to a commercial laboratory for chemical analysis.\nPROSTATE\nProstates are biopsied to evaluate nodules or to investigate an increased serum PSA. Transurethral resec\u00ad\ntions of the prostate (TURP) are performed to relieve urinary obstruction, generally for benign disease. \nHowever, tumor may be found incidentally. Prostates are resected for tumor (radical prostatectomy) or \nless commonly for benign hyperplasia (suprapubic prostatectomy).\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE)\nSee Table 20-10.\nTABLE 20\u201310.\u2003\nRELEVANT CLINICAL HISTORY \u2013 PROSTATE\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR PROSTATE SPECIMENS\nOrgan/tissue resected or biopsied\nPSA level\nPurpose of the procedure\nResults of prior biopsies\nGross appearance of the organ/tissue/lesion sampled\nAny unusual features of the \u00adclinical presentation\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nPrior malignancy\nPrior treatment (radiation \u00adtherapy, chemotherapy, drug \nuse that can change the histologic appearance of \ntissues)\n\u2192 Radiation or hormonal treatment\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_421.png", "summary": "The page provides guidelines for processing genitourinary specimens, specifically the prostate, and kidney and bladder calculi. It also discusses relevant clinical history for prostate specimens.", "questions": [ "What are the specific steps involved in processing a prostate specimen?", "What are the different types of kidney and bladder calculi mentioned and how are they described?", "Why is it important to consider the relevant clinical history when evaluating prostate specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 422, "text": "404\nGENITOURINARY SPECIMENS\u2003 Prostate\nNeedle Biopsy\nBiopsies are usually thin, obtained using a \u201cbiopsy gun,\u201d and are processed as described in Chapter 13. \nThree levels are needed to detect significant lesions. If focal glandular atypia is found in the first three \nslides, additional levels may show prostatic carcinoma.12-14\nIt can be helpful to request intervening unstained slides between the H&E levels. If a difficult-to-\nclassify glandular lesion is present, these slides can be used for immunoperoxidase studies (see \u201cImmu\u00ad\nnoperoxidase Studies,\u201d \u201c\u00adProstate\u201d).\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR PROSTATE CARCINOMA DIAGNOSED ON \nNEEDLE BIOPSY\n\t\u2022\t \u0007Histologic Type: Adenocarcinoma, other rare types\n\t\u2022\t \u0007Histologic Grade: Primary (predominant pattern), secondary (worst remaining) pattern; total score \n(Gleason pattern)\n\t\u2022\t \u0007Tumor Quantitation: Number of cores with carcinoma and total number of cores\n\t \u2022\t \u0007Proportion (percentage) of prostatic tissue involved by tumor and/or total linear millimeters of \n\u00adcarcinoma/length of core\n\t\u2022\t \u0007Periprostatic Fat Invasion: Not identified, present\n\t\u2022\t \u0007Seminal Vesicle Invasion: Not identified, present\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Additional Pathologic Findings: High-grade prostatic intraepithelial neoplasia (PIN), atypical \n\u00adadenomatous hyperplasia (adenosis), inflammation (type)\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nTransurethral Resection of Prostate (TURP)\nIn this procedure, multiple fragments are curetted from the central transitional zone of the prostate in \norder to relieve obstruction. TURPs are performed less commonly than in the past due to advances in \nthe non-surgical therapy of prostatic enlargement. The intent is not to diagnose cancer, as the majority \nof carcinomas (about 75%) arise in the unsampled peripheral zone.\nNevertheless, carcinoma is found in 7% to 8% of TURPs with limited sampling and 14% to 19% \nif the entire specimen is examined. The likelihood of finding cancer is 6.4% if preoperative PSA and \ndigital rectal examination are negative, 11.9% to 15% if either are positive, and 43.9% if both are posi\u00ad\ntive (Zigeuner). The majority (70% to 80%) are T1a (involving 5% or less of tissue) carcinomas and the \nremainder T1b (involving >5% of tissue).\nThe criteria for \u201cclinically significant\u201d prostate cancer have included extent, grade, and age of the \npatient, but there is no universally accepted definition. A quarter to a third of incidentally found prostate \ncarcinomas will progress if followed for 10 years, but the selection of patients for treatment remains \ncontroversial.\nBecause the likelihood of finding incidental carcinoma varies according to how much tissue is exam\u00ad\nined, and the amount of tissue from a TURP may be quite large, studies have been undertaken to deter\u00ad\nmine how much sampling is necessary.\nIn some studies, limited sampling has been effective in detecting all carcinomas defined to be clinically \nimportant. For example, examination of 6 grams of chips found all Stage A2 carcinomas.15 Examination \nof 12 grams revealed 90% of the incidental carcinomas, including all of the clinically significant cancers \n(i.e., excluding small well differentiated Stage A1 cancers). However, in other studies 6% to 7% of the \nincidental cancers were high grade and could have been missed if the entire specimen had not been \nexamined.16,17\nCAP recommends examining specimens weighing 12 grams or less in their entirety (see www.cap.org). \nFor larger specimens, the first 12 grams should be submitted (in 6 to 8 cassettes \u2013 in general", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_422.png", "summary": "The page discusses the processing and evaluation of prostate needle biopsies, including the need for multiple levels to detect significant lesions and the checklist for diagnosing prostate carcinoma. It also mentions the procedure of transurethral resection of the prostate (TURP) and the likelihood of finding carcinoma in TURPs.", "questions": [ "What are the key elements included in the pathologic prognostic/diagnostic features sign-out checklist for prostate carcinoma diagnosed on needle biopsy?", "Why are three levels needed to detect significant lesions in prostate needle biopsies?", "What is the likelihood of finding carcinoma in TURPs and how does it vary based on preoperative PSA and digital rectal examination results?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 423, "text": "405\nGENITOURINARY SPECIMENS\u2003 Prostate\n1 to 2 grams of tissue will fit in one cassette), with one more cassette for each additional 5 grams of tissue. \nIf an unsuspected carcinoma is found involving <5% of tissue, the remaining tissue is generally submitted \nfor examination.\nIf firm, yellow or yellow-orange chips are present, they should be submitted, as these chips are more \nlikely to contain carcinoma.18 Additional recommendations in the literature have been to submit the \nentire specimen in the following situations:\nPatients <60 years of age (small low grade carcinomas may be more likely to become clinically signifi\u00ad\ncant in this group).\nPatients with elevated PSA (may have centrally located carcinomas)\nEach institution may develop its own policy for the extent of examination.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the specimen. The easiest method is to weigh the entire container (without fixative) and sub\u00ad\ntract the weight of the container. Record the dimensions in aggregate. Describe the fragments includ\u00ad\ning color (gray/tan = normal, yellow suggests tumor), consistency (rubbery = normal, hard suggests \ntumor), and all areas with a different appearance (e.g., necrosis, hemorrhage).\nNote: The yellow or yellow-orange color seen in association with carcinoma is best seen in unfixed \ntissue.\n 2.\t \u0007Submit the entire specimen if possible, up to 12 blocks. For larger specimens, the institutional proto\u00ad\ncol should be followed (see discussion). Additional sampling should be considered for patients with an \nelevated PSA or under the age of 60.\nIf carcinoma is present on the initial slides, and involves <5% of tissue, all the remaining tissue is \ngenerally submitted.\n 3.\t \u0007Since carcinomas tend to be near the capsule, and the clinician may take smaller slices to avoid going \nthrough the capsule, smaller fragments may be more likely to contain carcinoma.\n 4.\t \u0007For cases with one to two cassettes, order two levels. For cases with three or more cassettes, order one \nlevel. \nThe proportion of prostatic tissue involved by tumor (\u22645% or >5%) is reported. The number of chips \nwith tumor and the number of total chips may also be reported. See the next section for reporting recom\u00ad\nmendations.\nSuprapubic Prostatectomy or Retropubic Simple Prostatectomy (Enucleation) for Benign Prostatic Hyperplasia\nThese enucleation procedures are performed rather than a TURP if the prostate is very enlarged or if \nthere are other contraindications for transurethral surgery (e.g., urethral disease, bladder diverticula). \nThe specimen usually looks like a large apple with a wedge cut out of one side, but may come in two or \nmore fragments. There are usually no orienting features. The entire prostate is not removed so margins \nare irrelevant.\nAs for TURP specimens, there is no consensus on the appropriate amount of sampling. From 4% to \n13% of cases will reveal unsuspected carcinoma. A minimum of one cassette for each 5 grams of tissue \nhas been suggested. CAP recommends submitting 8 cassettes. If an unsuspected carcinoma is found, and \nit involves <5% of tissue, additional blocks should be submitted.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the entire specimen and aggregate dimensions. Serially section the specimen at 3 to 4 mm. If \nthe urethra can be identified (usually it cannot) make the sections perpendicular to it.\n 2.\t \u0007Describe the parenchyma including color (white/tan, yellow, gray), consistency (firm, hard, soft, indu\u00ad\nrated), areas of necrosis or hemorrhage. Carcinomas may be more yellow and firmer than hyperplastic \nnodules.\n 3.\t \u0007Submit at least eight cassettes from different areas including (if recognizable) urethra, right and left \nlobes, and capsule and any areas suspicious for tumor.\nThe percent of tissue involved by carcinoma is reported. If a dominant nodule can be identified, the size \nshould be given.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_423.png", "summary": "Genitourinary specimens, particularly prostate tissue, should be carefully examined for carcinoma, with specific recommendations for submitting tissue based on various factors such as patient age and PSA levels.", "questions": [ "What are the recommendations for submitting prostate tissue if an unsuspected carcinoma is found?", "How should the processing of prostate specimens be approached, especially in terms of weighing and submitting the tissue?", "What are the differences in handling specimens from suprapubic prostatectomy or retropubic simple prostatectomy compared to TURP procedures?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 424, "text": "406\nGENITOURINARY SPECIMENS\u2003 Prostate\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR PROSTATE CARCINOMA DIAGNOSED ON \nTURP OR ENUCLEATION SPECIMENS\n\t\u2022\t \u0007Procedure: Transurethral prostatic resection, enucleation (subtotal prostatectomy)\n\t\u2022\t \u0007Specimen Size: Give weight in grams or size for enucleation specimens\n\t\u2022\t \u0007Histologic Type: Adenocarcinoma, other rare types\n\t\u2022\t \u0007Histologic Grade: Primary (predominant pattern), secondary (worst remaining) pattern; total score \n(Gleason pattern)\n\t\u2022\t \u0007Tumor Quantitation: TURP specimens:\n\t \u2022\t \u0007Proportion (percentage) of prostatic tissue involved by tumor or\n\t \u2022\t \u0007Incidental finding in \u22645% of tissue (cT1a), or\n\t \u2022\t \u0007Incidental finding in > 5% of tissue (cT1b), or\n\t \u2022\t \u0007Number of positive chips/total chips\n\t \u2022\t \u0007Enucleation specimens:\n\t \u2022\t \u0007Proportion (percentage) of prostatic tissue involved by tumor\n\t \u2022\t \u0007Tumor size (dominant nodule, if present), in centimeters\n\t\u2022\t \u0007Periprostatic Fat Invasion: Not identified, present\n\t\u2022\t \u0007Seminal Vesicle Invasion: Not identified, present\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Additional Pathologic Findings: High-grade prostatic intraepithelial neoplasia (PIN), atypical ade\u00ad\nnomatous hyperplasia (adenosis), inflammation (type), nodular prostatic hyperplasia\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nRadical Prostatectomy\nRadical prostatectomies are performed after carcinoma has been documented. Numerous protocols for \nsubmitting tissue have been proposed ranging from submission of the entire specimen in whole mount \nspecimens to limited sampling using standard slides.19,20 Any method used should be designed to evaluate \nthe extent of carcinoma, grade, stage, and margin status.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the entire specimen and record the outer dimensions including prostate and seminal vesicles. \nOrient the specimen (Fig. 20-3) to identify right and left, anterior and posterior, superior and inferior. \nIt may be helpful to place a probe through the urethra. Note any unusual appearance to the prostatic \ncapsule, which is normally relatively smooth (irregular areas may indicate tumor invasion or incom\u00ad\nplete surgical excision).\n 2.\t \u0007Ink the right and left halves of the specimen different colors, including the soft tissue around the \nseminal vesicles and ductus deferentia.\n 3.\t \u0007Amputate each seminal vesicle and submit the basal section of each one at the junction with the pros\u00ad\ntate (RSV and LSV). Carcinomas may penetrate the prostatic capsule at the base and invade through \nadipose tissue and into the seminal vesicle in this area.\n 4.\t \u0007The bladder neck base margin (also referred to as the proximal urethral margin [PUM]) surrounds the \nprostatic urethra nearest the seminal vesicles on the superior surface. This margin is cut perpendicular \nto the urethra as thin (0.7 cm) shaved wedges. This margin is cut perpendicular to the initial cut and \nsubmitted on edge (RPUM and LPUM). The right and left sides are submitted separately.\nThe apex (also referred to as the distal urethral margin - DUM) is cut perpendicular to the urethra \nas a thin (0.7 cm) shave margin. This margin is cut perpendicular to the initial cut and submitted on \nedge. The right and left sides are submitted separately (RDUM and LDUM).\n 5.\t \u0007Section the remaining prostate at 5 mm intervals using cuts perpendicular to the urethral axis. Alter\u00ad\nnate sections are quartered and submitted from apex (= slice #1) to base. Each cassette should be coded", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_424.png", "summary": "This page provides a checklist for reporting on prostate carcinoma diagnosed on TURP or enucleation specimens, including details on procedure, specimen size, histologic type and grade, tumor quantitation, invasion status, and additional pathologic findings.", "questions": [ "How is the tumor quantitation different for TURP specimens compared to enucleation specimens?", "What are the key elements that must be present in reports of cancer-directed surgical resection specimens?", "What are the recommended protocols for processing radical prostatectomy specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 425, "text": "407\nGENITOURINARY SPECIMENS\u2003 Prostate\nas to the slice number (e.g., \u201c1,\u201d \u201c3,\u201d \u201c5\u201d), right vs. left, and anterior vs. posterior (e.g., 1RA, 1RP, \n1LA, 1LP).\nExamine each slice for the presence of gross lesions (see below). Note the location of any lesions \n(ant/post, right/left, superior/inferior), color, extension to capsule or other structures, and their \nsize. However, many tumors are small (due to the effects of screening) and are not detectable \ngrossly.\nDescribe the remainder of the parenchyma including color, consistency, and nodularity. If a gross \nlesion is present, a photograph should be taken.\nGROSS DIFFERENTIAL DIAGNOSIS\nAdenocarcinoma.\u2002 Prostate carcinoma is the most difficult malignancy to detect grossly because of the \nunderlying firmness of the normal or hyperplastic gland, the small size of many tumors, and the tendency \nof many tumors to infiltrate into and around normal tissue or to grow in a nodular pattern mimicking \nnormal parenchyma.\nSUPERIOR\nINFERIOR\nA\nB\nC\nVas\nSeminal vesicle\nAmputate seminal\nvesicle and submit\neach base\nRight anterior/RA\nRight posterior/RP\nDivide into quadrants\nBlack\nBlue\nLeft anterior/LA\nLeft posterior/LP\nBladder neck margin,\nserial section and submit on edge\nApical margin,\nserial section and submit on edge\nEntirely submit each quadrant,\nin order from apex to base\nBladder neck\nProstatic urethra\nApex\nRIGHT\n(Black)\nLEFT\n(Blue)\nFigure 20\u20133.\u2002 Radical prostatectomy. A, Orientation. B, Margins and seminal vesicles. C, Quadrants.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_425.png", "summary": "The text provides guidelines for examining genitourinary specimens, specifically the prostate, including details on how to identify gross lesions, describe the parenchyma, and differentiate adenocarcinoma.", "questions": [ "How do the characteristics of prostate carcinoma make it challenging to detect grossly?", "What specific details should be noted when examining each slice of the prostate for gross lesions?", "Why is it important to take a photograph if a gross lesion is present in the prostate specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 426, "text": "408\nGENITOURINARY SPECIMENS\u2003 Prostate\nThe majority of carcinomas (about 75%) are located in the posterior peripheral zone. It is helpful to \nlook for smooth solid areas with effacement of the normal spongy or cystic appearance or an area where \nthe capsule appears to be effaced. An asymmetry of the right and left posterior lobes may indicate the \nlocation of a tumor. Tumors may have a slightly different color (sometimes yellow), but often do not. \nPalpation may be helpful in fresh tissues (carcinomas may be firm or gritty and less spongy than normal \ntissue), but is not helpful after fixation. Even experienced pathologists cannot identify at least 50% of \nprostate carcinomas grossly.\nHistorical data may be helpful. Prior biopsy reports may indicate location (i.e., right vs. left). Lesions \ndiagnosed by needle biopsy and/or as a palpable mass are most likely located in the posterior portion of \nthe gland. Lesions diagnosed by TURP specimens are often located centrally or anteriorly.\nNodular Hyperplasia (Benign Prostatic Hypertrophy or Hyperplasia).\u2002 The gland is diffusely \nenlarged due to centrally located nodules of variable size. The nodules may be soft and tan/pink and \nexude prostatic fluid or be firm and gray with a whorled appearance. The nodules often encroach laterally \non the prostatic urethra. The peripheral zone may appear compressed.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Lesions: Make sure all sections can be identified as either the right lobe or the left lobe (right inked \nblack, left inked blue, and designate in cassette code). Submit lesions in their entirety.\n\t\u2022\t \u0007Grossly normal prostate: Submit alternate sections.\n\t\u2022\t \u0007Margins: Submit bladder neck margin and apical margin (see Fig. 20-3 for details).\n\t\u2022\t \u0007Seminal vesicle: Submit one section from the base of each vesicle.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cprostate,\u201d is a 52 gram radi\u00ad\ncal prostatectomy specimen that measures 6 cm right to left, 5.5 cm anterior to posterior, and 4.7 cm \nsuperior to inferior. The right seminal vesicle measures 1.5 \u00d7 0.8 \u00d7 0.4 cm and the left seminal vesicle \nmeasures 1.7 \u00d7 0.6 \u00d7 0.4 cm. The right side of the prostate is inked in black, the left side in blue. The \nexternal surface of the prostate is smooth. There are multiple nodules grossly consistent with benign \nprostatic hyperplasia located centrally, the largest of which measures 1 \u00d7 1 \u00d7 0.5 cm. There is a 0.9 \u00d7 \n0.5 \u00d7 0.5 cm grey/yellow mass in the right posterior lobe that may represent tumor that does not extend \nacross the midline. This lesion is within 0.1 cm of the posterior margin, but is not grossly present at \nthe margins. The prostate is sectioned into 5 slices. Alternate slices are submitted completely from \napex (slice #1) to base (slice #5) for histologic examination. The remainder of the tissue is saved for the \ntumor bank.\nCassette 1: RSV, RSS, 1 frag.\nCassette 2: LSV, RSS, 1 frag.\nCassette 3: RPUM, ESS, 5 frags.\nCassette 4: LPUM, ESS, 6 frags.\nCassette 5: RDUM, ESS, 1 frag.\nCassette 6: LDUM, ESS, 1 frag.\nCassette 7: 1 RA, ESS, 1 frag.\nCassette 8: 1 LA, ESS, 1 frag.\nCassette 9: 1 RP, ESS, 1 frag.\nCassette 10: 1 LP, ESS, 1 frag.\nCassette 11: 3 RA, ESS, 1 frag.\nCassette 12: 3 LA, ESS, 1 frag.\nCassette 13: 3 RP, ESS, 1 frag.\nCassette 14: 3 LP, ESS, 1 frag.\nCassette 15: 5 RA, ESS, 1 frag.\nCassette 16: 5 LA, ESS, 1 frag.\nCassette 17, 5 RP, ESS, 1 frag.\nCassette 18: 5 LP, ESS, 1 frag.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_426.png", "summary": "Prostate carcinomas are mostly located in the posterior peripheral zone and may present as solid areas with effacement of normal appearance. Nodular hyperplasia can cause diffuse enlargement with centrally located nodules.", "questions": [ "How can experienced pathologists identify prostate carcinomas grossly?", "What are the differences in location between lesions diagnosed by needle biopsy versus TURP specimens?", "What are the key sections to submit for microscopic examination of prostate specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 427, "text": "409\nGENITOURINARY SPECIMENS\u2003 Prostate\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR PROSTATE CARCINOMAS IN RADICAL \nPROSTECTOMY SPECIMENS\n\t\u2022\t \u0007Procedure: Radical prostatectomy\n\t\u2022\t \u0007Prostate Size: Give weight and size in three dimensions\n\t\u2022\t \u0007Lymph Node Sampling: Pelvic lymph node dissection, no lymph node excision\n\t\u2022\t \u0007Histologic Type: Adenocarcinoma (acinar type), prostatic duct adenocarcinoma, mucinous (colloid) \nadenocarcinoma, signet ring cell carcinoma, adenosquamous carcinoma, others\n\t\u2022\t \u0007Histologic Grade: Primary (predominant pattern), secondary (worst remaining) pattern; total score \n(Gleason pattern)\n\t \u2022\t \u0007Gleason score is not used for carcinomas that have been treated.\n\t\u2022\t \u0007Tumor Quantitation: Proportion (%) of prostate involved by tumor\n\t \u2022\t \u0007Tumor size (dominant nodule, if present), in cm\n\t \u2022\t \u0007Number of blocks with tumor\n\t \u2022\t \u0007Various methods are used, some requiring submission of the entire gland and image analysis (Hum\u00ad\nphrey PA, Vollmer RT. Percentage carcinoma as a measure of prostatic tumor size in radical prosta\u00ad\ntectomy tissues. Mod Pathol 10:326-333, 1997). The greatest dimension of tumor on the glass slides \ncan be used to predict tumor volume (Renshaw AA, Chang H, D\u2019Amico AV. Estimation of tumor \nvolume in radical prostatectomy specimen in routine clinical practice. Am J Clin Pathol 107:704-\n708, 1997; Renshaw AA, Richie JP, Loughlin KR, et al. The greatest dimension of prostate carci\u00ad\nnoma is a simple, inexpensive predictor of prostate specific antigen failure in radical prostatectomy \nspecimens. Cancer 83:748-752, 1998).\n\t\u2022\t \u0007Extraprostatic Extension: Not identified, present. If present:\n\t \u2022\t \u0007Focal (site), nonfocal (established extensive, site)\n\t \u2022\t \u0007Unifocal or multifocal (extensive): The extent of extraprostatic invasion is of prognostic value. \nExtraprostatic invasion may be defined as \u201cfocal\u201d (\u2264 1HPF on \u22642 slides) or \u201cnonfocal\u201d (any degree \nof invasion more than focal).\n\t \u2022\t \u0007Defined as tumor beyond the confines of the prostatic gland:\n\t\n\u2022\t \u0007Tumor abutting on or admixed with fat\n\t\n\u2022\t \u0007Tumor involving perineural spaces in neurovascular bundles beyond the prostate\n\t\n\u2022\t \u0007Tumor beyond the confines of the normal glandular prostate (anterior prostate and bladder neck). \nHowever, a T4 designation usually requires gross involvement of the bladder neck.\n\t \u2022\t \u0007Skeletal muscle is present at the apex. Carcinoma in skeletal muscle at this site does not constitute \nextraprostatic extension.\n\t \u2022\t \u0007The prostatic capsule is ill defined and incomplete. Carcinomas typically extend along the periphery \nof the posterior lobes. Only unequivocal extraprostatic extension into adjacent adipose tissue should \nbe diagnosed as extraprostatic extension.\n\t\u2022\t \u0007Seminal Vesicle Invasion: Not identified, present (invasion of muscular wall), or no seminal vesicle \npresent\n\t \u2022\t \u0007Invasion must be into the muscular wall vesicle (invasion into the adventitia but not the wall does \nnot qualify as invasion into the seminal vesicle)\n\t\u2022\t \u0007Margins: Not identified, present, location (apical\u2014the most inferior portion of the prostate), bladder \nneck, anterior, lateral, posterolateral (neurovascular bundle), posterior, other\n\t \u2022\t \u0007Unifocal or multifocal, extent (e.g., focal or extensive, number of blocks, linear millimeters)\n\t \u2022\t \u0007Positive margins are defined as ink on tumor cells. Close margins (without ink on tumor cells) are \nreported as negative. A margin may be positive without the presence of extraprostatic invasion.\n\t \u2022\t \u0007Benign glands at the margin may be reported.\n\t\u2022\t \u0007Treatment Effect: No prior treatment, no effect present, radiation therapy effect, hormonal therapy \neffect\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present, within or outside the capsule. Perineural invasion is a \ncommon finding, and there is not a universal consensus as to its significance within the capsule.\n\t\u2022\t \u0007Extent of Invasion: Unilateral, involving one half of one lobe or less (T2a), unilateral involving more \nthan one half of one lobe (T2b), involving both lobes (T2c), extension beyond the prostate or micro\u00ad\nscopic invasion of bladder neck (T3a), extension into seminal vesicle (T3b), invasion of rectum, levator \nmuscles, and/or pelvic wall (T4)\n\t\u2022\t \u0007Regional Lymph Nodes: Present or absent, number of involved nodes, number of nodes examined", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_427.png", "summary": "This page outlines the pathologic prognostic/diagnostic features checklist for prostate carcinomas in radical prostatectomy specimens, including details on histologic type, grade, tumor quantitation, extraprostatic extension, and seminal vesicle invasion.", "questions": [ "What are the different histologic types of prostate carcinomas mentioned in the checklist?", "How is tumor quantitation measured in radical prostatectomy specimens?", "What criteria are used to define extraprostatic extension and seminal vesicle invasion in prostate carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 428, "text": "410\nGENITOURINARY SPECIMENS\u2003 Prostate\n\t\u2022\t \u0007Additional Pathologic Findings: High-grade prostatic intraepithelial neoplasia (PIN), inflammation \n(type), atypical adenomatous hyperplasia (adenosis), nodular prostatic hyperplasia\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 20-11). \nM0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nTABLE 20\u201311.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF PROSTATE TUMORS\nTUMOR\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nClinically inapparent tumor neither palpable nor visible by imaging\nT1a\nTumor incidental histologic finding in 5% or less of tissue resected\nT1b\nTumor incidental histologic finding in more than 5% of tissue resected\nT1c\nTumor identified by needle biopsy (e.g., because of elevated PSA). Includes \ntumors found in both lobes by needle biopsy.\npT2\nTumor confined within the prostate*\npT2a\nUnilateral, one half of one side or less\npT2b\nUnilateral, involving more than one half of one side but not both sides\npT2c\nBilateral disease\npT3\nExtraprostatic extension\npT3a\nExtraprostatic extension or microscopic invasion of bladder neck\u2020\npT3b\nSeminal vesicle invasion\npT4\nInvasion of rectum, levator muscles, and/or pelvic wall\n*Tumor found in one or both lobes by needle biopsy, but not palpable or reliably visible by imaging, is classified as T1c.\n\u2020Positive surgical margin should be indicated by an R1 descriptor (residual microscopic disease)\nRegional Lymph Nodes\nNX\nRegional nodes not sampled\nN0\nNo positive regional nodes\nN1\nMetastases in regional node(s)\nDistant Metastasis*\nM0\nNo distant metastasis\nM1\nDistant metastasis\nM1a\nNonregional lymph node(s)\nM1b\nBone(s)\nM1c\nOther site(s) with or without bone disease\n*When more than one site of metastasis is present, the most advanced category is used. pM1c is most advanced.\nNote: This classification system does not apply to sarcomas or urothelial (transitional) cell carcinomas. Urothelial (transitional) cell carcinomas of \nthe prostate should be classified as urethral tumors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_428.png", "summary": "This page provides information on additional pathologic findings, distant metastasis, and AJCC classification for prostate tumors.", "questions": [ "What are some of the additional pathologic findings mentioned for prostate specimens?", "How is distant metastasis determined in prostate cancer cases?", "What are the different classifications provided by the AJCC for prostate tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 429, "text": "411\nGENITOURINARY SPECIMENS\u2003 Prostate\nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nGLEASON GRADING OF PROSTATIC ADENOCARCINOMAS\nThe two predominant patterns are graded from one to five and added together to derive a Gleason\u2019s \nscore (Fig. 20-4 and Table 20-12). If there is only one pattern, the same grade is duplicated. The score \nand the grade should be reported with the predominant grade listed first (e.g., Gleason score 7 [3+4] or \nGleason score 7 [4+3]).\nCircumscribed nodule of closely packed but separate,\n uniform, rounded to oval, medium-sized acini (larger\n glands than pattern 3)\nLike pattern 1, fairly circumscribed, yet at the edge of\n the tumor nodule there may be minimal infiltration\nGlands are more loosely arranged and not quite as\n uniform as pattern 1\nFused microacinar glands\nIll-defined glands with poorly formed glandular lumina\nLarge cribriform glands\nCribriform glands with an irregular border\nHypernephromatoid\nEssentially no glandular differentiation, composed of\n solid sheets, cords, or single cells\nComedocarcinoma with central necrosis surrounded\n by papillary, cribriform, or solid masses\nDiscrete glandular units\nTypically smaller glands than seen in patterns 1 or 2\nInfiltrates in and among non-neoplastic prostate acini\nMarked variation in size and shape\nSmoothly circumscribed small cribriform nodules of tumor\n1\nPROSTATIC ADENOCARCINOMA\n(Histologic grades)\n2\n3\n5\n4\nFigure 20\u20134.\u2002 Gleason grade.\u2002 (Image from Gleason DF: Histologic grading of prostate cancer: A perspective. Hum Pathol \n23:273-279, 1992; text from Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL; ISUP Grading Committee: The 2005 \u00adInternational \nSociety of Urological Pathology (ISUP) Consensus Conference on Gleason grading of prostatic \u00adcarcinoma, Am J Surg Pathol \n29:1228-1242, 2005.)\nTABLE 20\u201312.\u2003\nGLEASON SCORE\n2-4\nWell differentiated\n5-6\nModerately differentiated\n7\nModerately poorly differentiated\n8-10\nPoorly differentiated\nData from Gleason DF: Histologic grading of prostate cancer: A perspective. Hum Pathol 23:273-279, 1992.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_429.png", "summary": "This page discusses the Gleason grading system for prostatic adenocarcinomas, which involves grading two predominant patterns from one to five and adding them together to derive a Gleason's score.", "questions": [ "How is the Gleason score calculated for prostatic adenocarcinomas?", "What are the different patterns described in the Gleason grading system?", "Why is it important to report the Gleason score with the predominant grade listed first?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 430, "text": "GENITOURINARY SPECIMENS\u2003 Testis\n412\nIn core needle biopsies, when more than two patterns are present, and the highest grade is not the \npredominant or second most common grade, the predominant pattern and the highest grade are used \nto derive a score. For example, if 70% of the carcinoma is grade 3, 20% grade 2, and 10% grade 4, this \nwould be reported as Gleason score 7 (3+4). If more than one tumor of different grade is found in a pros\u00ad\ntatectomy specimen, the grade of each should be reported.\nIf Gleason pattern 5 is present as a tertiary pattern, this finding should be reported (e.g., \u201cGleason \nscore 7 [3 + 4] with tertiary Gleason pattern 5\u201d).\nIn current practice, Gleason grade 1 carcinomas are vanishingly rare and grade 2 carcinomas are \nuncommon. Carcinomas are not graded if there has been prior \u00adtreatment.24,25\nTESTIS\nBiopsies are usually performed for the evaluation of infertility. Unilateral orchiectomies are performed \nto resect tumors (almost all germ cell tumors). Retroperitoneal lymph node dissections for testicular car\u00ad\ncinoma require special evaluation (see below). Bilateral orchiectomies are sometimes performed for the \ntreatment of prostate \u00adcarcinoma.\nRELEVANT CLINICAL HISTORY\nSee Table 20-13.\nBiopsy for Infertility\nBouin\u2019s is the preferred fixative. The yellow/tan tubules of the testicular parenchyma can be identified \ngrossly. The entire specimen is submitted. Order 2 H&E, trichrome, elastic stain, and PAS to aid in the \nevaluation of basement membranes.\nIn lesions in which some spermatogenesis is seen (Box 20-2, categories 3 and 4, rarely 5), count the sper\u00ad\nmatids in selected (10 to 20) tubules and derive an average spermatid per tubular cross section count. Count \nall small, elongated, compact oval nuclei (these cells have no tails yet). Then use Figure 20-5 to calculate \nthe predicted sperm count and report this number as well. 100 \u00d7 106 sperm/cc is considered a normal count.\nUnilateral Orchiectomy for Tumor\nGerm cell tumors are the most common tumors of the testis; they are readily locally controlled but often \nmetastasize.\nTABLE 20\u201313.\u2003\nRELEVANT CLINICAL HISTORY \u2013 TESTIS\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR TESTICULAR SPECIMENS\nOrgan/tissue resected or biopsied\nCryptorchidism (with or \u00adwithout prior orchiopexy)\nPurpose of the procedure\nRetroperitoneal or para-aortic lymphadenectomy\nGross appearance of the organ/tissue/lesion sampled\nPrior contralateral testicular tumor, prior ipsilateral \n\u00adintratubular germ cell \u00adneoplasia\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\nPrior surgery/biopsies \u2013 results\nSerum levels of alpha-\u00adfetoprotein (AFP) and human \nchorionic gonadotropin (\u03b2-hCG)\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug \nuse that can change the histologic appearance of \n\u00adtissues)\nGynecomastia (more frequently associated with sex \ncord/\u00adstromal tumors than with germ cell tumors)\nCompromised immune system\nIntersex syndrome (e.g., ambiguous genitalia or \nfeminization)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_430.png", "summary": "The page discusses the grading system for testicular tumors, including how to derive Gleason scores and report findings. It also outlines the relevant clinical history and procedures for testicular specimens.", "questions": [ "What is the significance of reporting the Gleason score for testicular tumors?", "Why is it important to consider prior treatment when grading carcinomas?", "What are the common procedures performed for testicular tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 431, "text": "GENITOURINARY SPECIMENS\u2003 Testis\n413\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the specimen and record the dimensions of the testis (three dimensions), epididymis (three \ndimensions), and spermatic cord (length and diameter).\n 2.\t \u0007Remove the proximal resection margin of the spermatic cord and place in a labeled cassette. Note: \nThe vas deferens often retracts. Try to find the end of the vas by looking for a thin firm white tubular \nstructure.\nSection through the remainder of the cord, looking for gross evidence of tumor spread.\nNote: Some germ cell tumors (particularly seminoma or necrotic tumors) are very loosely cohesive \nand are easily smeared on to other areas of the specimen. It is preferred to take the margin before \ncutting into the tumor. True margin involvement is rare and will usually be evident on gross \n\u00adexamination.\n 3.\t \u0007The tunica vaginalis is a closed peritoneal sac surrounding the front and sides of the testis and extends \nupward over the spermatic cord. It should not be adherent to the tunica albuginea away from the cord, \nunless there is tumor invasion or infiltration. Any areas of \u00adadherence should be noted. Open the sac \nalong the anterior \u00adborder.\nThe testis is surrounded by the thick white tunica albuginea. The epididymis is posterior and in conti\u00ad\nnuity with the spermatic cord. Bisect the testis parallel to, and through, the epididymis. Additional \ncuts can be made parallel to this plane.\nBOX 20\u20132.\u2003 Histologic patterns in testicular \u00adbiopsies\n\t1.\t \u0007Normal\n\t2.\t \u0007Prepubertal\n\t3.\t \u0007Sloughing\n\t4.\t \u0007Hypospermatogenesis\n\t5.\t \u0007Spermatogenic arrest\n\t6.\t \u0007Sertoli only\n\t7.\t \u0007Hyalinized\nQUANTITATIVE TESTICLE BIOPSY AND SPERM COUNT\nTestes biopsy\nnumber of mature\nspermatids per\ntubule\nCorrelation Fit\nr2 = .91\na = 10.39\nb = 0.31\ny = axb (power curve)\nSevere\noligospermia\nOligospermic nonobstructed patients\nPostoperative obstructed patients\nRegression line\nSperm count x 106/mL\n60\n50\n40\n30\n20\n10\n10\n20\n30\n40\n50\n60\n70\n80\n90\n100\n110\n0\nFigure 20\u20135.\u2002 Correlation between the number of mature spermatids per tubule and the sperm counts.\u2002 (From \n\u00adSilber\u00a0SJ, Rodriguez-Rigau LJ: Quantitative analysis of testicle biopsy: determination of partial obstruction and prediction \nof sperm count after surgery for obstruction, Fertil Steril 36:480-485, 1981.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_431.png", "summary": "This page provides guidelines on processing testicular specimens, including recording dimensions, removing resection margins, and identifying histologic patterns. It also discusses quantitative testicle biopsy and sperm count correlation.", "questions": [ "How important is it to accurately record the dimensions of the testis, epididymis, and spermatic cord?", "What are the implications of finding true margin involvement in germ cell tumors?", "How does the correlation between the number of mature spermatids per tubule and sperm counts impact diagnosis and treatment?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 432, "text": "GENITOURINARY SPECIMENS\u2003 Testis\n414\nDescribe any lesions including size, color, consistency, variegation (it is very important to sample \nall areas with a different gross appearance), hemorrhage or necrosis. Determine if tumor extends \nthrough the tunica \u00adalbuginea or into the epididymis. Invasion most commonly occurs at the junc\u00ad\ntion of the testis and the \u00adepididymis.\nDescribe the remainder of the testicular parenchyma including color (tan/yellow), consistency (stringy). \nThe normal seminiferous tubules can be demonstrated grossly by gently teasing them out with a forceps.\n 4.\t \u0007Take sections of all lesions, including all areas of different gross appearance, and relationship to tunica \nvaginalis and epididymis. Take one section of uninvolved testis.\nGROSS DIFFERENTIAL DIAGNOSIS\nSeminomas.\u2002 (40% of germ cell tumors) are usually solid homogeneous light-yellow to tan fleshy nod\u00ad\nules that often have sharply circumscribed areas of necrosis. Cystic areas or hemorrhage are unusual and \nmay indicate that another type of germ cell tumor is present. Some patients have elevated serum HCG \n(10% to 25%) due to the presence of syncytiotrophoblast cells. AFP is usually normal.\nEmbryonal Carcinomas are firm with a more heterogeneous gray/white coloration and may have \nareas of hemorrhage and necrosis.\nChoriocarcinomas are often small, gray/white, and usually very hemorrhagic and necrotic. Almost \nall patients will have elevated serum HCG.\nTeratomas (4% to 5% of germ cell tumors) are usually cystic or multiloculated and often have grossly \nevident cartilaginous differentiation. 57% are mature and 43% immature. Fat and bone may be present. \nImmature teratomas may grossly resemble brain tissue. 90% are associated with ITGCN. Teratomas are \naneuploid and have the i(12p) characteristic of other germ cell tumors.\nDermoid and Epidermoid Cysts can be benign and are not associated with ITGCN.\nEndodermal Sinus Tumors (yolk sac) are rarely seen in a pure form in adults, and are usually not \nevident grossly if a minor component. Pure tumors in children under 2 years of age may have a soft, \ngelatinous, microcystic appearance and be pale tan or yellow. Larger tumors may be focally necrotic. \nAlmost all patients have elevated serum AFP.\nRegressed Germ Cell Tumors may consist of a small fibrous scar or area of calcification. If a patient \nhas a known metastatic germ cell tumor, and a gross lesion cannot be found, the entire testis should be \nexamined histologically.\nLeydig Cell Tumors are well circumscribed or lobulated and yellow, tan, or brown. Hemorrhage and \nnecrosis are uncommon.\nSertoli Cell Tumors are gray/white, firm, and circumscribed.\nLymphomas are rare, usually seen in older males, and are usually part of more generalized involve\u00ad\nment (i.e., not solely present in testis). The testis is diffusely enlarged by homogeneous fleshy gray/\ncreamy white tissue that may be multinodular. About half of cases also involve epididymis or spermatic \ncord. Tissue is taken for hematopathologic studies (see Chapter 27).\nAcute and Chronic Leukemias frequently involve the testes. The tumors may closely resemble a \nseminoma with a creamy yellow to white homogeneous appearance. The testis is a frequent site of relapse \nafter treatment of leukemia due to decreased penetration of chemotherapy.\nPediatric Germ Cell Tumors are more commonly endodermal sinus tumors or teratomas and the \nbehavior may be \u00addifferent from that observed in adults.26 Cytogenetic studies may be useful as the genetic \nchanges have been reported to be different from those observed in adults and may predict different \nbehavior. Tissue for EM and snap-freezing is not used routinely for diagnosis but may be saved for pos\u00ad\nsible studies in unusual cases.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_432.png", "summary": "The page provides guidelines on how to describe and sample testicular lesions, including differentiating between various types of germ cell tumors and other testicular neoplasms.", "questions": [ "What are the key features to describe when examining testicular lesions?", "How do seminomas differ from embryonal carcinomas and choriocarcinomas in terms of gross appearance?", "Why is it important to take sections of all lesions and the uninvolved testis during examination?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 433, "text": "415\nGENITOURINARY SPECIMENS\u2003 Testis\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: 4 to 10 cassettes demonstrating all types of gross appearances including all hemorrhagic and \nnecrotic areas. In general, at least one cassette per 1 cm of greatest dimension should be examined. \nInclude sections demonstrating relationship to tunica vaginalis and near the base of the epididymis \n(this is the most common site to find tumor invasion outside the testis).\nIf serum \u03b2-HCG is increased in the absence of Leydig cell hyperplasia or choriocarcinoma, take more \nsamples to look for choriocarcinoma.\nIf serum alpha-fetoprotein is increased and yolk sac carcinoma is not seen, sample more to look for pos\u00ad\nsible yolk sac carcinoma.\n\t\u2022\t \u0007Testis: One cassette of uninvolved testis and epididymis. A section of the rete testis is needed for \n\u00adstaging.\n\t\u2022\t \u0007Spermatic cord: Resection margin, representative sections from center of cord, representative sec\u00ad\ntions from peritesticular cord.\nSAMPLE DICTATION\nReceived labeled with the patient\u2019s name and unit number and \u201cright testis\u201d is a 30 gm orchiectomy \nspecimen including testis (4.5 \u00d7 4 \u00d7 4 cm), epididymis (1 \u00d7 1 \u00d7 0.5), and \u00adspermatic cord (9 cm in length \u00d7 \n1.5 cm in diameter). There is a 3 \u00d7 2 \u00d7 2 cm tan/white firm circumscribed mass with focal areas of hemor\u00ad\nrhage and necrosis and small (0.2 cm) cystic spaces within the testis. The tumor does not grossly extend \ninto the tunica albuginea or into the epididymis. The remainder of the testicular parenchyma is brown/\ntan with grossly normal tubules present. The spermatic cord consists of vas deferens, arteries, and veins, \nand is grossly unremarkable.\nCassettes #1-2: Tumor with homogeneous appearance, 3 frags, RSS.\nCassettes #3-4: Tumor with necrosis and hemorrhage, 3 frags, RSS.\nCassettes #5-6: Tumor with small cystic areas, 2 frags, RSS.\nCassette #7: Tumor and tunica vaginalis, 1 frag, RSS.\nCassette #8: Tumor and epididymis, 1 frag, RSS.\nCassette #9: Uninvolved adjacent testis, 1 frag, RSS.\nCassette #10: Spermatic cord, resection margin, 1 frag, ESS.\nCassette #11: Spermatic cord, mid section, 1 frag, RSS.\nCassette #12: Spermatic cord, peri-testicular, 1 frag, RSS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR TESTICULAR TUMORS\n\t\u2022\t \u0007Serum Tumor Markers: Unknown, normal, alpha-fetoprotein (AFP) elevation, beta-subunit of \nhuman chorionic gonadotropin (\u03b2-hCG) elevation, lactate dehydrogenase (LDH) elevation\n\u0007If the serum markers are elevated and a histologic correlate is not found (i.e., yolk sac for AFP or \nchoriocarcinoma or Leydig cell hyperplasia for \u03b2-hCG) additional tumor sampling may be helpful.\n\t\u2022\t \u0007Specimen Laterality: Right, left, both\n\t\u2022\t \u0007Tumor Focality: Unifocal, multifocal\n\t\u2022\t \u0007Tumor Size: Greatest dimension of main tumor (additional dimensions are optional), greatest dimen\u00ad\nsion of additional tumor nodules. Seminomas > 4 cm in size have an increased risk for recurrence.\n\t\u2022\t \u0007Extent of Tumor: Rete testis, epididymis, hilar fat, spermatic cord, tunica vaginalis (perforates meso\u00ad\nthelium), scrotal wall\n\t \u2022\t \u0007Intratubular germ cell neoplasia (Tis), limited to testis (including rete testis and epididymis) with\u00ad\nout vascular/lymphatic invasion (tumor may invade tunica albuginea but not tunica vaginalis) (T1), \ntumor with vascular/lymphatic invasion or extension through tunica albuginea with involvement of \ntunica vaginalis (T2), tumor invades spermatic cord (T3), tumor invades scrotum (T4).\n\t \u2022\t \u0007Rete testis involvement (extension of tumor into testicular mediastinum without necessarily involv\u00ad\ning tubular lumens) is associated with increased risk for recurrence for seminoma (see Warde P, et \nal, Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J \nClin Oncol 20:4448-4452, 2002).\n\t \u2022\t \u0007Involvement of parenchyma beyond the area of the main tumor mass may also be of prognostic \nimportance for seminoma.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_433.png", "summary": "The page provides guidelines for examining testis specimens for tumors, including specific sections to be sampled and considerations for serum tumor markers.", "questions": [ "What are the recommended cassettes to be examined for tumor specimens from the testis?", "Why is it important to sample more if serum tumor markers are elevated without a histologic correlate?", "What are the prognostic features to consider when evaluating testicular tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 434, "text": "416\nGENITOURINARY SPECIMENS\u2003 Testis\n\t\u2022\t \u0007Histologic Type: Seminoma (classic type or with syncytiotrophoblastic cells), seminoma associated \nwith a scar, teratoma, embryonal carcinoma, choriocarcinoma, endodermal sinus (yolk sac) tumor, \nintratubular germ cell neoplasia, sex cord stromal tumors, others. Include the presence of syncytiotro\u00ad\nphoblasts.\n\t \u2022\t \u0007Many tumors are of mixed types. The proportion of each type is given.\n\t\u2022\t \u0007Margins: Spermatic cord, parietal layer of tunica vaginalis, scrotal skin\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Regional Lymph Nodes: Absent or present, number of involved nodes (number of nodes examined), \nsize of metastasis (< 2, < 5 cm, < 10 cm), presence of extranodal invasion\n\t \u2022\t \u0007If prior treatment has been given, see the section on \u201cRetroperitoneal Lymph Node Dissection for \nTesticular Carcinoma.\u201d\n\t\u2022\t \u0007Additional Pathologic Findings: Intratubular germ cell neoplasia, atrophy, fibrosis, hemosiderin-\nladen macrophages and intratubular calcifications (possibly regressed tumor), spermatogenesis present \nor absent, Leydig cell hyperplasia (may be associated with \u03b2-hCG elevation), Sertoli cells, abnormal \ntesticular development (e.g., due to dysgenesis or androgen-insensitivity syndrome)\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 20-14). \nM0 is conferred after clinical assessment; there is no pM0 category.\n\t \u2022\t \u0007The Modified Royal Marsden staging system may be used for classification of pure seminomas.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nRetroperitoneal Lymph Node Dissection for Testicular Carcinoma\nOften these procedures are performed following chemotherapy. Therefore, much of the tissue may be \nhemorrhagic, cystic, and/or necrotic. In such cases, it is especially important to take many sections to \ndocument the presence or absence of viable residual high-grade tumor (embryonal carcinoma, endoder\u00ad\nmal sinus tumor, or choriocarcinoma). The size of the largest lymph node metastasis (or confluent area \nof tumor involvement) and number of involved lymph nodes is recorded.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR RETROPERITONEAL LYMPHADENECTOMY \nFOR TESTICULAR TUMORS\n\t\u2022\t \u0007Prelymphadenectomy Treatment: None, chemotherapy, radiation therapy\n\t\u2022\t \u0007Serum Tumor Markers: Unknown, within normal limits, AFP elevation, \u03b2-hCG elevation, LDH \nelevation\n\u0007If the serum markers are elevated and a histologic correlate is not found (i.e., yolk sac for AFP or \nchoriocarcinoma or Leydig cell hyperplasia for \u03b2-hCG), additional tumor sampling may be helpful.\n\t\u2022\t \u0007Specimen Site(s): Nodal groups\n\t\u2022\t \u0007Number of Nodal Groups Present: Give number\n\t\u2022\t \u0007Size of Largest Metastasis: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Histologic Viability of Tumor: No tumor present, viable teratoma present, viable nonteratomatous \ntumor present\n\t\u2022\t \u0007Histologic Type of Metastatic Tumor: Same as for testicular tumors\n\t\u2022\t \u0007AJCC Classification: Number of nodes with metastases, number of nodes examined, size of largest \nmetastatic deposit\n\t\u2022\t \u0007Nonregional Lymph Node Metastasis: Not identified, present\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_434.png", "summary": "This page provides detailed information on the histologic types, margins, lymph-vascular invasion, regional lymph nodes, distant metastasis, and AJCC classification for testicular tumors. It also includes a checklist for retroperitoneal lymph node dissection for testicular carcinoma.", "questions": [ "What are the different histologic types of testicular tumors mentioned on this page?", "How is the presence of lymph-vascular invasion and distant metastasis assessed in testicular tumors?", "What is the significance of Leydig cell hyperplasia in testicular tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 435, "text": "417\nGENITOURINARY SPECIMENS\u2003 Testis\nTABLE 20\u201314.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF TESTICULAR TUMORS\nTumor\npTX\nPrimary tumor cannot be assessed.\npT0\nNo evidence of primary tumor (e.g., histologic scar in testis)\npTis\nIntratubular germ cell neoplasia (carcinoma in situ)\npT1\nTumor limited to the testis and epididymis without vascular/lymphatic invasion; tumor may \ninvade into the tunica albuginea but not the tunica vaginalis\npT2\nTumor limited to the testis and epididymis with vascular/lymphatic invasion, or tumor extending \nthrough the tunica albuginea with involvement of the tunica vaginalis\npT3\nTumor invades the spermatic cord with or without vascular/lymphatic invasion\npT4\nTumor invades the scrotum with or without vascular/lymphatic invasion\nRegional Lymph Nodes\npNX\nRegional lymph nodes cannot be assessed.\npN0\nNo regional lymph node metastasis\npN1\nMetastasis with a lymph node mass, \u2264 2 cm in greatest dimension and \u2264 5 nodes positive, none \n> 2 cm in greatest dimension\npN2\nMetastasis with a lymph node mass, > 2 but \u2264 5 cm in greatest dimension; or more than 5 nodes \npositive, none \u2264 5 cm; or evidence of extranodal extension of tumor\npN3\nMetastasis with a lymph node mass > 5 cm in greatest dimension\nNote: Regional lymph nodes include interaortocaval, para-aortic (peri-aortic), paracaval, preaortic, precaval, retroaortic, and retrocaval. Intrapelvic, \nexternal iliac, and inguinal nodes are considered regional only after scrotal or inguinal surgery before the presentation of the testis tumor. Lateral\u00ad\nity does not affect N classification.\nSerum Tumor Markers\nSX\nMarker studies not available or not performed\nS0:\nMarker study levels within normal limits\nLDH\nHCG (mIU/mL)\nAFP (ng/mL)\nS1\n< 1.5 \u00d7 N\nand\n< 5000\nand\n< 1000\nS2\n1.5-10 \u00d7 N\nor\n5000-50,000\nor\n1000-10,000\nS3\n> 10 \u00d7 N\nor\n> 50,000\nor\n> 10,000\n*N indicates the upper limit of normal for the LDH assay.\nMetastasis\nM0\nNo distant metastasis\nM1\nDistant metastasis\nM1a\nNonregional nodal or pulmonary metastasis\nM1b\nDistant metastasis other than to nonregional lymph nodes and lung\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_435.png", "summary": "This page outlines the AJCC classification of testicular tumors based on primary tumor characteristics, regional lymph node involvement, serum tumor marker levels, and presence of distant metastasis.", "questions": [ "How do the different categories of the AJCC classification impact treatment decisions for testicular tumors?", "What are the key markers used to assess serum tumor marker levels in testicular tumors?", "How does the AJCC classification system help in predicting the prognosis of patients with testicular tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 436, "text": "418\nGENITOURINARY SPECIMENS\u2003 Testis\nBilateral Simple Orchiectomy \u2013 Non-tumor\nBilateral orchiectomies are sometimes performed for the treatment of prostate cancer. A unilateral sim\u00ad\nple orchiectomy may be performed for torsion.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh each testis and record the measurements of the testis and spermatic cord (length and diam\u00ad\neter), if \u00adpresent.\n 2.\t \u0007Make a single incision through the testis. If focal lesions are present, follow the protocol above for \ntumors. If no lesions are present, describe the parenchyma (soft, yellow/tan), look for the presence of \ntubules, capsule (smooth, white).\n 3.\t \u0007Submit one representative section of each testis.\nREFERENCES\n\t\u2002 1.\t \u0007Racusen LC, et al: The Banff 97 working classification of renal allograft pathology,. Kid International 55:713-\n723, 1999.\n\t\u2002 2.\t \u0007Bijol V, Mendez GP, Hurwitz S, et al. Evaluation of the nonneoplastic pathology in tumor nephrectomy speci\u00ad\nmens: predicting the risk of progressive renal failure. Am J Surg Pathol 30:575-584, 2006.\n\t\u2002 3.\t \u0007Henriksen KJ, Meehan SM, Chang A. Non-neoplastic renal diseases are often unrecognized in adult tumor \nnephrectomy specimens: a review of 246 cases. Am J Surg Pathol 31:1703-1708, 2007.\n\t\u2002 4.\t \u0007Tickoo SK, dePeralta-Venturina MN, Harik LR, et al. Spectrum of epithelial neoplasms in end-stage renal \ndisease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those \nin sporadic adult renal neoplasia. Am J Surg Pathol 30:141-153, 2006.\n\t\u2002 5.\t \u0007Meng MV, Koppie TM, Duh Q-Y, Stoller ML. Novel method of assessing surgical margin status in laparo\u00ad\nscopic specimens. Urology 58:677-682, 2001.\n\t\u2002 6.\t \u0007Meng MV, Koppie TM, Stoller ML. Pathologic sampling of laparoscopically morcellated kidneys: a mathemati\u00ad\ncal model. J Endourology 17:229-233, 2003.\n\t\u2002 7.\t \u0007Meng MV, Miller TR, Stoller ML. Cytology of morcellated renal specimens: significance in diagnosis and dis\u00ad\nsemination. J Urol 169:45-48, 2003.\n\t\u2002 8.\t \u0007Qualman SJ, et al: Protocol for the examination of specimens from patients (children and young adults) with \nWilms tumor (nephroblastoma) or other renal tumors of childhood. Arch Pathol Lab Med 127:1280-1289, \n2003.\n\t\u2002 9.\t \u0007Zuppan CW. Handling and evaluation of pediatric renal tumors. Am J Clin Pathol 109(Suppl 1):S31-S37, \n1998.\n\t10.\t \u0007Gephardt GN, Baker PB. Interinstitutional comparison of bladder carcinoma surgical pathology report ade\u00ad\nquacy, A College of American Pathologists Q-probes study of 7234 bladder biopsies and curettings in 268 \ninstitutions. Arch Pathol Lab Med 119:681-685, 1995.\n\t11.\t \u0007Murphy WM, et al: Tumors of the kidneys, bladder and related urinary structures, Atlas of Tumor Pathology, \n3rd series Fascicle. Washington, DC, Armed Forces Institute of Pathology, 1994, p 199.\n\t12.\t \u0007Renshaw AA. Adequate tissue sampling of prostate core needle biopsies. Am J Clin Pathol 107:26-29, 1997.\n\t13.\t \u0007Reyes AO, Humphrey PA. Diagnostic effect of complete histologic sampling of prostate needle biopsy speci\u00ad\nmens. Am J Clin Pathol 109:416-422, 1998.\n\t14.\t \u0007Rubin MA, Bismar TA, Curtis S, Montie JE. Prostate needle biopsy reporting. How are the surgical members \nof the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients? Am \nJ Surg Pathol 28:946-952, 2004.\n\t15.\t \u0007Zigeuner R, Schips L, Lipsky K, et al: Detection of prostate cancer by TURP or open surgery in patients with \npreviously negative transrectal prostate biopsies, Urology 62:883-887, 2003.\n\t16.\t \u0007Murphy WM, Dean PJ, Brasfield JA, Tatum L. Incidental carcinoma of the prostate. How much sampling is \nadequate? Am J Surg Pathol 10:170-174, 1986.\n\t17.\t \u0007Moore GH, Lawshe B, Murphy J. Diagnosis of adenocarcinoma in transureethral resectates of the prostate \ngland. Am J Surg Pathol 10:165-169, 1986.\n\t18.\t \u0007Newman AJ, Graham MA, Carlton CE, et al: Incidental carcinoma of the prostate at the time of transurethral \nresection: Importance of evaluating every chip. J Urol 128:948-950, 1982.\n\t19.\t \u0007Geddy PM, Reid IN. Selective sampling of yellow prostate chips: a specific method for detecting prostatic \nadenocarcinoma. Urol Int 56:33-35, 1996.\n\t20.\t \u0007Humphrey PA, Walther PJ. Adenocarcinoma of the prostate. I. Tissue sampling considerations. Am J Clin \nPathol 99:746-759, 1993.\n\t21.\t \u0007Bova GS, Fox WM, Epstein JI. Methods of radical prostatectomy specimen processing: A novel technique for \nharvesting fresh prostate cancer tissue and review of processing techniques. Mod Pathol 6:201-207, 1993.\n\t22.\t \u0007Humphrey PA, Vollmer RT. Percentage carcinoma as a measure of prostatic tumor size in radical prostatectomy \ntissues. Mod Pathol 10:326-333, 1997.\n\t23.\t \u0007Renshaw AA, Chang H, D\u2019Amico AV. Estimation of tumor volume in radical prostatectomy specimen in routine \nclinical practice. Am J Clin Pathol 107:704-708, 1997.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_436.png", "summary": "Bilateral orchiectomies may be performed for prostate cancer treatment, while a unilateral simple orchiectomy may be done for torsion.", "questions": [ "What are the reasons for performing a bilateral orchiectomy?", "How is the processing of the testis specimen carried out?", "What information is important to record during the processing of a testis specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 437, "text": "419\nGENITOURINARY SPECIMENS\u2003 References\n\t24.\t \u0007Renshaw AA, Richie JP, Loughlin KR, et al. The greatest dimension of prostate carcinoma is a simple, inexpen\u00ad\nsive predictor of prostate specific antigen failure in radical prostatectomy specimens,. Cancer 83:748-752, 1998.\n\t25.\t \u0007Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL. ISUP Grading Committee. The 2005 International Society \nof Urological Pathology (ISUP) Consensus Conference on Gleason grading of prostatic carcinoma. Am J Surg \nPathol 29:1228-1242, 2005.\n\t26.\t \u0007Gleason DF. Histologic grading of prostate cancer: A perspective. Hum Pathol 23:273-279, 1992.\n\t27.\t \u0007Hawkins EP. Germ cell tumors. Am J Clin Pathol 109(Suppl 1):S82-S88, 1998.\n\t28.\t \u0007Warde P, et al: Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. \nJ Clin Oncol 20:4448-4452, 2002.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_437.png", "summary": "This page provides references related to genitourinary specimens, including studies on prostate carcinoma, Gleason grading, and germ cell tumors.", "questions": [ "What is the significance of the greatest dimension of prostate carcinoma in predicting prostate specific antigen failure?", "What was the outcome of the 2005 ISUP Consensus Conference on Gleason grading of prostatic carcinoma?", "How do prognostic factors for relapse in stage I seminoma differ when managed by surveillance?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 438, "text": "420\nGross Examination\nCertain specimens do not require submission for histologic examination. These specimens include inani\u00ad\nmate objects (that cannot be examined under the microscope) as well as tissue specimens that do not yield \nuseful diagnostic information.\nEach hospital must develop guidelines and policies for the types of specimens not to be examined \nhistologically. The following factors should be considered:\n\t\u2022\t \u0007The likelihood of a clinically significant finding.\n\t\u2022\t \u0007The need for documentation of surgical procedures for quality assurance.\n\t\u2022\t \u0007Educational value for doctors in training.\n\t\u2022\t \u0007Potential medicolegal issues.\nIn accordance with JCAHO guidelines and CAP,1 there can be an exception to mandatory submission \nof tissue when the following conditions are met:\n\t\u2022\t \u0007The quality of health care is not compromised by the exemption.\n\t\u2022\t \u0007Another suitable means of verification of removal is in place.\n\t\u2022\t \u0007There is an operative note or other official report that documents tissue removal.\nThese decisions are made by consensus of the hospital staff, including pathologists, and are put in \nwriting. All clinicians should be informed as to the types of specimens that are not examined routinely in \norder that a specific request can be made in those cases in which microscopic examination is indicated.\nA Q-Probes study by CAP revealed that 87.1% of institutions had written policies concerning speci\u00ad\nmens to be examined by gross examination only.2 Only four tissue specimens were exempt from submis\u00ad\nsion to the pathology department in more than 50% of institutions:\n 1.\t \u0007Placentas from routine uncomplicated pregnancies that were grossly normal\n 2.\t \u0007Foreskins from the circumcision of newborn children\n 3.\t \u0007Lens cataracts\n 4.\t \u0007Teeth\nThere were five types of tissue specimens that were exempt from microscopic examination in more \nthan 50% of institutions:\n 1.\t \u0007Calculi (renal, ureteral, bladder)\n 2.\t \u0007Teeth\n 3.\t \u0007Lens cataracts\n 4.\t \u0007Cartilage and bone from septorhinoplasty\n 5.\t \u0007Toenails and fingernails\nThus, most institutions continue to examine most specimens grossly and microscopically.\nINANIMATE OBJECTS GENERALLY NOT EXAMINED MICROSCOPICALLY\n\t\u2022\t \u0007Orthopedic hardware (see specific section in Chapter 28)\n\t\u2022\t \u0007Foreign bodies (see specific section in Chapter 28)\n\t\u2022\t \u0007Bullets (see specific section in Chapter 28)\n\t\u2022\t \u0007Gallstones (see specific section in Chapter 19)\n\t\u2022\t \u0007Bladder stones (usually sent for chemical analysis, see specific section in Chapter 20)\n\t\u2022\t \u0007Silicone implants (see specific section in Chapter 15)\n\t\u2022\t \u0007Vascular grafts may be submitted for histologic examination (see in Chapter 16, \u201cVascular Grafts\u201d).\n21", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_438.png", "summary": "Certain specimens do not require submission for histologic examination, including inanimate objects and tissue specimens that do not yield useful diagnostic information. Hospitals must develop guidelines and policies for these exceptions.", "questions": [ "What are the factors that hospitals should consider when determining which specimens do not need histologic examination?", "What are the exceptions to mandatory submission of tissue according to JCAHO guidelines and CAP?", "What are some examples of tissue specimens that are exempt from microscopic examination in more than 50% of institutions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 439, "text": "GROSS EXAMINATION\u2003 Other Specimens\n421\nTISSUE SPECIMENS GENERALLY EXAMINED GROSSLY BUT NOT MICROSCOPICALLY\n\t\u2022\t \u0007Teeth without attached soft tissue\n\t\u2022\t \u0007Skin from plastic surgery reconstruction if the surgeon does not request examination, no lesions are \npresent, and there is no history of malignancy.\n\t\u2022\t \u0007Skin with cicatrix (if there is no history of malignancy)\n\t\u2022\t \u0007Rib (as part of a resection if there is no history of malignancy and no gross lesions)\n\t\u2022\t \u0007Nasal septum (if part of a plastic surgery procedure or for chronic sinusitis)\n\t\u2022\t \u0007Stapes (removed to treat otosclerosis)\n\t\u2022\t \u0007Tonsils from children for hyperplasia without gross lesions\n\t\u2022\t \u0007Foreskins from newborns\n\t\u2022\t \u0007Saphenous vein harvest for CABG\n\t\u2022\t \u0007Placentas from routine pregnancies\n\t\u2022\t \u0007Fetuses from therapeutic abortions (if there is no clinical indication for examination)\n\t\u2022\t \u0007Finger and toenails (if there is no clinical indication for examination)\n\t\u2022\t \u0007Lens (if removed for cataracts)\n\t\u2022\t \u0007Pannus or bowel resections for treatment of obesity if grossly normal\nSPECIMENS THAT INSTITUTIONS MAY CHOOSE TO EXCLUDE FROM MANDATORY SUBMISSION TO THE PATHOLOGY \nDEPARTMENT\n\t\u2022\t \u0007Bone donated to a bone bank\n\t\u2022\t \u0007Bone fragments removed as part of reconstructive orthopedic procedures\n\t\u2022\t \u0007Cataracts removed by phacoemulsification\n\t\u2022\t \u0007Dental appliances\n\t\u2022\t \u0007Fat removed by liposuction\n\t\u2022\t \u0007Foreign bodies that are medicolegal evidence that are released directly to law enforcement personnel\n\t\u2022\t \u0007Foreskin from the circumcision of newborns\n\t\u2022\t \u0007IUDs without soft tissue\n\t\u2022\t \u0007Medical devices such as catheters, gastrostomy tubes, myringotomy tubes, stents, and sutures that have \nnot contributed to patient illness, injury, or death\n\t\u2022\t \u0007Middle ear ossicles\n\t\u2022\t \u0007Orthopedic hardware and other devices if there is an alternative policy to document their surgical removal\n\t\u2022\t \u0007Placentas from uncomplicated pregnancies that appear normal at the time of delivery\n\t\u2022\t \u0007Rib segments or other tissues removed for gaining surgical access, if the patient does not have a history \nof malignancy\n\t\u2022\t \u0007Saphenous vein segments harvested for coronary artery bypass\n\t\u2022\t \u0007Skin or other normal tissue removed during a cosmetic or reconstructive procedure, if the patient does \nnot have a history of malignancy\n\t\u2022\t \u0007Teeth without attached soft tissue\n\t\u2022\t \u0007Therapeutic radioactive sources\n\t\u2022\t \u0007Normal toenails and fingernails that are removed for cosmetic or hygienic purposes\nOTHER SPECIMENS\nIt has been suggested that some specimens (specifically gallbladders, tonsils in adults, appendices, bone \nfrom orthopedic procedures, and hernia sacs) need not be \u00adexamined, as the diagnostic yield is small. In \nsufficiently large studies, the incidence of clinically important unsuspected diagnoses in this group of \nspecimens is about 1 to 10 per 1,000 specimens. Thus, it becomes an economic decision as to whether \nit is of value to histologically examine all of these specimens. In a cost-benefit analysis, it was concluded \nthat at least 1 of every 2,000 specimens would need to show a clinically significant diagnosis to justify \nhistologic examination.3\nStudies have clearly shown that specimen types with a generally low diagnostic yield have a much \nhigher yield of important diagnoses if certain features are present. These include:\n\t\u2022\t \u0007Specimens from patients with a \u201cnon-routine\u201d clinical presentation (e.g., asymmetric tonsils)\n\t\u2022\t \u0007Grossly abnormal findings noted by the surgeon", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_439.png", "summary": "The page discusses various tissue specimens that are generally examined grossly but not microscopically, as well as specimens that institutions may choose to exclude from mandatory submission to the pathology department.", "questions": [ "What are some examples of tissue specimens that are examined grossly but not microscopically?", "Why might institutions choose to exclude certain specimens from mandatory submission to the pathology department?", "What is the suggested approach for specimens such as gallbladders, tonsils in adults, appendices, bone from orthopedic procedures, and hernia sacs that may not need to be examined?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 440, "text": "GROSS EXAMINATION\u2003 Other Specimens\n422\n\t\u2022\t \u0007Grossly abnormal findings noted by the pathologist\n\t\u2022\t \u0007Specimens from patients with a history of malignancy\n\t\u2022\t \u0007Specimens from patients in whom an infectious process is suspected\n\t\u2022\t \u0007Specimens from patients who are known to be immunocompromised or who are at higher risk for \nunusual infections (organ transplant, corticosteroid therapy, chemotherapy, chronic ambulatory peri\u00ad\ntoneal dialysis, diabetes mellitus, antibiotic therapy, antifungal therapy, assisted ventilation, extensive \nburns, implanted monitoring devices or catheters, or chronic sinusitis)\nThus, if a decision is made to not examine some types of \u201croutine\u201d specimens, it is important that \nnone of the features above are present. The absence of clinical history provided by the submitting \nphysician never can be interpreted to mean that no relevant clinical history exists. Figure 21-1 is \nan example of a requisition form that could be required from a submitting physician for such specimens.\nREFERENCES\n\t1.\u2002 \u0007Surgical Specimens to Be Submitted to Pathology for Examination, revised November 2007, CAP Reference \nResources and Publications, CAP Public Policy Compendium, www.cap.org.\n\t2.\u2002 \u0007Zarbo RJ, Nakhleh RE. Surgical pathology specimens for gross examination only and exempt from submission. A \nCollege of American Pathologists Q-Probes study of current policies in 413 institutions. Arch Pathol Lab Med \n123:133-139, 1999.\n\t3.\u2002 \u0007Raab SS. The cost-effectiveness of routine histologic examination,. Am J Clin Pathol 110:391-396, 1998.\n Request for pathologic examination.\n Yes \n No\n \n \nIs this a \u201croutine\u201d specimen (i.e., with the typical clinical presentation for this procedure)?\n \nIf no, explain:\n \n \nDid the tissue appear typical for a routine specimen?\n \nIf no, explain:\n \n \nIs the patient free of known malignancies?\n \nIf no, explain:\n \n \nDoes the patient lack conditions that could place him or her at higher risk for unusual infections or other\n \n \ndiseases, such as immunocompromise (e.g., HIV), organ transplant, corticosteroid therapy,\n \n \nchemotherapy, chronic ambulatory peritoneal dialysis, diabetes mellitus, antibiotic therapy, antifungal\n \n \ntherapy, assisted ventilation, extensive burns, implanted monitoring devices or catheters, or chronic\n \n \nsinusitis?\n \nIf no, explain:\n \n \nIs only a gross examination of tissue requested?\n \n \nIf a microscopic examination is requested, explain the reason\n \nfor the examination:\n \nIf the answers to the above questions are all \u201cyes\u201d and the tissue appears grossly unremarkable,\n \nthen the specimen may not be examined microscopically.\n \nIf any of the answers are \u201cno\u201d or unknown, or if the tissue appears to be abnormal, or at the discretion\n \nof the pathologist, the tissue may be examined microscopically.\nFigure 21\u20131.\u2002 Request for pathologic examination.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_440.png", "summary": "The page discusses the importance of examining grossly abnormal findings in specimens from patients with a history of malignancy, suspected infectious processes, or those at higher risk for unusual infections.", "questions": [ "Is this a 'routine' specimen with the typical clinical presentation?", "Did the tissue appear typical for a routine specimen?", "Is the patient free of known malignancies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 441, "text": "423\nUTERUS\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE)\nSee Table 22-1.\nEndometrial Biopsies or Curettings\nThe endometrium is biopsied to evaluate abnormal bleeding in postmenopausal women, to monitor \npatients at high risk for endometrial carcinoma (e.g., women taking tamoxifen), and in the evaluation of \ninfertility (Table 22-2).\nFor patients with trophoblastic disease, the history would include week of pregnancy, passage of tissue, \nprior history of hydatidiform mole, and human chorionic \u00adgonadotropin level.\nPROCESSING THE SPECIMEN\nThe entire specimen is submitted. One level is examined for women <45 years of age (usually luteal \nphase defect, increased bleeding to suspected polyps, endometritis); three levels for women \u226545 years \nof age or for women with any history or clinical question of hyperplasia (endometrial intraepithelial \nneoplasia = EIN) or carcinoma.\nTABLE 22\u20131.\u2003\nRELEVANT CLINICAL \u00adHISTORY - UTERUS\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR UTERINE SPECIMENS\nOrgan/tissue resected or biopsied\nDate of last menstrual period or if postmenopausal\nPurpose of the procedure\nCurrent or recent \u00adpregnancy.\nGross appearance of the organ/tissue/lesion \nsampled\nUse of exogenous \u00adhormones (type and duration)or \n\u00adhormonal treatment (e.g., tamoxifen)\nAny unusual features of the clinical presentation\nFamily history of breast or ovarian \ncarcinoma.\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nAbnormal bleeding\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, \ndrug use that can change the histologic appearance \nof tissues)\nCompromised immune system\n22\nGynecologic and Perinatal \nPathology", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_441.png", "summary": "Endometrial biopsies or curettings are performed to evaluate abnormal bleeding in postmenopausal women, monitor high-risk patients for endometrial carcinoma, and assess infertility. The entire specimen is submitted for processing, with different levels examined based on age and clinical history.", "questions": [ "What are the main reasons for performing endometrial biopsies or curettings?", "How does the processing of the specimen differ based on the age of the patient?", "What clinical history is considered relevant for uterine specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 442, "text": "424\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nHysterectomy and Salpingo-Oophorectomy\nThe type of hysterectomy (total or radical) and the disease (benign or malignant) determine the method \nfor processing the specimen. Specimens fall into three categories:\n \n1.\t \u0007Total hysterectomies for benign conditions (e.g., prolapse or fibroids).\n \n2.\t \u0007Total hysterectomies for malignant conditions (e.g., endometrial carcinoma).\n \n3.\t \u0007Radical hysterectomies for malignant conditions (e.g., cervical carcinoma) that include vaginal \ncuff, parametrium, and regional lymph nodes.\nGravid hysterectomies are rarely performed. These specimens are unusual and may have medicolegal \n\u00adimplications.\nORIENTATION OF HYSTERECTOMIES\nProceeding anterior to posterior are the round ligament, the fallopian tube, the ovary, and finally, the \novarian \u00adligament (Fig. 22-1).\nThe peritoneal reflection is lower on the posterior surface and often comes to a point. It is higher and \nblunter on the anterior surface where the bladder has been dissected away.\nIf a specimen cannot be oriented, designate the two sides \u201cA\u201d and \u201cB\u201d when submitting sections.\nTABLE 22\u20132.\u2003\nENDOMETRIAL DATING (NOYES CRITERIA)\nPROLIFERATIVE EM \n(PE)\nRound or tubular glands, pseudostratified nuclei, no cytoplasmic vacuolization, apical \n\u00admitoses, no vacuoles\nDay 16 EM\nLike PE, tubular glands with mitoses, but with scattered basal cytoplasmic vacuoles\nThese changes can be caused by estrogen alone and are not diagnostic of ovulation\nSECRETORY EM\nDay 17\nTubular glands with very regular, even subnuclear vacuoles (\u201cpiano keys\u201d). \nA few mitoses may be present\nDay 18\nIncreased glandular complexity (infolding) and intraglandular secretions, persistent \n\u00adcytoplasmic vacuoles\nDay 19\nLike Day 18 with only scattered \u00adcytoplasmic vacuoles. There are increased intraluminal \nsecretions. No mitoses are present.\nDay 20\nLike Day 19 without cytoplasmic \u00advacuoles. Secretions peak.\nDay 21-22\nLike Day 20 with maximal stromal edema; no decidual change. On day 22 the nuclei \nappear \u201cnaked\u201d.\nDay 23\nDecidual change cuffing around \u00adarterioles\nDay 24\nDecidual change expanding from gland-to-gland, but not going to surface\nDay 25\nA thin layer of decidual change \u00adunderneath the surface\nDay 26\nA thick layer of decidual change \u00adunderneath the surface\nDay 27\n\u201cInflammatory cells\u201d (stromal granulocytes) in decidua; scattered \u00adkaryorrhexis in \n\u00adglandular epithelium\nDay 28 (menstrual \nendometrium, \nME)\nHemorrhagic stroma (falling apart), prominent glandular karyorrhexis, and balls of \nnecrotic stroma (\u201cblue balls\u201d) surrounded by eosinophilic (\u201c\u00adreparative\u201d) epithelium\nAs a general rule of thumb, pathology residents are always one day off the correct day.\nModified from Noyes RW, Hertig AT, Rock J, Dating the endometrial biopsy, Fertil Steril 1:3-25, 1950.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_442.png", "summary": "Specimens from hysterectomies are processed differently based on whether they are for benign or malignant conditions, with radical hysterectomies for cervical carcinoma involving additional structures. Gravid hysterectomies are rare and may have legal implications.", "questions": [ "How does the type of hysterectomy and disease condition affect the processing of the specimen?", "What are the differences between total hysterectomies for benign conditions versus malignant conditions?", "Why are gravid hysterectomies considered unusual and potentially have medicolegal implications?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 443, "text": "425\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nTotal hysterectomy for benign conditions\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the specimen. Orient the specimen as to anterior and posterior.\nExamine the serosal surface for adhesions, \u00adendometriosis, tumor implants, or inflammation and \ndescribe.\nRecord the overall dimensions of the uterus (three dimensions), tubes (length and diameter), and \novaries (three dimensions).\nRecord the dimensions of the exocervix (two dimensions) and the diameter and shape (round or \nslit-like) of the external os. Describe the appearance (smooth, white, glistening) and any lesions of the \ncervix (ulcerated, irregular, granular). In cases of uterine prolapse, a vaginal cuff may be present and \nshould be described.\nSpecimens received as supracervical hysterectomies should be documented grossly, and the resec\u00ad\ntion margin should be inked prior to opening the uterus.\n 2.\t \u0007Open the uterus with scissors, along the lateral margins from the external os to the cornu. Never use a \nscalpel. It is useful to use a probe within the os to guide the scissors. Make transverse incisions through \nthe entire mucosa to, but not through, the serosa. Do not abrade the mucosa or wash with water.\nDescribe the endometrial cavity and lining including size (cornu to cornu, fundus to endocervical \ncanal), distortion (by leiomyomas), color (tan, hemorrhagic), thickness, and any lesions. If lesions are \npresent, describe location (anterior or posterior), size, color, consistency, and depth of invasion into \nmyometrium.\nANTERIOR\nANTERIOR\nPOSTERIOR\nPOSTERIOR\nCorpus\nFallopian tube\nOvary\nPeritoneal\nreflection\nPeritoneal\nreflection\nLower\nuterine\nsegment\nEndocervix\nExocervix\nRound\nligament\nFigure 22\u20131.\u2002 Total abdominal hysterectomy: orientation.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_443.png", "summary": "Total hysterectomy specimens for benign conditions should be carefully examined and documented, including dimensions of the uterus, tubes, ovaries, cervix, and external os. The endometrial cavity and lining should be described, noting any lesions present.", "questions": [ "What specific details should be recorded when examining the serosal surface of the uterus?", "Why is it important to make transverse incisions through the entire mucosa when opening the uterus?", "What are some key factors to consider when describing the endometrial cavity and lining?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 444, "text": "426\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nDescribe the endocervix including size (length and width), color, normal herringbone pattern, and \nany lesions.\nDescribe the myometrium including average thickness, normal trabeculated pattern, or adenomyo\u00ad\nsis (coarse trabeculations or cystic hemorrhagic areas). If leiomyomas are present describe number, \nsize (or range in size if many), location (subserosal, mural, submucosal, anterior or posterior), color, \npresence of hemorrhage or necrosis or variation in pattern.\nDescribe each fallopian tube (see \u201cFallopian Tube\u201d for instructions on sampling).\nDescribe each ovary (see \u201cOvary\u201d for instructions on sampling).\n 3.\t \u0007Hysterectomies for benign disease can have sections taken from unfixed tissue. The remainder of the \nspecimen is stored in formalin. However, if a neoplastic process is known or suspected, follow the \nprotocol for malignant uteri.\n 4.\t \u0007For certain high risk patients, the entire endometrial surface should be examined, even in the absence \nof any gross lesion, as small and/or grossly inconspicuous carcinomas may be present. Examples of \nhigh risk patients:\n\t \u2022\t \u0007Biopsy-proven endometrial intraepithelial neoplasia (EIN) or repeated biopsies raising suspicion for \nEIN.\n\t \u2022\t \u0007A concurrent ovarian endometrioid carcinoma.\n\t \u2022\t \u0007A concurrent estrogen-producing tumor (e.g., a granulosa cell tumor).\n\t \u2022\t \u0007Known germ line mutations causing HNPCC (Lynch syndrome) or Cowden syndrome\nIf the patient has a BRCA1 or 2 mutation, the entire endometrium does not need to be submitted. How\u00ad\never, the fallopian tubes should be examined using the SEE FIM protocol (see under \u201cFallopian Tube\u201d).\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Cervix: Anterior and posterior cervix taken, to include both exo- and endocervix and the transforma\u00ad\ntion zone.\n\t\u2022\t \u0007Lower uterine segment: One transmural section from each of the anterior and posterior sides.\n\t\u2022\t \u0007Endometrium and myometrium: Two transmural endometrial sections from anterior and posterior \nwalls; if the myometrium is very thick, include only a portion of wall. Sample any lesions (e.g., polyps). \nIf \u00adleiomyomata are present, section through each one and \u00adexamine grossly. Take up to three represen\u00ad\ntative sections TOTAL. More sections are taken if there are areas of necrosis, hemorrhage, or areas of \nunusual appearance.\nIf the hysterectomy is supracervical, take a section perpendicular to the resection margin (after inking) \nto determine at what level (endocervix or lower uterine segment) the resection was performed. If all \nendometrium is not removed, the patient may be at risk for developing carcinoma and decisions con\u00ad\ncerning hormonal treatment could be affected.\n\t\u2022\t \u0007Serosa: If serosa is not included in the sections of endometrium, submit a separate section.\n\t\u2022\t \u0007Fallopian tubes: Amputate the fimbria and serial section the remainder of the tube. Submit the entire \nfimbria as the representative section in all benign cases (including hysterectomies for leiomyomata). \nSubmit the entire tube in any uterine and pelvic epithelial malignancy, or in any case with a positive \nfamily history for breast or ovarian cancer, or otherwise risk-reducing \u00adsalpingo-oophorectomy, using \nthe SEE FIM protocol (see under \u201cFallopian Tube\u201d). Submit right and left tubes in \u00adseparate desig\u00ad\nnated cassettes.\n\t\u2022\t \u0007Ovary: Serially section the ovaries transversely to the long axis and submit one representative section \nfrom each ovary including the capsule. This section can be submitted with the fallopian tube in the same \ncassette.\nNote: If the woman has a personal or family history of breast carcinoma, the adnexal structures should \nbe ENTIRELY submitted.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cTAH-BSO,\u201d is a 350 gram specimen \nincluding an unopened uterus (10 \u00d7 6.5 \u00d7 4.0 cm), right fallopian tube (5 cm in length \u00d7 0.7 cm in diameter), \nright ovary (3.5 \u00d7 2.0 \u00d7 0.9 cm), left fallopian tube (4.3 cm in length \u00d7 0.7 cm in diameter), and left ovary (3.8 \n\u00d7 2.4 \u00d7 1.0 cm). The exocervix (3.0 \u00d7 2.8 cm) is covered by smooth glistening white mucosa. The external \nos is circular and measures 0.7 cm in diameter. The endocervical canal (2.7 cm in length) has a tan her\u00ad\nringbone mucosa. The endometrial cavity (6.5 cm from cornu to cornu, 5.0 cm in length) has a tan/pink", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_444.png", "summary": "This page provides detailed instructions on how to describe the endocervix, myometrium, leiomyomas, fallopian tubes, and ovaries in gynecologic pathology specimens.", "questions": [ "Why is it important to examine the entire endometrial surface in high-risk patients?", "What are the specific protocols for sampling different parts of the uterus in hysterectomy specimens?", "Why is it necessary to take sections from unfixed tissue in hysterectomies for benign disease?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 445, "text": "427\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nhemorrhagic endometrium (0.5 cm in average thickness). The myometrium measures 1.5 cm in maximum \nthickness and contains two subserosal leiomyomata (1.2 and 0.8 cm in greatest dimension) that have a white/\ntan whorled appearance without hemorrhage or necrosis. The serosa is dull and there are multiple fine \nadhesions.\nThe fallopian tubes are patent and have fimbriated ends. The left tube has a 0.3 cm in greatest dimen\u00ad\nsion, thin-walled, paratubal cyst filled with clear fluid.\nThe right ovary has a smooth white surface and a single smooth-walled cortical cyst (0.3 cm in greatest \ndimension). The left ovary has multiple fine adhesions on the outer surface and a golden yellow corpus \nluteum is present with a hemorrhagic center. Multiple corpora albicantia are present in both ovaries.\nCassette #1: Anterior cervix, 1 frag, RSS.\nCassette #2: Posterior cervix, 1 frag, RSS.\nCassette #3: Anterior lower uterine segment, 1 frag, RSS.\nCassette #4: Posterior lower uterine segment, 1 frag, RSS.\nCassette #5: Anterior endometrium, 1 frag, RSS.\nCassette #6: Posterior endometrium, 1 frag, RSS.\nCassette #7: Serosa including adhesions, 3 frags, RSS.\nCassette #8: Right fallopian tube (fimbria) and ovary with cyst, 4 frags, RSS.\nCassette #9: Left fallopian tube (fimbria) with cyst and left ovary with corpus luteum and adhesions, \n4 frags, RSS.\nTotal hysterectomy for uterine tumors\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the specimen and orient as above. Examine the serosal surface carefully for adhesions, sero\u00ad\nsal implants, or direct invasion by tumor. The vaginal reflection at the cervix should be examined \nfor tumor implants. Ink the parametrial surgical resection margin (disrupted areas) and the vaginal/\ncervical margin. The intact \u00adserosal surfaces need not be inked. If desired, the anterior and posterior \nresection margins may be inked in different colors, but this is not necessary if orientation is obvious. \nDo not ink surfaces exposed by cutting into the specimen. State in the description if the specimen was \nreceived intact or was previously opened.\n 2.\t \u0007Open with scissors along the lateral margins from external os to cornu. Avoid cutting through \nareas suspicious for involvement by tumor. Try to make clean cuts when opening the uterus so that \ntrue surgical margins and serosal surface will be apparent. Do not abrade the mucosa or wash with \nwater.\n 3.\t \u0007Make serial transverse incisions (with a blade larger than the uterus, i.e., not scissors or a scalpel) from \nthe mucosal surface to, but not through, the serosal surface at approximately 0.5 cm intervals. Leave \nall tissues attached in order to maintain orientation.\n 4.\t \u0007Describe as above, but include any irregularities or piling up of the mucosal surface, location of \nlesions (e.g., anterior vs. posterior), the portion of the endometrial surface involved, and gross inva\u00ad\nsion (depth). Gross invasion is appreciated as an effacement of the \u00adnormal myometrial texture but \nmay be difficult to appreciate grossly. For mesenchymal tumors, describe the location (mural and/or \nexophytic) including smooth vs irregular interfaces with normal tissues, and the \u00adtexture of the tumor, \nas well as areas of necrosis and hemorrhage.\n 5.\t \u0007Fix overnight in formalin. Paper towels (not gauze) should be placed between transverse sections to \nwick the formalin and ensure adequate fixation.\n 6.\t \u0007Sections are taken the following day. Search for all parametrial lymph nodes and note their location. \nUsually nodes are not found.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: Transmural sections demonstrating depth of invasion to the inked margin. In most cases four \nanterior and four posterior sections are adequate. If the tumor is in the LUS or near the cervix the \nentire vaginal margin (inked) is divided into quadrants and submitted and extra slides of the LUS and \nLUS/endocervical junction are also submitted. If no gross lesions are identified, or only EIN is sus\u00ad\npected, submit the ENTIRE endometrium (all sections do not need to be full thickness but all should \ninclude the endomyometrial interface to assess for invasion).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_445.png", "summary": "The specimen from a total hysterectomy for uterine tumors shows findings of hemorrhagic endometrium, leiomyomata in the myometrium, patent fallopian tubes with a paratubal cyst, and ovaries with cysts and corpora lutea.", "questions": [ "What are the characteristics of the leiomyomata in the myometrium?", "How are the fallopian tubes described in the specimen?", "What is the significance of the presence of corpora lutea in the ovaries?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 446, "text": "428\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nNote: The edges of transmural sections are trimmed to remove areas of myometrium without overly\u00ad\ning endometrium (Fig. 22-2).\nFor mesenchymal tumors (i.e., leiomyosarcomas or endometrial stromal sarcomas), submit one sec\u00ad\ntion per cm of tumor. Be sure to include the interface with the surrounding myometrium and areas \nof possible necrosis.\n\t\u2022\t \u0007Cervix: Anterior and posterior cervix taken to include both exo- and endocervix and the transforma\u00ad\ntion zone.\n\t\u2022\t \u0007Lower uterine segment: Two transmural sections from the posterior and anterior sides. See under \n\u201ctumor\u201d if the tumor is near the LUS.\n\t\u2022\t \u0007Fallopian tubes: Submit the entire tube using the SEE FIM protocol (\u201cSection and Extensively Exam\u00ad\nine the FIMbriated end of the fallopian tube\u201d) (see under \u201cFallopian Tube\u201d). The cassettes containing \nthe fimbriae must be indicated in the cassette key.\n\t\u2022\t \u0007Ovary: Submit the entire ovaries (sections taken transverse to the longitudinal axis) including \ncapsule.\n\t\u2022\t \u0007Serosa: If serosa is not included in the sections of endometrium, submit a separate section.\n\t\u2022\t \u0007Parametrium: Submit any parametrial nodules or lymph nodes.\n\t\u2022\t \u0007Other lesions: Submit sections of any other lesions (e.g., polyps, leiomyomata).\nAnterior\ncervix\nEndometrium\nAnterior\nendometrium\nLower\nuterine\nsegment\nPosterior\ncervix\nPosterior\nendometrium\nRight\nfallopian\ntube\nLeft\nfallopian\ntube\nRight\novary\nLeft\novary\nFull-thickness sections\nat deepest invasion\nSerosa\nFigure 22\u20132.\u2002 Total hysterectomy for malignant tumors (endometrial).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_446.png", "summary": "This page provides guidelines for the submission of specimens from the uterus, cervix, fallopian tubes, ovaries, and other lesions for pathological examination.", "questions": [ "What is the significance of submitting one section per cm of tumor for mesenchymal tumors?", "Why is it important to include the interface with the surrounding myometrium and areas of possible necrosis when submitting specimens?", "What is the SEE FIM protocol for submitting fallopian tubes and why is it recommended?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 447, "text": "429\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cHysterectomy,\u201d is a 400 gram \nspecimen including an unopened uterus (11 \u00d7 7 \u00d7 5.2 cm), right fallopian tube (4.5 cm in length \u00d7 0.7 cm \nin diameter), right ovary (3.0 \u00d7 2.0 \u00d7 1.0 cm), left fallopian tube (5.1 cm in length \u00d7 0.7 cm in diameter), \nand left ovary (3.5 \u00d7 3.2 \u00d7 0.9 cm). The exocervix (3.0 \u00d7 3.0 cm) is covered by smooth \u00adglistening white \nmucosa. The external os is circular and measures 0.6 cm in diameter. The endocervical canal (3.1 cm \nin length) has a tan herringbone mucosa. The endometrial cavity (7.1 cm from cornu to cornu, 6.0 cm \nin length) has a tan/pink hemorrhagic endometrial lining. There is a 2 \u00d7 2 cm mass of heaped up pink/\ngray mucosa on the posterior wall. There grossly appears to be myometrial invasion to a depth of one \nthird of the myometrial thickness. A \u00adrepresentative section was submitted for frozen section. The mass \nis located 3 cm from the lower uterine segment. The myometrium measures 2.1 cm in maximum thick\u00ad\nness. The serosa is shiny and glistening without adhesions.\nThe fallopian tubes are patent and have fimbriated ends. The entire tubes are submitted for micro\u00ad\nscopic \u00adexamination.\nThe right ovary has a smooth white outer surface and multiple corpora albicantia. The left ovary has \na smooth white outer surface and a single smooth walled simple cyst (0.8 cm in greatest dimension). The \nentire ovaries are submitted for microscopic examination.\nOne lymph node (0.6 cm) is located within parametrial soft tissue and is completely submitted for \nmicroscopic examination.\nCassette #1: Frozen section remnant, 1 frag, ESS.\nCassettes #2-5: Posterior wall of uterus including \u00addeepest extent of invasion, 4 frags, RSS.\nCassettes #6-9: Anterior wall of uterus including areas suspicious for tumor involvement, 4 frags, RSS.\nCassette #10: Anterior cervix, 1 frag, RSS.\nCassette #11: Posterior cervix, 1 frag, RSS.\nCassette #12: Lower uterine segment, posterior, 1 frag, RSS.\nCassette #13: Lower uterine segment, anterior, 1 frag, RSS.\nCassette #14: Left fallopian tube fimbria, 4 frags, ESS.\nCassette #15: Left tube and ovary, mult frags, ESS.\nCassette #16: Right fallopiman tube fimbria, 4 frags, ESS.\nCassette #17: Right tube and ovary, mult frags, ESS.\nCassette #18: Lymph node, 2 frags, ESS.\nRadical hysterectomy for cervical carcinoma\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the specimen and orient as described previously. Examine the serosal surface for adhesions, \nserosal tumor nodules, or direct invasion by tumor (Fig. 22-3).\nInk the parametrial and cervical resection margins (disrupted areas) and the vaginal cuff margin. \nThe intact serosal surface need not be inked. The anterior and \u00adposterior resection margins may be \ninked in two \u00addifferent colors, but this is not necessary if orientation is obvious.\nDo not spill ink onto the exocervix. Do not ink surfaces exposed by cutting into the specimen.\nState in the description whether the specimen was received intact or was previously opened.\n 2.\t \u0007Amputate the cervix with the vaginal cuff. Open anterior surface (12 o\u2019clock). Pin onto corkboard and \nfix in formalin overnight.\nOpen the uterine corpus with scissors along the lateral margins from external os to cornu. Avoid cutting \nthrough areas suspicious for involvement by tumor. Try to make clean cuts when opening the uterus so that \ntrue surgical margins and serosal surface will be apparent. Do not abrade the mucosa or wash with water.\n 3.\t \u0007Make serial transverse incisions (with a blade larger than the uterus, i.e., not scissors or a scalpel blade) \nfrom the mucosal surface to, but not through, the serosal surface at approximately 0.5 cm intervals. \nLeave all tissues attached in order to maintain orientation.\n 4.\t \u0007Describe as for a nontumor hysterectomy but include location of lesions (e.g., anterior vs. poste\u00ad\nrior, involvement of exocervix, endocervix, and/or LUS), distance from margins, and gross invasion \n(depth). Fix overnight in formalin.\n 5.\t \u0007Carefully search for parametrial lymph nodes and note their location, side, and number. Lymph nodes \nare \u00adfrequently received from the surgeons as separate \u00adspecimens.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_447.png", "summary": "A 400 gram hysterectomy specimen with various components including the uterus, fallopian tubes, and ovaries showing myometrial invasion and suspicious tumor involvement.", "questions": [ "What are the key components of the hysterectomy specimen and their characteristics?", "How is myometrial invasion assessed and what are the implications of one third invasion?", "What is the significance of the lymph node found within parametrial soft tissue?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 448, "text": "430\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor (cervix): Submit the entire cervix by clock positions (as described for cone biopsies \u2013 see \nbelow). The vaginal margin can be left on the cervix and included with these sections if small. If this \nmargin is large, representative sections can be submitted using clock positions. If tumor is close or \ninvolves the vaginal margin, the entire margin should be submitted as clock positions.\nIf the tumor extends beyond the cervix, sample these areas (e.g., parametrium and adjacent uterine \nserosa).\n\t\u2022\t \u0007Lower uterine: Two transmural section from the posterior and anterior sides. See under segment \n\u201ctumor\u201d if the tumor is near the LUS.\n\t\u2022\t \u0007Endometrium: Two sections (anterior and posterior).\n\t\u2022\t \u0007Fallopian tubes: At a minimum, submit the entire fimbriae and a representative cross section of the \ntube.\nAnterior\nlower\nuterine\nsegment\nAnterior\nendometrium\nPosterior\nendometrium\nLeft\nparacervical\nRight\nparacervical\n12:00\n1:00\n1\n2\n3\n4\n5\n6\n7\n8\n9\n10\n11\n12\nPosterior\nlower\nuterine\nsegment\nLeft\nfallopian\ntube\nRight\nfallopian\ntube\nLeft\novary\nRight\novary\nFigure 22\u20133.\u2002 Radical hysterectomy for malignant tumors (cervical carcinoma).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_448.png", "summary": "The page provides guidelines for submitting microscopic sections of various gynecologic tissues, including tumors in the cervix, lower uterine segment, endometrium, fallopian tubes, and ovaries.", "questions": [ "What are the specific guidelines for submitting tumor sections from the cervix?", "Why is it important to sample areas beyond the cervix if the tumor extends?", "What is the significance of submitting transmural sections from the lower uterine segment?", "How do the guidelines for submitting sections of the fallopian tubes differ from other tissues?", "Why is it necessary to include representative cross sections of the fallopian tubes?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 449, "text": "431\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nThe cassettes containing the fimbriae must be clearly indicated in the cassette key.\n\t\u2022\t \u0007Ovary: Submit at least 2 representative sections from each ovary (taken transverse to the longitudinal \naxis) including capsule.\n\t\u2022\t \u0007Serosa: If serosa is not included in the sections of endometrium, submit a separate section.\n\t\u2022\t \u0007Parametrium: Submit any parametrial nodules or lymph nodes. Note number, location, and side. If \nno gross tumor is present in this location, submit two representative sections (may be included as full \nthickness sections of the cervix).\n\t\u2022\t \u0007Other lesions: Submit sections of any other lesions (e.g., polyps, leiomyomata).\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cRadical Hysterectomy,\u201d is a 420 \ngram specimen including an unopened uterus (9.0 \u00d7 5.5 \u00d7 5.0 cm) with attached cervix and vaginal cuff, \nright fallopian tube (4.5 cm in length \u00d7 0.7 cm in diameter), right ovary (3.8 \u00d7 1.8 \u00d7 1.2cm), left fallopian \ntube (5.0 cm in length \u00d7 0.7 cm in diameter), and left ovary (4.2 \u00d7 3.0 \u00d7 1.2 cm). There is a white/tan \ncentrally ulcerated mass (1.5 \u00d7 1.0 \u00d7 0.5 cm) located on the posterior surface of the exocervix (3.0 \u00d7 2.8 \ncm). The mass appears to invade to a depth of 0.5 cm but is grossly 0.8 cm from the outer surface. The \nmass extends into the endocervical canal but not to the lower uterine segment. The mass is 4 cm from the \nvaginal cuff margin. The external os is distorted by the mass and is 0.2 cm in diameter. The endocervical \ncanal (3.1 cm in length) has a tan herringbone mucosa. The endometrial cavity (6.3 cm from cornu to \ncornu, 4.8 cm in length) has a tan/pink hemorrhagic endometrium (0.3 cm in average thickness). The \nmyometrium measures 1.2 cm in maximum thickness and contains one submucosal leiomyoma (2.5 cm \nin greatest dimension) that has a white/tan whorled appearance without hemorrhage or necrosis. The \nserosa is glistening with an adhesion on the posterior surface.\nThe fallopian tubes are patent and have fimbriated ends. The tubes are completely examined micro\u00ad\nscopically.\nThe right ovary has a smooth white surface and multiple corpora albancantia. The left ovary has \nmultiple \u00adcorpora albicantia and a golden yellow corpus luteum. The ovaries are completely examined \nmicroscopically.\nThree lymph nodes are located in the right \u00adparametrial soft tissue. The largest node measures 1.2 cm \nand is grossly white and firm. Two lymph nodes are located in the left parametrial soft tissue. Both are \ntan and the \u00adlargest \u00admeasures 0.8 cm in greatest dimension. The nodes are completely examined micro\u00ad\nscopically.\nCassettes #1-4: Posterior cervix including mass, 4 o\u2019clock to 7 o\u2019clock, 4 frags, ESS.\nCassettes #5-12: Remainder of cervix, 8 o\u2019clock to 3 o\u2019clock, 8 frags, ESS.\nCassettes #13-16: Vaginal cuff margin, sections at 12, 3, 6, and 9 o\u2019clock, 4 frags, RSS.\nCassette #17: Lower uterine segment, posterior, closest to mass, 1 frag, RSS.\nCassette #18: Lower uterine segment, anterior, 1 frag, RSS.\nCassette #19: Anterior endometrium, 1 frag, RSS.\nCassette #20: Posterior endometrium, 1 frag, RSS.\nCassette #21: Right fallopian tube fimbria, 4 frags, ESS.\nCassette #22: Right tube and ovary, mult frags, ESS.\nCassette #23: Left fallopian fimbria, 4 frags, ESS.\nCassette #24: Left tube and ovary, mult frags, ESS.\nCassette #25: Leiomyoma, 2 frags, RSS.\nCassette #26: Largest right lymph node, 2 frags, ESS.\nCassette #27: Two additional right lymph nodes (inked blue and black), 4 frags, ESS.\nCassette #28: Two left lymph nodes (inked blue and black), 4 frags, ESS.\nMorcellated laparoscopic hysterectomy\nLaparoscopic hysterectomies (complete or supracervical) are performed for benign conditions, and may \nbe received intact or morcellated (in small fragments). For the latter, weigh the specimen, take an aggre\u00ad\ngate measure of the total tissue, and attempt to identify and describe specific tissues (i.e., endometrium, \nmyometrium, serosa, leiomyomata, ovary, fallopian tube). Approximately 4 to 8 cassettes of the tissue \n(including all identifiable tissue) should be submitted for histologic examination. If certain tissues are not \nfound, or if an unsuspected malignancy is identified, additional tissue may need to be submitted.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_449.png", "summary": "The page provides guidelines for submitting various sections of the uterus, ovaries, serosa, parametrium, and other lesions for pathological examination.", "questions": [ "What are the specific guidelines for submitting sections of the ovaries, serosa, parametrium, and other lesions?", "What are the key findings in the received specimen of radical hysterectomy?", "How are the fallopian tubes, ovaries, and lymph nodes examined microscopically?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 450, "text": "432\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cUterus and cervix, both tubes and \novaries,\u201d are multiple tan/white fragments of soft tissue (232 g; 14.5 \u00d7 11.5 \u00d7 7.8 cm), grossly consistent \nwith a morcellated uterus. The segments of tissue average 1.0 cm in diameter, and range up to 10 cm in \ngreatest dimension. Identifiable structures include fibromuscular tissue with a possible endometrial lin\u00ad\ning, serosa, possible cervix, ovary with corpora albicantia, and a corpus luteum, and fallopian tube. Addi\u00ad\ntional tan/white whorled fragments are \u00adconsistent with leiomyomata without evidence of hemorrhage or \nnecrosis. Representative sections are submitted.\nCassette A1: Endomyometrium, 2 frags, RSS.\nCassette A2: Myometrium and serosa, 2 frags, RSS.\nCassette A3: Possible cervix, 2 frags, RSS.\nCassette A4: Ovary and fallopian tube, 3 frags, RSS.\nCassettes A4-A5: Leiomyomata, 5 frags, RSS.\nGROSS DIFFERENTIAL DIAGNOSIS OF ENDOMETRIAL AND MYOMETRIAL LESIONS\nLeiomyomas.\u2002 These tumors are firm whorled white to tan nodules present within myometrium, \nbulging into the endometrial lumen or protruding into the peritoneal cavity. Cystic degeneration and \nsoftening may be seen in the center of large leiomyomas. Hemorrhage and necrosis should not be seen \n(unless secondary to ischemic change).\n\t \u2022\t \u0007Subserosal: immediately below the serosa, some are pedunculated and can appear to be peri-uterine \nmasses\n\t \u2022\t \u0007Intramural: within the myometrium\n\t \u2022\t \u0007Submucosal: immediately below the endometrium\nLeiomyosarcoma.\u2002 Only one to three women out of 1,000 with a preoperative diagnosis of leio\u00ad\nmyoma will prove to have a sarcoma. Most are >40 years old. The risk is increased if there is a \u00adhistory \nof a mass increasing in size. A leiomyosarcoma is usually the dominant lesion (or often solitary) \nand is usually larger (>10 cm) and softer than leiomyomas. The color may be gray/yellow rather \nthan white. Areas of hemorrhage and necrosis (green) may be present. Invasion into the surrounding \n\u00admyometrium may be present. However, some are grossly indistinguishable from leiomyomas and are \ncircumscribed. Malignant lesions generally have complex karyotypes as compared to \u00adleiomyomas (see \nTable 7-47).\nStromal Nodules/Sarcomas.\u2002 May be well circumscribed (nodules) or diffusely infiltrative (sarco\u00ad\nmas). Lymphovascular invasion can often be seen as \u201cworm-like\u201d masses within the myometrium. About \none third will invade into adjacent tissues. Necrosis and hemorrhage are not uncommon in sarcomas.\nAdenomyosis.\u2002 Due to benign glands embedded within myometrium. The myometrium appears \nthickened with coarse trabeculations. Pinpoint hemorrhage may be \u00adpresent.\nEndometrial Polyps.\u2002 Usually large, broad-based, finger-like projections from the endometrial wall. \nThe center is comprised of fibrous stroma and the surface is covered by endometrium.\nEndometrial Carcinoma.\u2002 The endometrial lining may be heaped up, but a yellow, friable appearance \nis more characteristic of carcinomas. This may be best \u00adappreciated on cross section. Invasive carcinomas \nmay efface the normal myometrial texture. This finding may be subtle or obscured by adenomyosis.\nMalignant Mixed Mullerian Tumor (Carcinosarcoma).\u2002 Usually a very large friable mass com\u00ad\npletely filling the endometrial cavity and extending through the cervical os. The myometrium is typically \ndeeply invaded. Foci of bone or cartilage may be present.\nAdenomatoid Tumor.\u2002 A poorly circumscribed soft mass within the myometrium, near the serosal \nsurface. Large tumors may extend into the endometrium.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_450.png", "summary": "The sample dictation describes the gross findings of a morcellated uterus with identifiable structures including fibromuscular tissue, endometrial lining, cervix, ovaries, and fallopian tube. Leiomyomata without hemorrhage or necrosis are also noted.", "questions": [ "What are the identifiable structures mentioned in the sample dictation?", "How are leiomyomas described in the gross differential diagnosis?", "What are the key differences between leiomyomas and leiomyosarcomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 451, "text": "433\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nGestational Trophoblastic Tumors.\u2002 Complete or partial hydatidiform moles are usually received \nas products of conception and are grossly recognized by the numerous dilated grape-like vesicles. Fetal \nparts may be present in partial hydatidiform moles. Grossly, it will look like a hemorrhagic mass adherent \nto the wall of the uterus.\nGestational Choriocarcinoma.\u2002 can also arise from placental tissues from either a normal or abnor\u00ad\nmal pregnancy. It is a soft, fleshy, yellow-white tumor, often with large areas of necrosis, and usually with \nextensive hemorrhage. The tumor invades into the myometrium and may extend out into the serosa. \nThere is a separate AJCC staging system for these tumors.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR ENDOMETRIAL CARCINOMAS\n\t\u2022\t \u0007Specimen: Uterus, cervix, ovary (right, left), fallopian tube (right, left), parametrium (right, left), vagi\u00ad\nnal cuff, omentum\n\t\u2022\t \u0007Procedure(s): Hysterectomy (supracervical or simple), radical hysterectomy (including parametria), \noophorectomy (right, left), salpingectomy (right, left), omentectomy, peritoneal biopsies, pelvic exen\u00ad\nteration\n\t\u2022\t \u0007Lymph Node Sampling: Pelvic lymph nodes, para-aortic lymph nodes, no lymph nodes sampled\n\t\u2022\t \u0007Specimen Integrity: Morcellated hysterectomy specimen, intact hysterectomy specimen\n\t\u2022\t \u0007Tumor Site: Location (anterior, posterior)\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional margins are optional)\n\t \u2022\t \u0007Extent of surface area involved (< 4 cm versus > 4 cm) is correlated with higher stage disease.\n\t\u2022\t \u0007Histologic Type: Endometrioid carcinoma (and subtypes), mucinous adenocarcinoma, serous adeno\u00ad\ncarcinoma, clear cell adenocarcinoma, squamous cell carcinoma, undifferentiated carcinoma, other \nrare types. The WHO Classification is recommended.\n\t\u2022\t \u0007Histologic Grade: Different grading systems are used for different tumor types (see later).\n\t\u2022\t \u0007Myometrial Invasion: Report as depth of invasion in millimeters or percentage of myometrium \ninvolved (< 50%, \u2265 50%)\n\t\u2022\t \u0007Involvement of Cervix: Not involved, invasion of cervical stromal connective tissue\n\t\u2022\t \u0007Extent of Involvement of Other Organs: Involvement of fallopian tube, ovary, vagina, peritoneum, \nparametrium, omentum bladder wall, bladder mucosa, colon or rectal wall, bowel mucosa, pelvic wall\n\t\u2022\t \u0007Peritoneal Ascitic Fluid: Negative for malignancy, atypical or suspicious, malignant, nondiagnostic\n\t\u2022\t \u0007Margins: Uninvolved, involved, distance of invasive carcinoma from the margin\n\t \u2022\t \u0007Cervical, parametrial, and serosal margins\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Extent of Invasion: Carcinoma in situ (pTis), tumor limited to endometrium or invades less than one half \nof the myometrium (pT1a), tumor invades one half or more of the myometrium (pT1b), tumor invades \nstromal connective tissue of the cervix but does not extend beyond the uterus (pT2), tumor involves \nserosa and/or adnexa (direct extension or metastasis) (pT3a), tumor involves vagina (direct extension or \nmetastasis) or involves parametria (pT3b), tumor involves bladder mucosa and/or bowel mucosa (pT4)\n\t\u2022\t \u0007Regional Lymph Nodes: Number of nodes examined, number involved, location (pelvic, para-aortic)\n\t\u2022\t \u0007Additional Pathologic Findings: Hyperplasia (simple without cytologic atypia, complex without \ncytologic atypia), atypical hyperplasia (simple, complex), endometrial intraepithelial neoplasia (EIN), \natrophy, polyps\n\t\u2022\t \u0007Ancillary Studies: In some cases, estrogen and progesterone studies may be requested. Testing for \nmicrosatellite instability or DNA mismatch repair gene products may be requested for carcinomas \narising in patients < 50 years of age at risk for hereditary nonpolyposis colon carcinoma (Lynch syn\u00ad\ndrome; family history of endometrial or colorectal carcinoma)\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC or FIGO Classification: Categories should be provided, when possible (Table 22-3).\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_451.png", "summary": "The page discusses gestational trophoblastic tumors, including hydatidiform moles and choriocarcinoma, as well as a checklist for pathologic diagnostic and prognostic features for endometrial carcinomas.", "questions": [ "What are the gross characteristics of complete and partial hydatidiform moles?", "What are the diagnostic and prognostic features included in the checklist for endometrial carcinomas?", "How is the extent of myometrial invasion reported in endometrial carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 452, "text": "434\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR GESTATIONAL TROPHOBLASTIC \nMALIGNANCIES\n\t\u2022\t \u0007Specimen: Uterus\n\t\u2022\t \u0007Procedure: Dilation and curettage, hysterectomy, radical hysterectomy, pelvic exenteration\n\t\u2022\t \u0007Tumor Site: Location\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional margins are optional)\n\t\u2022\t \u0007Histologic Type: Hydatidiform mole (complete, partial, or invasive), choriocarcinoma, placental site \ntrophoblastic tumor, epithelioid trophoblastic tumor, malignant trophoblastic tumor, type cannot be \ndetermined\n\t\u2022\t \u0007Extent of Invasion: Tumor limited to uterus (pT1), tumor extends outside of uterus but is limited to the \ngenital structures (adnexa, vagina, broad ligament) (pT2), tumor extends to nongenital organs or structures\n\t \u2022\t \u0007Myometrial invasion: present (% of thickness), absent\n\t \u2022\t \u0007Serosal surface: involved, not involved\n\t\u2022\t \u0007Margins: Uninvolved, involved, distance to nearest margin\nTABLE 22\u20133.\u2003\nAJCC AND FIGO (7TH EDITION) CLASSIFICATION OF ENDOMETRIAL CARCINOMAS\nTNM CATEGORIES\nFIGO STAGES\nDEFINITIONS\nPrimary Tumor\nTX\n\u2014\nPrimary tumor cannot be assessed.\nT0\n\u2014\nNo evidence of primary tumor\nTis*\n\u2014\nCarcinoma in situ (preinvasive carcinoma)\nT1\nI\nTumor confined to corpus uteri\nT1a\nIA\nTumor limited to endometrium or invades less than one half of the myometrium\nT1b\nIB\nTumor invades one half or more of the myometrium\nT2\nII\nTumor invades stromal connective tissue of the cervix but does not extend \nbeyond uterus\u2020\nT3a\nIIIA\nTumor involves serosa and/or adnexa (direct extension or metastasis)\nT3b\nIIIB\nVaginal involvement (direct extension or metastasis) or parametrial involvement\nT4\nIVA\nTumor invades bladder mucosa and/or bowel mucosa (bullous edema is not \n\u00adsufficient to classify a tumor as T4)\n* FIGO no longer includes stage 0 (Tis).\n\u2020 Endocervical glandular involvement only should be considered as stage I and not stage II.\nRegional Lymph Nodes\nNX\n\u2014\nRegional lymph nodes cannot be assessed.\nN0\n\u2014\nNo regional lymph node metastasis\nN1\nIIIC1\nRegional lymph node metastasis to pelvic lymph nodes\nN2\nIIIC2\nRegional lymph node metastasis to para-aortic lymph nodes, with or without \n\u00adpositive pelvic lymph nodes\nDistant Metastasis\nM0\n\u2014\nNo distant metastasis\nM1\nIVB\nDistant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal \ndisease, or lung, liver, or bone. It excludes metastasis to para-aortic lymph nodes, \nvagina, pelvic serosa, or adnexa)\nNote: There are separate AJCC and FIGO classifications for leiomyosarcoma and endometrial stromal sarcoma and for adenosarcoma.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Committee on Cancer (AJCC), \nChicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_452.png", "summary": "This page provides a checklist for pathologic diagnostic and prognostic features of gestational trophoblastic malignancies in the uterus, as well as the AJCC and FIGO classification of endometrial carcinomas.", "questions": [ "What are the different histologic types of gestational trophoblastic tumors mentioned in the checklist?", "How is the extent of invasion of trophoblastic tumors classified?", "What are the TNM categories and FIGO stages for endometrial carcinomas according to the classification provided?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 453, "text": "435\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Uterus\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Fetal Tissue: Not identified, present (specify type)\n\t\u2022\t \u0007Fetal Anomalies: Cannot be determined, not identified, present (specify type)\n\t\u2022\t \u0007Additional Pathologic Findings: Implantation site, leiomyoma, adenomyosis\n\t\u2022\t \u0007Distant Metastasis: Present (give number and site of metastases). If distant metastasis is not present \non pathologic examination, the M category is a clinical classification.\n\t\u2022\t \u0007AJCC or FIGO Classification: T, N, and M classifications should be provided, when possible (Tables \n22-4 and 22-5). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nGRADING OF UTERINE TUMORS\nIn serous and clear cell adenocarcinomas, nuclear grading takes precedent. Most are high grade (i.e., \ngrade 3). Rare serous tumors with a solid growth pattern in small nests with a high degree of nuclear \nmaturation and psammoma bodies are assigned grade 1 to 2.\nThere is no universally accepted system for mucinous carcinomas. Architectural and nuclear features \nare \u00adevaluated.\nEndometrioid adenocarcinomas are graded according to the architectural configuration (see \u201carchi\u00ad\ntectural grading\u201d below). Squamous and mucinous differentiation are documented, if present.1\nTABLE 22\u20134.\u2003\n\u0007AJCC AND FIGO (7TH EDITION) CLASSIFICATION OF GESTATIONAL \nTROPHOBLASTIC TUMORS\nTNM CATEGORIES\nFIGO STAGES\nDEFINITIONS\nPrimary Tumor\nTX\n\u2014\nPrimary tumor cannot be assessed.\nT0\n\u2014\nNo evidence of primary tumor\nT1\nI\nTumor confined to uterus\nT2\nII\nTumor extends to other genital structures (ovary, tube, \nvagina, broad ligaments) by metastasis or direct extension\nIIA\nWith low-risk prognostic score\nIIB\nWith high-risk prognostic score\nDistant Metastasis\nM0\n\u2014\nNo distant metastasis\nM1\n\u2014\nDistant metastasis\nM1a\nIII\nLung metastasis\nIIIA\nWith low-risk prognostic score\nIIIB\nWith high-risk prognostic score\nM1b\nIV\nAll other distant metastasis\nIVA\nWith low-risk prognostic score\nIVB\nWith high-risk prognostic score\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_453.png", "summary": "This page provides information on the pathology of the uterus, including lymph-vascular invasion, fetal tissue, fetal anomalies, additional pathologic findings, distant metastasis, and AJCC or FIGO classification.", "questions": [ "What are the key elements that must be present in reports of cancer-directed surgical resection specimens?", "How are serous and clear cell adenocarcinomas graded?", "What is the TNM classification for gestational trophoblastic tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 454, "text": "436\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Ovary\nTABLE 22\u20135.\u2003\nGESTATIONAL TROPHOBLASTIC NEOPLASIA \u2013 PROGNOSTIC SCORE\nPROGNOSTIC FACTOR\n0\n1\n2\n4\nAge\n<40\n\u226540\nAntecedent pregnancy\nH. mole\nAbortion\nTerm pregnancy\nMonths from index pregnancy\n<4\n4-<7\n7\u201312\n>12\nPretreatment serum hCG (U/mL)\n<103\n103-<104\n104-<105\n\u2265105\nLargest tumor size including uterus\n<3 cm\n3-<5 cm\n\u22655 cm\nSites of metastasis\nLung\nSpleen, kidney\nGastrointestinal tract\nLiver, brain\nNumber of metastases\n1\u20134\n5\u20138\n>8\nPrevious failed chemotherapy\nSingle drug\n2 or more drugs\nRISK CATEGORIES:\n\t\n\u2022\t \u0007Low risk: 6 or less (add \u201cA\u201d to FIGO stage)\n\t\n\u2022\t \u0007High risk: 7 or more (add \u201cB\u201d to FIGO stage)\nThis classification is used for invasive hydatidiform mole, choriocarcinoma, placental site trophoblastic tumors, and epithelioid trophoblastic tumors.\nFIGO Grading of Endometrial Carcinomas.\u2002\nArchitectural grade (endometrioid carcinomas):\n\t \u2022\t \u0007Well differentiated (G1): 5% or less solid growth (excluding squamous or morular growth patterns)\n\t \u2022\t \u0007Moderately differentiated (G2): 6% to 50% solid growth (nonsquamous or nonmorular growth \u00adpattern)\n\t \u2022\t \u0007Poorly differentiated (G3): >50% solid growth (nonsquamous or nonmorular growth pattern)\nNotable nuclear atypia (grade 3 nuclear atypia), inappropriate for the architectural grade, raises the \ngrade of a grade 1 or grade 2 tumor by 1 grade.\nNuclear grade (clear cell, squamous, and serous carcinomas):\n \n1.\t \u0007Uniform nuclei (round to oval), small nucleoli, even chromatin, usually in a single row or moder\u00ad\nately stratified, rare mitoses.\n \n2.\t \u0007Variable size and shape of nuclei, larger nucleoli, more mitoses.\n \n3.\t \u0007Enlarged pleomorphic nuclei, prominent nucleoli, coarse chromatin, frequent mitoses.\nCriteria Defining Stromal Invasion of Endometrial \u00adCarcinomas.\u2002\nOne of the following should be present:\n \n1.\t \u0007Irregular infiltration of glands associated with an altered fibroblastic stroma (desmoplastic response).\n \n2.\t \u0007Confluent glandular pattern (cribriform growth).\n \n3.\t \u0007Extensive papillary growth pattern (at least 0.42 cm in diameter)\nOVARY\nOvaries are removed for evaluation of a mass, as part of a larger resection, or prophylactically in a patient \nwith a personal or family history of breast cancer or a BRCA mutation. Occasionally, biopsies are per\u00ad\nformed for incidental mass lesions (e.g., a corpus luteum of pregnancy during a Cesarean section), or for \ntreatment (e.g., Stein-Leventhal syndrome) (Fig. 22-4).\nNeoplasms generally have one of the three following appearances:\n 1.\t \u0007Simple cyst, thin-walled, without solid areas. Almost always benign. Most are follicular cysts (cystic fol\u00ad\nlicles), corpus luteum cysts, or cystadenomas (epithelial-lined cysts). This is the most common type of cyst.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_454.png", "summary": "The page discusses the prognostic score for gestational trophoblastic neoplasia and the classification of endometrial carcinomas based on architectural and nuclear grades. It also provides information on the evaluation of ovaries for masses and different types of neoplasms.", "questions": [ "How is the prognostic score for gestational trophoblastic neoplasia determined?", "What are the risk categories for gestational trophoblastic neoplasia based on the prognostic score?", "What are the different appearances of neoplasms in the ovaries and which types are considered benign?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 455, "text": "437\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Ovary\n 2.\t \u0007Complex cyst with or without a solid component. May be nonneoplastic (e.g., an endometriotic or \n\u201cchocolate\u201d cyst), a benign neoplasm (dermoid), a borderline tumor, or a malignant tumor.\n 3.\t \u0007Solid tumors. May be benign fibromas, Brenner tumors, granulosa cell tumors, or malignant \n\u00adcarcinomas. Most have cystic areas.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE)\nSee Table 22-6.\nIncidental Ovaries or Prophylactic Oophorectomies\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the overall dimensions of the ovary and describe the outer surface including color (white), \nsurface (smooth or convoluted, adhesions, papillary \u00adprojections), simple cysts (thin-walled without a \nsolid component).\nAvoid rubbing or abrading the outer surface in order to preserve the delicate (and very fragile) \n\u00adepithelial lining.\n 2.\t \u0007If any abnormality is present (e.g., cysts, papillary projections), ink the outer surface.\nSerially section the ovary, parallel to the short axis.\nDescribe the ovary including color and presence of corpus luteum and corpora albicantia. If cysts \nare present describe number, size, unilocular vs. multilocular, lining (smooth, irregular, \u00adpapillary \nTABLE 22\u20136.\u2003\nRELEVANT CLINICAL HISTORY \u2013 OVARY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR OVARIAN SPECIMENS\nOrgan/tissue resected or biopsied\nPregnancy\nPurpose of the procedure\nAbnormal uterine bleeding\nGross appearance of the organ/tissue/lesion sampled\nPersonal or family history or ovarian or breast carcinoma\nAny unusual features of the clinical presentation\nStein-Leventhal syndrome\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, \ndrug use that can change the histologic appear\u00ad\nance of tissues)\nCompromised immune system\nIsthmus\nAmpulla\nInfundibulum\nHilum\nFimbriae\nFigure 22\u20134.\u2002 Ovary and fallopian tube.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_455.png", "summary": "This page discusses the various types of ovarian cysts and tumors, including complex cysts with solid components, benign fibromas, Brenner tumors, granulosa cell tumors, and malignant carcinomas.", "questions": [ "What are the different types of ovarian cysts and tumors mentioned on this page?", "How should the processing of ovarian specimens be carried out to preserve delicate epithelial lining?", "What relevant clinical history should be considered for ovarian specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 456, "text": "438\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Ovary\n\u00adprojections, velvety as in endometriotic cyst), thickness of wall, contents (fluid vs. keratinaceous \n\u00admaterial and hair as in mature teratoma, serous vs. mucinous, hemorrhagic), calcified areas or bone. If \nit is a large cyst, try to identify remaining ovary as a focal thickening of the wall.\n 3.\t \u0007The usual unremarkable ovary with only small simple cysts can be sampled with one section demon\u00ad\nstrating any features noted above.\nIf the ovary was removed as a prophylactic procedure in a woman with a personal or family his\u00ad\ntory of ovarian or breast carcinoma or who has a known BRCA mutation, the entire specimen (ovary, \nfallopian tube, and adnexal soft tissue) is examined histologically. See under \u201cFallopian Tube\u201d for \nprocessing tubes removed for prophylaxis.\nLarge thin-walled cysts can be rolled into a \u201cjelly roll\u201d and fixed in formalin overnight. Submit \ntransverse sections of the roll. Try to submit a section of the residual ovary.\nIf there is any suspicion of malignancy (e.g., mucinous cyst, complex cyst, papillary projections, \nsolid areas) additional sections must be taken to document these areas and any extension into adjacent \ntissues (see below).\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cright ovary,\u201d is an ovary (3.0 \u00d7 2.5 \n\u00d7 1.0 cm) with a smooth white convoluted surface and multiple corpora albicantia. There is a smooth \nwalled 0.6 cm superficial intact cyst.\nCassette #1: Representative cross section including cyst, 1 frag, RSS.\nOvary with Simple Cyst\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the overall dimensions of the ovary and describe the outer surface including color (white), \nsurface (smooth or convoluted, adhesions, papillary projections), simple (thin-walled without a solid \ncomponent) cysts. Papillations or a \u201cnubby\u201d appearance on the surface of the ovary could indicate \neither invasion of a tumor through the capsule or a serosal implant.\nAvoid rubbing or abrading the outer surface in order to preserve the surface epithelial lining.\n 2.\t \u0007Ink the outer surface including all areas of irregularity.\nOvarian cysts are opened with great care as the cyst fluid may be under pressure. Wear goggles and \nappropriate clothing protection. Open in a pan or on sufficient numbers of surgical drapes to absorb \nall the fluid. Very large cysts may need to be opened in a sink. Make a small initial incision inferiorly \n(away from the face of the prosector) to allow the fluid to drain slowly.\nTry to identify remaining ovarian tissue. It can sometimes be seen as a thickened portion of the wall \nreadily visible on transillumination. Do not abrade the lining by excessive handling.\nDescribe the cyst including size, inner surface (smooth or with papillary areas or solid areas, velvety \ntexture as in endometriotic cysts), wall thickness, contents (blood, serous fluid, mucinous fluid, \nkeratinaceous and sebaceous material and hair as in mature teratoma), solid areas (color, texture, \nextension to serosal surface). If the fallopian tube is included, describe its relationship to the cyst. \nDescribe the remaining ovary including color, corpus luteum, corpora albicantia.\n 3.\t \u0007Large thin-walled cysts can be rolled into a \u201cjelly roll\u201d and fixed in formalin overnight. Submit trans\u00ad\nverse sections of the roll. Submit a section of the residual ovary.\nIf there is any suspicion of malignancy (e.g., mucinous cyst, complex cyst, papillary projections, solid \nareas) additional sections must be taken to document these areas and any extension into adjacent \ntissues. At least one cassette per cm greatest dimension of cyst must be taken if the cyst is mucinous \n(malignant features can be focal in this type of neoplasm). Submit a section with fallopian tube, if \npresent.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cleft ovary,\u201d is an intact 10 \u00d7 8 \u00d7 8 \ncm thin walled (0.3 cm) white/tan unilocular cyst with smooth inner and outer surfaces. A 1 \u00d7 1 \u00d7 0.8 cm \narea of white fibrotic tissue is present, possibly representing residual ovarian tissue. No corpora albicantia \nare seen. The cyst is filled with clear nonviscous fluid.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_456.png", "summary": "The page discusses the examination and processing of ovarian specimens, including the identification of cysts, sampling techniques, and considerations for prophylactic procedures or suspected malignancies.", "questions": [ "What are some key features to look for when examining an ovarian cyst?", "Why is it important to carefully open ovarian cysts during specimen processing?", "What are the considerations for examining ovarian specimens from patients with a history of ovarian or breast carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 457, "text": "439\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Ovary\nCassette #1: Transverse sections of cyst wall, 2 frags, RSS.\nCassette #2: Possible residual ovarian tissue, 1 frag, RSS.\nOvary with Complex Cyst\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the overall dimensions of the ovary and describe the outer surface including color (white), \nsurface (smooth or convoluted, adhesions, papillary projections), simple (thin-walled without \na solid component) cysts. Carefully examine the surface for invasion or adhesion to adjacent \n\u00adstructures.\nAvoid rubbing or abrading the outer surface in order to preserve the surface epithelial lining.\n 2.\t \u0007Ink the outer surface in all irregular areas. Open ALL cysts and examine carefully for papillary or solid \ncomponents. See section above for precautions on opening cysts with fluid under pressure.\nTry to identify remaining ovarian tissue. It can sometimes be seen as a thickened portion of the wall read\nily visible on transillumination. Do not abrade the lining by excessive handling.\nDescribe the cystic spaces including number, size, inner surface (smooth or with papillary areas \nor solid areas, velvety texture as in endometriotic cysts), wall thickness, contents (blood, serous \nfluid, mucinous fluid, keratinaceous and sebaceous material and hair as in mature teratoma), solid \nareas (color, texture, extension to serosal surface). If the fallopian tube is included, describe its \nrelationship to the cyst. Describe the remaining ovary including color, corpus luteum, corpora \nalbicantia.\n 3.\t \u0007Fix the specimen in formalin overnight. One cassette per cm largest cyst diameter should be submitted \nif there is any suspicion of malignancy. Include solid or papillary areas within wall and areas of gross \ninvasion. Submit a section of the residual ovary.\nAt a minimum, submit the entire fimbriae and a representative cross section of the tube, but consider \nsubmitting the ENTIRE fallopian tubes according to the SEE FIM (\u201cSection and Extensively \nExamine the FIMbriated end of the fallopian tube\u201d) protocol (see below in the \u201cFallopian Tube\u201d \nsection).\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cleft ovary,\u201d is an intact 18 \u00d7 15 \u00d7 \n10 cm multilocular tan/white cyst. Most of the cyst wall is thin (0.2 cm) but focal areas of thickening are \npresent measuring up to 0.8 cm. The outer surface is smooth. Within the inner surface of the cysts there \nare multiple minute papillary areas (all less than 0.4 cm in height). A representative frozen section was \ntaken of one of these areas. A 1 \u00d7 0.8 cm area of residual ovarian tissue is present with a single corpus \nalbicans. The cysts are filled with thick yellow viscous fluid.\nCassette #1: Frozen section remnant, papillary area, 1 frag, ESS.\nCassettes #2-19: Representative sections of cyst including papillary areas and areas of thickened wall, \n18 frags, RSS.\nCassette #20: Residual ovarian tissue, 1 frag, RSS.\nOvary with Solid Tumor\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the overall dimensions of the ovary and describe the outer surface including:\n\t \u2022\t \u0007Color: usually white\n\t \u2022\t \u0007Surface: smooth or convoluted, adhesions, papillary projections\n\t \u2022\t \u0007Presence of simple cysts: thin-walled cysts without a solid component \nCarefully examine the surface for invasion or adhesion to adjacent structures.\nAvoid rubbing or abrading the outer surface in order to preserve the surface epithelial lining.\n 2.\t \u0007Ink the outer surface. Serially section through the tumor. Describe size, surface, color, relationship to \nsurface and adjacent ovary (i.e., margins), the presence of a cystic component (describe as above), and \ntexture upon cutting.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_457.png", "summary": "This page discusses the processing of ovarian specimens with complex cysts and solid tumors, including steps for examination and submission of tissue for analysis.", "questions": [ "What precautions should be taken when opening cysts with fluid under pressure?", "What are some key factors to describe when examining the cystic spaces of an ovarian specimen?", "Why is it important to submit a section of the residual ovary for analysis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 458, "text": "440\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Ovary\n 3.\t \u0007Fix the specimen in formalin overnight. One cassette per cm largest tumor diameter should be sub\u00ad\nmitted if there is any suspicion of malignancy. Include at least one section to demonstrate relationship \nof tumor to adjacent ovary and peritoneal surface. Include all areas of gross invasion. Submit a section \nof the residual ovary.\nAt a minimum, submit the entire fimbriae and a representative cross section of the tube, but consider \nsubmitting the ENTIRE fallopian tubes according to the SEE FIM (\u201cSection and Extensively \nExamine the FIMbriated end of the fallopian tube\u201d).\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cleft ovary,\u201d is a 12 \u00d7 10 \u00d7 7 cm \nlobulated mass attached to the fallopian tube (5 cm in length \u00d7 0.8 cm in diameter with a fimbriated \nend). The mass has multiple small cysts of variable size (0.3 to 2 cm) filled with hemorrhagic viscous \nfluid occupying approximately half the area. The remaining portion of the mass is firm and solid with a \nmottled appearance ranging from dark red/brown to \u00adyellow. The outer surface is irregular with multiple \nshaggy adhesions. Definite residual ovarian tissue is not identified. The mass does not grossly involve the \nfallopian tube. During an intraoperative consultation a representative frozen section of a solid area was \ntaken as frozen section A.\nCassette #1: Frozen section remnant, solid area, 1 frag, ESS.\nCassettes #2-7: Representative sections of cystic areas of mass, 6 frags, RSS.\nCassettes #8-10: Representative sections of solid areas of mass, 3 frags, RSS.\nCassettes #11-12: Mass and relationship to surface, 2 frags, RSS.\nCassette #13: Mass and fallopian tube and additional section of fallopian tube, 2 frags, RSS.\nCassette #14: Possible residual ovarian tissue, 1 frag, RSS.\nOmental Biopsies for Staging Ovarian Malignancies\nPROCESSING THE SPECIMEN\n\t\u2022\t \u0007Carcinomas: If there is a grossly evident metastatic focus, one section is sufficient to document. If \nthe omentum is grossly negative, take 5 to 10 sections (or entire specimen if possible) to evaluate for \nsubgross metastases.\n\t\u2022\t \u0007Borderline tumors or immature teratomas: Multiple sections of grossly evident metastases are taken \nto evaluate invasive versus noninvasive implants (borderline tumors) and maturity of implants (terato\u00ad\nmas). If the omentum is grossly negative, take 5 to 10 sections (or entire specimen if possible) to evaluate \nfor subgross metastases.\nSPECIAL STUDIES\n\t\u2022\t \u0007Ovarian carcinoma: Special studies including hormone receptor analysis, DNA analysis, and genetic \nstudies are under investigation but none are routinely used for clinical decision making.\n\t\u2022\t \u0007Steroid producing tumors: It may be helpful to save frozen tissue of solid yellow tumors for oil red \nO stains. However, such stains are rarely necessary.\nGROSS DIFFERENTIAL DIAGNOSIS OF OVARIAN LESIONS\nSee Figure 22-5.\nFollicular Cysts.\u2002 Small (<2 cm) unilocular smoothly surfaced cysts filled with clear serous fluid.\nCorpus Luteum.\u2002 A yellow/orange 1.5 to 2.0 cm ovoid structure with convoluted borders and a hem\u00ad\norrhagic center. The corpus luteum associated with pregnancy is larger (i.e., may occupy half the area of \nthe ovary), brighter \u00adyellow, and has a cystic center.\nCorpora Albicantia.\u2002 A corpus luteum regresses to become a corpus albicans. Corpora albicantia are small, \nfibrotic, well-circumscribed white structures with convoluted borders, usually seen multiply in both ovaries.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_458.png", "summary": "The page provides guidelines on specimen fixation and submission for ovarian pathology, including details on submitting sections to demonstrate tumor relationships and areas of invasion. It also includes instructions for processing omental biopsies for staging ovarian malignancies.", "questions": [ "What are the specific instructions for submitting specimens in cases of suspected ovarian malignancy?", "What is the significance of submitting sections to demonstrate the relationship of the tumor to adjacent structures?", "What special studies are mentioned for ovarian carcinoma and steroid producing tumors, and how are they utilized?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 459, "text": "441\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Ovary\nPolycystic Ovaries (Stein-Leventhal syndrome).\u2002 Both ovaries are generally enlarged (2 to 5 times \nnormal) with a thick superficial cortex and multiple superficial, small, smooth-walled cysts measuring less than \n1 cm in size. Corpora lutea or albicantia are absent.\nBrenner Tumor.\u2002 Usually small (<2 cm) well-circumscribed white/tan or yellow solid fibrous tumors. \nCysts may be present. In 25% of cases, there will be a second tumor (most are mucinous cystadenomas).\nTeratomas (Dermoid Cysts).\u2002 Unilocular (less commonly multilocular) cysts containing hair and cheesy \nsebaceous material. Ten to 15% are bilateral. A nodule of tissue projects into the cyst cavity (Rokitansky\u2019s \nprotuberance) and often contains bone or teeth. Immature teratomas are more likely to be solid and resem\u00ad\nble brain tissue (gray and fleshy), and may have foci of necrosis. These tumors are more likely to spontane\u00ad\nously rupture. The immature elements may be intermingled with mature areas. Struma ovarii is red/brown \nand has small colloid-filled cysts (with brown or green/brown fluid) that correspond to thyroid tissue.\nEndometriotic (Chocolate) Cyst (\u201cEndometrioma\u201d).\u2002 Cyst with a dark red or brown (\u201cchocolate\u201d) \nshaggy lining containing coagulated blood. \u201cPowder burn\u201d is used to describe ecchymotic or brown \nareas of involvement. The surface is usually covered by dense fibrous adhesions. Solid areas or thickened \nplaque-like areas may represent a malignancy arising within the cyst (most commonly endometrioid \ncarcinoma or clear cell carcinoma).\nA\nB\nC\nD\nSerous cystadenoma\nSerous borderline tumor\nMucinous cystadenoma\nMucinous cystadenocarcinoma\nSingle cyst\nsmooth lining\nMulticystic\nsmooth lining\nPapillary projections\nSolid area\nFigure 22\u20135.\u2002 Gross appearance of ovarian tumors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_459.png", "summary": "This page discusses various ovarian pathologies including polycystic ovaries, Brenner tumors, teratomas, endometriotic cysts, and different types of ovarian tumors.", "questions": [ "What are the key characteristics of polycystic ovaries (Stein-Leventhal syndrome)?", "How can Brenner tumors be differentiated from other ovarian tumors?", "What are the distinguishing features of teratomas, including immature teratomas and struma ovarii?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 460, "text": "442\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Ovary\nMucinous Neoplasms.\u2002 These tumors tend to be large, and consist of multiple cysts of varying size \nand shape. The cysts are filled with viscous gelatinous fluid. About 10% are malignant and 10 to 15% \nborderline. Benign lesions will have thin delicate cyst walls and smooth inner linings. Malignant tumors \noften have solid areas of growth and may have areas of necrosis. Borderline tumors may have subtle areas \nof papillary projections from the inner cyst wall. Surface involvement is less common than that seen in \nserous tumors. Mucinous tumors may vary histologically within the tumor. Thus, extensive sampling is \nnecessary to exclude malignancy. About 5% of cystadenomas are bilateral and 20% of carcinomas are \nbilateral.\nSerous Neoplasms.\u2002 One to several cysts are generally present filled with watery clear fluid. Benign \nlesions have thin walls and smooth cyst linings. About 20% to 25% are malignant and 5% to 10% \nborderline. Malignant lesions have areas of solid growth and/or papillary growth with possible areas of \nnecrosis. Invasion into adjacent structures may be present. Borderline lesions usually have numerous \nsmall soft friable papillary projections. Surface involvement may be present. 25% to 30% are bilateral \nand 30% have extraovarian implants.\nEndometrioid Neoplasms.\u2002 There is usually a mixture of solid and cystic areas. Most are malignant. \nThe cysts may be filled with bloody or mucinous fluid. About 15% to 20% are associated with endome\u00ad\ntriosis. 40% are bilateral.\nClear Cell Carcinomas.\u2002 These tumors may be solid or have cystic areas (\u201cSwiss cheese-like\u201d). There \nmay be white/tan papillary projections into the lumens. Some arise in an endometriotic cyst and may look \nlike fleshy nodules in the wall of the cyst.\nMetastatic Carcinomas.\u2002 Most commonly from primaries in the breast, stomach, colon, biliary tract, \nand pancreas. Bilaterality is common, but some primary ovarian neoplasms can also be bilateral. The \ntumors may have a homogeneous appearance and may look like a fibroma or involve the ovary as multiple \nnodules. The classic Krukenberg tumor is a metastatic signet ring cell carcinoma (usually from stomach \nbut also arising in other sites) metastatic to the ovary.\nFibroma.\u2002 Circumscribed hard, chalky-white whorled appearance, usually 5 to 6 cm in size. Calcifi\u00ad\ncations may be present. >90% are bilateral. Fibrosarcomas are rare and are usually softer with areas of \nhemorrhage and necrosis.\nThecoma.\u2002 Lobulated, solid, yellow tumor, often large in size (10 cm). Most are unilateral. Foci of \ncalcification, cysts, hemorrhage, and necrosis may be present. Endometrial hyperplasia may be present \ndue to tumor secretion of estrogen.\nGranulosa Cell Tumor.\u2002 Most are unilateral and large (12 cm). The tumor is circumscribed, soft, and \nyellow to gray. Hemorrhagic cysts or necrosis may be present. Endometrial hyperplasia may be present \ndue to tumor secretion of estrogen. 5% are bilateral.\nPseudomyxoma Peritonei.\u2002 The tumor may involve one or both ovaries and mimic a primary muci\u00ad\nnous ovarian tumor. However, most cases arise from the appendix. The appendix should also be carefully \nexamined during surgery.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Ovary:\n\t \u2022\t \u0007Normal/incidental: One section\n\t \u2022\t \u0007Prophylactic for family history of ovarian or breast carcinoma or known BRCA mutation: Submit \nentire ovary, fallopian tube, and adnexal soft tissue.\n\t \u2022\t \u0007Simple cysts: One section of wall, one section of \u00adresidual ovary\n\t \u2022\t \u0007Complex cysts: One section per cm of greatest dimension including all thickened or papillary areas \nand relationship to surface, one section of residual ovary.\n\t \u2022\t \u0007Solid masses: One section per cm of greatest dimension including relationship to surface, one sec\u00ad\ntion of residual ovary.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_460.png", "summary": "The page discusses various types of ovarian neoplasms, including mucinous, serous, endometrioid, clear cell carcinomas, metastatic carcinomas, fibroma, thecoma, and granulosa cell tumors.", "questions": [ "What are the key differences between benign, borderline, and malignant ovarian neoplasms in terms of their characteristics?", "How common is bilaterality in different types of ovarian neoplasms?", "What are the potential implications of endometrial hyperplasia in relation to certain ovarian tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 461, "text": "443\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Ovary\n\t\u2022\t \u0007Fallopian tube: One or more (with malignancies) sections demonstrating relationship to ovary. The \nfimbrial sections must be clearly designated in the cassette key.\n\t\u2022\t \u0007Soft tissue: Sections of any abnormal areas of adjacent soft tissue (e.g., suspicion of tumor implant) or \nany lymph nodes found in soft tissue.\n\t\u2022\t \u0007Omentum: Multiple sections (5 to 10) including all gross lesions as well as grossly normal-appearing \nadipose tissue. Some metastases are not grossly apparent.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR OVARIAN CARCINOMAS\n\t\u2022\t \u0007Specimen: Ovary (right, left), fallopian tube (right, left), uterus, cervix, omentum, peritoneum\n\t\u2022\t \u0007Procedure(s): Oophorectomy (right or left), salpingo-oophorectomy (right or left), subtotal oopho\u00ad\nrectomy (right or left), removal of tumor in fragments, hysterectomy with salpingo-oophorectomy, \nomentectomy, peritoneal biopsies\n\t\u2022\t \u0007Lymph Node Sampling: Lymph nodes sampled, not sampled\n\t\u2022\t \u0007Specimen Integrity: Capsule intact, ruptured, fragmented. List separately for right and left ovary.\n\t \u2022\t \u0007If the capsule is ruptured, state relationship of rupture to carcinoma (i.e., Is the malignancy at the \nsite of the rupture?).\n\t\u2022\t \u0007Primary Tumor Site: Ovary (right or left), bilateral\n\t\u2022\t \u0007Ovarian Surface Involvement: Not identified, present\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Histologic Type: Serous carcinoma, mucinous carcinoma, endometrioid carcinoma, clear cell car\u00ad\ncinomas, transitional cell carcinoma, squamous carcinoma, undifferentiated carcinomas, borderline \ntumors, Brenner tumor, granulosa cell tumor, sex-cord stromal tumor, germ cell tumor\n\t \u2022\t \u0007The WHO Classification is recommended.\n\t\u2022\t \u0007Histologic Grade: Well differentiated (G1), moderately differentiated (G2), poorly differentiated \n(G3), undifferentiated (G4). The WHO Classification is recommended.\n\t \u2022\t \u0007Endometrioid, serous, and clear cell carcinomas: Use grading system for endometrial carcinomas \n(see prior section). A two-tier system (low grade and high grade) may be used for serous carcinomas.\n\t \u2022\t \u0007Transitional cell and Brenner tumors are graded based on cytologic atypia.\n\t \u2022\t \u0007Immature teratoma is graded based on the quantity of embryonal elements, almost always neuroec\u00ad\ntodermal (Table 22-7).\n\t\u2022\t \u0007Implants (for Serous and Seromucinous Borderline Tumors: Noninvasive (epithelial) implants: \nNot present, site\n\t \u2022\t \u0007Noninvasive (desmoplastic) implants: Not present, site\n\t \u2022\t \u0007Invasive implants: Not present, site\n\t \u2022\t \u0007Size of peritoneal metastases (< or >2 cm)\n\t\u2022\t \u0007Extent of Involvement of Other Organs and Tissues: Ovary (right, left), fallopian tube (right, left), \nomentum, uterus, peritoneum\n\t\u2022\t \u0007Treatment Effect: No prior treatment, prior treatment: no definite or minimal response identified \n(poor or no response); marked response (minimal residual carcinoma)\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t \u2022\t \u0007Seen more commonly in metastases to the ovary than associated with primary ovarian carcinomas.\n\t\u2022\t \u0007Extent of Invasion: Tumor limited to ovaries, involvement of capsule, presence or absence on ovar\u00ad\nian surface, presence or absence in ascites or peritoneal washings, extension and/or implants on uterus \nand/or tubes, microscopic or macroscopic peritoneal metastases\n\t \u2022\t \u0007Superficial tumors (< 0.5 cm invasion into ovary) may be primary peritoneal carcinomas or metasta\u00ad\nses. Tumors at the hilum are more commonly metastatic carcinomas.\nTABLE 22\u20137.\u2003\nIMMATURE TERATOMA \u2013 GRADE\nGrade I\nRare foci of immature neural tissue occupying <1\u00a0low power field per slide\nGrade II\nModerate amounts of immature neural tissue occupying >1 but <4 low power fields per slide\nGrade III\nLarge quantities of immature neural tissue \u00adoccupying \u22654 low power fields per slide\nOther germ cell tumors are not routinely graded.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_461.png", "summary": "The page discusses the necessary sections to include in the pathology report for ovarian carcinomas, including specimen details, tumor characteristics, grading, and treatment effects.", "questions": [ "What are the key components that should be included in the pathology report for ovarian carcinomas?", "How are ovarian carcinomas graded and classified based on histologic type?", "What implications does the presence of lymph-vascular invasion have on the prognosis of ovarian carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 462, "text": "444\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Fallopian Tube\n\t\u2022\t \u0007Regional Lymph Nodes: Number of nodes examined, number with metastases\n\t\u2022\t \u0007Cytology: Ascitic fluid or peritoneal washings: Positive or negative for malignant cells\n\t\u2022\t \u0007Additional Pathologic Findings: Endometriosis (ovarian or extraovarian), endosalpingiosis, ovarian \nor tubal cysts\n\t\u2022\t \u0007Distant Metastasis: Present (give number and site of metastases). If distant metastasis is not present \non pathologic examination, the M category is a clinical classification.\n\t\u2022\t \u0007AJCC or FIGO Classification: T, N, and M classifications should be provided, when possible (Table \n22-8). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nFALLOPIAN TUBE\nFallopian tubes are most commonly received as part of a TAH-BSO specimen but may be submitted after \ntubal ligation (small cross-sections), in cases of ectopic pregnancy, or very rarely for tumors.\nSome women present with a sudden discharge of clear fluid from the vagina accompanied by abdomi\u00ad\nnal pain and reduction of an abdominal mass.\nFallopian tubes are removed as part of a prophylactic oophorectomy in women at high risk for cancer \n(e.g., BRCA1 or BRCA2 carriers). Early papillary serous carcinomas may be found involving the fim\u00ad\nbriae, and specific guidelines are given below for processing.\nRoutine Cases\nPROCESSING THE SPECIMEN\n 1.\t \u0007Describe the size (length and diameter), and the presence or absence of a fimbriated end. \nCheck for patency with a probe. A plastic ring may be present if there has been a prior tubal \nligation.\n 2.\t \u0007Describe the serosal surface (normal = smooth and glistening) including adhesions, paratubal cysts, \npurulent or fibrinous exudates, and ruptures.\n 3.\t \u0007Make cross-sections across the tube. Note any luminal contents (purulent exudate, hemorrhage, pla\u00ad\ncental or fetal tissue or membranes, see below).\n 4.\t \u0007Submit three sections in one cassette including the fimbriated end, mid-portion, and cornual portion \nof the tube. Additional cassettes can be used to document any gross lesions. In cases of ectopic preg\u00ad\nnancy, also sample blood clot as this may contain the products of conception.\n 5.\t \u0007If the procedure was a tubal ligation, instruct the \u00adhistology laboratory to embed the specimen as cross \nsections. A complete cross-section of the tube is \u00adnecessary to document that a sterilizing procedure \nwas performed.\nMalignancies and Prophylactic Cases in High Risk Women\nPROCESSING THE SPECIMEN\nSEE FIM Protocol (\u201cSection and Extensively Examine the FIMbriated end of the fallopian tube\u201d):\n \n1.\t \u0007Describe the size (length and diameter), and the presence or absence of a fimbriated end. \nCheck for patency with a probe. A plastic ring may be present if there has been a prior tubal \nligation.\n \n2.\t \u0007Describe the serosal surface (normal = smooth and glistening) including adhesions, paratubal cysts, \npurulent or fibrinous exudates, and ruptures.\n \n3.\t \u0007The fallopian tube is submitted according to the SEE FIM protocol:\nThe distal (fimbriated) 1 to 2 cm of the fallopian tube is amputated and cut longitudinally.\nLongitudinal sections of the fimbriae are submitted to entirely evaluate 2 to 3 mm slices and to maximize \nthe examined surface area. This will usually require four sections, although in rare cases (where the \ntubes and fimbriae are particularly small), fewer than 4 sections may suffice.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_462.png", "summary": "This page provides guidelines for processing fallopian tube specimens, including descriptions of normal findings, potential pathologies, and specific considerations for malignancies and prophylactic cases in high-risk women.", "questions": [ "What are the key elements to describe when processing fallopian tube specimens?", "What are some indications for submitting fallopian tube specimens?", "How are fallopian tubes typically received in a pathology laboratory?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 463, "text": "445\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Fallopian Tube\nTABLE 22\u20138.\u2003\n\u0007AJCC AND FIGO (7TH EDITION) CLASSIFICATION OF OVARY AND PRIMARY \nPERITONEAL CARCINOMAS\nTNM CATEGORIES\nFIGO STAGES\nDEFINITION\nPrimary Tumor\nTX\n\u2014\nPrimary tumor cannot be assessed.\nT0\n\u2014\nNo evidence of primary tumor\nT1\nI\nTumor limited to ovaries (one or both)\nT1a\nIA\nTumor limited to one ovary; capsule intact, no tumor on \novarian surface, no malignant cells in ascites or perito\u00ad\nneal washings\nT1b\nIB\nTumor limited to both ovaries; capsules intact, no tumor \non ovarian surface, no malignant cells in ascites or \nperitoneal washings.\nT1c\nIC\nTumor limited to one or both ovaries with any of the \nfollowing: capsule ruptured, tumor on ovarian surface, \nmalignant cells in ascites or peritoneal washings.\nT2\nII\nTumor involves one or both ovaries with pelvic extension.\nT2a\nIIA\nExtension to and/or implants on the uterus and/or tube(s); \nno malignant cells in ascites or peritoneal washings\nT2b\nIIB\nExtension to and/or implants on other pelvic tissues, no \nmalignant cells in ascites or peritoneal washings\nT2c\nIIC\nPelvic extension and/or implants (T2a or T2b) with malig\u00ad\nnant cells in ascites or peritoneal washings\nT3\nIII\nTumor involves one or both ovaries with microscopically \nconfirmed peritoneal metastasis outside the pelvis.\nT3a\nIIIA\nMicroscopic peritoneal metastasis beyond the pelvis (no \nmacroscopic tumor)\nT3b\nIIIB\nMacroscopic peritoneal metastasis beyond pelvis 2 cm or \nless in greatest dimension\nT3c\nIIIC\nPeritoneal metastasis beyond pelvis more than 2 cm \nin greatest dimension and/or regional lymph node \nmetastasis\nRegional Lymph Nodes\nNX\n\u2014\nRegional lymph nodes cannot be assessed.\nN0\n\u2014\nNo regional lymph node metastasis\nN1\nIIIC\nRegional lymph node metastasis\nDistant Metastasis\nM0\n\u2014\nNo distant metastasis\nM1\nIV\nDistant metastasis (excludes peritoneal metastasis)\nNote: Liver capsule metastasis is classified as T3. Liver parenchymal metastasis is classified as M1. Pleural effusion must have positive cytology to \nbe classified as M1.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_463.png", "summary": "This page provides the AJCC and FIGO classification of ovary and primary peritoneal carcinomas, detailing TNM categories and FIGO stages.", "questions": [ "How does the classification of ovarian and primary peritoneal carcinomas help in determining the extent of the disease?", "What are the key differences between the TNM categories T1, T2, and T3 in relation to ovarian and primary peritoneal carcinomas?", "Why is it important to differentiate between regional lymph node metastasis and distant metastasis in the staging of these carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 464, "text": "446\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Fallopian Tube\nThe remaining tubal portion of the fallopian tube (infundibulum, ampulla, and isthmus) is entirely sub\u00ad\nmitted in cross sections.\nThe FIMBRIAL cassettes must be designated clearly in the gross description and on the grossing histol\u00ad\nogy worksheet.\nSPECIAL STUDIES\nTubal pregnancies: Tissue may be sent for karyotyping if requested.\nGROSS DIFFERENTIAL DIAGNOSIS OF FALLOPIAN TUBE LESIONS\nTubal Cysts.\u2002 Commonly seen are benign inclusion cysts - 0.1 to 0.2 cm unilocular smoothly surfaced \ncysts located beneath the serosal surface.\nTubal Pregnancies.\u2002 The tube is dilated and darkened due to blood within the lumen. An embryo \nor villi may be identifiable within the hemorrhagic area. The outer surface may be ruptured. Peritubal \nadhesions may be present indicative of prior salpingitis.\nTubal Carcinomas.\u2002 Microscopic foci of carcinoma (tubal intraepithelial carcinomas with or without \ninvasion) most frequently involve the fimbria (and may be present in >50% of women with BRCA muta\u00ad\ntions). Infundibulum or ampulla based carcinomas may appear enlarged (resembling a sausage) and filled \nwith a papillary or solid growth.\nTubes in Women Exposed to DES.\u2002 Abnormalities, such as hypoplasia, may be present.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Incidental tube: One cassette including fimbriated end, mid section, and cornual portion.\n\t\u2022\t \u0007Ectopic pregnancy: Representative sections of hemorrhagic areas and grossly evident placental or \nembryonic tissue.\n\t\u2022\t \u0007Carcinomas: Submit ENTIRE fallopian tube according to the SEE FIM protocol.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR FALLOPIAN TUBE CARCINOMA\n\t\u2022\t \u0007Specimen: Fallopian tube (right, left), ovary (right, left), uterus\n\t\u2022\t \u0007Procedure: Salpingectomy (right or left), salpingo-oophorectomy (right or left), hysterectomy with \nsalpingo-oophorectomy\n\t\u2022\t \u0007Lymph Node Sampling: Common iliac, external iliac, internal iliac (hypogastric), obturator, para-\naortic, inguinal, pelvic nodes\n\t\u2022\t \u0007Tumor Site: Fallopian tube (right or left)\n\t \u2022\t \u0007Relationship to ovary: not fused or fused\n\t \u2022\t \u0007Status of fimbriated end: open or closed\n\t \u2022\t \u0007The closure of the fimbriated end may be associated with a more favorable prognosis.\n\t\u2022\t \u0007Tumor Location: Fimbria, ampulla, infundibular portion, isthmus\n\t\u2022\t \u0007Specimen Integrity: Intact, ruptured, fragmented\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Histologic Type: Tubal intraepithelial carcinoma, serous carcinoma, mucinous carcinoma, endome\u00ad\ntrioid carcinoma, clear cell carcinoma, other rare types\n\t\u2022\t \u0007Histologic Grade: Use grading system for endometrial /ovarian carcinomas (see section above).\n\t\u2022\t \u0007Tumor Extension: Tubal intraepithelial carcinoma (limited to fallopian tube(s) (pTis), tumor limited \nto one tube without penetrating the serosal surface and without ascites (pT1a), tumor limited to both \ntubes without penetrating the serosal surface and without ascites (pT1b), tumor limited to one or both \ntubes with extension into or through the tubal serosa or with malignant cells in ascites or peritoneal \nwashings (pT1c), tumor involves one or both tubes with pelvic extension and/or metastasis to the \nuterus and/or ovaries (pT2a), extension to other pelvic structures (pT2b), pelvic extension with malig\u00ad\nnant cells in ascites or peritoneal washings (pT2c), tumor involves one or both tubes with microscopic \nperitoneal metastasis beyond pelvis (pT3a), macroscopic peritoneal metastasis beyond the pelvis \u2264 2 cm", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_464.png", "summary": "This page discusses the gross and microscopic examination of fallopian tube lesions, including tubal cysts, tubal pregnancies, tubal carcinomas, and abnormalities in tubes of women exposed to DES.", "questions": [ "How are tubal cysts typically described in gross examination?", "What are the potential findings in a fallopian tube with a tubal pregnancy?", "What are the key diagnostic and prognostic features to consider when evaluating fallopian tube carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 465, "text": "447\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Fallopian Tube\nin size (pT3b), peritoneal metastasis beyond the pelvis > 2 cm in size and/or regional lymph node \nmetastasis (pT3c).\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Lymph Nodes: Absent (N0), present (N1), number of nodes examined, number with metastases, loca\u00ad\ntion of nodes\n\t \u2022\t \u0007Note: Endosalpingiosis and m\u00fcllerian inclusions are common findings in lymph nodes. These \nshould be reported but distinguished from metastases.\n\t\u2022\t \u0007Cytology: Ascites or peritoneal washings: Positive or negative for malignancy\n\t\u2022\t \u0007Additional Pathologic Findings: Hyperplasia, in situ carcinoma, dysplasia, salpingitis isthmica \nnodosa, chronic salpingitis, mucosal metaplasia\n\t \u2022\t \u0007Severe salpingitis (e.g., tuberculous salpingitis) can be associated with pseudocarcinomatous changes. \nCarcinoma is rarely associated with salpingitis.\n\t \u2022\t \u0007Endometriosis, endosalpingiosis\n\t \u2022\t \u0007Endometriosis can be associated with endometrioid carcinoma of the tube.\n\t\u2022\t \u0007Ancillary Studies: p53 immunohistochemistry may be requested\n\t\u2022\t \u0007Distant Metastasis: Present (give number and site of metastases). If distant metastasis is not present \non pathologic examination, the M category is a clinical classification.\n\t\u2022\t \u0007AJCC or FIGO Classification: T, N, and M classifications should be provided, when possible (Table \n22-9). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nTABLE 22\u20139.\u2003\nAJCC AND FIGO (7TH EDITION) CLASSIFICATION OF FALLOPIAN TUBE TUMORS\nTNM CATEGORIES\nFIGO STAGES\nDEFINITION\nPrimary Tumor\nTX\n\u2014\nPrimary tumor cannot be assessed.\nT0\n\u2014\nNo evidence of primary tumor\nTis\n0\nCarcinoma in situ (limited to tubal mucosa)\nT1\nI\nTumor limited to the fallopian tube(s)\nT1a\nIA\nTumor limited to one tube, without penetrating the serosal surface; no \nascites\nT1b\nIB\nTumor limited to both tubes, without penetrating the serosal surface; \nno ascites\nT1c\nIC\nTumor limited to one or both tubes with extension onto or through the \ntubal serosa, or with malignant cells in ascites or peritoneal washings\nT2\nII\nTumor involves one or both fallopian tubes with pelvic extension\nT2a\nIIA\nExtension and/or metastasis to the uterus and/or ovaries\nT2b\nIIB\nExtension to other pelvic structures\nT2c\nIIC\nPelvic extension with malignant cells in ascites or peritoneal washings\nT3\nIII\nTumor involves one or both fallopian tubes, with peritoneal implants \noutside the pelvis.\nT3a\nIIIA\nMicroscopic peritoneal metastasis outside the pelvis\nT3b\nIIIB\nMacroscopic peritoneal metastasis outside the pelvis 2 cm or less in \ngreatest dimension\nT3\nIIIC\nPeritoneal metastasis outside the pelvis and more than 2 cm in greatest \ndimension", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_465.png", "summary": "The page discusses various pathological findings and classifications related to fallopian tube tumors, including lymph node involvement, cytology results, additional pathologic findings, and distant metastasis.", "questions": [ "How can endosalpingiosis and m\u00fcllerian inclusions be distinguished from metastases in lymph nodes?", "What are some of the additional pathologic findings that can be observed in fallopian tube specimens?", "Why is p53 immunohistochemistry requested as an ancillary study in fallopian tube tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 466, "text": "448\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Cervix\nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nCERVIX\nThe cervix is one of the most frequently sampled tissues due to the high incidence of dysplasia and carcinoma. \nCervical biopsies and cone biopsies are frequent surgical procedures to evaluate or treat cervical lesions.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE)\nSee Table 22-10.\nTABLE 22\u201310.\u2003\nRELEVANT CLINICAL HISTORY \u2013 CERVIX\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR CERVICAL SPECIMENS\nOrgan/tissue resected or biopsied\nResults of PAP smears or biopsies\nPurpose of the procedure\nHPV test results\nGross appearance of the organ/tissue/lesion \nsampled\nHormone use\nPregnancy\nAny unusual features of the clinical presentation\nIUD (intrauterine device) use\nAny unusual features of the gross appearance\nDES exposure in utero*\nPrior surgery/biopsies - results\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug \nuse that can change the histologic appearance of \ntissues)\nCompromised immune system\n*DES was used up until 1971 until it was banned by the FDA, due to the association with clear cell carcinomas of the cervix and upper vagina \nwhen women were exposed in utero. The risk of developing these types of carcinoma after exposure is about 1 in 10,000. DES is no longer used in \npregnant women and currently most women with clear cell carcinoma do not have a history of exposure. It is possible some exposed women may \ndevelop carcinomas at an older age.\nRegional Lymph Nodes\nNX\n\u2014\nRegional lymph nodes cannot be assessed.\nN0\n\u2014\nNo regional lymph node metastasis\nN1\nIIIC\nRegional lymph node metastasis\nDistant Metastasis\nM0\n\u2014\nNo distant metastasis\nM1\nIV\nDistant metastasis (excludes metastasis within the peritoneal cavity)\nNote: Liver capsule metastasis is classified as T3. Liver parenchymal metastasis is classified as M1. Pleural effusion must have positive cytology to \nbe classified as M1.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.\nTABLE 22\u20139.\u2003\n\u0007AJCC AND FIGO (7TH EDITION) CLASSIFICATION OF FALLOPIAN TUBE \nTUMORS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_466.png", "summary": "The cervix is a frequently sampled tissue due to the high incidence of dysplasia and carcinoma, with cervical biopsies and cone biopsies being common procedures.", "questions": [ "What are some relevant clinical history elements to consider for cervical specimens?", "Why is DES exposure in utero mentioned in relation to clear cell carcinomas of the cervix and upper vagina?", "What are the different classifications for regional lymph nodes and distant metastasis in cervical cancer staging?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 467, "text": "449\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Cervix\nCervical Biopsies\nDescribe color, number of fragments, and size, and submit the entire specimen.\nCone Biopsies\nCone biopsies are resections of the entire transition zone and the endocervical canal (Fig. 22-6). They \nare performed when dysplasia is present within the endocervical canal (i.e., the lesion cannot be treated \nadequately externally). LEEP specimens are discussed in the next section.\nPROCESSING THE SPECIMEN\n 1.\t \u0007The \u201cdeep\u201d (endocervical) margin is inked blue and the \u201cradial\u201d (lateral) margin is inked black.\n 2.\t \u0007Open along the cervical canal using scissors. If a suture marks the 12 o\u2019clock position, open at this \npoint. If not, make the cut at any site.\n 3.\t \u0007Pin the opened specimen on a wax board, with the mucosa side up and fix overnight. Fix the cone \nbiopsy as soon as possible.\n 4.\t \u0007Describe the length of the endocervical canal, the circumference at the external os, and the circumfer\u00ad\nence at the portio. Describe any visible lesions including size, color, location, relationship to margins, \nand invasion. Frequently, the lesions present will not be evident grossly.\n 5.\t \u0007Take sections along the axis of the cervical canal in order that each section contains external os, endo\u00ad\ncervical canal and portio. All the tissue in at least 12 sections is taken (corresponding to clock posi\u00ad\ntions). If the specimen is unoriented, submit in the same manner starting at some random point and \nstate that the specimen was not oriented.\n12 o\u2019clock\n1 o\u2019clock\n12 o\u2019clock\n12\n11\n10\n9\n8\n7\n6\n5\n4\n3\n2 1\nFigure 22\u20136.\u2002 Cervical cone biopsy.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_467.png", "summary": "Cervical biopsies and cone biopsies are important procedures in gynecologic pathology to evaluate dysplasia and lesions within the cervix.", "questions": [ "What is the purpose of inking the margins of a cone biopsy specimen?", "How are cone biopsies different from LEEP specimens?", "Why is it important to take sections along the axis of the cervical canal during processing?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 468, "text": "450\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Cervix\nLoop Electrocautery Excision Procedure (LEEP)\nThe majority of cases previously managed by cold knife cone are currently removed by electrocautery \nusing a thin wire loop. These specimens can be distinguished grossly from cold knife cone biopsies by \nthe presence of cauterization at the deep margin. The specimen may be submitted as a single fragment \nsimilar in appearance to a cone biopsy. More commonly, the procedure produces two or more specimens, \nincluding anterior and posterior cervix, and a deep endocervical specimen. Because of the fragmented \nnature of some of these specimens, it is critical that the specimen be evaluated and oriented grossly before \ntaking sections.\nPROCESSING THE SPECIMEN\n 1.\t \u0007The specimen is oriented with the mucosal side up and sectioned on the axis of the cervical canal, with \nportio and endocervix represented in each section, identical to the orientation of a cone biopsy.\nThe mucosal side will appear either shiny and white (portio) or pink and finely granular (endocervix). \nThe deep side will be irregular and cauterized.\n 2.\t \u0007Sections are obtained at 1 to 2 mm intervals. Inking of the specimen is not necessary, inasmuch as the \ncauterized margins are easily identified on histologic examination. However, ink the margin if uncertain.\nSPECIAL STUDIES\nThere are no special studies indicated for routine examinations. If HPV testing is requested, the test can \nbe performed on paraffin blocks.\nGROSS DIFFERENTIAL DIAGNOSIS OF CERVICAL LESIONS\nSquamous Intraepithelial Lesions (LSIL and HSIL)\u2002 appear as raised irregular plaques or papules, may \nbe white or red. These lesions are usually removed as small biopsies and are not well appreciated grossly.\nSquamous Cell Carcinomas\u2002 appear as red papules, white plaques, or irregular ulcerated hard masses. \nSmall carcinomas may be removed as cone biopsies.\nAdenocarcinomas\u2002 occur in the endocervix and are usually exophytic. These carcinomas are also \nassociated with HPV infections and can also be associated with squamous lesions/carcinomas.\nMICROSCOPIC SECTIONS\nCervix: Entirely sectioned with orientation from portio to endocervix\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201ccone,\u201d is a 1.5 cm in length by \n2.3 cm in circumference intact cone biopsy with a suture marking the 12 o\u2019clock axis. The distal 1 cm of \nthe mucosal surface is covered by shiny white mucosa without visible lesions. The proximal 0.5 cm of the \nmucosal surface is finely granular and pink, consistent with endocervix. The deep, proximal, and distal \nmargins are inked.\nCassettes #1-12: Longitudinal sections from 1 o\u2019clock to 12 o\u2019clock, 12 frags, ESS.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR CERVICAL CARCINOMAS\n\t\u2022\t \u0007Specimen: Cervix, uterus, ovary (right, left), fallopian tube (right, left), vagina, urinary bladder, rectum\n\t\u2022\t \u0007Procedure: Colpectomy, trachelectomy (cervicectomy), hysterectomy, radical hysterectomy, pelvic \nexenteration\n\t\u2022\t \u0007Tumor Size: Size in three dimensions\n\t\u2022\t \u0007Tumor Site: Right superior quadrant (12 to 3 o\u2019clock), right inferior quadrant (3 to 6 o\u2019clock), left \ninferior quadrant (6 to 9 o\u2019clock), left superior quadrant (9 to 12 o\u2019clock)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_468.png", "summary": "The Loop Electrocautery Excision Procedure (LEEP) is commonly used to remove cervical lesions, with specimens distinguished by cauterization at the deep margin. Proper orientation and evaluation of the specimen are crucial due to its fragmented nature.", "questions": [ "How does the Loop Electrocautery Excision Procedure (LEEP) differ from the cold knife cone biopsy in managing cervical lesions?", "What are the key steps in processing a LEEP specimen for histologic examination?", "What are the gross differential diagnoses of cervical lesions based on their appearance?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 469, "text": "451\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Cervix\n\t \u2022\t \u0007If no tumor is found (e.g., after a positive Pap smear), the adequacy of the specimen (including glan\u00ad\ndular and squamous epithelium) should be documented.\n\t\u2022\t \u0007Histologic Type: Squamous cell carcinoma (keratinizing or nonkeratinizing), adenocarcinoma (muci\u00ad\nnous, endometrioid, clear cell), other rare types. The WHO Classification is recommended.\n\t\u2022\t \u0007Histologic Grade: Squamous cell carcinoma: Nonkeratinizing or keratinizing well, moderately, and \npoorly differentiated\n\t \u2022\t \u0007Adenocarcinoma: The grade has prognostic value (Table 22-11).\n\t\u2022\t \u0007Margins: Endocervical, exocervical, and deep margin (give location if possible)\nTABLE 22\u201312.\u2003\nAJCC AND FIGO (7TH EDITION) CLASSIFICATION OF CERVICAL CARCINOMAS\nTNM CATEGORIES\nFIGO STAGES\nDEFINITION\nPrimary Tumor\nTX\n\u2014\nPrimary tumor cannot be assessed.\nT0\n\u2014\nNo evidence of primary tumor\nTis*\n\u2014\nCarcinoma in situ (preinvasive carcinoma)\nT1\nI\nCervical carcinoma confined to uterus (extension to corpus should be \ndisregarded)\nT1a\u2020\nIA\nInvasive carcinoma diagnosed only by microscopy. Stromal invasion \nwith a maximal depth of 5.0 mm measured from the base of the \nepithelium and a horizontal spread of 7.0 mm or less. Vascular space \ninvolvement, venous or lymphatic, does not affect classification.\nT1a1\nIA1\nMeasured stromal invasion 3.0 mm or less in depth and 7.0 mm or less \nin horizontal spread\nT1a2\nIA2\nMeasured stromal invasion more than 3.0 mm and not more than 5.0 mm \nwith a horizontal spread 7.0 mm or less\nT1b\nIB\nClinically visible lesion confined to the cervix or microscopic lesion \ngreater than T1a2/IA2\nT1b1\nIB1\nClinically visible lesion 4.0 cm or less in greatest dimension\nT1b2\nIB2\nClinically visible lesion more than 4.0 cm in greatest dimension\nT2\nII\nCervical carcinoma invades beyond uterus but not to pelvic wall or to \nthe lower third of vagina.\nT2a\nIIA\nTumor without parametrial invasion.\nT2a1\nIIA1\nClinically visible lesion 4.0 cm or less in greatest dimension\nT2a2\nIIA2\nClinically visible lesion more than 4.0 cm in greatest dimension\nT2b\nIIB\nTumor with parametrial invasion.\nT3\nIII\nTumor extends to the pelvic wall and/or involves the lower third of the \nvagina and/or causes hydronephrosis or nonfunctioning kidney.\nTABLE 22\u201311.\u2003\nGRADING OF CERVICAL ADENOCARCINOMA\nG1\nWell differentiated (small component of solid growth and mild to moderate nuclear atypia)\nG2\nModerately differentiated (intermediate between G1 and G3)\nG3\nPoorly differentiated (solid pattern with severe nuclear atypia)\nG4\nUndifferentiated carcinomas (no or minimal \u00addifferentiation in only rare small foci)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_469.png", "summary": "This page provides information on the histologic types, grades, and margins of cervical carcinomas, as well as the AJCC and FIGO classification of cervical carcinomas.", "questions": [ "How is the grade of squamous cell carcinoma determined?", "What is the significance of documenting the adequacy of the specimen when no tumor is found?", "How does the AJCC and FIGO classification system help in staging cervical carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 470, "text": "452\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Cervix\n\t \u2022\t \u0007Uninvolved: Give distance of carcinoma from the margin.\n\t \u2022\t \u0007Involved: Type of involvement (invasive or carcinoma in situ)\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Stromal Invasion: Depth: millimeters of invasion as measured from the base of the epithelium (either \nsurface or glandular) from which it originates. It is the distance from the epithelial-stromal junction of \nthe adjacent most superficial epithelial papilla to the deepest point of invasion. Vascular space involve\u00ad\nment is not included in the measurement.\n\t \u2022\t \u0007Horizontal extent: millimeters on mucosal surface or by using clock face labels (e.g., from 1 o\u2019clock \nto 6 o\u2019clock)\n\t\u2022\t \u0007Extent of Invasion: No invasion = carcinoma in situ\n\t \u2022\t \u0007Depth of invasion\n\t \u2022\t \u0007Tissues invaded: cervical stroma, uterus, vagina (upper two thirds or lower third), pelvic wall, para\u00ad\nmetrium, obstruction of ureter, bladder mucosa, mucosa of rectum, beyond true pelvis\n\t \u2022\t \u0007If the carcinoma involves the uterine corpus, a determination of the most likely primary site (cervix \nor uterus) should be made.\n\t\u2022\t \u0007Regional Lymph Nodes: Absent (N0), present (N1)\n\t \u2022\t \u0007Number of nodes examined, number of nodes with metastases\n\t\u2022\t \u0007Additional Pathologic Findings: Carcinoma in situ of cervix, glandular dysplasia or carcinoma in situ \nof endocervix, inflammation, koilocytosis\n\t\u2022\t \u0007Distant Metastasis: Present (give number and site of metastases). If distant metastasis is not present \non pathologic examination, the M category is a clinical classification.\n\t\u2022\t \u0007AJCC or FIGO Classification: T, N, and M classifications should be provided, when possible (Table \n22-12). M0 is conferred after clinical assessment; there is no pM0 category.\nTNM CATEGORIES\nFIGO STAGES\nDEFINITION\nT3a\nIIIA\nTumor involves lower third of the vagina, with no extension to the \npelvic wall.\nT3b\nIIIB\nTumor extends to pelvic wall and/or causes hydronephrosis or non\u00ad\nfunctioning kidney.\nT4\nIVA\nTumor invades mucosa of the bladder or rectum and/or extends \nbeyond the true pelvis (bullous edema is not sufficient to classify a \ntumor as T4).\n*FIGO no longer includes stage 0 (Tis).\n\u2020All macroscopically visible lesions, even with superficial invasion, are T1b/IB.\nRegional Lymph Nodes\nNX\n\u2014\nRegional lymph nodes cannot be assessed.\nN0\n\u2014\nNo regional lymph node metastasis\nN1\nIIIB\nRegional lymph node metastasis\nRegional lymph nodes include paracervical, parametrial, hypogastric (obturator), common, internal, and external iliac, presacral and sacral nodes.\nDistant Metastasis\nM0\n\u2014\nNo distant metastasis\nM1\nIVB\nDistant metastasis (including peritoneal spread, involvement of \nsupraclavicular, mediastinal, or para-aortic lymph nodes, lung, liver, \nor bone)\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.\nTABLE 22\u201312.\u2003\n\u0007AJCC AND FIGO (7TH EDITION) CLASSIFICATION OF CERVICAL \nCARCINOMAS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_470.png", "summary": "This page provides detailed information on the pathology assessment of cervical carcinoma, including factors such as depth of invasion, lymph-vascular invasion, regional lymph nodes, distant metastasis, and AJCC/FIGO classifications.", "questions": [ "How is the depth of invasion measured in cervical carcinoma?", "What are the different categories for regional lymph nodes in cervical carcinoma?", "What is the significance of distant metastasis in the pathology assessment of cervical carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 471, "text": "453\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Vagina\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nVAGINA\nPrimary neoplasms of the vagina are very rare. Specimens from the vagina are usually biopsies or part of \nlarger resections (e.g., radical hysterectomies or bladder resections).\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE)\nSee Table 22-13.\nVaginal Biopsies\nDescribe color, number of fragments, and size, and submit the entire specimen.\nVaginal Resections\nVaginal resections are rare specimens, usually performed for squamous cell carcinomas. If the uterus \nis also removed, the specimen can be processed as a radical hysterectomy with sampling of the primary \ntumor and deep soft tissue paravaginal margin.\nIf the uterus has been removed previously, the vagina will end in a blind pouch and this portion of the \nspecimen will not be a margin. The vagina can be opened and processed similar to a large skin excision. \nThe distal margin and deep soft tissue margins are sampled.\nSchiller\u2019s or Lugol\u2019s solutions stain glycogenated epithelium brown (either normal or glycogenated tumors). \nThey do not stain areas of vaginal adenosis or immature squamous metaplasia and can be useful to identify \nsuch areas. Microscopically, dark brown-black deposits are seen on the surface of epithelium. If the solution \nis too concentrated, the cells can become shrunken with nuclear pyknosis and can mimic squamous dysplasia.\nTABLE 22\u201313.\u2003\nRELEVANT CLINICAL HISTORY \u2013 VAGINA\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR VAGINAL SPECIMENS\nOrgan/tissue resected or biopsied\nDysplasia or cervical carcinoma\nPurpose of the procedure\nDES exposure in utero*\nGross appearance of the organ/tissue/lesion \nsampled\nGross features of vagina (cervical hypoplasia, pseudopolyps, \ncoxcomb deformity, vaginal adenosis, or vaginal ridge) \nthat are suggestive of DES exposure (present in about \none third of exposed patients).\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nPrior malignancy\nPrior treatment (radiation therapy, chemother\u00ad\napy, drug use that can change the histologic \n\u00adappearance of tissues)\nCompromised immune system\n*DES was used up until 1971 until it was banned by the FDA, due to the association with clear cell carcinomas of the cervix and upper vagina \nwhen women were exposed in utero. The risk of developing these types of carcinoma after exposure is about 1 in 10,000. DES is no longer used in \npregnant women, and currently, most women with clear cell carcinoma do not have a history of exposure. It is possible some exposed women may \ndevelop carcinomas at an older age.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_471.png", "summary": "Primary neoplasms of the vagina are very rare, with specimens usually being biopsies or part of larger resections. Reporting on cancer-directed surgical resection specimens must include scientifically validated data elements.", "questions": [ "What are the key elements that must be present in reports of cancer-directed surgical resection specimens from ACS CoC-approved cancer programs?", "What are some considerations for processing vaginal resections, especially if the uterus has been previously removed?", "What is the significance of Schiller's or Lugol's solutions in staining glycogenated epithelium in vaginal specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 472, "text": "454\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Vagina\nTABLE 22\u201314.\u2003\nAJCC AND FIGO (7TH EDITION) CLASSIFICATION OF VAGINAL CARCINOMAS\nTNM \nCATEGORIES\nFIGO \nSTAGES\nDEFINITION\nPrimary Tumor\nTX\n\u2014\nPrimary tumor cannot be assessed.\nT0\n\u2014\nNo evidence of primary tumor\nTis*\n\u2014\nCarcinoma in situ (preinvasive carcinoma)\nT1\nI\nTumor confined to the vagina\nT2\nII\nTumor invades paravaginal tissues but not to the pelvic wall.\nT3\nIII\nTumor extends to the pelvic wall.\u2020\nT4\nIVA\nTumor invades the mucosa of the bladder or rectum and/or extends beyond \nthe true pelvis (bullous edema is not sufficient to classify a tumor as T4).\n*FIGO no longer includes stage 0 (Tis).\n\u2020Pelvic wall is defined as muscle, fascia, neurovascular structures, or skeletal portions of the bony pelvis. On rectal examination, there is no cancer-\nfree space between the tumor and pelvic wall.\nRegional Lymph Nodes\nNX\n\u2014\nRegional lymph nodes cannot be assessed.\nN0\n\u2014\nNo regional lymph node metastasis\nN1\nIII\nPelvic or inguinal lymph node metastasis\nDistant Metastasis\nM0\n\u2014\nNo distant metastasis\nM1\nIVB\nDistant metastasis\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR VAGINAL CARCINOMAS\n\t\u2022\t \u0007Specimen: Vagina\n\t\u2022\t \u0007Procedure: Excisional biopsy, partial vaginectomy, radical vaginectomy\n\t\u2022\t \u0007Tumor Site: Upper third, middle third, lower third\n\t \u2022\t \u0007Circumferential, anterior, posterior, left lateral, right lateral\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Histologic Type: Squamous cell carcinoma, adenocarcinoma, clear cell carcinoma, other rare carci\u00ad\nnomas. The WHO Classification is recommended.\n\t\u2022\t \u0007Histologic Grade: Well, moderate, poor, undifferentiated\n\t\u2022\t \u0007Margins: Uninvolved, involved, distance of carcinoma to closest margin\n\t \u2022\t \u0007Invasive or carcinoma (dysplasia) in situ\n\t \u2022\t \u0007Distal vagina, paravaginal soft tissue\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Extent of Invasion: Carcinoma in situ (pTis), tumor confined to vagina (pT1), tumor invades para\u00ad\nvaginal tissues but not to pelvic wall (pT2), tumor extends to pelvic wall (pT3), tumor invades mucosa \nof bladder or rectum and/or extends beyond the true pelvis (pT4)\n\t \u2022\t \u0007Report depth in millimeters.\n\t\u2022\t \u0007Regional Lymph Nodes: Absent (N0), present (N1)\n\t \u2022\t \u0007Number of nodes examined, number of nodes with metastases\n\t\u2022\t \u0007Additional Pathologic Findings: Condyloma acuminatum, squamous dysplasia, carcinoma in situ, \nadenocarcinoma in situ, endometriosis, adenosis, atypical adenosis, dysplasia\n\t\u2022\t \u0007Distant Metastasis: Present (give number and site of metastases). If distant metastasis is not present \non pathologic examination, the M category is a clinical classification.\n\t\u2022\t \u0007AJCC or FIGO Classification: T, N, and M classifications should be provided, when possible (Table \n22-14). M0 is conferred after clinical assessment; there is no pM0 category.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_472.png", "summary": "The page discusses the AJCC and FIGO classification of vaginal carcinomas, outlining the TNM categories, FIGO stages, and pathologic diagnostic/prognostic features checklist.", "questions": [ "What are the different TNM categories for vaginal carcinomas?", "What is the significance of regional lymph node metastasis in the prognosis of vaginal carcinomas?", "How does the AJCC or FIGO classification help in determining the stage of vaginal carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 473, "text": "455\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Vulva\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nGRADING OF VAGINAL CARCINOMAS\nThere is no established grading system for vaginal carcinomas. The following system is suggested. Grades \n1 to 3 are used for carcinomas showing glandular or squamous differentiation. Grade 4 is used for carci\u00ad\nnomas without such differentiation.\n\t \u2022\t \u0007Grade 1: Well differentiated\n\t \u2022\t \u0007Grade 2: Moderately differentiated\n\t \u2022\t \u0007Grade 3: Poorly differentiated\n\t \u2022\t \u0007Grade 4: Undifferentiated\nVULVA\nThe vulva is subject to specific diseases of this site (e.g., lichen sclerosus), infectious disease (e.g., HPV \ninfection, syphilis), and, most commonly, squamous dysplasia and neoplasia.\nVulvar Biopsies\nSmall biopsies or excisional biopsies are processed like skin biopsies.\nVulvectomies\nMost vulvectomies are performed for the treatment of invasive squamous cell carcinoma or carcinoma \nin situ. Most carcinomas arise on the labia (majora > minora) or less commonly on the clitoris or poste\u00ad\nrior fourchette (Table 22-15) . Total vulvectomies will include all the perineum surrounding the vagina \n(Fig. 22-7). More commonly, partial vulvectomies are performed that will look grossly like large skin \nellipses and can be processed in a similar fashion.\nPROCESSING THE SPECIMEN\n 1.\t \u0007If a total vulvectomy is performed, it will look like an ellipse of skin with a central defect (correspond\u00ad\ning to the vaginal vault). Orient the specimen using the following landmarks. If inguinal fat is present, \nit will be in the superior portion of the specimen and to either side. The clitoris is present superiorly \nand midline. The hair-bearing labia majora are present laterally. Partial vulvectomies will require \norientation by the surgeon.\nRadical vulvectomies are complicated specimens which have numerous resection margins including \ndeep (soft tissue), exterior (lower abdomen, leg, groin, perineal, perianal) and central (vagina and pos\u00ad\nsibly urethral). It is prudent to study the specimen carefully to orient the probable tumor to these \nvarious resection margins. If there is any doubt as to orientation, contact the surgeon before \u00adsectioning. \nTABLE 22\u201315.\u2003\nLINGUISTIC NOTE\nSINGULAR\nPLURAL\nLabium\nLabia\nMajus\nMajora\nMinus\nMinora", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_473.png", "summary": "The page discusses grading of vaginal carcinomas, specific diseases of the vulva, and processing of vulvar biopsies and vulvectomies.", "questions": [ "What are the suggested grades for vaginal carcinomas showing glandular or squamous differentiation?", "What are some specific diseases that affect the vulva?", "How are vulvar biopsies processed?", "What are the indications for performing vulvectomies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 474, "text": "456\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Vulva\nBefore dissecting, it is usually helpful to sketch the specimen noting any lesions and the relationship \nto margins.\nMeasure length, width, and depth. Diagrams are mandatory for complicated specimens.\nLesions may be obvious ulcerating or fungating carcinomas or may be quite subtle if the procedure \nwas performed for VIN. VIN usually appears as a maculopapular lesion with color changes ranging \nfrom white to red to dark shades of brown. Sometimes, however, no gross lesion will be detectable. \nThe location of prior diagnostic biopsies may be helpful to guide sectioning.\nDescribe each gross lesion including the distance to the nearest skin and vaginal margin.\n 2.\t \u0007Ink the exposed epithelial and soft tissue margins. It may be helpful to ink the vaginal margin with a \ndifferent color.\nPin the specimen flat and fix overnight.\n 3.\t \u0007Sample all gross lesions. For invasive carcinomas, find the area of deepest invasion and sample with \ndeep margin. Sample all close margins with perpendicular (not en face) margins.\n 4.\t \u0007If there is attached inguinal fat, search diligently for lymph nodes. Submit each node in entirety and \nseparate right from left inguinal nodes.\nSPECIAL STUDIES\nNone indicated for routine evaluation of vulvar specimens.\nGROSS DIFFERENTIAL DIAGNOSIS OF VULVAR LESIONS\nSquamous Cell Carcinoma.\u2002 Exophytic irregular masses, often with invasion into the subcutaneous \ntissue. Central ulceration is common.\nVulvar Intraepithelial Neoplasia (VIN).\u2002 Flat or papular lesions that may be white, red, gray, brown, \nor black. In some cases, a gross lesion may not be apparent.\nLichen Sclerosus/Simplex Chronicus.\u2002 Flat white thinned plaque-like epidermis. This lesion is not \nusually resected, but may be an incidental finding in vulvar excisions.\nMons pubis\nLabia\nmajora\nClitoris\nVaginal\nmargin\nLabia\nminora\nPosterior\nfourchette\nPerineum\nInguinal soft tissue\nFigure 22\u20137.\u2002 Total vulvectomy.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_474.png", "summary": "The page provides guidelines for dissecting and evaluating vulvar specimens, including measuring dimensions, describing lesions, and sampling margins for invasive carcinomas.", "questions": [ "What are the key steps to follow before dissecting a vulvar specimen?", "How can VIN lesions appear grossly, and why may they be challenging to detect?", "Why is it important to sample all gross lesions and margins in cases of invasive carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 475, "text": "457\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Vulva\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: Submit sections of tumor to demonstrate the deepest invasion of tumor.\n\t\u2022\t \u0007Margins: Submit perpendicular sections of the margins in relationship to the tumor including the \nnearest skin and vaginal margins.\n\t\u2022\t \u0007Other lesions: Submit sections of all other lesions (e.g., areas suspicious for VIN associated with an \ninvasive tumor with the nearest margin[s]).\n\t\u2022\t \u0007Lymph nodes: Serially section and completely submit all lymph nodes. Separate right side and left side.\n\t\u2022\t \u0007Normal: Submit sections of clitoris, fourchette, perineum, and contralateral labia majora and minora.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cvulva,\u201d is an ovoid excision of \nwhite/tan skin (11 \u00d7 10 \u00d7 0.5 cm [depth]) with a centrally located circular defect (2 \u00d7 1.8 cm). The labia \nmajora and clitoral hood are identified. There is a 1.2 \u00d7 0.9 cm white exophytic lesion located on the right \nlabium majus which is 2.5 cm from the lateral margin and 2.1 cm from the vaginal margin. The lesion \ninvades into the superficial soft tissue but is grossly 0.3\u00a0cm from the deep soft tissue margin. There is a \ndepressed white fibrotic area (0.5 \u00d7 0.4 cm) located on the posterior fourchette which is 1 cm from the \nclosest (posterior) margin. No gross invasion is seen. The remainder of the epidermal surface is unre\u00ad\nmarkable. Two lymph nodes are located in the right inguinal soft tissue, the largest measuring 0.5\u00a0cm. \nOne lymph node is located in the left inguinal soft tissue measuring 0.6 cm. The deep and exterior epi\u00ad\ndermal margins are inked black. The vaginal epidermal margin is inked blue.\nCassettes #1-3: Exophytic lesion including deep margin, 3 frags, ESS.\nCassette #4: Closest right lateral margin, perpendicular, 1 frag, RSS.\nCassette #5: Closest vaginal margin, perpendicular, 1\u00a0frag, RSS.\nCassette #6: Flat lesion of posterior fourchette, including deep margin, 2 frags, ESS.\nCassette #7: Closest posterior margin to flat lesion, perpendicular, 1 frag, RSS.\nCassette #8: Clitoris, 1 frag, RSS.\nCassette #9: Left labium majus and minus, 2 frags, RSS.\nCassette #10: Right inguinal lymph nodes, inked green and red, 4 frags, ESS.\nCassette #11: Left inguinal lymph node, 2 frags, ESS.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR VULVAR CARCINOMAS\n\t\u2022\t \u0007Specimen: Vulva\n\t\u2022\t \u0007Procedure: Local excision, wide excision, partial vulvectomy, total vulvectomy, radical vulvectomy\n\t\u2022\t \u0007Lymph Node Sampling: Sentinel lymph node biopsy, inguinal-femoral nodes, pelvic nodes\n\t\u2022\t \u0007Lymphadenectomy: Not performed, sentinel lymph node biopsy, inguinal-femoral nodes, pelvic nodes\n\t\u2022\t \u0007Specimen Size: Greatest dimension (other dimensions optional)\n\t\u2022\t \u0007Tumor Site: Right vulva (labia major or minor), left vulva (labia major or minor), clitoris, other\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Tumor Focality: Unifocal, multifocal\n\t\u2022\t \u0007Histologic Type: Squamous cell carcinoma, verrucous carcinoma, Paget disease of the vulva, ade\u00ad\nnocarcinoma, basal cell carcinoma, Bartholin gland carcinoma, other rare malignancies. Melanomas \nshould be reported as for skin melanomas. The WHO Classification is recommended.\n\t\u2022\t \u0007Histologic Grade: Well, moderate, poor, undifferentiated\n\t\u2022\t \u0007Depth of Invasion: Squamous cell carcinoma: Report in millimeters measured from the deep border \nof the granular cell layer or, if absent, from the surface to deepest point of invasion\n\t\u2022\t \u0007Tumor Border: Squamous cell carcinoma: broad pushing front (verrucous carcinoma) or infiltrating \n(finger-like). The latter pattern is more likely to be associated with lymph node metastases.\n\t\u2022\t \u0007Margins: Uninvolved, involved, distance of carcinoma to closest margin\n\t \u2022\t \u0007Invasive or in situ carcinoma\n\t \u2022\t \u0007Cutaneous (give location as right or left, superior or inferior), perineal, vaginal, deep soft tissue\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Regional Lymph Nodes: Number of nodes examined, number of nodes with metastases\n\t \u2022\t \u0007Size of metastases (< 5 mm; \u2265 5 mm)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_475.png", "summary": "This page provides guidelines for submitting sections of tumor, margins, other lesions, lymph nodes, and normal tissue in cases of vulvar excisions.", "questions": [ "What are the specific instructions for submitting sections of tumor and margins in vulvar excisions?", "How are lymph nodes handled and submitted in cases of vulvar excisions?", "What are the key diagnostic/prognostic features that are checked for in vulvar carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 476, "text": "458\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Placenta\n\t \u2022\t \u0007Absence or presence of extranodal invasion (may correlate with an increased risk for recurrence).\n\t \u2022\t \u0007Unilateral, bilateral\n\t \u2022\t \u0007Fixed or ulcerated femoral-inguinal lymph nodes\n\t\u2022\t \u0007Extent of Invasion: Report in millimeters of invasion from the epithelial-stromal junction of \nthe adjacent most superficial dermal papillae to the deepest extent of invasion. Squamous cell \ncarcinomas that invade deeper than 0.1 cm may be more likely to be associated with lymph node \nmetastasis.\n\t \u2022\t \u0007Carcinoma in situ, invasion of vulva, perineum, lower urethra, vagina, anus, bladder mucosa, rectal \nmucosa, upper urethral mucosa, pubic bone\n\t\u2022\t \u0007Additional Pathologic Findings: Lichen sclerosus, VIN3 (severe dysplasia/carcinoma in situ), con\u00ad\ndyloma acuminatum\n\t\u2022\t \u0007Distant Metastasis: Present (give number and site of metastases). If distant metastasis is not present \non pathologic examination, the M category is a clinical classification.\n\t\u2022\t \u0007AJCC or FIGO Classification: T, N, and M classifications should be provided, when possible \n(Table 22-16). M0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nPLACENTA\nPlacentas are examined for many reasons: multiple gestations, abnormal labor, neonatal indications, \nunusual features of the placenta, or if there is a significant maternal medical history. Examination can \noften reveal significant findings relating to the health of the placenta and fetus prior to birth. The \nCollege of American Pathologists has issued a comprehensive guideline for the examination of the \nplacenta.2\nRELEVANT CLINICAL HISTORY FOR PLACENTAL EXAMINATION\n\t\u2022\t \u0007Number of gestations\n\t\u2022\t \u0007History of selective termination\n\t\u2022\t \u0007Any known abnormalities with the gestation including:\n\t \u2022\t \u0007Low birth weight\n\t \u2022\t \u0007Low Apgar scores\n\t \u2022\t \u0007Fetal demise\n\t \u2022\t \u0007Twin-twin transfusion syndrome\n\t \u2022\t \u0007Congenital malformations\n\t \u2022\t \u0007Trophoblastic disease\n\t\u2022\t \u0007Unusual features of the placenta noted at delivery (e.g., small size, green discoloration, knots in the \numbilical cord)\n\t\u2022\t \u0007Any abnormalities with the labor and delivery\n\t\u2022\t \u0007History of infection\n\t\u2022\t \u0007Maternal history of hypertension, malignancy, or compromised immune system.\nPROCESSING THE SPECIMEN\nThere are three major placental tissues to be examined: the umbilical cord, the membranes, and the pla\u00ad\ncental parenchyma itself. Additional procedures are indicated for multiple gestation placentas (see later). \nThe routine for processing a single gestation placenta is as follows:\n 1.\t Obtain standard measurements:\n\t \u2022\t Dimensions of disk\n\t \u2022\t Length of umbilical cord", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_476.png", "summary": "The page provides information on the examination of placenta specimens, including the importance of assessing for various abnormalities and clinical history.", "questions": [ "What are the major placental tissues to be examined?", "What are some relevant clinical history factors to consider for placental examination?", "What are some significant findings that can be revealed through placental examination?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 477, "text": "459\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Placenta\nTABLE 22\u201316.\u2003\nAJCC AND FIGO (7TH EDITION) CLASSIFICATION OF VULVAR CARCINOMAS\nTNM CATEGORIES\nFIGO STAGES\nDEFINITIONS\nPrimary Tumor\nTX\n\u2014\nPrimary tumor cannot be assessed.\nT0\n\u2014\nNo evidence of primary tumor\nTis*\n\u2014\nCarcinoma in situ (preinvasive carcinoma)\nT1a\nIA\nLesions 2 cm or less in size, confined to the vulva or perineum and with \nstromal invasion 1.0 mm or less\u2020\nT1b\nIB\nLesions more than 2 cm in size or any size with stromal invasion more \nthan 1.0 mm, confined to the vulva or perineum\nT2\u2021\nII\nTumor of any size with extension to adjacent perineal structures (lower/\ndistal one third of the urethra, lower/distal one third of the vagina, \nanal involvement)\nT3\u00a7\nIVA\nTumor of any size with extension to any of the following: upper/\nproximal two thirds of the urethra, upper/proximal two thirds of the \nvagina, bladder mucosa, rectal mucosa, or fixed to pelvic bone\n*FIGO no longer includes stage 0 (Tis).\n\u2020\u0007The depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal \npapilla to the deepest point of invasion.\n\u2021FIGO uses the classification T2/T3. This is defined as T2 in TNM.\n\u00a7FIGO uses the classification T4. This is defined as T3 in TNM.\nRegional Lymph Nodes\nNX\n\u2014\nRegional lymph nodes cannot be assessed.\nN0\n\u2014\nNo regional lymph node metastasis\nN1\n\u2014\nOne or two regional lymph nodes with the following features:\nN1a\nIIIA\nOne lymph node metastasis each 5 mm or less\nN1b\nIIIA\nOne lymph node metastasis 5 mm or greater\nN2\nIIIB\nRegional lymph node metastasis with the following features:\nN2a\nIIIB\nThree or more lymph node metastases each less than 5 mm\nN2b\nIIIB\nTwo or more lymph node metastases 5 mm or greater\nN2c\nIIIC\nLymph node metastasis with extracapsular spread\nN3\nIVA\nFixed or ulcerated regional lymph node metastasis\nNote: An effort should be made to describe the site and laterality of lymph node metastases.\nDistant Metastasis\nM0\n\u2014\nNo distant metastasis\nM1\nIVB\nDistant metastasis (including pelvic lymph node metastasis)\nNote: This classification system is not used for malignant melanoma.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_477.png", "summary": "The page provides the AJCC and FIGO classification of vulvar carcinomas based on TNM categories and FIGO stages.", "questions": [ "What are the different TNM categories used for classifying vulvar carcinomas?", "How does the depth of invasion impact the classification of vulvar carcinomas?", "Why is the classification system mentioned not used for malignant melanoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 478, "text": "460\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Placenta\n 2.\t Examine the membranes and cord:\nMembranes: Color and transparency\n\t \u2022\t Normal: shiny, translucent and thin\n\t \u2022\t Opaque or dull: suggests chorioamnionitis\n\t \u2022\t Green: suggests meconium staining and/or chorioamnionitis\n\t \u2022\t Yellow or white nodules on membrane: amnion nodosum\n\t \u2022\t Single yellow patch on membrane (possibly calcified): yolk sac\n\t \u2022\t \u0007Fetus papyraceus: a flattened fetus may be present within the membranes in cases of selective reduction\nUmbilical cord:\n\t \u2022\t \u0007Normal: Two arteries and a vein. Examine at least 5 cm above the chorionic plate, as the arteries \nmay normally fuse near the insertion. A single umbilical cord artery is associated with fetal cardiac \nand renal anomalies\n\t \u2022\t \u0007Twist: Helical twisting is normal. Left-handed twists (as observed looking down cord towards disc) \nare most common. Location of insertion of umbilical cord: central, eccentric, marginal, \u00admembranous\n\t \u2022\t \u0007In a partially membranous (velamentous) cord the cord vessels separate and run within the mem\u00ad\nbrane for a distance. Measure the length of the velamentous vessels.\n\t \u2022\t \u0007Furcate insertion: The cord vessels spread out over the placental disc within membranes.\n\t \u2022\t \u0007True knots in umbilical cord: Note presence and tightness and differences in cord color and diam\u00ad\neter on either side of knot. False knots appear as bulbous expansions of the cord and are formed \nby ectatic vessels with reduction in Wharton\u2019s jelly. If a true knot is present, photograph the knot \nbefore and after untying the knot, in order to best document the tightness of the knot.\n\t \u2022\t \u0007Thrombosis, congestion, thinning, or necrosis.\n 3.\t \u0007Examine the insertion of the membranes into the placental disc and estimate the percent of each type \nof insertion (Fig. 22-8):\n\t \u2022\t \u0007Inserts at edge (normal situation) = marginal\n\t \u2022\t Inserts inside edge = circummarginate\n\t \u2022\t Inserts inside edge with a prominent ridge as membrane is folded back upon itself = circumvallate\n 4.\t \u0007Selected sections are taken for fixation and histologic sections. The remainder of the placenta may be \nstored refrigerated until after final sign-out.\nPrepare one membrane roll. Cut a long strip of membrane approximately 3 cm wide from the point \nof rupture of the membrane inward toward the placental disc. Leave a small piece of disc at the end of \nthe strip. Grasp the disc in a pair of flat-tipped forceps and roll the membrane tightly around it. Slip \nthe roll off gently and drop into a formalin container.\n 5.\t Cut two sections of umbilical cord (proximal and distal) and add to the formalin container.\n 6.\t \u0007Cut off the entire umbilical cord and membranes and weigh the placenta.\nFor multiple gestation placentas, record a combined weight after trimming the cords and mem\u00ad\nbranes. Do not attempt to physically separate the two disks.\n 7.\t \u0007Examine the fetal surface (chorionic plate), paying close attention to the fetal vessels. These vessels \ncan be dilated and thrombosed in cases of gross cord abnormalities and/or intrauterine fetal demise. \nMake sure to include these fetal vessels in your full-thickness placental parenchymal \u00adsections.\n 8.\t \u0007With a large sharp knife, serially section the placenta in 0.5 cm sections. Examine the parenchyma \ncarefully for infarcts (firm white/yellow areas), intervillous thrombi, large, significant areas of hem\u00ad\norrhage, and any other unusual findings. Place two or three representative strips of placental paren\u00ad\nchyma into the formalin container.\nThe remainder of the placenta is stored in the freezer in routine cases until after sign-out, UNLESS \nTHERE IS ASSOCIATED INTRAUTERINE FETAL DEATH, in which case the remaining \ntissue is placed in formalin.\n 9.\t \u0007The following day, the fixed placental tissue can be sectioned. Submit two cross sections of the umbilical \ncord and two cross sections of the membrane roll. Sections of placental parenchyma showing both pathol\u00ad\nogy (if present) and adjacent normal tissue should be submitted for comparison. In patients with a history \nof hypertension, diabetes, lupus erythematosus, or eclampsia, submit an additional membrane roll.\nMultiple Gestation Placentas\nAt delivery, the placentas may be identified by clamping only one umbilical cord or using different num\u00ad\nbers of clamps on the two cords. Identify the placentas using the number of clamps when present. If \nclamps are not present, designate the placentas arbitrarily as \u201cA\u201d and \u201cB.\u201d The placentas should be", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_478.png", "summary": "This page discusses the examination of the membranes and cord of the placenta, including normal characteristics and abnormalities to watch for.", "questions": [ "What are some abnormalities in the membranes that may suggest chorioamnionitis?", "What are the implications of finding a single umbilical cord artery?", "How should the examination of the umbilical cord be conducted to identify true knots?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 479, "text": "461\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Placenta\n\u00adidentifiable after dissection. For example, the cord stump on placenta \u201cA\u201d may be left longer than the \ncord stump on placenta \u201cB.\u201d The disks should be left attached and not physically \u00adseparated.\nThere are four types of multiple gestation placentas (Fig. 22-9):\n 1.\t \u0007Diamniotic/dichorionic separated twin placentas (zygosity of the twins cannot be assessed).\nThe discs are completely separate but the membranes may be adherent. The membranes are sepa\u00ad\nrated by pulling on them gently. Each placenta is described separately.\n 2.\t \u0007Diamniotic/dichorionic fused twin placentas (zygosity of the twins cannot be assessed). See later.\n 3.\t \u0007Diamniotic/monochorionic fused twin placentas (implies monozygosity); may be associated with \ntwin-twin transfusions.\nCases 2 and 3 consist of a single placental disc with two umbilical cords, a common outer mem\u00ad\nbrane, and a twin dividing membrane separating the cords. The outer membrane may be ruptured in \ntwo separate places, or, more typically, have a single large rupture.\nIn case 2, the dividing membrane consists of two complete amnions and two complete fused chori\u00ad\nons. The dividing membrane is thick and opaque. Peel off the amnionic membranes from both sides of \nthe membrane, leaving a part of the fused thick chorionic membrane in the middle. Grossly, it appears \ntrilaminar (two amnions with attached chorion and fused center of chorion).\nIn case 3, the dividing membrane consists of two amnions on either side of a single chorion. \nThe membrane is thin and almost transparent. Separate the amnions, producing two membrane \nA\nB\nC\nD\nCentral insertion\nCircummarginate\nCircumvallate\nVelamentous\nFigure 22\u20138.\u2002 Insertion of membranes into the placental disc.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_479.png", "summary": "The text discusses different types of multiple gestation placentas, including diamniotic/dichorionic separated and fused twin placentas, as well as diamniotic/monochorionic fused twin placentas.", "questions": [ "How are diamniotic/dichorionic separated twin placentas different from diamniotic/dichorionic fused twin placentas?", "What are the characteristics of the dividing membrane in case 2 of diamniotic/monochorionic fused twin placentas?", "What implications are associated with diamniotic/monochorionic fused twin placentas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 480, "text": "462\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Placenta\nleaflets. Grossly, it appears dilaminar (two amnions with attached chorion, no thickened central \nchorion).\nSubmit the dividing membrane for microscopic examination in addition to routine sections of each \nplacenta.\n 4.\t \u0007Monoamniotic/monochorionic fused twin placentas (monozygous); associated with a high rate \nof complications, such as fetal death from cord entanglement. There are two umbilical cords, but no \ndividing membrane. Routine sections are taken from each cord, disc, and membranes.\nE\nC\nB \nD\nA\nDichorionic diamniotic separated twin\nplacentas\nDichorionic diamniotic fused twin placenta\nPosition of dividing membrane\nMonochorionic diamniotic fused twin \nplacenta\nVery delicate, filmy amniotic membrane\nThick separating\nmembrane due to\nchorion\nMonochorionic monoamniotic fused\ntwin placenta\nNo separating membrane\nDiamniotic/monochorionic\ndividing membrane\nDiamniotic/dichorionic\ndividing membrane\nFigure 22\u20139.\u2002 Twin placentas.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_480.png", "summary": "The page discusses different types of twin placentas, including monoamniotic/monochorionic fused twin placentas and dichorionic diamniotic separated twin placentas.", "questions": [ "What are the potential complications associated with monoamniotic/monochorionic fused twin placentas?", "How do the characteristics of the placenta differ between monoamniotic/monochorionic fused twin placentas and dichorionic diamniotic separated twin placentas?", "Why is it important to submit the dividing membrane for microscopic examination in addition to routine sections of each placenta?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 481, "text": "463\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Placenta\nTriplet placentas are processed similarly to twin placentas, except that there will be three umbilical \ncords and three dividing membranes to examine.\nSPECIAL STUDIES\nVascular Anastomoses.\u2002 Vascular anastomoses are searched for in monochorionic twin placentas. \nThese are usually superficial arterial-to-arterial and venous-to-venous connections which are inconse\u00ad\nquential, but there may be a deep A-V anastomosis which has implications for possible twin-twin trans\u00ad\nfusion syndrome. A\u00a0membrane roll from between the placentas is taken first (to document chorionicity). \nTo assess the presence of anastomoses, the entire amnion is peeled away from the chorionic surface. This \nallows optimal visualization of the fetal vessels. Arteries and veins can then be readily traced, and A-A, \nV-V, and A-V anastomoses can be visualized. The arteries run over the veins in the chorionic plate.\nMonochorionic placentas without twin-twin transfusion syndrome tend to have multiple anastomoses, \nwhereas monochorionic placentas with twin-twin transfusion syndrome almost always have a single deep \nanastomosis.3\nCytogenetics.\u2002 If there is a clinical suspicion of a genetic abnormality, or multiple congenital malfor\u00ad\nmations are present, or if the fetus is growth restricted or stillborn, it may be appropriate to send fresh \nsterile tissue taken from the midportion of the placenta for analysis. Sometimes the fetus is not available \n(or is very macerated) and the best tissue available is the placenta.\nInfectious Cases.\u2002 If there is suspected chorioamnionitis, premature rupture of membranes, maternal \nfever, or suspected neonatal infection, it may be appropriate to take fresh tissue for culture. Cultures \ntaken from the chorionic surface beneath the amnion may be the most representative. The most com\u00ad\nmon pathogens can be detected by aerobic and anaerobic bacterial cultures. If there is a clinical suspicion \nof unusual infectious agents (e.g., syphilis, tuberculosis, tularemia, listeria, toxoplasmosis, brucellosis, Q \nfever, or viruses) tissue can be taken and submitted for special cultures.\nPotentially infectious placentas that could place pathology workers at risk (e.g., those from mothers \nwith HIV or hepatitis) may be fixed for one week prior to processing unless there is a clinical reason for \nmore rapid evaluation. Place the entire placenta in a large specimen container and fill it with formalin. \nPut paper towels underneath and over the placenta. It is very difficult to fully fix a placenta.\nMetabolic Diseases.\u2002 In rare cases of suspected metabolic diseases, 10 to 20 grams of fresh tissue can \nbe rapidly \u00adfrozen.\nGROSS DIFFERENTIAL DIAGNOSIS OF PLACENTAL LESIONS\nChorioamnionitis.\u2002 The membranes are opaque and may be yellow to green in color. Candidal infec\u00ad\ntions can cause white microabscesses on the cord.\nSelective Reductions.\u2002 In multiple gestations due to infertility treatment (i.e., multiple fertilized \neggs introduced into the uterus), one or more fetuses may be terminated to reduce the total to two or \nthree. The fetuses may be found as thickenings in the membranes and are usually markedly flattened and \none to two centimeters in length (\u201cfetus papyraceus\u201d).\nAbnormal Lobation.\u2002 The placenta usually forms a single disc-shaped structure. Some placentas \nwill be comprised of two or more lobes. A smaller accessory (succenturiate) lobe may be present. \nThese variants are associated with velamentous/intramembranous vessels and may increase the risk \nof fetal bleeding.\nAmnion Nodosum.\u2002 Multiple small (<0.1 cm) white or gray irregular nodules on the fetal surface. \nThese can easily be rubbed off the surface. These are formed by aggregates of fetal cells (squames, vernix, \nhair) on the surface, associated with oligohydramnios.\nInfarction.\u2002 Infarcts are discrete solid lesions usually connected to the basal plate. Recent infarcts \nwill be dark red, and older infarcts will be orange to white. Small marginal infarcts are commonly found. \nCentrally located infarcts may be of clinical importance.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_481.png", "summary": "Triplet placentas are processed similarly to twin placentas, with three umbilical cords and dividing membranes. Special studies include searching for vascular anastomoses in monochorionic twin placentas, cytogenetic analysis for genetic abnormalities, and taking fresh tissue for infectious cases.", "questions": [ "What implications does the presence of vascular anastomoses in monochorionic twin placentas have?", "When is it appropriate to send fresh tissue from the placenta for cytogenetic analysis?", "How should potentially infectious placentas be handled to ensure safety for pathology workers?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 482, "text": "464\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Products of Conception\nIntervillous Thrombus.\u2002 Homogeneous red (recent) to white (old) aggregates of blood found within \nthe placental disc.\nRetroplacental Hematoma.\u2002 An aggregate of blood adherent to the basal plate. The age of the \nhematoma can be estimated by the degree of organization seen microscopically. The hematoma may \ncompress the placental disc and be associated with infarctions. May be associated with fetal hypoxia.\nSubchorionic Fibrin Deposition.\u2002 Small firm white nodules are seen below the fetal surface. Fibrin \ndeposition can be extensive and involve the entire subchorionic area.\nChorangioma.\u2002 Rare hamartoma (hemangioma) presenting as a circumscribed fleshy mass that is usu\u00ad\nally subchorionic. It may resemble an infarct or an intervillous thrombus.\nPlacenta Accreta.\u2002 Areas of disruption and/or attached smooth muscle (myometrium) may be \nattached to the maternal surface. These areas should be sampled with four additional sections of the \ndisrupted maternal surface.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Umbilical cord: Two cross sections\n\t\u2022\t \u0007Membranes: One membrane roll\nIn cases of intrauterine growth retardation, pre-eclampsia (hypertension), diabetes, or lupus erythe\u00ad\nmatosus, submit one additional membrane roll.\n\t\u2022\t \u0007Placenta: Three full thickness sections (make sure the fetal surface/chorionic plate vessels are repre\u00ad\nsented). If there is a suspicion of placenta accreta, submit an additional four sections of the disrupted \nmaternal surface.\n\t\u2022\t \u0007Lesions: Submit additional sections of any gross lesions\n\t\u2022\t \u0007Multiple gestations: Submit separate sections as above for each placenta. In addition, submit one \nmembrane roll of the dividing membranes.\nSAMPLE DICTATION\nPlacentas are most easily dictating using a standard template (Fig. 22-10).\nExamples of gross summaries:\n\t \u2022\t \u0007A 160 gram singleton placenta with diffuse infarctions\n\t \u2022\t \u0007A 410 gram singleton placenta with a succenturiate lobe and a 3 cm area of intramembranous \u00advessels\n\t \u2022\t \u0007An 800 gram diamnionic monochorionic fused twin placenta without superficial or deep vascular \nanastomoses\n\t \u2022\t \u0007A 500 gram green singleton placenta\nGraphs relating umbilical cord length to gestational age and placental weight to gestational age and \ncrown-rump length are available in Langston, et al.2 Placental weight standards are given in Table 22-17.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_482.png", "summary": "The page discusses various findings in products of conception, including intervillous thrombus, retroplacental hematoma, subchorionic fibrin deposition, chorangioma, and placenta accreta.", "questions": [ "How can the age of a retroplacental hematoma be estimated?", "What are the potential associations of retroplacental hematoma?", "What are the key features of chorangioma?", "Why is it important to sample areas of disruption and attached smooth muscle in placenta accreta?", "What additional sections should be submitted in cases of multiple gestations?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 483, "text": "Placenta type\n \n1. \nSingleton\n \n2. \nDiamniotic, dichorionic separated twin placenta\n \n3. \nDiamniotic, dichorionic fused twin placenta\n \n4. \nDiamniotic, monochorionic twin placenta\n \n5. \nMonoamniotic, monochorionic twin placenta\n \n6. \nTriplet placenta (describe)\n \n7. \nOther (describe)\n \nIf a multiple gestation placenta is examined, give each placenta a designation (e.g., one or\n \ntwo clamps or arbitrarily \u201cA\u201d and \u201cB\u201d) and dictate each placenta separately.\nCord\n \nLength: _____________ cm.\n \nInsertion: central/eccentric/marginal/membranous/unknown\n \nNumber of vessels: two arteries and a vein/other (describe)\n \nCord twist: left (most common)/right/none; # of twists per 10 cm\n \nOther findings:\nMembranes\n \nInsertion: ____________ % marginal/ _____________ % circummarginate/ \n \n_____________% circumvallate\n \nColor: normal/green/opaque/other\n \nPoint of rupture: ____________ cm from edge of disc\n \nOther findings:\nDisc\n \nWeight: ____________ gm ____________ (Combined weight if a multigestation placenta)\n \nSize: ____________ \u001f ____________ \u001f ____________ cm\n \nSubchorionic fibrin: normal/patchy (1\u20132 nodules)/extensive (3 or more nodules)\n \nRetroplacental hemorrhage: absent/present (describe size, old or recent, location)\n \nInfarcts: absent/present (describe size, central or marginal, % of parenchyma infarcted)\n \nIntervillous thrombi: absent/present (describe size, location, laminated or nonlaminated)\n \nOther findings:\nSpecial studies\n \nEvaluation of vascular anastomoses\n \nTissue saved for cytogenetic analysis, cultures, or metabolic analysis\nGross summary\n \nA single sentence summarizing the above findings.\nFigure 22\u201310.\u2002 Placental template for dictation.\nTABLE 22\u201317.\u2003\nPLACENTAL WEIGHT STANDARDS\nGESTATIONAL \nAGE (WEEKS)\nSINGLETONS PERCENTILES\nTWINS (COMBINED WEIGHT) PERCENTILES\n10\n25\n50\n75\n90\n10\n25\n50\n75\n90\n12\n56\n14\n83\n16\n110\n18\n137.8\n20\n145\n166\n190\n218\n245\n270\n22\n122\n138\n157\n176\n191\n191\n219\n251\n282\n310\n24\n145\n166\n189\n212\n233\n232\n267\n307\n346\n382\n26\n175\n200\n227\n255\n280\n284\n330\n380\n430\n475\n28\n210\n238\n270\n302\n331\n345\n401\n464\n527\n584\n30\n249\n281\n316\n352\n384\n409\n478\n554\n631\n700\n32\n290\n325\n364\n403\n438\n472\n554\n644\n734\n815\n34\n331\n369\n411\n453\n491\n531\n624\n727\n830\n923\n36\n372\n412\n457\n501\n542\n582\n684\n798\n912\n1014\n38\n409\n452\n499\n547\n589\n619\n728\n850\n972\n1082\n40\n442\n487\n537\n587\n632\n638\n753\n879\n1005\n1118", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_483.png", "summary": "This page outlines the different types of placentas, including those in multiple gestations, and provides a template for dictation of placental findings.", "questions": [ "What are the different types of placentas mentioned in the text?", "How should each placenta be designated and dictated if a multiple gestation placenta is examined?", "What are some of the key findings to be noted in the evaluation of the placenta?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 484, "text": "466\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Products of Conception\nPRODUCTS OF CONCEPTION\nProducts of conception (POC) are not considered routine surgical specimens by the woman, the family, \nor the law. These tissues represent the death of a potentially separate individual. Clinicians should be \ninformed about the routine procedure of specimen evaluation and disposal in order that this information \ncan be conveyed to the parents.\nState law will vary and must be consulted for specific requirements. In Massachusetts, fetal deaths that \nrequire a birth certificate and death certificate include any fetus of 20 weeks gestation or more, any fetus \nweighing 350 grams or more, or any fetus showing signs of life at birth. If the fetal death is the result \nof an induced abortion, the death need not be reported. However, if the fetus shows signs of life (at any \ngestational age or weight), the death must be reported.\nIf the POC is considered a fetal death, permission must be obtained before an autopsy can be per\u00ad\nformed. It is preferable to obtain permission from both parents. The parents may wish to view the fetus. \nThis should be done prior to the performance of the autopsy. A death certificate is required.\nTypes of POCs and Reasons for Examination\nSpontaneous abortions (SABs)\n\t\u2022\t \u0007First trimester \u201closses\u201d (missed abortion, empty sac, blighted ovum). The most common cause is a \nchromosomal abnormality. Fetal tissues are often not present.\n\t\u2022\t \u0007Second trimester miscarriages. Potential causes include incompetent cervix, preterm labor, intrauter\u00ad\nine fetal demise, structural malformations, and infections.\n\t\u2022\t \u0007Recurrent pregnancy loss (>2 losses at any gestational age).\nThese tissues are usually passed per vagina or removed by endometrial curettings. Examination of the \ntissues can document the site of the pregnancy, determine the etiology of the loss, and can obtain tissue \nfor special studies.\nTherapeutic abortions (TABs)\nThese abortions may be performed for several reasons:\n\t \u2022\t \u0007Social (maternal request for legal termination of pregnancy)\n\t \u2022\t \u0007Maternal indications (severe diseases exacerbated by pregnancy)\n\t \u2022\t \u0007Fetal indications (structural or chromosomal ano\u00admalies)\nExamination can verify the involvement of maternal disease in the gestational tissue and verify fetal \nanomalies.\nEctopic pregnancies\nWomen present with a first trimester pregnancy with pain and bleeding and an abnormal rise or fall in \nserum \u03b2-HCG levels. Endometrial curettings will be performed to identify chorionic villi or placental \nimplantation to document an in utero pregnancy (see also Chapter 6). If such a pregnancy cannot be \ndocumented, an ectopic pregnancy is likely and pelviscopy may be indicated.\nMolar pregnancies\nWomen present with an abnormally enlarged uterus and elevated \u03b2-HCG for gestational age. \u00adUltrasound \nreveals a cystic intrauterine mass. Examination can determine if the mole is partial or complete.\nPROCESSING THE SPECIMEN\nThese specimens should always be submitted fresh. This will allow possible special studies to be per\u00ad\nformed including karyotype analysis and microbiologic culture. It is also much easier to identify villi in \nfresh tissue.\nSpecimens are of three types:\n \n1.\t \u0007POCs without recognizable fetal parts\n \n2.\t \u0007POCs with a fetus <12 weeks of age\n \n3.\t \u0007POCs with a fetus >12 weeks of age", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_484.png", "summary": "Products of conception are not routine surgical specimens and represent the death of a potentially separate individual. State laws vary regarding requirements for fetal deaths.", "questions": [ "What are the criteria for a fetal death that require a birth certificate and death certificate in Massachusetts?", "Why is it important to obtain permission before performing an autopsy on a product of conception considered a fetal death?", "What are the reasons for performing therapeutic abortions and how can examination of the gestational tissue help in these cases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 485, "text": "467\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Products of Conception\nPROCESSING POCS WITHOUT RECOGNIZABLE FETAL PARTS\n 1.\t \u0007Decant the tissue into a container that will allow fluid to drain. If fetal tissues are identified, follow one \nof the subsequent protocols according to fetal age.\n 2.\t \u0007If villous tissue is clearly identified, process one cassette of villous tissue and save the remaining tissue \nin \u00adformalin.\nVilli can be identified by floating the specimen in saline in a petri dish and observing the tissue \nusing a dissecting microscope. Blood may need to be rinsed away. Villi are usually white (but may \nbe pink) and have acute angle branching. When gently squeezed with a forceps, villi will rapidly re-\nexpand when released. Decidualized endometrium is usually pink (but may be white) and more opaque \nthan villi. Endometrial tissue can have glandular and vascular structures that can be mistaken for villi. \nThese structures run in parallel (i.e., are not branched) and do not have the springy quality of villi.\nIf an ectopic pregnancy is suspected clinically, all tissue should be processed including the blood. \nThese specimens will often be evaluated as an OR consultation (see Chapter 6).\nIf hydropic villi are present (any villous structures of 1 cm or more), whether or not fetal tissue \nis present, the specimen should be evaluated as a possible molar pregnancy. Tissue may be sent for \nploidy studies (analytical cytometry; complete = diploid or tetraploid; partial = triploid) or may be \ncultured for karyotype analysis. Villi and fetal tissues must be sent separately for analysis. Photographs \nmay be useful. Five to ten cassettes of tissue should be processed.\nComplete moles are recognizable by multiple tiny thin-walled fluid filled vesicles. Look for them \ncarefully, as they are often not suspected clinically. Fetal parts are not present (unless there is a non\u00ad\nmolar twin). Partial moles may have fetal tissues and scattered vesicles as well, but may not be rec\u00ad\nognized until examined microscopically. If suspected, look for syndactyly of fingers or toes which is \nassociated with triploidy.\nPROCESSING POCS WITH EMBRYONIC OR FETAL TISSUE IDENTIFIED, <12 WEEKS\n 1.\t \u0007Obtain standard measurements (crown-rump, foot length, or hand length).\n 2.\t \u0007Evaluate for developmental stage (Table 22-18).\n 3.\t \u0007Evaluate for anomalies. A complete dissection is not necessary. Gross anomalies will usually be easily \n\u00adidentified with careful visual inspection. A single incision can be performed to check for normal situs. \nIf warranted or requested (e.g., anomalies known or suspected by prenatal ultrasound), dissection can \nbe performed with the aid of a dissecting microscope.\n 4.\t \u0007Sterile tissue may be saved for karyotype analysis if a chromosomal abnormality is suspected (see Spe\u00ad\ncial Studies).\n 5.\t \u0007Submit the embryonic tissue (longitudinal section or coronal sections of calvarium, thorax, abdomen, \npelvis) and villous tissue.\nTABLE 22\u201318.\u2003 TIMETABLE OF FETAL MORPHOGENESIS\nGESTATIONAL AGE (WEEKS)\nFOOT LENGTH\nCHARACTERISTICS\n6\nDigital rays in hand plate, paddle limbs\n7\nRetinal pigment, foot plates\n8\nDigital rays in feet, elbow\n9\nFingers\n10\nToes, gut herniation \u00ad(physiologic omphalocele)\n11\n7 mm\nEyes closing/closed\n12\n9 mm\nIntestines in abdomen, fingernails\n14\n14 mm\nGender identifiable by \u00adexternal examination\n16\n20 mm\nToenails", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_485.png", "summary": "The page discusses the processing of products of conception without recognizable fetal parts and with embryonic or fetal tissue identified, providing guidelines for handling and evaluating the specimens.", "questions": [ "What are the specific steps involved in processing products of conception without recognizable fetal parts?", "How can villous tissue be identified and differentiated from decidualized endometrium?", "What are the key considerations when processing products of conception with embryonic or fetal tissue identified?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 486, "text": "468\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Products of Conception\nIf the procedure was a therapeutic abortion without known or suspected fetal anomalies, and the \ngross examination does not reveal any abnormalities, then tissue need not be examined histologi\u00ad\ncally.\nPROCESSING POCS WITH EMBRYONIC OR FETAL TISSUE IDENTIFIED, >12 WEEKS\nFragmented POCs.\u2002 A thorough examination of the tissues is required.\n 1.\t \u0007Separate the solid tissues from blood. Use a sieve or separate by hand. Do not add tap water as it will \ndamage the tissues.\n 2.\t \u0007Examine all solid tissues.\n 3.\t \u0007Identify the major skeletal parts:\n\t \u2022\t \u0007Four extremities\n\t \u2022\t \u0007Spinal column\n\t \u2022\t \u0007Skull/base\nExamine for number of digits, nail development, palmar creases, edema, etc. Measure foot and/or \nhand length (heel to great toe/wrist to middle finger).\n 4.\t \u0007Examine all organs or possible organs including placental tissues, umbilical cord (check number of \nvessels). Weigh organs if they are reasonable complete. Dissect the heart if possible.\n 5.\t \u0007Describe normal and abnormal findings.\n 6.\t \u0007Consider karyotypic analysis if anomalies are present or cultures if infection is suspected.\n 7.\t \u0007Submit representative sections of organs and skeleton.\nSample Dictation.\u2002 The specimen is received fresh, labeled with the patient\u2019s name and unit number \nand \u201cPOC,\u201d and consists of multiple fragments of fetal and placental tissues and blood in a stockinette \n(in aggregate 10 \u00d7 5 \u00d7 1 cm). All four extremities are present and include a right foot length of 12 mm \nand a right hand length of 10 mm. There is no syndactyly, polydactyly, or abnormal palmar creases. The \nnail development is normal. A portion of the vertebral column and a fragment of calvarium are intact. \nThe right ear is present and is formed normally. Both eye globes are present. The fragmented calvarium \nreveals an intact hard palate. Fetal organs and tissues are present and include a relatively intact heart (1.3 \ngrams), fragments of gastrointestinal tract, two fragmented kidneys, and skin.\nDissection of the heart under a dissecting microscope reveals a small membranous ventricular septal \ndefect and an otherwise structurally normal heart, appropriate for gestational age. The great vessels are \navulsed and, therefore, the ductus arteriosus cannot be evaluated. The placental tissues include a 10 cm \nin length trivascular umbilical cord and fragmented villous and membranous tissues. Representative sec\u00ad\ntions of fetal and placental tissues are submitted in five cassettes.\nPOCs with an Intact Fetus and Placenta.\u2002 Intact fetuses should be examined with the placenta. The \nplacenta is examined as described in the section on placentas.\n 1.\t \u0007Photograph the fetus with anterior, posterior, lateral views. Photograph the face. This photograph \nshould be appropriate to provide to the family if requested.\n 2.\t \u0007Photograph any anomalies or dysmorphism.\n 3.\t \u0007Radiograph the fetus.\n 4.\t \u0007Freeze tissue (liver, skin).\n 5.\t \u0007Save tissue fresh if karyotype analysis is indicated. Usually karyotypic analysis is not indicated if the \nanomaly is hydrocephalus, renal agenesis/dysgenesis, or an isolated neural tube defect.\nIf the fetus is hydropic (ascites, pleural fluid, pericardial fluid) save fluid and tissues for bacterial and \nviral (HSV, parvovirus, CMV) culture.\n 6.\t \u0007Obtain the following measurements:\n\t \u2022\t \u0007Weight\n\t \u2022\t \u0007Crown-rump length (crown to ischial tuberosities, \u201csitting height\u201d)\n\t \u2022\t \u0007Crown-heel length (crown to heal of extended leg)\n\t \u2022\t \u0007Foot length\n\t \u2022\t \u0007Hand length\n\t \u2022\t \u0007Head circumference (above ears - as if wearing glasses)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_486.png", "summary": "The page discusses the processing of products of conception (POCs) with embryonic or fetal tissue identified, including the examination of fragmented POCs and intact fetuses with placenta.", "questions": [ "What are the steps involved in processing fragmented POCs with embryonic or fetal tissue identified?", "What findings should be documented during the examination of solid tissues and organs in POCs?", "Why is it important to photograph the fetus and any anomalies or dysmorphism during the examination of intact fetuses with placenta?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 487, "text": "469\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Products of Conception\n\t \u2022\t \u0007Chest circumference (around nipples)\n\t \u2022\t \u0007Abdominal circumference (at umbilical insertion)\n\t \u2022\t \u0007Inner canthal distance\n\t \u2022\t \u0007Outer canthal distance\n\t \u2022\t \u0007Any other potentially anomalous measurement (e.g., finger, lip, ear)\n 7.\t \u0007Make a generous Y-shaped incision.\nExamine the organs in situ. Photograph any anomalies.\nRemove the thymus and gonads before evisceration. They are small and often difficult to identify after \ndissection.\n 8.\t \u0007Take the block from the tongue (above the larynx at a minimum) to anus. Remove and save the ver\u00ad\ntebral column. Remove the brain (see below) and spinal cord, eyes, and pituitary. CNS tissues are \nfixed overnight. The organ block can be dissected prior to fixation, or fixed overnight if the tissues are \nautolyzed. Before tissues are fixed, ensure that fresh tissue is available for special studies, if needed. It \nis exceptional for fetuses to be embalmed. The body should be maintained in a presentable condition. \nProper respect for the fetus must be maintained during the examination.\n 9.\t \u0007Remove the brain into a large vessel filled with 4% paraformaldehyde that has been weighed previ\u00ad\nously. The brain can be weighed in the container with the fixative. Dissection can be carried out once \nthe brain is well fixed overnight. Identify each cranial nerve.\n 10.\t \u0007Submit the following tissues. More than one tissue can be placed in one cassette.\n\t \u2022\t \u0007Thymus\n\t \u2022\t \u0007Lung \u2013 portion of each lobe\n\t \u2022\t \u0007GI tract \u2013 take cross sections from each region with contents in place - do not open\n\t \u2022\t \u0007Pancreas\n\t \u2022\t \u0007Gonads\n\t \u2022\t \u0007Bivalved kidneys and adrenals (right and left)\n\t \u2022\t \u0007Cross section of neck at thyroid with trachea and esophagus\n\t \u2022\t \u0007Skin\n\t \u2022\t \u0007Skeletal muscle\n\t \u2022\t \u0007Vertebral column (after fixation and decalcification)\n\t \u2022\t \u0007Pituitary (fixed in situ and decalcified)\n\t \u2022\t \u0007Eye \u2013 cross section (right and left)\n\t \u2022\t \u0007Brain \u2013 include lateral ventricles, cerebellum, and brain stem\nThe following sections are optional:\n\t \u2022\t \u0007Longitudinal section of long bone (if skeletal dysplasia is suspected)\n\t \u2022\t \u0007Rib or sternum\n\t \u2022\t \u0007Nuchal region (if thickened or cystic hygroma)\n\t \u2022\t \u0007Bladder\n\t \u2022\t \u0007Prostate\nSample Dictation.\u2002 Received fresh and intact is a phenotypically female fetus with a fresh weight \nof 258 grams. There is mild skin maceration with slippage over approximately 10% of the surface. \nThe calvarial bones are not disarticulated. External examination reveals a well-developed female fetus \nwith:\n\t \u2022\t \u0007Two eyes with fused lids\n\t \u2022\t \u0007Small, anteverted nose with patent nares\n\t \u2022\t \u0007Intact lip and palate\n\t \u2022\t \u0007Slightly recessed chin\n\t \u2022\t \u0007Normally formed ears\n\t \u2022\t \u0007No nuchal thickening\n\t \u2022\t \u0007Two nipple buds\n\t \u2022\t \u0007Sternum ends approximately half the distance from nipple line to umbilicus\n\t \u2022\t \u0007No hip disarticulation\n\t \u2022\t \u0007Intact vertebral column\n\t \u2022\t \u0007Five digits on all extremities with no syndactyly or abnormal creases\n\t \u2022\t \u0007Patent vagina and anus\n\t \u2022\t \u0007No abnormal joint contractures", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_487.png", "summary": "This page provides detailed instructions on the examination and dissection of a fetus, including the removal of organs, submission of tissues for analysis, and maintaining respect for the fetus during the process.", "questions": [ "What is the purpose of removing specific organs before evisceration?", "Why is it important to maintain the body in a presentable condition?", "What special studies might require fresh tissue from the fetus?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 488, "text": "470\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Products of Conception\nGross measurements:\n\t \u2022\t \u0007Weight\n\t \u2022\t \u0007Crown-rump length\n\t \u2022\t \u0007Crown-heel length\n\t \u2022\t \u0007Foot length\n\t \u2022\t \u0007Hand length\n\t \u2022\t \u0007Head circumference\n\t \u2022\t \u0007Chest circumference\n\t \u2022\t \u0007Abdominal circumference\n\t \u2022\t \u0007Inner canthal distance\n\t \u2022\t \u0007Outer canthal distance\nGross photographs are taken of the face, anterior, posterior, and lateral views.\nA standard Y incision is made. There is approximately 3 cc of serous fluid in the abdomen. No thoracic \nor pericardial fluid is present. The in situ examination reveals the heart pointing to the left, the stomach \nand one spleen in the upper left abdomen, liver and gall bladder in right upper abdomen, and the appen\u00ad\ndix in the right sidewall. The thymus is mediastinal. The diaphragms are intact.\nEvisceration is performed from the tongue to anus without difficulty. The trachea and esophagus \nare probed to reveal no atresias or fistulas. Both kidneys are present with normal fetal lobulations. Both \nadrenal glands are present and normally placed. The internal genitalia are female and appear grossly \nnormal.\nDissection reveals three lobes of the right lung and two lobes of the left lung. The heart receives the \npulmonary veins in the left atria and superior and inferior vena cava in the right atrium. The great ves\u00ad\nsels are normally related. Opening the heart reveals an intact atrial septum with a patent and competent \nvalve of the foramen ovale. There is a persistence of the left superior vena cava draining into an enlarged \ncoronary sinus. The inflow into the right ventricle is normal with a normal tricuspid valve. The right \nventricular chamber is normal. The pulmonary valve is tricuspid. The left and right pulmonary arteries \nare patent and appear normal. The ductus arteriosis is patent into the descending aorta. The left atria, \nleft ventricular inflow, and mitral valves are normal. There is a ventricular septal defect in the membra\u00ad\nnous septum with extension anteriorly into the conal septum. The aortic valve is tricuspid with normally \nplaced coronary ostia. The aortic arch and branches are normal.\nThe esophagus empties into a stomach with scant mucous contents. The small and large bowel are \nnormal with no atresias, volvuli, or diverticula. The large bowel contains meconium.\nBoth kidneys have normal fetal lobulations and their pelvises are not dilated. The ureters connect to \nan empty bladder. The adrenal glands are normal and without hemorrhage. The liver has many subcap\u00ad\nsular petechial hemorrhages. The spleen and pancreas are normal in appearance.\nOrgan weights:\n\t \u2022\t \u0007Thymus\n\t \u2022\t \u0007Lungs (combined)\n\t \u2022\t \u0007Heart\n\t \u2022\t \u0007Liver\n\t \u2022\t \u0007Spleen\n\t \u2022\t \u0007Adrenals (combined)\n\t \u2022\t \u0007Kidneys (combined)\nThe vertebral column is removed. The spinal cord appears normal. The calvarium is opened. The \nbrain in situ reveals scant subdural hemorrhage over the convexities. The corpus callosum is present. \nThe brain and spinal cord are removed intact and fixed. The brain appears normal for gestational age. \nThe pituitary gland is removed with the sella and is fixed and decalcified. Both orbits are removed using \nan interior approach.\n\t \u2022\t \u0007Brain weight\nTissue from the placenta and skeletal muscle were sent for cytogenetic analysis. A portion of the \nright lung was sent for microbiological culture. A portion of the skin and liver were frozen in liquid \nnitrogen.\nThe fetus is fixed and returned to the specimen cabinet.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_488.png", "summary": "The page describes the gross measurements and examination findings of products of conception, including organ weights and anatomical details.", "questions": [ "What specific measurements are taken during the examination of products of conception?", "What are some of the key findings in the examination of the heart and other organs?", "Are there any abnormalities or pathologies noted in the examination of the products of conception?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 489, "text": "471\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 Products of Conception\nSPECIAL STUDIES\nExamination of Fetuses with Known or Suspected Anomalies.\u2002\nExamine the fetus for the following external features:\n\t\u2022\t \u0007Nuchal thickening: associated with trisomy 21 or monosomy X. Take a section through neck skin and \nsend for chromosome analysis.\n\t\u2022\t \u0007Cleft palate/lip: associated with trisomy 13. Send for chromosome analysis.\n\t\u2022\t \u0007Skin edema, dorsal pedal edema: associated with hydrops, monosomy X. Cultures may be taken to \nevaluate possible infection.\n\t\u2022\t \u0007Syndactyly: associated with triploidy and partial mole. Examine placenta carefully.\n\t\u2022\t \u0007Polydactyly: associated with trisomy 13.\n\t\u2022\t \u0007Short sternum: normally the sternum reaches halfway between the internipple distance and the umbi\u00ad\nlicus. A\u00a0short sternum is associated with trisomy 18.\n\t\u2022\t \u0007Ambiguous genitalia: most female fetuses have a large clitoris which can easily be confused with a phal\u00ad\nlus. Look carefully to see if the labia/scrotum are fused, indicating a male fetus. Describe the external \ngenitalia as being \u201cmale,\u201d \u201cfemale,\u201d or \u201cambiguous,\u201d but don\u2019t assign a sex to the fetus without first \nidentifying the gonads.\n\t\u2022\t \u0007Skeletal anomalies: short limbs or fractures. Make sure to get the history and radiographs. Submit \nbone sections (long bones, ribs, and vertebrae). All bony parts should be x-rayed. Arrange the bony \nstructures on the film in their anatomic positions.\n\t\u2022\t \u0007Other features: Number of hair whorls (there should be one, more than one suggests problems in brain gen\u00ad\nesis), dimples over the lumbosacral regions (spina bifida), abnormal hand/feet position (clenching = arthro\u00ad\ngryposes and neural problems; short dorsiflexed great toe or thumb/little finger overlap = trisomy 18; valgus \ndeformities of lower limbs = Potter\u2019s syndrome), protuberant tongue (Beckwith-Wiedemann syndrome).\nExamine the fetus for the following internal features:\n\t\u2022\t \u0007Shape of liver: the gallbladder should be to the right of the umbilical vein and the slope should be up \nto the left.\n\t\u2022\t \u0007Heart: anomalies\n\t\u2022\t \u0007Spleen: polysplenia or asplenia suggest visceral heterotaxy and associated cardiac abnormalities.\n\t\u2022\t \u0007Kidneys: Shape (horseshoe), bifid, cystic, absent.\n\t\u2022\t \u0007Adrenals: medullary hemorrhage (associated with infection, take cultures).\n\t\u2022\t \u0007Lobation of the lungs.\n\t\u2022\t \u0007Presence of thymus.\n\t\u2022\t \u0007Gonads and uterus.\n\t\u2022\t \u0007Diaphragm: make sure it is intact without herniations.\n\t\u2022\t \u0007Appendix: should be in the right lower quadrant.\n\t\u2022\t \u0007Tracheoesophageal fistula; anal atresia (check for patency with a probe)\n\t\u2022\t \u0007Meckel diverticulum\nChromosomal Analysis.\u2002\nKaryotype analysis may be helpful in the following cases:\n\t\u2022\t \u0007Two or more consecutive spontaneous abortions.\n\t\u2022\t \u0007Developmental stage is significantly discrepant from the clinical estimate of gestational age (severe \nintrauterine growth retardation).\n\t\u2022\t \u0007One or more malformations (isolated neural tube defects and renal agenesis/dysgenesis are possible \nexceptions).\n\t\u2022\t \u0007Ambiguous genitalia after 13 weeks.\nUsing sterile technique, remove a small sample of skin and one other tissue (e.g., lung or placenta). If \nthe embryonic tissue is macerated, portions of placental tissue may be used.\nPATHOLOGIC DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR PRODUCTS OF CONCEPTION\n\t\u2022\t \u0007State: Intact or fragmented, macerated or well preserved\n\t\u2022\t \u0007Gender: Male, female, intersex, or not determined", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_489.png", "summary": "This page discusses the special studies and examinations to be conducted on fetuses with known or suspected anomalies, including external and internal features to look for and the importance of chromosomal analysis.", "questions": [ "What are some external features that can be indicative of specific chromosomal abnormalities in a fetus?", "Why is it important to examine both external and internal features of a fetus with anomalies?", "In what situations is karyotype analysis recommended for fetal evaluation?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 490, "text": "472\nGYNECOLOGIC AND PERINATAL PATHOLOGY\u2003 References\n\t\u2022\t \u0007Estimated gestational age: Crown-rump length, foot length, estimated age\n\t\u2022\t \u0007Organs examined: List all organs examined and if normal or abnormal for gestational age\n\t\u2022\t \u0007Congenital anomalies: Present or absent, describe\n\t\u2022\t \u0007Placenta : List relevant features (e.g., mature or immature, umbilical cord normal or abnormal, infec\u00ad\ntion present or absent)\n\t\u2022\t \u0007Karyotype: Indicate if tissue was sent for analysis\nREFERENCES\n\t1.\t \u0007Kurman RJ, Norris HJ. Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-\ndifferentiated carcinoma. Cancer 49:2547-2559, 1982.\n\t2.\t \u0007Roberts DJ. Placental pathology, a survival guide. Arch Path Lab Med 132(4):641-651, 2008.\n\t3.\t \u0007Bajoria R, Wigglesworth J, Fisk NM. Angioarchitecture of monochorionic placentas in relation to the twin-twin \ntransfusion syndrome. Am J Obstet Gynecol 172:856-863, 1995.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_490.png", "summary": "This page discusses the examination of gynecologic and perinatal pathology, including estimation of gestational age, examination of organs for abnormalities, presence of congenital anomalies, placental features, and indication for karyotype analysis.", "questions": [ "How are gestational age estimates determined using crown-rump length and foot length?", "What are some examples of congenital anomalies that may be present in gynecologic and perinatal pathology?", "Why is it important to examine the placenta for features like maturity, umbilical cord abnormalities, and presence of infection?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 491, "text": "473\n23\nHead and Neck\nSINUS CONTENTS\nFunctional endoscopic sinus surgery (FESS) is used as a treatment for patients with chronic sinusitis who \nhave not responded to medical therapy. The contents of the sinuses are examined and obstructing areas \nand polyps are removed. A subset of these patients may have allergic sinusitis. If allergic mucin consisting \npredominantly of eosinophils and Charcot-Leyden crystals is seen histologically, special stains for fungi \nshould be performed to look for the hyphae of Aspergillus. Allergic sinusitis must be distinguished from \nobstructive aspergillosis (\u201cfungal ball\u201d) and invasive fungal disease.1-4\nPROCESSING THE SPECIMEN\n 1.\t \u0007The specimen consists of multiple minute fragments of bone and soft tissue. Describe color and \naggregate size. If polyps are present, see following section.\n 2.\t \u0007The specimen will generally need to be decalcified.\n 3.\t \u0007Submit a representative section of the tissue in one cassette including mucin if present. If a portion of \ngrossly normal nasal septum is submitted, it can be described but not examined histologically.\nNASAL POLYPS\nThe most common specimen consists of inflammatory nasal polyps. These polyps look like translucent, \ngelatinous, rounded masses ranging from 0.5 to 3 cm in diameter. The cut surface is homogeneous grey \nor pink. Small cystic areas may be present and areas of chronic inflammation appear as white patches. \nCalcification or bone may be found and if present must be decalcified before submission. If large, the \npolyps may be bisected and half of each one submitted.\nPolyps consisting of firm dense white tissue may be neoplastic. Benign (but locally aggressive) papil\u00ad\nlomas or squamous cell carcinomas can occur in the nasal passages. Attempt to identify the base of firm \npolyps and submit as a separate section, if possible, as well as thoroughly sample the lesion.\nORAL CAVITY/TONGUE RESECTIONS\nThese are often large resections that may include a portion of the mandible and teeth. Such resections are \nalmost always performed for invasive squamous cell carcinomas. These specimens are often accompanied \nby a radical neck dissection (see below). Lip resections are discussed under Dermatopathology.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Identify structures present including bone, teeth, mucosal surfaces, palate, tongue, muscle. Anatomi\u00ad\ncally complex specimens should be reviewed with the surgeon before processing. Record measure\u00ad\nments for each component. Major nerves or vessels should be identified by the surgeon.\nIf there is any clinical or gross suspicion of bone invasion, the specimen is radiographed.\n 2.\t \u0007Describe the lesion including location, size, invasion into adjacent structures, and distance from margins.\nSquamous cell carcinomas are usually raised irregular lesions with central ulceration. If the patient \nhas received prior irradiation, the lesion may be difficult to define and persist predominantly as a firm \nulcerated area.\n 3.\t \u0007Take sections of the lesion demonstrating relationship to mucosal and soft tissue margins and deepest \nextent of invasion. Margins are taken as perpendicular sections.\nSample all margins not included in above.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_491.png", "summary": "Functional endoscopic sinus surgery (FESS) is used to treat chronic sinusitis, with a focus on examining sinus contents and removing obstructing areas and polyps. Special stains for fungi should be performed if allergic mucin is present.", "questions": [ "How is FESS different from traditional sinus surgery?", "What are the key histological features that distinguish allergic sinusitis from obstructive aspergillosis?", "What are the considerations for processing specimens of nasal polyps?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 492, "text": "474\nHEAD AND NECK\u2003 Oral Cavity/Tongue Resections\n 4.\t \u0007After all soft tissue sections have been removed, the bone can be decalcified.\nIf there is possible bone invasion take sections demonstrating closest approach of tumor to bone. Also \ntake the bone margins.\nIf there is no gross, radiologic, or clinical suspicion of bone invasion, the only bone submitted may be \nthe margins.\nSPECIAL STUDIES\nSquamous cell carcinomas. Some head and neck squamous cell carcinomas (especially tonsillar car\u00ad\ncinomas in young patients (<40) with nonkeratinizing basal cell morphology) are associated with HPV. \nThese carcinomas are strongly positive for p16. HPV can be identified by PCR on formalin-fixed tissue.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Lesion: One to five sections demonstrating relationship to margins.\n\t\u2022\t \u0007Margins: Mucosal and soft tissue margins not included in the prior specimens.\n\t\u2022\t \u0007Bone: Margins and any areas with suspicion of invasion by tumor. Teeth are described grossly unless \nabnormal or thought to be involved by tumor.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cComposite resection,\u201d is a resec\u00ad\ntion specimen (12.5 \u00d7 10. 5 \u00d7 6.2 cm) consisting of left mandibular ramus (7 \u00d7 6 \u00d7 0.6 cm) containing \nthree molars, base of tongue (3.9 \u00d7 3.4 \u00d7 1.9 cm), floor of mouth (5.5 \u00d7 3.5 \u00d7 0.6 cm), soft tissue on the \nexternal portion of the ramus (6.5 \u00d7 2.6 \u00d7 1.2 cm), and soft tissue posterior and lateral to the base of the \ntongue (3.5 \u00d7 3.8 \u00d7 1.6 cm). A raised irregular white/tan tumor mass (4.8 \u00d7 3.5 \u00d7 1.9 cm in depth) is pres\u00ad\nent involving the soft tissue at the base of the tongue, extends into and through the bone, and is present \nin the soft tissue external to the bone. The tumor invades into the muscle of the tongue. The margins of \nresection are grossly free of tumor. The tumor is 0.3 cm from the lateral mucosal margin, 0.8 cm from \nthe posterior mucosal margin, 0.8 cm from the medial mucosal margin, and 0.5 cm from the anterior \nmucosal margin. The tumor is 0.5 from the inferior soft tissue margin at the base of the tongue and \n0.4\u00a0cm from the soft tissue margin in the external soft tissue to the ramus.\nThe specimen is radiographed and an irregular trabecular pattern is seen in the area of gross tumor \ninvolvement. The bone is fixed and decalcified prior to histologic sectioning.\nCassette #1: Anterior mucosa and tumor, perpendicular margin, 1 frag, RSS.\nCassette #2: Medial mucosa and tumor, perpendicular margin, 1 frag, RSS.\nCassette #3: Lateral mucosa and tumor, perpendicular margin, 1 frag, RSS.\nCassette #4: Posterior mucosa and tumor, perpendicular margin, 1 frag, RSS.\nCassette #5: Deepest extent of tumor at base of tongue, perpendicular margin, 1 frag, RSS.\nCassette #6: Tumor and bone, 1 frag, RSS.\nCassette #7: Tumor and soft tissue external to ramus, 1 frag, RSS.\nCassette #8: Bone, proximal margin, en face, 1 frag, ESS.\nCassette #9: Bone, distal margin, en face, 1 frag, ESS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR ORAL CAVITY AND TONGUE TUMORS\n\t\u2022\t \u0007Specimen: Lip (vermilion border, mucosa, commissure, upper or lower), tongue (lateral, ventral, dor\u00ad\nsal, anterior two thirds), gingiva (upper, lower), anterior floor of mouth, floor of mouth, hard palate, \nbuccal mucosa, vestibule of mouth (upper, lower), alveolar process (upper, lower), mandible, maxilla\n\t\u2022\t \u0007Procedure: Excisional biopsy, glossectomy, mandibulectomy, maxillectomy, palatectomy, lymph \nnode dissection,\n\t\u2022\t \u0007Specimen Integrity: Intact, fragmented\n\t\u2022\t \u0007Specimen Size: Greatest dimension (other dimensions optional)\n\t\u2022\t \u0007Specimen Laterality: Right, left, bilateral, midline\n\t\u2022\t \u0007Tumor Site: Lip (vermilion border, mucosa, commissure, upper or lower), tongue (lateral, ventral, \ndorsal, anterior two thirds), gingiva (upper, lower), anterior floor of mouth, floor of mouth, hard", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_492.png", "summary": "This page discusses the process of decalcifying bone in oral cavity/tongue resections, special studies for squamous cell carcinomas, and the microscopic sections to be examined.", "questions": [ "How is bone decalcification performed in oral cavity/tongue resections?", "What special studies are recommended for squamous cell carcinomas in the head and neck region?", "What specific sections are included in the microscopic examination of the resected specimen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 493, "text": "HEAD AND NECK\u2003 Radical Neck Dissection\n475\npalate, buccal mucosa, vestibule of mouth (upper, lower), alveolar process (upper, lower), mandible, \nmaxilla\n\t\u2022\t \u0007Tumor Focality: Single focus, multifocal (specify number)\n\t\u2022\t \u0007Tumor Size: Greatest dimension (other dimensions optional)\n\t\u2022\t \u0007Tumor Thickness: Give thickness in mm. This is important for small (T1 or T2) oral squamous cell \ncarcinomas.\n\t\u2022\t \u0007Surface ulcerated, or not ulcerated\n\t\u2022\t \u0007Tumor Description: Polypoid, exophytic, endophytic, ulcerated, sessile\n\t\u2022\t \u0007Histologic Type: Squamous cell carcinoma, minor salivary gland carcinoma, other rare types\n\t\u2022\t \u0007Histologic Grade: Well, moderate, poor\n\t\u2022\t \u0007Tumor Extension: Depth of invasion (see below), invasion into adjacent structures (bone, skin, \n\u00admuscle)\n\t\u2022\t \u0007Margins: Not involved, involved by invasive carcinoma or carcinoma in situ (includes moderate and \nsevere dysplasia). Give distance from closest margin.\n\t\u2022\t \u0007Mucosal, soft tissue, bone\n\t\u2022\t \u0007Treatment Effect: Not identified, present\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Lymph Nodes: Number and location of involved lymph nodes, size of metastatic deposits, extracap\u00ad\nsular invasion\n\t\u2022\t \u0007Tumor Necrosis: Present or absent, extent\n\t\u2022\t \u0007Additional Pathologic Findings: Carcinoma in situ, dysplasia (mild, moderate, severe; keratinizing \nor non-keratinizing), chronic inflammation, radiation atypia, colonization (fungal, bacterial)\n\t\u2022\t \u0007Ancillary Studies: EBV or HPV may be requested by clinicians. HPV-associated oropharyngeal car\u00ad\ncinomas are more frequent in younger patients without a history of tobacco or alcohol use and may \nhave a better prognosis.\n\t\u2022\t \u0007Depth of Invasion: These measurements should be recorded to the nearest millimeter. Depth is not \nused for T classification.\n\t\n\u2022\t \u0007Exophytic tumors: Measure the \u201ctumor thickness\u201d from the surface (A) to the deepest area of \ninvasion (B).\n\t\n\u2022\t \u0007Ulcerated tumors: Measure from the ulcer base (A) to the deepest area of invasion (B), as well as \nfrom the surface of the most lateral extent of the invasive carcinoma (C) to the deepest area (D).\n\t\n\u2022\t \u0007Endophytic tumors: Measure from the perpendicular surface of the invasive squamous cell carci\u00ad\nnoma (A) to the deepest area of invasion (B). The measurement should not be done on tangential \nsections or in lesions without a clearly recognizable surface component.\n\t\n\u2022\t \u0007Depth of invasion of lip and oral cavity tumors: see Figure 23-1.\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 23-1). M0 \nis conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/)and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nRADICAL NECK DISSECTION\nRadical neck dissections are uncommon specimens and are usually performed for squamous cell carci\u00ad\nnoma of the head and neck. Poor prognosis is associated with multiple affected nodes, bilateral vs. unilat\u00ad\neral involvement, extranodal extension, and positive nodes distal from the primary site.\n\t \u2022\t \u0007The standard radical neck dissection includes cervical lymph nodes, sternomastoid muscle, inter\u00ad\nnal jugular vein, spinal accessory nerve, and submaxillary gland; the tail of the parotid may be \nincluded.\n\t \u2022\t \u0007The modified radical neck dissection (functional or Bocca neck dissection) does not include the \nsternomastoid muscle, the spinal accessory nerve, or the internal jugular vein.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_493.png", "summary": "The page provides detailed information on the assessment and reporting of tumors in the head and neck region, including tumor characteristics, histologic features, lymph node involvement, and ancillary studies.", "questions": [ "What are some key factors to consider when describing the tumor characteristics?", "How is the depth of invasion measured for different types of tumors?", "Why is it important to provide T, N, and M classifications for head and neck tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 494, "text": "HEAD AND NECK\u2003 Radical Neck Dissection\n476\nA\nExophytic tumors: Measure the \u201ctumor\nthickness\u201d from the surface (A) to the\ndeepest area of invasion (B).\nUlcerated tumors: Measure from the ulcer\nbase (A) to the deepest area of invasion (B),\nas well as from the surface of the most lateral\nextent of the invasive carcinoma (C) to the\ndeepest area (D).\nEndophytic tumors: Measure from the\nperpendicular surface of the invasive\nsquamous cell carcinoma (A) to the deepest\narea of invasion (B). The measurement\nshould not be done on tangential sections or\nin lesions without a clearly recognizable\nsurface component.\nB\nC\nA\nD\nB \nA\nB\nFigure 23\u20131.\u2002 Depth of invasion of lip and oral cavity tumors\u2002 (From the AJCC Cancer Staging Manual, Sixth Edition. \nNew York, Springer-Verlag, 2002, p 26. Used with the permission of the American Joint Committee on Cancer (AJCC), \n\u00adChicago, Illinois.)\n\t \u2022\t \u0007The extended radical neck dissection includes retropharyngeal, paratracheal, parotid, suboccipital, \nand/or upper mediastinal nodes.\n\t \u2022\t \u0007The regional (partial or selective) neck dissection includes only the nodes of the first metastatic \n\u00adstation.\nThe specific lymph node groups can only be identified without orientation by the surgeon in the stan\u00ad\ndard and extended dissections. Many specimens lack the necessary anatomic landmarks. It is the recom\u00ad\nmendation of American Head and Neck Society that specimens be divided into levels and sublevels by \nthe surgeon and submitted as separate designated specimens.5", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_494.png", "summary": "This page discusses the measurement of tumor thickness for exophytic, ulcerated, and endophytic tumors in radical neck dissections. It also outlines the differences between extended radical neck dissection and regional neck dissection.", "questions": [ "What are the different measurements that need to be taken for exophytic, ulcerated, and endophytic tumors?", "What lymph nodes are included in an extended radical neck dissection?", "Why is it important to divide specimens into levels and sublevels in neck dissections?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 495, "text": "HEAD AND NECK\u2003 Radical Neck Dissection\n477\nPROCESSING THE SPECIMEN\n 1.\t \u0007Identify the type of dissection and record the overall dimensions. If muscle is present, orient the speci\u00ad\nmen and divide the lymph nodes into groups (Fig. 23-2). Call the surgeon if the specimen cannot be \noriented and there are features present that might allow orientation with additional information (e.g., \nsutures, salivary gland, fragments of muscle).\nIf not oriented by the surgeon, the specimen can be thought of as a letter Z. The upper horizontal line \ncontains level I and can be identified by the presence of the submandicular gland, the lower horizontal \nTABLE 23-1.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF TUMORS OF THE LIP AND ORAL CAVITY\nTumor\nTX\nPrimary tumor cannot be assessed\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ\nT1\nTumor 2 cm or less in greatest dimension\nT2\nTumor >2 cm but \u22644 cm in greatest dimension\nT3\nTumor more than 4 cm in greatest dimension\nT4a\nModerately advanced local disease* \nLip: Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or \nskin of face, that is, chin or nose\nOral Cavity: Tumor invades adjacent structures (e.g., through cortical bone [man\u00ad\ndible or maxilla], into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, \npalatoglossus, and styloglossus], maxillary sinus, skin of face).\nT4b\nVery advanced local disease\nTumor invades masticator space, pterygoid plates, or skull base and/or encases inter\u00ad\nnal carotid artery\nNote: Superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify a tumor as T4.\nRegional Lymph Nodes\nNX\nRegional lymph nodes cannot be assessed\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in a single ipsilateral lymph node, \u22643 cm\nN2\nMetastasis in a single ipsilateral lymph node, \u22643 cm but not more than 6 cm in great\u00ad\nest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in \ngreatest dimension; or in bilateral or contralateral lymph nodes, nnone more than \n6 cm in greatest dimension\nN2a\nMetastasis in a single ipsilateral lymph node >3 cm but \u22646 cm\nN2b\nMetastasis in multiple ipsilateral lymph nodes, none >6 cm\nN2c\nMetastasis in bilateral or contralateral lymph nodes, none >6 cm\nN3\nMetastasis in a lymph node >6 cm\nMetastasis\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: This classification does not include nonepithelial tumors.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \nCommittee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_495.png", "summary": "The page discusses the processing of specimens from radical neck dissections, including the identification of type, orientation of muscle, and division of lymph nodes into groups.", "questions": [ "How important is it to properly orient the specimen during processing?", "What are the potential consequences of not being able to orient the specimen?", "How does the presence of muscle in the specimen affect processing and analysis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 496, "text": "HEAD AND NECK\u2003 Radical Neck Dissection\n478\nline level V, and levels II, III, and IV comprise the upper, mid, and lower thirds of the oblique line \ndefined by the sternocleidomastoid muscle.\n 2.\t \u0007Record the dimensions and appearance of the sternocleidomastoid muscle including color and any \nirregular firm areas (possibly representing involvement by tumor). The jugular vein lies deep to this \nmuscle. Record the length, diameter and appearance (color, patency). Open the vein along its length \nand examine for thrombus or tumor involvement. Tumor invasion into the vein is usually found \nonly with extensive nodal disease. The soft tissue deep to the muscle is divided into three groups, \nhigh (level II), mid (level III), and low (level IV) jugular nodes, and placed in three separate labeled \n\u00adcontainers.\n 3.\t \u0007The submandibular region is the area superior to the muscle and contains the submandibular gland. \nRecord its size, consistency, color, and the presence of any lesions. Separate the nonmuscle tissue and \nsave in a separate container (level I).\n 4.\t \u0007The posterior triangle (level V) is the soft tissue inferior to the muscle. Record its dimensions and \nplace all soft tissue in a separate container.\n 5.\t \u0007If gross tumor is present, evaluate the surgical margins around the tumor. \nLymph node groups should be separated and reported using standard terminology as follows:\n\t \u2022\t \u0007Level I: Submental and submandibular lymph nodes\n\t \u2022\t \u0007Level II: Upper jugular lymph nodes\n\t \u2022\t \u0007Level III: Mid jugular lymph nodes\n\t \u2022\t \u0007Level IV: Lower jugular lymph nodes\n\t \u2022\t \u0007Level V: Posterior triangle lymph nodes\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Lymph nodes: Submit representative sections of each lymph node, separated into the five separate \ngroups described above. A typical specimen contains a total of 30 to 40 lymph nodes.\n\t\u2022\t \u0007Submandibular gland: One representative section.\n\t\u2022\t \u0007Muscle and vein: One representative section. If these structures are grossly involved by tumor, submit \none to two sections and specimen margins.\nIII\nII\nI\nIV\nV\nFigure 23\u20132.\u2002 Radical neck dissection.\u2002 (From Noble J [ed]: Textbook of Primary Care Medicine, 3rd ed., St. Louis, Mosby, \n2001.)", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_496.png", "summary": "The radical neck dissection involves the removal of lymph nodes and other structures in the head and neck region, with specific attention to the sternocleidomastoid muscle, jugular vein, submandibular gland, and posterior triangle.", "questions": [ "What are the key structures and areas of focus during a radical neck dissection?", "How is the presence of tumor involvement in the sternocleidomastoid muscle and jugular vein assessed during the procedure?", "Why is it important to separate and evaluate lymph node groups using standard terminology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 497, "text": "HEAD AND NECK\u2003 Salivary Gland\n479\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR RADICAL NECK DISSECTIONS\n\t\u2022\t \u0007Lymph nodes: Number nodes examined, number of involved nodes, location of involved nodes, size \nof metastatic deposits, extracapsular invasion\n\t\u2022\t \u0007Salivary gland: Normal, involvement by tumor, inflammation\n\t\u2022\t \u0007Muscle and vein: Normal, involvement by tumor\nMUCOSAL BIOPSIES\nSmall biopsies are often obtained from the oral cavity, pharynx, or larynx to rule out carcinoma or prema\u00ad\nlignant conditions. These biopsies are usually small unorientable fragments. Diagnostic problems often \ninclude distinguishing reactive atypia from dysplasia and carcinoma in situ in tangential sections from \ninvasive squamous cell carcinoma. Obtain three levels.\nSALIVARY GLAND\nMinor Salivary Gland Biopsy of the Lip\nPatients with Sj\u00f6gren syndrome will often have a labial biopsy of normal-appearing mucosa for diagnosis. \nIt will be a small fragment of tissue that is processed in its entirety. Obtain three levels.\nThe inflammation is scored to determine the likelihood of an autoimmune disease. A \u201cfocus\u201d is defined \nas a lymphoid aggregate containing at least 50 lymphocytes adjacent to normal-appearing mucous acini. \nGerminal centers may be present. Foci are counted per 4 mm2 area of glandular tissue (close to the size \nof the biopsy).\n\t \u2022\t \u0007Scores >1 focus per 4mm2 are diagnostic of autoimmune sialadenitis\n\t \u2022\t \u0007Score = 1 focus per 4mm2 are suggestive\n\t \u2022\t \u0007Scores <1 focus per 4mm2 are nondiagnostic\nUsually the lymphocytes are associated with acinar atrophy and fibrosis; this correlates with the \n\u00adclinical loss of salivary gland function. About 5% of patients with Sjogren\u2019s syndrome will have nondiag\u00ad\nnostic biopsies. However, re-biopsy at a later time often does reveal diagnostic changes.6\nSalivary Gland Resections\nThe most common specimen is a parotid gland resected for a pleomorphic adenoma (mixed tumor) or, \nless commonly, a Warthin tumor. Other tumors are very rare. A prior fine needle aspiration may have \nbeen performed.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the specimen and record the outer dimensions. Note whether any lesional tissue can be seen \nat the margin.\nIdentify any nerves that may have been resected.\n 2.\t \u0007Ink the outer surface. Serially section through the specimen looking for any lesions. Describe lesions \nincluding size, number (some tumors can be multifocal), color, consistency, involvement of nerve \ntrunks, relationship to remainder of gland and capsule, relationship to resection margin.\nDescribe uninvolved parenchyma including color, fibrosis, calculi in ducts, dilated ducts, hemorrhage, \nand cysts. Intraparenchymal lymph nodes may be present.\n 3.\t \u0007Examine the parotid gland and surrounding soft tissue for the presence of any lymph nodes.\nGROSS DIFFERENTIAL DIAGNOSIS\nPleomorphic Adenomas (Mixed Tumors)\u2002 are the most common type of salivary gland tumor; they are \ntypically well-circumscribed but may have small satellite nodules. They are usually white, very rubbery to firm, \nand translucent or cartilaginous. If diffuse infiltration or cystic degeneration is present, suspect an acinic cell \nor mucoepidermoid carcinoma (both can also be partially or completely circumscribed). Rarely, \u00adcarcinomas", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_497.png", "summary": "The page discusses the pathologic and prognostic features of salivary gland specimens, including lymph nodes, salivary gland involvement, and muscle/vein involvement. It also covers mucosal biopsies and minor salivary gland biopsies of the lip, particularly in patients with Sj\u00f6gren syndrome.", "questions": [ "What are the key factors to consider when examining lymph nodes in a radical neck dissection?", "How can diagnostic challenges be addressed when dealing with small, unorientable mucosal biopsies?", "What is the significance of scoring inflammation in minor salivary gland biopsies for autoimmune diseases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 498, "text": "480\nHEAD AND NECK\u2003 Salivary Gland\narise in pleomorphic adenomas and may be recognizable grossly as areas of hemorrhage, necrosis, or frank \ninvasion of adjacent tissue. A pleomorphic adenoma that is not completely excised at the initial operation can \nrecur as multiple nodules. Such a recurrence may be difficult to resect without also removing nerve trunks.\nWarthin Tumors\u2002 are circumscribed, orange/tan and often cystic. There is usually thick brown/black \nfluid (like \u201ccrank case oil,\u201d but may be clear) within the cyst spaces, which are lined by papillary nodules. Mul\u00ad\ntiple tumors occur more frequently with Warthin tumor more than any other salivary gland tumor. Approxi\u00ad\nmately 12% of patients develop more than one tumor and 5% to 10% of patients have bilateral tumors.\nMucoepidermoid Carcinoma\u2002 may be well circumscribed if low grade. These carcinomas may have cys\u00ad\ntic areas containing mucin. Higher grade tumors are usually infiltrative (with an appearance similar to inva\u00ad\nsive breast cancer) and solid in appearance. This is the most common malignant tumor in adults and children.\nAcinic Cell Carcinoma\u2002 is usually well circumscribed and may be grossly encapsulated. These tumors \nare grey/white to red/gray and lack the shiny surface of pleomorphic adenomas. Multiple cysts may be \npresent. This is the second most common malignant tumor.\nAdenoid Cystic Carcinoma\u2002 may appear deceptively well delimited but infiltrative areas are usually \npresent beyond the grossly apparent lesion. The tumors may show subtle effacement or blurring of normal \nlobular architecture. They are usually solid and grey/white. Cystic areas and hemorrhage are uncommon.\nSalivary Duct Carcinoma\u2002 is rare, and presents as a poorly demarcated scirrhous mass; it may invade \noutside the gland. This carcinoma closely resembles breast carcinoma in appearance.\nSome of these tumors may have or may mimic an intraductal growth pattern. Since pure intraductal \ngrowth is associated with a favorable prognosis, such tumors should be evaluated for myoepithelial cells \nwith immunohistochemical markers (e.g., p63, myosin heavy chain).\nLymphomas or Benign Lymphoepithelial Lesions\u2002 are very fleshy and soft to firm. These speci\u00ad\nmens should be processed like lymphomas, with tissue taken for special studies. Many patients with \nlymphoepithelial lesions will be HIV-positive. These patients may develop bilateral (or, less commonly, \nunilateral) swelling of the parotid glands with multiple cysts.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Lesions: Up to six cassettes including relationship to uninvolved gland, capsule. Routine pleomorphic \nadenomas or Warthin tumors only require three cassettes. All areas of hemorrhage, necrosis, and gross \ninvasion of adjacent tissue should be extensively sampled.\n\t\u2022\t \u0007Uninvolved gland: One to two cassettes\n\t\u2022\t \u0007Lymph nodes: All lymph nodes\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cparotid,\u201d is a 6 \u00d7 5 \u00d7 3 cm parotid \ngland surrounded by adipose tissue measuring in thickness from 0.1 to 0.5 cm. There is a 4 \u00d7 3 \u00d7 3 cm \nfirm tan white homogeneous well circumscribed lesion within the gland that is completely surrounded by \nsalivary gland tissue but approaches to within 0.2 cm of one margin. The remainder of the gland is tan/\nyellow and unremarkable. No lymph nodes are identified in the surrounding soft tissue.\nCassettes #1-3: Lesion including closest margin, 4 frags, RSS.\nCassette #4: Uninvolved gland, 1 frag, RSS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR SALIVARY GLAND CARCINOMAS\n\t\u2022\t \u0007Specimen: Parotid gland (superficial lobe, deep lobe), submandibular gland, sublingual gland\n\t\u2022\t \u0007Procedure: Excisional biopsy, resection of submandibular gland, resection of sublingual gland, super\u00ad\nficial parotidectomy, total parotidectomy, lymph node dissection\n\t\u2022\t \u0007Specimen Integrity: Intact, fragmented", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_498.png", "summary": "The page discusses various types of salivary gland tumors, their gross appearances, and common characteristics. It also provides guidelines for processing specimens for microscopic examination.", "questions": [ "What are the key differences in gross appearance between pleomorphic adenomas, Warthin tumors, Mucoepidermoid Carcinoma, Acinic Cell Carcinoma, Adenoid Cystic Carcinoma, and Salivary Duct Carcinoma?", "What are the implications of a pleomorphic adenoma not being completely excised during the initial operation?", "How can one differentiate between a benign lymphoepithelial lesion and a lymphoma based on their gross features?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 499, "text": "481\nHEAD AND NECK\u2003 Salivary Gland\n\t\u2022\t \u0007Specimen Size: Greatest dimension (other dimensions optional)\n\t\u2022\t \u0007Specimen Laterality: Right, left, bilateral\n\t\u2022\t \u0007Tumor Site: Parotid gland (superficial lobe, deep lobe), submandibular gland, sublingual gland\n\t\u2022\t \u0007Tumor Focality: Single focus, multifocal\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional) \u22642 cm, \u22652cm to \u22644 cm, >4 cm but \n\u22646 cm, >6 cm\n\t\u2022\t \u0007Tumor Description: Encapsulated/circumscribed, invasive, solid, cystic\n\t\u2022\t \u0007Histologic Type: Adenoid cystic, mucoepidermoid, acinic cell, salivary duct carcinoma, carcinoma \nex pleomorphic adenoma, adenocarcinoma, polymorphous low-grade adenocarcinoma (PLGA), other \nrare tumor types. The WHO Classification is recommended.\n\t\u2022\t \u0007Histologic Grade: See Table 23-2.\n\t \u2022\t \u0007Mucoepidermoid carcinomas may be graded (Tables 23-3 and 23-4).\n\t \u2022\t \u0007Grading systems have been developed for acinic cell and adenoid cystic carcinomas but are not \nuniversally accepted. Solid areas (>30% of tumor) in adenoid cystic carcinomas are associated with a \nworse prognosis.\n\t\u2022\t \u0007Tumor Extension: No extraparenchymal invasion and \u22642 cm (pT1), >2 but \u22644 cm without extrapa\u00ad\nrenchymal invasion (pT2), extraparenchymal invasion and/or >4 cm, without involvement of seventh \nnerve (pT3), invasion of skin, mandible, ear canal, or facial nerve (pT4a), invasion of skull, pterygoid \nplates, or carotid artery (pT4b).\n\t\u2022\t \u0007Margins: Uninvolved, involved (distance from closest margin); specify location if possible\n\t\u2022\t \u0007Treatment Effect: If there has been neoadjuvant therapy: not identified, present\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Additional Pathologic Findings: Sialadenitis, tumor-associated lymphoid proliferation\n\t\u2022\t \u0007Regional Lymph Nodes: Not present (pN0), present in 1 ipsilateral lymph node, \u22643 cm (pN1), pres\u00ad\nent in 1 ipsilateral lymph node, >3 but \u22646 cm (pN2a), present in multiple ipsilateral lymph nodes, none \n>6 cm (pN2b), present in bilateral or contralateral lymph nodes, none >6 cm (pN2c), metastasis in a \nlymph node >6 cm (pN3)\n\t \u2022\t \u0007Number of lymph nodes examined, number with metastases, size of largest metastasis\n\t \u2022\t \u0007Extranodal extension: not identified, present\nTABLE 23\u20132.\u2003\nGRADING OF SALIVARY GLAND CARCINOMAS\nLOW GRADE\nAcinic cell carcinoma\nBasal cell adenocarcinoma\nPolymorphous low grade adenocarcinoma\nHIGH GRADE\nPrimary squamous cell \u00adcarcinoma\nUndifferentiated carcinoma\nTUMORS OF VARIABLE GRADE\nAdenocarcinoma, NOS\nGrade according to histologic features\nAdenoid cystic carcinoma\nCribriform/tubular pattern versus solid (>30% of carcinoma)\nMucoepidermoid carcinoma\nSee Tables 23-3 and 23-4\nSalivary duct carcinoma\nGrade according to histologic features. Most are high grade.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_499.png", "summary": "This page provides detailed information on the pathology assessment of salivary gland tumors, including specimen size, tumor site, histologic type, grading, tumor extension, margins, and lymph node involvement.", "questions": [ "What are the different tumor sites within the salivary glands that are mentioned on this page?", "How is the grading of salivary gland carcinomas classified?", "What are the factors considered for tumor extension staging in salivary gland tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 500, "text": "482\nHEAD AND NECK\u2003 Salivary Gland\nTABLE 23\u20133.\u2003\nAFIP GRADING SYSTEM FOR MUCOEPIDERMOID CARCINOMAS\nPARAMETER\nPOINT VALUE\nIntracystic component <20%\n+2\nNeural invasion present\n+2\nNecrosis present\n+3\nFour or more mitoses per 10 HPF\n+3\nAnaplasia (nuclear pleomorphism, increased N/C ratio, large \nnucleoli, anisochromia, and hyperchromasia)\n+4\nGRADE\nTOTAL POINT SCORE\nLow grade\n0\u20134\nIntermediate grade\n5\u20136\nHigh grade\n7 or more\nFrom Auclair PL, Goode RK, Ellis GL, Mucoepidermoid carcinomas of intraoral salivary glands. Evaluation and application of grading criteria in 143 \ncases, Cancer 69:2021-2030, 1992 and Goode, RK, Auclair, PL, Ellis, GL, Mucoepidermoid carcinoma of the major salivary glands; clinical and histo\u00ad\npathologic analysis of 234 cases with evaluation of grading criteria, Cancer 82:1217-1224, 1998.\nThis grading system was not predictive of outcome in submandibular tumors.\nTABLE 23\u20134.\u2003\n\u0007MODIFICATION OF AFIP GRADING SYSTEM FOR MUCOEPIDERMOID \nCARCINOMAS\nFEATURE\nPOINTS\nIntracystic component <20%\n2\nTumor front invades in small \nnests and islands\n2\nPronounced nuclear atypia\n2\nLymphatic or vascular invasion\n3\nBony invasion\n3\nFour or more mitoses per 10 HPF\n3\nPerineural spread\n3\nNecrosis\n3\nSCORE (POINTS)\nCHARACTERISTIC FEATURES\nDEFINING FEATURES\nGrade I\n0\nProminent goblet cell component, \ncyst formation, intermediate cells \nmay be prominent, circumscribed \ngrowth pattern\nLack of grade III defining features, \nlack of aggressive invasion pat\u00ad\ntern", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_500.png", "summary": "The page discusses the AFIP grading system for mucoepidermoid carcinomas of salivary glands, as well as a modification to the grading system.", "questions": [ "How is the grading system for mucoepidermoid carcinomas determined?", "What are the defining features of Grade I mucoepidermoid carcinomas?", "Why was the grading system not predictive of outcome in submandibular tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 501, "text": "483\nHEAD AND NECK\u2003 Salivary Gland\nSCORE (POINTS)\nCHARACTERISTIC FEATURES\nDEFINING FEATURES\nGrade II\n2 to 3\nIntermediate cells predominate over \nmucinous cells, mostly solid tumor, \nsquamous cells may be seen\nAggressive invasion pattern, lack of \ngrade III defining features\nGrade III\n4 or more\nSquamous cells predominate, \n\u00adintermediate and mucinous cells \nmust also be present, mostly solid\nNecrosis, perineural spread, vascu\u00adlar \ninvasion, bony invasion, >4 mito\u00ad\nses/10 HPF, high grade nuclear \npleomorphism\nModified from Brandwein, MS, Ivanov, KI, Wallace, DI, et al, Mucoepidermoid carcinoma. A clinicopathologic study of 80 patients with special \n\u00adreference to histological grading, Am J Surg Pathol 25:835-845, 2001.\nTABLE 23\u20134.\u2003\n\u0007MODIFICATION OF AFIP GRADING SYSTEM FOR MUCOEPIDERMOID \nCARCINOMAS\u2014cont\u2019d\nTABLE 23-5.\u2003\n\u0007AJCC (7TH EDITION) CLASSIFICATION OF TUMORS OF MAJOR SALIVARY GLANDS\nTumor\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nTumor \u22642 cm without extraparenchymal extension*\nT2\nTumor >2 cm but \u22644 cm without extraparenchymal extension*\nT3\nTumor more than 4 cm and/or tumor having extraparenchymal extension*\nT4a\nModerately advanced disease\nTumor invades skin, mandible, ear canal, and/or facial nerve\nT4b\nVery advanced disease\nTumor invades skull base and/or pterygoid plates and/or encases carotid artery\nRegional Lymph Nodes\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in a single ipsilateral lymph node, \u22643 cm\nN2\nMetastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest \ndimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimen\u00ad\nsion, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension\nN2a\nMetastasis in a single ipsilateral lymph node >3 cm but \u22646 cm\nN2b\nMetastasis in multiple ipsilateral lymph nodes, none >6 cm\nN2c\nMetastasis in bilateral or contralateral lymph nodes, none >6 cm\nN3\nMetastasis in a lymph node >6 cm\nMetastasis\nM0\nNo distant metastasis\nM1\nDistant metastasis\n*Note: Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute \nextraparenchymal extension for classification purposes.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \nCommittee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_501.png", "summary": "The page discusses the grading system for mucoepidermoid carcinomas of the salivary glands, with Grade II having intermediate cells predominate and Grade III having squamous cells predominate. It also includes the AJCC classification of tumors of major salivary glands.", "questions": [ "What are the defining features of Grade II mucoepidermoid carcinomas?", "What are the defining features of Grade III mucoepidermoid carcinomas?", "How does the AJCC classification system categorize tumors of major salivary glands?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 502, "text": "484\nHEAD AND NECK\u2003 Tonsils and Adenoids\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 23-5). M0 \nis conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information form the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nSTAPES\nThe stapes is sometimes removed due to \u201cotosclerosis\u201d or \u201cotospongiosis.\u201d The footplate of the stapes \nattaches to the oval window leading to the inner ear. In this disease of unknown etiology, immature bone is \nproduced in this area resulting in fixation of the stapes to the oval window. This process is a relatively fre\u00ad\nquent cause of conductive deafness in young persons. Surgical repair involves reimplantment of the stapes.\nEarly lesions show collagen disarray with increased osteoclastic and osteoblastic activity. Older lesions \nlook like woven bone.\nHowever, this being said, the modern surgical procedure resects a portion of the stapes but does not \nremove the focus of sclerotic bone. The specimen usually consists of a minute fragment of bone, usually \nnot identifiable as the stapes footplate. The specimen is described grossly, but usually not submitted for \nhistologic sections.\nTEETH\nTeeth are generally removed because of caries or as part of a larger resection (e.g. mandible), and only \nrequire gross documentation.\nRarely, tumors of teeth or teeth from patients with systemic diseases involving teeth (e.g., some types \nof osteogenesis imperfecta) are removed. Teeth, as any other surgical specimen, need to be fixed well and \nnot allowed to dry out if of diagnostic importance.\nPROCESSING THE SPECIMEN (DOCUMENTATION)\n 1.\t \u0007Count the number of intact teeth and measure in aggregate. Measure the remaining fragments in \naggregate. Note the presence of caries and dental fillings.\nDentists and oral surgeons designate teeth using the Universal Numbering System. #1 is the right \nmaxillary third molar, proceeding on the maxilla to #16 (the left maxillary third molar). #17 is the left \nmandibular third molar, proceeding to #32 (the right mandibular third molar).\n 2.\t \u0007Describe, if possible the identity of the teeth, (molars, premolars or canine, and incisors).\n 3.\t \u0007In some cases, teeth will be removed with attached (pericoronal) cysts, including wisdom tooth \n\u00adextractions. If so, describe the location and size of attached soft tissue and submit in a separate \u00adcassette.\n 4.\t \u0007Sections of the teeth should be not be submitted except in unusual cases in which examination can be \nhelpful for diagnosis.\nTONSILS AND ADENOIDS\nTonsils and/or adenoids are commonly removed for the treatment of recurrent tonsillitis, middle ear dis\u00ad\nease, or sleep apnea. Rarely, tonsils will be involved by lymphomas or leukemias, infections (e.g., CMV, \nfungi, EBV), carcinomas, or granulomatous diseases.\nIn rare instances, one or both tonsils will be removed from a patient with a squamous cell carcinoma \nmetastatic to a cervical lymph node with no known primary. In such cases, the tonsil from the ipsilateral \nside should be \u00adexamined completely microscopically to evaluate the possibility of a clinically occult pri\u00ad\nmary arising in the tonsil. The presence of a basaloid morphology, p16 positivity, and HPV are highly \nsuggestive of a tonsil primary (see \u201cSpecial Studies\u201d).\nExamination of \u201croutine\u201d specimens from patients with a routine clinical history is controversial. \nA large study found that only 1% of such cases resulted in a diagnosis other than benign tonsillitis, or", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_502.png", "summary": "The page discusses distant metastasis in tonsils and adenoids, the surgical procedure for stapes in otosclerosis, and the documentation process for teeth specimens.", "questions": [ "How is distant metastasis in tonsils and adenoids diagnosed and classified?", "What is the surgical repair process for otosclerosis involving the stapes?", "How are teeth specimens processed and documented for pathological examination?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 503, "text": "485\nHEAD AND NECK\u2003 Tonsils and Adenoids\nhyperplasia and that in none of these cases was patient care changed. However, the decision to not exam\u00ad\nine these specimens can only be made if an adequate clinical history is available and there are no unusual \nfindings at surgery. Significant pathologic findings were found in 87% of specimens if there was a sig\u00ad\nnificant clinical history (history of malignancy, immunocompromise, asymmetric \u00adenlargement, etc.).7\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 23-6.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the dimensions. Describe the outer surface which is usually a convoluted squamous mucosa \noverlying a broad base of tan/pink soft tissue.\n 2.\t \u0007Serially section through the specimen. The convolutions can be appreciated better on cross section. \nFriable yellow/green \u201csulfur\u201d granules (sometimes mistaken for necrosis) are large colonies of Actino\u00ad\nmycetes that colonize the crypts.\n 3.\t \u0007Submit one representative section of each tonsil.\nSPECIAL STUDIES\nSquamous cell carcinomas. Tonsillar carcinomas in young patients (<40) with nonkeratinizing basal \ncell morphology are usually associated with HPV16 (rarely HPV31).8 These carcinomas are strongly \npositive for p16. HPV can be identified by PCR on formalin fixed tissue. These carcinomas may have \na better prognosis than non-HPV associated cancers. Metastatic squamous cell carcinomas to head and \nneck nodes are more likely to originate in the tonsil if they are HPV positive.\nSAMPLE DICTATION\nThe specimen is received fresh in two parts, each labeled with the patient\u2019s name and unit number.\nThe first part, labeled \u201cright tonsil,\u201d consists of a 4 \u00d7 3 \u00d7 3 cm tonsil covered by tan/white convoluted \nsquamous mucosa overlying tan/pink unremarkable soft tissue. Small focal friable yellow/green nodules \nare present in the tonsillar crypts.\nCassette #1: 1 frag, RSS.\nTABLE 23\u20136.\u2003\nRELEVANT CLINICAL HISTORY \u2013 TONSILS\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR TONSILLAR SPECIMENS\nOrgan/tissue resected or biopsied\nRecurrent tonsillitis\nPurpose of the procedure\nObstructive sleep apnea\nGross appearance of the organ/tissue/lesion sampled\nSleep apnea (\u201cPickwickian syndrome\u201d or sleep apnea \ndue to pharyngeal obstruction): usually both pala\u00ad\ntine tonsils as well as uvula and possibly additional \ntissue from Waldeyer\u2019s ring are resected\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nInfections (e.g., CMV, fungi, EBV)\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug \nuse that can change the histologic appearance of \ntissues)\nGranulomatous disease (e.g., sarcoid)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_503.png", "summary": "Specimens of tonsils and adenoids should be examined if there is a significant clinical history, as 87% of specimens with significant clinical history had pathologic findings. Squamous cell carcinomas in tonsils of young patients are usually associated with HPV16.", "questions": [ "What are the criteria for deciding whether or not to examine tonsil and adenoid specimens?", "How can HPV16 association be identified in tonsillar carcinomas?", "What are the relevant clinical history factors to consider for tonsillar specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 504, "text": "486\nHEAD AND NECK\u2003 Tonsils and Adenoids\nThe second part, labeled \u201cleft tonsil,\u201d consists of a 4.5 \u00d7 3.5 \u00d7 3 cm tonsil covered by tan/white con\u00ad\nvoluted squamous mucosa overlying tan/pink unremarkable soft tissue.\nCassette #2: 1 frag, RSS.\nREFERENCES\n\t1.\t \u0007de Carpentier JP, et al: An algorithmic approach to aspergillus sinusitis. J Laryngol Otol 108:314-318, 1994.\n\t2.\t \u0007Hartwick RW, Batsakis JG. Sinus aspergillosis and allergic fungal sinusitis. Ann Otol Rhinol Laryngol 100:\n427-430, 1991.\n\t3.\t \u0007Panda NK, Balaji P, Chakrabarti A, et al. Paranasal sinus aspergillosis: its categorization to develop a treatment \nprotocol. Mycoses 47:277-283, 2004.\n\t4.\t \u0007Waxman JE, Spector JG, Sale SR, Katzenstein AL. Allergic Aspergillus sinusitis: concepts in diagnosis and treat\u00ad\nment of a new clinical entity. Laryngoscope 97(3 Pt 1):261-266, 1987.\n\t5.\t \u0007Robbins KT, Shaha AR, Medina JE, et al: Consensus statement on the classification and terminology of neck \ndissection. Arch Otolaryngol Head Neck Surg 134:536-538, 2008.\n\t6.\t \u0007Daniels TE, Whitcher JP. Association of patterns of labial salivary gland inflammation with keratoconjunctivitis \nsicca. Analysis of 618 patients with suspected Sj\u00f6gren\u2019s syndrome. Arthritis Rheum 37:869-877, 1994.\n\t7.\t \u0007Netser JC, et al: Value-based pathology; a cost-benefit analysis of the examination of routine and nonroutine \ntonsil and adenoid specimens. Am J Clin Pathol 108:158-165, 1997.\n\t8.\t \u0007El-Mofty SK, Lu DW. Prevalence of Human Papillomavirus Type 16 DNA in squamous cell carcinoma of the \npalatine tonsil, and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity. \nAm J Surg Pathol 27:1463-1470, 2004.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_504.png", "summary": "The page describes the left tonsil, measuring 4.5 \u00d7 3.5 \u00d7 3 cm, covered by tan/white convoluted squamous mucosa overlying tan/pink soft tissue.", "questions": [ "What are the typical characteristics of the squamous mucosa covering the left tonsil?", "Are there any specific findings mentioned regarding the soft tissue underlying the left tonsil?", "How might the information provided on the left tonsil be relevant in a clinical setting?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 505, "text": "487\nHernia Sac\n24\nHernia sacs are common surgical specimens derived from the frequent repair of inguinal, femoral, and \numbilical hernias. The sacs usually consist of a small portion of fibroconnective tissue lined by mesothe\u00ad\nlial tissue.\nApproximately 22% of men undergoing hernia repair will also have a cord lipoma. Only 0.1% of her\u00ad\nnia sac operations yielded an incidental liposarcoma in one study.1 The two patients with liposarcoma \nwere older than the average patient with cord lipoma (56 and 64 years versus 35 years) and the tumors \nwere larger (13 and 10 cm versus 5.5 cm). A grossly evident fatty tumor of the cord is more likely to be \nmalignant than fatty tumors at other sites. Tissue should be sent for cytogenetics. Other rare soft tissue \nsarcomas have been reported from this region.\nOccasionally a groin mass (often an enlarged lymph node) is mistaken clinically for an inguinal hernia. \nIf a lymph node is found, it should be processed as a lymph node biopsy as the node may be involved by \nmetastatic tumor or infection.\nNot infrequently, there will be other findings in hernia sac specimens that may be of clinical signifi\u00ad\ncance.2-5 Some of the more common ones are listed here:\nOCCASIONAL FINDINGS IN HERNIA SACS\n\t\u2022\t \u0007Endometriosis (may be present in a true hernia or can simulate a hernia)\n\t\u2022\t \u0007Incarcerated bowel\n\t\u2022\t \u0007Vas deferens or epididymis (usually an inadvertent transection) is found in 0.53% of pediatric patients. \nThese structures must be distinguished from glandular inclusions, as there are medical and legal issues \nin such cases. A vas deferens should have a well defined muscular coat.\n\t\u2022\t \u0007Glandular inclusions from Mullerian remnants in prepubertal males\n\t\u2022\t \u0007Lymph nodes or metastatic tumor in inguinal nodes simulating a hernia\n\t\u2022\t \u0007Mesothelial hyperplasia, which may closely mimic a neoplastic process\n\t\u2022\t \u0007Tumors: a hernia may sometimes be the initial presentation of malignant mesothelioma, \n\u00adpseudomyxoma peritonei, or an intra-abdominal tumor (most frequently colon or ovarian \n\u00adcarcinoma).\nPROCESSING THE SPECIMEN\n 1.\t \u0007The specimen is a portion of thin tan/pink fibroconnective tissue with one shiny surface (the perito\u00ad\nneum) and one dull surface. Examine the specimen carefully to make sure that other structures are not \npresent (see above).\n 2.\t \u0007Submit one cassette containing three representative cross sections. Submit any focal lesions or addi\u00ad\ntional structures.\nSAMPLE DICTATION\nReceived fresh labeled with the patient\u2019s name and unit number and \u201chernia\u201d is a 4 \u00d7 3 \u00d7 0.4 cm fragment \nof pink/tan connective tissue. One side has a glistening surface.\nCassette: 3 frags, RSS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_505.png", "summary": "Hernia sac specimens are common in surgical pathology, often derived from repairs of inguinal, femoral, and umbilical hernias. They may contain incidental findings such as cord lipomas, liposarcomas, endometriosis, and other rare soft tissue sarcomas.", "questions": [ "What are some of the incidental findings that can be present in hernia sac specimens?", "What is the significance of finding a lymph node in a hernia sac specimen?", "Why is it important to distinguish between vas deferens or epididymis and glandular inclusions in pediatric patients?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 506, "text": "HERNIA SAC\u2003\ufeff\n488\nREFERENCES\n\t1.\u2002 \u0007Montgomery E, Buras R. Incidental liposarcomas indentified during hernia repair operations. J Surg Oncol \n71:50-53, 1999.\n\t2.\u2002 \u0007Gomez-Ramon JJ, Mayorga M, Mira C, et al. Glandular inclusions in inguinal hernia sacs: a clinicopathologic \nstudy of six cases. Pediatr Pathol 14:1043-1049, 1994.\n\t3.\u2002 \u0007Popek EJ. Embryonal remnants in inguinal hernia sacs. Hum Pathol 21:339-349, 1990.\n\t4.\u2002 \u0007Steigman CK Sotelo-Avila C, Weber TR. The incidence of spermatic cord structures in inguinal hernia sacs from \nmale children,. Am J Surg Pathol 23:880-885, 1999.\n\t5.\u2002 \u0007Walker AN, Mills SE. Glandular inclusions in inguinal hernia sacs and spermatic cords. Am J Clin Pathol 82:\n85-89, 1984.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_506.png", "summary": "The page discusses various studies on hernia sacs, including findings of liposarcomas, glandular inclusions, embryonal remnants, and spermatic cord structures.", "questions": [ "What are the implications of finding liposarcomas in hernia sacs?", "How common are glandular inclusions in inguinal hernia sacs?", "What is the significance of embryonal remnants in hernia sacs?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 507, "text": "489\n25\nLarynx\nThe larynx is virtually always removed for squamous cell carcinomas occurring near the true and false \nvocal cords. See the general section on \u201cBiopsies\u201d for biopsy specimens.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 25-1.\nLARYNGECTOMY\nThese are difficult specimens, not only because of the complicated anatomy but because of the calcification of \ncartilage in older individuals, which necessitates decalcification of parts of the specimen. Most specimens are \ntotal laryngectomies performed to resect invasive squamous cell carcinoma (i.e., thyroid, cricoid, and arytenoid \ncartilages with all attached soft tissue and mucosa; hyoid bone either totally or partially excised; strap muscles; \nthyroid gland partially or totally excised; several tracheal rings; base of tongue not usually included). Refer \nto the Figure 25-1 for orientation and terminology. There is often an accompanying radical neck dissection.\nLaryngectomies may also be performed to control chronic aspiration in mentally retarded patients. In \nthese cases, grossly normal specimens can be examined in three sections from the epiglottis, vocal cords, \nand trachea.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Carefully examine the outer surface of the specimen and record any evidence of tumor extension \nto a surgical resection margin. Although the anterior strap muscles form the anterior margin of the \nspecimen, these muscles retract after they are cut and may not completely cover this area. It may be \nTABLE 25\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR LARYNGEAL \nSPECIMENS\nOrgan/tissue resected or biopsied\nResults of prior biopsies\nPurpose of the procedure\nPrior treatment (e.g., radiation)\nGross appearance of the organ/tissue/lesion sampled\nHistory of HPV infection\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic appearance of tissues)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_507.png", "summary": "The larynx is typically removed for squamous cell carcinomas near the vocal cords, with most specimens being total laryngectomies for invasive squamous cell carcinoma.", "questions": [ "What are the challenges in processing laryngectomy specimens?", "What are the key components included in a total laryngectomy specimen?", "How are laryngectomies also used in cases of chronic aspiration in mentally retarded patients?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 508, "text": "LARYNX\u2003 Laryngectomy\n490\nnecessary to contact the surgeon to determine the true surgical margins if areas suspicious for tumor \nare present at an apparent margin.\nRecord overall dimensions and all identifiable attached structures, including the hyoid bone.\n 2.\t \u0007Ink the outer portion of the specimen, including all mucosal margins.\n 3.\t \u0007Open the specimen longitudinally along the posterior surface. The larynx can be opened to reveal \nthe true and false vocal folds and the ventricle. Describe any lesions including color, size, quality \n(exophytic, flat, verrucous, ulcerated, necrotic), location, and extent of involvement of anatomical \nlandmarks (e.g., vocal folds, ventricle, epiglottis, commissures, across midline). See the accompanying \ndiagrams for the relevant anatomical structures. Include the number of tracheal rings \u00adpresent.\n 4.\t \u0007Document the location of lesions by photography or diagrams. It is usually necessary to prop the \nposterior incision open (the cut ends of cotton swabs work well) or to hold the larynx open with hemo\u00ad\nstats. If the cartilage is not extensively calcified, the specimen can be cut in half and each cross section \nphotographed.\nOften a diagram is necessary to adequately record the location of the tumor and the location of micro\u00ad\nscopic sections.\n 5.\t \u0007Fix the specimen overnight in formalin.\n 6.\t \u0007If the cartilages are calcified, submit as many soft tissue sections as possible and then decalcify the \nremainder of the specimen before submitting the sections with cartilage. Document the point of maxi\u00ad\nmum tumor invasion through cartilage (if any). If there is soft tissue around the specimen (often there is \nnot), identify all lymph nodes.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: Up to four cassettes of tumor including relationship to anatomical landmarks (See \u201cPatho\u00ad\nlogic Diagnostic/Prognostic Features\u201d and Fig. 25-1) and deepest extent of tumor into, around, or \nthrough the surrounding cartilage.\n\t\u2022\t \u0007Margins: Lowest tracheal ring, all mucosal edges, strap muscles (anterior), base of tongue, soft tissue \nof lateral and posterior larynx. Mucosal margins not close to the gross tumor can be taken en face.\n\t\u2022\t \u0007Normal structures: True and false cords (vertical sections) bilaterally if uninvolved, anterior commis\u00ad\nsure, bilateral arytenoids and aryepiglottic folds, epiglottis.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201clarynx,\u201d is a total laryngectomy specimen \n(11 \u00d7 5 \u00d7 3.5 cm) including hyoid bone (8 \u00d7 0.3 \u00d7 0.3 cm), larynx from epiglottis to subglottis, and six \ntracheal rings. There is an irregular tan/white mass with central ulceration (2.5 \u00d7 1.5 \u00d7 0.9 cm) located in \nHyoid\nEpiglottis\nHyoid\nSuperior horn of\nthe thyroid\nPosterior\ncommissure\nAnterior\ncommissure\nAryepiglottic fold\nPyriform sinus\nArytenoid cartilage\nCricoid cartilage\nMID-SAGITTAL SECTION\nPOSTERIOR VIEW\nVentricular band\n(false cord)\nVocal fold\n(true cord)\nSupraglottis\nGlottis\nSubglottis\nTrachea\nFigure 25-1.\u2002 Anatomy of the larynx.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_508.png", "summary": "The surgical pathology manual provides guidelines for handling and documenting laryngectomy specimens, including ink marking, specimen opening, lesion description, photography, fixation, and microscopic section submission.", "questions": [ "What specific steps are recommended for documenting the location and extent of lesions in laryngectomy specimens?", "How should calcified cartilages in laryngectomy specimens be handled during processing?", "What are the key components of the microscopic sections to be submitted for analysis in laryngectomy specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 509, "text": "LARYNX\u2003 Laryngectomy\n491\nthe glottis completely involving the left true vocal cord. The mass crosses the midline and involves the \nmedial aspect of the right true vocal cord. The false vocal cords are not involved. The mass is 2.8 cm from \nthe closest proximal mucosal margin (left aryepiglottic fold) and 5 cm from the distal tracheal margin. \nThe mass invades into the lamina propria and focally appears to invade into, but not through, the thyroid \ncartilage. The anterior surface is covered by red/brown strap muscles which are grossly unremarkable. \n0.5 cm from the distal margin there is a 1.5 \u00d7 1 cm tracheal stoma. The cartilage is calcified and is fixed \nand decalcified prior to histologic sectioning.\nCassette #1: Left aryepiglottic fold, en face margin, 1 frag, ESS.\nCassette #2: Right aryepiglottic fold, en face margin, 1 frag, ESS.\nCassette #3: Epiglottis, margin, en face margin, 1 frag, ESS.\nCassette #4: Right arytenoid mucosa, en face margin, 2 frags, ESS.\nCassette #5: Left arytenoid mucosa, en face margin, 2 frags, ESS.\nCassette #6: Right anterior strap muscle, perpendicular margin, 1 frag, RSS.\nCassette #7: Left anterior strap muscle, perpendicular margin, 1 frag, RSS.\nCassette #8: Right lateral soft tissue, perpendicular \u00admargin, 1 frag, RSS.\nCassette #9: Left lateral soft tissue, perpendicular \u00admargin, 1 frag, RSS.\nCassette #10: Posterior soft tissue, perpendicular \u00admargin, 1 frag, RSS.\nCassette #11: Distal tracheal margin, en face, 1 frag, ESS.\nCassette #12: Mass including left true cord, 1 frag, RSS.\nCassette #13: Mass including right true cord, 1 frag, RSS.\nCassette #14: Mass including left false cord, 1 frag, RSS.\nCassette #15: Right false cord, 1 frag, RSS.\nCassette #16: Mass and deepest involvement of cartilage, 1 frag, RSS.\nCassette #17: Hyoid bone, 3 frags, RSS.\nCassette #18: Tracheal stoma site, 1 frag, RSS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR LARYNGEAL CARCINOMAS\n\t\u2022\t \u0007Specimen: Larynx (supraglottis, glottis, subglottis)\n\t\u2022\t \u0007Procedure(s): Excisional biopsy, laryngectomy (supraglottic, supracricoid, total), vertical hemilaryn\u00ad\ngectomy, lymph node dissection\n\t\u2022\t \u0007Specimen Integrity: Intact, fragmented\n\t\u2022\t \u0007Laryngectomy: Open, unopened\n\t\u2022\t \u0007Specimen Size: Greatest dimensions\n\t\u2022\t \u0007Tumor Laterality: Right, left, bilateral, midline\n\t\u2022\t \u0007Tumor Site: Larynx\u2014supraglottis (epiglottis [lingual or laryngeal aspect], aryepiglottic folds, ary\u00ad\ntenoids, false vocal cord, ventricle), larynx\u2014glottis (ture vocal cord, anterior commissure, posterior \ncommissure), larynx\u2014subglottis\n\t\u2022\t \u0007Tumor Focality: Single, multifocal\n\t\u2022\t \u0007Tumor Size: Greatest dimension (other dimensions optional)\n\t\u2022\t \u0007Tumor Description: Polypoid, exophytic, endophytic, ulcerated, sessile\n\t\u2022\t \u0007Histologic Type: Squamous cell carcinoma, all other types rare. The WHO Classification is recom\u00ad\nmended.\n\t\u2022\t \u0007Histologic Grade: Well, moderate, poor\n\t\u2022\t \u0007Tumor Extension: Supraglottis (ventricular bands [false cords], arytenoids, epiglottis, aryepiglottic \nfolds; the inferior boundary is a horizontal plane through the apex of the ventricle)\n\t \u2022\t \u0007Glottis (true vocal cords, anterior and posterior commissures; the lower boundary is a plane passing \n1 cm below the apex of the ventricle)\n\t \u2022\t \u0007Subglottis (area from the lower boundary of the glottis to the lower margin of the cricoid cartilage), \nthyroid and cricoid cartilages, postcricoid area, medial wall of pyriform sinus, pre-epiglottic tissue \n(base of tongue)\n\t\u2022\t \u0007Margins: Involved or not involved, location, distance from closest margin\n\t \u2022\t \u0007Invasive carcinoma, carcinoma in situ (including moderate and severe dysplasia)\n\t\u2022\t \u0007Treatment Effect: If there has been neoadjuvant chemotherapy: not identified, present\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Perineural Invasion: Not identified, present", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_509.png", "summary": "The surgical pathology report describes a laryngectomy specimen with a mass involving the left true vocal cord, crossing the midline to involve the right true vocal cord. The mass invades into the lamina propria and appears to invade into the thyroid cartilage.", "questions": [ "What are the margins involved in this laryngectomy specimen?", "What is the significance of the mass invading into the lamina propria and thyroid cartilage?", "What are the different types of laryngectomy procedures mentioned in the pathology report?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 510, "text": "LARYNX\u2003 Laryngectomy\n492\n\t\u2022\t \u0007Regional Lymph Nodes: Size (\u22643, \u22646, >6 cm), ipsilateral vs. contralateral, extranodal extension. \nKera\u00adtin debris may be evidence of previous tumor.\n\t\u2022\t \u0007Additional Pathologic Findings: Keratinizing dysplasia, nonkeratinizing dysplasia, inflammation, \nsquamous metaplasia, epithelial hyperplasia, colonization (fungal, bacterial)\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 25-2). M0 \nis conferred after clinlcal assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nTABLE 25-2.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF LARYNGEAL TUMORS\nTumor\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ\nSupraglottis\nT1\nTumor limited to one subsite of the supraglottis with normal vocal cord mobility\nT2\nTumor invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supra\u00ad\nglottis (e.g., mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx\nT3\nTumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, preepiglottic \nspace, paraglottic space, and/or inner cortex of thyroid cartilage\nT4a\nModerately advanced local disease\nTumor invades through the thyroid cartilage, and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of \nneck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)\nT4b\nVery advanced local disease\nTumor invades prevertebral space, encases carotid artery, or invades mediastinal structures\nGlottis\nT1\nTumor limited to the vocal cord(s) (may involve anterior or posterior commissures) with normal mobility\nT1a\nTumor limited to one vocal cord\nT1b\nTumor involves both vocal cords\nT2\nTumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility\nT3\nTumor limited to the larynx with vocal cord fixation and/or invasion of paraglottic space, and/or inner cortex of the \nthyroid cartilage\nT4a\nModerately advanced local disease\nTumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx \n(e.g., \u00adtrachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or \n\u00adesophagus)\nT4b\nVery advanced local disease\nTumor invades prevertebral space, encases carotid artery, or invades mediastinal structures", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_510.png", "summary": "The page discusses the pathology findings related to laryngectomy, including regional lymph nodes, additional pathologic findings, distant metastasis, and AJCC classification of laryngeal tumors.", "questions": [ "What are some examples of additional pathologic findings that may be observed in laryngectomy specimens?", "How is distant metastasis determined in laryngectomy specimens?", "Can you explain the significance of the AJCC classification in laryngeal tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 511, "text": "LARYNX\u2003 Laryngectomy\n493\nSubglottis\nT1\nTumor limited to the subglottis\nT2\nTumor extends to the vocal cord(s) with normal or impaired mobility\nT3\nTumor limited to the larynx with vocal cord fixation\nT4a\nModerately advanced local disease\nTumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of \nneck including deep extrinsic muscles of the tongue, strap muscles, thyroid, esophagus)\nT4b\nVery advanced local disease\nTumor invades prevertebral space, encases carotid artery, or invades mediastinal structures\nREGIONAL LYMPH NODES*\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in a single ipsilateral lymph node, \u22643 cm\nN2\nMetastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or \nin multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral \nlymph nodes, none more than 6 cm in greatest dimension\nN2a\nMetastasis in a single ipsilateral lymph node >3 cm but \u22646 cm\nN2b\nMetastasis in multiple ipsilateral lymph nodes, none >6 cm\nN2c\nMetastasis in bilateral or contralateral lymph nodes, none >6 cm\nN3\nMetastasis in a lymph node >6 cm\nNote: Metastases at level VII are considered regional lymph node metastases.\nMETASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: This classification system does not apply to nonepithelial tumors.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Committee on Cancer (AJCC), \nChicago, Illinois.\nTABLE 25\u20132.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF LARYNGEAL TUMORS\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_511.png", "summary": "This page outlines the AJCC classification system for laryngeal tumors, including criteria for tumor size and extent, regional lymph node involvement, and distant metastasis.", "questions": [ "What are the different stages of laryngeal tumors based on tumor size and extent?", "How is regional lymph node involvement classified in laryngeal tumors?", "What is the significance of metastasis in the staging of laryngeal tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 512, "text": "494\n26\nLung and Pleura\nLUNG\nNon-neoplastic diseases of the lung are usually diagnosed by bronchoalveolar lavage, transbronchial \nbiopsies, and open lung biopsies. In locations with lung transplant programs, chronically-diseased recip\u00ad\nient lungs are also submitted for examination and these patients are monitored by serial biopsies to \nexclude rejection or infection.\nLung tumors may be sampled by fine needle aspiration or endo/transbronchial biopsy, but often the \npatient proceeds directly to mediastinal staging, video-assisted closed chest lung biopsy, or open lung surgery.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 26-1.\nBiopsy, Endobronchial, Transbronchial\nThese biopsies are processed as described in Chapter 13. Special stains for organisms (Gram, AFB, MSS) \nare ordered if the patient is immunocompromised or if infection is suspected clinically.\nDuring these procedures cytology specimens are often obtained as well (e.g., bronchial brushings and/\nor bronchial lavage).\nTransplant Lung Biopsies\nTransbronchial biopsies of transplant lungs may be performed on an emergency basis for symptomatic \npatients, or as routine follow-up biopsies after transplantation. An adequate specimen should consist of \nat least five pieces of well-expanded alveolated lung parenchyma. Gentle agitation of the specimen in \nformalin will help to inflate the fragments.\nTABLE 26\u20131.\u2003\nRELEVANT CLINICAL HISTORY\u2013LUNG\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR LUNG SPECIMENS\nOrgan/tissue resected or biopsied\nOrgan transplantation\nPurpose of the procedure\nOccupational lung disease\nGross appearance of the organ/tissue/lesion sampled\nAsbestos exposure\nAny unusual features of the clinical presentation\nTobacco use\nAny unusual features of the gross appearance\n\u2192 Single mass, multiple masses, diffuse lung disease\nPrior surgery/biopsies - results\nInfection (known or suspected)\nPrior malignancy\nSystemic disease that affect the lungs (e.g., \n\u00adrheumatoid arthritis, sarcoidosis) \nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic appearance of \u00adtissues)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_512.png", "summary": "Non-neoplastic and neoplastic lung diseases are diagnosed through various biopsy techniques, including bronchoalveolar lavage, transbronchial biopsies, and open lung biopsies. Lung transplant recipients undergo serial biopsies to monitor for rejection or infection.", "questions": [ "What are the different biopsy techniques used to diagnose non-neoplastic and neoplastic lung diseases?", "How are lung transplant recipients monitored for rejection or infection?", "What clinical history is considered relevant for lung specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 513, "text": "LUNG AND PLEURA\u2003 Lung\n495\nThe revision of the 1996 working formulation for standardization of nomenclature in the diagnosis of \nlung rejection is summarized in Tables 26-2 to 26-4 and Box 26-1.1\nTABLE 26\u20132.\u2003\nACUTE REJECTION\nGRADE\nHISTOPATHOLOGIC FINDINGS\nA0 (none)\nNormal pulmonary parenchyma is present without evidence of mononuclear \ninflammation, hemorrhage, or necrosis.\nA1 (minimal)\nScattered infrequent perivascular mononuclear infiltrates in alveolated lung \nparenchyma.\nBlood vessels, particularly venules, are cuffed by small round, plasmacytoid, and \ntransformed lymphocytes forming a ring of two to three cells in thickness within \nthe perivascular adventitia. The cuffing may be loose or compact and is generally \ncircumferential. Eosinophils and endothelialitis are not present.\nA2 (mild)\nMore frequent perivascular mononuclear infiltrates are seen surrounding venules \nand arterioles, readily recognizable at low magnification. They may be densely \ncompacted or loose. These infiltrates usually consist of a mixture of small round \nlymphocytes, activated lymphocytes, plasmacytoid lymphocytes, macrophages, \nand eosinophils.\nFrequent subendothelial infiltration by the mononuclear cells with hyperplastic \nor regenerative changes in the endothelium (endotheliitis); although there is \nexpansion of the perivascular interstitium by inflammatory cells, there is no \nobvious infiltration by mononuclear cells into the adjacent alveolar septae or air \nspaces.\nConcurrent lymphocytic bronchiolitis may be seen with mild rejection and is less \ncommon in minimal rejection.\nMild rejection is distinguished from minimal rejection by the presence of \nunequivocal mononuclear infiltrates, which are more easily identified at scanning \nmagnification. Endothelialitis, the presence of eosinophils, and co-existent airway \ninflammation favor mild over minimal acute rejection.\nA3 (moderate)\nEasily recognizable cuffing of venules and arterioles by dense perivascular mononuclear \ncell infiltrates, which are commonly associated with endothelialitis; eosinophils and \noccasional neutrophils are common.\nThe grade is defined by extension of the inflammatory cell infiltrate into perivascular \nand peribronchiolar alveolar septae and air spaces, which may be associated \nwith collections of intra-alveolar macrophages in the zones of septal infiltration \nand Type 2 alveolar cell hyperplasia. The interstitial infiltration can take the form \nof cells percolating singly into alveolar walls or more sheet-like infiltration with \ncorresponding expansion of the septa. There is continuity with the perivascular \ninfiltrates. True interstitial infiltration characterizing moderate rejection should \nbe distinguished from the expansion of the potential space of the perivascular \nadventia in mild rejection.\nA4 (severe)\nDiffuse perivascular, interstitial, and air space infiltrates of mononuclear cells with \nprominent alveolar pneumocyte damage and endothelialitis. These may be \nassociated with intra-alveolar necrotic epithelial cells, macrophages, hyaline \nmembranes, hemorrhage, and neutrophils. There may be associated parenchymal \nnecrosis, infarction, or necrotizing vasculitis, although these features are more \nevident on surgical rather than on transbronchial biopsies. There may be a \nparadoxical diminution of perivascular infiltrates as cells extend into alveolar septa \nand spaces where they are admixed with macrophages.\nSevere rejection must be distinguished from post-transplantation acute lung injury by \nthe presence of numerous perivascular and interstitial mononuclear cells, which are \nnot a feature of reperfusion-related damage.\nModified from Stewart, S, Fishbein, MC, Snell, GI, et al, Revision of the 1996 working formulation for the standardization of nomenclature in the \ndiagnosis of lung rejection, J Heart Lung Transplant 26:1229-42, 2007.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_513.png", "summary": "The page discusses the histopathologic findings of acute lung rejection, ranging from minimal to severe grades.", "questions": [ "What are the key differences between the different grades of acute lung rejection?", "How is mild rejection distinguished from minimal rejection?", "What are the common histopathologic features seen in moderate and severe acute lung rejection?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 514, "text": "LUNG AND PLEURA\u2003 Lung\n496\nTABLE 26\u20133.\u2003\nCHRONIC AIRWAYS REJECTION: OBLITERATIVE BRONCHIOLITIS\nCLASSIFICATION\nHISTOPATHOLOGICAL FINDINGS\nC0\nNo evidence of obliterative \u00adbronchiolitis.\nC1\nDense eosinophilic hyaline fibrosis in the submucosa of membranous and \nrespiratory bronchioles, resulting in partial or complete luminal occlusion. This \ntissue can be concentric or eccentric and may be associated with fragmentation \nand destruction of the smooth muscle and elastica of the airway wall. It may \nextend into the peribronchiolar interstitium. Mucostasis and/or foamy histiocytes \nin the distal air spaces are commonly associated with obliterative bronchiolitis \nand may be observed in transbronchial biopsies in the absence of bronchiolar \nocclusion or any bronchiolar tissue.\nTABLE 26\u20134.\u2003\nAIRWAY INFLAMMATION\nGRADE\nHISTOPATHOLOGICAL FINDINGS IN SMALL AIRWAYS \n(BRONCHIOLES)\nB0 (no airway inflammation)\nNo evidence of bronchiolar inflammation.\nB1R (low-grade small airway inflammation)\nThere are mononuclear cells within the submucosa of the \nbronchioles, which can be infrequent and scattered or \nforming a circumferential band. Occasional eosinophils \nmay be seen within the submucosa. There is no evidence, \nhowever, of epithelial damage or intra-epithelial \nlymphocytic infiltration. This grade replaces the previous \nB1 and B2 grades.\nB2R (high-grade small airway inflammation)\nThe mononuclear cells in the submucosa appear larger \nand activated, with greater numbers of eosinophils \nand plasmacytoid cells. In addition, there is evidence \nof epithelial damage in the form of necrosis and \nmetaplasia and marked intraepithelial lymphocytic \ninfiltration. In its most severe form, there is epithelial \nulceration, fibrinopurulent exudate, cellular debris and \nneutrophils. The presence of a disproportionate number \nof neutrophils within the epithelium and submucosa in \nrelation to the numbers of submucosal mononuclear \ncells is highly suggestive of infection rather than \nrejection. Any accompanying lavage or aspirate may \nalso be purulent and/or show evidence of organisms.\nBX (ungradeable small airways inflammation)\nUngradeable because of sampling problems, infection, \n\u00adtangential cutting, artifact, etc.\nModified from Stewart, S, Fishbein, MC, Snell, GI, et al, Revision of the 1996 working formulation for the standardization of nomenclature in the \ndiagnosis of lung rejection, J Heart Lung Transplant 26:1229-42, 2007.\nBOX 26-1.\u2003 Chronic vascular rejection\nChronic vascular rejection/accelerated graft vascular sclerosis refers to fibrointimal thickening of arteries and veins. \nIn veins, the appearance is usually of poorly cellular hyaline sclerosis. Evaluation of this process is not applicable to \ntransbronchial biopsies, but can be evaluated in open biopsies.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_514.png", "summary": "The page discusses chronic airways rejection, specifically obliterative bronchiolitis, and airway inflammation grades in small airways.", "questions": [ "What are the histopathological findings associated with obliterative bronchiolitis?", "How is airway inflammation graded in small airways?", "What is chronic vascular rejection and how is it different from chronic airways rejection?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 515, "text": "LUNG AND PLEURA\u2003 Lung\n497\nOpen Biopsies\nOpen lung biopsies are usually performed on critically ill patients with a wide differential diagnosis, usu\u00ad\nally for diffuse pulmonary disease. These specimens are usually processed during an OR consultation (see \nChapter 6).\nWedge Resection\nWedge resections are open lung or video-assisted closed chest biopsies performed to sample focal suspi\u00ad\ncious areas (e.g., pleural-based nodules) or to resect tumors if the patient cannot tolerate a more extensive \nprocedure. Bullectomies may be performed on patients with severe emphysema to improve pulmonary \nfunction.\nPROCESSING THE SPECIMEN\n 1.\t \u0007The specimen is usually a triangular segment of lung and pleura with two intersecting staple lines at \nthe margin. Record the dimensions of the specimen. Examine the pleura for any evidence of disease:\n\t \u2022\t \u0007Smooth and glistening, freely mobile over an underlying mass: normal pleura not invaded \nby tumor. There is no need to ink normal pleura. The absence of pleural involvement is impor\u00ad\ntant to document for staging lung carcinomas and can usually be determined by a good gross \n\u00adexamination.\n\t \u2022\t \u0007Retracted pleura over a tumor: invasion by tumor into the pleura. The pleura will be fixed to the \nunderlying mass. If the pleura is smooth, it will be recognizable microscopically and there is no need \nto ink it. If there is adhesed tissue (fat or muscle) this may be an indication of chest wall invasion. \nUse a different color of ink to distinguish this area from the lung parenchymal margin.\n\t \u2022\t \u0007Tumor implants: usually gray/white nodules within the pleura\n\t \u2022\t \u0007Lymphangitic spread of tumor: white anastomising lines running through the pleura\n\t \u2022\t \u0007Pleural lymph nodes: small black firm nodules in the pleura\n\t \u2022\t \u0007Adhesions: roughened dull areas of pleura with attached tissue - usually adipose tissue\n 2.\t \u0007Record the length of the margin, which is usually a staple line. It is a worthless effort to try to remove \nall the staples as the tissue will be shredded and uninterpretable. Cut the staple line off the specimen \nwith a pair of scissors, staying as close to the staples as possible. The cut surface of the lung now visible \nis the margin, which can be taken en face or, if the tumor is close, taken perpendicularly after inking \nthe open surface. Blot the lung free of any fluid before inking to prevent the ink from smearing.\n 3.\t \u0007Serially section through the remainder of the specimen looking for any focal lesions. Describe all \nlesions including size, color, involvement of pleura, and distance from margin.\n 4.\t \u0007Describe remainder of lung parenchyma (emphysematous changes, consolidation, fibrosis).\n 5.\t \u0007The histologic appearance of even small specimens can be improved by inflating the fragment with a \nsyringe filled with formalin. However, great care must be taken not to injure unprotected fingers!\n 6.\t \u0007Submit representative sections of any lesion including relationship to the pleura and uninvolved lung. \nSubmit the closest margin. Submit one cassette of uninvolved lung parenchyma.\n 7.\t \u0007If the margin is close, an additional section of lung with two staple lines may be submitted as the \nnew margin. If no gross lesions are present, submit two representative sections perpendicular to the \n\u00admargin.\nPneumonectomy or Lobectomy\nPneumonectomies and lobectomies are almost always performed to resect tumors. An exception is the \nrecipient pneumonectomy prior to lung transplant. These are described in a separate section below. \nExtrapleural \u00adpneumonectomies are used to resect mesotheliomas and are also described separately.\nLung Tumors\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the specimen and record the dimensions of the bronchial margin (length and circumference). \nIdentify the lung (right or left) or lobe(s) (upper, lower, or middle) resected. Carefully examine the \npleural surface for any evidence of disease (smooth and glistening = normal; dull and irregular = tumor", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_515.png", "summary": "Open lung biopsies are usually performed on critically ill patients with a wide differential diagnosis, while wedge resections are done to sample focal suspicious areas or resect tumors. Processing the specimen involves examining the pleura for evidence of disease, recording dimensions, and describing any lesions.", "questions": [ "How are open lung biopsies different from wedge resections?", "What are the key features to look for in the pleura during specimen processing?", "Why is it important to record the dimensions of the specimen and describe any lesions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 516, "text": "LUNG AND PLEURA\u2003 Lung\n498\nimplants or adhesions; retraction = invasion by tumor; delicate white reticular pattern on pleural \n\u00adsurface = lymphangitic spread of tumor).\nNormal weights:\n\t\n\u2022\t \u0007Right lung 680 gm (male); 480 gm (female)\n\t\n\u2022\t \u0007Left lung 600 gm (male); 420 gm (female)\n 2.\t \u0007Inflate intact specimens through the remaining bronchus. If the bronchial resection margin has not \nalready been removed as an OR consultation, do so before inflating. Cut an en face section and place \nin a labeled cassette. After the lung is inflated, clamp off the bronchus with a hemostat. Note: This \nshould not be done if there is any gross abnormality of the bronchus (e.g., invasion by tumor, dys\u00ad\nplasia suggested by frozen section) that will be evaluated histologically. The appropriate sections are \ntaken and a cotton swab can be used to plug the remaining bronchial stump.\nIf the specimen is not intact (e.g., several sections have been cut into it), the specimen can be inflated \nusing a syringe. Some of the formalin will leak out, but the microscopic appearance will still be much \nimproved over no inflation at all. Many sites will need to be injected. Great care is needed to avoid \nhand injuries!\nThe overall dimensions are measured after inflation.\n 3.\t \u0007Fix the specimen overnight. Previously uncut specimens are cut with a long knife in a parasagittal \nplane (lateral to medial). However, other methods of sectioning may be appropriate (see special stud\u00ad\nies below). Photograph all lesions.\n 4.\t \u0007Describe lesions including size, color, consistency (e.g., firm = squamous or adenocarcinoma, soft = \nlymphoma or bronchioloalveolar carcinoma), location (bronchopulmonary segment), relationship to \nmajor bronchi (document tumor arising from a bronchus and/or obstruction of bronchi), vascular \ninvasion, relationship to (invading through, retracting) or distance from pleura, distance from bron\u00ad\nchial resection margin, presence of post-obstructive pneumonia.\n 5.\t \u0007Describe remainder of lung parenchyma including emphysematous changes (almost always centriaci\u00ad\nnar with sparing of the peripheral alveoli), fibrosis, consolidation, bullae, etc. Describe any abnormali\u00ad\nties of the bronchi (bronchiectasis, mucous plugging).\n 6.\t \u0007Remove the soft tissue around the hilum and look for lymph nodes. Describe number, range in size, \ncolor, and consistency (anthracotic and firm or white and hard).\n 7.\t \u0007Incidental ribs removed during thoracotomies can be processed as described under the section on \nbones.\nIf a portion of the chest wall is attached, see section below for processing.\nSPECIAL STUDIES\nThere are alternative methods for sectioning lungs to best demonstrate the pathologic lesions present.\n\t\u2022\t \u0007Coronal sections (anterior to posterior): These sections are better for demonstrating hilar lesions, as \nthe bronchi and major vessels are seen in longitudinal section.\n\t\u2022\t \u0007Superior to inferior (CT plane): These sections are useful for showing the relationship of mediastinal \nlesions to the adjacent lung and for correlation with CT images. However, surgical specimens rarely \ninvolve such extensive resections.\n\t\u2022\t \u0007Dissection of blood vessels: This type of dissection is useful for demonstrating vascular lesions (usually \npulmonary emboli). Such lesions would be unusual in surgical specimens. The lung is approached from \nthe lateral aspect within the fissure(s). A pair of scissors is used to cut towards the hilum until the pulmo\u00ad\nnary artery is entered. The major vessels can then be opened with the scissors. The vessels will not cross \nairways in this type of dissection.\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Fig. 26-1.\nSquamous Cell Carcinomas are usually central and arise from bronchi. The tumors often obstruct \nthe airway leading to atelectasis of the distal lung. They are usually gray/white, firm, and commonly \ndemonstrate necrosis or central cavitation.\nAdenocarcinomas are more often peripheral and frequently involve the pleura. The tumors are \ngrey/yellow and rarely cavitate.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_516.png", "summary": "The page provides guidelines for processing lung specimens in surgical pathology, including inflation of intact specimens, sectioning methods, description of lesions, evaluation of lung parenchyma, examination of lymph nodes, and special studies for sectioning lungs.", "questions": [ "What are the normal weights of the right and left lungs in males and females?", "What are the steps involved in inflating intact lung specimens?", "What are the alternative methods for sectioning lungs to best demonstrate pathologic lesions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 517, "text": "LUNG AND PLEURA\u2003 Lung\n499\nUndifferentiated Large Cell Carcinomas are more often peripheral and do not have a distinctive \ngross appearance.\nBronchioloalveolar Carcinomas (BACs) form indistinct soft (because there is no desmoplastic \nresponse) gray \u00adnodules. Lymphomas and focal areas of inflammation can also have this gross appear\u00ad\nance. BACs are commonly multifocal and may be associated with copious extracellular mucin.\nSmall Cell Carcinomas are rarely seen as surgical resections due to their propensity to metastasize \nearly. These carcinomas are most commonly seen centrally.\nCarcinoid Tumors may be central or peripheral. Central carcinoids form polypoid endobronchial \nmasses covered by nonulcerated bronchial mucosa. They often extend into adjacent soft tissue to form a \n\u201cdumbbell\u201d shape. Peripheral carcinoids are seen as one or more discrete gray/yellow nodules near the \npleura. Carcinoids are usually fleshy and homogenous in appearance and have circumscribed borders.\nA\nB\nC\nD\nSquamous cell carcinoma\nAdenocarcinoma\nBronchioloalveolar carcinoma\nCarcinoid\nPeripheral\nProximal\nPoorly circumscribed\nFigure 26-1.\u2002 Gross anatomy of lung tumors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_517.png", "summary": "Different types of lung tumors have varying gross appearances and locations, with some being peripheral and others central.", "questions": [ "What are the distinguishing features of Undifferentiated Large Cell Carcinomas?", "Why are Small Cell Carcinomas rarely seen as surgical resections?", "How do Carcinoid Tumors differ in appearance based on their location?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 518, "text": "LUNG AND PLEURA\u2003 Lung\n500\nPulmonary Chondroid Hamartomas are occasional incidental findings on chest x-rays. The \nlesions are very well circumscribed, glistening white to gray, and may \u201cpop out\u201d of the adjacent lung \nparenchyma.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: Up to five cassettes including relationship to uninvolved lung, pleura, and adjacent vessels and \nbronchi.\n\t\u2022\t \u0007Margins: Bronchial resection margin. Chest wall margins if attached chest wall is present (inferior, \nsuperior, anterior, posterior, and external). Pulmonary staple margin if the specimen is a lobectomy.\n\t\u2022\t \u0007Lymph nodes: All hilar lymph nodes.\n\t\u2022\t \u0007Pleura: Pleura closest to tumor if not previously submitted.\n\t\u2022\t \u0007Uninvolved lung: One representative section of each lobe in the specimen.\n\t\u2022\t \u0007Rib: If unattached to lung, a marrow squeeze may be performed. If attached to the lung, submit both \nmargins and a section showing deepest point of invasion of tumor in relation to the bone.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201clung,\u201d is a 150 gram upper lobe \nof the right lung (12 \u00d7 10 \u00d7 6 cm) and bronchial remnant (1.1 cm in length \u00d7 0.6 cm in diameter). In the \nanterior segment, there is a poorly circumscribed firm gray/white tumor (3 \u00d7 2.5 \u00d7 2.2 cm) with central \nnecrosis, which is 5 cm from the uninvolved bronchial margin. The tumor causes retraction of the over\u00ad\nlying pleura, but does not grossly invade through the pleura, which has a smooth glistening surface. The \ntumor grossly invades an adjacent bronchus. There are mild emphysematous changes in the remainder \nof the lung parenchyma and a fibrous pleural scar (1.3 \u00d7 1.0 \u00d7 0.5 cm) at the apex of the lung. There are \nthree anthracotic hilar lymph nodes, the largest measuring 1.4 cm in greatest dimension. The bronchial \nresection margin was frozen for intraoperative diagnosis. Tumor (0.5 \u00d7 0.5 \u00d7 0.5) and normal tissue (1 \u00d7 \n1 \u00d7 1) were given to Dr. Smith for special studies.\nCassette #1: Bronchial resection margin, en face, Frozen section remnant, 1 frag, ESS.\nCassettes #2-3: Tumor and pleura, 2 frags, RSS.\nCassettes #4-5: Tumor and adjacent lung, 2 frags, RSS.\nCassette #6: Tumor invading bronchus, 1 frag, RSS.\nCassette #7: Apical scar, 1 frag, RSS.\nCassette #8: Representative lung parenchyma, 2 frags, RSS.\nCassette #9: Three hilar lymph nodes, 3 frags, ESS.\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR LUNG TUMORS\n\t\u2022\t \u0007Specimen: Lung, lobe of lung, bronchus\n\t\u2022\t \u0007Procedure: Major airway resection, wedge resection, segmentectomy, lobectomy, pneumonectomy\n\t\u2022\t \u0007Specimen Integrity: Intact, disrupted\n\t\u2022\t \u0007Specimen Laterality: Right, left\n\t\u2022\t \u0007Tumor Site: Upper lobe, middle lobe, lower lobe\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Tumor Focality: Unifocal, separate tumor nodules in the same lobe, separate tumor nodules in dif\u00ad\nferent lobes, synchronous carcinomas\nHistologically distinct tumors may be separate synchronous primary carcinomas and may be staged \nseparately. Histologically similar tumors that are associated with carcinoma in situ, not associated with \nlymph-vascular invasion, and/or with differences in immunohistochemical or molecular studies, also \nmay be synchronous primary carcinomas. These carcinomas may also be staged separately.\n\t\u2022\t \u0007Histologic Type: Squamous cell carcinoma, adenocarcinoma, large cell carcinoma, bronchioloalveo\u00ad\nlar carcinoma, large cell neuroendocrine carcinoma, carcinoid tumor, atypical carcinoid tumor (well \ndifferentiated neuroendocrine carcinoma), small cell carcinoma (rarely resected), other rare types. The \nWHO classification is recommended (Table 26-5).\n\t\u2022\t \u0007Histologic Grade: Well, moderate, poor, undifferentiated (squamous cell and adenocarcinoma) \n(Table\u00a026-6).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_518.png", "summary": "Pulmonary Chondroid Hamartomas are occasionally found on chest x-rays, appearing as well-circumscribed, glistening white to gray lesions that may protrude from the lung parenchyma.", "questions": [ "What are the key microscopic sections that should be examined when evaluating a lung specimen with a chondroid hamartoma?", "What are the important gross findings and measurements to document when describing a chondroid hamartoma in a lung specimen?", "What are the pathological prognostic and diagnostic features that should be considered when evaluating lung tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 519, "text": "LUNG AND PLEURA\u2003 Lung\n501\n\t\u2022\t \u0007Visceral Pleura Invasion: Ntified, present (Table 26-7, Fig. 26-2)\n\t\u2022\t \u0007Tumor Extension: Lobar bronchus, main bronchus, carina\n\t \u2022\t \u0007Pleura: Not involved, into but not through visceral pleura, through visceral pleura into parietal \npleura. Elastic stains may be used to define the elastica of the visceral pleura (see below).\n\t \u2022\t \u0007Chest wall, diaphragm, mediastinal pleura, phrenic nerve, parietal pericardium, heart, great vessels, \nesophagus, trachea, vertebral body.\nTABLE 26\u20135.\u2003 WHO CLASSIFICATION OF PULMONARY NEUROENDOCRINE TUMORS\nFEATURE\nTYPICAL \nCARCINOID\nATYPICAL \nCARCINOID\nLARGE-CELL NE \nCARCINOMA\nSMALL-CELL LUNG \nCARCINOMA\nOrganoid pattern\nCharacteristic\nCharacteristic\nPresent, less extensive\nAbsent\nNecrosis\nAbsent\nUsually focal\nExtensive\nExtensive\nMitoses/10 HPF\n<2\n2-10\n>10 (mean 70)\nMean 70\nProminent nucleoli\nNo\nNo\nYes\nNo\nNuclear pleomorphism\nUsually absent\nOccasionally \npresent\nPresent\nPresent\nCell size\nLarge\nLarge\nLarge\nSmall\nCytoplasm\nAbundant\nAbundant\nAbundant\nScanty\nApproximate 5-year \nsurvival\n100%\n70%\n25%\n<10%\nFrom Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (eds): World Health Organization classification of tumors. Pathology and genetics of \ntumors of the lung, pleura, thymus, and heart. IARC, Lyon, France, 2004.\nTABLE 26\u20136.\u2003\nGRADING SYSTEM FOR LUNG CARCINOMAS\nGrade 1\nWell differentiated\nGrade 2\nModerately differentiated\nGrade 3\nPoorly differentiated\nGrade 4\nUndifferentiated\nThe least differentiated portion of the carcinoma is used for grading. Undifferentiated carcinomas do not exhibit either squamous or glandular dif\u00ad\nferentiation. Small cell and large cell carcinomas are given a grade 4.\nTABLE 26\u20137.\u2003 VISCERAL PLEURAL INVASION (VPI)\nPL0\nCarcinoma does not invade beyond the thick elastic layer of the pleura. Tumor cells may \nintermingle with elastic fibers, as long as they do not penetrate beyond the layer.\nPL1\nCarcinoma invades beyond the thick elastic layer, but is not present on the surface of the pleura.\nPL2\nCarcinoma invades beyond the elastic layer and is present on the surface of the pleura.\nPL3\nCarcinoma invades through the pleura and involves parietal pleura.\nNote: An elastic stain can be helpful to identify the elastic fibers of the pleura to distinguish PL1 from PL1.\nData from Shim HS, Park IK, Lee CY, Chung KY, Prognostic significance of visceral pleural invasion in the forthcoming (seventh) edition of TNM clas\u00ad\nsification for lung cancer, Lung Cancer, 2009 (in press) and Travis WD, Brambilla E, Rami-Porta R, Valliers E, Tsuboi M, Rusch V, Goldstraw P, on behalf \nof the International staging commitee, Visceral pleura invasion: pathologic criteria and use of elastic stains. Proposal for the 7th edition of the TNM \nclassification for lung cancer, J Thorac Oncol 3:1384-1390, 2008.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_519.png", "summary": "This page discusses the classification of pulmonary neuroendocrine tumors, grading system for lung carcinomas, and visceral pleural invasion criteria.", "questions": [ "What are the key features that differentiate typical carcinoid, atypical carcinoid, large-cell neuroendocrine carcinoma, and small-cell lung carcinoma?", "How is the grading system for lung carcinomas determined?", "What are the criteria for visceral pleural invasion and how is it classified?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 520, "text": "LUNG AND PLEURA\u2003 Lung\n502\n\t\u2022\t \u0007Margins: Uninvolved, involved (distance from closest margin)\n\t \u2022\t \u0007Note if squamous cell carcinoma is present at the bronchial margin.\n\t \u2022\t \u0007Specify margin (bronchial, vascular, parenchymal, parietal pleural, chest well, other attached tissue)\n\t\u2022\t \u0007Treatment Effect: If there has been prior neoadjuvant therapy: not identified, >10% residual viable \ntumor, <10% residual viable tumor\n\t\u2022\t \u0007Tumor Associated Atelectasis or Obstructive Pneumonitis: Extends to the hilar region (but not \nentire lung), involves entire lung\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Regional Lymph Nodes: Absent, present (number involved, number examined). Includes nodes \ninvolved by direct extension of the primary tumor (but include description in report).\n\t \u2022\t \u0007Location of lymph nodes. Locations designated by the surgeon must be faithfully transcribed to the \nfinal report.\n\t \u0007\u2022\t \u0007Extranodal extension should be reported if present.\n\t\u2022\t \u0007Additional Pathologic Findings: Atypical adenomatous hyperplasia, squamous dysplasia, metaplasia, \ndiffuse neuroendocrine hyperplasia, inflammation, granulomas, atelectasis, emphysema, fibrosis\n\t\u2022\t \u0007Ancillary Studies: Epidermal growth factor receptor (EGFR) analysis, KRAS mutational analysis\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classfication.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 26-8). M0 \nis conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nPneumonectomies with Partial Chest Wall Resection\nLung tumors that focally invade into the chest wall, but do not show evidence of metastatic spread, may \nbe resected in continuity with portions of several ribs. Usually the patients will have been treated with \nradiation and/or chemotherapy.\nVisceral pleura\nExternal elastic lamina\n(usually seen on H&E)\nInternal elastic lamina\n(usually requires elastic stain)\nT1\u2013 No invasion\nT2\u2013 Invasion of visceral pleura\nT3\u2013 Chest wall invasion\nT1\nT2\nT2\nParietal pleura\nChest wall\nPleural space\nFigure 26-2.\u2002 Pleural involvement by carcinomas. The inner pleural elastic lamina is best seen using special elastic \nstains. Invasion has been shown to have prognostic significance.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_520.png", "summary": "The page provides detailed guidelines for reporting on lung and pleura specimens, including margin status, treatment effect, lymphovascular invasion, regional lymph nodes, ancillary studies, distant metastasis, and AJCC classification.", "questions": [ "How does the presence of squamous cell carcinoma at the bronchial margin impact the diagnosis?", "What are the implications of tumor-associated atelectasis or obstructive pneumonitis extending to the hilar region or involving the entire lung?", "Why is it important to faithfully transcribe the locations of lymph nodes as designated by the surgeon in the final report?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 521, "text": "LUNG AND PLEURA\u2003 Lung\n503\nTABLE 26-8.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF LUNG TUMORS\nTUMOR\nTX\nPrimary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or \nbronchial washings but not visualized by imaging or bronchoscopy\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ\nT1\nTumor \u22643 cm in greatest dimension, surrounded by lung or visceral pleura without bronchoscopic \nevidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus)*\nT2\nTumor more than 3 cm but 7 cm or less or tumor with any of the following features (T2 tumors with \nthese features are classified T2a if 5 cm or less);\nInvolves main bronchus, 2 cm or more distal to the carina\nInvades visceral pleural (PL1 or PL2)\nAssociated with atelectasis or obstructive pneumonitis that extends to the hilar region but does \nnot involve the entire lung\nT2a\nTumor more than 3 cm but 5 cm or less in greatest dimension\nT2b\nTumor more than 5 cm but 7 cm or less in greatest dimension\nT3\nTumor more than 7 cm or one that directly invades any of the following:\nParietal pleura (PL3)\nChest wall (including superior sulcus tumors)\nDiaphragm\nPhrenic nerve\nMediastinal pleura\nParietal pericardium\nTumor in the main bronchus less than 2 cm distal to the carina,* but without involvement of the \ncarina\nAssociated atelectasis or obstructive pneumonitis of the entire lung\nSeparate tumor nodule(s) in the same lobe\nT4\nTumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, \nrecurrent laryngeal nerve, esophagus, vertebral body, carina, or separate tumor nodule(s) in a \ndifferent ipsilateral lobe\n*The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main \nbronchus, is also classified as T1a.\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary \nnodes including involvement by direct extension\nN2\nMetastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)\nN3\nMetastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or \nsupraclavicular lymph node(s)\nDISTANT LYMPH NODES\nM0\nNo distant metastasis\nM1\nDistant metastasis\ncontinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_521.png", "summary": "This page provides the AJCC (7th Edition) classification of lung tumors, detailing the criteria for primary tumor assessment and staging based on tumor size and invasion.", "questions": [ "How is the primary tumor assessed when it cannot be visualized by imaging or bronchoscopy?", "What are the key features that determine the T stage of lung tumors?", "What are the criteria for regional lymph node metastasis classification in lung cancer?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 522, "text": "LUNG AND PLEURA\u2003 Lung\n504\nThe portion of chest wall should be oriented including identification of the ribs present. Posterior \nresections may include portions of the vertebral bodies. Anterior resections may include costal cartilage.\nSpecimens should be radiographed to identify all bones present and to evaluate possible bone destruc\u00ad\ntion by tumor. The entire specimen should be fixed.\nSoft tissue margins on the chest wall will include the superficial soft tissue (lying beneath the subcuta\u00ad\nneous tissue of the chest wall) as well as superior, inferior, medial, and lateral soft tissue around the ribs. \nParietal pleura in these areas should also be sampled. These margins as well as sections of the tumor and \nlung are taken first.\nAfter soft tissue sections are removed, the lung may be removed from the chest wall portion. The \nbones are then decalcified. Rib margins are taken from the anterior and posterior portion of each rib. \nAdditional sections are taken demonstrating the relationship of the tumor to the adjacent ribs, including \nany areas suspicious for bone destruction on the specimen radiograph.\nTransplant Pneumonectomies\nThe common indications for lung transplantation are idiopathic pulmonary fibrosis, emphysema, cystic \nfibrosis, and pulmonary hypertension. The pathologist\u2019s role is to document the underlying disease in \nthe recipient lung and to identify any clinically unsuspected disease processes. Occasionally unused donor \nlungs will be submitted. If the contralateral lung has been transplanted, it is important to look for unsus\u00ad\npected disease processes that may affect the recipient (e.g., infection, malignancies). Both recipient and \ndonor lungs may be processed in the same manner.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh and measure the lung. Examine the pleura for any evidence of disease (smooth and glistening, \ndull and irregular, adhesions). Sterile tissue is submitted for \u00adcultures (bacterial, fungal, and viral) from \nan unused donor lung if the contralateral lung has been transplanted.\n 2.\t \u0007Inflate the lung with formalin, either through the bronchus or by using a syringe, and fix overnight.\n 3.\t \u0007Cut the lung into sagittal sections.\n 4.\t \u0007Examine the parenchyma carefully looking for any focal lesions or evidence of infection, ischemia \n(variations in color or texture), or trauma.\n 5.\t \u0007Submit from six to ten cassettes including central and peripheral lung parenchyma, bronchial \nresection \u00admargin, smaller airways, pulmonary vessels (both large and small), hilar lymph nodes, \nand any focal lesions. If infection is suspected, order AFB, gram, and MSS stains on a representa\u00ad\ntive cassette.\nSPECIAL STUDIES\nPulmonary hypertension. Angiograms may be performed on surgical specimens by filling the vessels \nwith contrast agent using the pressures observed clinically. Although unlikely to be necessary for clini\u00ad\ncal management of the patient, the demonstration of markedly diminished pulmonary vasculature can \nprovide an excellent teaching example. The tissue slices can also be radiographed.\nM1a\nSeparate tumor nodule(s) in a contralateral lobe, tumor with pleural nodules, or malignant pleural \n(or pericardial) effusion*\nM1b\nDistant metastasis\n*Most pleural (and pericardial) effusions with lung cancer are due to tumor. In a few patients, however, multiple cytopathologic examinations of \npleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and is not an exudate. Where these elements and clinical judgment \ndictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient should be classified as M0.\nNote: This classification includes carcinomas and carcinoid tumors.\nFrom the AJCC Cancer Staging Manual, Seventh Edition, New York, Springer-Verlag, 2009. Used with the permission of the American Joint \n\u00adCommittee on Cancer (AJCC), Chicago, Illinois.\nTABLE 26\u20138.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF LUNG TUMORS\u2014cont\u2019d\nDISTANT LYMPH NODES", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_522.png", "summary": "The page discusses the orientation and processing of lung specimens, including the importance of radiographing to identify bone destruction by tumor, sampling soft tissue margins, and examining the pleura for evidence of disease. It also covers the processing of lungs for transplantation, including documenting underlying diseases and performing special studies like angiograms.", "questions": [ "How are soft tissue margins on the chest wall sampled and why is this important?", "What are the common indications for lung transplantation?", "Why is it important to examine the pleura for evidence of disease during the processing of lung specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 523, "text": "LUNG AND PLEURA\u2003 Lung\n505\nExtrapleural Pneumonectomies\nThis procedure is a commando resection of malignant mesothelioma and, on rare occasions, of carci\u00ad\nnoma of the lung that has not spread beyond the lung, pleura, and local lymph nodes. The lung with \nattached hemidiaphragm is resected together with the surrounding parietal and mediastinal pleura and a \nportion of the pericardium.\nExtrapleural pneumonectomy is associated with a better prognosis in mesothelioma. However, \nwhether this is because this population tends to be younger, healthier, and with more limited disease, or \nwhether the procedure itself is beneficial, is still unclear.\nRelevant clinical history includes prior exposure to asbestos (e.g., by occupation), radiation exposure, \nextent of disease by radiologic studies, prior procedures and diagnoses, and prior treatment (e.g., talc \npoudrage).\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh the specimen and record the outer dimensions (total dimensions, dimensions of lung, dimen\u00ad\nsions of diaphragm, size of pericardium, bronchial margin).\n 2.\t \u0007Identify areas of tumor involvement in the pleura. Distinguish tumor from pleural plaque and talc \nreaction site (see below). The bases tend to be involved more extensively than the apex.\nIt may be helpful to save tissue for EM and cytogenetics. Adjacent tissue for permanent sections \nshould be matched with this tissue.\n 3.\t \u0007Inflate the lung through the bronchus and fix overnight.\n 4.\t \u0007Examine and describe the outer surface of the pleura (i.e., the parietal pleura).\n\t \u2022\t \u0007Rents in the parietal pleura: Location and size.\n\t \u2022\t \u0007Percent involvement of pleura by tumor: Occasionally the full extent of parietal pleural involvement \nis evident only after examining its inner aspect either via rents in the pleura or after coronal section\u00ad\ning. Describe the range of size of the nodules (three dimensions), and the range in thickness of the \nunfused pleura (defer to after sectioning in areas fused with visceral pleura).\n\t \u2022\t \u0007Chest wall tissue: Look for any areas of adherent muscle or soft tissue to the parietal pleura that may \nindicate invasion into the chest wall.\n\t \u2022\t \u0007Pericardium: Involvement by tumor, penetration through to pericardial surface (present or absent)\n\t \u2022\t \u0007Pleural plaques\n\t \u2022\t \u0007Talc reaction sites\n\t \u2022\t \u0007Mesothelioma: Usually less dense than plaque, firm (not as hard as plaque), gray/white, frequently \nnodular, and occasionally myxoid in appearance.\n 5.\t \u0007Serially section the specimen at 1 cm intervals in the coronal (frontal) plane. These sections are easy \nto cut, easy to orient, and demonstrate the pleural involvement well.\n 6.\t \u0007Describe the tumor involvement of the diaphragm including distance from margins (anterior, pos\u00ad\nterior, medial, and lateral), depth of invasion into the diaphragm (noting any invasion of skeletal \nmuscle), involvement of the peritoneal surface of the diaphragm (this is rare).\n 7.\t \u0007Describe visceral pleural involvement including the percentage of visceral pleura fused to parietal \npleura, the range in thickness of fused and unfused pleura, the percentage of unfused visceral pleura \ninvolved by tumor, the range of size of the nodules (unfused visceral pleura in three dimensions), and \nthe site and size of any loculated effusions.\nDescribe the lung parenchyma including any tumor involvement. Usually mesothelioma does not \ndirectly invade into lung parenchyma but pushes pleura ahead of it as it bulges into the lung. However, \ntumor often invades into and thickens interlobar fissures (note site and extent). Describe parenchymal \nfibrosis, emphysematous changes, and consolidation.\nRarely, a second malignancy may be detected within the lung parenchyma.\n 8.\t \u0007Describe (number and size) any hilar lymph nodes (anthracotic and soft = normal; white and hard = \ntumor). Mesothelioma may metastasize to lymph nodes; this is an adverse prognostic feature.\n 9.\t \u0007Selectively ink (before taking sections) areas of the resection margins that demonstrate the closest \nextension of tumor involvement to the pleural surface (tumor involvement of margins is an adverse \nprognostic factor) and diaphragmatic margins. Take sections (perpendicular to the pleura, two to \nthree per cassette if the pleura is less than 0.5 cm thick) from the apex of the lung, from the anterior, \nposterior, medial, and lateral pleura at one level and perpendicular sections from the anterior, lateral, \nmedial, posterior, and deep (= inferior) margins of the diaphragm.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_523.png", "summary": "Extrapleural pneumonectomy is a surgical procedure for malignant mesothelioma and select cases of lung carcinoma. The prognosis for mesothelioma patients undergoing this procedure is better, but the exact reason for this improvement is still uncertain.", "questions": [ "What are the key factors to consider when determining whether a patient is a candidate for an extrapleural pneumonectomy?", "How does prior exposure to asbestos or radiation impact the decision to perform an extrapleural pneumonectomy?", "What are the specific steps involved in processing a specimen from an extrapleural pneumonectomy for pathological analysis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 524, "text": "LUNG AND PLEURA\u2003 Lung\n506\n 10.\u2002 \u0007A small segment of rib is usually resected. Describe dimensions, color of bone, color of marrow \ncavity. A marrow squeeze can be submitted (see Chapter 14) unless gross lesions are identified or \nthe bone is attached to the chest wall. In the latter cases, the bone should be radiographed and all \nsections suspicious for bony involvement submitted. If a portion of chest wall is received attached to \nthe specimen, the margins of the chest wall are submitted.\nSPECIAL STUDIES\n\t\u2022\t \u0007Mesotheliomas: Usually the diagnosis will have been well established prior to resection. Mesothe\u00ad\nliomas can be distinguished from other tumors by characteristic findings by immunohistochemistry, \nEM, and cytogenetics (see specific tables in Chapter 7). It may be helpful to save tissue for these \nstudies.\n\t\u2022\t \u0007Asbestos body counts and asbestos fiber analysis: Formalin-fixed lung tissue (not tumor or plaque) \nis used for these studies, which have an important role in the determination of the causation of meso\u00ad\nthelioma. Asbestos bodies (asbestos fibers with an iron-protein coat and visible in by light microscopy), \nare quantified after digestion and millipore filtration. Asbestos fibers (invisible by light microscopy) \nare identified and quantified by energy dispersive x-ray analysis that affords separation of chrysotile, \namosite, tremolite, and crocidolite asbestos fibers derived from various asbestos-containing materials. \nThe periphery of the lung is preferred.\nGROSS DIFFERENTIAL DIAGNOSIS\nMesotheliomas.\u2002 Mesothelioma is usually white to gray, firm, and homogeneous. The tumors are \nonly rarely hemorrhagic or necrotic.\nMesotheliomas grow in a very characteristic pattern within the pleura. Early in the development of \nthe tumor, macules, polyps, and/or nodules form, probably first in the parietal pleura. In cases diagnosed \nprior to fusion of the parietal and visceral pleura, the parietal pleura is often more extensively involved. \nWith time, the involved areas enlarge, coalesce and thicken the pleura and the parietal and visceral pleura \nfuse to form a thick rind about the lung and extend into the interlobar fissure(s). Tumor is often more \nextensive in basal portions of the lung than in apical areas. It will be helpful to identify cases with limited \nearly involvement that would refute or support the limited evidence that mesotheliomas originate in the \nparietal pleura.\nThe tumor is usually sharply demarcated from the lung parenchyma. However, sampling of areas in which \nthe tumor bulges into peripheral parenchyma may reveal microscopic areas of invasion. Separate tumor nod\u00ad\nules within lung parenchyma are exceedingly uncommon and may represent a second primary tumor.\nInvasive areas into the soft tissue of the chest wall (adipose tissue, muscle, fascia, or bone) are usually small \nand focal in extrapleural pneumonectomy specimens, as invasion of the chest wall is generally a contraindica\u00ad\ntion to surgery. Tumor is sometimes seen in soft tissue at the site of prior surgical interventions (e.g., prior \nchest tube sites). Lymph node metastasis may occur, but involvement is not usually seen on gross examination.\nCarcinoma.\u2002 Extrapleural pneumonectomy is rarely performed for carcinomas with pleural involve\u00ad\nment. The carcinoma is usually present within the lung and often has central cavitation or necrosis. The \ninvolvement of the pleura may be diffuse, closely mimicking mesothelioma, but patchy involvement \nwith focal nodule formation and sparing of large areas of the pleura are clues suggesting carcinomatous \ninvolvement, especially when the parenchymal tumor is large. Invasion into soft tissue or bone may be \npresent. Lymph node metastases are frequent.\nTalc Pleurodesis.\u2002 Some patients will have undergone talc pleurodesis to control symptoms from \npleural effusions. The talc will be between the parietal and the visceral pleuras and will have caused them \nto fuse. The talc looks pale yellow grossly and is associated with a fibrotic reaction that can make it dif\u00ad\nficult to distinguish it from tumor. The tissue is softer than a pleural plaque, and is usually a thin well-\ndemarcated area measuring 1 to 3 cm \u00d7 0.2 to 0.3 cm. These areas can be distinguished from tumor by \nmaking scrape preparations to look for talc (polarizable).\nPleural Plaques.\u2002 Discrete patches of flat, thickened, hard white pleura, often with a shelf-like mar\u00ad\ngin, and sometimes with calcification. The surface is relatively smooth with characteristic small pits. The \nthickness is usually about 0.3 to 0.5 cm. These plaques are strongly related to prior asbestos exposure.2", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_524.png", "summary": "The page discusses the resection of lung tissue and ribs for pathology examination, as well as special studies and gross differential diagnosis for mesotheliomas.", "questions": [ "How are mesotheliomas distinguished from other tumors by immunohistochemistry, EM, and cytogenetics?", "What role do asbestos body counts and asbestos fiber analysis play in determining the causation of mesothelioma?", "What are the characteristic growth patterns of mesotheliomas within the pleura?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 525, "text": "LUNG AND PLEURA\u2003 Lung\n507\nDocumenting their presence may be helpful in determining the likelihood of occupational exposure to \nasbestos.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor and pleural margins: Take sections of resection margins (after selective inking) with underly\u00ad\ning tumor and superficial lung parenchyma perpendicular to the pleural surface.\nIn the usual case with extensive fusion of parietal and visceral pleura, nine to ten cassettes includ\u00ad\ning margins of parietal pleura chosen to demonstrate the closest approach of the tumor to the resec\u00ad\ntion margin (apex, and anterior, lateral, posterior, and medial pleura), and tumor and diaphragm, \ntumor and lung (demonstrating any invasion into lung), small and large nodules, any areas of variable \nappearance.\nIn the unusual case with limited or no areas of fusion of parietal and visceral pleura, take sections \nas above and also sample the unfused visceral pleura (apex, anterior, lateral, posterior, medial, and dia\u00ad\nphragmatic) to reflect areas of minimal (gray macules, nodules, or polyps) and maximal involvement \n(solitary or coalesced nodules).\n\t\u2022\t \u0007Pericardium: One to two sections to demonstrate tumor, deepest penetration of pericardium by \ntumor, closest margin.\n\t\u2022\t \u0007Diaphragmatic margins: Sections (inked, perpendicular) from anterior, lateral, posterior, and medial \nmargins. Take sections to demonstrate the site of deepest penetration of tumor into the diaphragmatic \nmuscle.\n\t\u2022\t \u0007Lung: Two generous sections (in separate cassettes) of representative lung from periphery of both \nupper and lower lobes (these may be essential in determining exposure to asbestos) and any focal \nlesions.\n\t\u2022\t \u0007Bronchial resection margin: One section, en face. This will usually have been taken as a frozen \n\u00adsection.\n\t\u2022\t \u0007Hilar lymph nodes: Submit each lymph node.\n\t\u2022\t \u0007Separate rib: A bone marrow squeeze may be performed if the rib is not attached to the specimen and \nis grossly normal. If the bone is attached or grossly abnormal the bone must be decalcified and cross \nsections submitted. See Chapter 14 for instructions.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number, are two specimens.\nThe first specimen is labeled \u201crib\u201d and consists of a 5 \u00d7 2 \u00d7 0.8 cm segment of grossly unremarkable \nrib. A marrow squeeze is performed.\nCassette #1: Rib, marrow squeeze, 1 frag, RSS.\nThe second specimen is labeled \u201clung\u201d and consists of a 750 gram right extrapleural pneumonectomy \nspecimen (26 \u00d7 20 \u00d7 15 cm) consisting of lung (24 \u00d7 18 \u00d7 14 cm), parietal pleura, pericardium (10 \u00d7 7 \u00d7 \n0.2 cm), and hemidiaphragm (21 \u00d7 14 \u00d7 0.3 to 1.4 cm). The parietal pleura is thickened, white, and intact \nexcept for a 6 \u00d7 0.5 cm linear rent over the lateral aspect of the mid portion of the lung. A few tags of \nfibrous tissue are adherent to the surface. Approximately 75% of the parietal pleura is occupied by nodules \nof firm gray tumor, ranging in size from 0.2 cm in diameter to 1.5 \u00d7 1.2 \u00d7 1.0 cm. Tumor is grossly present \nat the lateral pleural resection margin at the junction of upper and middle thirds of the lung. Apical and \nadjacent upper lobe pleura is relatively spared by tumor. The visceral and parietal pleura are thickened \n(to 1.2 cm maximum thickness, greatest basally) and are fused (75% of surface), except posteriorly and \ninferiorly where there is a loculated area of effusion (9 \u00d7 5 \u00d7 2 cm) filled with red cloudy fluid. Unfused \nvisceral pleura (adjacent to the effusion) is thickened (0.2 cm) and contains scattered tumor nodules rang\u00ad\ning from 0.2 to 0.5 cm in greatest dimension. The tumor bulges (0.5 cm) into lung parenchyma in several \nfoci (lower lobe) and thickens (to 0.5 cm) an interlobar septum for a distance of approximately 4 cm. The \ndiaphragmatic parietal and visceral pleura are thickened (1.2 cm) and fused. The diaphragmatic margins \nare grossly free of tumor with the closest approach of tumor being 0.2 cm at the lateral margin. Tumor \ninvades to a depth of 0.3 cm into the muscle of the diaphragm, but the inferior surface is free of tumor. \nA\u00a0flattened hard white pleural plaque (5 \u00d7 4 \u00d7 0.5 cm) is present in the lateral aspect of the \u00adparietal pleura. \nThere are mild emphysematous changes in the peripheral lung parenchyma. The bronchial margin is free \nof lesions and was examined by frozen section with an en face section. There are three firm anthracotic", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_525.png", "summary": "Documentation of lung and pleura involvement is crucial for determining occupational exposure to asbestos. Microscopic sections should be taken to assess tumor margins, pleural involvement, pericardium, diaphragmatic margins, lung parenchyma, bronchial resection margin, hilar lymph nodes, and separate rib.", "questions": [ "How does the presence of asbestos exposure affect the evaluation of lung and pleura specimens?", "What specific sections should be taken to assess tumor margins and pleural involvement?", "Why is it important to sample both fused and unfused visceral pleura in cases of limited fusion?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 526, "text": "508\nLUNG AND PLEURA\u2003 Lung\nlymph nodes in the perihilar soft tissue, the largest measuring 1.5 cm in \u00adgreatest \u00addimension. Tumor \nis saved for snap freezing, electron microscopy, and cytogenetics. Fixed tissue (5 \u00d7 5 \u00d7 5 cm) from the \n\u00adperiphery of the lower lobe is given to Dr. J. Godleski for asbestos fiber analysis. \u00adPhotographs are taken.\nCassette #2: Tumor, quick fix in formalin, 2 frags, area taken for special studies, RSS.\nCassette #3: Apical pleural margin, perpendicular, 1 frag, RSS.\nCassette #4: Medial pleural margin, perpendicular., 1 frag, RSS.\nCassette #5: Lateral pleural margin, site of gross extension to inked margin, perpendicular., 2 frag, \nRSS.\nCassette #6: Anterior pleural margin, perpendicular., 1 frag, RSS.\nCassette #7: Posterior pleural margin, perpendicular., 1 frag, RSS.\nCassette #8: Medial diaphragm margin, perpendicular., 1 frag, RSS.\nCassette #9: Lateral diaphragm margin, perpendicular., 1 frag, RSS.\nCassette #10: Anterior diaphragm margin, perpendicular, 1 frag, RSS.\nCassette #11: Posterior diaphragm margin, perpendicular, 1 frag, RSS.\nCassette #12: Tumor and diaphragm, central portion, deepest extent of tumor, 1 frag, RSS.\nCassettes #13-14: Tumor and interlobar fissure, 2 frags, RSS.\nCassette #15: Largest tumor nodule, parietal pleura, 2 frags, RSS\nCassette #16: Smallest and larger tumor nodules, visceral pleura, 3 frag, RSS\nCassette #17: Pleural plaque, 3 frags, RSS.\nCassette #18: Bronchial resection margin, frozen section remnant, 1 frag, ESS.\nCassettes #19-20: Upper lobe parenchyma, 1 frag each, RSS.\nCassettes #21-22: Lower lobe parenchyma, 1 frag each, RSS.\nCassette #23: Perihilar lymph nodes, 3 frags, ESS.\nCassettes #24-25: Pericardium, closest approach of tumor, 4 frags, RSS.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC SIGN-OUT CHECKLIST FOR MESOTHELIOMAS\n\t\u2022\t \u0007Specimen: Pleura, lung (right, left), diaphragm, chest wall\n\t\u2022\t \u0007Procedure: Pleural decortication, pleurectomy, pericardial resection, extrapleural pneumonectomy\n\t\u2022\t \u0007Specimen Integrity: Intact, disrupted\n\t\u2022\t \u0007Specimen Laterality: Right, left\n\t\u2022\t \u0007Tumor Site: Parietal pleura, visceral pleura, diaphragm, pericardium\n\t\u2022\t \u0007Tumor Size: For localized tumors \u2013 greatest dimension (additional dimensions optional)\n\t\u2022\t \u0007Tumor Focality: Localized, diffuse\n\t\u2022\t \u0007Histologic Type: Mesothelioma, epithelial type (best prognosis), sarcomatoid type, mixed epithelial \nand sarcomatoid type, mesothelioma (usually sarcomatoid) with extensive desmoplasia (desmoplastic \nmesothelioma), undifferentiated, other rare types\n\t\u2022\t \u0007Tumor Extension: Parietal pleura, visceral pleura, invasion of lung parenchyma, invasion of \n\u00addiaphragmatic muscle, invasion of endothoracic fascia, invasion of mediastinal fat, invasion of pericar\u00ad\ndium (partial or transmural), invasion of bone (rib or spine), invasion of contralateral pleura, invasion \nof myocardium, invasion of brachial plexus\n\t\u2022\t \u0007Margins: Parietal pleura (anterior, posterior, medial, lateral), chest wall, diaphragm (anterior, poste\u00ad\nrior, medial lateral, inferior or caudal), bronchus\n\t\u2022\t \u0007Treatment Effect: If there has been neoadjuvant treatment: not identified, greater than 50% residual \nviable tumor, less than 50% residual viable tumor\n\t\u2022\t \u0007Involvement of anatomic structures: % of parietal and of visceral pleura involved by tumor\n\u00adThickening of pleura by tumor (range/minimum and maximum)\nInvolvement of diaphragmatic \u00admuscle/pericardium/rib involvement of adipose tissue/endothoracic \nfascia/skeletal muscle of chest wall \nLung parenchyma or tissues in the contralateral chest\n\t\u2022\t \u0007Pleura: Plaque (present/absent), asbestos bodies, talc pleurodesis\n\t\u2022\t \u0007Additional Pathologic Findings: Fibrosis, pneumonia, emphysema, atelectasis, granulomas, ferrugi\u00ad\nnous bodies, talc, etc.\n\t\u2022\t \u0007Regional Lymph Nodes: Involved or not involved, number, location, extracapsular invasion if present\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_526.png", "summary": "The page describes the detailed sampling and processing of tissue specimens from a lung and pleura resection for various studies and analyses, including asbestos fiber analysis and tumor characterization.", "questions": [ "What are the different types of tissue specimens collected and processed in this case?", "What specific studies are being conducted on the tumor and tissue samples?", "How important is the information obtained from analyzing the pleural margins and diaphragm margins in the context of mesothelioma diagnosis and prognosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 527, "text": "509\nLUNG AND PLEURA\u2003 Lung\nTABLE 26-9.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF PLEURAL MESOTHELIOMA\nTumor\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nTumor limited to the ipsilateral parietal pleura with or without mediastinal pleura and with or \nwithout diaphragmatic pleural involvement\nT1a\nNo involvement of visceral pleura\nT1b\nTumor also involving the visceral pleura\nT2\nTumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and \nvisceral pleura), with at least one of the following:\nInvolvement of diaphragmatic muscle\nExtension of tumor from visceral pleura into the underlying pulmonary parenchyma\nT3\nLocally advanced but potentially resectable tumor\nTumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and \nvisceral pleura), with at least one of the following:\nInvolvement of the endothoracic fascia\nExtension into mediastinal fat\nSolitary, completely resectable focus of tumor extending into the soft tissues of chest wall\nNon-transmural involvement of the pericardium\nT4\nLocally advanced but potentially resectable tumor\nTumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and \nvisceral pleura), with at least one of the following:\nDiffuse extension or multifocal masses of tumor in the chest wall, with or without associated \nrib destruction\nDirect transdiaphragmatic extension of tumor to the peritoneum\nDirect extension of tumor to mediastinal organs\nDirect extension of tumor to the contralateral pleura\nDirect extension of tumor into the spine\nTumor extending through to the internal surface of the pericardium with or without a peri\u00ad\ncardial effusion or tumor involving the myocardium\nRegional Lymph Nodes\nNX\nRegional lymph nodes cannot be assessed\nN0\nNo regional lymph node metastasis\nN1\nMetastasis in the ipsilateral bronchopulmonary or hilar lymph nodes\nN2\nMetastasis in the subcarinal or the ipsilateral mediastinal lymph nodes including the ipsilateral \ninternal mammary and peridiaphragmatic nodes\nN3\nMetastasis in the contralateral mediastinal, contralateral internal mammary, ipsilateral or contra\u00ad\nlateral supraclavicular lymph nodes\nDistant Metastasis\nM0\nNo distant metastasis\nM1\nDistant metastasis present\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \nCommittee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_527.png", "summary": "The page outlines the AJCC (7th Edition) classification of pleural mesothelioma, detailing the criteria for tumor classification based on size and extent of involvement.", "questions": [ "What are the different categories for tumor classification in pleural mesothelioma according to the AJCC (7th Edition)?", "How does the presence of regional lymph node metastasis impact the staging of pleural mesothelioma?", "What are the criteria for determining distant metastasis in pleural mesothelioma staging?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 528, "text": "LUNG AND PLEURA\u2003 Pleura\n510\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 26-9). M0 \nis conferred after clinical assessment; there is no pM0 category.\n\t \u2022\t \u0007Other staging systems (such as the Revised Sugarbaker Staging System or the International Meso\u00ad\nthelioma Interest Group System) may also be used (Tables 26-10 and 26-11)\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nPLEURA\nThe pleura is usually biopsied when there is a question of mesothelioma (e.g., a typical radiologic appear\u00ad\nance or effusion). This diagnosis may be very difficult to make on small specimens.\nBiopsy\nIf mesothelioma is in the clinical differential diagnosis, and there is sufficient lesional tissue, tissue should \nbe taken for special studies. In the OR consultation room, pathologists must be aggressive and timely \nabout requesting additional tissue, especially if most or all of the lesional tissue has been taken for a fro\u00ad\nzen section. Freezing the tissue may alter the immunogenicity and may prevent a definitive diagnosis on \npermanent sections. For example, calretinin may only be weakly positive in previously frozen tissue from \n\u00admesotheliomas. The most important studies, after adequate tissue is available for light microscopy, are \nEM followed by cytogenetics.\nPleurectomy\nPleurectomies are occasionally performed for debulking of mesotheliomas if the tumor is unresectable. \nThe specimen consists of multiple fragments of pleura with tumor implants. Pleurectomy may also be \nperformed for diagnosis in cases of chronic fibrosing pleuritis, to rule out the presence of a desmoplastic \nmesothelioma.\nTABLE 26\u201310.\u2003\n\u0007REVISED SUGARBAKER STAGING SYSTEM FOR MALIGNANT PLEURAL \nMESOTHELIOMA\nSTAGE\nDESCRIPTION\nI\nDisease completely resected within the capsule of the parietal pleura without lymph node \ninvolvement (originally designated \u201cadenopathy\u201d in the published system), ipsilateral \npleura, lung, pericardium, diaphragm, or chest wall disease limited to previous biopsy \nsites\nII\nAll of stage I with positive resection margins and/or intrapleural lymph node involvement\nIII\nLocal extension of disease into the chest wall or mediastinum; to heart, or through \n\u00addiaphragm, peritoneum; or with extrapleural lymph node involvement (mediastinal \nand peridiaphragmatic lymph nodes not located within the pleural reflection)\nIV\nDistant metastatic disease\nFrom Sugarbaker DJ, Flores RM, Jaklitsch MT, Richards WG, Strauss GM, Corson JM, DeCamp Jr, MM, Swanson SJ, Bueno R, Lukanich JM, \nHealey Baldini E, Mentzer SJ, Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality \ntherapy of malignant pleural mesothelioma: results in 183 patients, J Thorac Cardiovasc Surg 117:54-65,1999.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_528.png", "summary": "The page discusses the staging and biopsy procedures for pleural mesothelioma, emphasizing the importance of obtaining sufficient tissue for special studies.", "questions": [ "What are the key staging systems used for malignant pleural mesothelioma?", "Why is it important to obtain sufficient lesional tissue for special studies in cases of suspected mesothelioma?", "What are the indications for performing a pleurectomy in cases of mesothelioma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 529, "text": "LUNG AND PLEURA\u2003 Pleura\n511\nTABLE 26\u201311.\u2003\nINTERNATIONAL MESOTHELIOMA INTEREST GROUP STAGING SYSTEM\nPRIMARY \nTUMOR T\nT1\nT1a\nTumor limited to the ipsilateral parietal pleura, including mediastinal and \ndiaphragmatic pleura. No involvement of the visceral pleura.\nT1b\nTumor involving the ipsilateral parietal pleura, including mediastinal and dia\u00ad\nphragmatic pleura. Scattered foci of tumor also involving the visceral pleura.\nT2\nTumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, \ndiaphragmatic, and visceral pleura) with at least one of the following features:\nInvolvement of diaphragmatic muscle\nConfluent visceral pleural tumor (including the fissures) or extension of \ntumor from visceral pleura into the underlying pulmonary parenchyma\nT3\nTumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, \ndiaphragmatic, and visceral pleura) with at least one of the following \nfeatures:\nInvolvement of the endothoracic fascia\nExtension into the mediastinal fat\nSolitary, completely resectable focus of tumor extending into the soft \ntissues of the chest wall\nNontransmural involvement of the pericardium\nT4\nTumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, \ndiaphragmatic, and visceral pleura) with at least one of the following fea\u00ad\ntures:\nDiffuse extension or multifocal masses of tumor in the chest wall with or \nwithout associated rib destruction\nDirect transdiaphragmatic extension of tumor to the peritoneum\nDirect extension to the contralateral pleura\nDirect extension of tumor to one or more mediastinal organs\nDirect extension of tumor into the spine\nTumor extending through to the internal surface of the pericardium with \nor without a pericardial effusion; or tumor involving the myocardium\nRegional Lymph \nNodes\nNX\nRegional lymph nodes cannot be assessed\nN0\nNo regional lymph node metastasis\nN1\nMetastasis to ipsilateral bronchopulmonary or hilar lymph nodes\nN2\nMetastasis to the subcarinal or the ipsilateral mediastinal lymph nodes, \n\u00adincluding the ipsilateral internal mammary nodes\nN3\nMetastasis to contralateral mediastinal, contralateral internal mammary, \n\u00adipsilateral or contralateral supraclavicular lymph node(s)\nDistant Metastasis\nMX\nDistant metastasis cannot be assessed\nM0\nNo distant metastasis\nM1\nDistant metastasis present\nFrom Rusch VW, A proposed new international TNM staging system for malignant pleural mesothelioma from the International Mesothelioma \n\u00adInterest Group, Chest 108:1122-1128, 1995.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_529.png", "summary": "The International Mesothelioma Interest Group Staging System provides detailed criteria for staging malignant pleural mesothelioma based on the extent of tumor involvement in the pleura, regional lymph nodes, and distant metastasis.", "questions": [ "What are the key features used to determine the T stages of malignant pleural mesothelioma?", "How does the staging system classify regional lymph node involvement in malignant pleural mesothelioma?", "What are the implications of distant metastasis in the staging of malignant pleural mesothelioma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 530, "text": "LUNG AND PLEURA\u2003 Pleura\n512\nREFERENCES\n\t1.\u2002 \u0007Stewart S, Fishbein MC, Snell GI, et al: Revision of the 1996 working formulation for the standardization of \nnomenclature in the diagnosis of lung rejection. J Heart Lung Transplant 26:1229-1242, 2007.\n\t2.\u2002 \u0007Bianchi C, Brollo A, Ramani L, Zuch C. Pleural plaques as risk indicators for malignant pleural mesothelioma: a \nnecroscopy-based study. Am J Industrial Med 32:445-449, 1997.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Describe each fragment of pleura separately, including size and thickness. However, if three or more \nfragments are present, describe the number of fragments, overall dimensions, dimensions of small\u00ad\nest and largest fragment. Describe any lesions including color, consistency, size, percent of pleural \ninvolvement, any variability in appearance, distance from margins (if received as a single fragment). \nRecord the presence, size, and tumor involvement of any other structures (e.g., lung, skeletal muscle, \nadipose tissue, pericardium).\nNote the presence or absence of pleural plaques and give dimensions.\n 2.\t \u0007Consider taking lesional tissue for EM, cytogenetics, and snap freezing \u2013 especially if a diagnosis has \nnot been established.\n 3.\t \u0007Selectively ink margins that appear involved by tumor if a single fragment is received.\n 4.\t \u0007Submit approximately one cassette for every cm of greatest dimension of tumor, generally to a maxi\u00ad\nmum of 12 to 15 cassettes. Document representative involved margins if a single fragment is received \n(ink selectively or submit en face if grossly involved).\nSearch carefully for lung tissue, usually adherent to tumor as a thin rim. Take multiple sections (up to \nfive) of lung and adjacent tissue, to facilitate possible asbestos fiber analysis.\n 5.\t \u0007If the differential diagnosis is fibrosing pleuritis vs. desmoplastic mesothelioma, search carefully for all \nareas suspicious for tumor nodules. Extensive sampling is often necessary in such cases to confirm, or \nexclude, a desmoplastic mesothelioma.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_530.png", "summary": "The page provides guidelines for processing pleural specimens, including describing fragments, considering additional testing for diagnosis, selectively inking margins, submitting appropriate cassettes, and differentiating between fibrosing pleuritis and desmoplastic mesothelioma.", "questions": [ "What specific details should be included when describing each fragment of pleura?", "Why is it important to consider taking lesional tissue for electron microscopy, cytogenetics, and snap freezing?", "How can one differentiate between fibrosing pleuritis and desmoplastic mesothelioma based on the guidelines provided?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 531, "text": "513\n27\nLymph Nodes, Spleen, \nand Bone Marrow\nThe lymph nodes, spleen, and bone marrow are affected by a wide variety of neoplastic, infectious, and \nsystemic diseases.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 27-1.\nBONE MARROW\nBone marrow biopsies are performed to evaluate suspected hematologic disorders, or for the staging of \ncarcinomas and lymphomas.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Biopsies are optimally fixed in Zenker\u2019s fixative, which provides excellent histologic detail as well as \ndecalcification of the specimen.\n 2.\t \u0007Specimens should, ideally, remain in Zenker\u2019s for a minimum of 12 hours and no more than 30 hours. \nIf the specimen is easily bent, decalcification is adequate. Always check the date on the requisition \nform (i.e., specimens may arrive the same day or the day after the biopsy) to make sure that specimens \nare not left in Zenker\u2019s too long.\nTABLE 27\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR LYMPH NODE, SPLEEN, \nAND BONE MARROW SPECIMENS\nOrgan/tissue resected or biopsied\nLymphadenopathy\nPurpose of the procedure\nOrganomegaly (liver or spleen)\nGross appearance of the organ/tissue/lesion sampled\nHematologic findings (e.g., pancytopenia or lympho\u00ad\ncytosis)\nAny unusual features of the clinical presentation\nHelicobacter pylori infection\nAny unusual features of the gross appearance\nLDH level (a poor prognostic factor that correlates \nwith tumor burden)\nPrior surgery/biopsies - results\nConstitutional symptoms (e.g., night sweats, fever)\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug \nuse that can change the histologic appearance of \ntissues)\nCongenital immune disorders\nOrgan transplantation (solid organ or bone marrow)\nSerology (e.g., HTLV-1, Epstein-Barr virus)\nCompromised immune system\nAutoimmune disease", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_531.png", "summary": "The lymph nodes, spleen, and bone marrow can be affected by a variety of neoplastic, infectious, and systemic diseases. Bone marrow biopsies are commonly performed to evaluate hematologic disorders or stage carcinomas and lymphomas.", "questions": [ "What are some common neoplastic diseases that can affect the lymph nodes, spleen, and bone marrow?", "What is the purpose of using Zenker's fixative for bone marrow biopsies?", "How long should specimens ideally remain in Zenker's fixative for optimal results?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 532, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Lymph Nodes\n514\n 3.\t \u0007Describe the number of fragments, shape (tubular, irregular), and dimensions (length and diameter). \nWrap in lens paper and submit the entire specimen. The cassette is rinsed in one or more water baths \nwith stirring (use a magnetic stirrer) for 20 to 30 minutes. Mercury waste, including the initial water \nbaths, must be disposed of into a special waste container.\n 4.\t \u0007Describe any blood smears received with the biopsy. Unstained smears should be stained with Wright \nGiemsa.\n 5.\t \u0007Order one H&E and two Giemsa stains for routine cases.\nSPECIAL STUDIES ON BONE MARROW BIOPSIES\n\t\u2022\t \u0007Suspected infectious disease (e.g., in immunocompromised patients): Special stains for organ\u00ad\nisms can be ordered on fixed sections (e.g., AFB and silver stains).\n\t\u2022\t \u0007Myelodysplastic or myeloproliferative syndromes: Reticulin stains may be ordered to evaluate \nmarrow fibrosis. Iron stains are examined to evaluate ring sideroblasts.\nSAMPLE DICTATION\nReceived in Zenker\u2019s fixative, labeled with the patient\u2019s name and unit number and \u201cright iliac,\u201d is a 1.5 \ncm in length by 0.4 cm in diameter bone marrow biopsy stained yellow by the fixative. Accompanying \nthe specimen are two unstained coverslips that are submitted for Wright Giemsa staining. The specimen \nis decalcified in Zenker\u2019s fixative prior to submission.\nCassette #1: 1 frag, ESS.\nLYMPH NODES\nLymph Nodes: Suspected Lymphoproliferative Disease\nA single enlarged lymph node is often biopsied. Common diagnoses are reactive hyperplasia, lymphoma, \nand occasionally metastatic carcinoma. Appropriate processing of fresh tissue is necessary in order to use \nthe special techniques available for analyzing lymphoproliferative disorders (immunoperoxidase stud\u00ad\nies on frozen sections, flow cytometry, cytogenetics, and DNA analysis). In general, if there is enough \nlesional tissue, some tissue is fixed in formalin, as non-lymphoid antigens may not be optimally preserved \nin B5 (e.g., keratin), and the lacunar variants of Reed-Sternberg cells in nodular sclerosing Hodgkin lym\u00ad\nphoma are seen best in formalin-fixed tissue.\nIf infectious disease is suspected, appropriate precautions are taken (see Part One) and cultures sent, \nif not already sent by the surgeon.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the outer dimensions of the lymph node. Make very thin (2 to 3 mm) serial sections perpendic\u00ad\nular to the long axis, looking for focal lesions. Describe the node, including color (uniform or irregular, \npigmentation), nodularity, consistency (rubbery, hard), cystic areas, necrosis or hemorrhage. If there is \na suspicion of infectious disease, save a small amount of sterile tissue for cultures (viral and bacterial).\nA touch prep can be useful to make a preliminary diagnosis to guide the distribution of tissue.\n 2.\t \u0007Fresh tissue is submitted for special studies if indicated (see below).\n 3.\t \u0007Fix most of the tissue (after slicing thinly) in B5 for 3 to 5 hours and representative sections in formalin. \nAfter fixation in B5, the tissue can be placed in formalin. Overfixation in B5 will make the tissue brittle.\n 4.\t \u0007All tissue is allowed to fix for at least 24 hours before submitting for processing. B5-fixed tissues must \nbe washed in one or more water baths with a magnetic stirrer for 20 to 30 minutes. The water must \nbe discarded in a mercury waste container. The tissue is then washed for an additional hour in cool \nrunning water. If there is sufficient tissue, one cassette may be processed the same day.\nSPECIAL STUDIES\n\t\u2022\t \u0007Frozen tissue: Some immunohistochemical markers in hematopathology are most sensitive on fro\u00ad\nzen tissue, and frozen tissue can also be used for mRNA and DNA analysis. Frozen tissue is saved on", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_532.png", "summary": "The page provides guidelines for processing lymph nodes, spleen, and bone marrow specimens, including descriptions of procedures and special studies.", "questions": [ "What are the common diagnoses for an enlarged lymph node?", "What special techniques are available for analyzing lymphoproliferative disorders?", "How should fresh tissue be processed for lymph nodes suspected of infectious disease?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 533, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Lymph Nodes\n515\nall lymph nodes with a suspicion of a lymphoproliferative disorder or without a prior diagnosis. Save \napproximately 5 to 10 fragments (0.4 to 0.5 cm in greatest dimension) for snap freezing.\n\t\u2022\t \u0007Flow cytometry: Flow cytometry may be useful for suspected lymphoproliferative disorders, difficult \nto classify processes, or typing of tissues from HIV+ patients. Tissue is not submitted for flow cytom\u00ad\netry in cases of Hodgkin lymphoma or small fragmented specimens as the only diagnostic lesion might \nbe in the fragment submitted for flow cytometry.\n\t\u2022\t \u0007DNA analysis: May be useful for some difficult-to-classify lymphoproliferative disorders, processes \nwith a suspected diagnostic rearrangement, EBV analysis, or leukemias. Fresh or frozen tissue may be \nused.\n\t\u2022\t \u0007Cytogenetics: May be useful for processes with suspected diagnostic chromosomal abnormalities. \nThe cells must be viable for karyotype analysis. In some cases, FISH on fixed tissue may be useful.\n\t\u2022\t \u0007EM: May be useful for unusual tumors or metastatic tumors.\nGROSS DIFFERENTIAL DIAGNOSIS\nLymphoma.\u2002 Lymphomas often cause diffuse expansion of the node, so that it appears rounded and \nloses the normal bean-shaped contour. Lymphomas have a homogeneous tan/white fleshy appearance.\nHodgkin Lymphoma.\u2002 The node looks very similar to non-Hodgkin lymphomas. The nodular scle\u00ad\nrosing variant may have gross areas of nodularity with sclerotic bands and a thick capsule.\nReactive Nodes.\u2002 The nodes can be quite large but are usually softer than lymphomas and tan-brown \nin color. Focal necrosis can be seen in cases of Kikuchi\u2019s disease.\nCarcinoma.\u2002 The nodes are often white and hard with necrotic areas. Cystic spaces may be present \n(especially if papillary thyroid carcinoma or teratoma). Focal involvement of the node is common.\nTuberculosis.\u2002 There are usually areas of geographic (caseating) necrosis. Tissue should be sent for \nculture and handled as little as possible prior to fixation. Avoid performing frozen sections, as this may \naerosolize infectious organisms. A presumptive diagnosis can usually be made using touch preparations, \nif necessary.\nSarcoidosis.\u2002 Lymph nodes are diffusely firm and white.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Lymph node: Usually the entire lymph node can be submitted. If very large, one cassette per cm \nis sufficient. Order H&E on all sections and one Giemsa (on the second level) on the best B5-fixed \ntissue, in cases of suspected lymphoma. Six to eight unstained sections for immunohistochem\u00ad\nistry on one block (B5 if there is a suspected lymphoid proliferation; formalin for nonlymphoid \ntumors) should only be ordered for special cases. Order levels if the specimen is small (e.g., in one \ncassette).\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES CHECKLIST FOR SIGN-OUT FOR LYMPHOMAS\n\t\u2022\t \u0007Specimen: Lymph node, extranodal site\n\t\u2022\t \u0007Procedure: Excisional biopsy, incisional biopsy, core needle biopsy, resection\n\t\u2022\t \u0007Tumor Site: Involvement of specific lymph node regions, spleen, bone marrow, other sites\n\t\u2022\t \u0007Histologic Type: Hodgkin lymphoma, non-Hodgkin lymphomas. The WHO Classification is \n\u00adrecommended.\n\t\u2022\t \u0007Extent of Tumor: Single lymph node region, two or more regions on the same side of the diaphragm, \nlymph node regions on both sides of the diaphragm, spleen, liver, bone marrow, other organs\n\t\u2022\t \u0007Histologic Grade: Follicular lymphoma and nodular sclerosing Hodgkin lymphoma (Tables 27-2 \nand\u00a027-3)\n\t\u2022\t \u0007Immunophenotyping Studies: Often used to classify lymphomas into B and T cell types and for fur\u00ad\nther subclassification. The method used should be included (flow cytometry vs IHC, paraffin sections \nvs frozen tissue). Use CD nomenclature and specific antibody designations when relevant.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_533.png", "summary": "The page discusses the handling and diagnostic approaches for lymph nodes suspected of lymphoproliferative disorders, including the use of flow cytometry, DNA analysis, cytogenetics, and electron microscopy. It also provides gross and microscopic differential diagnoses for lymphoma, Hodgkin lymphoma, reactive nodes, carcinoma, tuberculosis, and sarcoidosis.", "questions": [ "What are the different diagnostic techniques mentioned for lymph nodes suspected of lymphoproliferative disorders?", "How do lymphomas differ grossly from Hodgkin lymphoma, reactive nodes, carcinoma, tuberculosis, and sarcoidosis?", "What is the recommended approach for submitting lymph node specimens for microscopic examination?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 534, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Lymph Nodes\n516\n\t\u2022\t \u0007Ancillary Studies: Cytogenetics, molecular genectics, FISH, flow cytometry, viral identification\n\t\u2022\t \u0007Clinical Prognostic Factors and Indices: International Prognostic Index, International Prognostic \nScore, (IPS), Follicular \u00adLymphoma\u0007 International Prognostic Index (FLIPI), B symptoms\n\t\u2022\t \u0007AJCC Classification: Stage classification should be provided, when possible (Table 27-4).\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nLymph Nodes for Tumor Staging\nLymph nodes are the most important part of any major tumor resection. The status of lymph nodes \ndetermines whether disease is localized, and potentially cured by \u00adsurgery, or disseminated - not curable \nby surgery but possibly treatable systemically.\nTABLE 27\u20132.\u2003\n\u0007GRADING OF FOLLICULAR LYMPHOMA\nGrade 1\n0 to 5 centroblasts per HPF\nGrade 2\n6 to 15 centroblasts per HPF\nGrade 3\n>15 centroblasts per HPF\nGrade 3a\nCentrocytes are still present\nGrade 3b\nCentroblasts form solid sheets with no residual centrocytes\nReporting of Pattern\nFollicular\n>75% follicular\nFollicular and diffuse\n25% to 75% follicular\nFocally follicular\n<25% follicular\nCounts are for a 0.159 mm2 HPF. Count 10 HPFs and divide by 10. See in Chapter 9, \u201cMeasuring with the Microscope,\u201d for methods to determine field \nsize.\nTABLE 27\u20133.\u2003\n\u0007GRADING OF NODULAR SCLEROSIS HODGKIN LYMPHOMA\nGRADE I (NSI)\n1\n<25% of nodules show lymphocyte depletion, or\n2\n<25% of nodules show numerous anaplastic Hodgkin cells without depletion of lymphocytes\nGrade II (NSII)\n1\n25% or more of nodules show lymphocyte depletion, or\n2\n25% or more of nodules show numerous anaplastic Hodgkin cells without depletion of lympho\u00ad\ncytes\nSee reference 1.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_534.png", "summary": "The status of lymph nodes is crucial for determining the extent of disease and potential treatment options in tumor staging. Grading systems for follicular lymphoma and nodular sclerosis Hodgkin lymphoma are provided.", "questions": [ "What are some ancillary studies used in the evaluation of lymph nodes?", "How is the status of lymph nodes important in determining treatment options for cancer?", "Can you explain the grading system for follicular lymphoma and nodular sclerosis Hodgkin lymphoma in more detail?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 535, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Lymph Nodes\n517\nThe number of lymph nodes present and evaluated in a specimen is dependent upon many factors:\n\t\u2022\t \u0007Patient factors:\n\t \u2022\t \u0007Age: older patients tend to have fewer lymph nodes and may undergo less extensive surgery\n\t \u2022\t \u0007Prior treatment: treatment with radiation or chemotherapy can reduce the size and number of nodes\n\t \u2022\t \u0007Prior surgery: surgery to remove lymph nodes will reduce the number present at that site\n\t \u2022\t \u0007Host immune response: some systemic diseases can result in either increased size of lymph nodes \n(e.g., chronic inflammation or infection) or decreased size; is an indicator of the immunocompe\u00ad\ntency of the patient\n\t\u2022\t \u0007Surgical factors\n\t \u2022\t \u0007Size (length) of specimen\n\t \u2022\t \u0007Removal of the tissue likely to contain lymph nodes\n\t\u2022\t \u0007Cancer factors\n\t \u2022\t \u0007Some cancer types are associated with an increased size of lymph nodes not involved by cancer (e.g., \nmedullary carcinomas)\n\t \u2022\t \u0007Right-sided colon cancers are associated with more lymph nodes than left-sided cancers\n\t \u2022\t \u0007Lymph node metastases: metastatic carcinoma in lymph nodes often increases the size of the involved \nnode and makes involved nodes easier to find due to their firmness. Therefore, more nodes will typi\u00ad\ncally be found in patients with many lymph node metastases.\n\t\u2022\t \u0007Pathology factors\n\t \u2022\t \u0007Experience and technique of the person looking for the lymph nodes\n\t \u2022\t \u0007Methods of retrieving lymph nodes: special fixatives or clearing solutions can be used to find very \nsmall nodes; however, the additional nodes found compared to a good routine examination are very \nsmall and rarely change tumor staging. The significance of increased numbers of negative nodes \nfound by the use of extensive labor-intensive (and often toxic) procedures is unclear.\nAn increased number of lymph nodes examined is a favorable prognostic factor for patients with colon \ncarcinoma. It has been suggested that the number of nodes reported should be used as a quality assurance \nmeasure, based on the assumption that patients with small numbers of nodes had positive nodes missed, \nTABLE 27-4.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF HODGKIN AND NON-HODGKIN LYMPHOMAS\nStage I\nInvolvement of a single lymphatic site (i.e., nodal region, Waldeyer\u2019s ring, thymus or spleen) (I); or \nlocalized involvement of a single extralymphatic organ or site in the absence of any lymph node \ninvolvement (IE) (rare in Hodgkin lymphoma)\nStage II\nInvolvement of two or more lymph node regions on the same side of the diaphragm (II); or local\u00ad\nized involvement of single extralymphatic organ or site in association with regional lymph node \ninvolvement with or without other lymph node regions on the same side of the diaphragm (IIE). \nThe number of lymph node regions involved may be indicated by a subscript (e.g., II3).\nStage III\nInvolvement of lymph node regions on both sides of the diaphragm (III) which also may be \naccompanied by extralymphatic extension in association with adjacent lymph node involve\u00ad\nment (IIIE), or by involvement of the spleen (IIIS), or both (IIIE,S). Splenic involvement is desig\u00ad\nnated by the letter S.\nStage IV\nDiffuse or disseminated involvement of one or more extralymphatic organs with or without asso\u00ad\nciated lymph node involvement, or isolated extralymphatic organ involvement in the absence \nof adjacent regional lymph node involvement, but in conjunction with disease in distant site(s). \nStage IV includes any involvement of the liver or bone marrow, lungs (other than by direct \nextension from another site), or cerebrospinal fluid.\nModifiers\nE Extranodal\nS Spleen\nNote: There are separate staging systems for primary cutaneous lymphoma, multiple myeloma and plasma cell disorders, and pediatric lymphoid malignancy. This system \ndoes not include ocular adnexal lymphoma. The St. Jude Staging system may be used for children with NHL (usually Burkitt lymphoma, lymphoblastic lymphoma, \nor diffuse large cell lymphoma).\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint Committee on Cancer (AJCC), \nChicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_535.png", "summary": "Factors influencing the number of lymph nodes present and evaluated in a specimen include patient age, prior treatment, surgical factors, cancer type, and pathology factors.", "questions": [ "How does prior treatment, such as radiation or chemotherapy, affect the number of lymph nodes present in a specimen?", "What are some cancer types associated with an increased size of lymph nodes not involved by cancer?", "How does the number of lymph nodes examined impact the prognosis of patients with colon carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 536, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Lymph Nodes\n518\neither by the surgeon or by the pathologist. Such patients would be understaged and would not receive \nchemotherapy that could have improved their outcome. However, node-negative patients with greater \nnumbers of nodes reported also have a better prognosis. This indicates that the underlying reasons for \nthis phenomenon are complex and are not just due to the failure to find positive nodes. Factors related to \nthe type of cancer and the characteristics of patients undoubtedly also play an important role.\nPathologists can play an important role in patient care by striving to find all the nodes in specimens, \nusing good standard grossing techniques. A goal of finding at least 12 nodes in all colon specimens \nshould be attempted, although it will not be possible in every specimen. In any specimen where fewer \nthan expected nodes are found, the specimen should be re-examined and any additional tissue that \nmight contain nodes submitted. For optimal patient care, the report should document the extent of \npathologic examination (e.g., the reexamination of the specimen by a second person and/or the submis\u00ad\nsion of \u00adadditional blocks of tissue) in order to minimize the possibility of a positive lymph node being \nmissed.2-7\nPROCESSING THE SPECIMEN\n 1.\t \u0007Often nodes will be submitted surrounded by a large amount of adipose tissue.\nPalpation: This method is useful for OR consultations and is best performed when the tissue is unfixed. \nIf there is any question of a lymphoproliferative disorder, the lymph nodes must be examined prior to \nfixation in order to apportion tissue for appropriate special studies. This is the recommended method.\nLymph nodes are firmer than fat and can be found by gently \u201csquashing\u201d the fat with one finger. The \nnodes will be discrete ovoid areas that cannot be completely compressed. When bisected, they are well \ncircumscribed and tan compared to the surrounding yellow adipose tissue. Some lymph nodes may have \nthe central portion extensively replaced by fat, leaving only a thin rim of lymphoid tissue that can be dif\u00ad\nficult to see grossly.\nIf only a few lymph nodes are found using this method, the remainder of the specimen can be fixed in \nBouin\u2019s and processed as described below to look for small lymph nodes. Small nodes can sometimes be \nfound adjacent to blood vessels.\nSerial sectioning: Fix the entire specimen for several hours or overnight. Serially section through the \nspecimen. When a lymph node is encountered, bluntly \u00addissect it free. This is necessary to ensure that \nmultiple slices of the same node are not mistaken for multiple nodes.\nLymph nodes can be difficult to see in routinely fixed adipose tissue. In Bouin\u2019s fixative (and others8), \nthe lymph nodes will be white and the adipose tissue yellow. Specimens fixed in formalin can be postfixed \nin Bouin\u2019s. This can be a good method for finding very small (<0.5 cm) nodes. However, Bouin\u2019s is sub\u00ad\noptimal for immunoperoxidase studies (especially hormone receptors) and DNA studies and should be \navoided if additional studies may be necessary.\nSoft tissue attached to an organ (e.g., stomach, colon, kidney) can be stripped and placed in Bouin\u2019s \nafter all the margins have been identified. Most nodes will be located in the tissue close to the organ. \nLeave the soft tissue directly beneath the tumor in place in order to distinguish direct extension of the \ntumor into fat from nodes completely replaced by tumor.\n 2.\t \u0007Record the total dimensions of the specimen, number of lymph nodes, and size of the largest node. \nDescribe the nodes:\n\t \u2022\t \u0007Tan, homogeneous, firm: normal nodes\n\t \u2022\t \u0007Black: anthracotic pigment in mediastinal or bronchial lymph nodes, some metastatic melanomas\n\t \u2022\t \u0007White, firm to hard: metastatic carcinoma, sarcoid\n\t \u2022\t \u0007White/fleshy: lymphoma\n\t \u2022\t \u0007Cystic: metastatic teratoma, metastatic papillary thyroid carcinoma\n\t \u2022\t \u0007Necrosis: metastatic carcinoma, infection (e.g., TB)\nNormal lymph nodes will have a smooth outer surface. Describe if the capsule is irregular or effaced.\nIf there is extensive extracapsular extension and the nodes are attached to each other by firm tissue \n(corresponding to \u201cfixed\u201d or \u201cmatted\u201d nodes on physical examination), estimate the number of nodes \npresent and take a representative section of each separately identifiable involved node.\n 3.\t \u0007Each node is serially sectioned into 0.2 to 0.3 cm slices.\nMetastases first enter along the midline of the node. Although the node may be sectioned through the \nhilum and submitted so that this portion of the node is sectioned first in order to find small metastases, in \npractice this is difficult to do. Slicing the node into thin sections is more important than the exact plane \nof section.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_536.png", "summary": "Pathologists play a crucial role in patient care by ensuring all lymph nodes are found in specimens, as the number of nodes found can impact staging and prognosis. Techniques such as palpation and serial sectioning are used to locate lymph nodes in adipose tissue.", "questions": [ "How does the number of lymph nodes found in specimens impact patient staging and prognosis?", "What are the recommended methods for locating lymph nodes in specimens surrounded by adipose tissue?", "Why is it important to ensure that multiple slices of the same lymph node are not mistaken for multiple nodes during processing?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 537, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Lymph Nodes\n519\nCAP and ADASP have recommended that all grossly negative nodes be serially sectioned and com\u00ad\npletely submitted if removed for the evaluation of metastatic disease.\nThe total number of involved nodes must be determined. Small (<0.3 cm) unsliced lymph nodes can \nbe grouped into one cassette. Slices of larger lymph nodes can be combined in a cassette if the nodes are \ninked different colors. Nodes can also be combined with other types of tissue (e.g., a cassette could con\u00ad\ntain a nipple section and a bisected lymph node). Dictate how many nodes are in each cassette in order to \naccurately count the number of involved nodes.\nIf there is a gross metastasis present, submit one representative section of the area most suspicious for \nextracapsular invasion. Record the gross size of the metastatic deposit.\nRetroperitoneal lymph node dissections for testicular cancer often require extra sections (see Chapter 20).\nThis method will detect all macrometastases (>0.2 cm). The clinical signficance of smaller metastases \n(micrometastases and isolated tumor cells) has not been definitely established and is under investigation. \nThere is no practical routine method that will detect all tumor cells in lymph nodes \u2013 this would require \nIHC studies on the entire node (>300 slides).\nSPECIAL STUDIES9-16\nFrozen Sections.\u2002 Intraoperative consultation may be helpful to determine the need to remove addi\u00ad\ntional nodes or to determine the need to complete a cancer operation. If a node is to be examined by \nfrozen section, the entire node should be thinly sectioned and all slices frozen. A major reason for false \nnegative results is failure to examine the entire node.\nCytology preparations can also be used to examine lymph nodes intraoperatively.\nIf findings suggestive of infection or sarcoid are found, additional tissue should be requested to send \nfor culture.\nLevels.\u2002 In order to consistently find metastastic deposits smaller than 0.2 cm, additional levels need \nto be performed through the thickness of the tissue (Table 27-5).17\nIn order to examine the entire tissue slice, the levels need to be cut deeply into the block. Typical \n\u201clevels\u201d ordered from a histopathology laboratory are usually cut at a spacing of 10 to 20 microns. Thus \nthree \u201ctypical\u201d \u00adlevels might examine <10% of the thickness of the tissue. To completely examine a 0.2 to \n0.3\u00a0cm thick slice (or 2,000 to 3,000 microns), the levels need to be 500 to 1,000 microns apart. These \nvery deep levels need to be specifically requested from the histotechnologist. In some protocols, interven\u00ad\ning unstained slides are saved for possible later studies.\nIf multiple fragments of tissue are present in the block, levels may also ensure that all fragments are \nadequately sampled. Levels can also be helpful in determining the largest size of a small metastasis.\nImmunoperoxidase Studies.\u2002 Immunoperoxidase studies are used to further evaluate cells seen by \nH&E or to find very small metastases not seen by H&E.\nIHC for the Evaluation of Cells Seen by H&E.\u2002 There are many types of benign cells present in lymph nodes \nthat can resemble tumor cells (e.g., nevus cell nests, histiocytes, megakaryocytes). Alternatively, tumor \ncells can closely resemble benign cells (e.g., lobular breast cancer can mimic lymphocytes or histiocytes). \nTABLE 27\u20135.\u2003\n\u0007EXTENT OF SAMPLING NECESSARY TO FIND ALL METASTASES OF A GIVEN SIZE \nIN A 0.2 CM TISSUE SLICE\nSIZE OF METASTATIC DEPOSIT TO BE DETECTED\nNUMBER OF EQUALLY SPACED LEVELS THAT NEED \nTO BE EXAMINED TO FIND ALL METASTASES\n>0.2 cm (a macrometastasis)\n1\n0.1 cm\n3\n0.05 cm\n6\n0.02 cm\n20\nSingle cell\n500", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_537.png", "summary": "The manual provides guidelines for the evaluation of lymph nodes, spleen, and bone marrow in surgical pathology, including recommendations for sectioning and submitting nodes for metastatic disease evaluation.", "questions": [ "How are small unsliced lymph nodes handled during evaluation?", "What is the significance of micrometastases and isolated tumor cells in lymph nodes?", "Why are additional levels necessary to consistently find metastatic deposits smaller than 0.2 cm?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 538, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Lymph Nodes\n520\nIHC can help identify the type of cell present. Keratin is often used to identify metastastic carcinoma. \nHowever, other types of benign keratin positive cells must be excluded:\n\t \u2022\t \u0007Mullerian inclusions (usually pelvic or peritoneal lymph nodes)\n\t \u2022\t \u0007Breast lobules (axillary lymph nodes; rare)\n\t \u2022\t \u0007Mesothelial cells (mediastinal lymph nodes)\n\t \u2022\t \u0007Thyroid follicles (lymph nodes of the anterior neck)\n\t \u2022\t \u0007Interstitial reticulum cells (particularly with CAM5.2 [Xu])\n\t \u2022\t \u0007Plasma cells\nIHC is also used to distinguish melanoma metastases from other benign S100 cells in lymph nodes \n(see below).\nIHC Used to Find Small Metastases Not Seen by H&E.\u2002 Individual tumor cells or very small clusters of \ntumor can be detected by using IHC. The slide used for IHC is also a deeper level. Thus in some \ncases the new finding of metastastic tumor may be due to the deeper level, rather than to the use of \nIHC. Metastases should be classified by size or the number of cells present and not by the method \nof detection.\nIHC detects metastases not detected by H&E, depending on how many IHC studies are performed \nand how deeply the tissue is leveled. In general, the number of metastases found increases with the num\u00ad\nber of IHC levels examined. No study has attempted to examine every cell in a lymph node with IHC by \nperforming >300 IHC studies per node.\nFalse positive results can occur when benign cells are immunoreactive for the markers used (see \nabove for keratin and the melanoma section in Chapter 18). False negative results are less common, but \ncan occur when the tumor is not immunoreactive for the marker used. Because the entire node is not \nexamined by IHC, one or a few IHC studies do not exclude tumor cells in the portions of the node not \nstudied.\nThe clinical significance of micrometastases (i.e., <0.2 cm) to lymph nodes in untreated patients is \ncurrently unknown but is under investigation. \u201cIsolated tumor cell clusters\u201d measuring <0.02 cm are \ncurrently classified as N0 for breast carcinomas. This size is approximately equivalent to a linear array of \n20 cells. If a breast cancer patient has received prior therapy (i.e., \u201cneoadjuvant\u201d therapy), residual small \nmetastases have the same prognostic importance as larger metastases, as this is an indication of an incom\u00ad\nplete response of a previously larger metastasis.\nSmall foci of metastatic melanoma are often more difficult to diagnose by H&E than small foci of \nmetastastic carcinoma. S100 is a sensitive marker, but is also positive in nevus cells, dendritic cells, as well \nas nerves and ganglion cells. HMB45 and MART-1 can be used to more specifically identify tumor cells, \nbut these markers are negative in 5% to 20% of metastatic melanomas.\nIt has been recommended by CAP and ADASP that IHC be used for the evaluation of sentinel lymph \nnodes in breast carcinoma only in the context of clinical protocols to determine the significance of these \nsmall metastases.\nRT-PCR.\u2002 This technique can potentially detect one tumor cell among 106 to 107 cells by amplifying \nmRNA transcripts only produced by tumor cells. However, there are limitations to this method:\n\t \u2022\t \u0007False positive results are possible as non-tumor cells may transcribe \u201ctumor specific\u201d genes (e.g., \nnevus cells produce tyrosinase), benign epithelial lymph node inclusions may be present, or the \nspecimen may be contaminated during processing (e.g., with skin cells).\n\t \u2022\t \u0007False negative results are possible as some tumors may not produce the transcript used for \nthe assay.\n\t \u2022\t \u0007There is no histologic correlation for the RT-PCR findings (e.g., to rule out benign cells or \nartifacts).\n\t \u2022\t \u0007The size of the metastatic deposit cannot be determined with certainty.\n\t \u2022\t \u0007The significance of very rare tumor cells undetectable by other methods is unknown.\n\t \u2022\t \u0007Results are highly dependent on the experience of the person performing the assay.\nComparisons of RT-PCR to conventional techniques require dividing the nodal tissue for these two \nassays. Since small metastases are not evenly distributed in a node, how the tissue is divided will affect \nthe relative sensitivity of the methods. The significance of a positive RT-PCR result if the remainder of \nthe node is free of carcinoma is unclear. RT-PCR remains experimental and requires clinical validation.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_538.png", "summary": "IHC is used to identify the type of cells present in lymph nodes, including distinguishing metastatic carcinoma from other benign keratin positive cells. It can also detect small metastases not seen by H&E.", "questions": [ "How can IHC help in identifying the type of cells present in lymph nodes?", "What are some examples of benign keratin positive cells that must be excluded when identifying metastatic carcinoma?", "Why is it important to classify metastases by size or number of cells present rather than by the method of detection?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 539, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Lymph Nodes\n521\nSentinel Lymph Nodes\nThe sentinel lymph node is the first lymph node in the line of drainage from a tumor. If the sentinel node \nis free of tumor, it is highly unlikely that other nodes are involved and patients can be spared full lymph \nnode dissections.\nMethods to detect the sentinel node use either a dye (usually methylene blue) or radioactive isotopes. \nIf a radioactive isotope is used, the radiation safety department should be contacted to determine the best \nmethod of handling the node and the potential risks to pathology personnel. The type of isotope, the \ndose, and the method of injection will vary among institutions. The half-lives of the isotopes used are \ngenerally short, and often hours or a day will markedly decrease the amount of radioactivity remaining \nin the specimen. In most cases, the specimens can be handled safely by pathology personnel and do not \nrequire any special procedures or disposal.\nThe best method for processing sentinel nodes has not been determined. Typically, additional levels \nand/or IHC are performed (see above). At a minimum, the node or nodes are thinly sectioned and com\u00ad\npletely submitted in order to detect all macrometastases. Many protocols involve multiple H&E levels \nwith intervening unstained slides. If the H&E slides show cells that cannot be classified with certainty, \nthe unstained slides may be used for additional studies.\nProtocols for examining sentinel nodes from different sites must be developed at each institution. It \nis preferable that additional studies beyond H&E examination are performed in the context of protocols \ndesigned to determine the clinical significance of the small tumor deposits detected by these methods.\nThe reporting of sentinel nodes should include their appearance (blue or not blue), the presence of \nradioactivity as provided by the surgeon (hot or not hot or specific counts), and the methods used to \nexamine the nodes.18-21\nPROCESSING THE SPECIMEN\n 1.\t \u0007Grossly identify each node. On average, there will be two sentinel nodes for breast carcinomas.\nDescribe each node:\n\t \u2022\t \u0007Size\n\t \u2022\t \u0007Color (may be blue if dye is used)\n\t \u2022\t \u0007Capsule \u2013 smooth or irregular\n 2.\t \u0007Ink each node a different color if they are to be submitted in the same cassette.\nSlice each node thinly at 0.2 to 0.3 cm intervals.\nIf a frozen section is requested, freeze all the slices.\n 3.\t \u0007Submit all slices for histologic examination.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES CHECKLIST FOR SIGN-OUT FOR LYMPH NODE STAGING FOR \nCARCINOMAS\n\t\u2022\t \u0007Number: Number of lymph nodes examined. Some protocols require that a minimum number of \nlymph nodes be examined for adequate staging. If this number is not found, a re-examination of the \nspecimen and additional tissue sampling is warranted.\n\t\u2022\t \u0007Location: Location in relation to the primary tumor in large resections or location as defined by the \nsurgeon\n\t\u2022\t \u0007Number of metastatic deposits: Number of lymph nodes with metastatic deposits. Most staging \nsystems require this information. In some cases, only metastases of a certain size are used in the final \nnode count for N classification (e.g., in breast cancer, nodes with isolated tumor cells are not included \nin the number of positive lymph nodes)\n\t\u2022\t \u0007Size of metastasis: Size of the largest metastatic deposit. Macrometastases are defined as being \n>0.2 cm in size. For some carcinomas, the size of the largest metastatic deposit is used for \nstaging.\n\t \u2022\t \u0007Isolated tumor cell clusters \u22640.02 cm (approximately the size of a linear array of 20 tumor cells) are \nstaged as N0 (i+) for breast cancers.\n\t\u2022\t \u0007Method of detection: If metastatic cells are only found by immunohistochemistry or RT-PCR, this \nshould be stated, as very small tumor deposits detected by these methods may not be equivalent to \nfinding metastases by H&E. However, the size of the metastasis is more important than the method of \ndetection.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_539.png", "summary": "The sentinel lymph node is crucial in determining if other lymph nodes are involved in tumor spread, with methods using dye or radioactive isotopes for detection.", "questions": [ "What are the potential risks to pathology personnel when handling radioactive isotopes for detecting sentinel nodes?", "How are sentinel nodes processed and examined to detect metastases?", "Why is it important to develop protocols for examining sentinel nodes from different sites at each institution?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 540, "text": "522\nLYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Staging Laparotomies for Hodgkin Disease\n\t\u2022\t \u0007Extracapsular invasion: Present or absent, invasion extending to other structures (e.g., adjacent \nlymph nodes, muscle). In some cases, the extranodal invasion is so extensive that individual lymph \nnodes cannot be counted. The number of involved lymph nodes may need to be estimated. The clinical \nimpression may be of \u201cfixed\u201d or \u201cmatted\u201d lymph nodes.\n\t\u2022\t \u0007Treatment effect: If the patient has received neoadjuvant therapy, the presence of possible treatment \neffect on the tumor should be reported (e.g., change in histologic appearance, decreased cellularity, \nassociation with fibrosis). Evidence of prior tumor involvement in nodes without viable tumor should \nalso be reported (e.g., fibrosis, histiocytic infiltrate, hemosiderin). Small fibrous scars can be present \nin lymph nodes without prior tumor involvement. Conversely, previously involved lymph nodes may \nnot show any histologic changes after a complete response to treatment. The prognostic significance \nof micrometastases in this setting in breast cancer patients is equivalent to macrometastases.\nEXTRANODAL LYMPHOMAS\nLymphomas are most commonly diagnosed in lymph node specimens. Occasionally lymphomas will \npresent in extranodal sites in stomach, lung, breast, colon, or other unusual sites. Tissue is taken for spe\u00ad\ncial studies as described under \u201cLymph Nodes.\u201d\nSTAGING LAPAROTOMIES FOR HODGKIN DISEASE\nStaging laparotomies should only be performed after a diagnosis of Hodgkin disease (HD) has been \nmade. However, if the diagnosis is uncertain, consider saving tissue (formalin, B5, snap frozen, etc.) to \nexclude a non-Hodgkin lymphoma. If the diagnosis is well established, special studies are not required. If \nduring the gross examination of the specimens unusual lesions are encountered, proceed as if the tissue \nwere a diagnostic specimen (see sections above).\nPROCESSING THE SPLEEN\n 1.\t \u0007Weigh the spleen (normal is 125 to 195 gm) and record the outer dimensions. Cut away the fatty tis\u00ad\nsue at the hilum and process this tissue for lymph nodes (see below). Describe the capsule including \ntexture (smooth, irregular, nodular, plaques) and intactness.\n 2.\t \u0007Slice the spleen VERY thinly (2 to 3 mm) noting any small white lesions. These lesions may represent \nprominent white pulp, HD, or granulomata associated with HD. The number of lesions is important for \nclinical decision making. Each lesion is described including color, size, location (subcapsular, parenchymal), \nand consistency. Estimate the percentage of total splenic tissue occupied by the nodules. The sections are \nre-examined and recut into thinner sections the following day after fixation to look for additional lesions.\nDescribe the uninvolved splenic tissue including color, consistency, congestion, hemorrhage, and \nprominence of white pulp.\n 3.\t \u0007Cut cassette-sized sections of all nodules and five additional noninvolved representative sections. Fix \nin small container(s) of B5. Fix the remainder of the spleen in a LARGE container of formalin.\n 4.\t \u0007Wash the spleen briefly in water the following day and section further to identify any additional small \nnodules. Submit sections for processing. Do not submit more than one lesion per cassette in order \nto count accurately the total number of involved nodules. Submit all lesions up to a maximum of ten. \nIf no lesions are encountered, submit a total of five cassettes. Order one level (H&E) on each cassette. \nIf a lesion is very small, order two to three levels on that block.\nPROCESSING THE LYMPH NODES\n 1.\t \u0007Thinly section each specimen and describe the number of lymph nodes, and their size and appearance. \nFix in B5 for 3 to 5 hours and then transfer to formalin. Dispose all B5 into a mercury waste container, \nas well as the formalin, which may contain mercury salts.\n 2.\t \u0007Submit sections the following day. Order two levels (H&E).\nPROCESSING THE LIVER BIOPSIES\nNote the type of biopsy (needle or wedge), the size, the color, and the presence of any focal lesions. Slice \nwedge biopsies thinly and fix in B5 (see earlier).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_540.png", "summary": "The page discusses staging laparotomies for Hodgkin Disease, including the importance of extracapsular invasion and treatment effect evaluation. It also provides detailed instructions for processing the spleen in cases of lymphoma.", "questions": [ "How does extracapsular invasion impact the staging of Hodgkin Disease?", "What are the key considerations when processing the spleen for lymphoma evaluation?", "Why is it important to carefully examine and describe any lesions found in the spleen?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 541, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Spleen: Non-hematologic Disease\n523\nSections may be submitted after fixation for at least 3 hours or the following day. Order three levels \n(H&E).\nSPLEEN: HEMATOLOGIC DISEASE\nOccasionally, spleens will be removed for idiopathic thrombocytopenic purpura (ITP), chronic myelo\u00ad\nproliferative disorders, lymphomas, or other cases of splenomegaly. The spleen can be processed as \ndescribed above for a staging laparotomy. For all cases submit one section of formalin-fixed tissue and \nfive sections of B5-fixed tissue (make sure B5 is disposed of properly). A PAS stain is ordered on the best \nB5 block.\nGROSS DIFFERENTIAL DIAGNOSIS\nITP.\u2002 The spleen is usually normal in size and appearance or only mildly enlarged.\nCML and Hairy Cell Leukemia.\u2002 The spleen may be massively enlarged (over 5000 grams). Splenic \ninfarctions may be present. The spleen of hairy cell leukemia is usually dark red in color. In both condi\u00ad\ntions the lymph nodes are also enlarged.\nCLL.\u2002 There may be mild splenic enlargement (300 to 400 grams), with prominent malpighian \n\u00adcorpuscles.\nLymphomas.\u2002 Low-grade lymphomas usually show miliary (innumerable minute white nodules) or \ndiffuse involvement of the spleen. High-grade lymphomas may form a single or multiple large nodules. \nThe lymph nodes are often involved.\nSPLEEN: NON-HEMATOLOGIC DISEASE\nSpleens are occasionally removed after trauma, or as part of a larger resection for nonhematologic malig\u00ad\nnancies (e.g., distal pancreatectomy).\nPROCESSING THE SPECIMEN: SIMPLE SPLENECTOMY\n 1.\t \u0007Weigh the spleen (normal 125 to 195 gm), and record the outer dimensions. If the splenectomy has \nbeen performed due to trauma, photograph the specimen. Cut away the fatty tissue at the hilum \nand process like lymph nodes (see below). Describe the capsule including texture (smooth, irregular, \nnodular, plaques), and the presence of lacerations. It is generally not possible to distinguish preopera\u00ad\ntive lacerations from those occurring after removal of the spleen.\n 2.\t \u0007Slice the spleen thinly, noting any lesions. If lesions are present, the case is processed as a possible \nlymphoproliferative order (B5, snap freezing, possible other studies). Each lesion is described includ\u00ad\ning color, size, location (subcapsular, parenchymal), and consistency.\nDescribe the uninvolved splenic tissue including color, consistency, congestion, hemorrhage, and \nprominence of white pulp.\n 3.\t \u0007Submit two representative sections including capsule (if no lesions are present).\nREFERENCES\n\t\u2002 1.\t \u0007MacLennan KA, Bennett MH, Tu A, et al: Relationship of histopathologic features to survival in nodular scle\u00ad\nrosing Hodgkin\u2019s disease. Cancer 64:1686-1693, 1989.\n\t\u2002 2.\t \u0007Billmoria KY, Bentrem DJ, Stewart AK, et al. Lymph node evaluation as a colon cancer quality measure: a \nnational hospital report card. J Natl Cancer Inst 100:1310-1317, 2008.\n\t\u2002 3.\t \u0007Govindarajan A, Baxter NN. Lymph node evaluation in early-stage colon cancer. Clin Colorectal Cancer 7:240-\n246, 2008.\n\t\u2002 4.\t \u0007Johnson PM, Porter GA, Ricciardi R, Baxter NN. Increasing negative lymph node count is independently \nassociated with improved long-term survival in Stage IIIB and IIIC colon cancer. J Clin Oncol 24:3570-\n3575, 2006.\n\t\u2002 5.\t \u0007Simunovic M, Baxter NN. Lymph node counts in colon cancer surgery. Lessons for users of quality indicators \n[Editorial]. JAMA 298:2194-2195, 2007.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_541.png", "summary": "The page provides guidelines for processing spleen specimens for hematologic and non-hematologic diseases, including specific instructions for different conditions like ITP, CML, CLL, and lymphomas.", "questions": [ "What are the specific processing instructions for spleen specimens in cases of ITP, CML, CLL, and lymphomas?", "How does the spleen typically appear in cases of ITP, CML, CLL, and lymphomas?", "What are the differences in spleen size and appearance in various hematologic diseases mentioned on the page?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 542, "text": "LYMPH NODES, SPLEEN, AND BONE MARROW\u2003 Spleen: Non-hematologic Disease\n524\n\t\u2002 6.\t \u0007Washington MK. Colorectal carcinoma: selected issues in pathologic examination and staging and determina\u00ad\ntion of prognostic factors. Arch Pathol Lab Med 132:1600-1607, 2008.\n\t\u2002 7.\t \u0007Wong SL, Hong J, Hollenbeck BK, et al. Hospital lymph node examination rates and survival after resection for \ncolon cancer. JAMA 298:2149-2154, 2007.\n\t\u2002 8.\t \u0007Koren R, Kyzer S, Paz A, et al. Lymph node revealing solution: A new method for detection of minute axillary \nlymph nodes in breast cancer specimens. Am J Surg Pathol 21:1387-1390, 1997.\n\t\u2002 9.\t \u0007Association of Directors of Anatomic and Surgical Pathology (ADASP) recommendations for processing and \nreporting of lymph node specimens submitted for evaluation of metastastic disease. Mod Pathol 14:629-632, \n2001.\n\t10.\t \u0007Brennick JB, Yan S. False-positive cells in sentinel lymph nodes. Semin Diagn Pathol 25:116-119, 2008.\n\t11.\t \u0007Fitzgibbons PL, Page DL, Weaver D, et al. Prognostic factors in breast cancer. College of American Patholo\u00ad\ngists Consensus Statement 1999. Arch Pathol Lab Med 124:966-978, 2000.\n\t12.\t \u0007Gould VE, Bloom KJ, Franke WW, et al: Increased numbers of cytokeratin-positive interstitial reticulum cells \n(CIRC) in reactive, inflammatory and neoplastic lymphadenopathies: Hyperplasia or induced expression?. Vir\u00ad\nchows Arch 425:617-630, 1995.\n\t13.\t \u0007Scolyer RA, Murali R, McCarthy SW, Thompson JF. Pathologic examination of sentinel lymph nodes from \nmelanoma patients. Semin Diagn Pathol 25:100-111, 2008.\n\t14.\t \u0007Smith PAF, Harlow SP, Krag DN, Weaver DL. Submission of lymph node tissue for ancillary studies decreases \nthe accuracy of conventional breast cancer axillary node staging. Mod Pathol 12:781-785, 1999.\n\t15.\t \u0007Weaver DL. Sentinel lymph nodes and breast carcinoma: which micrometastases are clinically significant?. Am \nJ Surg Pathol 27:842-845, 2003.\n\t16.\t \u0007Xu S, Roberts SA, Pasha TL, Zhang PJ. Undesirable cytokeratin immunoreactivity of native nonepithelial cells \nin sentinel lymph nodes from patients with breast carcinoma. Arch Pathol Lab Med 124:1310-1313, 2000.\n\t17.\t \u0007Zhang PJ, Reisner RM, Nangia R, et al. Effectiveness of multiple-level sectioning in detecting axillary nodal \nmicrometastasis in breast cancer: a retrospective study with immunohistochemical analysis. Arch Pathol Lab \nMed 122:687-690, 1998.\n\t18.\t \u0007Fitzgibbons PL, LiVolsi VA, for the Surgical Committee of the College of American Pathologists and the \nAssociation of Directors of Anatomic Surgical Pathology, Recommendations for handling radioactive specimens \nobtained by sentinel lymphadenectomy, Am J Surg Pathol 24:1549\u20131551, 2000.\n\t19.\t \u0007Law M, Chow LWC, Kwong A, Lam CK. Sentinel lymph node technique for breast cancer: radiation safety \nissues. Seminars in Oncology 31:298-303, 2004.\n\t20.\t \u0007Morton R, Horton PW, Peet DJ, Kissin MW. Quantitative assessment of the radiation hazards and risks in \nsentinel node procedures. Br J Radiol 76:117-122, 2003.\n\t21.\t \u0007Stratmann SL, McCarty TM, Kuhn JA. Radiation safety with breast sentinel node biopsy. Am J Surg 178:454-\n457, 1999.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_542.png", "summary": "This page discusses various studies and recommendations related to lymph node examination, staging, and processing in different types of cancer.", "questions": [ "What are some key factors to consider when examining lymph nodes in breast cancer specimens?", "How do false-positive cells in sentinel lymph nodes impact diagnosis and treatment?", "What are the recommendations for handling radioactive specimens obtained by sentinel lymphadenectomy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 543, "text": "525\n28\nMedical Devices and Foreign \nMaterial\nAll foreign material removed from humans, whether of medical origin or not, is generally sent to pathol\u00ad\nogy for documentation (with the exception of temporary medical devices such as IV catheters). Some of \nthese specimens will be of legal significance (e.g., silicone implants, bullets) and others will be subject to \nlegislation that requires the tracing of certain medical devices.\nTHE SAFE MEDICAL DEVICES ACT OF 1990\nThe Federal Safe Medical Devices Act of 1990 (PL 101-629) went into effect in August of 1993. This act \nrequires manufacturers of medical devices, healthcare personnel who use or install them, and hospitals to \nkeep records of patients and the history of specific medical device (\u201ctracking\u201d). This will allow manufac\u00ad\nturers to remove devices from the market and/or notify patients should problems arise. The subsequent \nFood and Drug Administration Modernization Act (FDAMA) in 1997 eliminated automatic mandatory \ntracking for certain devices. Additional information can be found at www.fda.gov/medwatch.\nThe types of devices tracked include those with the following features (Box 28-1):\n\t \u2022\t \u0007If the device failed it would be reasonably likely to have serious adverse health consequences.\n\t \u2022\t \u0007The device is intended to be implanted in the human body for more than one year.\n\t \u2022\t \u0007The device is intended to be life-sustaining or life-supporting.\nBOX 28\u20131.\u2003 Current devices subject to tracking under the Safe Medical Devices Act\nPermanently implantable devices:\n \u2022 \u0007Vascular graft prostheses (see Chapter 16)\n \u2022 \u0007Vascular bypass (assist) devices (see Chapter 16)\n \u2022 \u0007Implantable pacemaker pulse generator\n \u2022 \u0007Cardiovascular permanent pacemaker electrode\n \u2022 \u0007Annuloplasty ring\n \u2022 \u0007Replacement heart valve (see Chapter 16)\n \u2022 \u0007Automatic implantable cardioverter/defibrillator\n \u2022 \u0007Tracheal prosthesis\n \u2022 \u0007Implanted cerebellar stimulator\n \u2022 \u0007Implanted diaphragmatic/phrenic nerve stimulator\n \u2022 \u0007Implantable infusion devices\nLife-sustaining or life-supporting devices:\n \u2022 \u0007Breathing frequency monitors (apnea monitors)\n \u2022 \u0007Continuous ventilator\n \u2022 \u0007CD-defibrillator and paddles\nFDA-designated devices:\n \u2022 \u0007Silicone inflatable breast prosthesis\n \u2022 \u0007Silicone gel-filled breast prosthesis\n \u2022 \u0007Silicone gel-filled testicular prosthesis\n \u2022 \u0007Silicone gel-filled chin prosthesis\n \u2022 \u0007Silicone gel-filled Angelchik reflux valve\n \u2022 \u0007Electromechanical infusion pumps", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_543.png", "summary": "Pathology receives all foreign material removed from humans for documentation, including medical devices subject to legal tracing. The Safe Medical Devices Act of 1990 requires tracking of certain medical devices for patient safety.", "questions": [ "What types of medical devices are subject to tracking under the Safe Medical Devices Act?", "How does the Safe Medical Devices Act of 1990 impact manufacturers, healthcare personnel, and hospitals?", "What are the implications of the FDA Modernization Act of 1997 on mandatory tracking of certain devices?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 544, "text": "MEDICAL DEVICES AND FOREIGN MATERIAL\u2003 Bullets\n526\nThe patient with a tracked device is allowed to refuse to release personal information for the purpose \nof tracking.\nPathologists play an important role in recognizing medical device-associated complications. Reports \nof problems with medical devices can be made on forms available at the MEDWATCH home page at \nwww.fda.gov/medwatch. The medical device should be saved.\nORTHOPEDIC HARDWARE\nAll orthopedic hardware (joint prosthesis, screws, plates, etc.) is usually sent to the pathology department \nfor documentation. The gross description includes the number, color, composition (plastic, metal), and \nany identifying numbers on the hardware. Any obvious cracks or worn areas should be noted. There is \nno need to photograph these specimens unless there is a history of trauma or there is obvious damage \nto the hardware. Some patients will request the return of their orthopedic hardware. The specimen will, \npreferably, be washed clean of blood and placed in a leakproof permanently-sealed bag before return.\nFOREIGN BODIES\nForeign bodies are defined as nonmedical objects within the human body. Photographs are frequently \nuseful because of the potential for lawsuits in some cases.\nInformation about illegal substances taken from a patient and submitted as pathology specimens \n(e.g., a bag of heroin extracted from a smuggler\u2019s GI tract) may be protected by medical confidentiality. \nThis information should not be released to outside parties without \u00adconsultation with the hospital\u2019s legal \ndepartment. The legal department should also be consulted before disposal or return of such objects to \npatients.\nBULLETS\nThe most important principle of handling bullets (or other specimens likely to be used as evidence in \na legal case) is to establish an \u201cunbroken chain of evidence\u201d identifying the bullet from the time it is \nremoved by the surgeon to the time that the bullet is released to the police. Any lapse in this procedure \ncould be legal grounds to have the bullet removed as evidence in a trial.\nDOCUMENTING THE SPECIMEN\nA doctor or nurse should transfer the bullet from the operating room directly to a pathologist. The \nname of the people delivering and receiving the bullet and the time of transfer is documented in the \nreport.\nDo not touch bullets or bullet fragments with metal tools (e.g., forceps) because scratches will obscure \nrifling marks used to identify the gun of origin. The gross \u00addescription should be detailed enough (includ\u00ad\ning accurate measurements, color, size, and shape) to allow identification of the bullet at a future date, \nincluding numbers and letters if present. Descriptive terms (e.g., \u201cconical silver metallic fragment\u201d) are \npreferred unless the prosector is a ballistics expert and can positively identify the specimen as a bullet \n(e.g., \u201cbullet from a .32 automatic pistol\u201d). The description could potentially become evidence in a trial.\nThree photographs including the surgical number and ruler are useful for documentation. Multiple \npictures may be useful if there is more information to be gained by different angles. Include any tissue \nsubmitted with the bullet. If there is soft tissue or bone present, it is submitted as a surgical specimen, up \nto one cassette for soft tissue and one cassette for bone.\nThe bullet should be kept in a locked secure storage compartment until requested by the police.\nThe name of the policeman or policewoman, his or her badge number, and the name of the person \nreleasing the bullet should be documented as well as the day and time of transfer. Bullets should not oth\u00ad\nerwise be released. If a question about releasing a bullet arises, legal advice should be sought.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_544.png", "summary": "Pathologists play a crucial role in recognizing complications associated with medical devices, such as orthopedic hardware and foreign bodies. Proper documentation and handling of specimens, particularly bullets, is essential to maintain the chain of evidence.", "questions": [ "What forms are available for reporting problems with medical devices?", "Why is it important to establish an unbroken chain of evidence when handling bullets?", "What steps should be taken when documenting and handling orthopedic hardware specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 545, "text": "527\n29\nNeuropathology Specimens\nNeuropathology cases include all brain and spinal cord specimens, pituitary glands, muscle and nerve \nbiopsies, and eyes.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 29-1.\nBRAIN BIOPSIES\nBiopsies and resections are often small. Most will be evaluated intraoperatively to ensure that diagnostic \ntissue is present and to provide a specific diagnosis. Cytologic smear preparations in addition to frozen \nsections are often needed for rapid diagnosis (see in Chapter 6, \u201cNeuropathology\u201d). Biopsies may be \nperformed for focal lesions (primary tumors, metastases, infectious disease) or to evaluate nonsurgical \ndiseases (e.g., dementia).\nPROCESSING THE SPECIMEN\nThe specimen will often consist of small fragments of tissue or a stereotactic core needle biopsy measur\u00ad\ning approximately 1 \u00d7 0.2 \u00d7 0.2 cm. It is sometimes possible to distinguish grey and white matter. If tissue \nis to be taken for intraoperative diagnosis or for special studies, a careful gross examination is necessary \nto select the areas most likely to be diagnostic (see below). A magnifying lens or dissecting microscope \nmay be helpful.\nTABLE 29\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR NEUROPATHOLOGY \nSPECIMENS\nOrgan/tissue resected or biopsied\nResults of previous CNS biopsies\nPurpose of the procedure\nDuration of symptoms (e.g., rapidly progressive \ndementia and myoclonus is suggestive of \nCreutzfeldt-Jakob disease)\nGross appearance of the organ/tissue/lesion sampled\nAny unusual features of the clinical presentation\nFamily history (present in 16% of patients with \nbrain tumors: neurofibromatosis type 1 [optic \nsystem gliomas], neurofibromatosis type 2 \n[acoustic neuroma, multiple \u00admeningiomas, \nspinal cord ependymoma], tuberous sclerosis \n[subependymal giant cell astrocytoma], von \nHippel-Lindau [hemangioblastomas of the \ncerebellum), Turcot syndrome (medulloblasto\u00ad\nmas and glioblastomas], Cowden, Li-\u00adFraumeni, \nGorlin syndrome)\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic appearance of tissues)\nCompromised immune system\nImaging features", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_545.png", "summary": "This page discusses neuropathology specimens, including brain and spinal cord specimens, pituitary glands, muscle and nerve biopsies, and eyes. It covers the relevant clinical history needed for these specimens and the processing of brain biopsies.", "questions": [ "What are the different types of neuropathology specimens mentioned in the text?", "Why is it important to evaluate brain biopsies intraoperatively?", "What are some of the relevant clinical history factors to consider for neuropathology specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 546, "text": "NEUROPATHOLOGY SPECIMENS\u2003 Brain Biopsies\n528\nAll small fragments of brain for permanent sections are wrapped in saline-moistened lens paper and \nsubmitted in entirety. The fragments must be handled gently as there is little supporting tissue and speci\u00ad\nmens are easily distorted. If possible, fix the tissue before processing it.\nDo not use sponges or toothed forceps with brain biopsies as artifacts are introduced when the soft \ntissue is pressed into the interstices of the sponge or the forceps teeth.\nSPECIAL STUDIES\nGliomas (Oligodendrogliomas).\u2002 A portion of tissue should be submitted for FISH to evaluate 1p/19q \ndeletions. If tumor tissue is limited, air-dried touch preps can also be used for FISH.\nMedulloblastoma.\u2002 DNA ploidy studies are useful for prognosis. This determination can be made using \ntouch preps and image analysis or by flow cytometric analysis on fresh (preferred) or fixed tissue.\nPineal Region Tumors.\u2002 Tissue for EM may be helpful to classify neoplasms in this region. Germ cell \ntumors can be subclassified using immunoperoxidase studies (PLAP, \u03b2-HCG, AFP).\nCreutzfeldt-Jakob Disease.\u2002 Creutzfeldt-Jakob disease must be suspected in any patient with a rapidly \nprogressive dementia. Most patients will die within 10 months. Immunoperoxidase studies and Western \nblotting for protease K resistant PrPsc are useful for diagnosis.\nSpecimens may be sent to the National Prion Disease Pathology Surveilance Center (www.cjdsurveil\nlance.com) for confirmation of the diagnosis.\nDr. Pierluigi Gambetti, Director\nNational Prion Disease Pathology Surveillance Center\nInstitute of Pathology\nCase Western Reserve University\n2085 Adelbert Road, Room 418\nCleveland, OH 44106\nTelephone: 216-368-0587 or 216-368-0822\nFax: 216-368-4090\ne-mail: cjdsurv@cwru.edu\nThe Center can be contacted for questions related to shipping specimens\nPrion proteins are highly resistant to normal \u00addecontamination procedures and every effort must be \nmade to prevent exposure of pathology personnel. Fixed and stained tissue on glass slides can transfer the \ndisease!!\nAll tissue (neural and nonneural) for histology must be fixed in formalin for 24 hours. The tissue is \nthen placed in formic acid for 1 hour and then placed again in formalin. The specimen must be clearly \nlabeled as coming from a patient with known or suspected Creutzfeldt-Jakob disease. The fixation is \nfollowed by a 1-hour treatment with formic acid followed by an additional 24-hour fixation in formalin.\nIf the biopsy is of adequate size, it is useful to freeze a sample at -80\u00b0C for potential Western blotting.\nEverything that touches the tissue (both disposable and non-disposable) must be soaked in bleach for \none hour prior to discarding or washing.1-3\nLymphoma.\u2002 Frozen tissue is useful for typing by immunoperoxidase studies. However, many antibod\u00ad\nies are now available for use on formalin- or B5-fixed tissues.\nInfections.\u2002 Immunoperoxidase studies for viral antigens (e.g., herpes) or Toxoplasma may be performed \non formalin-fixed tissue. It may be helpful to save tissue for EM for patients with suspected encephalitis \nto look for viral particles. Parasites are usually evident by light microscopy. PML (JC virus) is usually \ndiagnosable from light microscopy, although antibodies are available to detect the virus in tissues. Coor\u00ad\ndination with the surgeon at the time of OR consultation should be done in order that microbiologic \ncultures can be performed as appropriate.\nMetabolic Diseases/Storage Disorders.\u2002 Brain biopsies for these diseases are more often performed in \nchildren, but may be performed in adults as well. It is important to sample grey and white matter (ideally \nseparately) for standard histology, frozen sections, EM, and biochemical studies.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_546.png", "summary": "The page discusses the handling and processing of brain biopsies, as well as the importance of special studies for different types of brain tumors and diseases.", "questions": [ "What are the recommended handling techniques for brain biopsies to prevent distortion?", "What special studies are recommended for gliomas, medulloblastoma, pineal region tumors, and Creutzfeldt-Jakob disease?", "Why is it important to contact the National Prion Disease Pathology Surveillance Center for confirmation of a Creutzfeldt-Jakob disease diagnosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 547, "text": "NEUROPATHOLOGY SPECIMENS\u2003 Brain Biopsies\n529\nGROSS DIFFERENTIAL DIAGNOSIS\nNormal Tissue.\u2002 Grey matter and white matter can often be identified, even in small core biopsies. The \ntissue is slightly firm and will maintain its shape. Inflammatory lesions may have a similar appearance, \nbut may be congested or softened.\nTumors.\u2002 The color is usually abnormally yellow/gray and necrosis may be grossly apparent. The tissue \nis soft and gelatinous and does not maintain the shape of the biopsy.\nMeningiomas.\u2002 Usually firmer than normal tissue, but can be soft, or gelatinous, or whorled. Calcifica\u00ad\ntions are commonly present. If attached dura and brain tissue can be identified, take sections to demon\u00ad\nstrate the relationship of the meningioma to these structures. If the specimen is large, submit at least one \nsection per centimeter of tumor.\nMetastatic Tumors.\u2002 The tissue is often gray in color and necrosis may be present. The boundary \nwith the normal brain, if present, is usually sharp. The most common primary tumors are lung carci\u00ad\nnoma, breast carcinoma, melanoma, renal cell carcinoma, and colon carcinoma. If the primary site is \nunknown, immunohistochemistry on formalin-fixed tissue may be useful to determine the most likely \nsite of origin.\nVascular Malformations.\u2002 These lesions in general are not biopsied but removed in one piece and are, \ntherefore, usually larger than other lesional biopsies. The tissue usually appears hemorrhagic and small \nvascular structures may be apparent. Elastic stains may be helpful to classify the types of vessels present.\nAcoustic Neuromas.\u2002 The tissue is usually firm and fibrotic.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cparietal,\u201d are five fragments of \ngelatinous soft yellow/gray tissue, each measuring 0.5 \u00d7 0.3 \u00d7 0.2 cm. Normal gray and white matter is \nnot apparent. One fragment was used for cytologic preparations for intraoperative consultation and a \nsecond fragment was used for frozen section.\nCassette #1: frozen section remnant, 1 frag, ESS.\nCassette #2: remainder of specimen, 3 frags, ESS.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES CHECKLIST FOR SIGN-OUT FOR BRAIN TUMORS\n\t\u2022\t \u0007Specimen Type: Core needle biopsy, open biopsy, subtotal/partial resection, total resection\n\t\u2022\t \u0007Specimen Size: Greatest dimension\n\t\u2022\t \u0007Specimen Handling: Squash/smear/touch preparation, frozen section, EM, permanent paraffin sec\u00ad\ntions\n\t\u2022\t \u0007Laterality: Right, left, bilateral, not applicable\n\t\u2022\t \u0007Tumor Site: Brain/cerebrum (frontal, temporal, parietal, occipital), basal ganglia, thalamus, hypo\u00ad\nthalamus, suprasellar, pineal, cerebellum, cerebellopontine angle, ventricle, brain stem, spinal cord, \nnerve root, skull (frontal, parietal, temporal, occipital), dura, leptomeninges\n\t\u2022\t \u0007Histologic Type: Astrocytomas, oligodendrogliomas, medulloblastomas, ependymal and choroid \nplexus tumors, others (use WHO classification)\n\t\u2022\t \u0007Tumor Size: Greatest dimension\n\t\u2022\t \u0007Grade: WHO grade is recommended4\n\t\u2022\t \u0007Margins: Involved, uninvolved, cannot be assessed, not applicable\n\t \u2022\t \u0007Margins are often not applicable except for completely resected gliomas of the temporal or frontal \ntip. Meningeal or dural margin assessment may be important for meningiomas. Cranial or spinal \nnerve sheath tumor resection margins should be evaluated.\n\t \u2022\t \u0007Invasion into the brain is prognostically important for meningiomas.\n\t\u2022\t \u0007Change Over Time: If the tumor is a recurrence, compare to previous biopsies to determine if there \nhas been a change in grade.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_547.png", "summary": "This page discusses the gross differential diagnosis of brain biopsies, including normal tissue, tumors, meningiomas, metastatic tumors, vascular malformations, and acoustic neuromas.", "questions": [ "How can normal tissue be distinguished from inflammatory lesions in brain biopsies?", "What are the common primary tumors that may metastasize to the brain?", "What specimen handling techniques are recommended for brain tumor specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 548, "text": "NEUROPATHOLOGY SPECIMENS\u2003 Brain Resections\n530\n\t\u2022\t \u0007Treatment Affect: Evaluate treatment effects (usually radiation) on tumor and adjacent brain (extent \nof necrosis, viability).\n\t\u2022\t \u0007Ancillary Studies: IHC, EM, cytogenetic\nThis checklist incorporates information from the ADASP (see www.adasp.org) and the CAP Can\u00ad\ncer Committee protocols for reporting on cancer \u00adspecimens (see www.cap.org/). The underlined ele\u00ad\nments are considered to be scientifically validated or regularly used data elements that must be present in \nreports of cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The \nspecific details of reporting the elements may vary among institutions.\nBIOPSIES OF THE DURA\nRarely, dural biopsies are performed for the evaluation of pachymeningitis or vasculitis. The specimen is \nsmall and can be entirely submitted and examined in fixed permanent sections.\nCAVITRON ULTRASONIC SURGICAL ASPIRATOR SPECIMENS\nThe Cavitron Ultrasonic Surgical Aspirator (CUSA) causes localized ultrasonic fragmentation of tissue \nthat can then be removed by irrigation and suction. This technique minimizes the effects of surgery on \nadjacent normal tissues. It is used to remove some intracranial tumors. The procedure may be performed \nwithout a prior histologic diagnosis.\nThe specimen will consist of small fragments of tissue in a volume of fluid. The fragments can be col\u00ad\nlected by straining the fluid through gauze pads. The tissue is gently placed in mesh bags or wrapped in \npaper. Tissue sufficient to fill two to three cassettes is usually adequate for diagnosis. If the tissue frag\u00ad\nments are quite small, cytologic smears and cell blocks prepared from the fluid are often diagnostic and \ncan be used for immunohistochemical studies, if \u00adnecessary.\nSUBDURAL AND SUBARACHNOID HEMATOMA EVACUATIONS\nBlood removed for therapeutic reasons after intracranial bleeds may be submitted for histologic exam\u00ad\nination. Any tissue fragments within the blood are identified grossly and submitted for histologic \nexamination.\nOccasionally, Congophilic (amyloid) angiopathy will be diagnosed in such specimens. Amyloid can be \ndetected in meningeal or cortical vessel walls using a Congo red stain or immunoperoxidase studies on \nfixed tissue for \u00df amyloid.\nMetastatic carcinoma can also be the cause of a hematoma and must be excluded by careful sampling \nand microscopic analysis.\nBRAIN RESECTIONS\nLarge areas of the brain are sometimes resected to remove an epileptic focus, and rarely, for \nother lesions. The failure to find an abnormality may correlate with recurrence of seizures after \nsurgery.\nPROCESSING THE SPECIMEN\n\t1.\t \u0007Determine the location of the resection and orient the specimen. A photograph of the intact specimen \nis helpful. Describe each component present:\n\t \u2022\t \u0007Meninges: Describe any areas of fibrosis or hemorrhage.\n\t \u2022\t \u0007Brain surface: Describe the gyral pattern including normal, distorted, tubers (tuberous sclerosis), or \npolymicrogyria.\n\t \u2022\t \u0007Identify white matter and gray matter. Measure the width of the gray matter and the range of \nwidths. Describe the gray/white junction (distinct or blurred).\n\t \u2022\t \u0007Describe any other abnormalities present (e.g., alteration in color or consistency, focal masses).\nIn general, it is not necessary to ink margins. However, \u00adcolored inks are sometimes useful to indicate \u00ad\norientation.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_548.png", "summary": "The page discusses various neurosurgical specimens, including brain resections, dural biopsies, CUSA specimens, and hematoma evacuations. It also outlines the importance of processing brain resections to determine the location of abnormalities.", "questions": [ "What are the different types of neurosurgical specimens mentioned on this page?", "How is the Cavitron Ultrasonic Surgical Aspirator (CUSA) used in neurosurgery?", "Why is it important to carefully process brain resections?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 549, "text": "NEUROPATHOLOGY SPECIMENS\u2003 Eyes\n531\n\t2.\t \u0007The specimen is sliced (perpendicular to the pial surface) at thicker intervals than the final sections \nto be submitted for processing (about 1.0 to 1.5 cm). Examine the gray and white matter for abnor\u00ad\nmal appearance or consistency. Samples of gray and white matter should be frozen for histology (in \nembedding medium), taken for EM, and snap frozen in liquid nitrogen.\nAfter sectioning, the slices should be photographed as a composite in an oriented manner. Indi\u00ad\nvidual slices containing lesions should be photographed separately as well.\nPrior to placing the slices in formalin (in a manner that will preserve orientation), small pieces of \npaper towel are placed against each face of the slice to minimize retraction.\n\t3.\t \u0007Fix the slices in 20\u00d7 volume of formalin overnight.\n\t4.\t \u0007Serially submit sections from the slices, but maintain orientation. The photograph will help document \nthe areas used for histologic examination. One section per 1 to 1.5 cm of greatest dimension is submit\u00ad\nted for the initial evaluation.\nOrientation of the specimen can be maintained by separating each piece of tissue in a specimen \ncontainer with a paper towel and stacking in order. If diagnostic abnormalities are found in one of the \ninitial \u00adsections, it is possible to find the same area and submit more sections at a later time.\nEYES\nEyes may be removed due to primary tumors (most commonly melanomas), nonfunctioning painful eyes, \nor as part of a large face resection for deeply invasive tumors.\nPROCESSING THE SPECIMEN\n\t1.\t \u0007If part of a larger face resection, the eye is removed by cutting around the extraocular muscles.\nThe eye is fixed intact for at least 24 hours. Slicing the unfixed globe or injecting fixative into the \nvitreous will disrupt the intraocular structures.\nWash in tap water for at least one hour.\n\t2.\t \u0007Orient the globe by observing the posterior surface. The posterior ciliary vessels will be on the medial \naspect of the optic nerve. The superior and inferior oblique muscles will be lateral to the optic nerve \n(Fig. 29-1).\nTake the following measurements:\n\t \u2022\t \u0007Globe:\n\t\n\u2022\t \u0007Anterior/posterior\n\t\n\u2022\t \u0007Horizontal\n\t\n\u2022\t \u0007Vertical\n\t \u2022\t \u0007Optic nerve: Length\n\t \u2022\t \u0007Cornea: Vertical (normal 11 mm) and horizontal (normal 11.5 mm).\nSuperior oblique\nSuperior rectus\nMedial rectus\nVortex veins\nPosterior ciliary\nvessel\nInferior oblique\nPupil-optic nerve section\nPosterior left eye\nOptic nerve\nLateral rectus\nInferior rectus\nFigure 29-1.\u2002 Eye anatomy and dissection.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_549.png", "summary": "Neuropathology specimens of eyes are sliced and examined for abnormalities. Eyes may be removed for various reasons, such as tumors or invasive tumors.", "questions": [ "What are the different reasons for which eyes may be removed?", "How should the slices of neuropathology specimens be processed and examined?", "Why is it important to maintain orientation of the specimen during processing?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 550, "text": "NEUROPATHOLOGY SPECIMENS\u2003 Eyes\n532\nDescribe corneal clarity or opacities, size and shape of pupil, iris color and abnormalities (e.g., arcus \nsenilus), scars of the superior limbus (present after surgery for glaucoma or cataracts), or a silicone \nband or sponge (present after surgery for retinal detachment).\nTumors: If melanoma is present, examine the outer surface for tumor including the vortex veins. \nIf retinoblastoma is present, examine the optic nerve for involvement (this is an important margin).\n\t3.\t \u0007Transilluminate the globe in a darkened room, using a bright light source. Increased light transmis\u00ad\nsion can be seen in defects of the iris. Decreased light transmission may be due to hemorrhage or \ntumor. Mark any abnormal shadows on the sclera with a marking pencil. The cornea and sclera are \nbest examined under a dissecting microscope. Radiography is indicated if intraocular foreign bodies \nor retinoblastoma is suspected.\n\t4.\t \u0007Cut off the distal segment of the optic nerve and submit en face.\n\t5.\t \u0007The globe is sectioned to best demonstrate any lesions present. A razor blade is adequate for \u00ad\nsectioning.\nIf no lesions are apparent, section the globe in a plane to include the optic nerve, macula, and \npupil. Make a horizontal section 0.5 cm superior to the optic nerve and 0.5 cm central to the superior \nlimbus. After this section is removed, examine the eye contents (lens, iris, ciliary body, vitreous, cho\u00ad\nroid, retina, and optic nerve) under a dissecting microscope. Note the size and location of any lesions. \nIf a lesion is present, note its location with respect to the ora serrata, optic disc, and macula. Finish \nsectioning the eye by making a parallel section just below, through the inferior \u00adlimbus.\nIf a focal lesion is present, the globe is sectioned vertically or obliquely to include the lesion in \nthe plane with the optic nerve and pupil.\n\t6.\t \u0007Usually only the tissue in the central section is submitted for histologic examination. Portions of the \nother sections can be submitted if additional lesions are present. Include sections of optic nerve (trans\u00ad\nverse), retina, choroid, ciliary body, pupil, lens, and cornea. A PAS stain should be obtained.\nGROSS DIFFERENTIAL DIAGNOSIS\nMalignant Melanoma.\u2002 Lobulated pigmented masses that arise in the choroid or ciliary body. Choroid \ntumors may extend into the subretinal space and form a mushroom shaped tumor. The size, presence at \nciliary body, and location over the optic nerve are poor prognostic factors. Some may extend beyond the \nsclera into scleral canals with vortex veins or into the subconjunctival space.\nRetinoblastoma.\u2002 The majority present before the age of 3 years, and about one third are due to a germ\u00ad\nline mutation. These latter tumors are more likely to be multifocal or bilateral. The tumors are chalky \nwhite and arise from the retina. The tumor may grow into the vitreous, the subretinal space, or both.\nAJCC (7TH EDITION) CLASSIFICATION OF TUMORS OF THE EYE\nThere are separate classification systems for carcinoma of the eyelid, carcinoma of the conjunctiva, \nmalignant melanoma of the conjunctiva, malignant melanoma of the uvea, retinoblastoma, carcinoma of \nthe lacrimal gland, and sarcoma of the orbit. The seventh edition of the AJCC Cancer Staging Manual \nshould be consulted for the specifics of these systems.\nLens\nLenses are removed when they are involved by cataracts.\nDescribe the specimen grossly including diameter, thickness, shape (lentiform, ovoid), color, and the \npresence of opacities (central or peripheral).\nThese specimens are usually not examined histologically but may be examined if requested. A PAS \nstain should be obtained.\nCornea\nThe central portion of the cornea may be removed during transplantation and can be involved by endo\u00ad\nthelial decompensation, post-inflammatory scarring, and traumatic changes, or keratoconus, or the spec\u00ad\nimen may be a failed graft. The specimen is embedded and cut on edge, perpendicular to the epithelial \nsurfaces. A PAS stain should be obtained.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_550.png", "summary": "The page provides guidelines for examining and processing neuro-ophthalmic specimens, particularly eyes, for tumors such as melanoma and retinoblastoma.", "questions": [ "How can abnormalities in the cornea, iris, and optic nerve be identified during examination?", "What are the key steps involved in sectioning and examining the globe for lesions?", "What are the distinguishing characteristics and prognostic factors of malignant melanoma and retinoblastoma in the eye?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 551, "text": "NEUROPATHOLOGY SPECIMENS\u2003 Muscle Biopsies\n533\nNERVE BIOPSIES\nPeripheral nerve biopsies are usually performed to evaluate peripheral neuropathy; the final diagnosis \nshould be correlated with clinical and neurophysiologic data (e.g., a history of an inherited metabolic \ndisease or toxic insult, biopsy of other tissues, etc.).\nPROCESSING THE SPECIMEN\nNerve biopsies are processed routinely for light microscopy and EM and a small portion is saved \nfrozen.\n\t\u2022\t \u0007EM: Submit a 5 to 6 mm length of nerve - preferably from the center of a larger segment so that crush \nartifact from the ends can be avoided. Semithin sections can be examined to determine if EM is neces\u00ad\nsary.\n\t\u2022\t \u0007Light microscopy: After specimens have been taken for special studies, the remainder of the specimen \nis kept intact. Wrap the specimen in lens paper. Longitudinal and cross-sections may be prepared by \nthe histology laboratory. Routine stains are H&E (two levels) and a trichrome stain.\n\t\u2022\t \u0007Frozen tissue: A small cross-section should be frozen in embedding medium.\nSPECIAL STUDIES\n\t\u2022\t \u0007Vasculitis or history of collagen vascular disease: Immunofluorescence studies may be indicated. \nEither fresh or frozen tissue can be used.\n\t\u2022\t \u0007Demyelinating disease: Evaluation of these diseases requires an extra portion of nerve for \u201cteasing.\u201d \nA 5 mm length of nerve is saved in formalin. The nerve must be flat, but not stretched, during fixa\u00ad\ntion. Individual nerve fibers are gently separated under a dissecting microscope. The fibers can then be \nembedded and sectioned longitudinally and stained with osmium to look for segmental loss of myelin, \nor \u201conion balls\u201d seen in remyelination.\nMUSCLE BIOPSIES\nMuscle biopsies are used to evaluate myopathies or neurogenic atrophy. Specimens are often processed \nfor electron microscopy and saved as frozen sections for enzyme studies.\nPROCESSING THE SPECIMEN\n\t1.\t \u0007Two unfixed specimens wrapped in saline-moistened gauze may be submitted. #1 is submitted on a \nclamp and #2 is unclamped.\n\t2.\t \u0007Specimen #1 (clamped):\nEM: submit a specimen large enough to be oriented for cross sections. Place in glutaraldehyde.\nHistochemistry: A cross section is frozen in isopentane (see below).\n\t3.\t \u0007Specimen #2 (unclamped):\nParaffin sections: Submit both a cross section and longitudinal section.\nAn additional section is frozen for special studies if needed.\nFREEZING MUSCLE BIOPSIES\n\t1.\t \u0007Label a scintillation vial with the surgical pathology number and place in the cryostat to cool. \nA second vial will be needed if biochemistry studies are required.\n\t2.\t \u0007Pour liquid nitrogen into a large Dewar flask kept cold in a freezer.\n\t3.\t \u0007Pour cold isopentane (only enough to cover the specimen) into a precooled small metal cup, and \nimmerse the base of the clamp in liquid nitrogen.\n\t4.\t \u0007The isopentane bath is ready to use when white drops form on the bottom of the cup.\n\t5.\t \u0007Cut one section from the middle of the specimen, approximately 5 to 7 mm in length.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_551.png", "summary": "Nerve biopsies are performed to evaluate peripheral neuropathy, with processing for light microscopy, EM, and frozen tissue. Muscle biopsies are used to evaluate myopathies or neurogenic atrophy, with processing for electron microscopy and frozen sections.", "questions": [ "How are nerve biopsies processed for evaluation?", "What special studies may be indicated for nerve biopsies?", "What is the significance of freezing muscle biopsies for enzyme studies?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 552, "text": "NEUROPATHOLOGY SPECIMENS\u2003 Muscle Biopsies\n534\n\t\u2002 6.\t \u0007Lightly powder the muscle with baby powder to prevent the outer fibers from detaching. This step \nis optional.\n\t\u2002 7.\t \u0007Take a small piece of stiff paper (e.g., a piece of an index card small enough to fit in a vial) and write \nthe surgical number on one end. Fold the other end to form an \u201cL\u201d shape. The bottom of the \u201cL\u201d is \nwhere the tissue will be placed for freezing.\n\t\u2002 8.\t \u0007Place a drop of the freezing medium on the short arm of the paper. Orient the muscle cross section \nand place on this end. DO NOT cover the muscle with the freezing medium as this interferes with \nthe freezing process.\n\t\u2002 9.\t \u0007Immerse the paper and specimen in the isopentane for about 10 seconds. Place the frozen specimen \non the paper in the precooled vial and store in the \u201370\u00b0C freezer.\n\t10.\t \u0007Tissue for biochemical studies can be frozen en bloc in liquid nitrogen and placed into another pre\u00ad\ncooled vial.\nREFERENCES\n\t\u2002 1.\t \u0007Brown, et al: A simple and effective method for inactivating virus infectivity in formalin-fixed tissue samples \nfrom patients with Creutzfeldt-Jakob disease. Neurology 40:887-890, 1990.\n\t\u2002 2.\t \u0007Budka H, Aguzzi A, Brown P, et al. Tissue handling in suspected Creutzfeldt-Jakob disease (CJD) and other \nhuman spongiform encephalopathies (prion diseases). Brain Pathol 5:319-322, 1995.\n\t\u2002 3.\t \u0007Fichet G, Comoy E, Duval C, et al. Novel methods for disinfection of prion-contaminated medical devices. \nLancet 364:521-526, 2004.\n\t\u2002 4.\t \u0007Cavenee WK, Louis DN, Ohgaki H, Wiestler. WHO Classification of Tumours of the Central Nervous Sys\u00ad\ntem. Lyon, IARC Press, 2007.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_552.png", "summary": "The page provides instructions for preparing muscle biopsies for freezing and storage, including using baby powder to prevent fiber detachment and proper labeling of specimens.", "questions": [ "Why is it important to lightly powder the muscle with baby powder before freezing?", "What is the purpose of using stiff paper to label and freeze the muscle biopsy?", "Why is it necessary to immerse the paper and specimen in isopentane before freezing?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 553, "text": "535\n30\nParaganglioma\nThe adrenal medullary paraganglioma, pheochromocytoma, is discussed in Chapter 11. The extra-\u00ad\nadrenal paragangliomas are classified according to their location and site of origin, which correspond to \nthe paravertebral sympathetic chain:\n\t\u2022\t \u0007Abdominal extra-adrenal paragangliomas\n\t \u2022\t \u0007Organ of Zuckerkandl\n\t \u2022\t \u0007Urinary bladder\n\t\u2022\t \u0007Paragangliomas of the head and neck\n\t\u2022\t \u0007Carotid body paraganglioma\n\t\u2022\t \u0007Jugulotympanic paragangioma\n\t\u2022\t \u0007Vagal paraganglioma\n\t\u2022\t \u0007Laryngeal paraganglioma\n\t\u2022\t \u0007Aortic pulmonary paraganglioma\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 30-1.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Examine the specimen to identify any attached structures. Usually the tumor is surrounded by a small \namount of soft tissue. Record the overall specimen dimensions. Ink the outer surface.\nTABLE 30\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR PARAGANGLIOMA SPECIMENS\nOrgan/tissue resected or biopsied\nSigns and symptoms due to excess catecholamine production.\nPurpose of the procedure\nFamily history (see Table 7-47)\nGross appearance of the organ/tissue/lesion \nsampled\nAny unusual features of the \u00adclinical \n\u00adpresentation\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nPrior malignancy\nPrior treatment (radiation therapy, \n\u00adchemotherapy, drug use that can change \nthe histologic appearance of tissues)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_553.png", "summary": "This page discusses extra-adrenal paragangliomas, classified by location and site of origin. Relevant clinical history and specimen processing guidelines are provided.", "questions": [ "What are the different types of extra-adrenal paragangliomas mentioned on this page?", "How should the specimen be processed for identification of paragangliomas?", "What specific clinical history is relevant for paraganglioma specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 554, "text": "PARAGANGLIOMA\u2003\ufeff\n536\n 2.\t \u0007Serially section through the specimen. Describe the tumor, including size, color, consistency, borders \n(well-circumscribed, infiltrating, multinodular), capsule, necrosis or hemorrhage.\n 3.\t \u0007Carefully examine the surrounding soft tissue for adjacent lymph nodes.\n 4.\t \u0007Submit one cassette per 1 cm of greatest dimension of tumor. Submit sections of all lymph nodes \n\u00adpresent.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Paraganglioma: One section per 1 cm of greatest dimension\n\t\u2022\t \u0007Lymph nodes: Submit any lymph nodes present\nSPECIAL STUDIES\nParaganglioma. The gross and microscopic appearance is similar to a pheochromocytoma. These \ntumors are usually well-circumscribed with a thin capsule and have a homogeneous fleshy yellow surface. \nThey are often adherent to the carotid artery (if present), but this is not a sign of malignancy. Special \nstudies are not required for the diagnosis of paragangliomas and should only be considered if the diag\u00ad\nnosis is uncertain or the gross appearance is atypical. The diagnosis can be confirmed on formalin fixed \ntissue by immunoperoxidase staining (\u201czellballen\u201d are positive for chromogranin and the surrounding \nsustentacular cells are positive for S100).\nPATHOLOGIC PROGNOSTIC/DIAGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR PARAGANGLIOMAS\n\t\u2022\t \u0007Tumor size: Greatest dimension\n\t\u2022\t \u0007Tumor configuration: Single or multiple nodules\n\t\u2022\t \u0007Invasion: Encapsulated or with invasion into surrounding tissue\n\t\u2022\t \u0007Necrosis: Present or absent\nCRITERIA FOR MALIGNANCY IN PARAGANGLIOMAS\nAbout 10% of paragangliomas are malignant based on either extensive local invasion or metastasis. \nHistologic features may be suggestive of, but cannot accurately predict malignant behavior. The likeli\u00ad\nhood of such behavior can be determined using these four features. 71% of malignant paragangliomas \nhave two or three of these features whereas 89% of benign tumors have none or one of the features:\n\t \u2022\t \u0007Extra-adrenal location\n\t \u2022\t \u0007Coarse nodularity or multiple nodules on gross examination\n\t \u2022\t \u0007Confluent tumor necrosis\n\t \u2022\t \u0007Absence of hyaline globules", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_554.png", "summary": "Paragangliomas are tumors that are usually well-circumscribed with a thin capsule and have a homogeneous fleshy yellow surface. Special studies are not required for diagnosis, but may be considered if the diagnosis is uncertain or if the gross appearance is atypical.", "questions": [ "What are the key features to look for when describing a paraganglioma?", "How can the diagnosis of paragangliomas be confirmed on formalin-fixed tissue?", "What are the criteria for malignancy in paragangliomas and how accurate are histologic features in predicting malignant behavior?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 555, "text": "537\n31\nPenis\nAmputations of the penis are almost always for the resection of invasive squamous cell carcinomas. Fore\u00ad\nskin evaluation is discussed in Chapter 18.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the dimensions of the total specimen (length, circumference) and foreskin (length, width, \nthickness) (Fig. 31-1).\nTumors usually affect the glans and coronal sulcus. Describe the lesion including size, color, growth \npattern (fungating, papillary, verrucous, ulcerated), consistency (friable, soft, rubbery, hard), contour \n(well-defined, infiltrating, pushing margins), location, and distance from the proximal resection mar\u00ad\ngin.\nCorpus spongiosum\nCorpus cavernosa\nUrethra\nIschial tuberosity\nFrenu-\nlum\nGlans penis\nCorona\nCorpus spongiosum\nFigure 31-1.\u2002 Penis anatomy.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_555.png", "summary": "Amputations of the penis are typically performed for invasive squamous cell carcinomas, with tumors usually affecting the glans and coronal sulcus.", "questions": [ "How is the foreskin evaluation relevant in cases of amputations of the penis?", "What specific characteristics of the lesion are important to describe during processing the specimen?", "Why is it important to record the dimensions of the total specimen and foreskin?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 556, "text": "538\nPENIS\u2003\ufeff \u0018PENIS\u2003\ufeff\ufeff\n 2.\t \u0007Open the urethra along the ventral aspect where it is closest to the surface. Extend this cut deeper to \nbisect the penis. Record the depth of invasion, and involvement of foreskin, frenulum, glans, meatus, \ncorpora cavernosa, urethra, and corpus spongiosum.\n 3.\t \u0007Fix the specimen overnight in formalin.\n 4.\t \u0007Microscopic sections may be taken the following day. Additional cuts can be taken at right angles to \nfurther evaluate the tumor.\nMICROSCOPIC SECTIONS\n\t \u2022\t \u0007Tumor: Up to four cassettes demonstrating deepest extent of invasion, relationship to adjacent \nstructures.\n\t \u2022\t \u0007Margin: Up to two cassettes of proximal resection margin, including skin, corpora, and urethra.\nSubmit more if there is grossly suspicious involvement.\n\t \u2022\t \u0007Other structures: Any structure not included above.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR TUMORS OF THE PENIS\n\t \u2022\t \u0007Type of Procedure: Penectomy, partial penectomy\n\t \u2022\t \u0007Type of Tumor: Squamous cell carcinoma (and subtypes), others rare\n\t \u2022\t \u0007Grade: Well, moderate, or poor\n\t \u2022\t \u0007Size: In centimeters\n\t \u2022\t \u0007Extent of Invasion: In situ, subepithelial connective tissue (depth in cm), corpus spongiosum (depth \nin cm), cavernosum (depth in cm), urethra, prostate, other adjacent structures\n\t\n\u2022\t \u0007Lymphovascular invasion: Present or absent\n\t\n\u2022\t \u0007Blood vascular invasion: Present or absent\n\t\n\u2022\t \u0007Perineural invasion: Present or absent\n\t \u2022\t \u0007Nodal status: Regional lymph nodes are inguinal. Single vs. multiple, unilateral vs. bilateral.\n\t \u2022\t \u0007Margins: Involved or not involved \u2013 urethral, corpus spongiosum, corpus cavernosum, cutaneous\n\t \u2022\t \u0007Associated lesions: Squamous hyperplasia, balanitis xerotica obliterans, condyloma acuminatum, \nbowenoid papulosis, Paget disease, basal cell carcinoma\nThis checklist includes recommendations from the ADASP (see www.adasp.org). Underlined ele\u00ad\nments and AJCC staging are considered to be required elements (Table 31-1).", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_556.png", "summary": "The page provides instructions on how to process a penile specimen for pathological evaluation, including recording depth of invasion and involvement of various structures. It also includes a checklist for reporting diagnostic and prognostic features of penile tumors.", "questions": [ "What are the key steps involved in processing a penile specimen for pathological evaluation?", "What are the important diagnostic and prognostic features that should be included in the sign-out checklist for penile tumors?", "How does lymphovascular invasion, blood vascular invasion, and perineural invasion impact the prognosis of penile tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 557, "text": "539\nPENIS\u2003\ufeff \u0018PENIS\u2003\ufeff\ufeff\nTABLE 31\u20131.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF TUMORS OF THE PENIS\nTumor\nTX\nPrimary tumor cannot be assessed\nT0\nNo evidence of primary tumor\nTis\nCarcinoma in situ\nT1\nNon-invasive verrucous carcinoma*\nT1a\nTumor invades subepithelial connective tissue without LVI** and is not poorly differentiated (i.e., \nnot grade 3-4)\nT1b\nTumor invades subepithelial connective tissue with LVI or is poorly differentiated\nT2\nTumor invades corpus spongiosum or cavernosum\nT3\nTumor invades urethra\nT4\nTumor invades other adjacent structures\n*Broad pushing penetration (invasion) is permitted \u2013 destructive invasion is against this diagnosis.\n**LVI: lymph vascular invasion\nRegional Lymph Nodes*\npNX\nRegional lymph nodes cannot be assessed\npN0\nNo regional lymph node metastasis\npN1\nMetastasis in a single inguinal lymph node\npN2\nMetastasis in multiple or bilateral inguinal lymph nodes\npN3\nExtranodal extension of lymph node metastasis or pelvic lymph node(s) unilateral or bilateral\n*Based upon biopsy or surgical excision\nNote: Regional lymph nodes include superficial inguinal (femoral), deep inguinal (Rosenmuller\u2019s or Cloquet\u2019s node), external iliac, internal iliac \n(hypogastric), and pelvic nodes.\nDistant Metastases\nM0\nNo distant metastases\nM1\nDistant metastases*\n*Lymph node metastasis outside the true pelvis in addition to visceral or bone sites.\nNote: Primary urethral carcinomas and melanomas are not included in this classification.\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \u00adCommittee \non Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_557.png", "summary": "This page provides the AJCC classification of tumors of the penis, including primary tumor assessment, regional lymph node involvement, and distant metastases.", "questions": [ "What are the different stages of primary tumors of the penis according to the AJCC classification?", "What is the significance of lymph vascular invasion (LVI) in the classification of penile tumors?", "Which lymph nodes are considered regional lymph nodes in the context of penile cancer staging?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 558, "text": "540\n32\nSoft Tissue Tumors (Sarcomas)\nSoft tissue tumors are among the most difficult neoplasms to diagnose. Often special studies (immuno\u00ad\nperoxidase studies, EM, cytogenetics) are required for the appropriate classification of these tumors and \nfor reliable separation from carcinomas, melanomas, and lymphomas.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 32-1.\nBIOPSIES\nBiopsies are usually performed to make decisions about the use of preoperative therapy and the extent \nof definitive surgery to obtain adequate margins. Either incisional or needle biopsies are used. It may \nnot be possible to provide a specific diagnosis or grade based on very small specimens.\nPROCESSING THE SPECIMEN\n \n1.\t \u0007Relevant clinical history should be provided or obtained to establish a preoperative differential \ndiagnosis (i.e., patient gender, age, location and depth of mass, involvement of soft tissue and/or \nbone, prior history of malignancies). The likely diagnosis will aid in deciding how to apportion \nlimited amounts of lesional tissue.\n \n2.\t \u0007Describe the specimen, including type (needle, incisional), size, color, necrosis or hemorrhage. \nIndicate what proportion of the specimen appears to be lesional and nonlesional (fibrous, fatty, etc.).\n \n3.\t \u0007Very small or very heterogeneous (i.e., little tissue is available and viable tumor is difficult to iden\u00ad\ntify grossly) specimens are fixed in formalin and submitted in entirety.\nTABLE 32\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR SARCOMA SPECIMENS\nOrgan/tissue resected or biopsied\nLocation and depth of mass\nPurpose of the \u00adprocedure\nInvolvement of soft tissue or bone\nGross appearance of the organ/tissue/lesion sampled\nRate of growth (duration of lesion)\nAny unusual features of the clinical presentation\nPresenting symptoms and signs.\nAny unusual features of the gross appearance\nPreoperative therapy\nPrior surgery/\u00adbiopsies \u2013 results\nFamily history (e.g., \u00adLi-Fraumeni syndrome, familial \n\u00adretinoblastoma syndrome)\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug use \nthat can change the histologic \u00adappearance of tissues)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_558.png", "summary": "Soft tissue tumors are challenging to diagnose and often require special studies for accurate classification. Biopsies are crucial for treatment decisions, but specific diagnoses may be difficult with small specimens.", "questions": [ "What are some of the special studies commonly used for the classification of soft tissue tumors?", "Why is it important to provide relevant clinical history when processing soft tissue tumor specimens?", "What challenges may arise when trying to provide a specific diagnosis or grade based on very small specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 559, "text": "541\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Lipomas\nLarger specimens should be apportioned for special studies if lesional tissue can be identified. Also \nsee Chapters 6 and 7.\nIn selected cases, a frozen section or cytologic preparation may be helpful to narrow the differential \ndiagnosis to guide apportionment of limited \u00adtissue.\nSPECIAL STUDIES\n\t \u2022\t \u0007Formalin: Formalin-fixed tissue remains the cornerstone of diagnosis. Make sure there are suffi\u00ad\ncient representative samples in formalin before submitting for special studies, which are listed below \nin order of importance.\n\t \u2022\t \u0007EM: Requires a small amount of tissue that can be examined by light microscopy as well as by EM. If \nthe tumor is heterogeneous, submit multiple specimens paired with formalin sections. EM is useful \nfor distinguishing carcinoma from sarcoma (intercellular junctions), melanoma (premelanosomes), \nand subtyping round cell sarcomas (e.g., rhabdomyosarcoma) and some spindle cell sarcomas (e.g., \nmalignant peripheral nerve sheath tumors) (see in Chapter 7, \u201cElectron Microscopy\u201d).\n\t \u2022\t \u0007Frozen tissue: One or more 1 cm3 fragments are optimal. Smaller samples are acceptable if the \n\u00adspecimen is limited. The tissue is cut into 0.2 cm fragments and stored at -70\u00b0C.The tissue can be \nused for molecular analysis (DNA, RNA, FISH, Southern blotting, PCR, RT-PCR). Frozen tissue \nmay be required for some treatment protocols.\n\t \u2022\t \u0007Cytogenetics: It is helpful to save tissue for cytogenetics if sarcoma is suspected clinically and there \nis a sufficient sample. Cytogenetics is a very useful technique for classifying some tumors (see in \nChapter 7, \u201cCytogenetics\u201d) but may require a large volume of tissue that cannot be examined histo\u00ad\nlogically. The equivalent amount of two needle biopsies may be sufficient for highly cellular tumors, \nbut 1 to 2 cm3 of tumor is preferred.\nLIPOMAS\nLipomas are common benign soft tissue tumors that are often removed for cosmetic reasons. However, \nmalignancy must always be excluded. The likelihood of malignancy is increased if any of the following \nfeatures are present:\n\t \u2022\t \u0007Large size (over 5 cm).\n\t \u2022\t \u0007Infiltration into surrounding tissues.\n\t \u2022\t \u0007Location in deep tissues or near the spermatic cord.\n\t \u2022\t \u0007History of recurrence.\n\t \u2022\t \u0007Unusual gross appearance \u2013 any appearance other than apparently normal fat (e.g., white or cream-\ncolored, homogeneous, firm, fibrotic areas, attached tissues). \nApproximately 22% of patients undergoing hernia repair will also have an incidental cord lipoma. \nIn the cited study by Montgomery and Buras1, only 0.1% of hernia sac operations yielded an incidental \nliposarcoma. The two patients with liposarcoma were older than the average patient with cord lipoma \n(56 and 64 years versus 35 years) and the tumors were larger (13 and 10 cm versus 5.5 cm). Palpable cord \ntumors are more likely to be malignant.\nLipomas are usually enucleated without removal of the adjacent tissue. Thus, the lesion is often frag\u00ad\nmented. There is no reason to ink these specimens, as the lesion is present at the margin and margins are \nirrelevant for the vast majority of benign lesions.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record overall or aggregate measurements if fragmented. Thinly section through the specimen. Eval\u00ad\nuate the specimen for tissues present (usually adipose tissue, occasionally muscle, all other tissues are \nrare).\n 2.\t \u0007Sample the lesion with one section per centimeter of greatest dimension, including all areas of varying \nappearance. Two fragments can be placed in one cassette.\n 3.\t \u0007It is helpful to send tissue for cytogenetics if any of the following features are present:\n\t \u2022\t \u0007Subcutaneous lipomas >10 cm in size", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_559.png", "summary": "Soft tissue tumors, specifically lipomas, may require special studies for diagnosis and treatment planning. Lipomas are common benign tumors that may need to be differentiated from liposarcomas.", "questions": [ "What are the key special studies recommended for diagnosing soft tissue tumors?", "What are the features that may indicate malignancy in lipomas?", "How common are incidental cord lipomas in patients undergoing hernia repair?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 560, "text": "542\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Resections\n\t \u2022\t \u0007Lipomas in deep-seated locations (i.e., subfascial, intramuscular, intra-abdominal, retroperitoneal; \nincluding all clinically-evident cord lipomas)\n\t \u2022\t \u0007Lipomas with unusual gross appearance (e.g., creamy color, firm consistency)\n\t \u2022\t \u0007Request by surgeon.\nRESECTIONS\nResections are often large and may include organs and limbs. It is usually advisable to discuss and ori\u00ad\nent large complicated resections with the surgeon at the time of resection and to identify all anatomic \nlandmarks.\nTypes of resections:\n\t \u2022\t \u0007Intralesional: Gross tumor is left in the patient. These may be debulking procedures for palliation \nwhen complete resection is not possible (e.g., for sarcomas involving the abdominal cavity at mul\u00ad\ntiple sites).\n\t \u2022\t \u0007Marginal: The tumor with its pseudocapsule is removed with a small amount of surrounding tissue. \nTumor is generally microscopically present at the margin.\n\t \u2022\t \u0007Wide: This is an intracompartmental resection. The tumor is removed with a rim of at least 2 cm of \nnormal tissue, but an entire compartment is not removed. The margin width may be less if there is \na fascial plane.\n\t \u2022\t \u0007Segmental/en bloc resection for bone: The portion of involved bone is removed with a cuff of \nnormal bone.\n\t \u2022\t \u0007Radical: An entire soft tissue compartment or bone is removed. This type of procedure includes \namputations and disarticulations.\nMargins are extremely important! Complete resection of the tumor with adequate width of margins \nor an uninvolved fascial plane, are important determinants of long-term outcome. Distance from the \nmargin may determine the need for further surgery or postoperative radiation therapy.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Evaluate the outer surface of the specimen for structures present (muscle, bone, nerve, vessels, organs) \nand gross tumor involvement. Record measurements (outer dimensions, structures present). For very \nlarge retroperitoneal lesions, the weight may be requested by clinicians.\n 2.\t \u0007Selectively ink the outer margins if they appear closer than 2 cm, excluding skin if present. Avoid \ninking any nonmarginal tissue (e.g., soft tissue exposed by overlying retracted muscle). In general, \nmargins more than 2 cm from the tumor need not be inked and those more than 5 cm from the tumor \nneed not be sampled.\n 3.\t \u0007Serially section, leaving the sections attached at one side. Describe the lesion, including size in three \ndimensions (very important!), color, borders (infiltrating, pushing, satellite nodules), necrosis (percent \nof tumor involved) or hemorrhage, variation in gross appearance, involvement of adjacent structures \n(arising from a structure such as nerve, vessel, or muscularis propria), and location (skin, subcutaneous \ntissue, fascia, muscle, visceral).\nThe closest gross distance from all margins and the type of tissue at each margin (e.g., fascial plane, \nperiosteum, muscle, strands of soft tissue) are documented. Most specimens should have at least six \nmargins evaluated (visualize the specimen as if it were a box with six sides).\nComplicated specimens will require a diagram documenting the location of the tumor and adjacent \nstructures and the site of microscopic sections.\nIf bone is included in the specimen, a specimen radiograph is performed to document the location \nof the bone(s) and areas of possible tumor involvement. See also Chapter 12.\nLymph nodes are not usually resected along with soft tissue sarcomas and are rarely involved (other \nthan in certain uncommon tumor types). However, any lymph nodes present in a resection specimen \nshould be examined.\n 4.\t \u0007Pin the oriented specimen on wax and fix in an adequate volume of formalin for at least 10 to 12 \nhours to facilitate taking sections from the margins and the interface between normal and tumor \ntissue.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_560.png", "summary": "This page discusses resections of soft tissue tumors (sarcomas), including different types of resections and the importance of margins in determining long-term outcomes.", "questions": [ "What are the different types of resections for soft tissue tumors?", "Why is it important to discuss and orient large complicated resections with the surgeon?", "How is the specimen processed for evaluation after resection?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 561, "text": "543\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Resections\n 5.\t \u0007Submit tumor for special studies as indicated above. It is helpful to take tissue from all areas that have \na different gross appearance (e.g., different consistencies or colors) and to match adjacent sections \nsubmitted for light microscopy and special studies. Avoid necrotic areas when taking tissue for \nspecial studies. If the specimen is a re-excision and gross tumor is not apparent, do not submit tissue \nfor special studies.\nAs a general rule, at least one section per centimeter of the tumor\u2019s greatest dimension should be \nexamined including all areas of different gross appearance.\nTake sections to document the extent of necrosis in the absence of prior treatment.\nPerpendicular margins are taken to assess the distance of the tumor from each margin. If the mar\u00ad\ngin is greater than 5 cm from the tumor, it need not be sampled except in cases of epithelioid sarcoma \nand angiosarcoma. Margin involvement by these two types of sarcoma may be difficult to evaluate \ngrossly. En face blocks of margins are not recommended. If gross tumor is not apparent, the distance \nof the scar tissue/biopsy site to each margin is documented.\nIf the patient has received neoadjuvant therapy, it is important to document the extent of response. \nAn entire representative slice of the tumor should be sampled with the location of the blocks of tissue \nindicated on a diagram, photograph, or radiograph. This will allow an estimation of the percent of \ntumor that is necrotic or replaced by fibrous tissue or granulation tissue.\nSPECIAL STUDIES\nTissue may be taken for special studies as described in Chapter 13. Frozen tissue may be required for \nsome treatment protocols.\nGROSS DIFFERENTIAL DIAGNOSIS\nSarcomas.\u2002 In general, sarcomas grow as circumscribed white/tan fleshy masses, often with a pseu\u00ad\ndocapsule. The invasion into adjacent tissues may be subtle and not appreciated grossly. Some sarcomas \nhave distinctive appearances (see below).\nLipomas.\u2002 These tumors are well circumscribed or lobulated and have a thin delicate capsule. The \ntumor usually resembles normal adipose tissue. Lipomas are often enucleated and, thus, are often frag\u00ad\nmented and the capsule cannot be appreciated.\nLiposarcomas.\u2002 Low-grade lipoma-like liposarcomas may be soft and resemble normal fat. However, \nthese tumors are usually paler and have a more coarsely lobulated appearance. Higher grade liposarcomas \nare more likely to have firm solid areas as well as areas of necrosis.\nSchwannoma.\u2002 Circumscribed encapsulated mass consisting of tan/white to yellow firm tissue. It \nmay be possible to identify an associated nerve.\nNeurofibroma.\u2002 Circumscribed mass with a thin capsule consisting of soft tan/white tissue. The nerve \nis incorporated into the lesion and may not be separately identified. In patients with neurofibromatosis, \nthe lesions may be plexiform (multiple lesions along a nerve \u2013 \u201cbag of worms\u201d).\nMalignant Peripheral Nerve Sheath Tumor.\u2002 Often infiltrative, and hemorrhage and necrosis may \nbe present. These tumors sometimes arise from a nerve that may be identifiable entering one side of the \ntumor. Tumors arising in patients with neurofibromatosis may be plexiform (i.e., multiple finger-like \nprojections of tumor in the surrounding tissue - \u201cbag of worms\u201d appearance).\nLeiomyosarcomas.\u2002 These tumors are often found in association with the smooth muscle from which \nthey arise (e.g., a large vein or the myometrium). They often have a whorled appearance.\nGastrointestinal Stromal Tumors (GIST).\u2002 These tumors are found throughout the gastrointes\u00ad\ntinal tract. They are composed of cells similar to Cajal cells of the smooth muscle lining, and are \ntherefore found associated with smooth muscle. The gross appearance is similar to leiomyomas. 80% \nof GISTs have a mutation in the KIT tyrosine kinase gene. A smaller group (5% to 7%) have muta\u00ad\ntions in the KIT-homologous tyrosine kinase PDGFRA. About 10% to 15% of GISTs are negative", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_561.png", "summary": "The page discusses the proper handling and submission of soft tissue tumors (sarcomas) for special studies during resections, emphasizing the importance of documenting gross appearance, extent of necrosis, margin involvement, and response to neoadjuvant therapy.", "questions": [ "What are the key considerations when submitting soft tissue tumors for special studies during resections?", "How should necrotic areas be handled when taking tissue for special studies?", "Why is it important to document the extent of response to neoadjuvant therapy in soft tissue tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 562, "text": "544\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Resections\nfor KIT and \u00adPDGFRA mutations (termed \u201cwild-type GISTs\u201d). The type of mutation can be of \nprognostic importance and can correlate with response to different drugs. Sequence analysis may \nbe requested at the time of diagnosis or for tumors negative for KIT by immunohistochemistry or \ntumors resistant to treatment. Resistance may be due to additional mutations in KIT or PDGFRA. \nFixed tissue can be used.\nAngiosarcomas.\u2002 The tumor may subtly infiltrate the tissue, producing a grossly indistinct mass. \nExtensively involved areas are often very hemorrhagic.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Tumor: The general rule of thumb is one cassette per cm of greatest dimension. Document all areas \nwith different appearances, edges (e.g., capsule, infiltration), and involvement of any adjacent struc\u00ad\ntures or organs.\nMore extensive sampling is indicated for low-grade lesions, as the finding of a high-grade area would \nchange stage and prognosis.\nIf the tumor has not been treated, one section to document necrosis including an adjacent area of \nviable tumor is sufficient.\nIf prior neoadjuvant therapy has been given, a complete representative cross section of tumor should \nbe submitted with the location of the blocks of tissue recorded, in order to determine the extent of \ntumor response.\n\t\u2022\t \u0007Margins: Document all close margins with at least one cassette. If the tumor is very close to a margin \n(i.e., within 2 cm), multiple sections may be submitted. Take only perpendicular margins. If a margin \nis >5 cm from the tumor, and the tumor is not an angiosarcoma or an epithelioid sarcoma, the margin \nneed not be submitted.\nMargins should be 1 to 2 cm or an uninvolved fascial plane for sarcomas.\n\t\u2022\t \u0007Other structures: Document any other anatomical struc\u00adtures present. Document any prior biopsy \nscars/sites.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR SOFT TISSUE TUMORS\n\t\u2022\t \u0007Procedure: Needle core biopsy, intralesional resection, marginal resection, wide resection, radical \nresection, amputation\n\t\u2022\t \u0007Tumor Site: Location of tumor\n\t\u2022\t \u0007Tumor Size: Greatest dimension (other dimensions optional)\n\t\u2022\t \u0007Extent of Tumor: Superficial (dermal, subcutaneous/suprafascial), deep (fascial, subfascial, intramus\u00ad\ncular, mediastinal, intra-abdominal, retroperitoneal, head and neck)\n\t\u2022\t \u0007Histologic Type: Liposarcoma, rhabdomyosarcoma, leiomyosarcoma, malignant peripheral nerve \nsheath tumor, numerous other types. The WHO Classification system is recommended.\n\t\u2022\t \u0007Mitotic Rate: Number of mitoses per 10 HPF (1 HPF = 0.1734 mm2) in the most mitotically active \narea of the tumor. Count at least 50 HPF. If specific grading systems are used (see below) the mitotic \ncount should be adjusted for the size of the HPF.\n\t\u2022\t \u0007Necrosis: Present or absent and extent (% of tumor)\n\t\u2022\t \u0007Histologic Grade: Some tumors are by definition high grade or low grade, and some cannot be \ngraded. Other types can be divided into grades and this provides prognostic information (see below for \nthe FNCLCC systems). Grading of malignant peripheral nerve sheath tumor, embryonal and alveolar \nrhabdomyosarcoma, angiosarcoma, extraskeletal myxoid chondrosarcoma, alveolar soft part sarcoma, \nclear cell sarcoma, and epithelioid sarcoma is not recommended.\n\t\u2022\t \u0007Margins: The distance to each margin should be recorded. Margins less than 2 cm should be speci\u00ad\nfied as to location and distance. In re-excision specimens, the distance of scarring or granulation tissue \nfrom margins should also be measured. Margins bounded by a fascial plane or periosteum should be \nidentified as a smaller distance may be adequate.\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present. Rarely observed in sarcomas.\n\t\u2022\t \u0007Tumor Margin Characteristics: Circumscribed, focally infiltrative, diffusely infiltrative\n\t\u2022\t \u0007Regional Lymph Nodes: Rarely involved. Most common in alveolar rhabdomyosarcomas, angiosar\u00ad\ncomas, epithelioid sarcomas, and clear cell sarcomas", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_562.png", "summary": "Soft tissue tumors, including sarcomas, may require testing for specific mutations for prognostic and treatment purposes. Extensive sampling and documentation of margins and other structures are important for accurate diagnosis and prognosis.", "questions": [ "How do KIT and PDGFRA mutations impact the prognosis and treatment of soft tissue tumors?", "Why is extensive sampling and documentation of margins important in the evaluation of soft tissue tumors?", "What are the key diagnostic and prognostic features that should be included in the sign-out checklist for soft tissue tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 563, "text": "545\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Resections\n\t\u2022\t \u0007Preexisting Lesion: If the tumor is a nerve-sheath neoplasm, state whether there is evidence of a \npreexisting benign lesion\n\t\u2022\t \u0007Inflammatory Response: Optional (no known relevance) \u2013 present or absent, extent, type\n\t\u2022\t \u0007Treatment Effect: If patient has received prior treatment: extent of tumor necrosis, percentage of \nviable tumor\n\t\u2022\t \u0007Ancillary Studies: Cytogenetics, molecular pathology, if appropriate\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the \nM category is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 32-2). \nM0 is conferred after clinical assessment; there is no pM0 category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/). The underlined elements are considered to be scientifically vali\u00ad\ndated or regularly used data elements that must be present in reports of cancer-directed surgical resection \nspecimens from ACS CoC-approved cancer programs. The specific details of reporting the elements may \nvary among institutions.\nTABLE 32-2.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF SOFT TISSUE SARCOMAS\nTumor\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nTumor \u22645 cm in greatest dimension*\nT1a\nSuperficial tumor\nT1b\nDeep tumor\nT2\nTumor >5 cm in greatest dimension*\nT2a\nSuperficial tumor\nT2b\nDeep tumor\n*Superficial tumor is located exclusively above the superficial fascia without invasion of the fascia; deep tumor is located either exclusively beneath \nthe superficial fascia, superficial to the fascia with invasion of or through the fascia, or both superficial yet beneath the fascia.\nRegional Lymph Nodes\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1*\nRegional lymph node metastasis\n*Presence of positive nodes (N1) in M0 tumors is considered stage III.\nDistant Metastases\nM0\nNo distant metastasis\nM1\nDistant metastasis\nNote: This classification system does not apply to inflammatory myofibroblastic tumor, infantile fibrosarcoma, Kaposi sarcoma, fibromatosis (des\u00ad\nmoid tumor), mesothelioma, or sarcomas arising in tissues apart from soft tissue (e.g., parenchymal organs). There is a separate AJCC staging system \nfor gastrointestinal stromal tumor. There is an alternative staging system for rhabdomyosarcoma of children and young adults (see CAP Protocol for \nthe Examination of Specimens from Patients with Rhabdomyosarcoma, www.cap.org).\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \nCommittee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_563.png", "summary": "This page provides guidelines for reporting on soft tissue sarcomas, including information on preexisting lesions, inflammatory response, treatment effects, ancillary studies, distant metastasis, and AJCC classification.", "questions": [ "What are the key elements that must be included in reports of cancer-directed surgical resection specimens?", "How is the presence of distant metastasis determined in soft tissue sarcomas?", "Why is the AJCC classification important in the evaluation of soft tissue sarcomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 564, "text": "546\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Resections\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR PEDIATRIC RHABDOMYOSARCOMA \nAND RELATED NEOPLASMS\n\t\u2022\t \u0007Procedure: Excision (local, wide, or radical), compartectomy, amputation (type, neural, vascular, soft \ntissue margins), other (e.g., piecemeal, needle core biopsy, incisional biopsy)\n\t\u2022\t \u0007Specimen Laterality: Right, left, midline\n\t\u2022\t \u0007Tumor Site: Bladder/prostate, cranial parameningeal, extremity, genitourinary, head and neck \n(excluding parameningeal), orbit, other\n\t\u2022\t \u0007Tumor Size: Greatest dimension (other dimensions optional)\n\t\u2022\t \u0007Tumor Depth: Dermal, subcutaneous, subfascial, intramuscular, intra-abdominal, retroperitoneal, \nintracranial, organ based\n\t\u2022\t \u0007Histologic Type: Embryonal (botryoid, spindle cell, or not otherwise specified), alveolar (solid or not \notherwise specified), mixed (give percentage of each type), undifferentiated\n\t\u2022\t \u0007Anaplasia: Not identified, focal (single or few scattered anaplastic cells), diffuse (clusters or sheets of \nanaplastic cells)\n\t \u2022\t \u0007May be associated with any histologic type\n\t \u2022\t \u0007Defined as large, lobate hyperchromatic nuclei (at least 3 times the size of neighboring nuclei) and \natypical (obvious, multipolar) mitotic figures.\n\t\t\n\u0007Focal anaplasia (group I): A single or a few cells scattered amongst non-anaplastic cells\n\t\t\n\u0007Diffuse anaplasia (group II): Clusters or sheets of anaplastic cells present\n\t\u2022\t \u0007Margins: Cannot be assessed, uninvolved, distance from closest margin, involved margin (specify)\n\t\u2022\t \u0007Regional Lymph Nodes: Cannot be assessed, negative, metastases present (specify number of nodes \nexamined and number with metastases)\n\t\u2022\t \u0007Mitotic Rate: Give number of mitoses per 10 HPF using a 40\u00d7 objective in the most proliferative area.\n\t\u2022\t \u0007Necrosis: Absent, present (extent in %)\n\t\u2022\t \u0007Distant Metastases: Cannot be assessed, present (specify sites, if known)\n\t\u2022\t \u0007Stage: The Intergroup Rhabdomyosarcoma Study Postsurgical Clinical Grouping System or the \nModified Site, Size, Metastasis Staging for Rhabdomyosarcoma may be used if sufficient information \nis available (Table 32.3).\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/). The underlined elements are considered to be scientifically vali\u00ad\ndated or regularly used data elements that must be present in reports of cancer directed surgical resection \nspecimens from ACS CoC-approved cancer programs. The specific details of reporting the elements may \nvary among institutions.\nGRADING OF SOFT TISSUE SARCOMAS\n\t\u2022\t \u0007The Intergroup Rhabdomyosarcoma Study (IRS) post-surgical clinical grouping system: If \napplicable, the appropriate stage group may be assigned by the pathologist (Table 32-3).\n\t\u2022\t \u0007The F\u00e9d\u00e9ration Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading \nsystem for soft tissue sarcomas of adults (updated version): Tables 32-4 and 32-5. Do not grade:\n\t \u2022\t \u0007Treated tumors\n\t \u2022\t \u0007Benign lesions\n\t \u2022\t \u0007Bone sarcomas\n\t \u2022\t \u0007Visceral sarcomas (uterine and gastrointestinal sarcomas)\n\t \u2022\t \u0007Pediatric sarcomas\n\t \u2022\t \u0007Dermatofibrosarcoma protuberans\n\t \u2022\t \u0007Atypical fibroxanthoma\n\t \u2022\t \u0007Fine needle or core biopsies (sampling error is likely to be high)\nHowever, recurrent tumors should be graded.3-5\n\t\u2022\t \u0007Gastrointestinal stromal tumor (GIST): There are several suggested methods of dividing GIST \ninto groups according to the risk of progression or metastasis. Most are based on the number of metas\u00ad\ntases and size (Tables 32-6 and 32-7).6,7", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_564.png", "summary": "This page outlines the pathologic diagnostic and prognostic features checklist for pediatric rhabdomyosarcoma and related neoplasms, including details on specimen characteristics, histologic types, anaplasia, margins, lymph nodes, mitotic rate, necrosis, distant metastases, and staging.", "questions": [ "How is the mitotic rate determined in pediatric rhabdomyosarcoma specimens?", "What are the key elements that must be present in reports of cancer-directed surgical resection specimens?", "How does the FNCLCC grading system for soft tissue sarcomas of adults differ from the IRS post-surgical clinical grouping system?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 565, "text": "547\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Resections\nTABLE 32\u20134.\u2003 \u0007THE F\u00c9D\u00c9RATION NATIONALE DES CENTRES DE LUTTE CONTRE LE CANCER \n(FNCLCC) GRADING SYSTEM FOR SOFT-TISSUE SARCOMAS OF ADULTS \n(UPDATED VERSION)\nTUMOR DIFFERENTIATIONa\nFEATURES\nScore 1\nSarcomas closely resembling normal, adult, mesenchymal tissue \n(e.g., well-differentiated liposarcoma)\nScore 2\nSarcomas of certain histologic types (see Table 32-5)\nScore 3\nSynovial sarcomas, embryonal sarcomas, undifferentiated sarcomas, \nand sarcomas of doubtful tumor type (see Table 32-5)\nMITOTIC COUNTb\nScore 1\n0 to 9 mitoses per 10 HPF\nScore 2\n10 to 19 mitoses per 10 HPF\nScore 3\n20 or more mitoses per 10 HPF\nTABLE 32\u20133.\u2003 \u0007THE INTERGROUP RHABDOMYOSARCOMA STUDY (IRS) \u00adPOST-SURGICAL \nCLINICAL GROUPING SYSTEM\nGROUP I\nA\nLocalized tumor, confined to site of origin, completely resected\nB\nLocalized tumor, infiltrating beyond site of origin, completely resected\nGROUP II\nA\nLocalized tumor, gross total resection, but with microscopic residual disease\nB\nLocally extensive tumor (spread to regional lymph nodes), completely resected\nC\nLocally extensive tumor (spread to regional lymph nodes), gross total resection, but with micro\u00ad\nscopic residual disease\nGROUP III\nA\nLocalized or locally extensive tumor, gross residual disease after biopsy only\nB\nLocalized or locally extensive tumor, gross residual disease after major resection (>50% debulking)\nGROUP IV\nAny size primary tumor, with or without regional lymph node involvement, with distant metastases, without \nrespect to surgical approach to primary tumor\nFrom CAP Protocol for the Examination of Specimens from Patients (Children and Young Adults) with Rhabdomyosarcoma \n(available at www.cap.org, Cancer Protocols and Checklists).\nContinued", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_565.png", "summary": "This page discusses the FNCLCC grading system for soft-tissue sarcomas of adults and the Intergroup Rhabdomyosarcoma Study post-surgical clinical grouping system.", "questions": [ "How does the FNCLCC grading system categorize soft-tissue sarcomas based on tumor differentiation?", "What are the different mitotic count scores in the FNCLCC grading system and what do they indicate?", "Can you explain the different groups in the Intergroup Rhabdomyosarcoma Study post-surgical clinical grouping system?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 566, "text": "548\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Resections\nTABLE 32\u20135.\u2003 TUMOR DIFFERENTIATION \u00adSCORE \u2013 FNCLCC SYSTEM\nHISTOLOGIC TYPE\nSCORE\nLiposarcoma\nWell differentiated\n1 (always Grade I)\nMyxoid\n2\nRound cell\n3\nPleomorphic\n3 (always Grade III)\nDedifferentiated\n3\nFibrosarcoma\n2\nMalignant triton tumor\n3\nLeiomyosarcoma\nWell differentiated\n1\nConventional\n2\nPoorly differentiated/pleomorphic/epithelioid\n3\nPleomorphic rhabdomyosarcoma\n3\nChondrosarcoma\nWell differentiated\n1\nMyxoid\n2\nMesenchymal\n3 (always Grade III)\nTUMOR NECROSISc\nScore 0\nNo tumor necrosis on any examined slides\nScore 1\n\u226450% tumor necrosis over all the examined tumor surface\nScore 2\n>50% tumor necrosis over all the examined tumor surface\naThe three scores are added together to determine the histologic grade:\nGrade I: Total score = 2 or 3\nGrade II: Total score = 4 or 5\nGrade III: Total score = 6, 7, or 8\nbMitotic count: The count is made in most mitotically active areas in ten successive high power fields (defined as \u00d7 400 measuring 0.174 mm2). This \ncount is taken to establish the score. Ulcerated, necrotic, and hypocellular areas should not be counted. Only definitive mitotic figures (not pyknotic \nor apoptotic cells) should be counted.\ncTumor necrosis: The necrosis should appear spontaneous and not related to prior surgery or ulceration. Areas of hyalinization or hemorrhage are \nnot scored.\nTABLE 32\u20134.\u2003 \u0007THE F\u00c9D\u00c9RATION NATIONALE DES CENTRES DE LUTTE CONTRE LE CANCER \n(FNCLCC) GRADING SYSTEM FOR SOFT-TISSUE SARCOMAS OF ADULTS \n(UPDATED VERSION)\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_566.png", "summary": "This page provides a scoring system for tumor differentiation in soft tissue sarcomas, as well as guidelines for assessing tumor necrosis and mitotic count to determine histologic grade.", "questions": [ "How is the histologic grade of soft tissue sarcomas determined using the FNCLCC system?", "What is the significance of tumor necrosis in the grading of soft tissue sarcomas?", "How is the mitotic count assessed in the grading of soft tissue sarcomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 567, "text": "549\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Resections\nTABLE 32\u20136.\u2003\nRISK STRATIFICATION OF PRIMARY GIST BY MITOTIC INDEX, SIZE, AND SITE\nTUMOR PARAMETERS\nRISK OF PROGRESSIVE DISEASE (%)a\nMITOTIC INDEX\nSIZE\nGASTRIC\nDUODENUM\nJEJUNUM/ILEUM\nRECTUM\n\u22645 per 50 HPF\n\u22642 cm\nNone (0%)\nNone (0%)\nNone (0%)\nNone (0%)\n>2 but \u22645 cm\nVery low (1.9%)\nLow (4.3%)\nLow (8.3%)\nLow (8.5%)\n>5 but \u226410 cm\nLow (3.6%)\nModerate (24%)\nInsufficient data\nInsufficient data\n>10 cm\nModerate (10%)\nHigh (52%)\nHigh (34%)\nHigh (57%)\n>5 per 50 HPF\n\u22642 cm\nNoneb\nHighb\nInsufficient data\nHigh (54%)\n>2 but \u22645 cm\nModerate (16%)\nHigh (73%)\nHigh (50%)\nHigh (52%)\n>5 but \u226410 cm\nHigh (55%)\nHigh (85%)\nInsufficient data\nInsufficient data\n>10 cm\nHigh (86%)\nHigh (90%)\nHigh (86%)\nHigh (71%)\naDefined as metastasis or tumor-related death.\nbRisk assessment based on small numbers of cases.\nAdapted from Miettinen M, Lasota J, Gastrointestinal stromal tumors: pathology and prognosis at different sites, Semin Diagn Pathol 23:70-83, 2006.\nHISTOLOGIC TYPE\nSCORE\nExtraskeletal osteosarcoma\n3 (always Grade III)\nHemangiopericytoma\nWell differentiated malignant\n2\nConventional malignant\n3\nMalignant fibrous histiocytoma (MFH)\nMyxofibrosarcoma (myxoid MFH)\n2\nTypical storiform MFH (sarcoma, not otherwise specified)\n2\nPleomorphic type (patternless \u00adpleomorphic sarcoma)\n3\nGiant-cell and inflammatory MFH (pleomorphic sarcoma, not \u00adotherwise specified with \ngiant cells or \u00adinflammatory cells)\n3\nEwing sarcoma/PNET\n3 (always Grade III)\nMalignant rhabdoid tumor\n3\nSynovial sarcoma\nBiphasic or monophasic synovial sarcoma\n3\nPoorly differentiated synovial sarcoma\n3\nUndifferentiated sarcoma\n3\nTABLE 32\u20135.\u2003 TUMOR DIFFERENTIATION \u00adSCORE \u2013 FNCLCC SYSTEM\u2014cont\u2019d", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_567.png", "summary": "The page provides risk stratification of primary GIST based on mitotic index, size, and site, as well as histologic type scores for various soft tissue tumors.", "questions": [ "How does the risk of progressive disease vary based on the mitotic index, size, and site of primary GIST?", "What is the significance of the risk assessment based on small numbers of cases for GIST with a mitotic index >5 per 50 HPF and size \u22642 cm?", "How do the histologic type scores for different soft tissue tumors impact prognosis and treatment?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 568, "text": "550\nSOFT TISSUE TUMORS (SARCOMAS)\u2003 Abdominal Fat Pad Biopsy for the Diagnosis of Amyloidosis\nABDOMINAL FAT PAD BIOPSY FOR THE DIAGNOSIS OF AMYLOIDOSIS\nThere are several methods of sampling tissues to establish the diagnosis of systemic amyloidosis. Rectal \nbiopsies are reported to be the most sensitive (97%) followed by fine needle aspiration of the abdominal \nfat pad (75%), oral biopsy (64%), and biopsy of the abdominal fat pad (50%). These latter biopsies can \nbe either excisional or by core biopsy.\nThe tissue can be fixed in formalin and stained with Congo Red. Both false positive and false negative \nresults have been reported. If there is sufficient tissue, some can be saved for EM, which may be helpful \nin confirming a diagnosis. Immunohistochemical studies can be used to identify subtypes of amyloid.\nThe abdominal fat pad biopsy technique is not helpful in the evaluation of dialysis patients with \u03b2-2 \nmicroglobulin amyloidosis as this type of amyloid is preferentially found near joints.\nREFERENCES\n\t1.\t \u0007Montgomery E, Buras R. Incidental liposarcomas indentified during hernia repair operations. J Surg Oncol \n71:50-53, 1999.\n\t2.\t \u0007Qualman SJ, et al: Protocol for the Examination of Specimens from patients (children and young adults) with \nrhabdomyosarcoma. Arch Pathol Lab Med 127:1290-1297, 2003.\n\t3.\t \u0007Trojani M, Contesso G, Coindre J-M, et al: Soft-tissue sarcomas of adults: study of pathological prognostic vari\u00ad\nables and definition of a histopathological grading system. Int J Cancer 33:37-42, 1984.\n\t4.\t \u0007Guillou L, Coindre JM, Bonichon F, et al: A comparative study of the NCI and FNCLCC grading systems in a \npopulation of 410 adult patients with soft tissue sarcoma. J Clin Oncol 15:350-362, 1997.\n\t5.\t \u0007Guillou L, Coindre J- M. How should we grade soft tissue sarcomas and what are the limitations? Pathology Case \nReviews 3:105-110, 1998.\n\t6.\t \u0007Goh BK, Chow PK, Yap WM, et al. Which is the optimal risk stratification system for surgically treated localized \nprimary GIST? Comparison of three contemporary prognostic criteria in 171 tumors and a proposal for a modi\u00ad\nfied Armed Forces Institute of Pathology risk criteria. Ann Surg Oncol.15 :2153-2163, 2008.\n\t7.\t \u0007Huang H-Y, Li C-F, Huang W-W, et al. A modification of NIH consensus criteria to better distinguish the \nhighly lethal subset of primary localized gastrointestinal stromal tumors: a subdivision of the original high-risk \ngroup on the basis of outcome. Surgery 141:748-756, 2007.\nTABLE 32-7.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF GASTROINTESTINAL STROMAL TUMORS\nTumor\nTX\nPrimary tumor cannot be assessed.\nT0\nNo evidence of primary tumor\nT1\nTumor 2 cm or less\nT2\nTumor more than 2 cm but not more than 5 cm\nT3\nTumor more than 5 cm but not more than 10 cm\nT4\nTumor more than 10 cm in greatest dimension\nRegional Lymph Nodes\nNX\nRegional lymph nodes cannot be assessed.\nN0\nNo regional lymph node metastasis\nN1\nRegional lymph node metastasis\nDistant Metastases\nM0\nNo distant metastasis\nM1\nDistant metastasis\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-Verlag, 2009. Used with the permission of the American Joint \u00adCommittee \non Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_568.png", "summary": "Abdominal fat pad biopsy is a method used to diagnose systemic amyloidosis, with rectal biopsies being the most sensitive.", "questions": [ "What are the different methods of sampling tissues to diagnose systemic amyloidosis?", "What staining technique is used on tissue samples from abdominal fat pad biopsies?", "Why is the abdominal fat pad biopsy technique not helpful for evaluating dialysis patients with \u03b2-2 microglobulin amyloidosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 569, "text": "551\n33\nThymus\nThe thymus may be removed due to disease (both benign and malignant tumors), for the treatment of \nmyasthenia gravis, or, rarely, incidentally during thoracic surgery (e.g., open heart surgery). If the speci\u00ad\nmen is of an anterior mediastinal mass, one must consider lymphoma and teratoma as well as thymoma.\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 33-1.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record outer dimensions and weight of the specimen (normal 15 to 30 gm).\nExamine the outer portion of the specimen, looking for adherent structures such as pleura or \n\u00adpericardium. \u00adCapsular and soft tissue invasion is one of the \u00adcriteria separating benign from malignant \nneoplasms; therefore,these areas should be well sampled.\nInk the outer surface if the specimen is intact.\n 2.\t \u0007Serially section the specimen. Describe any lesions including size, color, external appearance (lobu\u00ad\nlated or smooth), relationship to capsule and surrounding structures, edges (encapsulated, infiltrat\u00ad\ning), fibrous bands, calcification, necrosis or hemorrhage, relationship to uninvolved thymus.\nDescribe uninvolved thymus including color, consistency (cystic, nodular, gritty, uniform), relative \nproportions of fat and thymic parenchyma.\n 3.\t \u0007Carefully look for lymph nodes in any attached soft tissue.\n 4.\t \u0007If a lymphoma is suspected, tissue is saved in B5, and submitted for snap freezing and possibly for flow \ncytometry. The remainder of the specimen can be fixed in formalin.\nTABLE 33\u20131.\u2003\nRELEVANT CLINICAL HISTORY\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR THYMUS SPECIMENS\nOrgan/tissue resected or biopsied\nMyasthenia gravis\nPurpose of the procedure\nFindings at surgery (infiltration of adjacent structures)\nGross appearance of the organ/tissue/lesion sampled\nAny unusual features of the clinical presentation\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug \nuse that can change the histologic appearance of \ntissues)\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_569.png", "summary": "The thymus may be removed due to various reasons such as disease, myasthenia gravis treatment, or incidentally during thoracic surgery. When examining a thymus specimen, it is important to consider differentiating between benign and malignant neoplasms.", "questions": [ "What are some common reasons for the removal of the thymus?", "Why is it important to differentiate between benign and malignant neoplasms when examining a thymus specimen?", "What are some key steps in processing a thymus specimen for pathological examination?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 570, "text": "552\nTHYMUS\u2003\ufeff \nSPECIAL STUDIES\n\t\u2022\t \u0007Suspected lymphoma: Save tissue for hematopathologic workup (see above).\n\t\u2022\t \u0007Thymic carcinomas versus carcinomas originating from other sites: The epithelial cells of most \nthymic carcinomas (but not thymomas or invasive thymomas) will be immunoreactive for CD5, \nwhereas carcinomas from other sites will be CD5 negative.\n\t\u2022\t \u0007Thymomas and invasive thymomas versus other tumors: Thymomas and invasive thymomas (but \nnot thymic carcinomas or non-thymic neoplasms) retain a complement of immature cortical thymo\u00ad\ncytes. These cells can be detected by immunohistochemistry for CD99 (=HBA-17 or O13 or MIC-2), \nTdT, or CD19.\nGROSS DIFFERENTIAL DIAGNOSIS\nNormal Thymus.\u2002 The thymus is usually atrophic in the adult, with tan lobules of thymic parenchyma \nseparated by fibrous septae and abundant adipose tissue. Hassell\u2019s corpuscles may be prominent and must \nbe distinguished from metastatic squamous cell carcinoma in a lymph node.\nMyasthenia Gravis.\u2002 Thymectomy is a treatment for myasthenia gravis. The thymus may be normal \nin size or slightly enlarged, but has a grossly normal appearance.\nThymomas are solid, yellow/gray, and divided into lobules by fibrous septae. Most are surrounded \nby a distinct capsule. Invasion into adjacent soft tissue is an important prognostic factor. Cystic degenera\u00ad\ntion is common. Several staging systems are in use.1\nThymic Carcinomas may be hard and white with areas of necrosis and hemorrhage. The broad \nfibrous septae characteristic of thymomas are absent. Invasion into adjacent soft tissue is usually \ngrossly evident.\nGerm Cell Tumors.\u2002 Any type of germ cell tumor can occur in the anterior mediastinum. The gross \nappearance is similar to that seen in tumors arising in the testes.\nLymphomas.\u2002 Hodgkin disease and non-Hodgkin lymphomas can occur at this site. They usually \npresent as lobulated fleshy masses.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Lesions: Four to six cassettes (depending on the size of the specimen) including relationship to cap\u00ad\nsule, remainder of thymus.\n\t\u2022\t \u0007Margins: If the specimen is intact and there is a focal lesion, submit sections of the margin.\n\t\u2022\t \u0007Thymus: Submit two cassettes of uninvolved thymic parenchyma.\n\t\u2022\t \u0007Other structures: Submit representative sections of lymph nodes, pleura, and pericardium if \npresent.\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name and unit number and \u201cmediastinal mass,\u201d is a 7.5 \u00d7 4 \u00d7 4 \ncm \u00adfragment of tissue, composed of a mass with a smoothly lobulated surface on one side and a 5 \u00d7 3 cm \nportion of glistening smooth pericardium on the opposite side. The mass has two major lobes separated \nby a fibrous septum. The mass is pink and gelatinous with fine trabeculae throughout. There are small \ncystic areas filled with pink fluid (largest 0.4 cm). There are small areas of necrosis. The mass is encapsu\u00ad\nlated, except for a 1 \u00d7 1 cm area where it appears to invade into the pericardium and is present at the inked \nmargin. Tissue is taken for snap freezing, cytogenetics, and EM. The majority of the lesion is fixed in B5 \nand quick fixed in formalin.\nCassettes #1-2: B5 fixed tumor with adjacent pericardium, 2 frags, RSS.\nCassettes #3-4: B5 fixed tumor with areas of necrosis and cysts, 3 frags, RSS.\nCassettes #5-6: Formalin fixed tumor and capsule, 2 frags, RSS.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_570.png", "summary": "The page provides information on special studies, gross differential diagnosis, and microscopic sections related to thymus pathology.", "questions": [ "How can thymic carcinomas be distinguished from carcinomas originating from other sites?", "What are the key characteristics of thymomas and invasive thymomas?", "What is the recommended approach for handling thymus specimens in terms of submitting sections for analysis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 571, "text": "THYMUS\u2003\ufeff\n553\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR THYMIC LESIONS\n\t\u2022\t \u0007Specimen: Thymus, other\n\t\u2022\t \u0007Procedure: Thymectomy, partial thymectomy\n\t\u2022\t \u0007Specimen Integrity: Intact, disrupted\n\t\u2022\t \u0007Specimen Weight: In grams\n\t\u2022\t \u0007Tumor Size: Greatest dimension (additional dimensions optional)\n\t \u2022\t \u0007Tumors >15cm have a worse prognosis.\n\t\u2022\t \u0007Histologic Type: Thymoma, thymic carcinoma (several classification schemes are used; Tables 33-2, \n33-3, and 33-4)\n\t\u2022\t \u0007Tumor Extension:\n\t \u2022\t \u0007Grossly and microscopically encapsulated\n\t \u2022\t \u0007Microscopic capsular invasion\n\t \u2022\t \u0007Macroscopic capsular invasion\n\t \u2022\t \u0007Macroscopic invasion into adjacent adipose tissue and/or pleura.\n\t \u2022\t \u0007Macroscopic invasion into adjacent structures of mediastinum including pericardium, great vessels \nand lung.\n\t \u2022\t \u0007Hematogenous or lymphatic dissemination\n\t\u2022\t \u0007Margins: Uninvolved, distance from closest margin, involved (specify margin)\nTABLE 33\u20132.\u2003\nMASAOKA\u2019S CLINICAL STAGE AS MODIFIED BY KOGA et al.\nStage I\nGrossly and microscopically completely encapsulated (including microscopic invasion \ninto the capsule)\nStage IIa\nMicroscopic transcapsular invasion\nStage IIb\nMacroscopic capsular invasion into thymic or surrounding fat, or grossly adherent but \nnot breaking through mediastinal pleura or pericardium\nStage III\nMacroscopic invasion into neighboring organs (e.g., pericardium, great vessels, or lung)\nStage IVa\nPleural or pericardial dissemination\nStage IVb\nLymphogenous or hematogenous metastasis\nFrom Masaoka A, MondenY, Nakahara K, Tanioka T, Follow-up study of thymomas with special reference to their clinical stages, Cancer 48:2485-2495, \n1981 and Koga K, Matsuno Y, Noguchi M, et al, A review of 79 thymomas: modification of staging system and reappraisal of conventional division \ninto invasive and non-invasive thymoma, Pathol Int 44:359-367, 1994.\nTABLE 33\u20133.\u2003 YAMAKAWA-MASAOKA TNM CLASSIFICATION AND STAGING\nT\nT1\nMacroscopically completely encapsulated and microscopically no capsular invasion\nT2\nMacroscopically adhesion or invasion into surrounding fatty tissue or mediastinal \npleura, or microscopic invasion into capsule\nT3\nInvasion into neighboring organs, such as \u00adpericardium, great vessels, and lung\nT4\nPleural or pericardial dissemination\nN\nN0\nNo lymph node metastasis\nN1\nMetastasis to anterior mediastinal lymph nodes\nN2\nMetastasis to intrathoracic lymph nodes except anterior mediastinal lymph nodes\nN3\nMetastasis to extrathoracic lymph nodes\nM\nM0\nNo hematogenous metastasis\nM1\nHematogenous metastasis\nFrom Yamakawa Y, Masaoka A, Hashimoto T, et al, A tentative tumor-node-\u00admetastasis classification of thymoma, Cancer 68:1984-1987, 1991.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_571.png", "summary": "The page provides a checklist for the pathologic diagnostic and prognostic features of thymic lesions, including specimen details, tumor size, histologic type, tumor extension, and margins. It also includes tables outlining different staging systems for thymomas.", "questions": [ "How do tumor size and histologic type impact the prognosis of thymic lesions?", "What are the different stages of thymic lesions according to Masaoka's clinical stage and the Yamakawa-Masaoka TNM classification?", "How do the different staging systems mentioned in the tables help in determining the severity and spread of thymic lesions?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 572, "text": "THYMUS\u2003\ufeff\n554\n\t\u2022\t \u0007Treatment Effect: If there has been neoadjuvant therapy: not identified, present (% residual viable \ntumor)\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present\n\t\u2022\t \u0007Regional Lymph Nodes: Absent, present (number of nodes involved, number of nodes examined)\n\t\u2022\t \u0007Implants/Distant Metastasis: Not identified, present (specify site if known)\n\t\u2022\t \u0007Stage: The Modified Masaoka Stage or the proposed TNM system may be used\n\t\u2022\t \u0007Additional Pathologic Findings: Age-appropriate involution changes, fibrosis, cortical hyperplasia, \ncystic changes in tumor, cystic changes in adjacent thymus\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/). The underlined elements are considered to be scientifically vali\u00ad\ndated or regularly used data elements that must be present in reports of cancer-directed surgical resection \nspecimens from ACS CoC-approved cancer programs. The specific details of reporting the elements may \nvary among institutions.\nREFERENCE\n\t1.\u2002 \u0007Wick MR: Prognostic factors for thymic epithelial \u00adneoplasms, with emphasis on tumor staging. Hematol Oncol \nClin North Am 22:527-542, 2008.\nTABLE 33\u20134.\u2003\n\u0007PROPOSED PATHOLOGICAL TNM AND STAGING OF THYMIC EPITHELIAL TUMOR \n(THYMOMAS AND THYMIC CARCINOMAS)\npT\npT1\nCompletely encapsulated tumor\npT2\nTumor breaking through capsule, invading thymus or fatty tissue (may be adherent to \nmediastinal pleura but not invading adjacent organs)\npT3\nTumor breaking through the mediastinal pleura or pericardium, or invading \n\u00adneighboring organs, such as great vessels or lung\npT4\nTumor with pleural or pericardial implantation\npN\npN0\nNo lymph node metastasis\npN1\nMetastasis in anterior mediastinal lymph nodes\npN2\nMetastasis in intrathoracic lymph nodes \u00adexcluding anterior mediastinal lymph nodes\npN3\nMetastasis in extrathoracic lymph nodes\npM\nM0\nNo distant organ metastasis\nM1\nWith distant organ metastasis\nFrom Tsuchiya R, Koga K, Matsuno Y, Mukai K, Shimosato Y, Thymic carcinoma: proposal for pathological TNM and staging, Pathol Int 44:505-512, \n1994.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_572.png", "summary": "This page provides information on the pathological TNM and staging of thymic epithelial tumors, including thymomas and thymic carcinomas.", "questions": [ "What are the key factors to consider when determining the stage of thymic epithelial tumors?", "How does the presence of lymph node metastasis impact the staging of thymic epithelial tumors?", "What are the differences between the proposed TNM system and the Modified Masaoka Stage for staging thymic epithelial tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 573, "text": "555\nThyroid and Parathyroid \nGlands\nTHYROID\nThyroidectomies are usually performed to remove \u00adsolitary nodules, either benign or malignant, multi\u00ad\nnodular \u00adgoiters, or rarely for the treatment of Graves\u2019 disease. Most thyroidectomies are total, but some \nmay be \u00adunilateral. Many nodules will have been evaluated by fine needle \u00adaspiration prior to excision.\nRELEVANT CLINICAL HISTORY INCLUDES THE FOLLOWING (IN ADDITION TO AGE AND GENDER)\nSee Table 34-1.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Weigh and record the dimensions of the right and left lobes and isthmus. Glands can usually be easily \noriented, because the posterior surface is concave or flat, the lobes taper superiorly, and the isthmus is \ninferior. The posterior surface should be examined carefully for parathyroid glands (brown or yellow/\nbrown ovoid bodies, 2 to 3 mm in size). Save in a separate cassette if found.\n 2.\t \u0007Ink the entire outer surface. Due to the highly proteinaceous colloid material, the thyroid fixes more \nslowly than other organs.\n 3.\t \u0007Serially section through the entire gland from superior to inferior. Describe each lesion including \nsize, color, consistency (papillary, rubbery, firm, gelatinous, or \u00adfriable), cysts, necrosis or hemorrhage, \nlocation (upper, lower, right, left), encapsulation or infiltration, relationship to capsule (intact or with \ninvasion of capsule).\nTABLE 34-1.\u2003\nRELEVANT CLINICAL HISTORY \u2013 THYROID GLAND\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR THYROID SPECIMENS\nOrgan/tissue resected or biopsied\nThyroid function test results\nPurpose of the procedure\nAutoantibodies\nGross appearance of the organ/tissue/lesion sampled\nHistory of radiation exposure\nAny unusual features of the clinical presentation\nResults of prior FNA\nAny unusual features of the gross appearance\nSingle or multiple nodules\nPrior surgery/biopsies - results\nFamily history of thyroid \u00addisease or MEN syndromes\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, drug \nuse that can change the histologic appearance of \ntissues)\nDrug use (amiodarone or minocycline)\nCompromised immune system\n34", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_573.png", "summary": "Thyroidectomies are commonly performed to remove solitary nodules, multi-nodular goiters, or for the treatment of Graves' disease. Specimens should be carefully processed by weighing, recording dimensions, inking the outer surface, and serially sectioning through the entire gland.", "questions": [ "What are the common reasons for performing thyroidectomies?", "What steps are involved in processing a thyroid specimen?", "Why is it important to carefully examine the posterior surface of the thyroid gland for parathyroid glands?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 574, "text": "THYROID AND PARATHYROID GLANDS\u2003 Thyroid\n556\n\t \u2022\t \u0007Normal: beefy red/brown\n\t \u2022\t \u0007Pale: lymphocytic thyroiditis or Hashimoto \u00adthyroiditis\n\t \u2022\t \u0007Amber colored with a plastic-like consistency: amiodarone thyroid disease\n\t \u2022\t \u0007Black: side effect of minocycline therapy\nWhenever possible, nodules that have been previously sampled by FNA should be identified and \nspecifically designated in the cassette code to facilitate correlation between the cytologic and histologic \nfindings.\n 4.\t \u0007Describe the remainder of the parenchyma, \u00adincluding color (dark red/brown), consistency (fibrotic, \nhard, \u00adfriable, soft), contour (lobulated, multinodular, \u00aduniform), and calcifications.\nEvaluate any adjacent soft tissue for composition (adipose tissue, skeletal muscle, nerves (!), para\u00ad\nthyroid glands), presence of lymph nodes, or extension of tumor into soft tissue.\nGROSS DIFFERENTIAL DIAGNOSIS\nSee Figure 34-1.\nAdenoma.\u2002 This is the most common thyroid neoplasm. An adenoma is usually a solitary, completely \nencapsulated, pale tan to gray mass, soft, gelatinous, or fleshy, and rarely larger than 3 cm. There may be \nareas of hemorrhage, fibrosis, or calcification. The capsule is usually thin.\nA\nB\nC\nD\nMultinodular goiter\nEncapsulated follicular lesion\nPapillary carcinoma\nMedullary carcinoma\nPapillations\nEncapsulated\nNon-encapsulated\nFigure 34-1.\u2002 Thyroid lesions.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_574.png", "summary": "The text discusses the gross differential diagnosis of thyroid lesions, including adenoma, multinodular goiter, encapsulated follicular lesion, papillary carcinoma, and medullary carcinoma.", "questions": [ "What are the characteristics of an adenoma in the thyroid gland?", "How can nodules previously sampled by FNA be identified and designated?", "What are the key features of multinodular goiter, encapsulated follicular lesion, papillary carcinoma, and medullary carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 575, "text": "THYROID AND PARATHYROID GLANDS\u2003 Thyroid\n557\nPapillary Carcinoma.\u2002 This is the most common type of thyroid malignancy. The tumor is usually \nwhite/tan and may have a granular or finely nodular texture due to the papillae. Tumors are often firm \ndue to fibrosis, but may be soft. Calcification is common. The tumor may have a poorly developed cap\u00ad\nsule but rarely has a complete capsule, which may be thick or thin. The tumor may grossly invade the \ncapsule. Cysts may be present. Size ranges from microscopic to huge (average 2 to 3 cm). 20% to 60% \nare multicentric. An occult papillary carcinoma may appear as a tiny pale gray depressed scar.\nFollicular Carcinoma.\u2002 Less common than papillary carcinomas or adenomas; fewer than 20% of \nfollicular lesions are carcinomas. The tumor may be a small encapsulated mass that can only be dis\u00ad\ntinguished from adenoma by histologic examination (i.e., microscopic evidence of \u00adcapsular or vascular \ninvasion). Larger tumors may have areas of hemorrhage and necrosis and have infiltrative borders. The \ncapsule may be thick. These tumors are usually solitary.\nMedullary Carcinoma.\u2002 These tumors are less common than papillary and follicular carcinomas. \nThe diagnosis may be known clinically due to family history (familial medullary thyroid carcinoma syn\u00ad\ndrome, MEN 2, and variants), other tumors, and/or an elevated serum calcitonin level. C-cells are pres\u00ad\nent at the junction of the middle and upper third of the central portion of each lobe, and medullary \ncarcinomas usually arise in this location. The tumors are often multicentric and non-encapsulated but \nare well-circumscribed, with a soft and fleshy or firm and gritty consistency. The color ranges from gray/\nwhite to yellow/brown. Areas of necrosis and hemorrhage may be present. Their size ranges from <1 cm \nto replacement of the entire thyroid.\nAbout 25% are associated with germline mutations (see in Chapter 7, \u201cTumors and Diseases Associ\u00ad\nated with Germline Mutations\u201d). An intraoperative diagnosis may be important in order to evaluate the \ngland for multiple tumors and to evaluate the parathyroid glands for hyperplasia.\nPatients at risk for familial medullary carcinoma may undergo prophylactic thyroidectomies. Because \nC-cells are located within the middle and upper thirds of the lateral lobes, the entire central-to-superior \nportion of each lobe should be examined microscopically to assess for C-cell hyperplasia and incipient \nmedullary carcinoma. In such cases, immunoperoxidase studies for calcitonin and CEA may be helpful \nto evaluate C-cell hyperplasia.\nAnaplastic Carcinoma.\u2002 This is a very rare tumor. It is often pale gray, and firm to hard in consis\u00ad\ntency. Necrosis and hemorrhage are often present. Because of its tendency to invade locally and widely, a \nrecognizable thyroid may not be present. Skeletal muscle may be resected with infiltrating tumor.\nNodular Hyperplasia (Multinodular Goiter).\u2002 The gland is enlarged and distorted (one lobe is \nusually larger than the other lobe). There is a diffuse heterogeneous nodularity, and some of the nodules \nmay appear to be encapsulated. There may be random irregular scarring, hemorrhage, \u00adcalcifications, \nand cysts. It is often difficult to distinguish a dominant nodule in hyperplasia from an adenoma. There\u00ad\nfore, the \u00adsurrounding parenchyma must be carefully evaluated grossly (for multiple nodules) and \n\u00admicroscopically.\nGraves Disease.\u2002 The gland is diffusely enlarged, but with a very homogeneous texture without nod\u00ad\nularity. It is usually a beefy red color.\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Lesions: Follicular lesions: It is very important to submit the entire tumor capsule, as invasion of the \ncapsule distinguishes carcinomas from adenomas. In general, the invasion is only apparent on micro\u00ad\nscopic \u00adexamination.\nPapillary carcinoma: At least one section per 1 cm including relationship to any perithyroidal tissue.\nNodular hyperplasia: Submit one representative section of each nodule, up to five nodules, if homo\u00ad\ngeneous in appearance. Additional sections should be submitted from all nodules with different gross \nappearances (e.g., with hemorrhage, fibrosis, or calcifications).\n\t\u2022\t \u0007Thyroid (nonlesional): Two representative uninvolved sections from each lobe. Submit all areas that \nshow discoloration or increased consistency.\n\t\u2022\t \u0007Lymph node/parathyroid: Submit representative sections of all lymph nodes and entirely submit \nparathyroids.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_575.png", "summary": "The page discusses different types of thyroid malignancies including papillary carcinoma, follicular carcinoma, medullary carcinoma, anaplastic carcinoma, and nodular hyperplasia.", "questions": [ "What are the distinguishing features of papillary carcinoma compared to other types of thyroid malignancies?", "How can medullary carcinoma be clinically diagnosed?", "Why is an intraoperative diagnosis important in cases of medullary carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 576, "text": "THYROID AND PARATHYROID GLANDS\u2003 Thyroid\n558\nSAMPLE DICTATION\nReceived fresh, labeled with the patient\u2019s name, unit number, and \u201cthyroid,\u201d is a 75 gram total thyroid\u00ad\nectomy \u00adspecimen consisting of right lobe (6 \u00d7 3.5 \u00d7 3 cm), left lobe (8 \u00d7 5 \u00d7 4 cm), and isthmus (2 \u00d7 2 \u00d7 1 \ncm). There is a 4 \u00d7 3 \u00d7 3 cm ovoid white/tan firm tumor mass with a finely granular appearance present \nin the left lobe. The central portion is densely white and firm and depressed. The tumor is poorly cir\u00ad\ncumscribed and grossly invades into the adjacent capsule but is 0.1 cm from the inked resection margin. \nThe remainder of the parenchyma is red/brown and homogeneous without other lesions noted. There is \na small (0.5 \u00d7 0.5 \u00d7 0.3 cm) soft tan/brown ovoid nodule adherent to the capsule of the right lobe that is \ngrossly consistent with a parathyroid gland.\nCassettes #1-2: Tumor to inked thyroid excision margin, 2 frags, ESS.\nCassettes #3-7: Remainder of tumor including the entire tumor capsule, 1 to 3 frags each, ESS.\nCassettes #8-9: Left lobe, away from tumor, 2 frags, RSS.\nCassette #10: Isthmus, 1 frag, RSS.\nCassettes #11-12: Representative section of right lobe, 2 frags, RSS.\nCassette #13: Small brown nodule, possible parathyroid tissue, 2 frags, ESS.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR THYROID TUMORS\n\t\u2022\t \u0007Specimen: Thyroid (right lobe, left lobe, isthmus), lymph nodes\n\t\u2022\t \u0007Procedure: Nodulectomy, lobectomy, subtotal thyroidectomy (right or left lobe), total thyroidec\u00ad\ntomy, lymph nodes (biopsy, central compartment dissection, right neck dissection, left neck dissection, \nbilateral neck dissection)\n\t\u2022\t \u0007Specimen Integrity: Intact, fragmented\n\t\u2022\t \u0007Specimen Size: Give size of each lobe and isthmus in three dimensions and size of any lymph node \ndissection\n\t\u2022\t \u0007Specimen Weight: In grams\n\t\u2022\t \u0007Tumor Focality: Unifocal, multifocal (ipsilateral, bilateral, midline). If more than one carcinoma is \npresent, the characteristics of each carcinoma should be reported.\n\t\u2022\t \u0007Tumor Laterality: Right or left lobe (superior/central/inferior pole), isthmus\n\t\u2022\t \u0007Tumor Size: Largest nodule: greatest dimension (additional dimensions optional) \nIf there are multiple nodules, give the range in sizes.\n\t \u2022\t \u0007Papillary carcinomas <1 cm have an excellent prognosis, and carcinomas >4 cm have a worse prog\u00ad\nnosis. Follicular carcinomas >3.5 cm have a worse prognosis than smaller follicular carcinomas. \nSmall medullary carcinomas detected by screening have an excellent prognosis. Medullary carcino\u00ad\nmas detected as palpable nodules and >1 cm have a worse prognosis.\n\t\u2022\t \u0007Histologic Type: Papillary carcinoma (variant type, architecture, and cytomorphology), follicular \ncarcinoma (variant type), medullary carcinoma, undifferentiated (anaplastic) carcinoma, other rare \ntypes. The WHO classification is recommended.\n\t\u2022\t \u0007Histologic Grade: Well, moderately, poorly, or undifferentiated. The majority of thyroid carcinomas \nare well differentiated. Grade is not as helpful as other features for predicting prognosis.\n\t\u2022\t \u0007Margins: Uninvolved (distance of carcinoma from nearest margin optional), involved (site of involvement)\n\t\u2022\t \u0007Tumor Capsule: Totally encapsulated, partially encapsulated, capsule not present\n\t\u2022\t \u0007Tumor Capsular Invasion: Invasion of the tumor capsule: not identified, present (minimal, widely \ninvasive) (most important for follicular and H\u00fcrthle cell carcinomas) (Fig. 34-2)\n\t \u2022\t \u0007There is not complete consensus on the definition of capsular invasion. All pathologists can agree \nthat invasion has occurred when carcinoma is present at the outer surface of the capsule. It is not yet \nclear how to classify carcinomas that invade into, but not through, the capsule.\n\t\u2022\t \u0007Lymph-Vascular Invasion: Not identified, present (focal, <4 vessels; extensive, \u22654 vessels)\n\t \u2022\t \u0007Blood vessels should be the size of veins and located outside the tumor but within or immediately \noutside the capsule. Tumor cells are attached to the vessel wall and protrude into the lumen and are \nusually covered by endothelial cells (see criteria later).\n\t\u2022\t \u0007Perineural Invasion: Not identified, present\n\t\u2022\t \u0007Extrathyroidal Extension: Not identified, present (minimal, extensive)\n\t \u2022\t \u0007Note: In some cases adipose tissue or skeletal muscle may be present within the thyroid gland. Care\u00ad\nful correlation with gross findings and targeted sampling is helpful to determine if the carcinoma has \ninvaded beyond the thyroid.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_576.png", "summary": "The surgical pathology manual describes a thyroidectomy specimen with a tumor mass in the left lobe and a possible parathyroid gland in the right lobe.", "questions": [ "What are the dimensions of the tumor mass in the left lobe?", "How close is the tumor mass to the inked resection margin?", "What are the recommended diagnostic and prognostic features to be reported for thyroid tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 577, "text": "THYROID AND PARATHYROID GLANDS\u2003 Prophylactic Thyroidectomy\n559\n\t\u2022\t \u0007Extent of Invasion: Tumors except for anaplastic carcinoma: Tumor size \u2264 2 cm, limited to thyroid \n(T1), tumor > 2 cm but \u2264 4 cm, limited to the thyroid (T2), tumor > 4 cm, limited to the thyroid, or \nwith minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tis\u00ad\nsues (T3), extension beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, \nesophagus, or recurrent laryngeal nerve (T4a), invasion of perivertebral fascia or encases carotid artery \nor mediastinal vessels (T4b)\n\t \u2022\t \u0007Anaplastic carcinoma: carcinoma within the thyroid (T4a), carcinoma with gross extrathyroid exten\u00ad\nsion (T4b)\n\t\u2022\t \u0007Regional Lymph Nodes: Absent (N0), nodal metastases to Level IV (N1a), nodal metastases to cervi\u00ad\ncal or superior mediastinal lymph nodes (ipsilateral or contralateral) (N1b)\n\t \u2022\t \u0007Number of nodes examined, number with metastases, size of largest metastasis\n\t \u2022\t \u0007Extranodal invasion: present or not identified\n\t\u2022\t \u0007Additional Pathologic Findings: Thyroiditis (advanced, focal [nonspecific], palpation), diffuse hyper\u00ad\nplasia (Graves\u2019disease), nodular hyperplasia (adenomatoid nodules, nodular follicular disease, goitrous \nthyroid), adenoma, C-cell hyperplasia (associated with familial cases of medullary carcinoma)\n\t \u2022\t \u0007Diffuse: involves both lobes with \u2265 50 C cells per LPF\n\t \u2022\t \u0007Nodular: extensive, bilateral, multifocal\n\t\u2022\t \u0007Parathyroid Glands: Number, location (if possible, indicate intrathyroidal vs. extrathyroidal, right vs. \nleft, upper vs. lower), size, cellularity (normal, hypercellular)\n\t\u2022\t \u0007Distant Metastasis: Present. If distant metastasis is not present on pathologic examination, the M \ncategory is a clinical classification.\n\t\u2022\t \u0007AJCC Classification: T, N, and M classifications should be provided, when possible (Table 34-2). M0 \nis conferred after clinical assessment; there is no pMO category.\nThis checklist incorporates information from the CAP Cancer Committee protocols for reporting on \ncancer specimens (see www.cap.org/) and the ADASP (see www.adasp.org). The underlined elements are \nconsidered to be scientifically validated or regularly used data elements that must be present in reports \nof cancer-directed surgical resection specimens from ACS CoC-approved cancer programs. The specific \ndetails of reporting the elements may vary among institutions.\nPROPHYLACTIC THYROIDECTOMY\nProphylactic thyroidectomy may be performed for patients with a history of familial medullary carci\u00ad\nnoma (familial MTC, MEN2, or variants) if a germline mutation in the RET proto-oncogene has been \ndetected.\nThe thyroid should be examined to document the extent of C-cell hyperplasia and to determine \nwhether a small medullary carcinoma is present. Normal C-cells are restricted to a zone within the mid\u00ad\ndle to upper third of the lateral lobes and are normally absent from the extreme upper and lower poles \nof each lobe and the isthmus. Serial sections of the entire central and upper thirds of each lobe should be \nexamined microscopically. Additional representative sections of the lower poles, isthmus, and any gross \nlesions are also examined.\n A. A tumor bud has invaded beyond the\ncontour of the capsule, but is still\ncovered by a thin new fibrous capsule.\n B. A tumor bud has extended through the\nouter capsular surface.\n C. The classic mushroom-shaped bud\nhas completely transgressed the fibrous capsule\nand grown out into the surrounding thyroid.\n D. A satellite nodule with cytoarchitectural and\ncellular features identical to the cell is present\noutside of the capsule. The point of\ncapsular rupture is not seen in the sections.\nCriteria for Capsular Invasion\nTumor\nA\nB\nC\nD\nSurrounding thyroid\nCAPSULE\nFigure 34-2.\u2002 Thyroid capsular invasion.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_577.png", "summary": "The page discusses the criteria for prophylactic thyroidectomy, including the extent of invasion, regional lymph nodes, extranodal invasion, additional pathologic findings, parathyroid glands, distant metastasis, and AJCC classification.", "questions": [ "What are the criteria for determining the extent of invasion in tumors except for anaplastic carcinoma?", "Why is prophylactic thyroidectomy performed for patients with a history of familial medullary carcinoma?", "How are normal C-cells distributed within the thyroid gland?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 578, "text": "THYROID AND PARATHYROID GLANDS\u2003 Parathyroid Gland\n560\nPARATHYROID GLAND\nParathyroidectomy is performed for hyperparathyroidism due to either adenoma or hyperplasia (most \ncommonly secondary to chronic renal failure). Malignancies are vanishingly rare.\nThe specimens are usually evaluated intraoperatively (see Chapter 6 for further information). How\u00ad\never, \u00adintraoperative PTH assays may replace frozen section evaluation.\nTABLE 34-2.\u2003\nAJCC (7TH EDITION) CLASSIFICATION OF THYROID TUMORS\nTUMOR\nTX\nPrimary tumor cannot be assessed\nT0\nNo evidence of primary tumor\nT1\nTumor \u2264 2 cm in greatest dimension limited to the thyroid\nT1a\nTumor 1 cm or less, limited to the thyroid\nT1b\nTumor more than 1 cm but not more than 2 cm in greatest dimension, limited to the thyroid\nT2\nTumor > 2 cm but \u2264 4 cm in greatest dimension, limited to the thyroid\nT3\nTumor > 4 cm in greatest dimension limited to the thyroid or any tumor with minimal extrathyroid \nextension (e.g., extension to sternothyroid muscle or perithyroid soft tissue)\nT4a\nModerately advanced disease\nTumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, \nlarynx, trachea, esophagus, or recurrent laryngeal nerve\nT4b\nVery advanced disease\nTumor invades prevertebral fascia or encases carotid artery or mediastinal vessels\nT4a\nIntrathyroidal anaplastic carcinoma\nT4b\nAnaplastic carcinoma with gross extrathyroid extension\nNote: All categories may be subdivided: (s) solitary tumor and (m) multifocal tumor (the largest determines the classification).\nAll anaplastic carcinomas are considered T4 tumors\nREGIONAL LYMPH NODES\nNX\nRegional lymph nodes cannot be assessed\nN0\nNo regional lymph node metastasis\nN1\nRegional lymph node metastasis\nN1a\nMetastasis to Level VI (pretracheal, paratracheal, and prelaryngeal/delphian lymph nodes)\nN1b\nMetastasis to unilateral, bilateral, or contralateral cervical (Levels I, II, III, IV, or V) or retropharyn\u00ad\ngeal or superior mediastinal lymph nodes (Level VII)\nNote: Regional lymph nodes are the central compartment, lateral cervical, and upper mediastinal lymph nodes.\nDISTANT METASTASIS\nM0\nNo distant metastasis\nM1\nDistant metastasis\nFrom the AJCC Cancer Staging Manual, Seventh Edition. New York, Springer-\u00adVerlag, 2009. Used with the permission of the American Joint Commit\u00ad\ntee on Cancer (AJCC), Chicago, Illinois.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_578.png", "summary": "Parathyroidectomy is performed for hyperparathyroidism due to adenoma or hyperplasia, with malignancies being rare. Intraoperative PTH assays may replace frozen section evaluation.", "questions": [ "What are the common reasons for performing a parathyroidectomy?", "How are specimens from a parathyroidectomy usually evaluated?", "What are the different categories for thyroid tumors according to the AJCC classification?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 579, "text": "THYROID AND PARATHYROID GLANDS\u2003 Parathyroid Gland\n561\nRELEVANT CLINICAL HISTORY (IN ADDITION TO AGE AND GENDER)\nSee Table 34-3.\nPROCESSING THE SPECIMEN\n 1.\t \u0007Record the weight and dimensions of each specimen. Describe, including color (brown to brown/\nyellow), and any lesions (an adenoma may compress \u00adnormal adjacent parenchyma). It should be \nevident from the description if the specimen is the entire gland (smoothly contoured surface) or a \nbiopsy (small irregular fragment of tissue).\n\t \u2022\t \u0007Average normal weight:\n\t\n\u2022\t \u000730 +/\u2013 3.5 mg for men\n\t\n\u2022\t \u000735 +/\u2013 5.2 mg for women\n\t\n\u2022\t \u0007Any gland >50 mg is enlarged\n\t \u2022\t \u0007Normal size: 2-7 mm \u00d7 2-4 mm \u00d7 0.5-2 mm\n 2.\t \u0007Submit small specimens in entirety. Larger glands have representative sections submitted in a single \ncassette.\nGROSS DIFFERENTIAL DIAGNOSIS\nAdenomas (85% of Surgical Cases).\u2002 Are almost always solitary lesions (96%) and usually weigh \nfrom 300 mg to several grams (size 1 - 3 cm). There is loss of stromal fat, and the adjacent normal gland \nmay be compressed. Rarely, a parathyroid gland may be located completely within the thyroid gland.\nHyperplasia (15% of Surgical Cases, Almost All Secondary).\u2002 Usually involves multiple glands, but \neach gland may not be involved to the same degree. Fat may be decreased or absent.\n\t \u2022\t \u0007Secondary: Usually due to renal disease. All four glands are markedly increased in size but may vary \nin size. Three may be removed and the fourth biopsied.\n\t \u2022\t \u0007Primary: All four glands may be increased in size. However, only one or two glands may be enlarged \nor all glands may be minimally enlarged. 20% of patients will have an MEN syndrome (usually \nMEN I or 2A). Very rare.\nCarcinoma (Rare, 2% of Cases).\u2002 More common in older adults (4th to 6th decade). The carcinoma is \nusually a firm lobulated tan/gray mass often adherent to adjacent soft tissue. The tumors are often large \n(2 - 6 cm; over 40 gms). Histologically there may be capsular or vascular invasion, mitoses, and necrosis.\nTABLE 34-3.\u2003\nRELEVANT CLINICAL HISTORY \u2013 PARATHYROID GLAND\nHISTORY RELEVANT TO ALL SPECIMENS\nHISTORY RELEVANT FOR PARATHYROID SPECIMENS\nOrgan/tissue resected or biopsied\nPrimary hyperparathyroidism (elevated serum calcium) \n\u2013 usually due to one adenoma, rarely due to multiple \nadenomas or primary hyperplasia.\nPurpose of the procedure\nGross appearance of the organ/tissue/lesion sampled\nAny unusual features of the clinical presentation\nSecondary hyperparathyroidism (decreased serum \ncalcium) - usually due to chronic renal failure \u2013 all four \nglands enlarged\nAny unusual features of the gross appearance\nPrior surgery/biopsies - results\nIntraoperative PTH assays \u2013 if PTH did not decrease, the \nadenoma may not have been removed.\nPrior malignancy\nPrior treatment (radiation therapy, chemotherapy, \ndrug use that can change the histologic appear\u00ad\nance of tissues)\nPersonal or family history of MEN syndrome\nGross appearance of gland at surgery \u2013 adherence to \nadjacent tissue could suggest carcinoma\nCompromised immune system", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_579.png", "summary": "This page provides information on processing specimens of the thyroid and parathyroid glands, including recording weight and dimensions, submitting small specimens in entirety, and identifying different differential diagnoses such as adenomas, hyperplasia, and carcinoma.", "questions": [ "What are the average normal weights for the thyroid and parathyroid glands in men and women?", "How can adenomas of the parathyroid gland be distinguished from other lesions?", "What are the clinical implications of finding a parathyroid gland located completely within the thyroid gland?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 580, "text": "THYROID AND PARATHYROID GLANDS\u2003 Parathyroid Gland\n562\nMICROSCOPIC SECTIONS\n\t\u2022\t \u0007Enlarged glands: Representative sections (one cassette). If there is attached soft tissue and a possibil\u00ad\nity of carcinoma (i.e., potential invasion into soft tissue), more sections should be taken.\n\t\u2022\t \u0007Small glands or biopsies: Entire specimen (one \u00adcassette)\nSAMPLE DICTATION\nThe specimen is received fresh, labeled with the patient\u2019s name and unit number, in three parts.\nThe first part labeled \u201cright upper adenoma\u201d consists of a 100 mg ovoid smoothly surfaced gland \n(2 \u00d7 2 \u00d7 1 cm) with a homogenous tan/brown parenchyma. A representative portion was used for a frozen \nsection A.\nCassette #1: FSR A, 1 frag, ESS.\nCassette #2: Representative sections, 2 frags, RSS.\nThe second part, labeled \u201cright lower,\u201d consists of an irregular fragment of tan/brown soft tissue mea\u00ad\nsuring 0.5 \u00d7 0.5 \u00d7 0.4 cm, which was entirely frozen for FSB.\nCassette #3: FSR B, 1 frag, ESS.\nThe third part, labeled \u201cleft upper,\u201d consists of an irregular fragment of tan/brown soft tissue measur\u00ad\ning 0.6 \u00d7 0.3 \u00d7 0.2 cm, which was entirely frozen for FSC.\nCassette #4: FSR C, 1 frag, ESS.\nPATHOLOGIC DIAGNOSTIC/PROGNOSTIC FEATURES SIGN-OUT CHECKLIST FOR PARATHYROIDS\n\t\u2022\t \u0007Type of lesion: Adenoma, atypical adenoma, carcinoma, hyperplasia, cysts, parathyromatosis, normal \ngland, or secondary tumors\n\t\u2022\t \u0007Size and weight: Specify for glands completely excised\n\t\u2022\t \u0007Prognostic factors: For carcinomas, some histologic features may be associated with malignant \nbehavior (Table 34-4).\n\t\u2022\t \u0007Percent adipose tissue: Usually 15% to 20% in normal glands, reduced in young individuals, adeno\u00ad\nmas, and hyperplasia\nTABLE 34-4.\u2003\nPARATHYROID ADENOMA VS ATYPICAL ADENOMA VS CARCINOMA\nHISTOLOGIC \nFEATURE\nADENOMA\nATYPICAL ADENOMA\nCARCINOMA\nRelationship to \n\u00adsurrounding tissue\nConfined within \ncapsule\nAdherence of tumor to \nadjacent structures\nInvasion through the capsule into \nadjacent soft tissues or thyroid \nin about one half\nThick fibrous bands\nUsually absent\nUsually present\nUsually present\nMitotic activity\nMay be present\nPresent (<5 per 50 HPFs \nor Ki-67 <3%)\nPresent (>5 per 50 HPFs or Ki-67; \n>6% is more common in \n\u00adcarcinomas)\nPerineural invasion\nAbsent\nAbsent\nMay be present\nVascular invasion\nAbsent\nAbsent\nMay be present\nNecrosis\nMay be present\nMay be present\nPresent in about one third\nNuclear atypia\nScattered cells with \nmarkedly atypi\u00ad\ncal nuclei may be \n\u00adpresent.\nScattered cells with \n\u00admarkedly atypical \nnuclei may be present.\nMarked nuclear pleomorphism \nwith macronuclei may be pres\u00ad\nent in about half of tumors.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_580.png", "summary": "This page provides guidelines for handling and examining thyroid and parathyroid gland specimens, including the types of lesions, size and weight considerations, and histologic features associated with adenoma, atypical adenoma, and carcinoma.", "questions": [ "What are the different types of lesions that can be identified in parathyroid glands?", "How is the size and weight of completely excised glands specified in the diagnostic/prognostic features checklist?", "What histologic features differentiate parathyroid adenoma, atypical adenoma, and carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 581, "text": "THYROID AND PARATHYROID GLANDS\u2003 Parathyroid Gland\n563\nPARATHYROID ADENOMA VERSUS ATYPICAL ADENOMA VERSUS CARCINOMA\nParathyroid carcinomas are very rare, accounting for less than 5% of cases of primary hyperparathyroid\u00ad\nism. In the absence of metastasis, a definitive diagnosis of malignancy is difficult to make. Some cases \ndiffer minimally from chief cell adenomas, while others are obviously anaplastic. The histologic features \nin Table 34-4 can be used to help predict malignant behavior.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_581.png", "summary": "Parathyroid carcinomas are rare and can be difficult to definitively diagnose without metastasis. Histologic features can help predict malignant behavior.", "questions": [ "What percentage of primary hyperparathyroidism cases are accounted for by parathyroid carcinomas?", "How do parathyroid adenomas differ from parathyroid carcinomas?", "What histologic features are used to predict malignant behavior in parathyroid carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 582, "text": "", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_582.png", "summary": "No summary generated.", "questions": [] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 583, "text": "565\nIndex\n1D5 see Estrogen receptors\n6F/3D see Beta-amyloid\n6F11 see Estrogen receptors\n12E7 see CD antigens, CD99\n34\u03b2E12 (keratin), 109t\u2013150t\nA\nA32 antigen see CD antigens, CD146\nA60 see NeuN\nA103 see Melan-A\nA0485 see HER-2/neu\nAAT see Alpha 1-antitrypsin\nAbdomen, metastatic adenocarcinomas in, \n94t\nAbdominal aortic aneurysm, 305\nAbdominal fat pad biopsy, amyloidosis, 550\nAbdominoperineal (A-P) resection, 340, 341f\nABH blood group antigens, tissue \nidentification, 33\nAbiomed ventricular assist device, 303\nAbortion\nspontaneous (SAB), 466\ntherapeutic, 466\nAbsence of lesions, 10\nAcalculous cholecystitis, acute, 367, 369\nAccessory pancreatic ducts, 56\nAccuracy, operating room consultations, \n50\u201351\nAcetylcholinesterase studies, Hirschsprung \ndisease, 338\nACH see Alpha 1-antichymotrypsin\nAcid alcohol, hematoxylin and eosin \ntechnique, frozen sections, 48\nAcid fuchsin orange G (AFOG), 67t\u201370t\nAcid-fast bacilli, stains, 67t\u201370t\nAcinar (acinic) cell carcinoma\nimmunohistochemistry panel, 75t\u201376t\npancreas, 377\nsalivary glands, 480\nACKD see Acquired cystic kidney disease\nAcoustic neuroma\nbrain biopsy, 529\ngermline mutations, 179t\u2013180t\nAcquired cystic kidney disease (ACKD), \n386, 391t\nrenal cell carcinomas, 389\nAcrochordon, 313\nACS CoC see American College of \nSurgeons Commission on Cancer\nActinomycetes, tonsils, 485\nAcute airway rejection, 495t\nAcute cholecystitis\nacalculous, 367, 369\ncalculous, 369\nAcute lymphoblastic lymphoma (ALL), \ngenetics, 172t\u2013178t\nAcute myeloblastic leukemia (AML), 79t, \n172t\u2013178t\nAcute promyelocytic leukemia, genetics, \n172t\u2013178t\nAdamantinoma, 74t, 254f\nADASP see Association of Directors of \nAnatomic and Surgical Pathology\nAddenda, reports, 37, 220, 223\nAdenocarcinomas\nanal, grading, 355t\nappendix, 357\nbladder, 98t\ncervix, 450\ngrading, 451t\ncolon, immunohistochemistry panel, 74t\nelectron microscopy, 158t\nesophagus, 324, 325f\ngrading system, 327t\nimmunohistochemistry panel, 74t\ngallbladder, 368\u2013369\ngrading, 370t\ngynecology, grading, 435\u2013436\nlung, 75t\u201376t, 101, 101t\u2013102t, \n163t\u2013171t, 498, 499f\nbronchial extension, 60\nepithelial mesothelioma vs, 101, 101t\npancreas, 372, 375\u2013376\nductal, 376f\nprostate, 407\u2013408, 411\u2013412\nrectum, 98t\nsquamous cell carcinoma v., 102t\nstomach\ngrading systems, 333t\nimmunohistochemistry panel, 74t\nintestinal type, 330, 331f\nAdenoids, 484\u2013486\nAdenoid cystic carcinoma\ngenetics, 163t\u2013171t\nimmunohistochemistry panel, 75t\u201376t\nsalivary gland, 480\nAdenomas\nadrenal gland, 228\u2013229, 229f\nbile ducts, 364\nliver, 362\u2013363, 363f\nparathyroid, 63\u201364, 64t, 560\u2013563, 562t\natypical, 562t, 563\nAdenomas (Continued)\npituitary, myeloma vs, 223\nthyroid see Thyroid gland, adenoma\nAdenomatoid tumor\nimmunohistochemistry panel, 80t\u201383t\nuterus, 432\nAdenomyosis, 58\nuterus, 432\nAdenovirus, histological appearance, \n190t\u2013194t\nADH see Atypical ductal hyperplasia\nAdhesions, pleura, 497\nAdipose tissue\nbladder, 396\nlymph nodes in, 518\nthyroid tissue mistaken for, 64\nsee also Fatty tissues\nAdnexal carcinoma, histologic grade, \n314t\u2013315t\nAdrenal cortex\ncarcinoma\ngenetics, 163t\u2013171t\ngermline mutations, 179t\u2013180t\ntumors, immunohistochemistry panels, \n75t\u201376t, 97t\nAdrenal gland, 227\ncolor, 17t, 228\ncysts, 230\nnormal, 228, 229f\ntumors, 227\nadenoma,, 228\u2013229, 229f\nAJCC classification, 231t\ncarcinoma, 229, 231t\ncriteria for malignancy, 232\u2013233, 233t\nimmunohistochemistry, 97t\nmetastatic, 229\u2013230\nmyelolipoma, 230\nneuroblastoma, 229, 232f\npheochromocytoma, 228\u2013229, 229f, \n233, 234t\u2013235t\nAdrenocorticotropic hormone, secreting \ntumor, pancreas, 379t\nAdriamycin, cardiotoxicity, 289\nAdult polycystic kidney disease, 391t\nAdult T-cell, lymphoma/leukemia, \n105t\u2013106t, 172t\u2013178t\ngenetics, 172t\u2013178t\nAE1, AE3 (monoclonal antibodies), 101t\nAerosol sprays, frozen sections, 47\nAFIP grading, mucoepidermoid carcinoma, \n482t\u2013483t\nNote: Page numbers followed by f, t, or b indicate figures, tables, or boxes, respectively.", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_583.png", "summary": "This page from a surgical pathology manual covers a wide range of topics including different types of adenocarcinomas, genetic information on lymphomas and leukemias, and various types of tumors in different organs.", "questions": [ "What are some common immunohistochemistry panels used for diagnosing adenocarcinomas in different organs?", "How does genetic information play a role in the diagnosis and classification of lymphomas and leukemias?", "What are the key differences in histologic grade between different types of tumors like adenocarcinomas and adenomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 584, "text": "566\nIndex\nAFOG see Acid fuchsin orange G\nAFP see Alpha-fetoprotein\nAIDS, gallbladder, 369\nAir bubbles, microscope slides, 215\nAir dried smears\nfine needle aspirations, 309\nhazard, 196, 201\nAirway inflammation, 496t\nAirway rejection\nacute, 495t\nchronic, 496t\nAJCC classifications\nadrenal gland tumors, 233t\nampulla of Vater tumors, 337t\nbone tumors, 256t\ncarcinomas\nanal, 356t\nappendix, 359t\nbladder, 401t\nbreast, 262t, 279t\ncervix, 434t\nendometrium, 434t\u2013445t\nesophagus, 327, 328t\ngallbladder, 367t\nlarynx, 492t\u2013493t\nlip and oral cavity, 477t\nlung, 503t\novary, 445t\npancreatic, 381, 381t\nprostate, 410t\nrenal cell, 393t\u2013417t\nrenal pelvis and ureter, 394t\nsalivary duct, 483t\nsmall intestine, 336, 337t\nstomach, 333, 334t\nvagina, 434t\nvulva, 459t\ncolon carcinoma, 351, 353t\u2013354t\neye tumors, 532\nFallopian tube tumors, 462f\nfor GIST, 550t\nHodgkin and non-Hodgkin lymphomas, \n517t\nliver tumors, 361t, 366\nmelanoma, 311, 318t\nMerkel cell carcinoma, 320t\nmesothelioma, 510t\npenis tumors, 539t\nreporting, 36\u201337, 225\nskin carcinoma, 314t\u2013319t\nsoft tissue tumors, 545t\ntesticular tumors, 417t\nthyroid tumors, 560t\nAlcian blue, 67t\u201370t, 101t\nwith hyaluronidase, 101t\nsulfated, amyloidosis, 289\u2013290\nAlcian blue-PAS, 67t\u201370t\nAlcian yellow, 67t\u201370t\nAlcohol-based fixatives, 23\nAlizarin red S, 67t\u201370t\nALK protein, 109t\u2013150t\nfusions, 163t\u2013178t\nimmunoreactivity, 72\nAllergic sinusitis, 473\nAllred score (H-score), hormone \nreceptors, breast carcinoma, \n86, 86t\nAlpha 1-antichymotrypsin (ACH), \n109t\u2013150t\nAlpha 1-antitrypsin (AAT), 109t\u2013150t\ndeficiency, 362\nAlpha smooth muscle actin see Smooth \nmuscle alpha-actin\nAlpha-fetoprotein, 109t\u2013150t\ntestis tumors, 415\nAlpha-methylacyl-CoA racemase \n(AMACR), 109t\u2013150t\nAlveolar rhabdomyosarcoma, genetics, \n163t\u2013171t\nAlveolar soft part sarcoma, 80t\u201383t, \n158t\u2013160t, 163t\u2013171t\nAlzheimer\u2019s, 107t\nAMACR see Alpha-methylacyl-CoA \nracemase\nAmbiguous genitalia, fetus, 471\nAmeloblastoma, 74t\nAmended reports, 36\u201338, 220, 223\nAmerican College of Surgeons Commission \non Cancer (ACS CoC), standards for \nreporting, 220, 225\nAmiodarone thyroid disease, specimen \nappearance, 556\nAML see Acute myeloblastic leukemia\nAML1-ETO fusion, 172t\u2013178t\nAmmonia water, hematoxylin and eosin \ntechnique, frozen sections, 48\nAmnion nodosum, 463\nAmpulla of Vater\ntumors affecting, 379, 382\nAJCC classification, 326\ngrading, 382t\nsign-out checklists, 326\nWhipple procedure, 374\u2013382, 374f\nAmputation specimens, 237\ndigits, 238\nlower extremity, 239\u2013241, 240f\ntrauma, 238\nfor tumors, 241\u2013242\nAmyloid, 107\u2013108, 107t, 158t\u2013160t, \n206t\u2013212t\nCongo red, 67t\u201370t\nsee also Beta-amyloid\nAmyloidosis, 107\u2013108, 107t\nbiopsy, 550\nabdominal fat pad, 550\nendomyocardial, 289\u2013290\ndialysis-related, 260\nsynovium, 260\nsee also Beta-2 microglobulin amyloidosis\nAnal canal, 340\nsee also Anus\nAnal carcinoma\nAJCC classifications, 356t\ngrading, 355t\nsign-out checklist, 352\u2013355\nAnal papillae, 340\nAnalytical cytology see Flow cytometry\nAnalyzers (microscopy), 205b\nAnaplasia, rhabdomyosarcoma, 546\nAnaplastic carcinoma, thyroid, 557\nAnaplastic large cell lymphoma, 105t\u2013106t, \n172t\u2013178t\nAnaplastic lymphoma, missed diagnosis, \n223\nAnaplastic lymphoma kinase see ALK \nprotein\nAnatomic position, 7f\nAndrogen receptor, 109t\u2013150t\nAneurysmal bone cyst, 254\ngenetics, 163t\u2013171t\nAneurysms, abdominal aortic, 305\nAngell-Shiley heart valve, 300f\nAngiodysplasia, colon, 345\nAngiography, lung specimens, 504\nAngioimmunoblastic lymphoma\ngenetics, 172t\u2013178t\nimmunohistochemistry, 105t\u2013106t\nAngiomatous fibrous histiocytoma, genetics, \n163t\u2013171t\nAngiomyolipoma, kidney, 391\ngermline mutations, 179t\u2013180t\nAngiomyxoma, genetics, 163t\u2013171t\nAngiosarcoma, 544\nbreast, grading, 285t\nimmunohistochemistry panel, 80t\u201383t\npapillary endothelial hyperplasia vs, 223\nAnnular calcium, mitral valve, 292, 293f\nAnterior aspect, 7f\nAnterior tibial neurovascular bundle, \ndissection, 239\nAnthracotic pigment, 17t, 206t\u2013212t\nAnthracycline cardiotoxicity, 289\nAnthrax, 198, 199t\u2013200t\nAntibodies, for immunohistochemistry, 108, \n109t\u2013150t\nAntigenicity of specimens\nbreast carcinoma, 265\nfactors affecting, 70\u201371\nAntigens\nalternative names for, 151t\u2013157t\ndecalcification and, 24, 33\nfixation and, 21\nformalin and, 12\nfor immunohistochemistry, 70, \n109t\u2013150t\nretrieval procedures, 71\nAntiviral agents, postexposure HIV \nprophylaxis, 197\nAnus, 340, 342t\nperianal Paget disease, 89t\nAorta, 305\naneurysm, 305\nAortic valve, 291\u2013295, 293f\u2013294f\nfunction, 296t\ngross morphologic assessment, 295t\npostinflammatory scarring, rheumatic \nvalve disease, 292\nA-P resection see Abdominoperineal \nresection\nAPC gene, mutations, 163t\u2013171t\nAperture iris diaphragms, microscopes, \n204b\nApex, radical prostatectomy specimen, \n406\nAphthous ulcers, Crohn disease, 345\nApical cores, heart, 304\nApoJ see Clusterin\nApolipoprotein J see Clusterin\nAppendicitis, 357\nAppendix, 340f, 342t, 355\u2013359, 356f\ncarcinoma, 357\nadenocarcinoma, 94t\nAJCC classification, 359t\nsign-out checklist, 358\u2013359\nmetastasis to ovary, \nimmunohistochemistry, 92t\nApple-core lesion, 18t", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_584.png", "summary": "The page discusses various topics related to surgical pathology, including AJCC classifications for different types of carcinomas, staining techniques like Alcian blue and Alizarin red S, and specific markers like Alpha-fetoprotein.", "questions": [ "What are some common AJCC classifications mentioned for different types of carcinomas?", "How are staining techniques like Alcian blue and Alizarin red S used in surgical pathology?", "Why is Alpha-fetoprotein mentioned in relation to testis tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 585, "text": "567\nIndex\nAprons, 201\ninfection precautions, 65\nAR see Androgen receptor\nArchitectural grades, of uterine tumors, 436\nArenaviruses, 199t\u2013200t\nArmed Forces DNA Identification \nLaboratory, 33\nArrows, specimen photography, 216\nArtery-to-vein anastomoses, twin placentas, \n463\nArthrogryposis, 471\nArthroplasty\nrevision, 250\u2013251\noperating room consultations, 52, 52t\ntotal joint, 246\u2013251\nsee also Prosthetic joints; Total joint \narthroplasty\nArticular surfaces, 247\nAsbestos fibers, 206t\u2013212t, 506\nAscending colon, 340f, 342t\nAseptic necrosis see Osteonecrosis\nAspergillus spp., 186t\u2013189t\nallergic sinusitis, 473\nintervertebral discs, 261\nASPL-TFE3 fusion, 163t\u2013171t\nAssociation of Directors of Anatomic \nand Surgical Pathology (ADASP), \nstandards for reporting, 220, 225\nbreast carcinoma, 268\nfor cervix, 448\nAstrocytoma, immunohistochemistry, 95t\nAtherectomy specimens, 305\nAtherosclerosis\ncoronary arteries, 301\u2013303\nlung transplants, chronic vascular \nrejection, 496b\n\u2018Atlantis phenomenon,\u2019, 31\nAtria (heart), 301, 301f\nmyocardium, 304\nAtypical adenoma, parathyroid, 562t, 563\nAtypical carcinoid, lung, 501t\nAtypical ductal hyperplasia (ADH), breast, \nexcisional biopsy, 269\nAtypical fibroxanthoma, 80t\u201383t\nAtypical teratoid, immunohistochemistry, \n95t\nAtypical teratoid/rhabdoid tumor, genetics, \n163t\u2013171t\nAutopsy, TB infection risk, 197\nAvascular necrosis see Osteonecrosis\nAxillary dissections, 276\u2013279\nAJCC classification, 279t\nAxillary tail, mastectomy, 274\nB\nB1 see CD antigens, CD20\nB2 see CD antigens, CD21\nB4 see CD antigens, CD19\nB5 (fixative)\nliver biopsy, 362\nlymph nodes, 514\u2013516\nHodgkin disease, staging laparotomy, \n522\nB72.3 (tumor-associated glycoprotein), \n109t\u2013150t\nBAC see Bronchioloalveolar carcinoma\nBacillus anthracis, 198, 199t\u2013200t\nBackground positivity, immunoperoxidase \nstudies, 72\u201373\nBackgrounds, photography, 216\nBacteria, cultures, 185\u2013186\nBAF47/Snf5 see INI-1\n\u2018Bag of worms\u2019 appearance, nerve tumors, \n543\nBags (specimen bags), 245\nBannayan-Riley-Ruvalcaba syndrome, \n181t\u2013183t\nBarium sulfate, microscopy, 206t\u2013212t\nBarrett\u2019s esophagus, 55, 323\u2013324, 325f\nBasal cell carcinoma, 313\ngermline mutations, 179t\u2013180t\nBasal cell hyperplasia, diagnostic pitfalls, 222\nBasaloid carcinoma, tonsil, 484\nBasaloid squamous cell carcinoma, small \ncell carcinoma v., 102t\nB-cell lymphoma 2 see bcl-2\nB-cell neoplasms, 103t\u2013104t, 172t\u2013178t\nB-cell Oct-binding protein 1 see BOB.1\nB-cell specific activator protein see BSAP\nBcI-6, 109t\u2013150t\nbcl-1 see Cyclin D1\nbcl-2, 109t\u2013150t\nBCR-ABL fusion, 172t\u2013178t\nBeall 104 heart valve, 298f\nBeall-Surgitool heart valves, 298f\nBeckwith-Wiedemann syndrome, \n181t\u2013183t, 471\nBenign lymphoepithelial lesions, salivary \nglands, 480\nBenign prostatic hyperplasia, 408\nBer-EP4, 109t\u2013150t\nBERH2 see CD antigens, CD30\nBeta-2 microglobulin, 109t\u2013150t\nBeta-2 microglobulin amyloidosis\nbiopsy and, 550\ncolor, 247, 260\nBeta-amyloid, 109t\u2013150t\nBeta-catenin, 109t\u2013150t\nnuclear immunoreactivity, 72\nBeta-HCG see Human chorionic \ngonadotropin\nBG8, 109t\u2013150t\nBicuspid heart valves, 293f\nBieer-Val heart valve, 298f\nBile, 206t\u2013212t\nstain, 67t\u201370t\nBile ducts\nadenomas, 364\nhamartomas, 364\nWhipple procedure see Whipple \nprocedure\nBilling documentation, consultations, 40, 43\nBiologic terrorism, 198\nBioprosthetic heart valves, 295, 297, 297f, \n300f\npathologic analysis, 300t\nBiopsy\nabdominal fat pad, amyloidosis, 550\nbladder, 32t\u201333t, 395\u2013396\nbone, 251\u2013252\noperating room consultations, 51\u201352\nreasons, 246t\nbone marrow see Bone marrow, biopsy\nbrain, 61\u201362, 527\u2013530\nbreast see Breast, biopsy\ncervix, 449, 449f\ncolon, 338, 339f see Colon, biopsy\ndura, 530\nBiopsy (Continued)\nendometrium, 423, 424t\nendomyocardial, 289\u2013290\nesophagus, 323\nheart, 32t\u201333t\njoints, reasons, 246t\nkidney see Kidney, biopsy\nliver, 360\u2013362\nHodgkin disease staging, 522\u2013523\npre-transplant operating room \nconsultations, 56 see Liver, \nbiopsy\nlung, 60\u201361, 494\u2013495, 497 see Lung, \nbiopsy\nmucosa, 479\nmuscle, 4t, 533\u2013534\nnipple, 285\noral cavity, 550\novarian tumors, 440\u2013444\npancreas, 372\nperipheral nerve, 533\npleura, 510\nprostate see Prostate, biopsy\nrectum, 550\nsarcomas, 540\u2013541\nskin see Skin, biopsy\nsmall, 243, 244f\nsmall intestine, 335 see Small intestine, \nbiopsy\nsoft tissue tumors, operating room \nconsultations, 62\nstains and levels for, 32t\u201333t\nstomach, 329\nsubungual melanoma, 322\ntemporal artery, 306, 306t\ntestis, 412, 413b see Testis, biopsy\nsee also Core biopsy\nBirbeck granules, 158t\u2013160t\nBirefringence (polarizability), 205\u2013213\ncrystals, 247\u2013248\nBj\u00f6rk-Shiley tilting disk valve, 297f\u2013298f\nBK virus, histological appearance, \n190t\u2013194t\nBLA.36 see CD antigens, CD77\nBladder, 395\u2013400\nbiopsy, 32t\u201333t\ncarcinoma, 395\u2013400, 399t, 401t\nadenocarcinoma, \nimmunohistochemistry panel, \n98t\nurothelial, grading, 399t\nclinical history, 384t\u2013385t\nfungal infection of, 186t\u2013189t\ninflation, 396\nsee also Cystectomy\nBladder neck base margin, radical \nprostatectomy, 406, 407f\nBlastic NK-cell lymphoma, 105t\u2013106t, \n172t\u2013178t\nBlastomyces dermatitidis, 186t\u2013189t\nBL-CAM see CD antigens, CD22\nBlocks, 29f\nextraneous tissue, 33\u201334\nfrozen sections, 46\u201348\nremoval from chuck, 47\u201348\ninstitutional consultations, 42\nrelease for research, 43\nsee also Cell blocks\nBlood, HIV infection risk, 197", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_585.png", "summary": "The page covers a wide range of topics in surgical pathology, including various diseases, procedures, and immunohistochemistry markers.", "questions": [ "What are some common immunohistochemistry markers mentioned on this page?", "How is Barrett's esophagus described in relation to other conditions?", "What are some key surgical procedures discussed in this text?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 586, "text": "568\nIndex\nBlood group antigens, \nimmunohistochemistry, 109t\u2013150t\nBlood vessels, 305\u2013306\ninvasion\nthyroid tumor, 560t\nsee also Lymphovascular invasion\nlung, 498\nBlood-borne viruses\nas hazards, 196\u2013198\npostexposure prophylaxis, 197\nBlue cells, crushed, lung, diagnostic pitfalls, \n222\nBlue dome cyst, breast, color, 17t\nBOB.1, immunohistochemistry, 109t\u2013150t\nBocca neck dissection, 475\nBodian\u2019s, 67t\u201370t\nBone, 206t\u2013212t, 246\nfrozen sections and, 51\nfungal infection, 186t\u2013189t\nlarge resections, 241\u2013242\noperating room consultations, 51\u201352\ntumors\nAJCC classifications, 256t\nbiopsy, 251\u2013252\ngrading, 257t\nresections, 252\u2013258\nsee also Skeletal anomalies\nBone cement, 251\nBone cyst, 254f\nsee also Aneurysmal bone cyst\nBone dust artifacts, avoidance, 241, 253\nBone marrow, 513\u2013514\nbiopsy, 513\u2013514\nstains and levels, 32t\u201333t\nsubmission, 4t\nZenker\u2019s acetic fixative, 23\nclinical history, 513t\nlower limb dissection, 239\nrib squeeze method, 259\nBorderline tumors, ovary, 442\nomental biopsy, 440\noperating room consultations, 57\nserous, 441f\nBorders, in gross description, 18t\nBosselated, for gross description, 18t\nBotulinum toxin, 198\nterrorism, 199t\u2013200t\nBouin\u2019s solution, 23\nlymph nodes, 10, 518\nmordant for inks, 12\nBovine bioprosthetic heart valves, 297f\nBowel rings, 340\nB-Plus (fixative), 23\nlymphoproliferative disorders, 61\nsoft tissue tumors, 62\nBR-2\nsee also Gross cystic disease fluid protein-15\nBrain\nbiopsy, 61\u201362, 527\u2013530\nclinical history, 527t\nfetus, dissection, 469\u2013471\nresections, 530\u2013531\nBraunwald-Cutter heart valve, 299f\nBRAx mutations, breast carcinoma, \n163t\u2013171t\nBRCA1, mutations, 179t\u2013183t\nBRCA2, mutations, 181t\u2013183t\nBRD4-NUT fusion, upper aerodigestive \ncarcinoma, 163t\u2013171t\nBreast, 262\nangiosarcoma, grading, 285t\nbiopsy\noperating room consultations, 53\u201354\nsite, 267\nstains and levels, 32t\u201333t\nsee also Core needle biopsy; \nExcisional biopsy, breast\nblue dome cyst, color, 17t\ncalcification\nsee also Calcification, breast\ncarcinoma\nsee also Breast carcinoma\ndiagnostic pitfalls, 222\nerrors, 219\nestrogen receptor evaluation, 86\u201387, 86t\nexcisional biopsy, 263\u2013267\nfibroblastic/myofibroblastic lesions of, \n91t\nimplants, 286\u2013287\nincisional biopsy, 263\nlarge core needle biopsy, 262\u2013263\nmastectomy, 272\u2013276, 275f\nmetastases, lung, 102t\nreexcisions, 270\u2013272\nreports, example headings, 36t\nshave margins, 272\nsignet ring cell carcinomas of, 90f, 90t\ntumor, marker, 84t\u201385t\nBreast carcinoma, 265\u2013266, 266f, 275\nadenocarcinoma, 94t\nAJCC classifications, 262t, 279t\naxillary dissections, 276\u2013279\nductal, 75t\u201376t\ngenetics, 163t\u2013171t\ngermline mutations, 179t\u2013180t\ngrading, 278b, 281t\u2013285t\nhormone receptors and HER-2/neu, \n263, 265\nimmunohistochemistry panel, 75t\u201376t\nincisional biopsy, 263\nlobular\nimmunohistochemistry panel, \n75t\u201376t\nmetastases, diagnostic pitfalls, 222\nlymph nodes\nimmunohistochemistry, 519\u2013520\nsentinel, 521\u2013522\nsee also Axillary dissections\nin males, 89t\nmastectomy, 272\nmeasurement, 213\nmyoepithelial markers, 88t\nsign-out checklists, 276\u2013279\nBrenner tumor, 75t\u201376t, 441\nBreslow depth of invasion, melanoma, 316t\nBrevity, gross descriptions, 19\nBronchi\nlung lobectomies, operating room \nconsultations, 60\nsee also Endobronchial biopsy; \nTransbronchial biopsy\nBronchiolitis obliterans, chronic airway \nrejection, 496t\nBronchioloalveolar carcinoma (BAC), 75t\u2013\n76t, 102t, 158t\u2013160t, 499, 499f\nBronchoalveolar lavage, 308\u2013309\nBronchocentric granulomatosis, fungal \ninfection of, 186t\u2013189t\nBrown-Brenn stain, 67t\u201370t\nBrown-Hopps stain, 67t\u201370t\nBRST-2 see Gross cystic disease fluid \nprotein-15\nBSAP, immunohistochemistry, 109t\u2013150t\nBullectomy, 497\nBullets, 526\nrelease from laboratory, 25\nsubmission, 4t\nBurial, specimens, 25\nBurkitt lymphoma, 103t\u2013104t\ngenetics, 172t\u2013178t\nBurkitt-like lymphoma, 103t\u2013104t\ngenetics, 172t\u2013178t\nBypass grafts, coronary arteries, 301\u2013303, \n306\nC\nC cells, medullary thyroid carcinoma, 557\nC3b/C4b R see CD antigens, CD35\nCA 15-3 see Epithelial membrane antigen\nCA 19-9, 109t\u2013150t\nCA 27.29 see Epithelial membrane antigen\nCA 72-4 see B72.3\nCA125, 109t\u2013150t\nCadavers\nbioterrorism and, 198\nhuman immunodeficiency virus, 197\nCaged ball valves, 297f, 299f\nCaged disk valves, 298f\nCalcification\nbreast, 263\nmammographic lesions, 269\nafter treatment, 273\nheart valves, 292, 293f\nprosthetic, 296\nCalcified substances\ncutting, 28 see Decalcification\nCalcitonin, 109t\u2013150t\nCalcium\nserum, hyperparathyroidism, 561t\nvon Kossa stain, 67t\u201370t\nCalcium oxalate, 206t\u2013212t, 248\nbreast calcifications, 263\nCalcium phosphate, 206t\u2013212t\nbreast calcifications, 263\nCalcium pyrophosphate dihydrate crystals \n(CPPD crystals), 206t\u2013212t, 247\u2013248\narthroplasty specimens, 248\nsynovium, 259\u2013260\nCalculi, gallbladder, 368\nchemical analysis, 370\nCalculi (biliary) see Gallstones\nCalculi (urinary), 403\nCalculous cholecystitis, acute, 369\nCaldesmon, 109t\u2013150t\nCalgranulin see MAC 387\nCalibration, for microscopic measurement, \n214, 214b\nCALLA see CD antigens, CD10\nCALP see Calponin\nCalponin, 109t\u2013150t\nbreast carcinoma, 88t\nCalprotectin see MAC 387\nCalretinin, 101t, 109t\u2013150t\npleural biopsy, frozen section, 510\nCAM 5.2, 109t\u2013150t\nCandida spp., 186t\u2013189t\nCAP see College of American Pathologists", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_586.png", "summary": "The page discusses various topics related to surgical pathology, including blood group antigens, blood vessels, bone marrow, breast tumors, and brain biopsies.", "questions": [ "What are the key considerations when evaluating breast carcinoma?", "How are bone tumors classified and graded?", "What techniques are commonly used for bone marrow biopsy?", "What are the implications of lymph node involvement in breast carcinoma?", "How do immunohistochemistry panels aid in the diagnosis of breast tumors?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 587, "text": "569\nIndex\nCapsular invasion, thyroid tumors, 559, \n559f\nCarbohydrate antigen 19-9 see CA 19-9\nCarbohydrates, fixation and, 21\nCarboMedics (CPHV) bileaflet tilting disk \nvalve, 297f\nCarcinoembryonic antigen (CEA), \n109t\u2013150t\nCarcinoid\nappendix, 357\ndense core granules, 158t\u2013160t\nimmunohistochemistry, 77t\u201378t\nmetastases, 99t\nlarge cell neuroendocrine carcinoma v., \n102t\nlung, 60, 102t, 499, 499f, 501t\nmarker, 84t\u201385t\npancreas, 379t\nsmall cell carcinoma v., 102t\nsmall intestine, 335\nCarcinoma in situ see Ductal carcinoma in \nsitu\nCarcinomas\nadrenal gland, 229, 233t\nanal\nAJCC classifications, 356t\ngrading, 355t\nsign-out checklist, 352\u2013355\nappendix, 357\nAJCC classification, 359t\nsign-out checklist, 358\u2013359\nbreast, 263, 265\u2013266, 266f, 275\nAJCC classifications, 279, 279t\naxillary dissections, 276\u2013279\ngrading, 278b, 281t\u2013285t\nincisional biopsy, 263\nsign-out checklists, 276\u2013279\ncolon, 342\u2013343, 347\u2013349, 348f\nAJCC classification, 351, 353t\u2013354t\nHNPCC, 343\u2013344, 344t\ninfiltrative border, 352b\ninflammatory bowel disease, \n345\u2013346, 346t, 347f\nmargins, 324, 348\u2013349\nmetastases to liver, 363f\nrecurrent, 348\nsign-out checklist, 350\u2013352\nelectron microscopy, 158t, 541\nesophagus\nadenocarcinoma, 324, 325f, 327t\nAJCC classification, 327, 328t\ngastrectomy specimens, 326\nafter radiotherapy, 325\nsign-out checklist, 326\u2013328\nsquamous cell carcinoma, 324\u2013325, \n325f, 327t\ngallbladder, 367\u2013369\nAJCC classifications, 334t\ngrading, 370t\nsign-out checklist, 326\nhepatocellular, 362\u2013363, 363f\nEdmondson and Steiner grading, \n365t\nimmunohistochemistry and, 70\nlip, 321, 321f\nlymph node staging, sign-out checklist, \n521\u2013522\nmarkers, 85t\nMerkel cell, AJCC classification, 320t\nCarcinomas (Continued)\noperating room consultations\nbreast, 53\u201354\ncolon, 55\nendometrium, 57\u201358\nlung, 59\npancreas, 56\nskin, 52\u201353\nthyroid, 62\u201363\npancreas, 343, 372, 375\u2013377\nAJCC classifications, 334t, 381\nductal, 376f, 380t\nsign-out checklists, 332\nrectum, 347\u2013348, 348f\nAJCC classification, 351, 353t\u2013354t\ninfiltrative border, 352b\nsign-out checklist, 350\u2013352\nsarcomas vs, electron microscopy, 541\nskin, 313\nAJCC classifications, 315, \n315t\u2013319t\nhistologic grade, 314t\u2013315t\nsign-out checklist, 314\nsmall intestine, 335\u2013336\nAJCC classification, 336, 337t\ngrading, 336t\nstomach\nadenocarcinoma, 333t\nAJCC classification, 333, 334t\ndiffuse type, 330, 331f\nesophagectomy specimens, 324\nintestinal type, 330, 331f\nsign-out checklist, 332\u2013333\nthyroid, parathyroid, 561\nsee also specific sites\nCarcinosarcoma, uterus, 432\nCardiomyopathy, 301\u2013302\nendomyocardial biopsy, 289\u2013290\nCardiovascular specimen see Heart\nCarney complex, 181t\u2013183t\ntype 2, adrenal cortex carcinoma \ngenetics and, 163t\u2013171t\nCarney triad, 181t\u2013183t\nCarnoy\u2019s fixative, acid-fast bacilli and, 67t\u201370t\nCarpal tunnel syndrome, release specimens, \n260\nCarpentier-Edwards bovine bioprosthetic \nheart valve, 297f, 300f\nCartilage, rib, 258\nCaseous necrosis, 18t\nCassettes, 29f\ngross descriptions, 15\nidentification of tissue, 31\u201333\nlost specimens, 12\u201313\nCatheters, 2\nCaudal aspect, 7f\nCaudal-related homeobox transcription \nfactor see CDX2\nCavitron Ultrasonic Surgical Aspirator \n(CUSA), specimens, 530\nC-cell hyperplasia, thyroid gland, 559\nCD antigens\nCD1a, 109t\u2013150t\nCD2, 109t\u2013150t\nCD3, 109t\u2013150t\nCD4, 109t\u2013150t\nCD5, 84t\u201385t, 109t\u2013150t\nCD7, 109t\u2013150t\nCD8, 109t\u2013150t\nCD antigens (Continued)\nCD10, 109t\u2013150t\nbreast carcinoma, 88t\nCD11b, 109t\u2013150t\nCD11c, 109t\u2013150t\nCD13, 109t\u2013150t\nCD15 (LeuM1), 109t\u2013150t\ninternal control, 71\nCD16, 109t\u2013150t\nCD19, 109t\u2013150t\nCD20, 109t\u2013150t\nCD21, 109t\u2013150t\nCD22, 109t\u2013150t\nCD23, 109t\u2013150t\nCD25, 109t\u2013150t\nCD30, 109t\u2013150t\nCD31, 109t\u2013150t\ninternal control, 71\nCD33, 109t\u2013150t\nCD34, 109t\u2013150t\nliver tumors, 99t\nCD35, 109t\u2013150t\nCD38, 109t\u2013150t\nCD43, 109t\u2013150t\nCD44v3 (variant 3), 109t\u2013150t\nCD45 (leukocyte common antigen or \nLCA), 109t\u2013150t\nas lymphoma marker, 85t\nCD45RA, 109t\u2013150t\nCD45RO, 109t\u2013150t\nCD56, 109t\u2013150t\nT-cell neoplasms, 105t-106t\nCD57, 109t\u2013150t\nCD61, 109t\u2013150t\nCD63, 109t\u2013150t\nCD66e see Carcinoembryonic antigen\nCD68, 109t\u2013150t\nCD74, 109t\u2013150t\nCD77, 109t\u2013150t\nCD79a, 109t\u2013150t\nCD79b, 109t\u2013150t\nCD95, 109t\u2013150t\nCD99, 109t\u2013150t\nCD103, 109t\u2013150t\nCD117 (c-kit), 97t, 109t\u2013150t\ninternal control, 71\nas marker, 84t\u201385t\nmastocytosis, 172t\u2013178t\nrenal carcinomas, genetics, 163t\u2013171t\nCD123, 109t\u2013150t\nCD138, 109t\u2013150t\nCD141, 109t\u2013150t\nCD146, 109t\u2013150t\nCD147, chaperoning monocarboxylase \ntransporter 1, 158t\u2013160t\nCD163, 109t\u2013150t\nCD207, 109t\u2013150t\nCD246 see ALK protein\nCDK4, 109t\u2013150t\nCDKN2 see p16\nCDKN2A deletion, 163t\u2013171t\nCDP see Gross cystic disease fluid \nprotein-15\nCDw75, 109t\u2013150t\nCDX2 (CDX-88), 109t\u2013150t\nCDX-88 see CDX2\nCEA see Carcinoembryonic antigen\nCecum, 342t\nsolitary diverticulum, 345, 357", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_587.png", "summary": "This page covers various types of carcinomas, including their classifications, grading, and sign-out checklists for different anatomical sites.", "questions": [ "What are some common markers used in the diagnosis of carcinoid tumors?", "How do AJCC classifications differ for different types of carcinomas?", "What is the significance of Carney complex and Carney triad in relation to adrenal cortex carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 588, "text": "570\nIndex\nCell blocks, 308\u2013309\nCell surface marker analysis, indications, \n184\nCellular mesoblastic nephroma, 390\ncytogenetics, 390\nCellulitis, necrotizing fasciitis vs, operating \nroom consultations, 53\nCenters for Disease Control (CDC), \nbiologic terrorism and, 198, \n199t\u2013200t\nCentral insertion, placental membranes, \n461f\nCentral neurocytoma, \nimmunohistochemistry, 95t\nCentrifugation, cell blocks, 308\nCephalic aspect, 7f\nc-erb B2 see HER-2/neu\nCerebrospinal fluid, storage for cytology, \n309\nCervical lymph nodes, thyroid inclusions, \n63\nCervix, 448\u2013453\ncarcinoma\nendometrial carcinoma vs, 92t\ngrading, 451t\nradical hysterectomy, 429\u2013431\nreporting, 435\u2013436\nsign-out checklist, 450\u2013453\nsquamous cell carcinoma, 75t\u201376t, \n450\nclinical history, 448t\nmicroscopy, 426, 428\nCetuximab, 163t\u2013171t\ncolorectal carcinoma, 163t\u2013171t\nCharcot-Leyden crystals, 206t\u2013212t\nChecklists\nmalignant tumors, 36\nsign-out, 37, 225\nsee also under specific conditions\nChemicals, disposal, 24\nChemotherapy\nbone resection, 242, 253\u2013255, 258t\nclinical history of, 3\nMiller-Payne grading system, 283t\nRCB grading system, 284t\nChest wall\nmesothelioma invasion, 506\nsee also Ribs\nChicken fat (food analogy), 18t\nChloroacetate esterase, 67t\u201370t\nChloroma, color, 17t\nChocolate cyst, 18t\nsee also Endometriotic cyst\nCholangiocarcinoma, 363\u2013364\ngrading, 365t\nimmunohistochemistry, 74t, 99t\nCholecystectomy, laparoscopic, 366\nCholecystitis, 367, 369\nCholesterol, microscopy, 206t\u2013212t\nCholesterolosis, gallbladder, 18t, 367\nChondroblastoma, 80t\u201383t, 254f\nChondrocalcinosis\narthroplasty specimens, 248\ncolor, 17t, 247\nCPPD crystals, 206t\u2013212t, 247\u2013248\nsynovium, 259\u2013260\nChondroid hamartoma, pulmonary, 500\nChondromyxoid fibroma, 254f\ngenetics, 163t\u2013171t\nChondrosarcoma, 254, 254f\ndifferentiation score, 548t\u2013549t\ngrading, 257t\nChorangioma, 464\nChordae tendineae, 291\nChordoma, 75t\u201376t, 158t\u2013160t\nChorioamnionitis, 463\nChoriocarcinoma, 433\nimmunohistochemistry, 93t, 96t\ntestis, 414\nsee also Gestational trophoblastic tumors\nChoroid, melanoma, 532\nChoroid plexus\ncarcinoma, genetics, 163t\u2013171t\nimmunohistochemistry, 95t\nimmunohistochemistry panel, 75t\u201376t\nChromaffin reaction, adrenal masses, 228\nChromoblastomycosis, fungal infection, \n186t\u2013189t\nChromogranin(s), 158t\u2013160t\ncarcinoid, 84t\u201385t\nparaganglioma, 536\nChromogranin A, 109t\u2013150t\nChromophobe renal cell carcinoma, 388\ngenetics, 163t\u2013171t\nChronic airway rejection, 496t\nChronic cholecystitis, 369\nChronic eosinophilic leukemia, genetics, \n172t\u2013178t\nChronic eosinophilic leukemia/\nhypereosinophilic syndrome, \ngenetics, 172t\u2013178t\nChronic lymphocytic leukemia, ribs, 258\ndiagnostic pitfalls, 223\nChronic lymphocytic lymphoma, genetics, \n172t\u2013178t\nChronic myelocytic leukemia (CML), \n172t\u2013178t\ngenetics, 172t\u2013178t\nspleen, 523\nChronic myelomonocytic leukemia with \neosinophilia, genetics, 172t\u2013178t\nChronic pancreatitis, 377\nChronic vascular rejection, lung transplants, \n496b\nChronic viral hepatitis, grading and staging, \n361t\nCircumcision, 321\u2013322\nCircummarginate insertion, placental \nmembranes, 460, 461f\nCircumvallate insertion, placental \nmembranes, 460, 461f\nCirrhosis\ncolor, 17t\nmicronodular, 363f\nc-kit see CD antigens, CD117\nClark level, melanoma, 317t\nClaudin-1 (CLDN1), 80t\u201383t, 109t\u2013150t\nCLDN1 see Claudin-1\nCleaning\ninfection precautions, 65\nmicroscopes and slides, 214\u2013215\nClear cell adenocarcinoma, gynecology, \ngrading, 435\u2013436\nClear cell carcinoma\ndiethylstilbestrol and, 448t\nkidney, 98t, 388, 388f\nadrenal metastases, 97t\ngenetics, 163t\u2013171t\nClear cell carcinoma (Continued)\novary, 92t, 442\nsign-out checklist, 443\u2013444\nClear cell sarcoma, 158t\u2013160t\ngenetics, 163t\u2013171t\nimmunohistochemistry panel, 80t\u201383t\nkidney, 390\nClearing, 28\nCleft palate/lip, 471\nClinical history, 3\u20135, 225\nbladder, 395t\nbrain, 527t\ncervix, 448t\nchemotherapy, 3\ndrugs, 3\u20135\nerrors and, 221\nimmunocompromise, 3\nkidney, 384t\u2013385t\nlarynx, 489t\nlung, 494t\nmastectomy, 272\noperating room consultations, 46, 51\novary, 437t\nparaganglioma, 535t\nparathyroid glands, 561t\nplacenta, 458\u2013460\npregnancy, 3\nprostate, 403t\nradiotherapy, 3\nsarcomas, 540t\nskin, 310t\ntestis, 412t\nthymus, 551t\ntonsils, 485t\ntreatment, 3\nuterus, 423t\nvagina, 453t\nClinical trials, reporting and, 35\nClinicians\nerrors and, 219\u2013221\nidentification of, 2\u20133\nClippings, nails, 322\nClitoris, fetus, 471\nClostridium botulinum, 199t\u2013200t\nClusterin, 109t\u2013150t\nCML see Chronic myelocytic leukemia\nCMV see Cytomegalovirus\nCoatings, slides, immunohistochemistry, 71\nCoccidioides spp., 186t\u2013189t\nCoccidioides immitis, as hazard, 196b\nCOL1A1-PDGFB fusion, 163t\u2013171t\nCollagen, 206t\u2013212t\nCollagen IV, 109t\u2013150t\nCollecting duct carcinoma, 389\nCollege of American Pathologists (CAP)\ngastric adenocarcinoma grading, 333t\nguidelines for retention of tissues, 24\nretention of gross specimens, 5t\nspecimens not needing histology, 420\nstandards for reporting, 220, 225\nfor cervix, 448\nskin carcinoma, 314\nColloidal iron, 67t\u201370t\nColon, 337\u2013355\nbiopsy, 338, 339f\nstains and levels, 32t\u201333t\ncarcinoma, 342\u2013343, 347\u2013349, 348f\nadenocarcinoma, 74t, 94t\nAJCC classification, 351, 353t\u2013354t", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_588.png", "summary": "The page covers a wide range of topics in surgical pathology including cell blocks, cytogenetics, cervical carcinoma, chemotherapy, and various types of tumors.", "questions": [ "How are cell blocks used in pathology?", "What are the key differences between endometrial carcinoma and cervical carcinoma?", "How is chemotherapy graded and what systems are commonly used for grading?", "What is the significance of Chondrosarcoma differentiation score?", "How is chronic lymphocytic leukemia diagnosed and what are the potential pitfalls?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 589, "text": "571\nIndex\nColon (Continued)\nbeta-catenin, 72\ngenetics, 163t\u2013171t\ngermline mutations, 179t\u2013180t\nhereditary nonpolyposis syndrome, \n181t\u2013183t\nHNPCC, 343\u2013344, 344t\ninfiltrative border, 352b\ninflammatory bowel disease, \n345\u2013346, 346t, 347f, 350\nmargins, 326, 348\u2013349\nmetastases\nto liver, 363f\nlung, 102t\novary, 92t\nphotography, 216\nrecurrent, 348\ndiverticulosis, 344\u2013345, 344f, 349\u2013350\nidentifying segments, 338\u2013355, \n340f\u2013341f, 342t\ninflammatory bowel disease, 345\u2013346, \n346t, 347f, 350\nmeasurement of specimen, 16\noperating room consultations, 55\npolyposis syndromes, 346\nreports, example headings, 36t\nrupture, plant material microscopy, \n206t\u2013212t\nColors\nbone and joint specimens, 247\nprostate carcinoma, 405\nsmall biopsies, 244\nadrenal gland, 228\nof specimens, 17, 17t\nCommissures, heart valves, 291\nCommon acute leukemia antigen see CD \nantigens, CD10\nCommon bile duct, Whipple procedure, \n374\u2013382, 374f\nCommunication, of urgent results, 38\u201339\nComplement lysis inhibitor see Clusterin\nComplete mole, 93t\nComplex cysts, ovary, 437, 439\nCondensers, microscopes, 204\nCone biopsy, cervix, 449, 449f\nConfidentiality, research and, 43\nCongestion, color, 17\nCongo red, 67t\u201370t, 206t\u2013212t\namyloidosis, 289\u2013290\nConn syndrome, 228\u2013229\nspironolactone bodies, 206t\u2013212t\nConsistency, specimens, 17\nConsultations\nbilling documentation, 40, 43\nfrozen sections and, 40\ninstitutional, 41\u201342\nminimizing errors, 220\nreporting, 35\u201338, 40\nfor special studies, 41\nsee also Operating room consultations\nContainers\ndisposal, 24\ninfection precautions, 65\nspecimen transport, 5\nempty, 12\nContamination, cryostats, 65\nContrast (optical), microscopy, 204\nContrast media (radiographic), thorotrast, \nmicroscopy, 206t\u2013212t\nControls, immunohistochemistry, 71\nCooley-Cutter heart valve, 298f\nCopper metabolism disease, liver special \nstudies, 362\nsubmission of specimens, 4t\nCord lipomas, 487, 541\u2013542\nCore biopsy\nosteonecrosis, 251\nsee also Prostate, biopsy\nCore needle biopsy, breast\nhistological processing, 32t\u201333t\nlarge, 262\u2013263\nmastectomy after, 273\nCornea, 531\u2013532\nCornstarch, microscopy, 206t\u2013212t\nCoronal section, 7f\nCoronary arteries, 301\u2013303, 301f\nCoronary artery bypass grafts, 301\u2013303, 306\nCorpora albicantia, 440\nCorpora amylacea, 206t\u2013212t\nCorpus luteum, 440\nCost, microscopy, 20\nCost-benefit analysis, specimens not \nneeding histology and, 421\nCotton fibers, microscopy, 206t\u2013212t\nCoverslips, 215\nCowden syndrome, 181t\u2013183t\nCPPD crystals see Calcium pyrophosphate \ndihydrate crystals\nCR1 see CD antigens, CD35\nCranial arteritis (temporal arteritis), scoring \nsystem, 306t\nCraniopharyngioma, 75t\u201376t\nCreeping substitution, Crohn disease, 345, \n346t\nCreutzfeldt-Jakob disease, 527t\nas hazard, 196b, 198, 528\nreturn of specimens to patients and, 21\nspecial studies, 528\nspecimen fixation and, 198, 528\n\u201cCritical values,\u201d communication of, 38\u201339\nCrohn disease, 345\u2013346, 346t, 347f\noperating room consultations, 55\nCross-Jones heart valve, 298f\nCrown-rump length, placental weight vs, \n464, 465t\nCrushed blue cells, lung, diagnostic pitfalls, \n222\nCryostats\ncontamination, 65\ninfection hazard and, 201\nCryptococcus neoformans, 186t\u2013189t\nCryptosporidium, as hazard, 196b\nCrystals, 206t\u2013212t, 247\u2013249\nbreast calcifications, 263\ncalcium oxalate, 248\nCPPD, 247\u2013248\ndihydrate (CPPD), 206t\u2013212t\nsynovium, 259\u2013260\nuric acid, 206t\u2013212t, 247\u2013248\nCulture, infectious organisms, 185\u2013186, \n185t\nCulture of safety (Sirota), 218, 218t\nCurettings\nbone lesions, 52\nbone tumor, 251\u2013252\nendometrium, 423, 424t\nskin, 312\nCurrant jelly (food analogy), 18t\nCUSA see Cavitron Ultrasonic Surgical \nAspirator\nCushing syndrome, 228\u2013229\nCusps, heart valves, 291\nCyclin D1, 109t\u2013150t\nCyclin-dependent kinase 4 see CDK4\nCyst(s)\nadrenal, 230\nbreast, 267\nendometriotic, 441\ncolor, 17t\nepidermal inclusion, 313\novary, 436\nfollicular, 440\noperating room consultations, 57\nsee also Dermoid cyst\npericoronal, 484\nsafety precautions, 201\u2013202, 438\ntubal, 446\nsee also specific types\nCystadenocarcinoma see Mucinous cystic \ntumors\nCystadenomas\novary, 441f\nsee also Mucinous cystic tumors\nCystectomy, 396\u2013400, 397f\noperating room consultations, 57\nCystic fibrosis antigen see MAC 387\nCystic kidney disease, 390\nacquired, 386, 391t\nCystic lesions, pancreas, 373, 376f, 377\npseudocyst, 377\nCystine, calculi, 403\nCytogenetics, 162\u2013184\nadrenal tumors, 228\nbone biopsy, 252\ncarcinoma, 101t\nfixation and, 22\nlipomas, 541\u2013542\nlymphoproliferative disorders, 515\npediatric renal tumors, 389b\nplacenta, 463\nsarcoma biopsy, 541\nsoft tissue tumors, specimen preparation, \n62\nsubmission of specimens, 4t, 184\nCytokeratin(s) (keratins)\nimmunohistochemistry, 71, 109t\u2013150t\nmalignant cells, 519\u2013520\nmelanoma markers, 85t\nsarcoma, 158t\nCytokeratin 5/6, 109t\u2013150t\nCytokeratin 7\nwith cytokeratin 20, 73, 74t\u201378t, 84\nimmunohistochemistry, 109t\u2013150t\nCytokeratin 14, immunohistochemistry, \n109t\u2013150t\nCytokeratin 20\nwith cytokeratin 7, 73, 74t\u201378t, \n84\nimmunohistochemistry, 109t\u2013150t\nCytology, 308\nanalytical see Flow cytometry\nintraoperative, 48\u201349\nlaparoscopic nephrectomy, retrieval bag \nwashings, 387\nlymph nodes, operating room \nconsultations, 61\nthyroid carcinoma, 63", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_589.png", "summary": "This page from a surgical pathology manual covers a wide range of topics related to colon pathology, including genetics, hereditary syndromes, metastases, inflammatory bowel disease, diverticulosis, and specimen measurements.", "questions": [ "How are genetics and hereditary syndromes related to colon pathology?", "What are the implications of metastases to the liver, lung, and ovary in colon cancer?", "How is inflammatory bowel disease diagnosed and managed in the context of colon pathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 590, "text": "572\nIndex\nCytomegalovirus (CMV), histological \nappearance, 109t\u2013150t\nCytoplasmic immunoreactivity, 71, 72f\nD\nD2-40, 109t\u2013150t\nD5 see MITF\nDacron\ngraft material, 306\nmicroscopy, 206t\u2013212t\nDALM see Dysplasia-associated lesion or \nmass\nDates, of procedures producing specimens, \n3\nDating, endometrium, Noyes Criteria, 424t\nDBA.44, immunohistochemistry, 109t\u2013150t\nDCIS see Ductal carcinoma in situ\nDebakey-Surgitool, 299f\nDecalcification, 23\u201324\namputations, 238\nantigens and, 33\nbone biopsy, 252\u2013253\nbone marrow biopsy, 513\u2013514\nimmunogenicity and, 70\u201371\nlarge resections, 241\nribs, 258\u2013259\nDecidualized endometrium, placental villi \nvs, 59t\nDecompression, osteonecrosis, 251\nDeep aspect, 7f\nDeferred diagnoses, operating room \nconsultations, 49, 51\nDegeneration, heart valves, 292, 293f, 296t\nDegenerative joint disease, 249\narthroplasty specimens, 248\nDehydration\nhematoxylin and eosin technique, frozen \nsections, 48\nhistologic processing, 28\nDemyelinating diseases, peripheral nerves, \n533\nDendritic cells, immunohistochemistry of \nmelanoma, 317t\nDense core granules, 158t\u2013160t\nDentate line, anus, 340\nDermatiaceous fungi, 186t\u2013189t\nDermatitis herpetiformis, \nimmunofluorescence, 161\nDermatofibroma, 80t\u201383t\nDermatofibrosarcoma protuberans (DFSP), \n80t\u201383t, 163t\u2013171t\nDermatopathology see Skin\nDermatophytes, 186t\u2013189t\nDermoid cyst\novary, 441\noperating room consultations, 57\ntestis tumors, 414\nsee also Teratomas\nDescending colon, 340f, 342t\nDesmin, 109t\u2013150t\nDesmoplastic melanoma, diagnostic pitfalls, \n222\nDesmoplastic mesothelioma\ndiagnostic pitfalls, 222\nfibrosing pleuritis vs, 510\nDesmoplastic response, 17\nDesmoplastic small round cell tumor, 79t, \n158t\u2013160t, 163t\u2013171t\nDetritic synovitis, 250\u2013251, 260\nDF3 see Epithelial membrane antigen\nDFSP see Dermatofibrosarcoma \nprotuberans\nDFSP (dermatofibrosarcoma protuberans), \n163t\u2013171t\nDiagnosis\nvs description, 19, 19t\nerrors and pitfalls, 219\u2013221\nlung lesions, 60, 222\ngross descriptions and, 13\ninfections, 185\u2013186\ninstitutional consultations, 41\u201342\noperating room consultations, 49\u201350\ndeferred, 57, 62\nprior to pathology request, 3\nreporting, 36\u201337, 36t\nrevision, 37\u201338\nrush, 4\u20135\nDiagrams, with gross descriptions, 13\nDialysis-associated amyloidosis, 107t\nDialysis-related amyloidosis, 260\nsee also Beta-2 microglobulin amyloidosis\nDiamniotic twin placentas, 460\u2013464, 462f\nDiaphragm, margins, 507\nDichorionic twin placentas, 460\u2013464, 462f\nDieterle, 67t\u201370t\nDiethylstilbestrol\nclear cell carcinoma and, 448t\nFallopian tubes and, 446\nDifferential diagnosis, gross, 225\nDiff-Quik stain, 67t\u201370t\nintraoperative cytology, 49\nDiffuse type gastric carcinoma, 330, 331f\nDiffuse type giant cell tumor, 247, 260\ndiagnostic pitfalls, 223\nDigital images, processing, 215\nDigits, amputations, 238\nDilaminar multiple gestation placentas, \n460\u2013464\nDilated cardiomyopathy, 302\nDirect immunofluorescence, 161\nDiscovered on GIST-1 see DOG1\nDiscrepancies\nbreast pathology, 219\ngross descriptions, 13\noperating room consultations, 50\u201351\nsecond reviews, 41\u201342\nsee also Errors\nDiscs, intervertebral, 260\u2013261\nDisposal\nbiological materials, 201\u2013202\ngross specimens, 5, 24\nchemicals, 24\nsharps, 24\nDissection, 10, 13\naortic, 305\naxillary, 276\u2013279\nAJCC classification, 279t\nbreast ducts, 285\nfetus, 468\u2013469\nlower extremity, 239\u2013241, 240f\nneck, 475\u2013479\nfor photography, 215\nretroperitoneal lymph nodes, \n416\nDistal aspect, 7f\nDistal pancreatectomy, 372\u2013374, 372f\nDistal urethral margin, radical \nprostatectomy specimen, 406\nDistant metastases\nanal adenocarcinoma, 356t\nbreast carcinoma, 262t, 279t\ncolon carcinoma, 350, 353t\u2013354t\nesophagus carcinoma, 323t, 328t\nmelanoma, 311, 318t\npancreatic carcinoma, 381\nskin carcinoma, 314, 315t\u2013319t\nsmall intestine carcinoma, 337t\nstomach carcinoma, 334t\nDiverticula\nMeckel\u2019s, 336\u2013337\nsolitary cecal, 345, 357\nZenker\u2019s, 336\u2013337\nDiverticulosis, 344\u2013345, 344f, 349\u2013350\nDNA\nfixation and, 21\u201322\nlymphoproliferative disorders, 515\nsee also Ploidy analysis\nDocumentation, gross descriptions and, 13\nDOG1, 109t\u2013150t\nDorsal aspect, 7f\nDorsalis pedis artery, 239\nDPB see CD antigens, CD45RA\nDPC4\ngene mutations, 163t\u2013171t\nimmunohistochemistry, 109t\u2013150t\nDrugs\nof abuse, 526\nclinical history, 3\u20135\nDuct dissection, nipple, 285\nDuctal adenocarcinoma, pancreas, 376f\nDuctal carcinoma, breast, \nimmunohistochemistry panel, \n75t\u201376t\nDuctal carcinoma in situ (DCIS), breast, \n266, 266f, 269\ndiagnostic pitfalls, 222\nestrogen receptors, 86\nexcisional biopsy, 269\nHER-2/neu, 87\nmyoepithelial markers, 88t\nnuclear grades, 283t\noperating room consultations, 53\u201354\nreexcisions, 270\nsign-out checklists, 276\u2013279\nDuodenectomy see Whipple procedure\nDuodenum see Whipple procedure\nDura, biopsy of, 530\nDysplasia-associated lesion or mass \n(DALM), inflammatory bowel \ndisease, 345\nE\nE2 antigen see CD antigens, CD99\nEar, stapes, 484\nEBERS see EBV-encoded \nnonpolyadenylated early RNAs\nEBNA 2, immunohistochemistry, 109t\u2013150t\nEburnation, 247\u2013248\nfor gross description, 18t\nEBV see Epstein-Barr virus\nEBV-encoded nonpolyadenylated early \nRNAs, 109t\u2013150t\nE-cadherin, 109t\u2013150t\nEctopic pregnancy, 466\ntubal, 446\nEdema, fetus, 471\nEdge artifact, immunoperoxidase studies, 71", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_590.png", "summary": "The page covers various topics in surgical pathology including histological appearance of cytomegalovirus, immunohistochemistry, decalcification, degeneration of heart valves, and differential diagnosis.", "questions": [ "What are some common pitfalls in diagnosing desmoplastic melanoma and desmoplastic mesothelioma?", "How does decalcification affect different types of specimens like bone biopsy and large resections?", "What are the key differences between dialysis-associated amyloidosis and dialysis-related amyloidosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 591, "text": "573\nIndex\nEdmondson and Steiner grading, \nhepatocellular carcinoma, 365t\nEDTA, antigenicity and, 70\u201371\nEdwards-Duromedics heart valve, 298f\nEGFR see Epidermal growth factor receptor\nEIC see Extensive intraductal component\nElastic laminae, pleura, 502f\nElastic stains, 67t\u201370t\nElectron microscopy (EM), 157\ncells, tumors, and structures, 158t\u2013160t\nendomyocardial biopsy, 289\nmesothelioma vs lung carcinoma, 101t\nperipheral nerves, 533\npoorly differentiated tumors, 158t\nsarcomas, 541\nsoft tissue tumors, specimen preparation, \n62\nEllipse biopsy, stains and levels for, 32t\u201333t\nEllipses, skin, 53, 312\u2013319\nElston-Ellis modification, Scarff-Bloom-\nRichardson grading system, breast \ncarcinoma, 281t, 326\nEM see Electron microscopy\nEM ACT (HHF-35), 109t\u2013150t\nEMA see Epithelial membrane antigen\nEmbedding of tissues, 30\nfrozen sections, 47\norientation, 30\u201331\nEmboli, breast carcinoma, 278b\nEmbryonal carcinoma\nimmunohistochemistry panel, 75t\u201376t, 96t\ntestis, 414\nEmbryonal rhabdomyosarcoma, genetics, \n163t\u2013171t\nEmbryonal sarcoma, 364\nEmbryos, 467\u2013468\nE-MEL see HMB-45\nEmergencies, peritonitis, diverticular \ndisease, 345\nEmphysema, 498\nEn face margins, 11\u201312, 11f\nEncapsulated follicular lesion, thyroid \ngland, 556f\nEncephalitis, brain biopsy, 528\nEnchondroma, 254, 254f\nEndarterectomy specimens, 305\nEndobronchial biopsy, 494\nstains and levels, 32t\u201333t\nEndocarditis, 292, 293f, 296t\nEndocrine tumors\npancreas, 376, 376f, 379t\u2013380t\nWHO classification, 380t\nsee also Neuroendocrine tumors\nEndodermal sinus tumor, testis, 414\nEndometrial carcinoma, 432\ncervix carcinoma vs, 92t\nimmunohistochemistry panel, 75t\u201376t\noperating room consultations, 57\u201358\nreporting, 436\nsign-out checklist, 433\nstaging classifications, 434t\u2013445t\nEndometrial stromal sarcoma, 80t\u201383t, \n163t\u2013171t, 432, 436\nleiomyosarcoma vs, 92t\nEndometrioid carcinoma\ngrading, 436\novary\nimmunohistochemistry, 92t\nsign-out checklist, 443\u2013444\nEndometrioid neoplasms, ovary, 442\nEndometrioma see Endometriotic cyst\nEndometriosis\nappendix, 357\nFallopian tube, 426\nhernia sacs, 487\nEndometriotic cyst, 441\ncolor, 17t\nEndometrium\nbiopsy, 423, 424t\ndating, Noyes Criteria, 424t\ndecidualized, placental villi vs, 59t\ngross differential diagnosis, 432\u2013433\nmicroscopy, 426, 430\nspecimens, 466\ntumors\nhysterectomy, 427\u2013429\nsee also Endometrial carcinoma; \nEndometrial stromal sarcoma\nEndomyocardial biopsy, 289\u2013290\nEndophytic\nfor gross description, 18t\ntongue and oral tumors, 476f\nEndosalpingiosis, 444\nEndoscopic sinus surgery, functional, 473\nEndothelial cells, 158t\u2013160t\nEndothelial cell antigen see HECA-452\nEndotracheal tubes, 2\nEnteropathy-type T-cell lymphoma, \n105t\u2013106t, 172t\u2013178t\nEntire specimen submitted (ESS), 15\nEnvironmental exposure, infectious agents, \n197t\nEosin, hematoxylin and eosin technique, \nfrozen sections, 48\nEpendymoma, immunohistochemistry, \n95t\nEpidermal growth factor receptor (EGFR)\ncolon carcinoma, 163t\u2013171t\nimmunohistochemistry, 109t\u2013150t\nmutations, lung adenocarcinoma, 84t\u2013\n85t, 163t\u2013171t\nEpidermal inclusion cyst, 313\nEpidermoid cysts, testis tumors, 414\nEpididymis, 413\u2013416\nin hernia sac, 487\nEpiploic appendages, colon segments, 340f, \n342t\nEpithelial membrane antigen (EMA)\ncarcinomas, 158t\nimmunohistochemistry, 109t\u2013150t\nEpithelial mesothelioma, lung \nadenocarcinoma vs, 101, 101t\nEpithelial specific antigen see Ber-EP4\nEpithelioid hemangioendothelioma, 80t\u2013\n83t, 163t\u2013171t\nEpithelioid sarcoma\ngenetics, 163t\u2013171t\nimmunohistochemistry panel, 77t\u201378t, \n80t\u201383t\nEpithelioid trophoblastic tumor, 93t\nEpstein-Barr virus (EBV)\nhistological appearance, 184\nsee also EBNA 2; EBV-encoded \nnonpolyadenylated early RNAs; \nLMP-1 (latent membrane \nprotein)\nER see Estrogen receptors\nErrors, 219\u2013221\nErysipelas, necrotizing fasciitis vs, operating \nroom consultations, 53\nESA see Ber-EP4\nEsophagectomy, 324\u2013328, 325f\noperating room consultations, 54\u201355\nEsophagus, 323\u2013328\nbiopsy, 323\ncarcinoma, 15\nadenocarcinoma, 74t, 324, 325f, 327t\nAJCC classification, 327, 328t\ngastrectomy specimens, 326\nafter radiotherapy, 325\nsign-out checklist, 326\u2013328\nsquamous cell carcinoma, 77t\u201378t, \n324\u2013325, 325f, 327t\nesophagectomy, 324\u2013328, 325f\nfungal infection of, 186t\u2013189t\nESS see Entire specimen submitted\nEssential thrombocythemia, genetics, \n172t\u2013178t\nEsthesioneuroblastoma, 79t\nEstrogen receptors (ER)\nbreast carcinoma, 84t\u201385t, 86\u201387, 265\nevaluation of, 86\u201387, 86t\nimmunohistochemistry, 109t\u2013150t\ninternal control for, 71\nEthanol (laboratory chemical)\ndisposal, 24\nspecimen preparation for photography, \n215\nEthics, research, 43\nETV6-NTRK3 fusion, 163t\u2013171t\nEwing\u2019s sarcoma, 158t\u2013160t\ndifferentiation score, 548t\u2013549t\ngenetics, 163t\u2013171t\nimmunohistochemistry panel, 79t\nresection, 253\u2013255, 254f\ntreatment response grades, 258t\nEwing\u2019s sarcoma marker see CD antigens, \nCD99\nExcisional biopsy, breast, 263\u2013267\nmammographic lesions with wire \nlocalization, 268\u2013270\npalpable masses, 264\u2013267\nExcisions\nlip, 321, 321f\nskin (large), 319\u2013320\nExcrescence, for gross description, 18t\nExfoliation, skin, frozen sections, 53\nExophytic\nfor gross description, 18t\ntongue and oral tumors, 476f\nExpert consultants, legal cases, 42\nExtensive intraductal component (EIC), \nbreast carcinoma, 262t\nExtracapsular invasion, lymph node \nmetastases, 522\nExtracellular immunoreactivity, 72f\nExtraneous tissue, 33\u201334\nExtranodal lymphoma, 522\nExtranodal NK/T-cell lymphoma, nasal \ntype, 106t, 172t\u2013178t\nExtrapleural pneumonectomy, \n505\u2013510\noperating room consultations, 62\nExtraprostatic extension, prostate \ncarcinoma, 186t\u2013189t\nExtraskeletal myxoid chondrosarcoma, \n80t\u201383t, 163t\u2013171t", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_591.png", "summary": "This page covers a variety of topics related to surgical pathology, including staining techniques, specific tumor types, and surgical procedures.", "questions": [ "What are some common staining techniques mentioned on this page?", "How are embryonal carcinoma and embryonal rhabdomyosarcoma distinguished?", "What is the significance of the En face margins mentioned in the text?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 592, "text": "574\nIndex\nExtraskeletal osteosarcoma, differentiation \nscore, 548t\u2013549t\nEye protection, infection precautions, 65\nEyepieces, 204\nreticles, 214\nEyes, 531\u2013532\nF\nFace masks, infection precautions, 65\nFactor VIII, internal control for \nimmunohistochemistry, 71\nFactor VIII-related antigen, 109t\u2013150t\nFactor XIIIa, 109t\u2013150t\nFading, chromogens, 73\nFalcon tubes, fine needle aspirations, 309\nFallopian tubes, 444\u2013448\nmicroscopy\ncervical carcinoma, 430\u2013431\nmicroscopy, 426, 428\novarian specimens, 443\nsecondary carcinoma, 446\ntumor staging classifications, 462f\nFalse knots, umbilical cord, 460\nFamilial adenomatous polyposis, 181t\u2013183t\nFamilial medullary thyroid carcinoma, \n181t\u2013183t\nprophylactic thyroidectomy, 557, 559\nFamilial nephrolithiasis, 391t\nFamily history, neuropathology, 527t\nFasciitis, operating room consultations, 53\nFascin, 109t\u2013150t\nFast myosin, 109t\u2013150t\nFat\nmicrovesicular, liver biopsy, 362\nsee also Lipids\nFatty change, liver, pregnancy, 362\nFatty tissues\nfrozen sections, 46\nhistologic processing, 28\u201330\nF\u00e9d\u00e9ration Nationale des Centres de Lutte \nContre le Cancer (FNCLCC)\nsarcoma grading, 546, 547t\u2013548t\ntumor differentiation score, \n548t\u2013549t\nFeminization, adrenal adenomas, \n228\u2013229\nFemoral head, 249\u2013250\ndecalcification, 23\u201324\nFerruginous bodies, 206t\u2013212t\nFESS see Functional endoscopic sinus \nsurgery\nFetal death, Massachusetts law, 466\nFetus, 467t, 468\u2013470, 488\nhydrops fetalis, 93t\nsign-out checklist, 471\u2013472\nFetus papyraceus, 460, 463\nFibrin stains, 67t\u201370t\nFibroadenoma, breast, 266, 266f, 284t\nFibrocystic changes, breast, 267\nFibroepithelial polyp, 313\nFibrolamellar hepatocellular carcinoma, \n99t, 363, 363f\nFibroma, ovary, 442\nFibromatosis, 91t\ndesmoid, genetics, 163t\u2013171t\nimmunohistochemistry panel, 80t\u201383t\nFibromyxoid sarcoma, low grade, genetics, \n163t\u2013171t\nFibronectin, 109t\u2013150t\nFibrosarcoma\ndifferentiation score, 548t\u2013549t\nimmunohistochemistry panel, 80t\u201383t\ninfantile, genetics, 163t\u2013171t\novary, 442\nFibrosing pleuritis, desmoplastic \nmesothelioma vs, 510\nFibrous dysplasia, 253\u2013254, 254f\nFibroxanthoma, atypical, \nimmunohistochemistry panel, \n80t\u201383t\nField diameters, microscopy, 213\nField diaphragms, microscopes, 204b\nFIGO classifications\ncarcinomas\ncervix, 434t\nendometrium, 434t\u2013445t, 436\novary, 445t\nvagina, 434t\nFallopian tube tumors, 462f\nFiloviruses, 199t\u2013200t\nFimbriated, for gross description, 18t\nFine needle aspiration (FNA), 309\ninstitutional consultations, 42\nintraoperative cytology specimens, 49\nthyroid carcinoma, operating room \nconsultations, 63\nFingernails, 322\nFingers, amputations, 238\nFIP1L1-PDGFRalpha fusion, 172t\u2013178t\nFish-mouth stenosis, 18t\nFite-Faraco stain, 67t\u201370t\nFixation, 21\u201324\nbone biopsy, 252\u2013253\non breast carcinoma antigenicity, 265\ncalcification and, 263\nby clinicians, 5\ndisposal of chemicals, 24\nfor electron microscopy, 157\nfine needle aspirations, 309\nfrozen sections after, 48\ngout and, 4t\nhistological processing and, 30\nimmunogenicity and, 70\u201371\ninfection hazard and, 201\nCreutzfeldt-Jakob disease, 21, 198, \n528\nlymph nodes, 514\u2013516, 518\nmolecular genetics and, 161\u2013162\nreturn of specimens to patient, 24\u201325\nstudies, 541\ntime recorded, 3\nurinary calculi and, 403\nsee also specific fixatives\nFLI-1 (Friend leukemia integrin site 1), \n109t\u2013150t\nFloaters (extraneous tissue), 33\u201334\nFlow cytometry, 184\nbladder carcinoma, 400\nbreast carcinoma, 265\nbreast masses, 265\nfixation and, 22\nlymph nodes, operating room \nconsultations, 61\nlymphoproliferative disorders, \n514\u2013515\npediatric renal tumors, 389b\nsubmission of specimens, 4t\nFluids, consistency descriptions, 18t\nFluorescence in situ hybridization (FISH), \nHER-2/neu, breast carcinoma, 87, \n87t, 263, 265\nFMC 29 see CD antigens, CD99\nFMC7, immunohistochemistry, 109t\u2013150t\nFNA see Fine needle aspiration\nFNCLCC see F\u00e9d\u00e9ration Nationale des \nCentres de Lutte Contre le Cancer\nFNH see Focal nodular hyperplasia\nFocal glandular atypia, prostate biopsy, 404\nFocal nodular hyperplasia (FNH), liver, \n362, 363f\nFoci (lymphoid aggregates), lip biopsy, 479\nFollicular adenoma, thyroid, \nimmunohistochemistry panels, 100t\nFollicular carcinoma, thyroid, 557, 558\nencapsulated, 556f\ngenetics, 163t\u2013171t\nimmunohistochemistry, 75t\u201376t, 84t\u2013\n85t, 100t\noperating room consultations, 63\nFollicular cyst, ovary, 440\nFollicular lymphoma\nB-cell, 103t\u2013104t\ngenetics, 172t\u2013178t\ngrading, 516t\nFontana-Masson stain, 67t\u201370t\nFood analogies, gross descriptions, 18t\nFood consumption, laboratory hazard, 65, \n201\u2013202\nFoot length, gestational age vs, fetus, 467t\nFootplates, microscope slides, 215\nForeign bodies, 2, 526\nForeign materials, 525\njoint prostheses, 251\nmicroscopy, 206t\u2013212t\nForeskin, 321\u2013322\nFormalin, 22, 206t\u2013212t\ncalcification and, 263\nCreutzfeldt-Jakob disease, 198, 528\ndisposal, 24\nfrozen sections of fixed specimens, 48\nimmunogenicity and, 70\ninfection hazard and, 201\nlymphoproliferative disorders, 61\nreturn of specimens to patient, 25\nstudies, 541\nsee also Quick-fix formalin\nFormalin pigment, malaria pigment vs, \n206t\u2013212t\nFormats, gross descriptions, 13\u201315\nFormic acid, Creutzfeldt-Jakob disease, 198, \n528\nFractures, hip, 250\nFragmented specimens\nbiopsies, 243, 244f\nfrozen sections, 46\u201348, 50\nhistologic processing, 30, 33\nmeasurement, 16\nFrancisella tularensis, 199t\u2013200t\nFreezing\nmuscle biopsy, 533\u2013534\nsarcoma biopsy, 541\nsee also Frozen sections; Snap freezing\nFreezing artifact\ndiagnostic pitfalls, 222\nsee also Ice crystal artifact\nFriable, for gross description, 18t\nFriend leukemia integrin site 1 see FLI-1", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_592.png", "summary": "The page covers a wide range of topics in surgical pathology, including factors related to immunohistochemistry, tissue processing, and specific conditions like fibromatosis and fibrosarcoma.", "questions": [ "What is the significance of Factor VIII in immunohistochemistry?", "How does fixation impact the antigenicity of breast carcinoma?", "Can you explain the differences between fibromatosis and fibrosarcoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 593, "text": "575\nIndex\nFrozen sections, 45\naccuracy, 50\u201351\nbreast biopsy, 54\ncolon, 55\ninappropriate, 45\u201346\ninfection hazard, 47, 65, 201\nlymphoproliferative disorders, 514\u2013515\nperipheral nerves, 533\npleural biopsy, 510\nproducts of conception, 58\nradial sclerosing lesions of breast and, \n267\nreport headings, 37\nsentinel lymph nodes, 54\nskin lesions, 52, 310\nsoft tissue tumors, 62\nspecimen processing, 46\u201349\nsubmission of specimens, 4t\nthyroid carcinoma, 63\nFuhrman nuclear grading system, renal cell \ncarcinoma, 393t\nFunctional endoscopic sinus surgery \n(FESS), 473\nFunctional neck dissection, 475\nFungi, histological appearance, 67t\u201370t\nFurcate insertion, umbilical cord, 460\nFused twin placentas, 460\u2013464, 462f\nFVIII:RAg see Factor VIII-related \nantigen\nG\nGal-3 see Galectin-3\nGalectin-3, 109t\u2013150t\nGallbladder, 366\u2013370\ncarcinoma, 367\u2013369\nAJCC classifications, 334t\ngrading, 370t\nsign-out checklist, 326\nstrawberry, 18t, 367\nGallstones, 368\ncase of ingestion, 25\nchemical analysis, 370\nreturn to patient, 25, 368\nGamna-Gandy nodules, 206t\u2013212t\nGanglioglioma, immunohistochemistry, 95t\nGanglion cells, immunohistochemistry of \nmelanoma, 317t\nGanglioneuroblastoma, adrenal, 229\nShimada classification, 232, 232f\nGanglioneuroma, adrenal, 229\nGangrene, gallbladder, 367, 369\nGardner syndrome, 181t\u2013183t\nGastrectomy, 329\u2013333\noperating room consultations, 54\u201355\npartial see Whipple procedure\nGastric, adenocarcinoma, 74t\nGastric lymph nodes, pancreatic carcinoma, \n380\nGastrinoma, 379t\nGastroesophageal junction, 326\ncarcinoma, 326\ngastrectomy specimens, 326\nGastrointestinal stromal tumor (GIST), \n84t\u201385t, 163t\u2013171t, 331, 543\u2013544\nAJCC classification for, 550t\nrisk stratification of, 549t\nGastrointestinal tract, 323\nappendix, 340f, 342t, 355\u2013359, 356f\ncarcinoma, 357\u2013359, 359t\nGastrointestinal tract (Continued)\ncolon, 337\u2013355\nbiopsy, 338, 339f\ncarcinoma, 326, 342\u2013351, 344t\u2013346t, \n347f\u2013348f, 352b, 353t\u2013354t\ndiverticulosis, 344\u2013345, 344f, \n349\u2013350\nidentifying segments, 338\u2013355, \n340f\u2013341f, 342t\ninflammatory bowel disease, \n345\u2013346, 346t, 347f, 350\npolyposis syndromes, 346\ndiagnostic pitfalls, 222\nesophagus, 323\u2013328\nbiopsy, 323\ncarcinoma, 324\u2013328, 325f, 327t\u2013328t\nesophagectomy, 324\u2013328, 325f\nfungal infection of, 186t\u2013189t\ngallbladder, 366\u2013370\ncarcinoma, 324, 367\u2013369, \n327t, 370t\nstrawberry, 367\nhemorrhoids, 359\u2013360\nliver, 360\u2013366\nbiopsy, 360\u2013362\ncopper metabolism disease, 362\nhepatocellular carcinoma, 362\u2013363, \n363f, 365t\nlobectomy, 362\u2013366\ntumors, 36, 328t\nMeckel\u2019s diverticulum, 336\u2013337\nneuroendocrine tumors, germline \nmutations, 179t\u2013180t\noperating room consultations, 54\u201356\nsmall intestine, 334\u2013336\nbiopsy, 335\ncarcinoid tumor, 335\ncarcinoma, 335\u2013336, 336t\u2013337t\nresection, 335\u2013336\nstomach, 329\u2013333\nbiopsy, 329\ncarcinoma, 330, 331f, 332\u2013333, \n333t\u2013334t\nesophagectomy specimens, 324, 326\ngastrectomy, 329\u2013333\nstromal tumors, 80t\u201383t\nGauze, artifacts from, 244\nGCDFP15 see Gross cystic disease fluid \nprotein-15\nGefitinib (Iressa), 84t\u201385t, 163t\u2013171t\nlung carcinomas responding, genetics, \n163t\u2013171t\nGel bleed, breast implants, 286\nGelfoam, microscopy, 206t\u2013212t\nGenitourinary tract, 384\nambiguous genitalia, 471\ndiagnostic pitfalls, 222\noperating room consultations, \n56\u201357\nGerm cell tumors\ngenetics, 163t\u2013171t\nimmunohistochemistry, 96t\nmarkers, 84t\u201385t\ntestis, 414\nthymus, 552\nGermline mutations\nadrenal tumors, 228\nlesions, 178\u2013184, 181t\u2013183t\nGerota\u2019s fascia, 387\nGestational age\nfetus, 467t\nplacental weight vs, 465t\numbilical cord length vs, 464\nGestational trophoblastic tumors, 433\nclassification, 435t\u2013452t\nprognostic score, 436t\nsign-out checklist, 326\nsee also Choriocarcinoma\nGFAP see Glial fibrillary acidic protein\nGiant cell tumors, 254, 254f, 260\ndiffuse type, 247\ndiagnostic pitfalls, 223\ngenetics, 163t\u2013171t\nGiemsa stain, 67t\u201370t\nsee also Diff-Quik stain\nGIST see Gastrointestinal stromal tumor\nGleason grading, prostate carcinoma, \n411\u2013412, 411t\nGleevec (imatinib mesylate), 84t\u201385t, \n163t\u2013178t\nGlial fibrillary acidic protein (GFAP), \n109t\u2013150t\nGlioblastoma multiforme, genetics, \n163t\u2013171t\nGlioma, brain biopsy, 61\u201362, 528\nGlobe, eye, 531, 531f\nGlomus tumor, 80t\u201383t\nGlottis, 489\u2013490, 490f\nGloves, 201\nhandling fixatives, 22\ninfection precautions, 65\nGlucagonoma, 379t\nGlucose transporter 1 see GLUT-1\nGLUT-1 (glucose transporter 1), 109t\u2013150t\nGlutaraldehyde (fixative), 23\nGlycogenated tumors, vagina, staining, \n453\nGlycophorin A (GPA), 109t\u2013150t\nGold, microscopy, 206t\u2013212t\nGomori stains, 67t\u201370t\ntrichrome, 67t\u201370t\nGordon and Sweets stain, 67t\u201370t\nGore-Tex (graft material), 206t\u2013212t, 306\nGorlin syndrome, 181t\u2013183t\nGout, 247\u2013248\narthroplasty specimens, 248\ncolor of tophi, 17t\nfixation of specimens, 23\nsubmission of specimens, 4t\nsynovium, 259\u2013260\nsee also Uric acid\nGowns, infection precautions, 65\ngp80 see Clusterin\ngp200 see RCC\nGPA see Glycophorin A\nGPIIIa see CD antigens, CD61\nGrading, anal adenocarcinoma, 355t\nGrading systems, 326\nampulla of Vater tumors, 382t\nbreast carcinoma, 278b, 281t\u2013285t\ncardiac transplantation rejection, \nISHLT, 291t\ncholangiocarcinoma, 365t\ncolon carcinoma, AJCC, 354t\nesophagus carcinoma, 327t\ngallbladder adenocarcinoma, 370t\nhepatocellular carcinoma, Edmondson \nand Steiner, 365t", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_593.png", "summary": "The page covers a wide range of topics in surgical pathology, including frozen sections, lymphoproliferative disorders, skin lesions, soft tissue tumors, thyroid carcinoma, and various gastrointestinal tract conditions.", "questions": [ "How are frozen sections used in surgical pathology?", "What are some common skin lesions that are discussed on this page?", "Can you explain the significance of the Fuhrman nuclear grading system for renal cell carcinoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 594, "text": "576\nIndex\nGrading systems (Continued)\ninfiltrating ductal carcinomas, pancreas, \n380t\nsmall intestine carcinoma, 336t\nsquamous cell carcinoma, 314t\u2013315t\nstomach adenocarcinomas, 333t\nGrafts (vascular), 306\ncoronary artery bypass grafts, 301\u2013303, \n306\nmaterials, microscopy, 206t\u2013212t\nGram stain, 67t\u201370t\nGranular cell tumors, 80t\u201383t, 158t\u2013160t\nneural, 80t\u201383t\nGranulomas, silicone, 286\nGranulomata, Gamna-Gandy nodules, \n206t\u2013212t\nGranulosa cell tumors, 96t, 442\nGranzyme B, 109t\u2013150t\nGrape vesicle (food analogy), 18t\nGraves\u2019 disease, 557\nGreater omentum, tumor invasion, 330\nGreek derivations\ncolor, 17t\nmedical terms, 19\u201320\nGrimelius stain, 67t\u201370t\nGrocott methenamine-silver nitrate, \n67t\u201370t\nGross appearance, before removal from \npatient, 3\nGross cystic disease fluid protein-15 \n(GCDFP15), 109t\u2013150t\nas breast carcinoma marker, 84t\u201385t\nGross descriptions, 13\u201319, 35\nbreast masses, 264\nconsult cases, 43\u201344\nerror avoidance, 220\u2013221\nexample of, 16\nformatting of, 13\u201315\noperating room consultations, 46\nfor specialist consultations, 40\nstyle of, 19\nGross differential diagnosis, 225\nGross examination, 9\u201310, 420\nerrors, 219\nphotography, 215\u2013216\nrepeat after microscopy, 222\nGross sectioning, 10\nGynecology, 423\ncarcinoma grading, 435\u2013436\noperating room consultations, 57\u201358\nGynecomastia, 287, 412t\nH\nH222 see Estrogen receptors\nHaemozoin, 206t\u2013212t\nHair, 2, 28\nHair whorls, fetus, 471\nHairy cell leukemia\ngenetics and, 172t\u2013178t\nimmunohistochemistry, 103t\u2013104t\nspleen, 523\nHamartomas\nbile ducts, 364\nchondroid, pulmonary, 500\nmesenchymal, liver, 364\nsee also PTEN hamartoma syndrome\nHamartomatous polyps\njuvenile, germline mutations, 179t\u2013180t\nsee also Peutz-Jeghers syndrome\nHamazaki-Wesenberg bodies, 206t\u2013212t\nHancock porcine aortic valve bioprosthesis, \n297f, 300f\nHand washing, 201\u2013202\nHarken heart valves, 298f\u2013299f\nHashimoto\u2019s thyroiditis, specimen \nappearance, 556\nHassell\u2019s corpuscles, 552\nHAV see Hepatitis A virus\nHazards see Safety aspects\nHb see Hemoglobin\nHBME-1, 109t\u2013150t\nHBV see Hepatitis B virus\nH-caldesmon see Caldesmon\nH-CAM see CD antigens, CD44v3 \n(variant 3)\nhCG see Human chorionic gonadotropin\nHCL see DBA.44\nHCV see Hepatitis C virus\nHead and neck, 473\ndiagnostic pitfalls, 223\nresections, operating room \nconsultations, 58\u201359\nsquamous cell carcinoma\ndiagnostic pitfalls, 223\nimmunohistochemistry panel, \n77t\u201378t\nHeadings, reports, 35\u201337, 36t\nHeart, 289\nanatomy, 301f\nbiopsy, stains and levels, 32t\u201333t\nendomyocardial biopsy, 289\u2013290\nfetus, 468\nfungal infection of, 186t\u2013189t\nmyocardium, 304\nmyxoma, germline mutations, 179t\u2013180t\nrhabdomyoma, germline mutations, \n179t\u2013180t\nrhabdomyosarcoma, spider cells, \n158t\u2013160t\ntransplantation\nendomyocardial biopsy, 289\u2013290\nrejection grading, 291t\nspecimens (recipient\u2019s heart), \n299\u2013303\nvalves, 291\u2013295, 293f\u2013294f\netiologic assessment, 296t\ngross morphologic assessment, 295t\nprosthetic, 295\u2013299, 297f, 300t\nventricular assist devices, 303\u2013304, 304f\nHeartMate ventricular assist device, 303, \n304f\nHeavy immunoglobulin chains, \n109t\u2013150t\nHECA-452, 109t\u2013150t\nHelicobacter pylori\nAlcian yellow, 67t\u201370t\nas hazard, 196b\nsee also Diff-Quik stain\nHemangioblastoma, immunohistochemistry, \n95t\nHemangiopericytoma\ndifferentiation score, 548t\u2013549t\nimmunohistochemistry, 95t\nHematin, 206t\u2013212t\nHematolymphoid proliferations, molecular \ngenetics, 161\u2013162\nHematopoietic progenitor cell, class 1 see \nCD antigens, CD34\nHematoxylin and eosin, 67t\u201370t\nfrozen sections, technique, 48\nintraoperative cytology, 49\nHemochromatosis\nendomyocardial biopsy, 290\ncolor, 247\nsynovium, 260\nliver biopsy, 361\nHemoglobin (Hb), immunohistochemistry, \n109t\u2013150t\nHemorrhage\ncolor, 17t\nmicroscopy, 206t\u2013212t\nHemorrhoids, 359\u2013360\nHemosiderin, microscopy, 206t\u2013212t\nHemosiderosis, endomyocardial biopsy, 290\nHepatitis, chronic viral, grading and \nstaging, 361t\nHepatitis A virus (HAV), as hazard, 196b\nHepatitis B virus (HBV)\nas hazard, 196, 196b\nexposure risk, 197t\nhistological appearance, 184\nHepatitis C virus (HCV)\nas hazard, 196\u2013197, 196b\nexposure risk, 197t\nhistological appearance, 184\nHepatoblastoma, 99t, 163t\u2013171t, 364\nHepatocellular carcinoma, 362\u2013363, 363f\ngrading, Edmondson and Steiner, 365t\nimmunohistochemistry, 77t\u201378t, 99t\nTTF-1, 71\nHepatocyte paraffin-1 see HepPar-1\nHepatosplenic T-cell lymphoma, \n105t\u2013106t, 172t\u2013178t\nHepPar-1 (hepatocyte paraffin-1), \n109t\u2013150t\nHER1 see Epidermal growth factor receptor\nHER-2/neu, 265\nHER-2/neu amplification, breast \ncarcinoma, 163t\u2013171t, 263, 265\nas breast carcinoma marker, 84t\u201385t\nimmunohistochemistry, 109t\u2013150t\nscore, 87\u201388\nHerceptin see Trastuzumab\nHereditary cancer susceptibility, 178, \n181t\u2013183t\nHereditary diffuse gastric cancer syndrome, \n181t\u2013183t\nHereditary nonpolyposis colorectal \ncarcinoma (HNPCC), 163t\u2013171t, \n179t\u2013180t, 343\u2013344, 344t\nHereditary nonpolyposis syndrome, \n181t\u2013183t\nHernia sacs, 487\nlipomas, 541\u2013542\nHerpes gestationis, immunofluorescence, \n161\nHerpes simplex virus (HSV), histological \nappearance, 190t\u2013194t\nHHF-35 (actin antibody), 109t\u2013150t\nHHV-8 see Human herpes virus 8\nHHV-8 antibody, 109t\u2013150t\nHibernoma, genetics, 163t\u2013171t\nHigh power fields, microscopic \nmeasurement, 213\nHigh-grade papillary carcinoma, bladder, \n399t\nHilar cholangiocarcinoma, 363\u2013364", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_594.png", "summary": "This page covers topics such as grading systems for various carcinomas, vascular grafts, granulomas, and gross examination techniques.", "questions": [ "What are some common grading systems used for infiltrating ductal carcinomas?", "How are vascular grafts used in medical procedures, and what materials are typically used?", "What are some key characteristics of granulomas and how are they different from granulomata?", "What is the significance of Gross cystic disease fluid protein-15 (GCDFP15) as a breast carcinoma marker?", "How are Hamartomas and Hamartomatous polyps distinguished, and what are their implications in diagnosis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 595, "text": "577\nIndex\nHilar lymph nodes, 507\nHip see Total joint arthroplasty\nHirschsprung disease, 338\ngermline mutations, 179t\u2013180t\nHistochemistry, 67, 67t\u201370t\nsectioning for, 31\nstains, 67t\u201370t\nHistologic sectioning, 10\nHistology, 28\nprocessing, 28\u201330\nreporting, 15\nsectioning see Sectioning, histologic\nspecimens not needing, 420\ntissue selection, 20\nreporting of, 35\nsee also Microscopy\nHistoplasma capsulatum, 186t\u2013189t\nHistory see Clinical history\nHIV see Human immunodeficiency virus\nHLA typing, for tissue identification, 33\nHLA-DR, immunohistochemistry, 109t\u2013150t\nHMB-45\nimmunohistochemistry, 109t\u2013150t\nlymph node metastases, 520\nmelanoma marker, 85t, 317t\nmelanosomes, 158t\nHMFG see Epithelial membrane antigen\nhMLH1 (Human mutL homologue 1), \n109t\u2013150t\nmutation, colon carcinoma, 163t\u2013171t\nhMSH2 (Human mutS homologue 2), \n109t\u2013150t\nmutation, colon carcinoma, 163t\u2013171t\nHNK-l see CD antigens, CD57\nHNPCC see Hereditary nonpolyposis \ncolorectal carcinoma\nHodgkin disease\nAJCC classification, 516\nimmunohistochemistry, 106t\nlymph nodes, 515, 522\nnodular sclerosing, formalin for, 22\nstaging laparotomy, 522\u2013523\nsee also Nodular sclerosing\nHollende\u2019s solution, small intestine biopsy, \n335\nHollow structures, gross dissection, 10\nHomozygously deleted in pancreatic \ncarcinoma, locus 4 see DPC4\nHormone receptors, breast carcinoma, 263, \n265\nHP1 see HepPar-1\nHPCA-1 see CD antigens, CD34\nHPL see Human placental lactogen\nHPV see Human papilloma virus\nH-score see Allred score\nHSV see Herpes simplex virus\nHTLV-1 see Human T-cell leukemia virus\nHuLy-m6 see CD antigens, CD99\nHuman chorionic gonadotropin (hCG)\nimmunohistochemistry, 109t\u2013150t\nseminomas, 414\ntestis tumors, 415\nHuman herpes virus 8 (HHV-8), \nhistological appearance, 109t\u2013150t\nHuman immunodeficiency virus (HIV)\nas hazard, 196b, 197\nexposure risk, 197t\nundiagnosed, 64\u201365\nhistological appearance, 184\nHuman mutL homologue 1 see hMLH1\nHuman mutS homologue 2 see hMSH2\nHuman papilloma virus (HPV)\ncervix, testing, 450\nhistological appearance, 184\ntumors, 84t\u201385t\nHuman placental lactogen (HPL), \n109t\u2013150t\nHuman T-cell leukemia virus (HTLV-1), \nhistological appearance, 109t\u2013150t\nHurthle cell nodules, parathyroid tissue \nresembling, 64\nHydatidiform moles, 93t, 433, 467\nsee also Molar pregnancy\nHydrochloric acid, on antigenicity, 70\u201371\nHydropic fetus, 93t\nHydropic villi, products of conception, 467\nHyperparathyroidism, 560, 561t\noperating room consultations, 63\u201364, 64t\nHyperplasia\nadrenal gland, 228, 229f\nmesothelial, hernia sacs, 487\npapillary endothelial, angiosarcoma vs, \n222\nparathyroid, 561\nprostate, 408\nthyroid gland, C-cells, 559\nHyperplastic nodule, thyroid, 100t\nHypertension, heart valves, 293f\nHypertrophic cardiomyopathy, \nendomyocardial biopsy, 290\nHysterectomy, 424\u2013436\nbenign conditions, 425\u2013427\nendometrial tumors, 427\u2013429\nmorcellated laparoscopic, 431\u2013436\nI\nIatrogenic materials\nbreast calcifications vs, 263\nmicroscopy, 206t\u2013212t\nIBD see Inflammatory bowel disease\nIce crystal artifact, 45\nsee also Freezing artifact\nIdentification\nclinicians, 2\u20133\npatients, 2\nspecimens and materials, 2, 9\nfor consultations, 43\u201344\nerrors, 219\nhistology, 32t\u201333t\nreporting and, 35\nresearch and, 43\nIdentification numbers, 9\nIdiopathic dilated cardiomyopathy, 302\nIdiopathic thrombocytopenic purpura, \nspleen, 523\nIL-2 receptor see CD antigens, CD25\nIleoanal pull-through reconstruction, total \ncolectomy with, 340\u2013341\nIleum, 340f, 342t\nImatinib mesylate, 84t\u201385t, 163t\u2013178t\nImmature teratoma, 440\u2013441, 443t\nomental biopsy, 440\nImmunocompromise, clinical history, 3\nImmunofluorescence, 161\nof skin lesions, 161\nImmunogenicity, factors affecting, 70\u201371\nImmunohistochemical markers, melanoma, \n317t\nImmunohistochemistry\nalternative names for antigens, \n151t\u2013157t\nantibodies for, 108, 109t\u2013150t\nB-cell neoplasms, 103t\u2013104t\nbreast carcinoma, 84t\u201385t, 86\u201388\ncontrols for, 28\nHodgkin lymphoma, 106t\nimmunofluorescence, 161\nliver tumors, 99t\nlymph nodes, 519\u2013520\nparathyroid lesions, 100t\nslides, 30, 70\nT-cell neoplasms, 109t\u2013150t\nthymus tumors, 552\nthyroid lesions, 100t\nuse of, 70\nsee also specific tumors\nImmunoperoxidase studies, 70\u2013108\nABH blood group antigens, for tissue \nidentification, 33\nevaluation, 71\u201373, 73t\nlymph nodes, 519\u2013520\nlymphoproliferative disorders, 514\u2013515\nparaganglioma, 536\nresults of, 108\nsectioning for, 31\nsee also specific lesions\nImmunoreactive cells\nidentification of, 72\nlocation of, 71\u201373, 72f\nnumber of, 72\nImplants (pathological), ovarian tumors, 440\nImplants (prosthetic), breast, 286\u2013287\nIncidental ovaries see Prophylactic \noophorectomy\nIncidental ribs, 258\u2013259\nIncidental tube, 446\n\u2018Incidentalomas,\u2019 adrenal adenomas, \n228\u2013229\nIncisional biopsy, breast carcinoma, 263\nInclusion cyst, epidermal, 313\nIndia ink, microscopy, 206t\u2013212t\nIndirect immunofluorescence, 161\nInfantile polycystic kidney disease, 391t\nInfarction, placenta, 463\nInfections, 49, 184, 196\naerosol sprays for freezing tissues, 47, \n196\nair-dried smears (hazard), 201\nappendix, 357\nbone marrow, 514\nbrain biopsy, 528\nbronchoalveolar lavage, 308\u2013309\ncritical values of, 39\ndiagnosis of, 185\u2013186\nfine needle aspirations, 309\nidentification of, 185t\nimmunohistochemistry and, 70\nintervertebral discs, 261\nopen lung biopsy, 60\u201361\noperating room consultations and, 64\u201365\nplacentas (hazard), 201, 463\nrevision arthroplasty, 250\u2013251\noperating room consultations, 52\nspecimen fixation and, 25\nsubmission of specimens, 4t\nsynovium, 260\nsee also Creutzfeldt-Jakob disease", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_595.png", "summary": "This page covers various topics related to histology, histochemistry, immunohistochemistry, and specific markers used in pathology.", "questions": [ "What is the significance of HLA typing for tissue identification?", "How are hormone receptors used in the evaluation of breast carcinoma?", "What are the implications of Human immunodeficiency virus (HIV) exposure in histopathology?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 596, "text": "578\nIndex\nInfective endocarditis, 292, 293f, 296t\nInferior aspect, 7f\nInferior oblique muscles (ocular), 531, 531f\nInfertility, testis biopsy, 412, 413b\nInfiltrating carcinoma, vulva, 457\nInfiltrating ductal carcinoma, pancreas, \ngrading, 380t\nInfiltration\ncolorectal carcinoma, 352b\nhistologic processing, 28\nInflammation, airway, 496t\nInflammatory bowel disease (IBD), \n345\u2013346, 346t, 347f, 350\noperating room consultations, 55\u201356\nInflammatory carcinoma, breast, 265\nskin biopsy, 285\nInflammatory myofibroblastic tumor, \ngenetics, 163t\u2013171t\nInflation\nbladder, 396\nlung resections, 498\nInformation for histology laboratory, 30\u201331\nInhibin, 84t\u201385t\nalpha subunit, 109t\u2013150t\nINI-1, 109t\u2013150t\nINII, mutations, 163t\u2013171t\nInjuries to health care staff, prevention, \n201\u2013202\nsee also Safety aspects\nInk marking\nmordants for, 12\nslides for measurement, 213\nspecimens, 3, 10\u201312, 541\nbreast biopsy, 264\nbreast mastectomy, 274\nembedding and, 30\nhysterectomy, 427\u2013429\nlung resections, 497\nprior to morcellation, 386\nskin ellipses, 312\nstomach, 329\nInstitute of Medicine, report on errors, 218\nInstitutional consultations, 41\u201342\nas legal consultations, 42\nInsulinoma, 379t\nInsurance\ninstitutional consultations, 42\nlegal consultations, 42\nInterest Group staging system, 511t\nIntergroup Rhabdomyosarcoma Study \n(IRS), postsurgical clinical grouping \nsystem, 546, 547t\nInterinstitutional consultations see \nInstitutional consultations\nInterleukin-3 receptor alpha chain see CD \nantigens, CD123\nInternal controls, immunohistochemistry, \n71\nInternational Mesothelioma Interest Group \nstaging system, 511t\nInternational Society for Heart and Lung \nTransplantation (ISHLT), grading of \ncardiac rejection, 291t\nInterpretative errors, operating room \nconsultations, 50\u201351\nIntervertebral discs, 260\u2013261\nIntervillous thrombus, placenta, 464\nIntestinal type gastric carcinoma, 330, 331f\nIntracranial hemorrhage, 530\nIntradepartmental consultations, reporting, \n35\u201336\nIntraductal papillary mucinous neoplasms, \npancreas, grading, 377\nIntrainstitutional consultations, 40\nIn-transit metastases, melanoma, definition, \n318t\nIntraoperative consultations see Operating \nroom consultations\nIntraoperative cytology, 48\u201349\nIntratubular germ cell neoplasms, 96t\nInvasion depth, melanoma, 315t\u2013317t\nInvasive carcinoma, breast, 265, 275\naxillary dissections, 276\u2013279\ngrading, 281t\nsign-out checklists, 276\u2013279\nInverted papilloma, ureter, 395\nIonescu-Shiley bovine pericardial \nbioprosthesis, 297f, 300f\nIressa see Gefitinib\nIris diaphragms, microscopes, 204b\nIron compounds, microscopy, 206t\u2013212t\nIron stain, 67t\u201370t\nIrregular borders, for gross description, 18t\nIRS see Intergroup Rhabdomyosarcoma \nStudy\nIschemic heart disease, 301\u2013303\nISHLT see International Society for Heart \nand Lung Transplantation\nIsotopes, radioactive see \nRadiopharmaceuticals\nJ\nJ5 see CD antigens, CD10\nJagged borders, for gross description, 18t\nJatene-Macchi heart valve, 298f\nJC virus\nbrain biopsy, 528\nhistological appearance, 184\nJCAHO see Joint Commission on \nAccreditation of Healthcare \nOrganizations\nJewett and Strong staging, Marshall \nmodification, bladder carcinoma, \n395t\nJoint Commission on Accreditation of \nHealthcare Organizations (JCAHO)\nguidelines for submitting specimens, 2\nretention of gross specimens, 5t, 24\nspecimens not needing histology, 420\nJoint mice, knee, 259\nJoints\nfungal infection, 186t\u2013189t\nmenisci, 259\ntotal arthroplasty, 246\u2013251\nrevision, 52, 52t, 250\u2013251\nsee also Prosthetic joints\nsee also Synovium\nJone\u2019s silver methenamine, 67t\u201370t\nJOVI 1 see TCR\nJugular vein, radical neck dissections, 478\nJunctional nests, melanocytes, 316t\nJuvenile hamartomatous polyps, germline \nmutations, 179t\u2013180t\nJuvenile myelomonocytic leukemia, \ngenetics, 172t\u2013178t\nJuvenile polyposis syndrome, \n181t\u2013183t\nJuxtaoral organ of Chievitz, 59\nK\nKaposi sarcoma-associated herpesvirus \n(KSHV), histological appearance, \n109t\u2013150t\nKaposi\u2019s sarcoma, 80t\u201383t\nKaryotyping see Cytogenetics\nKatskin tumor, 363\u2013364\nKayexalate (sodium polystyrene sulfonate), \n206t\u2013212t\nKay-Shiley heart valve, 298f\nKay-Suzuki heart valve, 298f\nKeratins see Cytokeratin(s)\nKi-1 see CD antigens, CD30\nKi-1 lymphoma (anaplastic large cell \nlymphoma), 105t\u2013106t, 172t\u2013178t\nKi-67 (MIB-1), 109t\u2013150t\ncytoplasmic and membranous \nimmunoreactivity, 71\nKidney, 384\u2013395\nangiomyolipoma, 391\ngermline mutations, 179t\u2013180t\nbiopsy, 384\u2013385\noperating room consultations, 57\nstains and levels, 32t\u201333t\nsubmission of specimens, 4t\nclinical history, 384t\u2013385t\nfungal infection of, 186t\u2013189t\ntumors\nimmunohistochemistry, 97t\nsign-out checklist, 392 \nsee also specific tumors\nsee also Nephrectomy\nKikuchi disease, lymph nodes, 515\nKimura scoring system, \npheochromocytoma, 233, 235t\nKinyoun stain, 67t\u201370t\nKip 2 see p57\nKIT protein, 84t\u201385t, 163t\u2013178t\nsee also CD antigens, CD117 (c-Kit)\nKnee\nmenisci, 259\ntotal joint arthroplasty, 246\u2013251\nsee also Total joint arthroplasty\nKnots, umbilical cord, 460\nKoehler illumination, 204, 204b\nKP1 see CD antigens, CD68\nKrukenberg tumor, 442\nKSHV see Kaposi sarcoma-associated \nherpesvirus\nL\nL1 antigen see MAC 387\nL26 see CD antigens, CD20\nLabeling\nconfusion with diagnoses, 221\nphotography, 216\nsee also Paperwork\nLabia\nfetus, 471\nlinguistics, 455, 455t\nLaboratory Response Network (LRN), \n198\nLacerations, spleen, 523\nLaminin, 109t\u2013150t\nLandmarks see Orientating specimens\nLangerhans cell histiocytosis, 158t\u2013160t\nLangerin see CD antigens, CD207\nLaparoscopic cholecystectomy, 366", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_596.png", "summary": "This page covers a wide range of topics in surgical pathology, including various types of carcinomas, inflammatory conditions, and consultative practices.", "questions": [ "What are some key considerations when grading infiltrating ductal carcinoma of the pancreas?", "How are ink markings used in different types of surgical procedures?", "What are the roles of International Mesothelioma Interest Group staging system and International Society for Heart and Lung Transplantation in grading and classification?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 597, "text": "579\nIndex\nLaparoscopic nephrectomy with \nmorcellation, 386\u2013387\nLaparotomy, staging Hodgkin disease, \n522\u2013523\nLaplace\u2019s law, 345\nLardaceous spleen, 18t\nLarge B-cell lymphoma, 103t\u2013104t\nanaplastic large cell lymphoma, 106t, \n172t\u2013178t\nLarge cell calcifying Sertoli cell tumors, \ngermline mutations, 179t\u2013180t\nLarge cell carcinoma, lung, 102t, 499\ngrade, 501t\nLarge cell neuroendocrine carcinoma\ncarcinoid tumor v., 102t\nlung, 501t\nLarge core needle biopsy, breast, 262\u2013263\nLarge excisions, skin, 319\u2013320\nLarge resections, 241\u2013242\nLaryngectomy, 489\u2013492\nLarynx, 489\nanatomy, 490f\nbiopsy, stains and levels, 32t\u201333t\ncarcinoma, 489\u2013492\nclinical history, 489t\ntumor classification, 492t\u2013493t\nLatent membrane protein see LMP-1\nLateral aspect, 7f\nLatex gloves, 201\u2013202\nLatin derivations, medical terms, 19\u201320, 20t\nLCA (leukocyte common antigen) see CD \nantigens, CD45\nLeaflets, heart valves, 291\nLeaf-like protuberances, phyllodes tumor, \n267\nLEEP see Loop electrocautery excision \nprocedure\nLegal aspects\namputations, 238\nbreast implants, 286\u2013287\nconsultations, 40\u201341\ndisposal and release of specimens, 5, 25\nforeign bodies, 526\nmodified reports, 37\u201338\nproducts of conception, 466\nLegal consultations, 42\nLeiomyomas\nbreast lesions v., 91t\nesophagus, 326\nimmunohistochemistry panel, 80t\u201383t\noperating room consultations, 58\nuterus, 425\u2013426, 432\ngenetics, 163t\u2013171t\nLeiomyosarcomas, 432, 543\ndifferentiation score, 548t\u2013549t\nendometrial stromal sarcoma vs, 92t\nimmunohistochemistry panel, 80t\u201383t\nLens (eye), 532\nLens paper\ncleaning of microscopes, 214\nsmall biopsies, 244\nLesions\ngross descriptions, 14\nimmunohistochemistry and, 70\nLetters\ninstitutional consultations, 42\u201343\nspecialist consultations, 40\nLeu 1 see CD antigens, CD5\nLeu 2 see CD antigens, CD8\nLeu 3 see CD antigens, CD4\nLeu 5a+b see CD antigens, CD2\nLeu 7 see CD antigens, CD57\nLeu 9 see CD antigens, CD7\nLeu 16 see CD antigens, CD20\nLeu 22 see CD antigens, CD43\nLeukemias\ngenetics, 172t\u2013178t\nspleen, 523\ntestis, 414\nsee also specific types\nLeukocyte common antigen see CD \nantigens, CD45\nLeukocytoclastic vasculitis, 44\nLeuM1 see CD antigens, CD15\nLevels\nClark, melanoma, 317t\nlymph nodes, 519\naxillary, 276\nradical neck dissections, 478\nin sections, 28\nsee also Sectioning\nLewis blood group y antigen, 109t\u2013150t\nLeydig cell tumors, 96t, 414\nLFA-2 see CD antigens, CD2\nLibman-Sacks endocarditis, 292, 293f\nLichen sclerosus, vulva, 456\nLiesegang rings, 206t\u2013212t\nLi-Fraumeni syndrome, 181t\u2013183t\nLight, microscopes, 204\nLight immunoglobulin chains, 109t\u2013150t\nLillehei-Kaster heart valve, 298f\nLinitis plastica, 330, 331f\nLip\nexcisions, 321, 321f\nsalivary gland biopsy, 479\nLipids\nfixation and, 21\nmicroscopy, 206t\u2013212t\nLipoblastoma, genetics, 163t\u2013171t\nLipofuscin, microscopy, 206t\u2013212t\nLipomas, 541\u2013543\ngenetics, 163t\u2013171t\nsee also Cord lipomas\nLiposarcomas, 543\ndifferentiation score, 548t\u2013549t\ngenetics, 163t\u2013171t\nhernia sacs, 487, 541\u2013542\nLiver, 360\u2013366\nacute fatty, submission of specimens, 4t\nbiopsy, 360\u2013362\nHodgkin disease staging, 522\u2013523\npre-transplant operating room \nconsultations, 56\nstains and levels, 32t\u201333t\ncopper metabolism disease\nspecial studies, 362\nsubmission of specimens, 4t\nfungal infection of, 186t\u2013189t\nhepatocellular carcinoma, 362\u2013363, \n363f, 365t\nlobectomy, 362\u2013366\nnutmeg, 18t\ntumors\nAJCC classification, 328, 366\nhepatoblastoma, 99t, 163t\u2013171t\nimmunohistochemistry, 99t\nsign-out checklist, 326\nsee also Hepatocellular carcinoma\nLKB1/STK11, loss of heterozygosity, \n163t\u2013171t\nLMP-1 (latent membrane protein), \n109t\u2013150t\nLN1 see CDw75\nLN2 see CD antigens, CD74\nLobation, placentas, 463\nLobectomies\nliver, 362\u2013366\nlung, 497\noperating room consultations, 60\nLobular carcinoma, breast, 90f, 90t\nimmunohistochemistry panel, 75t\u201376t\nmetastases, diagnostic pitfalls, 222\nLobular carcinoma in situ (LCIS), breast, \nsign-out checklists, 276\u2013279\nLoop electrocautery excision procedure \n(LEEP), cervix, 450\u2013453\nLoose bodies, knee, 259\nLost specimens, 12\u201313\nLower extremity, amputations, 239\u2013241, \n240f\nLower uterine segment, microscopy, 426, \n428\ncervical carcinoma, 430\nLow-grade papillary carcinoma, bladder, \n399t\nLRN see Laboratory Response Network\nLugol\u2019s solution, vagina, 453\nLumpectomy see Reexcisions\nLung, 494\nadenocarcinoma, 75t\u201376t, 84t\u201385t, 101, \n101t\u2013102t, 163t\u2013171t, 498, 499f\nbronchial extension, 60\nepithelial mesothelioma vs, \n101, 101t\nbiopsy, 60\u201361, 494\u2013495, 497\nstains and levels, 32t\u201333t\ncarcinoma, 102t\nbronchioloalveolar, 75t\u201376t, 102t, \n158t\u2013160t, 499f\nclassification, 501t, 503t\ngrading system, 77t\npleural involvement, 497, 502f, 506\nsign-out checklist, 500\nsquamous cell carcinoma, 77t\u201378t, \n102t, 498, 499f\nsee also Small cell carcinoma\nclinical history, 494t\ndiagnostic pitfalls, 222\nfungal infection of, 186t\u2013189t\nneuroendocrine tumors, 501t\noperating room consultations, 59\u201361\nreports, example headings, 36t\nsclerosing hemangioma, Ki-67, 71\nLupus band test, 161\nLVI see Venous/lymphatic Invasion \n(lymphovascular invasion)\nLymph nodes, 10\u201311, 514\u2013522\nanal adenocarcinoma, 354, 356t\naxillary dissections, 276\u2013279\nAJCC classification, 279t\nbladder carcinoma, 396\nBouin\u2019s solution, 10, 518\nbreast carcinoma, 262t, 266, 279t\nAJCC classification, 279t\nimmunohistochemistry, 519\u2013520\nsentinel, 521\u2013522\nsee also Axillary dissections", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_597.png", "summary": "The page covers various topics related to surgical pathology, including different types of tumors, procedures, anatomical structures, and legal aspects.", "questions": [ "What are some examples of large cell tumors mentioned on this page?", "How are breast leiomyomas differentiated from leiomyosarcomas?", "What legal aspects related to pathology are discussed in this page?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 598, "text": "580\nIndex\nLymph nodes (Continued)\nclinical history, 513t\ncolon carcinoma, 342\u2013343, 350, \n353t\u2013354t\ncystic duct, 367\u2013368\nesophagectomy, 324, 326, 426\nFallopian tube specimens, 426\nhernia operations, 487\nHodgkin disease, 515, 522\nstaging laparotomy, 522\nlymphoproliferative disorders, 514\u2013516\noperating room consultations, 61\nmastectomy, 274, 276\nmediastinum, operating room \nconsultations, 59\nmelanoma, 311, 318t, 520\nmicroscopy, 515\nneck, radical dissections, 476\npancreatic carcinoma, 372, 373, 375, \n377\u2013379\nparaganglioma, 536\nparathyroid tissue vs, 64\npleura, 497\nretroperitoneal dissection, testis \ncarcinoma, 326\nsecond reviews, 41\nsentinel\nbreast carcinoma, 521\u2013522\nhistological processing, 31\nimmunohistochemistry, 520\noperating room consultations, 54\nstains and levels, 32t\u201333t\nskin carcinoma, 314, 315t\u2013319t\nsmall intestine carcinoma, 336, 337t\nsoft tissue tumors, 542\nstomach carcinoma, 332, 334t\nthyroid carcinoma, operating room \nconsultations, 63\ntonsillectomy, squamous cell carcinoma, \n484\u2013485\ntumor staging, 516\u2013520\nureteric tumors, 392\nLymphangitic spread, lung carcinoma, \npleural involvement, 497\nLymphocyte-depleted Hodgkin disease, \n106t\nLymphocyte-rich Hodgkin disease, 106t\nLymphocytic thyroiditis, specimen \nappearance, 556\nLymphoepithelial carcinoma, 74t\nLymphoid aggregates (foci), lip biopsy, 479\nLymphomas\nbone, 254f\nbrain biopsy, 528\nelectron microscopy, 158t\nextranodal, 522\nfine needle aspirations, 309\ngenetics, 172t\u2013178t\nimmunohistochemistry, 79t, 95t, \n103t\u2013104t, 106t\nkidney, 390\nliver biopsy, 362\nlymph nodes, 515\nmarkers, 84t\u201385t\nmissed diagnosis, 223\nribs, 258\u2013259\nsalivary glands, 480\nsign-out checklist, 515\u2013516\nspleen, 523\nLymphomas (Continued)\nstaging, 517t\nstomach, 330\nsubmission of specimens, 4t\ntestis, 414\nthymus, 552\nspecimen processing, 551\u2013552\nLymphoplasmacytic lymphoma, 103t\u2013104t\ngenetics, 172t\u2013178t\nLymphoproliferative disorders, lymph \nnodes, 514\u2013516\noperating room consultations, 61\nLymphovascular invasion (venous/lymphatic \ninvasion)\nbreast carcinoma, 262t\nRosen criteria, 278b\nstromal sarcoma, uterus, 432\nLynch syndrome see Hereditary \nnonpolyposis colorectal carcinoma\nLysozyme, 109t\u2013150t\nM\nM2-7C10 see Melan-A\nM2A see D2-40\nM130 see CD antigens, CD163\nM3558 see Smooth muscle myosin heavy \nchain\nM4276 see Fast myosin\nMAC 387 (antibody), 109t\u2013150t\nMac-1 see CD antigens, CD11b\nMac-M see CD antigens, CD68\nMacule, for gross description, 18t\nMagnification, photomicroscopy, 215\nMalaria pigment, 206t\u2013212t\nMalignant fibrous histiocytoma (MFH), \ndifferentiation score, 548t\u2013549t\nMalignant mixed mesodermal tumor, \nuterus, 432\nMalignant peripheral nerve sheath tumor \n(MPNST), 543\nimmunohistochemistry panel, 80t\u201383t\nMalignant rhabdoid tumor, differentiation \nscore, 548t\u2013549t\nMalignant triton tumor, differentiation \nscore, 548t\u2013549t\nMalignant tumors\ndifferentiation score, 548t\u2013549t\nreporting, 36\nMallory\u2019s PTAH (phosphotungstic acid-\nhematoxylin), 67t\u201370t\nMALT lymphoma see Marginal zone \nlymphoma\nMammaglobin, 109t\u2013150t\nMammographic lesions with wire \nlocalization, excisional biopsy, breast, \n268\u2013270\nMammoplasty, reduction, 281\u2013285\nMandible, frozen sections, 52\nMantle cell lymphoma, 103t\u2013104t\ngenetics, 172t\u2013178t\nMarginal insertion, placental membranes, \n460\nMarginal zone lymphoma (MALT), \n103t\u2013104t\ngenetics, 172t\u2013178t\nMargins\nbreast carcinoma, 266\nexcisional biopsy, 263\u2013264, 270\nmastectomy, 274\u2013276\nMargins (Continued)\noperating room consultations, 54\nreexcisions, 271\ncolon carcinoma, 343, 348\u2013349\nen face, 11\u201312, 11f\nesophagectomy, 326\ngastrectomy, 332\nhead and neck resections, 58\u201359\nmelanoma, 311\noperating room consultations\nbreast carcinoma, 54\nbreast DCIS, 54\npancreatic carcinoma, 377, 379\nperpendicular, 11f, 12\nskin carcinoma, 314t\nsmall intestine resection, 336\nsoft tissue tumors, 542\nMarshall modification, Jewett and Strong \nstaging, bladder carcinoma, 395t\nMART-1\nlymph node metastases, 520\nmelanoma marker, 85t, 317t\nsee also Melan-A\nMasaoka\u2019s staging, thymic tumors, 553t\nMassachusetts, law on products of \nconception, 466\nMasson\u2019s lesion, angiosarcoma vs, 223\nMasson\u2019s trichrome, 67t\u201370t\nmodified, 67t\u201370t\nMast cells, 158t\u2013160t\nMast cell tryptase, 109t\u2013150t\nMastectomy, 272\u2013276, 275f\nfor gynecomastia, 287\nprophylactic, 280\u2013281\nMastocytosis, genetics, 172t\u2013178t\nMature teratoma see Dermoid cyst\nMaude cell lymphoma, 172t\u2013178t\nMayer stain (mucicarmine), 67t\u201370t, 101t\nmb-1 protein see CD antigens, CD79a\nMCAM see CD antigens, CD146\nMcGovern-Cromie heart valve, 299f\nMCV see Merkel cell polyoma virus\nMDM2, 109t\u2013150t\nME491 see CD antigens, CD63\nMeasles virus, histological appearance, \n190t\u2013194t\nMeasurement, 10\nbreast lesions, operating room \nconsultations, 53\nin gross descriptions, 14, 16\nmicroscopy, 213\u2013214, 213t\nMeckel\u2019s diverticulum, 336\u2013337\nMediastinal large B-cell lymphoma, \n103t\u2013104t\nMediastinal staging, lung carcinoma, \noperating room consultations, 59\nMedical devices, 2, 525\nMedical records, pathology reports as, 38\nMedtronic Freestyle stentless porcine aortic \nvalve prosthesis, 297f\nMedtronic-Hall tilting disk valve, \n297f\u2013298f\nMedullary carcinoma\nbreast, 265, 266f\nthyroid, 158t\u2013160t, 556f, 557\nfamilial, 181t\u2013183t\nfamilial prophylactic thyroidectomy, \n557, 559\ngenetics, 163t\u2013171t", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_598.png", "summary": "This page discusses various lymph nodes related to different clinical conditions and procedures, as well as lymphomas and malignant tumors.", "questions": [ "What are some common procedures or conditions that involve lymph nodes?", "How is lymphoma diagnosed and staged?", "What is the significance of lymphovascular invasion in different types of carcinomas?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 599, "text": "581\nIndex\nMedullary carcinoma (Continued)\ngermline mutations, 179t\u2013180t\nimmunohistochemistry, 75t\u201376t, \n84t\u201385t, 100t\noperating room consultations, 63\nMedullary carcinoma-associated \namyloidosis, 107t\nMedullary cystic kidney disease, 391t\nMedullary sponge kidney, 391t\nMedulloblastoma\nbrain biopsy, special studies, 528\ngenetics, 163t\u2013171t\ngermline mutations, 179t\u2013180t\nimmunohistochemistry, 95t\nimmunohistochemistry panel, 79t\nMEDWATCH home page (website), \n525\u2013526\nMelan-A, immunohistochemistry, 109t\u2013150t\nMelanin, microscopy, 206t\u2013212t\nMelanin bleach, 67t\u201370t\nMelanocytes, junctional nests, 316t\nMelanocytic lesions, frozen sections and, 52\nMelanoma, 313\nAJCC classification, 315, 318t\nbiopsy, stains and levels, 32t\u201333t\ncolor, 17t\ndiagnostic pitfalls, 222\nelectron microscopy, 158t\neye, 532\nimmunohistochemical markers, 317t\nimmunohistochemistry, 95t\nimmunohistochemistry panels, 79t\u201383t\ninvasion depth, 315t\u2013317t\nlymph nodes, 520\nmarkers, 85t\nmetastases, 317, 318t\ndefinition, 318t\ndiagnostic pitfalls, 222\nnipple, 89t\nshave biopsy, 311\u2013312\nsign-out checklist, 314\nsubungual, 322\nMelanoma antigen recognized by T cells see \nMelan-A\nMelanoma cell adhesion molecule see CD \nantigens, CD146\nMelanoma-associated antigen see CD \nantigens, CD63\nMelanoma-specific antigen see HMB-45\nMelanosis coli, 206t\u2013212t, 349\nMelanosomes, 158t\nMELCAM see CD antigens, CD146\nMembranes, placenta, 458\u2013460, 464\nMembranous immunoreactivity, 71, 72f\nMEN1 gene, mutations, 179t\u2013183t\nMEN2A gene, mutations, 181t\u2013183t\nMEN2B gene, mutations, 181t\u2013183t\nMeningioma\nbrain biopsy, 529\ngenetics, 163t\u2013171t\nimmunohistochemistry, 75t\u201376t, 80t\u2013\n83t, 95t\nMeningoencephalitis, fungal infection, \n186t\u2013189t\nMenisci (knees), 259\nMercuric chloride, microscopy, 206t\u2013212t\nMercury, in fixatives, 23\u201324\nMerkel cell carcinoma, 77t, 79t, 158t\u2013160t\nAJCC classification, 320t\nMerkel cell polyoma virus (MCV), \nhistological appearance, 190t\u2013194t\nMesenchymal chondrosarcoma, 80t\u201383t\nMesenchymal hamartoma, liver, 364\nMesentery, colon segments, 340f, 342t\nMesh, small intestine biopsy specimens, 30\nMesoblastic nephroma\ncellular, 390\ncytogenetics, 390\ncongenital, 390\ngenetics, 163t\u2013171t\nMesodermal tumor, malignant mixed, \nuterus, 432\nMesorectal envelope, 351b\nMesothelial hyperplasia, hernia sacs, 487\nMesothelioma, 158t\u2013160t, 505\u2013510\nAJCC classification, 510t\ndesmoplastic\ndiagnostic pitfalls, 222\nfibrosing pleuritis vs, 510\nepithelial, lung adenocarcinoma vs, \nimmunohistochemistry, 101, 101t\ngenetics, 163t\u2013171t\nhernia sacs, 487\nimmunohistochemistry panels, 75t\u201376t, \n80t\u201383t\nInternational Mesothelioma Interest \nGroup staging system, 511t\noperating room consultations, 62\novarian carcinoma v., 91t\nperitoneum, 91t\npleura specimens, 510\u2013512\nrevised Sugarbaker staging system, \n509t\u2013510t\nsign-out checklist, 500\nMetabolic bone disease, biopsy, 251\nMetabolic diseases\nbrain biopsy, 528\nendomyocardial biopsy, 290\nplacental, 463\nMetal, microscopy, 206t\u2013212t\nMetanephric adenoma, 389\nMetastases\nadenocarcinomas, 101t\nin abdomen, 94t\nadrenal, clear cell renal cell carcinoma, \n97t\nadrenal gland, 229\u2013230\narthroplasty specimens, 248\nbone and joint specimens, 248\nbrain biopsy, 529\nbreast carcinoma, 266\nAJCC classification, 279t\ncarcinoid, 99t\ncolon, 348\nliver, 363f\ncolon carcinoma\nlung, 102t\novary, 92t\ndistant\nanal adenocarcinoma, 356t\nbreast carcinoma, 262t, 279t\ncolon carcinoma, 350, 353t\u2013354t\nesophagus carcinoma, 262t, 328t\nmelanoma, 311, 318t\npancreatic carcinoma, 378t, 381\nskin carcinoma, 314t\u2013319t\nsmall intestine carcinoma, 337t\nstomach carcinoma, 334t\nMetastases (Continued)\ngallbladder, 369\nimmunohistochemistry, 84t\u201385t, 95t\nintervertebral discs, 261\nintracranial hemorrhage, 530\nliver, 362, 363f, 364\ncolon carcinoma, 363f\nimmunohistochemistry, 99t\nlobular breast carcinoma, diagnostic \npitfalls, 222\nlung, 102t\ncolon, 102t\nlymph nodes, 515\nanal adenocarcinoma, 354, 356t\nbreast carcinoma, 266, 262t, 279t\nsee also Axillary dissections\ncolon carcinoma, 342\u2013343, 350, \n353t\u2013354t\nesophagus carcinoma, 262t, 328t\nmelanoma, 311, 318t\npancreatic carcinoma, 378t, 379\nsecond reviews, 41\nskin carcinoma, 314, 315t\u2013319t\nsmall intestine carcinoma, 336, 337t\nsquamous cell carcinoma, \ntonsillectomy, 484\u2013485\nstomach carcinoma, 332, 334t\ntumor staging, 516\u2013520\nmelanoma\ndefinition, 318t\ndiagnostic pitfalls, 222\novary, 442\ndiagnostic pitfalls, 223\nrenal cell carcinoma, diagnostic pitfalls, \n222\nribs, 258\u2013259\nthrombus, abdominal aortic aneurysms, \n305\nthyroid gland, immunohistochemistry, \n100t\ntonsillectomy, lymph nodes, squamous \ncell carcinoma, 484\u2013485\nof unknown origin, 84, 84t\u201385t\nsee also Lymph nodes; Micrometastases\nMetatarsophalangeal joint, great toe, lower \nlimb dissection, 239\nMethacarn, 23\nMethanol\ndisposal, 24\nfrozen sections, 47\nintraoperative cytology, 49\nmordant for inks, 12\nMethyl green-pyronin Y, 67t\u201370t\nMeyenburg complexes, 364\nMFH see Malignant fibrous histiocytoma\nMGB1 see Mammaglobin\nMIB-1 see Ki-67\nMIC-2 see CD antigens, CD99\nMichaelis-Gutmann body macrophages, \n206t\u2013212t\nMicrobiology, 185\u2013186\nopen lung biopsy, 61\nMicrometastases\nbreast carcinoma, frozen sections, 54\nlymph nodes, 519\u2013520, 522\nstage significance, 522\nmelanoma, definition, 318t\nMicrometers, 214\nMicronodular cirrhosis, 363f", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_599.png", "summary": "The page covers various topics related to pathology, including medullary carcinoma, melanoma, meningioma, Merkel cell carcinoma, mesothelioma, and metabolic diseases.", "questions": [ "What are the key differences between medullary carcinoma, melanoma, meningioma, Merkel cell carcinoma, mesothelioma, and metabolic diseases?", "How are these diseases diagnosed and classified?", "What are the common genetic mutations associated with these diseases?", "What are the specific immunohistochemical markers used in the diagnosis of these diseases?", "What are the staging systems and diagnostic pitfalls to be aware of for each of these diseases?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 600, "text": "582\nIndex\nMicrophthalmia transcription factor see \nMITF\nMicrosatellite markers, for tissue \nidentification, 33\nMicroscopes, 204\nMicroscopic descriptions, 35\nMicroscopic sections, 225\nMicroscopy, 204\nerrors, 219\u2013220\nperipheral nerves, 533\ntissue selection for, 20\nsee also Histology\nMicrotomes, 29f, 30\nMicrovesicular fat, liver biopsy, 362\nMicrovilli, mesothelioma vs lung carcinoma, \n101t\nMiliary nodules, spleen, 523\n\u2018Milk of calcium,\u2019 263\nMiller-Payne grading system, response to \nchemotherapy, 283t\nMinocycline\nmicroscopy, 206t\u2013212t\nthyroid specimen appearance, 556\nMiscarriage (spontaneous abortion), 466\nMissing specimens, 12\u201313\nMITF, 109t\u2013150t\nMit-f see MITF\nMitochondrial myopathies, endomyocardial \nbiopsy, 290\nMitosis scores, measurement, 213\nMitotic count scoring, breast carcinoma, \n282t\nMitral valve, 291\u2013295, 293f\u2013294f\nfunction, 296t\ngross morphologic assessment, 295t\nmyxomatous degeneration, 292, 296t\npostinflammatory scarring, rheumatic \nvalve disease, 292\nprolapse, 293f\nMixed mesodermal tumor, malignant, \nuterus, 432\nMixed tumor (pleomorphic adenoma), \n75t\u201376t, 163t\u2013171t, 479\u2013480\nMixed-cellularity Hodgkin disease, 106t\nMN-4 see CD antigens, CD146\nMNF-116 see PAN-K\nModernization Act (FDAMA), 525\nModified radical mastectomy, 272, 273f\nModified reports, 37\u201338, 220, 223\nMolar pregnancy, 466\u2013472\nMolecular genetics, 161\u2013162\nMolluscum contagiosum, histological \nappearance, 190t\u2013194t\nMonoamniotic twin placentas, 460\u2013464, \n462f\nMonocarboxylase transporter 1, 158t\u2013160t\nMonochorionic twin placentas, 460\u2013464, \n462f\nvascular anastomoses, 463\nMonozygous twin placentas, 460\u2013464\nMorcellation\nlaparoscopic hysterectomy with, 431\u2013\n436\nlaparoscopic nephrectomy with, 386\u2013387\nMordants, for inks, 12\nMounting medium, 215\nMouse double minute 2 homolog\n see MDM2\nMPO see Myeloperoxidase\nMRF-4 see Myf-4\nMSA (HHF-35), actin antibody, 109t\u2013150t\nMSH6, 109t\u2013150t\nMSI-H colon carcinoma, MSS colon \ncarcinoma v., 344t\nMSS colon carcinoma, MSI-H colon \ncarcinoma v., 344t\nMTS1 see p16\nMUC1 see Epithelial membrane antigen\nMUC2, 109t\u2013150t\nMUC18 see CD antigens, CD146\nMucicarmine see Mayer stain\nMucin, appendix, 327, 357\nMucinous, for fluid consistency \ndescriptions, 18t\nMucinous bronchioloalveolar carcinoma, \n158t\u2013160t\nMucinous carcinomas\nbreast, 92t, 94t\nbronchioloalveolar, 102t\ncolon, metastasis to ovary, 92t\ngynecology, grading, 435\u2013436\nlung, metastatic colon cancer v., 102t\novary\nimmunohistochemistry, 91t\u201392t, 94t\noperating room consultations, 57\nsign-out checklist, 443\u2013444\nMucinous cystadenocarcinoma, ovary, 441f\nMucinous cystadenoma, ovary, 441f\nMucinous cystic tumors, pancreas, 376f, 377\nMucinous neoplasms\novary, 74t, 442\npancreas, intraductal papillary, 377\nMuciphages, gallbladder, 369\nMucoceles\nappendix, 357\ngallbladder, 369\nMucocutaneous exposure, infectious agents, \n197\nMucoepidermoid carcinoma\ngenetics, 163t\u2013171t\ngrading systems, 482t\u2013483t\nMucoepidermoid tumor, salivary gland, 480\nMucosa\ngallbladder, 367\u2013368\nupper respiratory tract, biopsy, 479\nMullerian inclusions, lymph nodes, 447\nMullerian remnants, hernia sacs, 487\nMultilocular cysts, operating room \nconsultations, 57\nMultinodular thyroid gland, 63, 556f\nMultiple endocrine neoplasia, 179t\u2013183t\nparathyroid hyperplasia, 561\nMultiple gestation placentas, 460\u2013464, 462f\nmicroscopy, 464\nspecial studies, 463\nMultiple lesions, specimen processing, 12\nMultiple myeloma see Myeloma\nMuscle\nbiopsy, 4t, 533\u2013534\ndifferentiation, Zenker\u2019s acetic fixative, \n23\ntumors, immunohistochemistry panels, \n80t\u201383t\nMuscle common actin antibody, \n109t\u2013150t\nMuscularis mucosae, bladder, 395\nMuscularis propria, streaming dissection, \ncolon carcinoma, 352b\nMy 7 see CD antigens, CD13\nMy 9 see CD antigens, CD33\nMY-32 see Fast myosin\nMyasthenia gravis, 552\nMycetoma, fungal infection, 186t\u2013189t\nMycoplasma, cultures, 185\u2013186\nMycosis fungoides, 105t\u2013106t, 172t\u2013178t\nMycotic aneurysm, 305\nMyelodysplastic syndromes, bone marrow, \n514\nMyelolipoma, adrenal, 230\nMyeloma\nbone, 254f\ngenetics, 172t\u2013178t\nimmunohistochemistry, 103t\u2013104t\npituitary adenoma vs, 223\nribs, 258\ndiagnostic pitfalls, 223\nMyeloperoxidase (MPO), 109t\u2013150t\nMyeloproliferative syndromes, bone \nmarrow, 514\nMyf-4, immunohistochemistry, 109t\u2013150t\nMyocardium, 304\nsee also Endomyocardial biopsy\nMyoD1, immunohistochemistry, 109t\u2013150t\nMyoepithelial markers, breast carcinoma, \n88, 88t\nMyofibroblastic tumors, \nimmunohistochemistry panel, breast, \n80t\u201383t, 91t\nMyogenin see Myf-4\nMyoglobin, 109t\u2013150t\nMyomectomy, operating room \nconsultations, 58\nMyometrium\nendometrial carcinoma invasion, 57\u201358, \n443\ngross differential diagnosis, 432\u2013433\nmicroscopy, 426\nMyospherulosis, 206t\u2013212t\nMyxoid chondrosarcoma, extraskeletal, \n80t\u201383t, 163t\u2013171t\nMyxoma, heart, germline mutations, \n179t\u2013180t\nMyxomatous degeneration, mitral valve, \n292, 296t\nN\nNails, 2, 322\nNANOG, 109t\u2013150t\nNasal polyps, 473\nNasal type extranodal NKIT-cell \nlymphoma, 105t\u2013106t, 172t\u2013178t\nNational Prion Disease Pathology \nSurveillance Center, 528\nNCAM see CD antigens, CD56\nNeck, radical dissections, 475\u2013479\nNecrosis, on immunoperoxidase studies, 71\nNecrotizing fasciitis, operating room \nconsultations, 53\nNeedle biopsy, 243, 244f\nbone tumor, 251\u2013252\nbreast, histological processing, 32t\u201333t\nliver, 360\u2013362\nsee also Core needle biopsy; Liver, \nbiopsy; Prostate, biopsy\nNeedlestick injury\nhepatitis B virus, 196\ninfectious agent exposure risk, 197t", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_600.png", "summary": "This page covers various topics related to microscopy, including descriptions, errors, tissue selection, and specific examples like microvesicular fat in liver biopsy and milk of calcium.", "questions": [ "What are some common errors that can occur during microscopy?", "How is tissue selection important in the process of microscopy?", "Can you explain the significance of microvesicular fat in a liver biopsy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 601, "text": "583\nIndex\nNeoplasms\nNephrectomy, 385\u2013395\npartial, 57\ntransitional cell carcinoma, 57\nNephroblastoma, 389\u2013390\ncytogenetics, 389\u2013390\ngenetics, 163t\u2013171t\nimmunohistochemistry panel, 79t\nsee also Wilms tumor\nNephrogenic rests, 390t\nWilms tumor, 389b\nNephrolithiasis, familial, 391t\nNeprilysin see CD antigens, CD10\nNerve biopsy, peripheral, 533\nNerve sheath tumor see Malignant \nperipheral nerve sheath tumor\nNestin, 109t\u2013150t\nNeuN, 109t\u2013150t\nNeural tumors, immunohistochemistry \npanels, 80t\u201383t\nNeuroblastoma, 158t\u2013160t\nadrenal gland, 229\nShimada classification, 232, 232f\nNeuroendocrine tumors\nappendix, 357\ngastrointestinal tract, germline \nmutations, 179t\u2013180t\nlung, 501t\npulmonary, classification, 501t\nradiography for, 185\nNeurofibromas, 80t\u201383t, 527t, 543\ngermline mutations, 179t\u2013180t\nimmunohistochemistry panel, 80t\u201383t\nNeurofibromatosis type 1, 181t\u2013183t\nNeuro-filaments (NFP), 109t\u2013150t\nNeuronal nuclei see NeuN\nNeurons, immunohistochemistry of \nmelanoma, 317t\nNeuron-specific enolase (NSE), 109t\u2013150t\nNeuropathology specimens, 527\nNevi, 313\nNevoid basal cell carcinoma syndrome, \n181t\u2013183t\nNevus cells, 317t, 520\nNF2, inactivation, 163t\u2013171t\nNFP see Neuro-filaments\nNipple\nbiopsy/duct dissection, 285\nmastectomy, 274, 275f, 276\nPaget\u2019s disease, 89t, 266\nNitrile gloves, 201\u2013202\nNK1-betab see HMB-45\nNK1/C3 see CD antigens, CD63\nNK-cell lymphoma, blastic, 105t\u2013106t, \n172t\u2013178t\nNK/T-cell lymphoma, nasal type \nextranodal, 105t-106t, 172t\u2013178t\nNodular fasciitis, 91t\ndiagnostic pitfalls, 223\nNodular hyperplasia\nprostate, 408\nthyroid, 557\nNodular lymphocytic predominant \nHodgkin disease, 106t\nNodular sclerosing Hodgkin disease, 206t\u2013212t\nformalin, 22, 61\ngrading, 516t\nimmunohistochemistry, 106t\nlymph nodes, 515\nNodular thyroid gland, 63\nNodule within a nodule, hepatocellular \ncarcinoma, 363\nNonbacterial thrombotic endocarditis, 292, \n293f\nNon-Hodgkin lymphomas, staging, 85t\nNoninvasive papillary urothelial \ncarcinomas, high grade and low \ngrade, 399t\nNonossifying fibroma, 254f\nNonspecific positivity, immunoperoxidase \nstudies, 72\nNormal structures, gross descriptions, 15\nNose, fungal infection of, 186t\u2013189t\nNotched borders, for gross description, 18t\nNottingham Histologic Score, breast \ncarcinoma, 277, 281t\nNoyes Criteria, endometrial dating, 424t\nNPM see Nucleophosmin\nNSE see Neuron-specific enolase\nNuchal thickening, fetus, 471\nNuclear antigen 2 see EBNA 2\nNuclear grades\nDCIS of breast, 283t\nof uterine tumors, 436\nNuclear immunoreactivity, 72, 72f\nNuclear medicine see Radiopharmaceuticals\nNucleic acids, fixation and, 21\u201322\nNucleophosmin (NPM), immunoreactivity, \n72\nNumbers, identification of specimens, 9, \n31\u201333, 35\nNumbers (counts), gross descriptions, 16\nNutmeg liver, 18t\nNylon specimen bags, 245\nO\nO13 see CD antigens, CD99\nObjectives (lens assemblies), microscopy, \n204\nOC125 see CA125\nOchronosis, color, 17t\nOCT blocks, safety precautions, 201\u2013202\nOct2 (octomer transcription factor), \n109t\u2013150t\nOCT-4, 84t\u201385t, 109t\u2013150t\nOctomer transcription factor see Oct2\nOctreotide nodes, radiography for, 185\nOcular reticles, microscopic measurement, \n214\nOil immersion microscopy, 204\u2013205, \n205b\nOil red O, 67t\u201370t\nOLIG2, 109t\u2013150t\nOligodendroglioma\ngenetics, 163t\u2013171t\nimmunohistochemistry, 95t\nOmentum\ncolon segments, 340f, 342t\novarian malignancy staging, 440\u2013444\nOmnicarbon heart valve, 298f\nOmniscience heart valve, 298f\nOn Line Mendelian Inheritance in Man \n(OMIM), 163t\u2013171t\nOncocytoma, 158t\u2013160t\ngenetics, 163t\u2013171t\nimmunohistochemistry panel, 97t\nkidney, 388f, 389\nOpen lung biopsy, 60\u201361, 497\nOperating room consultations, 45\naccuracy of, 50\u201351\nbone, 51\u201352\ncommon, 51\u201364\ncytology, 48\u201349, 184\ninfection in, 64\u201365\nperforming, 46\npleural biopsy, 510\npurpose of, 45\nquality control of, 51\nreporting, 35, 49\u201350\nskin, 52\u201353\nOptic nerve, 531, 531f\nOptical properties of microscopic objects, \n205\u2013213\nOptics, microscopes, 204\nOral cavity, 473\u2013475\nbiopsy, amyloidosis, 550\nsign-out for, 474\ntumor classification, 477t\nOrchiectomy\nbilateral simple, 418\nunilateral for tumor, 412\u2013416\nOrgan transplantation\nheart\nendomyocardial biopsy, 289\u2013290\nheart specimens (recipient\u2019s heart), \n299\u2013303\nrejection grading, 291t\nkidney, resection, 385\u2013386\nlung\nbiopsy, 494\u2013495\nrejection, 494\u2013495\nresections, 502\u2013504\nOrientating specimens, 6f\u20137f, 7\u201310\nexcisional biopsy, breast carcinoma, 264\nhistology, 30\u201331\nhysterectomy, 424, 425f\nlarge skin excisions, 319\u2013320\npartial nephrectomy, 392\nradical neck dissections, 477\u2013478, 478f\nOropharynx, biopsy, stains and levels, \n32t\u201333t\nOrthopedic hardware, 526\nOsseofibrous dysplasia, 254f\nOsteoarthritis see Degenerative joint disease\nOsteoblastoma, 254f\nOsteochondroma, 254, 254f\ngenetics, 163t\u2013171t\nOsteoid osteoma, 253, 254f\nOsteomyelitis, lower limb dissection, 239\nOsteonecrosis (aseptic necrosis, avascular \nnecrosis), 247, 249\narthroplasty specimens, 248, 250\ncore biopsy, 251\nOsteosarcomas, 253\u2013255, 254f\ndifferentiation score, 548t\u2013549t\ngenetics, 163t\u2013171t\nimmunohistochemistry panels, 80t\u201383t\ntreatment response grades, 258t\nOtosclerosis, 484\nOvary, 436\u2013444, 437f\ncarcinoma\nadenocarcinoma, 94t\nclassification of, 445t\ndiagnostic pitfalls, 223\ngermline mutations, 179t\u2013183t\nmesothelioma v., 91t\nomental staging biopsy, 440", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_601.png", "summary": "This page covers a wide range of topics related to neoplasms, including nephrectomy, nephroblastoma, neuroblastoma, neurofibromatosis, and nodular lymphocytic predominant Hodgkin disease.", "questions": [ "What are the key differences between nephroblastoma and Wilms tumor?", "How is neuroblastoma classified according to the Shimada classification?", "What are the diagnostic pitfalls associated with nodular fasciitis?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 602, "text": "584\nIndex\nOvary (Continued)\nprimary v. metastatic, 92t\nreporting, 436\nserous, 75t\u201376t, 91t\nsign-out checklist, 443\u2013444\nspecial studies, 440\ncervical carcinoma, 431\nclinical history, 437t\nendometrioid tumors, 75t\u201376t, 91t\u201392t\nimmunohistochemistry, 92t\nmicroscopy, 426, 428\nmucinous tumors, 74t, 91t\u201392t\noperating room consultations, 57\nsolid tumors, 437, 439\u2013440\nOversampling, 20\nOwl-eye bodies, 206t\u2013212t\nOwnership of specimens, 24\u201325\nOxalate\ncalculi, 403\nthyroid tissue vs parathyroid tissue, 64\nsee also Calcium oxalate\nP\np16 (protein), 109t\u2013150t\np53 (protein), 109t\u2013150t\np55 see Fascin\np57 (protein), 109t\u2013150t\np63 (protein), 109t\u2013150t\nbreast carcinoma, 88t\np80 (protein) see ALK protein\nP504S, 109t\u2013150t\nPackaging, sending slides for consultations, \n43\u201344\nPaget\u2019s disease\nof nipple, 89t, 266\nperianal, 89t\nvulvar, 89t\nPancreas, 370\u2013382\nbeta cells, dense core granules, 158t\u2013160t\nbiopsy, 372\ncarcinoma, 326, 372, 375\u2013377\nadenocarcinoma, 94t\nAJCC classifications, 334t, 381\nductal, 376f, 380t\nmetastasis to ovary, 92t\noperating room consultations, 56\nsign-out checklists, 332\ndiagnostic pitfalls, 222\ndistal pancreatectomy, 372\u2013374, 372f\nresection, 372\ntumors\nbeta-catenin, 72\nimmunohistochemistry panel, 74t\nWhipple procedure, 374\u2013382, 374f\nPancreatectomy\ndistal, 372\u2013374, 372f\npartial see Whipple procedure\nPancreatic duct, 373\nWhipple procedure, 374\u2013382, 374f\nPancreatic polypeptide, tumor producing, \n379t\nPancreatitis, chronic, 377\nPancreatoblastoma, 377\nPanels, immunohistochemistry markers, 70, \n73\u2013108\nPAN-K, 109t\u2013150t\nPanniculitis-like T-cell lymphoma, \n105t\u2013106t, 172t\u2013178t\nPAP see Prostate acid phosphatase\nPaperwork, 2, 9\nPapillary, for gross description, 18t\nPapillary carcinomas\nbladder, 399t\nkidney, genetics, 163t\u2013171t\npitfalls, 223\nthyroid, 556, 557, 556f\ncytology, 63\ngenetics, 163t\u2013171t\nimmunohistochemistry, 75t\u201376t, \n84t\u201385t, 100t\noperating room consultations, 63\nPapillary endothelial hyperplasia, \nangiosarcoma vs, 223\nPapillary muscles, heart valves, 291\nPapillary renal cell carcinoma, 388\nPapillary transitional cell carcinoma, 388f\nPapillary urothelial neoplasm of low \nmalignant potential (PUNLMP), \n395, 399t\nPapillary-like carcinoma, kidney, genetics, \n163t\u2013171t\nPapillomas\nbladder, 399t\nbreast duct dissection, 285\nureter, 392\nPapule, for gross description, 18t\nPapyraceous, for gross description, 18t\nParacoccidioides brasiliensis, 186t\u2013189t\nParaffin, histology, 28\nParaganglioma, 77t\u201378t, 97t, 535\nclinical history, 535t\nParametrium, microscopy, 428, 431\nParanasal sinuses, contents, 473\nParathyroid glands, 560\u2013563\nadenoma, 561, 562t, 563\ncarcinoma, 561, 562t\nclinical history, 561t\nimmunohistochemistry panels, 100t\noperating room consultations, 63\u201364, 64t\nin thyroid specimens, 555, 585\nthyroid tissue vs, 64\nParathyroid hormone\nhyperparathyroidism, 561t\noperating room consultations, 64\nPartial chest wall resection, \npneumonectomy with, 502\u2013504\nPartial cystectomy, 396\u2013400, 397f\nPartial gastrectomy see Whipple procedure\nPartial mole, 93t\nPartial neck dissections, 476\nPartial nephrectomy, 392\u2013395\nPartial pancreatectomy see Whipple \nprocedure\nParvovirus, as hazard, 196b\nParvovirus B19, histological appearance, \n190t\u2013194t\nPAS see Periodic acid Schiff\nPAS-D see Periodic acid Schiff with diastase \ndigestion\nPASS scoring system, pheochromocytoma, \n233, 234t\nPathologic evaluation, requests for, 2\nPathology errors, 219\u2013220\nPatients\nidentification, 2\u20133\nchange in, 38\ninstitutional consultations, 43\nresearch and, 43\nPatients (Continued)\ninitiating second reviews, 41\u201342\nreturning specimens to, 24\u201325\ngallstones, 367\northopedic hardware, 526\nPBX1-E2A fusion, 172t\u2013178t\nPear, unripe (food analogy), 18t\nPECAM-1 see CD antigens, CD31\nPEComa, immunohistochemistry panel, \n80t\u201383t\nPectoralis minor, axillary lymph node levels \nand, 276\nPediatrics\nadrenal tumors, 228, 232\nShimada classification, 232, 232f\ngerm cell tumor, testis, 414\nliver tumors, 364\nnon-Hodgkin lymphomas, staging, 517t\nrenal tumors, 389\u2013390, 389b\nrhabdomyosarcoma, sign-out checklist, \n546\nvas deferens in hernia sac, 487\nsee also Retinoblastoma\nPedunculated, for gross description, 18t\nPelviscopy, operating room consultations, \n58\nPEM see Epithelial membrane antigen\nPemphigoid, immunofluorescence, 161\nPemphigus, immunofluorescence, 161\nPenis, 537, 537f\ndorsal aspect, 7f\nPercutaneous injury, infectious agent \nexposure risk, 197t\nPerforation, diverticular disease, 345\nPerforin, 109t\u2013150t\nPerianal Paget disease, 89t\nPericardium, 507\nPericoronal cysts, 484\nPerineural invasion\nbreast carcinoma, 262\nhead and neck tumors, operating room \nconsultations, 59\nprostate carcinoma, 396\nPerineurioma, 80t\u201383t, 158t\u2013160t, \n163t\u2013171t\nPeriodic acid Schiff (PAS), 67t\u201370t\nPeriodic acid Schiff with diastase digestion \n(PAS-D), 67t\u201370t, 101t\nPeripancreatic lymph nodes, pancreatic \ncarcinoma, 381\nPeripheral nerve biopsy, 533\nPeripheral nerve sheath tumor see \nMalignant peripheral nerve sheath \ntumor\nPeripheral T-cell lymphoma, NOS, \n105t\u2013106t\nPeritoneum\ncarcinoma, classification of, 445t\ncolon carcinoma, 343, 350\nlaparoscopic cholecystectomy, 366\nmesothelioma, 91t\ntumor invasion, 330\nsee also Pseudomyxoma peritonei\nPeritonitis, diverticular disease, 345\nPermanent implants, breast, 286\nPerpendicular margins, 11f, 12\nPertussis, as hazard, 196b\nPeutz-Jeghers syndrome, 181t\u2013183t\nPgR see Progesterone receptors", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_602.png", "summary": "This page from the surgical pathology manual covers various topics related to the ovary, pancreas, and other related issues.", "questions": [ "What are the key differences between primary and metastatic ovarian tumors?", "How are serous and mucinous tumors of the ovary distinguished in pathology?", "What diagnostic pitfalls should be considered when examining pancreatic specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 603, "text": "585\nIndex\nPhaeohyphomycosis, fungal infection, \n186t\u2013189t\nPheochromocytoma, 229, 229f\nchromaffin reaction, 228\ncolor, 17t\ndense core granules, 158t\u2013160t\ngermline mutations, 179t\u2013180t\nimmunohistochemistry panels, \n77t\u201378t, 97t\nKimura scoring system, 233, 235t\nmalignancy features, 233\nmedullary carcinoma of thyroid and, 63\nPASS scoring system, 233, 234t\nZenker\u2019s acetic fixative, 23\nPhiladelphia chromosome, 172t\u2013178t\nPhimosis, 321\nPhosphate, calculi, 403\nPhosphotungstic acid hematoxylin (PTAH), \n67t\u201370t\nPhotography, 9, 215\u2013216, 215b\nbullets, 526\ninfection hazard and, 201\nPhotomicroscopy, 215\nPhyllodes tumor\nbreast, 266f, 267\ngrades, 284t\nimmunohistochemistry, 91t\nPhysaliphorous appearance, chordoma, \n158t\u2013160t\n\u2018Piano keys,\u2019 endometrium, 424t\nPickwickian syndrome, tonsils, 485t\nPigmented villonodular synovitis see Diffuse \ntype giant cell tumor\nPilocytic astrocytoma, \nimmunohistochemistry, 95t\nPIN see Prostatic intraepithelial neoplasia\nPineal region tumors, 528\nPitfalls, diagnosis, 222\u2013223\nPituitary tumors, 529\nmyeloma vs, 223\nPlacenta, 458\u2013464\nclinical history, 458\u2013460\ndisposal of, 25\ninfection hazard and, 201, 463\nvilli vs decidualized endometrium, \n59t\nweight, 464, 465t\nPlacenta accreta, 464\nPlacental alkaline phosphatase (PLAP), \n84t\u201385t, 109t\u2013150t\nPlacental site\nnodule, 93t\ntrophoblastic tumor, 93t\nPlague, 199t\u2013200t\nPlant material, microscopy, 206t\u2013212t\nPLAP see Placental alkaline phosphatase\nPlaques, pleura, 506\u2013507\nmesothelioma vs, 505\nPlasmacytoma, 103t\u2013104t, 172t\u2013178t\ngenetics, 172t\u2013178t\nPlatelet glycoprotein IIIa see CD antigens, \nCD61\nPlatelet-endothelial cell adhesion molecule \nsee CD antigens, CD31\nPleomorphic adenoma (mixed tumor), \n75t\u201376t, 163t\u2013171t, 479\u2013480\nPleomorphic rhabdomyosarcoma, \ndifferentiation score, \n548t\u2013549t\nPleura, 510\u2013512\ninvolvement in lung carcinoma, 497, \n502f, 506\u2013507\nlymphangitic spread, 497\noperating room consultations, 59\u201361\nplaques, 506\u2013507\nmesothelioma vs, 505\nwedge resections of lung, 497\nsee also Extrapleural pneumonectomy\nPleural fluid, storage for cytology, 309\nPleurectomy, 510\u2013512\nPleuritis, 222\nfibrosing, desmoplastic mesothelioma \nvs, 510\nPlexiform neurofibroma, 543\nPloidy analysis, molar pregnancy, 467\nPMS2, 109t\u2013150t\nPNET see Ewing\u2019s sarcoma\nPneumonectomy, 497\nextrapleural, 505\u2013510\noperating room consultations, 62\nwith partial chest wall resection, 502\u2013\n504\ntransplant, 504\nPOC see Products of conception\nPodoplanin see D2-40\nPolarizability (optical), 205\u2013213\ncrystals, 247\u2013248\nPolarization, thyroid tissue vs parathyroid \ntissue, 64\nPolarizers, 205\u2013213, 205b\nPolycystic kidney disease, 391t\nPolycystic ovaries, 441\nPolycythemia, genetics, 172t\u2013178t\nPolydactyly, fetus, 471\nPolyethylene, in tissues, 206t\u2013212t\nPolymerase chain reaction (PCR)\nspecimens for, 161\u2013162\nsee also Reverse transcriptase polymerase \nchain reaction\nPolymethylmethacrylate, in tissues, \n206t\u2013212t\nPolymorphic microsatellite markers, for \ntissue identification, 33\nPolymorphonuclear leukocytes, revision \narthroplasty, operating room \nconsultations, 52\nPolyomavirus, histological appearance, \n190t\u2013194t\nPolyps\nbiopsy, stains and levels, 32t\u201333t\ncolon, 338, 339f\noperating room consultations, 55\nendometrium, 432\nfibroepithelial, 313\ngastrointestinal, diagnostic pitfalls, 222\ngermline mutations, 179t\u2013180t\nnasal, 473\nPolyposis syndromes\ncolon, 346\njuvenile, 181t\u2013183t\nPolyurethane, breast implant shells, 286\nPopcorn calcification breast, 269\nPorcelain gallbladder, 367\nPorcine bioprosthetic heart valves, 297f\nPosterior aspect, 7f\nPosterior ciliary vessels, 531, 531f\nPosterior tibial neurovascular bundle, \ndissection, 239\nPosterior triangle, radical neck dissections, \n478\nPostexposure prophylaxis, blood-borne \nviruses, 197, 197t\nPostinflammatory scarring, rheumatic valve \ndisease, 292, 293f, 296t\nPostoperative spindle cell nodule, 80t\u201383t\nPost-pathology errors, 220\u2013221\nPost-treatment changes, carcinomas, \nesophagus, 325\u2013326\nPotassium dichromate chromaffin reaction, \n228\nPotassium iodide, chromaffin reaction, 228\nPotter\u2019s syndrome, 471\nPOU5F1 see OCT-4\n\u2018Powder burn,\u2019 endometriotic cyst, 441\nPPNAD see Primary pigmented nodular \nadrenocortical disease\nPP-oma, 379t\nPR see Progesterone receptors\nPRAD1 see Cyclin D1\nPrAP see Prostate acid phosphatase\nPrealbumin, 109t\u2013150t\nPrecursor lymphoblastic lymphoma/\nleukemia\nB-cell, 103t\u2013104t\ngenetics, 172t\u2013178t\nT-cell, 105t\u2013106t\nPregnancy\nclinical history, 3\nfatty change of liver, 362\noperating room consultations, 58\nsee also Ectopic pregnancy; Tubal \npregnancy\nPreoperative therapy\nbreast carcinoma, 262t\nmastectomy after, 273\nPre-pathology errors, 219\nPreservation\nof antigenicity, 70\u201371\nsee also Fixation\nPrimary AL, 107t\nPrimary effusion lymphoma, genetics, \n103t\u2013104t, 172t\u2013178t\nPrimary myelofibrosis, genetics, 172t\u2013178t\nPrimary pigmented nodular adrenocortical \ndisease (PPNAD), 228\ngermline mutations, 179t\u2013180t\nPrion diseases see Creutzfeldt-Jakob disease\nPrior, specimens, reports, 36\nProbes, specimen photography, 216\nProducts of conception (POC), 466\u2013472\ninfection hazard and, 201\noperating room consultations, 58\nsign-out checklist, 471\u2013472\nsee also Hydatidiform moles\nProgesterone receptors (PR)\nbreast carcinoma, 84t\u201385t, 86\u201387, \n265\nevaluation of, 86\u201387, 86t\nimmunohistochemistry, 109t\u2013150t\ninternal control, 71\nProlymphocytic leukemia T-cell, 105t\u2013106t, \n172t\u2013178t\nProphylactic mastectomy, 280\u2013281\nProphylactic oophorectomy, 437\u2013438\nProphylactic thyroidectomy, familial \nmedullary, thyroid carcinoma, 557, \n559", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_603.png", "summary": "The page discusses various topics related to surgical pathology, including different types of tumors, placental abnormalities, pleural conditions, and molecular techniques.", "questions": [ "What are some key differences between pleural plaques and mesothelioma?", "How is placental alkaline phosphatase (PLAP) used in pathology?", "What are the main features of pleomorphic rhabdomyosarcoma?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 604, "text": "586\nIndex\nProstate, 403\u2013412\nbiopsy, 404\ncarcinoma, 326, 404\nGleason grading, 411\u2013412, 411t\ninstitutional consultations, 42\nstains and levels, 32t\u201333t\nclinical history, 403t\ncystectomy specimens, 396, 397f\nintraepithelial neoplasia, 404\nreports, example headings, 36t\nProstate acid phosphatase (PrAP), \n109t\u2013150t\nProstate carcinoma, 407\u2013408\nAJCC classification, 410t\nbiopsy, 395, 404\nbreast cancer in males v., 89t\nchromogranin, 158t\u2013160t\ncrystalloids, 206t\u2013212t\ncystectomy, 396\u2013400, 397f\ndiagnostic pitfalls, 222\nextraprostatic extension, 409\ngenetics, 163t\u2013171t\nGleason grading, 411\u2013412, 411t\nimmunohistochemistry, 77t\u201378t, 98t\nmarkers, 84t\u201385t\nradical prostatectomy, 406\u2013412, 407f\nsign-out checklist, 392\ntransurethral resection of prostate, 404, \n408\nProstatectomy\nradical, 406\u2013412, 407f\nsuprapubic, 405\u2013406\nsee also Transurethral resection of \nprostate\nProstate-specific antigen (PSA)\nimmunohistochemistry, 109t\u2013150t\nprostate carcinoma incidence, 404\u2013405\nProstatic crystalloids, 206t\u2013212t\nProstatic intraepithelial neoplasia (PIN), \n404\nProsthetic heart valves, 295\u2013299, 297f\npathologic analysis, 300t\nProsthetic implants (breast implants), \n286\u2013287\nProsthetic joints, 250\u2013251, 526\nmaterial fragments, microscopy, 206t\u2013212t\nsee also Total joint arthroplasty\nProtective clothing, 201\u2013202\nProtein, fixation and, 21\nProximal aspect, 7f\nProximal urethral margin radical \nprostatectomy, 406, 407f\nPSA see Prostate-specific antigen\nPsammoma bodies, microscopy, 206t\u2013212t\nPsammomatous melanotic schwannoma, \ngermline mutations, 179t\u2013180t\nPseudocyst, pancreas, 377\n\u2018Pseudogout,\u2019 crystals, 206t\u2013212t, 247\u2013248\narthroplasty specimens, 248\nsynovium, 259\u2013260\nPseudomyxoma peritonei, 442\nhernia sacs, 487\nPseudopapillary tumor, pancreas, 376, 376f\nPseudopolyps, inflammatory bowel disease, \n346t\nPTAH see Phosphotungstic acid \nhematoxylin\nPTEN hamartoma syndrome, 181t\u2013183t\nPublication, consultation cases, 40\nPull-through reconstruction, ileoanal, total \ncolectomy with, 340\u2013341\nPulmonary chondroid hamartoma, 500\nPulmonary hypertension, 504\nPunch biopsy\nskin, 311, 311f\nspecimen embedding, 30\u201331\nstains and levels for, 32t\u201333t\nsubungual melanoma, 322\nPUNLMP see Papillary urothelial neoplasm \nof low malignant potential\nPushing borders, for gross description, 18t\nPyloric lymph nodes, pancreatic carcinoma, \n380\nQ\nQBEnd10 see CD antigens, CD34\nQ-probes study\npre-pathology errors, 219\nspecimens not needing histology, 420\nQuadrantectomy see Reexcisions\nQuality control, operating room \nconsultations, 51\nQuick-fix formalin, 21\nsoft tissue tumors, 62\nR\nRabies virus, histological appearance, \n190t\u2013194t\nRadial growth phase, melanoma, 317\nRadial scars, breast, 267\nRadial sclerosing lesions, breast, 267\nRadical cystectomy, 396\u2013400, 397f\nRadical hysterectomy, carcinoma of cervix, \n429\u2013431\nRadical mastectomy, 272\nRadical neck dissections, 475\u2013479\nRadical nephrectomy, 387\u2013392\nRadical vulvectomy, 455\nRadioactive isotopes see \nRadiopharmaceuticals\nRadiography\nbreast calcifications, 263\nchest wall, 506\neye globe, 532\nmammographic lesions, 268, 275\nosteoid osteoma, 253\nsamples v. patient, 184\u2013185\nspecimens, 504\nRadiopharmaceuticals\nsafety precautions, 202\nsentinel lymph nodes, 521\nRadiotherapy\nbone resection, 242, 253\u2013255, 258t\nclinical history of, 3\nesophagus carcinoma after, 325\nhead and neck resections, operating \nroom consultations, 59\nRCB grading system see Residual cancer \nburden grading system\nRCC (renal cell carcinoma marker), \n109t\u2013150t\nReactive lymph nodes, 515\nReactive pleuritis, diagnostic pitfalls, 222\nReceiving materials for consultations, 43\nRectal examination, prostate carcinoma \nincidence, 404\u2013405\nRectosigmoid colon, 339, 340f\u2013341f\nRectosigmoid junction, 339, 341f\nRectum, 339, 340f\u2013341f, 342t\nbiopsy, amyloidosis, 550\ncarcinoma, 347\u2013348, 348f\nAJCC classification, 351, 353t\u2013354t\nimmunohistochemistry panel, 98t\ninfiltrative border, 352b\nsign-out checklist, 350\u2013352\nsee also Colon, carcinoma\nresections, 341\u2013342\nRecurrent, colon carcinoma, 348\nRecurrent pregnancy loss, 466\nReduction mammoplasty, 281\u2013285\nRedundant systems, 221\nReexcisions\nbreast, 270\u2013272\nskin, 312\nRefractility (optical), 205\nRegional neck dissections, 476\nRegional nodal metastases, melanoma, \ndefinition, 318t\nRegressed germ cell tumor, testis, 414\nRegression, melanoma, 317\nReimbursement\nlegal consultations, 42\nsee also Billing documentation\nReinke crystals, 206t\u2013212t\nRejection\ncardiac transplantation, ISHLT grading, \n291t\nlung transplantation, 494\u2013495\nRelease of specimens from laboratory, 24\u201325\nforms, 26f\nRelevant clinical history, 225\nRenal cell carcinomas, 385\u2013395\nacquired cystic disease, 389\nAJCC classifications, 393t\u2013417t\nclear cell, 98t\nadrenal metastases, 97t\ncolor, 17t\nFuhrman nuclear grading system, 393t\ngenetics, 163t\u2013171t\nimmunohistochemistry panels, \n75t\u201378t, 97t\u201398t\nmarker see RCC\nmetastases\ndiagnostic pitfalls, 222\nimmunohistochemistry, 95t\noncocytoma vs, 158t\u2013160t\nsign-out checklist, 392\nRenal cortical adenoma, 389\nRenal fascia, 387\nRenal sinus, pediatric tumors, 389\u2013390\nRenal vein, renal tumors, 387\npediatric, 389\u2013390\nReporting, 35\nconsultations, 35\u201338, 40\ndiagnosis, 36\u201337, 36t\nelectron microscopy, 157\nerrors, 220\nhistology, 15\nhormone receptors, breast carcinoma, \n86t\nhysterectomy, 435\u2013436\nimmunoperoxidase studies, 108\noperating room consultations, 35, 49\u201350\novary carcinoma, 436\nspecial studies, 35, 15\nstandards, 220\nurgent results, 38\u201339", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_604.png", "summary": "This page from the surgical pathology manual covers various aspects related to prostate pathology, including biopsies, carcinoma, Gleason grading, stains, levels, and institutional consultations.", "questions": [ "What is the significance of Gleason grading in prostate carcinoma?", "How does immunohistochemistry play a role in the diagnosis of prostate carcinoma?", "What are some common diagnostic pitfalls in the evaluation of prostate specimens?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 605, "text": "587\nIndex\nRepresentative sections submitted (RSS), 15\nRequests for pathologic evaluation \n(requisition forms), 2\nspecimens not needing histology, 422, \n422f\nResearch\nbreast biopsy, 265\nmaterials requested for, 43, 185\u2013186\nResections\nbone tumors, 252\u2013258\nbrain, 530\u2013531\ncolon, identifying segments, 338\u2013355, \n340f\u2013341f, 342t\nlarge, 241\u2013242\npancreas, 372\nrectal, 341\u2013342\nsmall intestine, 335\u2013336\nsoft tissue tumors, 542\u2013546\nvaginal, 453\u2013455\nsee also specific structures\nResidents, standardized reports and, 37\nResidual cancer burden (RCB) grading \nsystem, 284t\nRespiratory syncytial virus (RSV), \nhistological appearance, 190t\u2013194t\nRespiratory tract, fungal infection, \n186t\u2013189t\nResponse to treatment, tumor reporting, \n278 283t\u2013284t\nRET (proto-oncogene), \nimmunohistochemistry, 109t\u2013150t\nRete testis, tumor involvement, 415\nRetention, gross specimens, 5, 25\nReticles, microscopic measurement, 214, \n214b\nReticular fibers, stains, 67t\u201370t\nReticulin stains, hepatocellular carcinoma, 99t\nRetinoblastoma, 532\ngenetics, 163t\u2013171t\ngermline mutations, 179t\u2013180t\n\u2018Retrognosis,\u2019 legal cases, 42\nRetroplacental hematoma, 464\nReturning specimens to patients, 24\u201325\ngallstones, 367\northopedic hardware, 526\nReverse transcriptase polymerase chain \nreaction (RTPCR)\nlymph node metastases, 520\nspecimens for, 161\u2013162\nRevision, diagnosis, 37\u201338\nRevision arthroplasty, 250\u2013251\noperating room consultations, 52, 52t\nReye\u2019s syndrome, liver biopsy, 362\nRhabdoid predisposition syndrome, \n163t\u2013171t\nRhabdoid tumors\ngenetics, 163t\u2013171t\nimmunohistochemistry, 95t\nkidney, 158t\u2013160t, 390\ncytogenetics, 390\nRhabdomyoma, heart, germline mutations, \n179t\u2013180t\nRhabdomyosarcoma, 158t\u2013160t\ndifferentiation score, 548t\u2013549t\ngenetics, 163t\u2013171t\ngrouping system, 546, 547t\nimmunohistochemistry panel, 79t\u201383t\npediatric, sign-out checklist, 546\nRheumatic valve disease, 292, 293f, 296t\nRheumatoid arthritis, arthroplasty \nspecimens, 248\nRib squeeze method, 259\nRibs, 258\u2013259\ndiagnostic pitfalls, 223\nextrapleural pneumonectomy, 506\nRice bodies, 18t\nRight colectomy, 339, 341f\nRNA, fixation and, 21\u201322\nRokitansky\u2019s protuberance, 441\nRosen criteria, lymphovascular invasion, \nbreast carcinoma, 278b\n\u2018Routine\u2019 specimens\nhistology not required, 420\ntonsils, 484\u2013485\nRSS see Representative sections submitted\nRSV see Respiratory syncytial virus\nrT3 see CD antigens, CD2\nRule scales, 213\u2013214, 213t, 214b\nRulers, photography, 216\nRush diagnosis, 4\u20135\nS\nS100 protein\nimmunohistochemistry, 109t\u2013150t\ninternal control, 71\nlymph node metastases, 520\nmelanoma marker, 85t, 317t\nparaganglioma, 536\nSafe Medical Devices Act (SMDA), 525\nbreast implants, 286\nSafety aspects, 24, 196\nair dried smears, 201\nbiologic terrorism, 198\nCreutzfeldt-Jakob disease, 21, 198, 528\nculture of safety (Sirota), 218, 218t\ncyst(s), 201\u2013202, 438\nfrozen sections, infection hazard, 47, 201\ninfected placentas, 201, 463\ninfectious disease, 196\u2013198\nlung inflation, 498\nmercury, 23\u201324\noperating room consultations and \ninfections, 64\u201365\nradiopharmaceuticals, 202\nreturn of specimens to patients, 25\nsharps, 24, 201\u2013202\nspecimen transport, 5\nSagittal section, 7f\nSago spleen (food analogy), 18t\nSaline\nbreast implants, 286\u2013287\nspecimen photography, 216\nSalivary duct carcinoma, 480\nAJCC classification for, 483t\nSalivary glands, 479\u2013484\ncarcinomas, 480\nmorphology, lung carcinoma, 60\nSalpingitis, 447\nSalpingo-oophorectomy, hysterectomy and, \n424\u2013436\nSample dictations, 225\nSampling\nerrors, operating room consultations, 50\nfrozen sections, 45\nSaphenous vein grafts, 306\nSarcoidosis\ninclusions, 206t\u2013212t\nlymph nodes, 515\nSarcomas, 543\nbiopsy, 540\u2013541\nclinical history, 540t\ndiagnostic pitfalls, 222\nelectron microscopy, 158t, 541\nembryonal, liver, 364\ngermline mutations, 179t\u2013180t\ngrading, 546, 547t\u2013548t\nimmunohistochemistry panels, 80t\u201383t\nmicroscopy, 544\noperating room consultations, 62\nsign-out checklist, 544\ntransmission to health care personnel, \n201\u2013202\nsee also Soft tissue tumors\nSarcomatoid features, renal tumors with, \n389\nSarcomatoid mesothelioma, 80t\u201383t\nSARS see Severe acute respiratory syndrome\nSatellite metastases, melanoma, 318t\u2013319t\nScabies, as hazard, 196b\nScabrous, for gross description, 18t\nScalded skin syndrome, operating room \nconsultations, 53\nScalpel blades\nhandling, 24\ninfection precautions, 65\nmanagement, 201\u2013202\nScarff-Bloom-Richardson grading system, \nElston-Ellis modification, breast \ncarcinoma, 326, 281t\nScars, mastectomy, 274\nSchaumann bodies, 206t\u2013212t\nSchiller\u2019s solution, vagina, 453\nSchwannoma, 80t\u201383t, 543\ngenetics, 163t\u2013171t\nimmunohistochemistry, 95t\nimmunohistochemistry panel, \n80t\u201383t\npsammomatous melanotic, germline \nmutations, 179t\u2013180t\nvestibular\nbrain biopsy, 529\ngermline mutations, 179t\u2013180t\nsee also Acoustic neuroma\nSclerosing adenosis, breast carcinoma vs, \ndiagnostic pitfalls, 222\nSclerosing hemangioma, lung, Ki-67, 71\nScrotum, fetus, 471\nSebaceous carcinoma, germline mutations, \n179t\u2013180t\nSeborrheic keratosis, 313\nSecond reviews\nconsultation cases, 41\nsending slides for consultations, \n43\u201344\nSecondary AA, 107t\nSectioning\ngross, 10\nlung, 498\nspleen, Hodgkin disease, 522\nhistologic, 10, 28, 29f, 31\nbone, 247, 253\nfrozen sections, 47\nreporting, 15\nSelective neck dissections, 476\nSelective reduction, multiple gestations, \nplacentas, 463\nSemilunar valves, anus, 340", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_605.png", "summary": "The page discusses various topics related to surgical pathology, including requests for pathologic evaluation, research materials, resections of different structures, residents' standardized reports, and safety aspects.", "questions": [ "What are some examples of specimens that do not need histology?", "How are bone tumors and brain resections identified?", "What is the significance of the residual cancer burden grading system?", "How is the retroplacental hematoma diagnosed?", "What safety aspects are highlighted in the text?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 606, "text": "588\nIndex\nSeminal vesicles\ncarcinoma\ndiagnostic pitfalls, 222\nimmunohistochemistry panel, 98t\ncystectomy specimens, 397\nprostate carcinoma, 396, 406\u2013407, \n407f\nSeminiferous tubules, 414\nSeminomas\nimmunohistochemistry panels, \n77t\u201378t, 96t\nlocal spread, 412, 414\ntestis, 414\nSending slides for consultations, 43\u201344\nS-Endo-1 see CD antigens, CD146\nSenile degeneration, heart valves, 296t\nSentinel lymph nodes, 521\u2013522\nbiopsy, stains and levels, 32t\u201333t\nhistological processing, 10\u201311\nimmunohistochemistry, 520\noperating room consultations, 54\nradiography for, 185\nSeparated twin placentas, 460\u2013464, \n462f\nSerosa\ncervical carcinoma, 431\ncolon segments, 342t\nendometrial carcinoma, 57\u201358\nhysterectomy, 428\nSerosanguinous, for fluid consistency \ndescriptions, 18t\nSerous, for fluid consistency descriptions, \n18t\nSerous cystic neoplasms, pancreas, 377\nSerous ovarian neoplasms, 442\nadenocarcinoma, 94t\nborderline tumor, 441f\ncarcinoma, 75t\u201376t, 91t\ncystadenoma, 441f\nsign-out checklist, 443\u2013444\nSerous uterine adenocarcinoma, grading, \n435\u2013436\nSerpiginous borders, for gross description, \n18t\nSertoli cell tumors, 414\nimmunohistochemistry panel, 96t\nlarge cell calcifying, germline mutations, \n179t\u2013180t\nSessile, for gross description, 18t\nSevere acute respiratory syndrome (SARS), \nhazard, 197\u2013198\nSex-cord stromal tumors, 96t\nSezary syndrome, 105t\u2013106t, 172t\u2013178t\nSGP-2 see Clusterin\nShape, gross descriptions, 17, 18t\nSharps, 24, 201\u2013202\nShave biopsy, skin, 311\u2013312\nspecimen embedding, 30\nstains and levels for, 31, 32t\u201333t\nShave margins, breast, 272\nShimada classification, pediatrics, adrenal \ntumors, 232, 232f\nShrinkage, fixation and, 21\nSiderotic granulomata, 206t\u2013212t\nSigmoid colon, 338\u2013355, 340f\u2013341f, 342t\nSignet ring cell carcinoma\ndiagnostic pitfalls, 222\ngastric, 330, 331f\nstomach and breast, 90f, 90t\nSign-out\nchecklists, 225, 37\nsee also under specific conditions\nconsult cases, 43\u201344\nerror avoidance, 220\u2013221\nSilica, microscopy, 206t\u2013212t\nSilicone\nbreast implants, 286\u2013287\ngranulomas, 286\nmicroscopy, 206t\u2013212t\nSilver stain, 67t\u201370t\nSimple cysts, ovary, 436, 438\u2013439\nSimplex chronicus, vulva, 456\nSinus\ncontents, head and neck, 473\nfungal infection of, 186t\u2013189t\nSirota, Ronald, culture of safety, \n218, 218t\nSj\u00f6gren syndrome, lip biopsy, 479\nSkeletal anomalies, fetus, 471\nSkin, 310\nbiopsy\ncurettings, 312\nellipses, 312\u2013319\ninflammatory carcinoma of breast, \n285\npunch, 311, 311f\nshave, 311\u2013312\nspecimen embedding, 30\nstains and levels, 31, 32t\u201333t\nsubmission of specimens, 4t\ncarcinoma, 313\nAJCC classifications, 315, 315t\u2013319t\nhistologic grade, 314t\u2013315t\nsign-out checklist, 314\nsee also Basal cell carcinoma; \nSquamous cell carcinoma\ndiagnostic pitfalls, 222\nfungal infection of, 186t\u2013189t\nimmunofluorescence of lesions, 161\nlarge excisions, 319\u2013320\nmastectomy, 273\u2013275\noperating room consultations, 52\u201353\nreports, example headings, 36t\nSleep apnea, tonsils, 485t\nSlides\ncleaning, 215\nimmunohistochemistry, 30, 70\ninstitutional consultations, 42\nmeasurement on, 213\nphotomicroscopy, 215\npreparation, 30\nrelease for research, 43\nsending for consultations, 43\u201344\nfor specialist consultations, 40\nSMA (marker)\nbreast carcinoma, 88t\nsee also Smooth muscle alpha-actin\nSM-ACT (marker) see Smooth muscle \nalpha-actin\nSmad4 see DPC4\nSmall biopsy, 243, 244f\nSmall blue cell tumors, 79t\nSmall cell carcinoma, 84t\u201385t\nbasaloid squamous cell carcinoma v., \n102t\ncarcinoid tumor v., 102t\nimmunohistochemistry panel, 79t\nlung, 102t, 499, 501t\nSmall cell carcinoma (Continued)\ndiagnostic pitfalls, 60, 222\ngrade, 501t\nimmunohistochemistry panel, 77t\u201378t\nSmall intestine, 334\u2013336\nbiopsy, 30, 335\nhistological processing, 31\nstains and levels for, 32t\u201333t\ncarcinoid tumor, 335\ncarcinoma, 335\u2013336\nAJCC classification, 336, 337t\ngrading, 336t\nresection, 335\u2013336\nSmall lymphocytic lymphoma, 103t\u2013104t\ngenetics, 172t\u2013178t\nSmall vascular segments, 305\nSmallpox virus, 199t\u2013200t\nbioterrorism, 198\nhistological appearance, 184\nSMDA see Safe Medical Devices Act\nSmears\nfine needle aspirations, 309\ninfection hazard and, 201\nintraoperative cytology, 49, 184\nopen lung biopsy, 61\nstereotactic brain biopsy, 61\nSmell, specimens, 17\u201319\nSmeloff-Sutter heart valve, 299f\nSM-MHC see Smooth muscle myosin heavy \nchain\nSMM-HC (marker), breast carcinoma, \n88t\nSMMS-1 see Smooth muscle myosin heavy \nchain\nSmooth muscle alpha-actin\nimmunohistochemistry, 109t\u2013150t\nimmunohistochemistry control, 71\nSmooth muscle myosin heavy chain \n(SM-MHC), 109t\u2013150t\nSmoothelin, 109t\u2013150t\nSmoothly lobulated, for gross description, \n18t\nSnap freezing, 161\nlymphoproliferative disorders, 61, \n514\u2013515\npediatric renal tumors, 389b\nsoft tissue tumors, 62\nSnook stain, 67t\u201370t\nSodium borate, hematoxylin and eosin \ntechnique, frozen sections, 48\nSodium polystyrene sulfonate, 206t\u2013212t\nSoft tissue tumors\nAJCC classifications, 545t\ndiagnostic pitfalls, 222\u2013223\nimmunohistochemistry panels, 80t\u201383t\noperating room consultations, 62\nresections, 542\u2013546\nSolid pseudopapillary tumor, pancreas, \n376, 376f\nSolitary cecal diverticulum, 345, 357\nSolitary fibrous tumor, 80t\u201383t, 91t\nimmunohistochemistry, 95t\nSomatostatinoma, 379t\nSouthern blot, specimens for, \n161\u2013162\nSOX2, 109t\u2013150t\nSP1 see Estrogen receptors\nSP3 see HER-2/neu\nSP40 see Clusterin", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_606.png", "summary": "The page provides information on various topics related to surgical pathology, including seminal vesicles carcinoma, seminomas, sentinel lymph nodes, serous ovarian neoplasms, and skin biopsies.", "questions": [ "What are some common diagnostic pitfalls associated with seminal vesicles carcinoma?", "How is the grading of serous uterine adenocarcinoma determined?", "What are the different types of skin biopsies mentioned on the page?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 607, "text": "589\nIndex\nSpecial studies, 225, 67\nbrain biopsy, 528\nconsultations for, 41\nfetus, 471\nfrozen sections and, 40\nhuman papilloma virus testing, 450\nliver biopsy, 361\u2013362\nlymph nodes, 519\u2013520\nlymphoproliferative disorders, 514\u2013515\nmesothelioma, 506\novarian tumors, 440\npediatric renal tumors, 389b\nplacentas, 463\u2013464\nreporting, 36, 15\nrequest, 4\nsarcoma biopsy fixation for, 541\nsoft tissue tumors, 543\nSpecialist consultations, 40\u201341\nSpecimens\nantigenicity, factors affecting, 70\u201371\nbreast carcinoma antigenicity, factors \naffecting, 265\ncytology, storage, 309\ndisposal, 24\nfine needle aspiration, intraoperative \ncytology, 49\nflow cytometry, 184\nfungi appearance in, 186t\u2013189t\nhistology, 28\u201330\ninfection hazard, 201\nmissing, 12\u201313\nmolecular genetics, 162\nnot needing histology, 420\nphotography, 215\u2013216, 215b\nprior, reports, 36\nprocessing, 225, 9\nfrozen sections, 46\u201349\nreturning to patients, 24\u201325\ngallstones, 367\northopedic hardware, 526\nsterility, 186\nsubmitting, 2\u20135\npre-pathology errors, 219\nterrorism and, 198\nsee also Fragmented specimens; \nIdentification, specimens \nand materials; Ink marking; \nOrientating specimens; \nRadiography\nSpecimen bags, nylon, 245\nSpecimen heading, 35\nSperm counts, spermatid counts vs, 413f\nSperm identification, operating room \nconsultations, 56\nSpermatid counts\nsperm counts vs, 413f\ntesticular biopsy, 412\nSpermatocytic seminoma, 96t\nS-phase fraction, 184\nSpiculated borders, for gross description, \n18t\nSpider cells, cardiac rhabdomyosarcoma, \n158t\u2013160t\nSpindle cell carcinoma, 80t\u201383t\nbreast lesions v., 91t\nSpindle cell lesions, 80t\u201383t\nSpindle cell lipoma, 91t\nSpindle cell nodule, postoperative, 80t\u201383t\nSpironolactone bodies, 206t\u2013212t\nSpleen, 523\nclinical history, 513t\ngross descriptions, food analogies, 18t\nHodgkin disease, staging laparotomy, \n522\ntumor, genetics, 172t\u2013178t\nSplenectomy, 523\nSplenic lymph nodes, pancreatic carcinoma, \n381\nSponges\nartifacts, 245\nsmall biopsies, 245\nSpontaneous abortion (SAB), 466\nSporothrix schenckii, 186t\u2013189t\nSquamo-columnar junction (Z line), 324\nSquamous cell carcinoma, 313\nadenocarcinoma v., 102t\nbronchial extension, 60\ncervix, 75t\u201376t, 450\nelectron microscopy, 158t\nesophagus, 324\u2013325, 325f\ngrading system, 327t\nimmunohistochemistry panel, \n77t\u201378t\ngynecology, grading, 435\u2013436\nhead and neck\ndiagnostic pitfalls, 223\nimmunohistochemistry panel, \n77t\u201378t\nhistologic grade, 314t\u2013315t\nimmunohistochemistry panels, \n77t\u201378t, 80t\u201383t\nlarynx, 489\u2013492\nlip excisions, 321, 321f\nlung, 77t\u201378t, 102t, 498, 499f\nlymph node metastases, tonsillectomy, \n484\u2013485\nmarkers, 84t\u201385t\nnipple, 89t\noral, 474\nvulva, 455, 456\nSquamous intraepithelial lesions, cervix, 450\nSquamous metaplasia, lung, diagnostic \nerrors, 60\nSqueeze method, rib, 259\nSt. Jude Medical tilting disk valve, \n297f\u2013298f\nSt. Jude staging system, 517t\nStage micrometers, 214\nStaging laparotomy, Hodgkin disease, \n522\u2013523\nStains\nfine needle aspirations, 309\nfrozen sections, 48\nhistochemistry, 67t\u201370t\nprion protein infectivity resistant to, 528\nspecial, 31\nfor copper, 362\nvagina, 453\nStandardization, gross descriptions, 13\nStandardized diagnosis forms, 37\nStandards, for reporting, 225, 220\nStapes, 484\nStaphylococcal scalded skin syndrome, \noperating room consultations, 53\nStaples, 12\nbowel rings, 340\nlung resections, 494\nStarr-Edwards heart valves, 297f\u2013299f\nSteiner stain, 67t\u201370t\nStein-Leventhal syndrome, 441\nStem cell factor receptor see CD antigens, \nCD117\nStem cell leukemialymphoma syndrome, \ngenetics, 172t\u2013178t\nStereotactic brain biopsy, 61\u201362\nSterility\nmicrobiology specimens, 186\nopen lung biopsy, 61\nSternocleidomastoid muscle, radical neck \ndissections, 477\u2013478\nSternum, short, fetus, 471\nSteroids\nosteonecrosis, 248\ntumors producing\ncolor, 17t\nspecial studies, 440\nStomach, 329\u2013333\nbiopsy, 329\nstains and levels for, 32t\u201333t\ncarcinoma\nadenocarcinoma, 74t, 94t, 333t\nAJCC classification, 333, 334t\ndiffuse type, 330, 331f\nesophagectomy specimens, 324, 326\nhereditary diffuse gastric cancer \nsyndrome, 181t\u2013183t\nintestinal type, 330, 331f\nsign-out checklist, 332\u2013333\ngastrectomy, 329\u2013333\nsignet ring cell carcinomas of, 90f, 90t\nsee also Whipple procedure\nStorage, cytology specimens, 309\nStrawberry gallbladder, 18t, 367\nStreaming dissection, muscularis propria, \ncolon carcinoma, 352b\nStroma, invasion by endometrial carcinoma, \n326, 436\nStromal sarcoma, uterus, 80t\u201383t, 92t, \n163t\u2013171t, 432\nStruma ovarii, 441\nSubarachnoid hematoma, evacuations, 530\nSubchorionic fibrin deposition, 464\nSubdivision, specimens, 8\nSubdural hematoma, evacuations, 530\nSubendocardial myocyte vacuolization, 290\nSubglottis, 489\u2013490, 490f\nSubmandibular region, radical neck \ndissections, 478\nSubpoenas, 42\nSubstage condensers, microscopes, 204b\nSubungual melanoma, 322\nSuccenturiate lobe, placenta, 463\nSugarbaker staging system (revised), \nmesothelioma, 509t\u2013510t\nSugar-coated spleen (food analogy), 18t\nSulfated Alcian blue, 67t\u201370t\namyloidosis, 289\u2013290\n\u2018Sulfur\u2019 granules, tonsils, 485\nSuperficial aspect, 7f\nSuperior aspect, 7f\nSuperior limbus, cornea, 532\nSuperior oblique muscles, ocular, 531, 531f\nSuppurative, for fluid consistency \ndescriptions, 18t\nSupraglottis, 489\u2013490, 490f\nSuprapubic prostatectomy, 405\u2013406\nSurgeons, communication with, 46", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_607.png", "summary": "The page discusses various special studies, consultations, and specimens related to surgical pathology, including brain biopsies, liver biopsies, lymph nodes, frozen sections, and human papilloma virus testing.", "questions": [ "What are some factors affecting antigenicity in specimens?", "How are fine needle aspirations and intraoperative cytology related?", "Why is prion protein infectivity resistant to certain stains mentioned on this page?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 608, "text": "590\nIndex\nSurgical drapes, submission of specimens, 8\nSurgitool heart valve, 299f\nSutures\nmicroscopic appearances, 206t\u2013212t\norientating specimens, 6f, 7\u20138\nSynaptophysin, 109t\u2013150t\nSyndactyly, fetus, 471\nSyndecan-1 see CD antigens, CD138\nSynoptic reports, 37, 220\nSynovitis, detritic, 250\u2013251, 260\nSynovium, 259\u2013260\ncrystal disease, 248\nnormal, 260\nsarcoma of\ndifferentiation score, 548t\u2013549t\ngenetics, 163t\u2013171t\nimmunohistochemistry panel, \n80t\u201383t\nSynuclein-1, 109t\u2013150t\nSyphilis, as hazard, 196b\nSystemic lupus erythematosus \nimmunofluorescence, 161\nskin biopsy, submission of \nspecimens, 4t\nSystemic mastocytosis, genetics, 172t\u2013178t\nT\nT3 see CD antigens, CD3\nT4 see CD antigens, CD4\nT6 see CD antigens, CD1a\nT8 see CD antigens, CD8\nT11 see CD antigens, CD2\nT64 see Clusterin\nTacky, for fluid consistency descriptions, \n18t\nTaenia coli, colon segments, 340f, 342t\nTAG-72 see B72.3\nTalc, microscopy, 206t\u2013212t\nTalc pleurodesis, 506\nTamoxifen, breast carcinoma response, \n86, 86t\nTargetoid bodies, 206t\u2013212t\nTau (protein), 109t\u2013150t\nT-cell antigen receptor see TCR\nT-cell intracellular antigen see TIA-1\nT-cell neoplasms, 105t\u2013106t, 172t\u2013178t\nT-cell prolymphocytic leukemia, 105t\u2013106t, \n172t\u2013178t\ngenetics, 172t\u2013178t\nTCR (T-cell antigen receptor), 109t\u2013150t\nTdT see Terminal deoxytransferase\nTE see CD antigens, CD2\nTechnical problems, operating room \nconsultations, 51\nTeeth, 484\nnumbering, 484\nTEL-AML1 fusion, 172t\u2013178t\nTemperature\nfixation, 21\nfrozen sections, 47\nimmunogenicity and, 71\nTemporal arteritis, scoring system, \n306t\nTemporal artery, biopsy, stains and levels, \n31, 32t\u201333t\nTemporal artery biopsy, 306, 306t\n10% rule, pheochromocytoma, 229\nTenosynovium (carpal tunnel syndrome), \nrelease specimens, 260\nTeratomas\nmature see Dermoid cyst\noperating room consultations, 57\ntestis, 414\nsee also Immature teratoma\nTerminal deoxytransferase (TdT), \n109t\u2013150t\nTerminal ileum, 340f\nTerrorism, biologic, 198\nTestis, 412\u2013418\nbiopsy, 412, 413b\nstains and levels, 32t\u201333t\ncarcinoma, retroperitoneal lymph node \ndissection, 416\nclinical history, 412t\nTexture, gross descriptions, 17, 18t\nTFE3, 109t\u2013150t\nalveolar soft part sarcoma, 163t\u2013171t\nTFE3 (marker), renal carcinomas, genetics, \n163t\u2013171t\nTFEB (marker), renal carcinomas, genetics, \n163t\u2013171t\nTH see CD antigens, CD4\nThecoma, ovary, 442\nTherapeutic abortion, 466\nTherapy related acute lymphoblastic \nleukemia, genetics, 172t\u2013178t\nTherapy related acute myeloblastic \nleukemia, genetics, 172t\u2013178t\nThoratec ventricular assist device, 303, 304f\nThorotrast, microscopy, 206t\u2013212t\nThrombomodulin see CD antigens, CD141\nThrombotic endocarditis, nonbacterial, \n292, 293f\nThrombus\nabdominal aortic aneurysms, 305\nintervillous, placenta, 464\nThymoma, 552\nimmunohistochemistry panel, 77t\u201378t\nstaging, 553t\nThymus, 551\ncarcinoma, 552\nimmunohistochemistry panel, \n77t\u201378t\nstaging, 553t\nclinical history, 551t\nsign-out checklist, 553\ntumor staging and classification, 554t\nThyroglobulin, 109t\u2013150t\nThyroid gland, 100t, 555\nadenoma, 556\nfollicular, 100t\nKi-67, 71\nrenal cortical, 389\ncarcinomas, 75t\u201376t, 84t\u201385t, 100t, \n163t\u2013171t, 557\nsee also Medullary carcinoma, thyroid\nclinical history, 555t\nimmunohistochemistry, 75t\u201376t\nmetastases, immunohistochemistry, 100t\nnodules, operating room consultations, \n62\u201363\ntumor sign-out checklist, 558\nThyroid inclusions, cervical lymph nodes, \n63\nThyroid tissue, parathyroid tissue vs, 64\nThyroid transcription factor 1 see TTF-1\nTIA-1, immunohistochemistry, 109t\u2013150t\nTilting disk valves, 297f\u2013298f\nTime\non antigenicity, 70\nchromogen fading, 73\nfixation, 21\nTissue, processing for histology, 28\nproblems with, 28\u201330\ntypes of, 30\nTissue arrays, material for, 43\nTissue expanders, breast implants, 286\nTissue typing, patient identification, 2\u20133\nTM see CD antigens, CD141\nToenails, 322\nToes, amputations, 238\nToker cells, nipple epidermis, 89t\nToluidine blue, 67t\u201370t\nTombstone appearance, pemphigus, 161\nTongue, 473\u2013475\nsign-out for, 474\ntumor classification, 477t\nTonsils, 484\u2013486\ncarcinoma, 84t\u201385t, 484\nclinical history, 485t\nTotal colectomy with ileoanal pull-through \nreconstruction, 340\u2013341\nTotal joint arthroplasty, 246\u2013251\nrevision, 52, 52t, 250\u2013251\nTouch preparations\nintraoperative cytology, 49, 184\npediatric renal tumors, 389b\nToxic epidermal necrolysis, operating room \nconsultations, 53\nTracking, medical devices, 525, 525b\nTraf-1, immunohistochemistry, 109t\u2013150t\nTransbronchial biopsy, 494\nstains and levels, 32t\u201333t\nTransillumination, eye globe, 532\nTransitional cell carcinoma\nimmunohistochemistry panels, 74t, \n97t\u201398t\noperating room consultations, 57\npapillary, 388f\nsign-out checklist, 392\nsee also Urothelial carcinoma\nTransplant pneumonectomy, 504\nTransplant rejection, 44\nTransplantation see Organ transplantation\nTransport of specimens, 5\nTransthyretin see Prealbumin\nTransurethral resection of bladder tumors \n(TURBT), 395\nTransurethral resection of prostate \n(TURP), 404\u2013405\nprostate carcinoma, 404, 408\nTransverse colectomy, 339, 341f, 342t\nTransverse section, 7f\nTrastuzumab (Herceptin), 84t\u201385t, \n163t\u2013171t\nbreast carcinoma response, 87t\nTrauma, amputations, 238\nTreatment\nbrain tumors, 530\nclinical history of, 3\nTrichilemmoma, multiple facial, germline \nmutations, 179t\u2013180t\nTrichrome stains, 67t\u201370t\nTrilaminar multiple gestation placentas, \n460\u2013464\nTriplet placentas, 463\nTriploidy, partial mole, 467", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_608.png", "summary": "This page covers a wide range of topics in surgical pathology, including specimens submission, microscopic appearances of sutures, syndromes, immunohistochemistry panels, and genetics of various diseases.", "questions": [ "How are surgical drapes used in the submission of specimens?", "What are the key features of synovitis and synovium discussed on this page?", "How is the differentiation score determined in sarcoma of the synovium?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 609, "text": "591\nIndex\nTrophoblastic lesions endometrial biopsy, \n423\nTrophoblastic tumors gestational, 433\nclassification, 435t\u2013452t\nprognostic score, 436t\nsign-out checklist, 326\nsee also Choriocarcinoma\nTRPM2 see Clusterin\nTTF-1\ncytoplasmic immunoreactivity, 71\nimmunohistochemistry, 84t\u201385t, \n109t\u2013150t\nas lung tumor marker, 84t\u201385t, 101t\nTTR see Prealbumin\nTubal carcinoma, 446\nsign-out checklist, 446\u2013448\nTubal cysts, 446\nTubal ligation, 444\nTubal pregnancy, 446\nTuberculosis\ninfection hazard, 196b, 197\naerosol sprays for frozen sections, \n65, 196\nexposure risk, 197t\nlymph nodes, 515\nTuberous sclerosis, 181t\u2013183t\nangiomyolipoma of kidney, 391\nTubular structures, histologic processing, \n30\nTularemia, 198, 199t\u2013200t\nTumor(s)\namputations and large resections, \n241\u2013242\nbone\nAJCC classifications, 256t\nbiopsy, 251\u2013252\ngrading, 257t\nresections, 252\u2013258\nbrain biopsy, 529\ndifferentiation score, 548t\u2013549t\ngrading, 451t\ngross dissection, 10\nhernia sacs, 487\nimmunohistochemistry and, 70\nlymph nodes, staging, 516\u2013520\nmalignant, reporting, 36\nmuscle differentiation, Zenker\u2019s acetic \nfixative, 23\nreporting standards, 221\nsolid, ovary, 437, 439\u2013440\nsteroid-producing, color, 17t\nsubmission of specimens, 4t\ntransmission to health care personnel, \n198\u2013201\nTumor bank, 185\nTumor emboli, breast carcinoma, 278b\nTumor necrosis factor receptor associated \nfactor see Traf-1\nTumor-associated amyloidosis, 107t\nTumor-associated glycoprotein (TAG-72) \nsee B72.3\nTumor-infiltrating lymphocytes, melanoma, \n311\nTunica vaginalis, 413\u2013414\nTURBT see Transurethral resection of \nbladder tumors\nTurcot syndrome, 181t\u2013183t, 527t\nTurnaround time, 37\nfrozen sections, 46\nTwin placentas, 460\u2013464, 462f\nspecial studies, 463\nTwin-twin transfusion syndrome, 463\nTypical carcinoid, lung, 501t\nTypographical errors, 220\nTyrosinase, 109t\u2013150t\nU\nUCHL-1 see CD antigens, CD45RO\nUlceration\nmelanoma, 311\nstomach, 330, 331f\ntongue and oral tumors, 476f\nUlcerative colitis, 345\u2013346, 346t, 347f\noperating room consultations, 55\nUlex, 109t\u2013150t\nUltracor heart valve, 298f\nUmbilical cord, 460\nlength vs gestational age, 464, 465t\nmicroscopy, 464\nUncinate process, pancreas, 377\nUndersampling, 20\nUnderstanding, failures of, 220\u2013221\nUnilocular cysts, operating room \nconsultations, 57\nUnsuspected findings, 36\nUpper aerodigestive tract, carcinoma, \ngenetics, 163t\u2013171t\nUpper respiratory tract, mucosa, biopsy, \n479\nUreter, 400\u2013402\ncarcinomas, AJCC classifications, \n394t\ncystectomy specimens, 396\u2013397\nUreterectomy, transitional cell carcinoma, \noperating room consultations, 57\nUreteropelvic junction, 402\u2013403\nUrethra, cystectomy specimens, 397\nUrgent results, communication of, \n38\u201339\nUric acid\ncalculi, 387\ncrystals, 206t\u2013212t, 247\u2013248\narthroplasty specimens, 248\nsynovium, 259\u2013260\nUrine, storage for cytology, 309\nUrothelial carcinoma, 387\u2013391\nbladder, grading, 399t\ngynecology, grading, 435\u2013436\nimmunohistochemistry, 97t\u201398t\nnephrectomy, 386\noperating room consultations, 57\npapillary, 388f\nsign-out checklist, 392\nureter, 392\nUrothelial papilloma, ureter, 399t\nUterus, 423\u2013436\ncarcinoma, adenocarcinoma, 94t\nclinical history, 423t\nleiomyomas, 425\u2013426, 432\ngenetics, 163t\u2013171t\noperating room consultations, 57\u201358, \n59t\nV\nVaccination\nhepatitis B virus, 196\nsmallpox, 199t\u2013200t\nVADs see Ventricular assist devices\nVagina, 453\u2013455\ncarcinoma\ngrading, 455\nsign-out checklist, 454\u2013455\nclinical history, 453t\nValves, cardiac, 291\u2013295, 293f\u2013294f\netiologic assessment, 296t\ngross morphologic assessment, \n295t\nprosthetic, 295\u2013299, 297f\npathologic analysis, 300t\nVaricella zoster (VZ), histological \nappearance, 190t\u2013194t\nVaricose veins, 306\nVas deferens, 413\nbiopsy, stains and levels, 31, 32t\u201333t\nhernia sac, 487\nVascular anastomoses, monochorionic twin \nplacentas, 463\nVascular ectasia, colon, 345\nVascular grafts, 306\ncoronary artery bypass grafts, \n301\u2013303, 306\nmaterials, microscopy, 206t\u2013212t\nVascular insufficiency, lower extremity \namputations, 239\nVascular invasion see Lymphovascular \ninvasion; Venous invasion\nVascular malformations, brain, 529\nVascular rejection, chronic, lung \ntransplants, 496b\nVascular tumors, immunohistochemistry \npanels, 80t\u201383t\nVasculitis, peripheral nerves, 533\nVasoactive intestinal peptide, tumor \nproducing, 379t\nVegetation (food analogy), 18t\nVegetations, heart valves, 292\nVelamentous cord, 460, 461f\nVelvety, for gross description, 18t\nVenous invasion\nliver tumors, 366\nrenal tumors, 387, 389\u2013390\nVenous/lymphatic invasion (lymphovascular \ninvasion)\nbreast carcinoma, 262t\nRosen criteria, 278b\nstromal sarcoma, uterus, 432\nVentricles (heart), myocardium, \n301, 301f, 304\nVentricular assist devices (VADs), \n303\u2013304, 304f\nVerbal reports, operating room \nconsultations, 50\nVerhoeff-van Gieson stain, 67t\u201370t\nVerner-Morrison tumor, 379t\nVernier scales, 213\u2013214, 213t, 214b\nVerrucous, for gross description, 18t\nVerrucous carcinoma, vulva, 457\nVertical growth phase, melanoma, 317\nVesicles, skin, 310\nVessels, lower extremity, dissection, \n239\u2013241\nVestibular schwannoma\nbrain biopsy, 529\ngermline mutations, 179t\u2013180t\nVilli, products of conception, 466\nhydropic, 467\nVillous, for gross description, 18t", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_609.png", "summary": "This page from the surgical pathology manual covers various topics related to tumors, including classifications, grading, reporting standards, and special studies.", "questions": [ "What are some key considerations when reporting malignant tumors?", "How are tumors in different organs graded and classified?", "What are the specific procedures and checklists involved in handling tubal carcinoma and tubal pregnancy?" ] }, { "doc_name": "51940670-Manual-of-Surgical-Pathology-Third-Edition_1", "page_number": 610, "text": "592\nIndex\nVimentin, immunohistochemistry, \n109t\u2013150t\ncontrol, 71\nVIPoma, 379t\nViral hepatitis, chronic, grading and \nstaging, 361t\nVirilization, adrenal adenomas, 228\u2013229\nViruses\nbrain biopsy, 528\ncultures, 185\u2013186\nhistological appearance, 190t\u2013194t\nsee also Blood-borne viruses\nViscous, for fluid consistency descriptions, \n18t\nVon Hippel-Lindau syndrome, 181t\u2013183t, \n527t\nVon Kossa stain, 67t\u201370t\nVon Willebrand factor see Factor VIII-\nrelated antigen\nVulva, 455\u2013458\ncarcinoma, sign-out checklist, 433\nfetus, 471\nintraepithelial neoplasia, 456\nPaget disease, 89t\nVulvar Paget disease, 89t\nVulvectomy, 455\u2013458, 456f\noperating room consultations, 58\nVWF see Factor VIII-related antigen\nVZ see Varicella zoster\nW\nWada-Cutter heart valve, 298f\nWAGR syndrome, 179t\u2013180t\nWaldenstrom macroglobulinemia, genetics, \n172t\u2013178t\nWarthin Starry, 67t\u201370t\nWarthin\u2019s tumor, salivary glands, 480\nWash, infection precautions, 65\nWaste containers, lost specimens, 12\u201313\nWaterchestnut, unripe (food analogy), 18t\nWebsites, MEDWATCH home page, \n525\u2013526\nWedge resections, lung, 497\noperating room consultations, 59\u201360\nWeibel-Palade bodies, 158t\u2013160t\nWeight\nkidney, 386\nlungs, 497\u2013498\nplacenta, 464, 465t\nreduction mammoplasty, 281\u2013285\nspecimens, 16\u201317\ntransurethral resection of prostate \nspecimens, 404\u2013405\nWeiss criteria, adrenal cortex tumors, 232, \n233t\nWell-circumscribed borders, for gross \ndescription, 18t\nWhipple procedure, 374\u2013382, 374f\nspecimen photography, 216\nWHO classifications\nbrain tumors, 529\ncarcinomas, bladder, 399t\nendocrine tumors of pancreas, 380t\npulmonary neuroendocrine tumors, 501t\nurothelial carcinoma of bladder, 399t\nWHO grading, urothelial carcinoma of \nbladder, 399t\nWilms tumor, 389\u2013390\ngenetics, 163t\u2013171t\ngermline mutations, 179t\u2013180t\nwebsite for checklist \nWilms tumor 1 protein (WT1) (protein), \nimmunohistochemistry, 101t, \n109t\u2013150t\nWilson\u2019s disease, liver biopsy, 362\nWire localization, mammographic lesions \nwith, excisional biopsy, breast, \n268\u2013270\nWright\u2019s stain, 67t\u201370t\nWritten reports, operating room \nconsultations, 49\nWT1 see Wilms tumor 1 protein\nWT1 gene, mutations, 163t\u2013171t\nX\nXanthogranulomatous inflammation, color, \n17t\nXanthogranulomatous pyelonephritis, 390\nXylene, 24\ncleaning of microscopes, 214\nclearing, 28\nhematoxylin and eosin technique, frozen \nsections, 48\nY\nYamakawa-Masaoka staging, thymic \ntumors, 553t\nYersinia pestis, 198, 199t\u2013200t\nYolk sac tumors\nimmunohistochemistry panel, 96t\ntestis, 414\nZ\nZ line, 324\n\u2018Zellballen,\u2019 immunoperoxidase studies, 536\nZenker\u2019s acetic fixative, 23\nbone marrow, 513\u2013514\nchloroacetate esterase and, 67t\u201370t\nchromaffin reaction, 228\nZenker\u2019s diverticulum, Meckel\u2019s \ndiverticulum vs, 336\u2013337\nZiehl-Neelsen stain, 67t\u201370t\nZinc, formalin fixation, 22\nZygomycetes, 186t\u2013189t", "image_path": "page_images/51940670-Manual-of-Surgical-Pathology-Third-Edition_1_page_610.png", "summary": "This page includes information on various topics such as Vimentin, VIPoma, Virilization, Viruses, Von Hippel-Lindau syndrome, Vulva, Von Kossa stain, Vulvectomy, Weight, Weiss criteria, Whipple procedure, WHO classifications, Wilms tumor, Wilson's disease, Wire localization, and more.", "questions": [ "What are some key immunohistochemistry markers for diagnosing yolk sac tumors?", "How is the Whipple procedure related to pancreatic pathology?", "What are the implications of Wilson's disease on liver biopsy findings?" ] } ]