An 85-year-old woman with a history of arthritis, hypercholesterolemia, hypertension, and glaucoma presented to the clinic for evaluation of chronic sinusitis

Symptoms included a several-year history of frontal pain, pressure, clear nasal discharge, and progressive nontender facial swelling above her glabella

She denied nasal disturbance, prior sinus surgery, asthma, or acetylsalicylic acid (aspirin) sensitivity

Symptoms were refractory to treatment with several rounds of oral antibiotics and oral steroids

Physical examination findings revealed symmetric facial movement with prominent glabellar swelling and soft tissue thickening

Nasal endoscopy findings revealed a soft tissue mass anterior to the axilla of the middle turbinates bilaterally, with normal-appearing mucosa overlying

Computed tomography and magnetic resonance imaging (MRI) scans were obtained for further evaluation (Figure, A)

Recommendations were made to proceed to the operating room for biopsy of the nasal mass

Pathology results revealed uniform, epithelioid cells arranged in a whorled, lobulated growth pattern without atypia, necrosis, increased cellularity, or diffuse growth pattern (Figure, B and C)

A, T1-Weighted postcontrast magnetic resonance imaging scan, sagittal view, showed hyperintense soft tissue mass on anterior septum with extension into frontal sinus

Adjacent soft tissue thickening noted on skin overlying frontal sinus and nasal bones

B, Hematoxylin-eosin stain (original magnification ×10) results showed lobules of neoplastic cells with whorled architecture (arrowhead)

C, Hematoxylin-eosin stain (original magnification ×20) results showed intranuclear inclusions (arrowhead)


A 71-year-old man with no history of smoking was referred to our tertiary center in August 2018 for an asymptomatic left level 5 neck mass that had been present for 6 months

Biopsy of the mass demonstrated metastatic p16-positive (human papillomavirus [HPV]-related) squamous cell carcinoma

Examination revealed a large left base of tongue mass filling the vallecula

Computed tomography (CT) demonstrated an enhancing mass within the left base of tongue and bilateral cervical adenopathy

The patient was treated with concurrent radiation therapy and cetuximab, completing treatment without breaks in November 2018. His 3-month posttreatment fluorodeoxyglucose (FDG) positron-emission tomography/CT (FDG-PET/CT) imaging results demonstrated resolution of the activity at the base of tongue mass and the involved cervical lymph nodes, consistent with complete treatment response

In July 2019, the patient presented with a palpable left supraclavicular lymph node

Restaging FDG-PET/CT demonstrated avid supraclavicular and anterolateral neck adenopathy

Additionally, there was moderately intense activity isolated to the left thyroid lobe

Ultrasonography of the thyroid demonstrated a 4-cm mass within the gland, and subsequent biopsy was performed with immunohistochemistry staining positive for p16, CK5, and p40 and negative for thyroid transcription factor 1 (TTF-1) (Figure, A, B)

After multidisciplinary review of the case, the patient was offered salvage left modified radical neck dissection and total thyroidectomy

Surgical pathology confirmed the diagnosis (Figure, C)

Fine-needle aspiration of the left thyroid lesion showing sheets and clusters of tumor cells with indistinct cell borders, with immunohistochemical staining positive for p16 (A) and negative for TTF-1 (B) (both panels, original magnification ×20)

C, Lesional specimen showing tumor cells arranged in irregular nests and cords invading the thyroid parenchyma

normal thyroid tissue shown by the arrowhead (original magnification ×4)


An older adult presented with a history of a mildly pruritic plaque on the elbow at the site of a prior injury

The medical history was unremarkable, and findings of a review of systems were negative

The patient had been treated in the past with topical steroids without improvement, and the size of the lesion had continued to grow slowly

Physical examination findings revealed a solitary, well-circumscribed pink plaque with overlying yellow-white micaceous scale with interspersed punctate hemorrhagic crusts (Figure, A)

Punch biopsy for histopathologic examination was performed, with representative sections shown (Figure, B and C)

A, Well-circumscribed pink, scaly plaque on the right elbow

B and C, Hematoxylin-eosin–stained sections reveal psoriasiform epidermal hyperplasia overlying suppurative granulomatous infiltrates with multinucleate giant cells and rare eosinophilic spheroid forms


A 45-year-old male professional voice user with a history of asthma being treated with inhaled steroids presented with a 1-year history of dysphonia

He reported throat tightness after significant voice use and consistent voice roughness that worsened over several weeks

On examination, he had moderate to severe dysphonia with predominant roughness and strain

Videostroboscopy findings were consistent with fungal laryngitis

a 2-week course of fluconazole was administered

Follow-up videostroboscopy findings demonstrated resolution of the fungal laryngitis but revealed residual fullness of the left false vocal fold and appearance of prolapsed ventricular mucosa obstructing the lateral extent of the left true vocal fold

There was a reduction of lateral excursion of the mucosal wave on the left

The patient continued to report dysphonia and increased vocal effort

A computed tomography scan with contrast showed no specific abnormalities

A direct laryngoscopy for evaluation and treatment was planned

Intraoperatively, there was a firm lesion in the left paraglottic space extending to the lateral aspect of the true vocal fold (Figure, A)

A subtle but similar finding was seen on the right true vocal fold, not causing any mass effect (Figure, B)

An incision was made in the mucosa of the ventricle overlying the lesion at its lateral extent, and a mucosal flap was elevated over the lesion

This revealed a cartilaginous lesion, which was removed using an AcuBlade CO2 laser (Lumenis) and cup forceps until the cartilaginous edge was smooth within the paraglottic space (Figure, C and D)

The histologic specimen showed fragments of cartilage with no nuclear atypia or mitosis (Figure, E and F)

At 3-months’ follow-up, the patient reported improvement in his voice with decreased effort and strain, which correlated with improvement in the Voice Handicap Index score and objective assessment by the clinicians

Direct laryngoscopy intraoperative images demonstrating left lesion (A), right lesion (B), submucosal firm, white mass excised with a CO2 laser (C), and postoperative view (D)

hematoxylin-eosin stain of the left lateral vocal fold lesion showing fragments of cartilage (arrow indicates a peripheral thin fibroblastic rim with a transition to mature chondrocytes of the fibroelastic cartilage toward the center of the nodule) (E) and cartilage with mild nuclear atypia without mitosis (F)


Focal melanotic macule (focal melanosis)

A 57-year-old African American man presented to an oral and maxillofacial surgeon for evaluation of a brown pigmented patch on the left side of the hard palate

The lesion was of unknown duration and was reported by the patient to be asymptomatic, although he did endorse occasional pruritus

An extraoral examination was performed without any abnormal findings

On intraoral soft tissue examination, a brown pigmented patch located predominantly on the hard palate was observed

The lesion had well-defined but irregular borders, measured 2 × 1.2 cm in size, and was nontender to palpation (Figure, A)

Findings of the remainder of the intraoral soft tissue examination were within normal limits

An incisional biopsy was performed, and the specimen was sent for microscopic diagnosis

A, Intraoral photograph demonstrating the brown pigmented palatal patch with irregular, albeit sharply demarcated borders

B and C, Medium-magnification and high-magnification hematoxylin-eosin–stained images demonstrate slender, elongated dendritic melanocytes (marked by arrows) throughout the epithelium

Histologic examination findings revealed soft tissue covered by benign-appearing stratified squamous epithelium, focally spongiotic and acanthotic

Within the epithelium, numerous benign dendritic melanocytes were identified (Figure, B and C)

The underlying connective tissues were unremarkable


A 34-year-old man presented with a 3-month history of progressive, unilateral lower lip and chin numbness and ipsilateral facial fullness

The hypoesthesia was limited to the distribution of the mandibular branch of the left trigeminal nerve (V3)

On review of systems, the patient denied experiencing visual changes, dizziness, headaches, oral or neck pain, voice changes, weight or appetite changes, or swallowing dysfunction

however, he did report biting his lip occasionally due to the numbness

On examination, there were no palpable masses noted in the head, neck, or face

Aside from the V3 sensory deficit, the patient had no cranial nerve deficits

The patient had no significant medical history

prior surgical history was notable for tonsillectomy

Magnetic resonance imaging of the face revealed a T1 isointense, T2 hyperintense 5.9-cm lesion in the left masticator space, which appeared to be centered in the lateral pterygoid muscle with benign-appearing remodeling of the posterior maxillary wall (Figure)

A, The lesion (indicated by the arrow) is isointense on T1-weighted magnetic resonance imaging (MRI) without contrast

B, The lesion enhances with contrast on fat-suppressed T1-weighted imaging

C, The mass is hyperintense on the T2-weighted sequence

D, Computed tomography imaging reveals bony erosion and expansion of the lesion into the maxillary sinus


A young adult nonsmoker patient with a history of asthma presented with a palpable mass on the left side of the neck that had been present for several months, reportedly unchanged

The patient had been treated presumptively for infection with antibiotics, with no improvement

No fever, odynophagia, dysphagia, otalgia, or other constitutional symptoms were reported

Physical examination findings demonstrated a palpable, soft, nontender left level II/III neck mass

Clinical examination findings of the thyroid and upper aerodigestive tract were unremarkable

Contrast-enhanced neck computed tomography (CT) showed a large avidly enhancing mass centered at the left carotid bifurcation splaying the internal and external carotid arteries and extending cranially along the cervical internal carotid artery

The left internal jugular vein was displaced posteriorly

There was also a smaller mass with similar appearance at the right carotid bifurcation (Figure 1A)

Contrast-enhanced abdominal CT showed several enhancing masses in the liver (not shown)

Based on CT findings, gallium Ga 68 (68Ga) dotatate positron emission tomography (PET)/magnetic resonance imaging (MRI) was performed

results demonstrated intense radiotracer avidity in bilateral carotid space masses, hepatic masses, and numerous CT occult osseous lesions (Figure 1B)

A, Axial contrast-enhanced neck computed tomography (CT) demonstrates large left (black asterisk) and small right (white arrowhead) avidly enhancing bilateral carotid space masses

The left tumor circumferentially encases the left external carotid artery (black arrowhead) and partially encases the left internal carotid artery (yellow arrowhead)

B, Coronal gallium 68 dotatate positron emission tomography/magnetic resonance imaging (PET/MRI) demonstrates intense radiotracer uptake of bilateral carotid space masses (left, black asterisk

right, white arrowhead), hepatic masses (black arrowhead), and CT occult osseous lesions as seen in the right femoral neck (yellow arrowhead)


An African American woman in her 30s presented with a 6-month history of 1-cm to 2-cm erythematous and scaly plaques on her lower legs associated with 30-kg weight loss

The plaques began around her ankles and spread proximally, reaching the upper thighs by the time of presentation

She also noted new lesions on her arms and abdomen in the preceding weeks

The eruption was asymptomatic, and the plaques were preceded by lower extremity edema and weakness, resulting in difficulty ambulating and frequent falls

The patient also reported allodynia, tingling, and numbness in her lower legs

She took no medications and her medical history was significant for a first-trimester miscarriage

She was a schoolteacher and had not traveled outside of the country in the past 10 years

Physical examination of her lower extremities revealed erythematous and indurated plaques, some with overlying coarse scale (Figure, A and B)

Her neurological examination showed symmetric 4/5 strength and decreased reflexes in her lower extremities

Sensation to light touch and proprioception were diminished below the knee

Two punch biopsies were performed for histologic review (Figure, C and D)

A, Dark brown, coarse, ichthyosiform scale on the bilateral lower legs

B, Firm pink plaques with overlying coarse scale

C, Granulomatous inflammation throughout the dermis with mild hyperparakeratosis around a hair follicle (hematoxylin-eosin)

D, Well-formed, epithelioid granulomas (hematoxylin-eosin)


A 75-year old woman with a history of follicular lymphoma and breast cancer presented with a 3-month history of gradual vision loss and 1-month history of confusion and difficulty with word finding

She had been diagnosed with hormone receptor–positive right breast cancer 8 years prior and underwent lumpectomy and treatment with an aromatase inhibitor, with remission since

Five years later, she subsequently developed left inguinal adenopathy, which biopsy results showed was follicular lymphoma

At that time, she was treated with a course of bendamustine and rituximab with subsequent maintenance treatment with rituximab for 2 years

Magnetic resonance imaging (MRI) of the brain was performed, demonstrating T2 fluid-attenuated inversion recovery hyperintensity in the left occipital and temporal lobes, crossing the corpus callosum and extending into the right occipital lobe without enhancement (Figure)

A, Axial T2 fluid-attenuated inversion recovery precontrast magnetic resonance imaging (MRI) of the brain

B, Axial T1 magnetization-prepared rapid acquisition gradient-echo postcontrast MRI of the brain


A man in his 30s with a history of treatment-naive HIV (CD4 count < 200 cells/mm3) and untreated syphilis presented to the emergency department with 3 weeks of progressively worsening dysphonia, dyspnea, and biphasic stridor

On arrival to the hospital, the patient had a computed tomography scan performed

results demonstrated an obstructive laryngeal mass but no signs of local invasion or lymphadenopathy

The patient was taken urgently to the operating room where an awake tracheostomy was performed without complication

Findings of a direct laryngoscopy demonstrated violaceous nodules of the base of the tongue as well as a mass of the infraglottis and subglottis, which was nearly completely obstructing the airway (Figure, A and B)

Full physical examination findings also demonstrated violaceous nodules involving the patient’s lower extremities

Results of an excisional biopsy demonstrated a subepithelial spindle cell lesion with extravasation of erythrocytes and stained strongly for human herpesvirus-8 (Figure, C)

Left base of tongue mass with a violaceous hue (A), obstructive mass of the subglottic airway (B), and subepithelial spindle cell lesion with extravasation of erythrocytes and stained strongly for human herpesvirus-8 (hematoxylin-eosin


A 44-year-old woman presented with an asymptomatic enlarging right parotid mass of about 6 years’ duration

She had no prior medical or surgical history and took no medications

Ultrasonography demonstrated a solid and hypoechoic mass, 1.5 × 1.0 × 0.9 cm, in the inferior right parotid gland with minimal vascularity and without extraparotid extension

Fine-needle aspiration was performed, and the smear was extremely cellular and showed sheets and clusters of bland polygonal epithelial cells admixed with bright pink filamentous matrix

Because of the size and location, extracapsular dissection II was carried out.1  The final pathology of the lesion showed histologic findings compatible with salivary gland carcinoma, with microcystic and papillary architecture (Figure, A and B)

Abundant bubbly secretion was present within these microcystic spaces, and this material was positive for periodic acid–Schiff (Figure, C)

Immunohistochemically, there was positivity for epithelial membrane antigen, cytokeratin (CK) 7 and CK19, S100 protein, and gross cystic disease fluid protein 15 (GCDFP-15)

Stains for gastrointestinal stromal tumors 1 (DOG1) and p63 were negative

The tumor appeared to be contained within the surgical excision margins

There was perineural invasion without evidence of neoplastic emboli in the peritumoral lymphovascular spaces

The patient underwent a right parotidectomy I to IV1 and a level II superselective neck dissection

A, Hematoxylin-eosin, original magnification ×40. Tumor cells with oval and rounded nuclei with fine chromatin and centrally localized nucleolus, with papillary architecture

B, Microcystic growth pattern (hematoxylin-eosin, original magnification ×40)

C, The secretory material stains positive for periodic acid–Schiff


Herpes simplex virus–associated pseudolymphoma

A white woman in her early 40s presented with generalized pruritus of 10-years’ duration

The patient provided the report of a skin biopsy performed 2 years before presentation

It was described as indicating spongiotic dermatitis

She had been treated with topical corticosteroids with no control of the symptoms

Physical examination revealed erythematous papules, some of them crusted, and some excoriations located over the trunk and upper extremities (Figure 1A)

In addition, some scales and fissures were seen on her lower lip (Figure 1B), sparing the surrounding skin, as well as inner mouth and upper lip

A new biopsy sample was taken to rule out actinic cheilitis

A, Clinical image of actinic prurigo in the skin of the patient showing unspecific erythematous papules on the arm

B, Clinical image of actinic prurigo cheilitis in the patient showing scales, crusts, and fissures on the lower lip


A woman in her late 20s presented with an asymptomatic hyperpigmentation on the right side of the trunk, right upper arm, and right leg, strictly following the lines of Blaschko (Figure, A and B)

A slight atrophy of the hyperpigmented skin was palpable without any signs of induration

Clinical images show slightly atrophic hyperpigmented macules following the lines of Blaschko on the right side of the (A) trunk and (B) upper arm

Histopathologic images of punch biopsy specimen show (C) normal epidermis and dermis with a slight hyperpigmentation of the basal epidermis layer (hematoxylin-eosin stain), and (D) preserved elastic fibers in the reticular dermis (Elastic van Gieson stain)

The first onset was in her childhood, at the age of 6 years, with a small hyperpigmentation on the right side of her lower chest remaining stable for years

In her early 20s the area of hyperpigmentation started to spread slowly over the above-mentioned areas and became more and more intense

Intravenous penicillin G therapy with 10 million units 3 times daily over 1 week combined with a UV-A1 phototherapy in 18 sessions with a maximum dose of 40 J/cm2 and a cumulative overall dose of 670 J/cm2 showed no effects

A punch biopsy was obtained (Figure, C and D)


a history of congestive heart failure, coronary artery disease, atrial fibrillation, transient ischemic attack, and Parkinson disease

and dependence in all activities of daily living presented to the dermatology department with a 4-month history of new-onset persistent facial eruption

The patient was initially treated for rosacea at an outside hospital with topical 1% metronidazole cream for 1 month without improvement and developed acute facial purpura after 1 day of treatment with oral doxycycline, which was discontinued

Because of the eruption’s rapid onset and violaceous appearance, as well as empirical treatment failure, the patient was referred for further evaluation

On examination, the patient had asymmetric, centrofacial, erythematous-violaceous indurated telangiectatic and ecchymotic plaques over a phymatous background (Figure, A)

A series of punch biopsies were performed (Figure, B-D)

A, Clinical image showing erythemato-violaceous plaques with ecchymotic areas

B, Histopathologic image showing ectatic vessels with plump endothelia involving the deep dermis and hypodermis (hemotoxylin-eosin)

C, On higher magnification, ectatic vascular channels were lined by atypical plump endothelial cells (hemotoxylin-eosin)

D, Immunohistochemistry was negative for Human herpesvirus 8 (original magnification ×100)


Progressive encephalomyelitis with rigidity and myoclonus (PERM)

A 39-year-old woman presented to the emergency department with a 3-week history of worsening spasms in her axial and lower limb muscles and new-onset urinary retention

Sudden episodes of painful involuntary spasms first appeared in her abdominal muscles 2 weeks after a cold

Soon after, spasms spread to all of her axial muscles and both lower limbs

These paroxysmal episodes lasted a few seconds, occurred up to 20 times a day, and were exacerbated by external stimuli

There was no impairment of consciousness during the attacks

A review of her previous records revealed a diagnosis of Hashimoto thyroiditis 1 month earlier

She had no history of tobacco, alcohol, or drug use

She had hyperhidrosis and tachypnea on admission

Neurological examination results disclosed an abnormal mental status

Cranial nerve examination results demonstrated slow saccades

Motor system examination results revealed a symmetric and severe hypertonia and rigidity throughout her trunk and all 4 extremities

Further notable occurrences were severe spasms (Figure, A

Video 1) and patella clonus associated with brisk deep tendon reflexes (Video 2)

She demonstrated marked myoclonus on tactile and acoustic stimulation

Extensor plantar responses were present bilaterally

B, Electromyography examination of the patient

Laboratory results were significant for an elevated level of thyroperoxidase antibodies (50.85 IU/mL

normal, <5.16 IU/mL) and thyroglobulin antibodies (88.35 ng/mL

to convert to micrograms per liter, multiply by 1)

Cerebrospinal fluid testing results revealed normal protein level and cell counts, as well as absent oligoclonal bands or evidence of infection

Her paraneoplastic panel results were negative

Cranial and spinal magnetic resonance imaging yielded no abnormalities

Needle electromyography (EMG) results showed a continuous firing of normal motor unit potentials at rest within the axial and lower limb muscles (Figure, B

A routine electroencephalogram (EEG) showed mild background slowing without periodic discharges

Computed tomography scan results of the thorax, abdomen, and pelvis were negative

An electrocardiogram showed sinus tachycardia


Intravascular natural killer/T-cell lymphoma

A 47-year-old woman presented with a 7-month history of multiple painful erythematous plaques on her lower legs

The lesions appeared as erythematous nodules on the left leg with tenderness and pruritus and rapidly progressed to both legs

Marked lower-leg edema was noted 20 days prior to the visit

She also had an intermittent fever during the past 3 months that did not respond to antibiotic therapy

The patient’s medical history was unremarkable

Physical examination revealed ill-defined, indurated erythematous-violaceous plaques on the lower extremities with substantial edema (Figure, A and B)

Complete blood cell count revealed a normal white blood cell count with moderate anemia (hemoglobin level, 87 g/L

Additional laboratory tests demonstrated an elevated level of serum lactate dehydrogenase (749 U/L

normal range 100-240 U/L) (to convert to μkat/L, multiply by 0.0167)

Quantification of Epstein-Barr virus (EBV) DNA in sera showed a high viral load of EBV in peripheral blood (1 800 000 copies/mL, normal range <500 copies/mL)

A skin biopsy specimen was obtained from a violaceous plaque (Figure, C)

A and B, Ill-defined, irregular erythematous plaques with substantial edema of lower extremities

C, Lesional skin biopsy specimen revealed dilated vessels filled with atypical large lymphoid cells throughout the dermis (hematoxylin-eosin)


CD30-positive primary cutaneous anaplastic large cell lymphoma

Giant condyloma acuminatum (Buschke-Löwenstein tumor)

A woman in her 80s presented with an 8-month history of a growing, painful tumor on her right buttock

The patient felt well otherwise and denied experiencing fevers, chills, sweats, weight loss, or malaise

Her medical history was notable for chronic kidney disease and genital herpes simplex virus (HSV)

She reported no history of genital warts, HIV, or inflammatory bowel disease

A biopsy was performed, and results were consistent with a noninfectious, granulomatous ulcer

Based on the clinical appearance and prior pathologic findings, the patient received treatment of oral antibiotics, intralesional steroids, topical steroids, and immunomodulators, without improvement

Findings from colorectal surgical evaluation of the internal anal mucosa were negative for malignant neoplasm

At referral, physical examination findings revealed a 5 × 7-cm verrucous, exophytic tumor with scant yellow drainage on the right medial buttock extending to the perianal skin (Figure 1A)

Findings from the remaining skin examination were normal

Superficial bacterial cultures were obtained from the lesion and grew methicillin-resistant Staphylococcus aureus

An incisional biopsy was performed for diagnostic clarification (Figure 1B and C)

A, Clinical image of 5 × 7-cm verrucous, exophytic tumor with scant yellow drainage on the right medial buttock extending to the perianal skin

B, Hematoxylin-eosin stain image from the incisional biopsy featuring a hyperplastic epidermis with ulceration, necrosis, and a very dense inflammatory infiltrate

C, Hematoxylin-eosin stain demonstrating plasma cells composing the infiltrate while the epithelium shows focal multinucleated keratinocytes, some with gray-blue cytoplasm


A woman in her 50s presented to a tertiary dermatology referral center with scaly erythematous patches and plaques covering 10% of her total body surface area without clinically appreciable lymphadenopathy

Histopathological testing demonstrated an epidermotropic infiltrate of hyperchromatic, convoluted, atypical CD3+, CD4−, and CD8+ lymphocytes with haloed nuclei with basilar tagging and papillary dermal fibrosis

Studies of T-cell gene rearrangements identified a clonal population

Blood-flow cytometry did not reveal aberrant T-cell immunophenotypes

She was treated initially with topical and intralesional corticosteroids and narrow band UV B phototherapy

Oral bexarotene was subsequently added for recalcitrant disease

Within 2 months, she developed isolated, painful tumors

A second biopsy was performed, which was notable for an epidermotropic infiltrate of CD3+, CD4−, and CD8− weak lymphocytes, which were positive for TIA-1, granzymes, and B factor (Bf) 1 and negative for CD30 and CD56. The results of flow cytometry and imaging were unremarkable

After an initial favorable response with chlorambucil, she developed expanding ulcerated tumors complicated by a polymicrobial superinfection

Chlorambucil was discontinued in favor of antimicrobial treatment

She then received liposomal doxorubicin, although skin involvement continued to progress rapidly, with ulcerating tumors making up as much as 80% of her total body surface area

She was hospitalized for worsening disease and pain (Figure, A)

Repeated histopathologic analysis was done (Figure, B, C, and D)

B, Original magnification ×50. C, Considerable lymphocytic epidermotropism in a pagetoid reticulosis–like pattern without striking Pautrier microabscesses (original magnification ×230)

D, Original magnification ×50.Primary cutaneous aggressive epidermotropic cytotoxic CD8+ T-cell lymphoma


A 55-year old woman presented with a 6-week history of an enlarging, tender, pruritic, 4-cm erythematous patch with central inflammatory papules distributed on the medial forehead (Figure, A)

No inciting events, such as arthropod bite or trauma, were noted

She was initially treated for presumed shingles with valacyclovir, cephalexin, gabapentin, and hydrocortisone 2.5% topical ointment with no improvement in appearance or symptoms

No other cutaneous abnormalities were noted

A punch biopsy specimen of the left medial forehead was obtained, and histological and immunohistochemical analyses were performed (Figure, B and C)

A, Erythematous patch with central inflammatory papules on the forehead

B, Histopathological results revealed dissecting vascular channels (black arrowheads) and spindle cells (white arrowheads) (hematoxylin-eosin)

C, Immunohistochemical staining revealed CD31 and diffuse expression of FLI-1 and ERG in the vascular and spindle cell components


Dianzani autoimmune lymphoproliferative disease

A 17-year-old white male patient was referred to the otolaryngology clinic with a 6-month history of a left-sided neck mass

His primary care physician initially obtained an ultrasonographic image, which demonstrated a left, level 2 lymph node measuring 4.0 × 1.5 × 2.8 cm

The patient then underwent several courses of antibiotic treatment, but the mass persisted

After a period of conservative management, he developed a sore throat and fever

He subsequently underwent a computed tomographic scan of the neck and chest with contrast, which demonstrated an isolated, enlarged, homogenously enhancing left-neck level 2B lymph node measuring 3.4 × 2.8 × 2.1 cm (Figure 1A)

When he presented to our facility, he was found to have an asymptomatically enlarged left level 2/5A neck mass that was nontender and fixed

The patient had an unremarkable medical, surgical, and social history and no known infectious exposures

A white blood cell count and C-reactive protein level were both elevated, at 11 310 cells/μL (to convert to cells × 109 per liter, multiply by 0.001) and 56.2 mg/L (to convert to nanomoles per liter, multiply by 9.524), respectively

Studies for influenza A and B, HIV, cytomegalovirus, American foulbrood, Bartonella henselae, infectious mononucleosis, and Epstein-Barr virus had negative results

An ultrasonography-guided needle biopsy was performed

Fine-needle aspiration and flow cytometry had negative results for lymphoproliferative disorders or a malignant condition

Given the inconclusive diagnosis, the patient underwent a left neck dissection of levels 2A, 2B, and 5A

Intraoperative frozen sections did not show a malignant process

On final analysis, a pathologic examination of the largest lymph node was performed (Figure 1B)

A, Axial computed tomographic (CT) scan of neck with contrast, showing homogenously enhancing 3.4-cm left level 2B neck mass

B, Low-power histology of resected lymph node, demonstrating a regressed germinal center penetrated by a hyalinized vessel and small lymphocytes in mantle zone palisading around the residual germinal centers


Pulmonary tumor thrombotic microangiopathy

Chronic thromboembolic pulmonary hypertension

An 82-year-old woman presented with dyspnea on exertion and weight gain of 5 kg over the past month

Her medical history included atrial fibrillation and lung adenocarcinoma (a lung lobectomy was performed 8 years ago)

Her blood pressure was 112/60 mm Hg, her heart rate was 100 beats per minute, her respiratory rate was 37 breaths per minute, her body temperature was 36.6°C, and her oxygen saturation was 100% while breathing 10 L of oxygen

A cardiac examination was clinically significant for an irregular rhythm, an increased pulmonic closure sound, and jugular venous distension

Bibasilar coarse crackles and pretibial edema were also noted

A complete blood count had results within normal limits

The serum lactate dehydrogenase level was 278 U/L (to convert to microkatal per liter, multiply by 0.0167)

A chest radiographic image showed bibasilar infiltrates

An electrocardiogram was notable for atrial fibrillation, and echocardiography revealed normal left ventricular function, mild right atrial and ventricular dilatation, and severe tricuspid regurgitation (transtricuspid pressure gradient, 40 mm Hg)

A contrast-enhanced computed tomography image revealed bilateral ground-glass opacities and right basilar consolidations, with no evidence of thromboembolisms (Figure, A)

Para-aortic and inguinal lymphadenopathies were also noted

Presumptive diagnoses of pulmonary hypertension (PH) and right-sided heart failure were made

The patient began receiving dobutamine and furosemide, but she continuously required 2 to 10 L of oxygen, and further invasive evaluations could not be performed

An echocardiogram identified aggravating PH (transtricuspid pressure gradient, 57 mm Hg)

A thorough physical examination identified scaly, crusty genital skin lesions pathologically compatible with extramammary Paget disease

The patient deteriorated and died despite treatment

A, The chest computed tomography showed ground-glass opacities (white arrowheads) and consolidative lesions (a yellow arrowhead), but no evidence of thromboembolism was obtained

B, Hematoxylin-eosin stain of the lung showed proliferation of intimal fibromuscular cells with (yellow arrowheads) or without (black arrowheads) the presence of Paget cells

Yellow arrowheads show embolized Paget cells

The encircled area (black arrowheads) indicates the vascular lumen, the inside of which is filled with proliferated fibromuscular cells but not Paget cells (original magnification ×400)


A 29-year-old man with a history of reactive airway disease and eczema presented to the clinic with progressive odynophagia, hoarseness, and dysphagia of solids, liquids, and secretions for the past 6 months

There were no respiratory symptoms, and results of a complete head and neck physical examination were unremarkable

Flexible nasolaryngoscopy was performed and revealed erythema and swelling to the right arytenoid

A 2-week course of doxycycline was completed for presumed infectious supraglottitis without a change in symptoms

A biopsy and culture of the lesion was then collected in the office and revealed inflammatory disease but ultimately was nondiagnostic

The patient chose observation vs further workup at that time

The patient returned 6 months later with worsening symptoms

Repeat flexible nasolaryngoscopy was performed and revealed significant edema of the right arytenoid extending into the aryepiglottic fold, limiting the mobility of the right vocal fold (Figure 1)

Microdirect laryngoscopy and biopsy under general anesthesia was performed, and a specimen was sent to the pathology department for permanent section analysis and flow cytometry

Permanent sections showed unremarkable squamous mucosa

Flow cytometry revealed mixed inflammatory infiltrate and an increased plasma cell component

Results of stains for infectious organisms were negative

Further immunohistochemical analysis confirmed the diagnosis

A full-body nuclear magnetic resonance positron emission tomography/computed tomography scan was performed to rule out systemic disease


A 31-year-old female patient presented with right nasal pain and radiating facial pain over the previous 3 years

She reported feeling a mass in her right nostril that had not changed in size, as well as associated nasal tenderness to the external nose, worsening pain with exposure to cold temperatures, and frequent sneezing

Prior to presentation, she had been prescribed fluticasone and loratadine for allergic rhinitis without resolution of symptoms

She denied difficulty breathing, epistaxis, rhinorrhea, fever, chills, weight loss, or night sweats

On physical examination, her external nose had no visible lesions

A rhinoscopy revealed normal mucosa with a submucosal, round, firm, tender lesion, measuring approximately 1 cm and located on the right anterior nasal septum

The patient underwent surgical excision of the septal lesion under general anesthesia for definitive diagnosis

The specimen measured 1.1 × 0.7 × 0.2 cm and was erythematous, soft, vascular, and adherent, with a broad base to the anterior superior nasal septal mucosa just inferior to the upper lateral cartilage (Figure 1A and B)

The lesion was excised down through the perichondrium

A, Intraoperative view and intraoperative photograph of a mucosal lesion on the anterior septum after the initial incision

B, Elevation with a suction shows attachments to the underlying perichondrium


Acute localized exanthematous pustulosis

A man in his 60s was referred to our clinic because of a well-demarcated, circular erythematous plaque that had been present at the area of median sternotomy for 3 months

Physical examination findings revealed a 20-cm–diameter plaque that consisted of multiple concentric annular formations with raised erythematous margins and studded with numerous blisters and pustules, some coalescing into lakes of pus (Figure 1A)

Nikolsky sign was not elicited, and oral, ocular, and genital mucosa involvement was absent

The patient did not report other symptoms, and findings of the overall physical examination were normal

A, A crusted, focally vesiculating, well-demarcated erythematous plaque at the area of median sternotomy

B, Histopathologic examination of lesional skin (hematoxylin-eosin)

C, Histopathologic examination of lesional skin (hematoxylin-eosin)

Over the past 5 years, the patient’s medications consisted of metoprolol and acetylsalicylic acid for treatment of established ischemic heart disease

Nine months prior to being referred to our department, he was given oral furosemide and amiloride and then underwent median sternotomy and coronary artery bypass surgery 2 months later

Four days after the operation, he developed a red patch at the area of the incision that was accompanied by mild pruritus

Over the following months, the lesion showed a marked tendency for centrifugal extension over the chest area

Results of routine laboratory studies, Mantoux test, chest radiography, and chest computed tomography of the area were within the normal range

Gram stain, periodic acid–Schiff stain, and tissue culture results were negative (Figure 1B and C)


Lupus panniculitis (subcutaneous lupus erythematosus)

A woman in her 40s presented to the dermatology clinic with a 10-year history of progressive skin thickening and subcutaneous enlargement of the right side of her nose and right cheek

She had been seen by several dermatologists and otolaryngologists and had undergone nondiagnostic skin biopsies

She underwent a septorhinoplasty 6 months prior to presentation because of collapse of her right nasal ala

During the surgical procedure, the surgeon noted a significant amount of submucosal tissue in the right nasal cavity, which was removed

histopathological analysis was performed, and the results were reported as fibroadipose tissue and vascular proliferation

A skin biopsy was performed at the time of the surgical procedure and was interpreted as sebaceous hyperplasia

The patient initially had improvement in her skin, but she again noticed enlargement of the soft tissue with thickening of the overlying skin on her right cheek and right side of her nose several months later

Clinical examination revealed slightly hyperplastic soft tissue with dilated patulous follicles involving the right medial malar cheek and right nasal ala in addition to deviation of the nasal tip (Figure, A)

The surgical pathology specimens from her septorhinoplasty were obtained and reviewed

A, Clinical image shows facial asymmetry with deviation of the nasal tip

B, Hematoxylin-eosin stain of an interstitial proliferation of spindle cells within mature adipocytes that extends between bundles of skeletal muscle

C, Hematoxylin-eosin stain of mature adipocytes that are separated by a proliferation of spindle cells associated with fragments of thickened collagen


Bone marrow–liver–spleen type of large B-cell lymphoma

A 71-year-old man had a 3-year history of a recurrent seronegative autoimmune constrictive pericarditis and pleural effusions, which were treated with pericardiectomy and prednisone and azathioprine

The pleural fluid was transudative and sterile, and the pericardium contained focal lymphoplasmacytic aggregates

Attempts to taper immunosuppressive drugs failed because of a recrudescence of the inflammatory syndrome and pericardial effusion

The patient was admitted with fever of unknown origin with a surge of the inflammatory syndrome and pancytopenia

He reported night sweats beginning 3 weeks prior associated with fever and unintentional weight loss

Laboratory evaluations demonstrated a C-reactive protein level of 133 mg/L (reference range, <10 mg/L)

ferritin level of 2607 ng/mL (reference, 30-300 ng/mL)

lactate dehydrogenase (LDH) level of 289 U/L (reference, 135-214 U/L)

pancytopenia with a hemoglobin level of 9.3 g/dL (reference, 13.3-17.7 g/dL), white blood cell count of 2700/μL (reference, 4000-10 000/μL), and platelet count of 99 ×103/μL (reference, 150-350 ×103/μL)

and prerenal acute kidney injury (Acute Kidney Injury Network stage 1) with a serum creatinine level of 1.4 mg/dL (reference, 0.7-1.2 mg/dL)

Results of a comprehensive serologic workup were negative

Gastroscopy results showed mycotic distal esophagitis

The patient was readmitted 3 weeks later with fever and hypotension without improvement despite broad-spectrum antibiotics and antifungals

Considering the increase in ferritin and LDH levels and pancytopenia, a hematologic disease was suspected

The patient did not report any bone pain

Computed tomography (CT) results showed a splenomegaly without evidence of metastatic disease or lymph node enlargement

Positron emission tomography (PET)–CT imaging (Figure, A and B) and a bone-marrow biopsy (Figure, C and D) were performed

A rapidly evolving sepsislike syndrome led to the patient’s death

Fluorodeoxyglucose/positron emission tomography–computed tomography imaging results show diffuse hypercaptation in the bone marrow (A) and spleen (B)

The entire skeleton is highly metabolic, which suggests advanced bone-marrow involvement

C, Bone-marrow biopsy results show a diffuse infiltrate of large lymphoid cells with scattered residual hematopoietic elements (immunoperoxidase, original magnification ×200)

D, Immunostaining shows lymphoid infiltrate strongly positive for paired box protein Pax-5 (immunoperoxidase, original magnification ×200)


A 69-year-old man with a history of metastatic squamous cell carcinoma in the left parotid gland had undergone left parotidectomy and modified neck dissection followed by adjuvant radiation therapy 12 years previously

Ten years later, he developed a second primary tumor in the hypopharynx requiring total laryngectomy and bilateral neck dissection

He presented with new-onset headaches, left ear pain, and persistent unsteadiness during the previous month

There was no palpable lymphadenopathy, neurological deficits, or mastoid tenderness, and otoscopic examination results of the tympanic membrane appeared normal

Magnetic resonance imaging of the head showed an enhancing lesion in the left infratemporal fossa (3.4 × 3.4 × 2.8 cm) abutting the cerebellum, and subsequent computed tomographic imaging of the head demonstrated osseous destruction of the left temporal bone extending along the left internal jugular vein (Figure, A)

Fine-needle aspiration of the left mastoid showed atypical spindle cells

The patient underwent tumor excision with a left infratemporal approach

A large mass with rubbery texture was noted, extending into the jugular foramen and adherent to the dura mater without evidence of intradural invasion

The lower cranial nerves were identified, and the mass was resected to the external wall of the jugular bulb

The patient tolerated the procedure without complications or neurological deficits

Histopathologic assessment demonstrated myogenin-positive spindle cells with no tumor necrosis (Figure, B and C)

In addition, the tumor expressed desmin-positive and CD34-positive cells

The tumor focally infiltrated into the fibrous tissue, skeletal muscle, and bone

A, Axial computed tomography of the head and neck demonstrating osseous destruction of the left temporal bone

B, High-powered view of hematoxylin-eosin stain (original magnification ×40) demonstrating spindle cell morphologic features with admixed fragments of bone (pink-red areas)

C, High-powered view of myogenin stain (original magnification ×40) depicting small-cell or spindle cell morphologic features with rare positive results for myogenin (brown cells)


A 45-year-old woman was referred to a tertiary care center for hoarseness

She had a left vocal fold polyp that was removed 2 months earlier at an outside institution, with benign pathology reported

Subsequent stroboscopy revealed a hemorrhagic-appearing polyp (2-3 mm)

She was sent for preoperative voice therapy, with plans for excision

However, her voice worsened with therapy, and she returned to the otolaryngology clinic after a few weeks

A larger, 6- to 7-mm, irregular, left vocal fold mass was noted

Preoperative imaging was nonspecific, revealing a small soft-tissue density along the true vocal fold

The patient was taken to the operating room for excision (Figure, A)

After the final pathology results were obtained, the patient was taken back to the operating room for cordectomy with negative margins

A, The left vocal fold lesion has a hemorrhagic exophytic mass that has prolapsed into the subglottis

B, Lesional spindled, fibroblastic-myofibroblastic, and inflammatory cells (both plasma cells and lymphocytes) appear in a myxoid background with abundant blood vessels

Even within this field, the denser collagenized stroma interrupts looser edematous areas

The overlying squamous epithelium demonstrates only minimal reactivity with some acanthosis and parakeratosis

C, Neoplastic, spindled, fibroblastic-myofibroblastic cells have diffuse, strong, granular cytoplasmic staining with the ALK1 (D5F3 clone)

The intralesional blood vessels and inflammatory cells and overlying epithelium do not stain

Pathologic results revealed spindle-shaped cells with variable atypia noted and inflammatory cells, including lymphocytes and plasma cells (Figure, B)

Cellular proliferation was present in a myxomatous and focally fibrous-appearing stroma

Immunohistochemical analysis revealed that the lesional cells were negative for desmin, S100, P63, and cytokeratin (Figure, C)

They were reactive for vimentin and anaplastic lymphoma kinase 1 (ALK1)

These findings were confirmed at the time of the initial excision

She has had no recurrent disease for the past 3 years


A full-term, 7-month-old male infant presented to an outpatient pediatric otolaryngology clinic with a firm, irregularly shaped posterior neck mass

He had been diagnosed prenatally with cerebellar hypoplasia, so a magnetic resonance imaging study of the brain was performed at 1 month of age

This study demonstrated an incidental solid, homogenous mass in the subcutaneous fat of the right occiput with irregular borders and infiltration into the paraspinal musculature (Figure, A)

On examination, the upper posterior neck mass was deep to palpation without overlying skin changes

The patient had no discomfort, and neck movement was not restricted

A, Axial T2-weighted magnetic resonance imaging of the neck without contrast

The arrowhead points to a 1.1-cm × 0.8-cm × 1.7-cm right occipital soft tissue mass with irregular borders and infiltration into the deep paraspinal musculature

B and C, Hematoxylin-eosin–stained images demonstrating cells with oval nuclei and multiple small nucleoli surrounded by a pale eosinophilic and slightly fibrillary stroma

At 7 months of age, the patient underwent ultrasonography to assess interval change of the lesion, which confirmed a 3.4-cm × 1.6-cm × 3.7-cm mass that had grown proportionally with the patient and was relatively avascular

Shortly thereafter, the mass was excised en bloc along with a cuff of adjacent posterior neck muscle and subcutaneous tissue

Grossly, the lesion was firm, round, and white in color with a smooth intact border but no discrete capsule

Histologic examination revealed cells with oval nuclei and multiple small nucleoli surrounded by a pale eosinophilic and slightly fibrillary stroma (Figure, B and C)

Immunohistochemical studies were diffusely positive for glial fibrillary acidic protein and vimentin, and focally positive for S100, NeuN, and synaptophysin


A woman in her 30s with a medical history of epilepsy and alcohol use disorder who was taking lamotrigine presented with severe head trauma

Her Glasgow Coma Score (GCS) was 11 M5V4E2 on admission, and a computed tomographic (CT) scan showed a right frontal epidural hematoma with a maximum thickness of 19 mm and a volume of 30 cm3 (Figure 1A)

The hematoma was evacuated by neurosurgery, and her GCS improved to 14 postoperatively

On postoperative day 2, she developed isolated dysphagia and dysphonia

Laryngoscopic examination revealed right vocal cord paralysis (Figure 1B)

A, Computed tomographic (CT) image of the head shows a right frontal epidural hematoma

B, Clinical laryngoscopic image at day 2 shows right vocal cord palsy

C and D, Computed tomographic images with contrast show a thrombosis of the right sigmoid-jugular complex (yellow arrowheads), which causes acute compression of the recurrent nerve as it follows the course of the cranial accessory nerve then the vagus nerve


A 31-year-old Hispanic woman had a 3-year history of a steadily growing, increasingly pruritic, painless mass behind the right ear

The patient denied bleeding from the mass, ear pain, trauma, fever, fatigue, night sweats, or recent illnesses

Her medical history included eczema treated with triamcinolone acetonide cream

Otherwise, the patient had no family history or exposure to tobacco or alcohol

On physical examination, a 2-cm, nontender, mobile retroauricular mass with superficial excoriations was palpable over the right mastoid cortex

The patient had no hearing deficits and no fistula into the external auditory canal

There was no palpable head and neck lymphadenopathy

Serologic studies revealed an elevated absolute eosinophil count of 790/μL  (reference range, <700/μL

to convert to ×109 per liter, multiply by 0.001) and an eosinophilia percentage of 9.7% (reference range, <6.0%)

The T1-weighted postcontrast magnetic resonance imaging of the head and neck showed a heterogeneously enhancing mass with irregular borders in the right retroauricular space, with a tract coursing anteriorly toward the parotid gland (Figure, A)

A, Axial T1-weighted postcontrast magnetic resonance image of the head and neck

B, Lesional specimen of the excised mass (original magnification ×10)

The excised mass was an enlarged, 2.2 × 1.5 × 2.2-cm lymph node with a smooth, pale core and no hemorrhage or necrosis

The capsule was moderately thickened by collagen fibrosis with focal areas of interstitial fibrosis

Reactive follicular hyperplasia was present with prominent eosinophilia in the interfollicular areas and within follicles, forming eosinophilic microabscesses and follicular cysts (Figure, B)

A few small and ill-defined granulomas were present

Results of Gomori methenamine silver and acid-fast stains were negative


Primary cutaneous large B-cell lymphoma, leg type

A woman in her early 80s presented with a 6-month history of an asymptomatic, enlarging, partly infiltrated erythematous cutaneous patch localized to the periareolar area of her left breast (Figure, A)

She had no history of cancer or chronic diseases

Physical examination did not show adenopathies, hepatosplenomegaly, or other remarkable findings

Peripheral blood test results were within normal limits

Tests for tumor markers including cancer antigen (CA) 15-3, carcinoembryonic antigen, CA 19-9, and CA 125 were unremarkable

No palpable breast masses were identifiable

Breast ultrasonography and mammography did not reveal parenchymal nodules

A local steroid therapy was administered, with no benefit

A biopsy of the skin lesion was performed (Figure, B and C)

A, Clinical image of the cutaneous breast lesion shows a large, erythematous, and slightly infiltrated patch in the periareolar region

B and C, Hematoxylin-eosin–stained lesional specimens show a dense dermal infiltrate of cells with focal epidermis involvement (B) and large atypical cells with scanty cytoplasm (C)


A 30-year-old man had involuntary orofaciolingual movements for 7 years and unsteady gait for 2 months

At age 23 years, he began experiencing involuntary orofaciolingual movements and vocalizations

At age 27 years, he developed dysphagia, dysarthria, and involuntary tongue- and lip-biting

This oral dyskinesias worsened while eating

However, a handkerchief in the mouth markedly reduced involuntary tongue-biting and mouth movements

No neuropsychiatric symptoms or seizures were exhibited

Neurological examination results revealed mild cognitive decline, with a Montreal Cognitive Assessment score of 18/30. Orofacial dyskinesia (Video 1), involuntary vocalizations, and mild dysarthria were exhibited

His muscle strength and tone were normal, but his deep reflexes were diminished or absent

The patient’s sensory and coordination examination results were unremarkable, and bilateral Babinski signs were negative

The patient’s gait was mildly wide based (Video 2)

Laboratory examination results, including blood electrolytes and lactate, liver, kidney, and thyroid function, antinuclear antibodies, ceruloplasmin levels, and vitamin A and E levels were normal

Routine and biochemical examination results, oligonucleotide band, antibodies against antiaquaporin 4, and autoimmune encephalitis-related antibodies (ie, N-methyl-d-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic, γ-aminobutyric acid-B, leucine-rick glioma inactivated 1, contactin-associated protein 2, and IgLON5) of cerebrospinal fluid were normal

Creatine kinase (CK) levels were significantly elevated at 2304 U/L (to convert to microkatals per liter, multiply by 0.0167

Low-density lipoprotein and apolipoprotein B levels were slightly decreased at 61 mg/dL (to convert to micromoles per liter, multiply by 0.0357

normal range, 80-119 mg/dL) and 58 mg/dL (to convert to grams per liter, multiply by 0.01

normal range, 66-133 mg/dL), respectively

Acanthocytes were found in the blood smear via Wright staining (Figure, A)

Electrophysiological examination results revealed reduced compound muscle action potential and sensory nerve action potential of bilateral median and ulnar nerves

Electromyogram results showed neurogenic damage in lower limb muscles

Cerebral magnetic resonance imaging results revealed a marked bilateral caudate head atrophy (Figure, B)

A, Acanthocytes in the peripheral blood smear shown via Wright staining (original magnification, ×1000)

B, Axial T2-weighted magnetic resonance image of the patient’s brain


A man in his 50s was referred to the dermatology clinic with a diagnosis of granuloma annulare made on the basis of prior skin biopsy results

He had been treated by a rheumatologist for polyarticular inflammatory arthritis involving the wrists, metacarpophalangeal joints, and proximal interphalangeal joints, as well as fatigue and dyspnea on exertion

Examination revealed numerous, pink-purple dermal papules on the trunk and extremities, with preference for the extensor surfaces of the arms (Figure, A) and legs

The patient reported a 5- to 7-kg weight loss without fever or sweats

His pulmonary and joint symptoms were relieved by daily oral prednisone and flared with taper below 10 mg

Other medications prescribed included hydroxychloroquine, 400 mg, daily for 18 months and weekly adalimumab injections for 7 months, without improvement

A, Pink-purple papules on the extensor surface of the arms

B, Biopsy results show a nodular to diffuse lymphohistiocytic infiltrate (hematoxylin-eosin)

C, Admixed atypical, irregularly contoured lymphocytes with numerous histiocytes are present

D, Biopsy results show low CD4 signal and robust CD8 signal (magnification ×20)

Pulmonary function testing revealed mild restrictive disease with decreased forced vital capacity and total lung capacity

Results of a complete blood cell count and metabolic panel

viral and rheumatologic panels, including HIV blood tests

high-resolution chest computed tomographic scan

and serum and urine protein electrophoresis were normal or otherwise unremarkable

The results of lesional skin biopsies obtained from multiple involved sites initially revealed nonspecific granulomatous dermatitis before a diagnostic biopsy was performed (Figure, B, C, and D)


Porokeratotic eccrine ostial and dermal duct nevus

A girl in her teens presented for evaluation of asymptomatic, punctate, keratotic papules localized to the right palm and right third proximal finger that had been present since age 2 years

Prior treatments included cryotherapy, pulsed dye laser, and 40% salicylic acid, with partial improvement reported but never complete clearance

Medical history and family history were unremarkable

Physical examination revealed grouped and circumscribed, firm, skin-colored, 1- to 3-mm papules with a central punctate dark core (Figure, A and B)

A 4-mm punch biopsy from a papule on the palm was performed (Figure, C and D)

A and B, Grouped, dome-shaped, skin-colored, punctate papules with central keratotic plugging localized to the right palm and finger

C and D, Dilated follicular infundibulum with keratinous core and absent hair shaft (hematoxylin-eosin)


A 58-year-old white woman with history of metastatic human papillomavirus–positive cervical adenocarcinoma presented with multiple joint deformities

Her initial symptoms started 1 month after the initiation of nivolumab, which was 1 year prior to the index visit

Treatment with nonsteroidal anti-inflammatory drugs failed, and the patient had a partial response to intra-articular steroids

She refused systemic therapies owing to concern about diminishing the effectiveness of nivolumab

Despite the joint symptoms, nivolumab treatment was continued for a year

Evaluation showed fixed swan neck deformities in multiple fingers (Figure, A)

There was evidence of chronic synovial hypertrophy with no active synovitis on examination

The results of a comprehensive autoantibody blood panel, including antinuclear antibody, rheumatoid factor, and anti-citrullinated peptide antibody, were unremarkable

Plain radiographs of the hands demonstrated diffuse osteopenia, joint space narrowing, and multiple deformities

Magnetic resonance imaging of both hands revealed multifocal osseous erosions (Figure, B), synovitis, and tenosynovitis

Erosive deforming inflammatory arthritis

A, Fixed swan neck deformities in multiple fingers (arrowheads)

B, Magnetic resonance images of both hands reveal multifocal osseous erosions (arrowheads)


A 48-year-old woman presented to the emergency department with a 2-month history of progressive lower extremity weakness, sensory loss, and sphincter dysfunction

In the weeks prior to onset, she traveled to Yosemite National Park but denied any particular infectious exposures or symptoms including rash

She reported no personal or family medical history

Although she did consume a variety of nutraceuticals, she denied medication and recreational drug use

On examination, mental status, cranial nerves, and upper extremities were normal

Lower extremities were significant for her right side having greater pyramidal weakness than the left, with brisk reflexes and right ankle clonus, as well as a sensory level to pinprick at T6. Magnetic resonance imaging (MRI) of the total spine with and without gadolinium is seen in Figure 1. Initial investigations were notable for normal complete blood cell count, electrolytes, kidney and liver function, B12, and thyrotropin as well as an unremarkable MRI of the brain

Three lumbar punctures were performed over the course of the patient’s hospitalization, each with a white blood cell count less than 5 /µL (to convert to ×109/L, multiply by 0.001), normal IgG index, absent oligoclonal bands, normal protein and glucose levels, and benign cytology

A comprehensive infectious and inflammatory workup including HIV, herpes simplex virus, varicella-zoster virus, Lyme disease, antinuclear antibodies, astrocyte aquaporin-4 autoantibody, myelin oligodendrocyte glycoprotein autoantibody, and serum and cerebrospinal fluid autoimmune panels were negative

Whole-body positron emission tomography demonstrated hypermetabolism of the midthoracic cord

A, Long-segment, expansile T2 hyperintense lesion spanning C5 through T12 and involving greater than two-thirds of the cord diameter

The spinal cord is mildly diffusely swollen without an appreciated focal mass

B, Associated extensive ill-defined enhancement of the spinal cord spanning T3 through T9.


A healthy Asian man in his 20s presented with a 5-month history of progressive bilateral nasal obstruction

He also complained of recurrent epistaxis

He had no notable medical history except stable asthma

On physical examination, nasopharyngoscopy showed a pedunculated mass with a smooth mucosal surface arising from the roof of the nasopharynx

Computed tomographic (CT) imaging (Figure, A and B) revealed a midline, well-defined, pedunculated polypoid lesion with areas of calcifications in the nasopharynx, measuring approximately 1.2 × 1.5 × 2.0 cm

An endoscopic resection via retrovelar approach using a 70-degree endoscope combined with transnasal approach was performed under general anesthesia

The mass was completely resected with its stalk and with adequate surgical margin

Histopathological results (Figure, C and D) showed that the tumor cells were arranged in papillary structures with fibrovascular cores and these cells also had nuclear grooves

Results of other investigations after surgery were negative for cancer, including magnetic resonance imaging (MRI) of the neck and thyroid ultrasonography

In addition, no residual tumor or systemic metastasis was observed on positron emission tomography (PET)-CT results

There was no evidence of recurrence at 12-month postoperative follow-up

A and B, Computed tomography images with contrast enhancement reveal a 1.2 × 1.5 × 2.0-cm soft-tissue–density mass (white arrowheads) with multiple nodular calcifications (red arrowhead) in the nasopharynx

C and D, Lesional histopathologic images (hematoxylin-eosin) show tumor cells arranged in papillary structures with fibrovascular cores (asterisk)

Nuclear grooves (black arrowheads) in these cells were also identified


A 66-year-old man presented to the emergency department for painful and pruritic ulcerative cutaneous lesions involving his back, nose, lips (Figure, A), and mucosal lesions involving his oral cavity and oropharynx

The lesions initially only involved his lips and nasal bridge, and appeared 5 months prior while he was living on a ranch in Mexico

The lesions did not respond to treatment with an unknown oral antibiotic

His medical history included hypertension treated with captopril and a remote history of psoriasis

Physical examination demonstrated several dry, crusted skin lesions with blistering and ulceration, and shallow erythematous ulcerations of his oral mucosa

Internal medicine, otolaryngology, and dermatology departments were consulted

Results of flexible fiberoptic laryngoscopy demonstrated erythematous and ulcerative lesions with surrounding leukoplakia involving the base of tongue, glossoepiglottic fold, lingual and laryngeal surfaces of the epiglottis, and aryepiglottic folds (Figure, C and D)

A QuantiFERON-TB Gold test was obtained, and results were found to be positive

Serum antigen testing for blastomyces, histoplasmosis, syphilis, HIV, hepatitis B virus, hepatitis C virus, human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, human polyomavirus 2, and West Nile virus were performed, and all results were found to be negative

A biopsy of the skin lesion was obtained from the edge of the lesion found on the patient’s back (Figure, B)

Enzyme-linked immunosorbent assay serological testing was subsequently performed, and results demonstrated elevated levels of antidesmoglein 1 immunoglobulin G (IgG) and antidesmoglein 3 IgG

A, Lesions involving the patient’s nose and lower lip

B, Direct immunofluorescence staining for immunoglobin G of an intralesional biopsy at magnification ×34 demonstrating autoantibody deposition in a lacelike pattern localized to the intracellular matrix of the stratified squamous epithelium

C, Bullous lesion involving the epiglottis (black arrowhead)

D, Bullous lesions involving the left posterior true vocal fold, left false vocal fold, and right vestibule (black arrowheads)


Angiolymphoid hyperplasia with eosinophilia

A woman presented with a 2-year history of recurring left submandibular gland swelling and pain

She reported no associated fevers, chills, dryness of mouth, nausea, vomiting, dysphagia or odynophagia

Her medical history was unremarkable except for allergic rhinitis

On physical examination, she had slight enlargement of the left submandibular gland, which was not tender on palpation

Ultrasonography results revealed normal submandibular and parotid glands bilaterally without any mass or calcifications

Blood examinations and basic metabolic panel results were all within normal limits

Sialoendoscopy of the left submandibular duct was performed under general anesthesia

The patient was found to have a cast at the opening of the Wharton duct, which was removed and sent for pathological evaluation (Figure)

Using sialoendoscopy with saline irrigation, the entire duct was examined up to the hilum of the gland

There were areas of mild partial webbing without complete obstruction

The areas of webbing were broken up with irrigation, and at the end of the procedure steroid instillation and irrigation were performed

There were no complications during or after the procedure

Hematoxylin-eosin–stained histological slide of the cast showing numerous eosinophils


A 59-year-old man with nonalcoholic steatohepatitis was found to have a 12.4-cm liver mass, with imaging characteristics concerning for malignant neoplasm (Figure, A)

A biopsy was performed, and pathology results were consistent with a well-differentiated hepatocellular carcinoma

He enrolled in a phase 1 clinical trial (NCT03299946) using neoadjuvant cabozantinib plus nivolumab followed by definitive resection for patients with locally advanced disease

A, Magnetic resonance image of the abdomen shows a liver mass

B, On single-fiber electromyography, the mean consecutive difference of the tested pairs was abnormal, and there was no blocking

Five weeks after the first dose of nivolumab, he developed diplopia and myalgia that mostly affected proximal muscle groups

Physical examination revealed ptosis, modest restriction of ocular motility in all directions bilaterally, and esotropia with left hypertropia in the primary gaze

Muscle strength was 5/5 on hip flexion and extension bilaterally

There was no weakness with repetitive and sustained testing of power

Workup revealed elevated creatine kinase (1222 U/L

reference range, 24-195 U/L [to convert to μkat/L, multiply by 0.0167]), aldolase (24.5 U/L

reference range, <8.1 U/L [to convert to μkat/L, multiply by 0.0167]), and C-reactive protein levels (106 mg/L

reference range, <5 mg/L [to convert to nmol/L, multiply by 9.524])

Acetylcholine receptor binding and modulating antibody levels were elevated (0.69 nmol/L [reference range, <0.3 nmol/L] and 48% [reference range, 0%-20%], respectively)

Results of the striated muscle antibody titer were also abnormal (1:160

Blood test results were negative for acetylcholine receptor blocking and muscle-specific receptor tyrosine kinase antibodies

Nerve conduction studies showed a normal response to repetitive nerve stimulation

Single-fiber electromyography was pathologic and revealed an abnormal mean consecutive difference in more than 50% of the tested pairs (Figure, B), and no blocking was seen

Myopathic action potentials were not present

A chest computed tomographic scan ruled out the presence of a thymoma


A man in his 20s presented with a 6-year history of multiple growing papules superimposed on an asymptomatic firm plaque on the occipital scalp

The lesions were never ulcerated or inflamed, but hemorrhage occurred occasionally after rubbing

At 3 years of age, scarlike macules appeared on the occipital scalp and coalesced to form a larger plaque with sparse hair

Simultaneously, multiple brown-red, dome-shaped papules developed on the nose and gradually evolved to involve the cheeks

Rubbery plaques also developed on the sacrococcygeal area, along with hypopigmented patches on the right buttock

The patient has no systemic symptoms or mental impairment and denied a family history of genetic disease

Physical examination revealed a group of unevenly distributed skin–colored-to-pink, discrete, coalescing papules superimposed on a firm plaque on the occipital scalp (Figure, A)

A biopsy specimen was obtained from one of these papules (Figure, B, C, and D)

Another biopsy from a facial papule demonstrated features of angiofibroma

A, Clinical photograph shows a firm plaque with superimposed papules and decreased hair density

Biopsy specimens from one of the papules demonstrate diffuse dense fibrosis (B), capillary vessel proliferation with some ectasia (C) (hematoxylin-eosin), and perifollicular fibroblastic proliferation (D)


Dermatofibrosarcoma protuberans, atrophic variant

Medallionlike dermal dendrocyte hamartoma

A young man in his late teens presented with numerous atrophic papules and plaques on his trunk and extremities that developed gradually over several years

Although most were asymptomatic, the patient was concerned about the ongoing appearance of new lesions and the associated pain that some lesions were causing

His medical history was significant for adenosine deaminase–deficient severe combined immunodeficiency (ADA-SCID), which had been managed since childhood with twice weekly intramuscular injections of pegademase bovine enzyme replacement, thrice weekly trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis, and monthly infusions of intravenous immunoglobulin

Physical examination revealed 9 smooth-surfaced, skin-colored to hyperpigmented, 0.5- to 1.5-cm atrophic papules and plaques that exhibited the buttonhole sign on palpation (Figure, A)

The multicentric lesions were located on the left knee, left thigh, bilateral chest, and back

Punch biopsies of lesions on his trunk and extremities were sent for histopathological examination with hematoxylin-eosin (H&E) staining (Figure, B and C), immunohistochemical (IHC) studies, and molecular evaluation with reverse transcription polymerase chain reaction

A, The patient presented with 2 distinct, smooth-surfaced, 0.5- to 1.0-cm atrophic plaques with overlying hyperpigmentation on the left thigh

Both lesions exhibited the buttonhole sign on palpation

B and C, Histopathology shows poorly circumscribed hypercellular proliferation of spindle cells occupying the lower reticular dermis with lacelike infiltration of the subcutaneous fat (hematoxylin-eosin)

The somewhat whorled, uniform appearing spindle cells with mildly hyperchromatic, elongated, wavy nuclei surrounded by pale cytoplasm

Mitotic figures and nuclear pleomorphism are uncommon


A 29-year-old healthy woman presented with a 2-month history of left-sided epiphora, headache, and facial pressure

A polypoid lesion was identified at the left lateral nasal wall

Noncontrasted computed tomography showed a hyperdense mass involving the left medial canthus extending through the nasolacrimal duct into the left nasal cavity

The patient underwent endoscopic left maxillary antrostomy, ethmoidectomy, and biopsy of mass, with results of pathology analysis showing poorly differentiated squamous cell carcinoma

Immunohistochemical (IHC) staining was positive for cytokeratin 5/6 and p63, and negative for Epstein-Barr virus, p16, CD45 (leukocyte common antigen), and synaptophysin

The patient was referred to a tertiary care facility for further treatment

On examination, there was a palpable subcutaneous nodule 1 cm inferior to the left medial canthus with normal overlying skin

On nasal endoscopy, residual tumor was visible at the anterior aspect of the lateral nasal wall

Computed tomography showed postoperative changes with enhancement of left medial canthus extending into nasolacrimal duct and along the lateral nasal sidewall (Figure, A)

A, Coronal view of contrast-enhanced maxillofacial computed tomography obtained after initial biopsy and before resection showing tumor involvement of lateral nasal sidewall and nasolacrimal duct

B and C, Hematoxylin eosin–stained histologic sections of tumor after resection showing bony invasion by sheets of undifferentiated cells (B) and focal areas of abrupt keratinization (C)

The patient subsequently underwent left medial maxillectomy via lateral rhinotomy approach, with resection of residual tumor

The tumor appeared to originate from left lateral nasal wall, with involvement of nasal floor and extension into the orbit and periorbita

Histologically, the tumor extensively eroded maxillary bone, with abundant necrosis and widespread involvement of surgical margins

Microscopic examination showed sheets of monomorphic undifferentiated tumor cells with interspersed areas of abrupt squamous differentiation and keratinization (Figure, B and C)


Cutaneous metastasis from small cell lung cancer

Primary cutaneous lymphoma (Sézary syndrome)

An 81-year-old woman presented with a 30 cm-wide, easily bleeding, violaceous, cutaneous lesion of the left scapular region with a superinfected necrotic central portion surrounded by satellite telangiectatic papules (Figure, A)

The patient first noticed a rapidly expanding, itchy, painful nodule, which measured 3 cm in diameter, 5 months prior to presentation (Figure, B)

Lesion appearance at the first visit (A) and 5 months earlier (B)

C, Hematoxylin-eosin stain, magnification ×20.The patient reported decreased appetite with weight loss of 7 kg over 5 months and denied fever, itching aside from the lesion, vomiting, or bowel alterations

Owing to intense and continuous pain from the lesion, she began opioid treatment with oxycodone/naloxone association at an initial dose of 5 mg/2.5 mg twice a day and titrated to 10 mg/5 mg twice a day after a week to achieve pain control

Abdominal ultrasonography revealed only a left adrenal gland mass, consistent with adenoma

On physical examination, there were no other cutaneous lesions though multiple ipsilateral axillary lymph nodes, and enlarged supraclavicular and cervical lymph nodes were present

All other physical and laboratory findings were unremarkable

A skin punch biopsy of the lesion was obtained (Figure, C)


Intraoperative cutaneous electrical injury (Lichtenberg figure)

A man in his 80s presented with an 18-month history of an irregularly linear, rusty-brown, atrophic, streaklike plaque extending from the tip of his right shoulder to the right biceps, where it ended in arborizing purple plaque with scattered, slightly indurated, irregular papules within it (Figure, A and B)

There was no warmth, thrills, or pulsations across the affected area

The patient complained about a mild tingling sensation within the lesion

The patient could not think of any triggers or causes for his condition and denied any aggravating or alleviating factors as well as any treatment attempts

Complete review of systems yielded negative results except for easy bruising

He was taking finasteride, montelukast, enalapril, and metoprolol

His medical history was significant for right total reverse shoulder replacement 5 years prior

Apart from the previously described lesion, his physical examination was unremarkable, and he had full range of motion of his right shoulder

A punch biopsy of the slightly indurated papule from the involved area on the right biceps was completed (Figure, C and D)

A and B, An irregularly linear, rusty-brown, atrophic, streaklike plaque extends from the tip of the right shoulder to the right biceps, where it ends in arborizing purple plaque with scattered, slightly indurated, irregular papules within it

C, Hematoxylin-eosin staining demonstrates a dermal infiltrate arranged in nodules with clefting between nodules

some inflammatory aggregates are also seen within dilated vessels

D, Immunohistochemical staining for CD68 antigen reveals that the infiltrate is composed mostly of histiocytes


A white man in his early 40s with a medical history of chronic lymphocytic leukemia (Rai stage 0) reported a 6-month history of a growing mass in his right axilla and weight loss

Physical examination revealed palpable right axillary lymphadenopathy

The patient was an active smoker (1 pack per day) with an unremarkable family history

A positron emission tomography scan showed a hypermetabolic right axillary lymph node that measured 5 × 5 cm as well as multiple liver lesions, the largest of which measured 8 cm

The results of a core needle biopsy specimen from the right axillary lymph node were consistent with malignant neoplasm, with immunohistochemistry staining positive for S100, HMB-45, and MART-1. He began pembrolizumab therapy

After starting treatment, the patient began to notice slowly worsening painless, nonpruritic, diffuse dark gray skin, nail beds, and eye discoloration (Figure)

The results of laboratory studies revealed normal electrolytes, normal kidney function, mild elevation of liver function, and mild anemia with a hemoglobin level of 12 g/dL (for SI unit conversion, multiply by 10.0 to convert to liters)

Computed tomography of the chest, abdomen, and pelvis showed worsening hepatic metastases and right axillary adenopathy


A 45-year-old man was admitted to the hospital following 3 weeks of dysphagia

1 week of nasal regurgitation, nonproductive cough, and breathy voice

and a 25-pound weight loss over the preceding 2 months

He had been diagnosed a year earlier with HIV infection and hepatic tuberculosis

Baseline CD4 count was 7 cells/μL, and following treatment with HAART (highly active antiretroviral therapy) consisting of dolutegravir, emtricitabine, and tenofovir-disoproxil-fumarate, he achieved full virological suppression

however, CD4 counts remained low at 31 cells/μL

He had completed 12 months of directly observed therapy with ethambutol, moxifloxacin, and rifabutin—a liver-sparing regimen—owing to toxic effects from the first-line regimen 1 month prior to admission

Physical examination revealed evidence of perforation of the hard palate (Figure, A)

A computed tomographic scan of the chest revealed necrotic lymph nodes, and a palatine biopsy was performed (Figure, B and C)

A, Clinical view of the perforation of the hard palate

B, Low-power microscopic view of a biopsy specimen from the hard palate (hematoxylin-eosin)

C, Oil immersion image of the same tissue shown panel B stained with Grocott methenamine silver


A 30-year-old woman presented with a 4-month history of widespread thickened, verrucous, hyperpigmented plaques distributed symmetrically on her body, especially on the axillae (Figure 1A), anogenital region, inguinal skin, and both palms, with slight itching

The verrucous plaques also involved the conjunctiva, lips, and gingiva (Figure 1B)

The patient had experienced a weight loss of 6 kg during the last 3 months

Within the last month, the patient’s thyroid became enlarged, and she developed anorexia and abdominal discomfort

Laboratory test results revealed remarkably elevated levels of carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, tissue polypeptide antigen and carbohydrate antigen 242. Biopsy specimens of lesions on the axillae and lips both revealed a papillary structure with hyperkeratosis

An endoscopic examination and computed tomographic scan of the abdomen were performed

Axilla with velvety, hyperpigmented skin (A) and verrucous plaques on the lips and gingiva (B)


A 70-year-old Indian woman presented with a generalized rash over the lower extremity associated with pedal edema extending up to the shins

The onset was gradual and started on the lower extremities and gradually extended to involve the lower trunk

The rash was associated with mild discomfort

The patient denied itching, weeping, or bleeding from the rash

She denied any constitutional symptoms (weight loss, fever, night sweats), joint pains, history of blood in urine, periorbital edema, and recent intake of medications or herbal medications

Social history was significant for 25 pack-years of smoking

Physical examination revealed multiple well-defined, coalescent, erythematous, palpable, purpuralike lesions that were predominantly present over the trunk and lower extremities (Figure, A and B)

Laboratory test results at presentation included a hemoglobin level of 11.2 g/dL (to convert to g/L, multiply by 10), mean corpuscular volume of 84 fL, erythrocyte sedimentation rate of 72 mm/h, and a lactate dehydrogenase level of 412 IU/L

Hepatic and renal function levels were within normal limits

Hepatitis B and C and HIV profiles were negative

A chest radiograph showed a 2-cm lesion in the upper lobe of the left lung

A computed tomographic scan of the chest showed a spiculated mass in the same region along with mediastinal lymphadenopathy

An ultrasound of the abdomen showed bilateral adrenal masses

A lesional skin biopsy specimen was obtained (Figure, C)

Coalescent, erythematous, palpable lesions on the lower extremity (A) and trunk (B)


A 59-year-old Hispanic woman presented with a 6-month history of intermittent pain in the right posterior mandibular gingiva

Her local dentist had prescribed an antibiotic and performed a tooth extraction in the area 6 months prior with no improvement in symptoms

Ultimately, her pain became persistent and radiated to the right lower lip

She had a history of stage IV endometrial serous adenocarcinoma (ESA) 4 years prior that was treated with total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and peritoneal lavage

She had developed a recurrence for which she had just completed 3 cycles of treatment with carboplatin

She also had a history of anxiety, hypertension, and pterygium, and she was taking gabapentin, lorazepam, prochlorperazine, metoprolol succinate, bromfenac and ketorolac ophthalmic solution, and aprepitant

Intraoral examination revealed a 1.5 × 1.0-cm firm, erythematous gingival mass in the area of missing right mandibular second bicuspid and first molar with buccal and lingual expansion (Figure 1A)

The right mandibular first bicuspid was grade 3 mobile

A periapical radiograph was obtained, and results showed a diffuse, poorly demarcated radiolucency measuring approximately 1.2 × 0.8 cm (Figure 1B)

Findings from an incisional biopsy of the mass showed an infiltrative tumor (Figure 1C)

Tumor cells were positive for CK7, PAX8, and WT-1, and negative for CK20 and TTF-1 (Figure 1C, inset)

A, A 1.5 × 1-cm gingival mass is distal to the right mandibular first bicuspid

B, Diffuse, poorly demarcated radiolucency is seen in the area of the missing right mandibular second bicuspid and first molar (arrowheads)

C, Multiple nests of round to ovoid epithelial cells form ducts (hematoxylin-eosin stain, original magnification ×100)

Diffuse nuclear positivity for PAX8 (immunohistochemistry, original magnification ×200) (inset)


Type 2 herpes simplex virus (HSV-2) pharyngitis

A 27-year-old man with a history of pharyngeal gonorrhea presented with a 7-day history of severe sore throat and odynophagia, worse when swallowing solids than liquids

Owing to the odynophagia, he had presented to the emergency department for dehydration

At that time, he was febrile to 101°F and denied any dysphonia or dyspnea

The results of a rapid Streptococcus test, recent HIV screen, and a rapid plasma reagin test were all negative

He denied any genital lesions or symptoms at that time

He had been taking prophylactic emtricitabine-tenofovir daily and had received his last diphtheria booster 2 years prior to presentation

Treatment with amoxicillin clavulanate over several days had not prevented a worsening of his symptoms

On physical examination, there was no cervical lymphadenopathy, and there were no genital lesions

Flexible fiber-optic nasopharyngoscopy showed ulcerative lesions with exudate and erythema extending diffusely along the base of tongue, oropharynx, nasopharynx, hypopharynx, and epiglottis (Figure 1)


A woman in her 60s with a history of end-stage renal disease who had a kidney transplant 9 months previously presented with progressive cough, dyspnea, and hoarseness

Her history also included chronic gastroesophageal reflux disease and a 14-pack-year smoking history

She initially presented 3 months prior with upper respiratory symptoms, which continued to worsen despite oral antibiotic therapy

Her cough became productive with white, frothy phlegm that was accompanied by fever, wheezing, hoarseness, and fatigue

Her dyspnea worsened in the supine position

Flexible laryngotracheoscopy results revealed diffuse, white-to-yellow pseudomembranous changes involving the glottis and supraglottis (Figure, A), posterior tracheal wall, and left mainstem bronchus with skip lesions in the subglottis and distal 1 cm of the trachea (Figure, B)

Glottic mobility was limited in both abduction and adduction with substantial airway obstruction

Computed tomographic findings revealed posterior tracheal wall thickening with the loss of the fat plane between the trachea and esophagus, and a moderate to severe obstruction within the distal left mainstem bronchus

Laryngoscopic images demonstrate pseudomembranous plaques lining supraglottis and glottis (A) and posterior wall of the trachea (B)

Supraglottic biopsy demonstrates branching organisms superficial to squamous epithelium (original magnification ×400) (C)


An 80-year-old man with acromegaly due to a hypoenhancing pituitary microadenoma opted for transsphenoidal resection

Preoperative magnetic resonance imaging examination of the sella revealed a left-sided pituitary microadenoma (Figure, A) and lobulated polypoid soft tissue masses in the superior nasal cavities arising from the olfactory clefts

These lesions demonstrated avid post–contrast enhancement with small areas of cystic change and heterogeneously hyperintense T2 signal

There was mild widening of the olfactory clefts, particularly on the left side (Figure, B)

The intervening nasal septum was intact, and there was no intracranial extension

The patient did not have any noteworthy rhinological symptoms on review

He later underwent nasal endoscopy, and results showed tan-colored polypoid lesions emanating from the olfactory clefts of both nasal cavities (Figure, C)

Biopsy findings revealed submucosal proliferation of seromucinous and respiratory epithelial glands (Figure, D)

A, An incidental polypoid-enhancing mass in the nasal cavity demonstrating avid post–contrast enhancement (yellow arrowheads) was observed on the magnetic resonance imaging examination

The white arrowhead points to the pituitary adenoma

B, Widening and remodeling of the olfactory clefts (yellow arrowheads) was also observed on the magnetic resonance imaging examination

C, The incidental polypoid-enhancing mass in the nasal cavity (yellow arrowheads) as seen on nasal endoscopic analysis

D, Results of the nasal cavity mass biopsy (original magnification ×100) revealed submucosal proliferation of bland-appearing seromucinous and respiratory epithelial glands


Cutaneous T-cell lymphoma (mycosis fungoides [MF])

A man in his 50s presented with dysphagia, arthritis, joint contractures, carpal tunnel syndrome, and infiltrated and redundant skin with sheets of 1- to 2-mm-wide waxy, firm, skin-colored papules

The patient first noticed papules on his forehead 1 year prior to presentation that spread to his face, trunk, and extremities

He had mild dysphagia and severe joint pain in his hands and wrists, with carpal tunnel of his right wrist

Additionally, his daily activities were impaired owing to decreased mobility

During clinical evaluation, he denied cough, shortness of breath, chest pain, Raynaud phenomenon, fevers, night sweats, weight loss, seizures, or confusion

Physical examination revealed diffuse skin-colored to pink papules coalescing into plaques on the entire face, with exaggerated skin folds of the forehead (Figure, A), glabella, periocular regions, and superior cutaneous lip

This was accompanied by swelling and erythema of both ears

On his extremities and trunk, he had diffuse infiltration of the skin, with exaggerated skin folds (Figure, B), decreased finger flexion, and four-fifths grip strength

A, Clinical image of the exaggerated skin folds of the forehead and glabella

B, Clinical image of the wrist and hand depicting the exaggerated skin folds and decreased finger flexion

C, Hematoxylin-eosin stain image from the punch biopsy featuring fibroblastic proliferation from the papillary to the reticular dermis (original magnification ×40)

D, Hematoxylin-eosin and Alcian blue stain image featuring mucin deposition in the reticular dermis

Notable laboratory results included a normal level of thyroid-stimulating hormone, macrocytic anemia, normal creatinine and calcium levels, and a monoclonal spike on a serum protein electrophoresis test

Serum free light chains revealed normal κ free light chains, λ free light chains, and a normal κ/λ ratio

Immunofixation results revealed IgG λ monoclonal gammopathy

A punch biopsy was obtained for diagnostic clarification (Figure, C and D)


Disseminated superficial actinic porokeratosis

A man in his 60s presented with a 10-year history of a slowly progressive, asymptomatic cutaneous eruption on his left leg (Figure 1A)

He had a 16-year history of diabetes mellitus that was being treated with metformin

Hematological and biochemical test results were unremarkable

There was no history of another endocrine disorder or malignant neoplasm

There was no family history of similar cutaneous findings

Physical examination revealed reddish brown hyperkeratotic papules 1 to 10 mm wide on the front and back of the left leg from knee to ankle

The rest of the physical examination findings were unremarkable

Removal of the scales caused slight bleeding

A lesional skin biopsy was performed (Figure 1B and C)

A, Clinical image of the reddish brown hyperkeratotic papules on the front of the left leg

B and C, Hematoxylin-eosin–stained lesional skin biopsy specimens revealing compact hyperkeratosis, epidermal atrophy, and bandlike lymphocyte infiltrate in the superficial dermis


A man in his 60s was evaluated in the epilepsy monitoring unit for various spells he had been having up to 5 times a day over the previous 8 months

He described transient episodes of expressive speech difficulties, paroxysmal dizziness, and involuntary nonsuppressible jerks of the right arm, which occurred without warning and were associated with mild disorientation

Video electroencephalography (EEG) captured the movements (Figure, A)

They consisted of involuntary, synchronous contractions of the right face, arm, and leg that were sustained for a few seconds before muscle relaxation occurred (Figure, B and C

The movements were not elicited by action or exertion

There was no epileptic abnormality that correlated with the movements on EEG, and head magnetic resonance imaging was unremarkable

A, Electroencephalogram (EEG) during the event (bipolar montage, 60-Hz filter, 7-uV/mm sensitivity)

C, Patient position while experiencing an involuntary, sustained contraction of the right lower face, arm, and leg lasting almost 2 seconds before spontaneous resolution

The event took place during the time span marked with red vertical lines on the EEG and did not show a clear change from baseline rhythm

Muscle artifacts are seen prior to and during the event


A 31-year-old gravida 1, para 1 woman with a history of Wolff-Parkinson-White disease and recently diagnosed stage II Hodgkin lymphoma presented with a pruritic rash

She was diagnosed with Hodgkin lymphoma at 35 weeks’ gestation, and 1 week later she underwent cesarean delivery

At 3 weeks’ postpartum, she began chemotherapy (cycle 1, day 1) with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD)

On day 15 of cycle 1, she presented with linear, hyperpigmented streaks and welts on her arms, back, and legs

Intense, diffuse pruritus had developed within 24 hours of the patient’s first day of treatment, and her symptoms were poorly responsive to antihistamines and topical steroids

Pruritus was followed by the appearance of dark scratch marks as demonstrated in the Figure

Laboratory test results revealed a white blood cell count of 1.6 ×103 cells/mm3, with an absolute neutrophil count of 500 cells/mm3 and a total bilirubin of 0.3 mg/dL (to convert to μmol/L, multiply by 17.104), which was unchanged from the baseline total bilirubin

Clinical photograph of the patient’s back shows scratch marks that appeared after diffuse pruritus

Prior to the diagnosis of Hodgkin lymphoma, she was receiving routine prenatal care, and the only complication was pruritus without a rash that developed during the first trimester

She was evaluated for right supraclavicular adenopathy that was unresponsive to antibiotics during the third trimester

Findings from a lymph node biopsy were consistent with classic Hodgkin lymphoma, nodular sclerosis subtype

Staging imaging revealed bilateral supraclavicular jugular chain, paratracheal and mediastinal lymphadenopathy, and the erythrocyte sedimentation rate was 67 mm/h

She was diagnosed with stage II, unfavorable-risk Hodgkin lymphoma


A man in his 30s presented with painless swelling of the left upper limb and nodules on the left side of the chest and abdomen

The lesions had started a month previously as red nodules on the left axilla, ipsilateral chest, and back

Twenty days later, he developed edema in the left upper limb

While being evaluated for the cutaneous lesions, the patient was diagnosed with AIDS and began antiretroviral therapy

On examination, 6 erythematous, firm, subcutaneous nodules were present on the left side of the chest, abdomen, and left upper limb, varying in size from 2 × 2 cm to 4 × 4 cm (Figure, A)

There was diffuse erythema and edema on the left upper limb, leading to difficulty in limb movement (Figure, A)

Multiple dilated superficial vessels were present on the posterior aspect of the left arm and ipsilateral chest wall

Left axillary lymph nodes were grossly enlarged, firm, nontender, and nonmatted, with the largest lymph node measuring 6 × 4 cm

The patient’s CD4 cell count was 141/μL (to convert to ×109/L, multiply by 0.001), and his HIV load was 504 473 copies/mL

A skin biopsy sample was obtained from the plaque and sent for histopathologic examination (Figure, B and C)

A, Multiple erythematous indurated plaques and nodules confined to the left side of the chest and abdomen with axillary lymphadenopathy and upper limb edema

B, Skin biopsy sample showing infiltration with lymphoid cells and few histiocytes in the subcutaneous tissue (hematoxylin-eosin, original magnification ×400)

C, On immunohistochemical analysis, these cells showed nuclear positivity for c-Myc (c-Myc, original magnification ×400)


A woman in her 30s presented with a 1-year medical history of a painless, slowly enlarging, midline neck mass without associated dysphagia, odynophagia, weight loss, or history of infection

The mass was soft, mobile, and compressible in midline level IA, measuring 7 cm and posterior-superiorly displacing the tongue

The mass was visible as a clear blue lesion in the floor of the mouth and was nontender

Computed tomographic (CT) scan of the neck with IV contrast was performed (Figure)

The patient was taken to the operating room for a successful combined intraoral and transcervical approach to excision


Cocaine-induced midline destructive lesion

Extranodal natural killer/T-cell lymphoma, nasal type

A 36-year-old otherwise healthy white woman with a history of chronic sinusitis presented with progressive left facial pain and swelling of 5 months’ duration

Associated symptoms included epistaxis and left-sided epiphora

Prior to presentation, she had been treated as an outpatient with multiple rounds of oral antibiotics and steroids for presumed sinusitis without improvement

Social history included routine cocaine use 10 years ago

Physical examination demonstrated substantial erythema and edema of the left infraorbital region and left nasal sidewall and purulent nasal secretions (Figure 1A)

Endoscopic nasal examination revealed substantial swelling of the left nasal vestibule completely obstructing the left naris, swelling of the left nasolacrimal duct orifice, nearly total septal perforation with areas of necrotic bone, and no identifiable intranasal landmarks except for a remnant of the left middle turbinate (Figure 1B)

Laboratory evaluation revealed a white blood cell count of 12 300/μL with normal neutrophil count

erythrocyte sedimentation rate of 83 mm/h

and a C-reactive protein level of 134 mg/L

(To convert white blood cells to ×109/L, multiply by 0.001

C-reactive protein to nanomoles per liter, multiply by 9.524.) A maxillofacial computed tomographic (CT) scan demonstrated cartilaginous and anterior osseous nasal septal perforation and left nasal and preseptal soft-tissue thickening with associated periosteal reaction of the nasal process of the maxilla

B, Nasal endoscopic examination demonstrating significant soft-tissue necrosis