A male in his late teens presented with asymptomatic congenital papules, plaques, and nodules in a linear bilateral distribution following Blaschko lines on the scalp and face region

The papules and nodules appeared to grow as the boy grew, and some pedunculated lesions tended to fall off spontaneously

The patient had no other significant medical history and denied having a family history of similar lesions

Clinical examination findings revealed multiple skin-colored, nontender soft papules of varying sizes protruding from the skin surface on the right cheek, forehead, and jaw, as well as on the anterior surface of the scalp, distributed along Blaschko lines, with sparse vellus hairs and multiple hair follicles on the lesions (Figure, A and B)

However, no hair was observed on the lesion because the patient had shaved the hair on his face

An incisional biopsy of a pedunculated lesion above the left eyebrow was performed (Figure, B)

A and B, Papules, plaques, and nodules on the skin surface of the right cheek (A, B), forehead (B), intercilium (B), and jaw (B)

White arrowhead indicates the biopsy site (B)

Presence of sebaceous glands and the perifollicular fibrous sheath within a fibrotic stroma can be clearly seen (hematoxylin-eosin)


Eosinophilic granulomatosis with polyangiitis

A previously healthy 25-year-old woman presented with headache, dysarthria, double vision, and dizziness for 1 week

She denied any history of fever, head trauma, vomiting, diarrhea, abdominal pain, or cough

She had traveled to northeastern Brazil 2 months before the onset of the neurological symptoms

On examination, she had a mild right-side hemiparesis with hyperreflexia and hemiataxia

She could walk unassisted but presented with a broad base

She did not present with hepatosplenomegaly of lymphadenopathy

Her cranial magnetic resonance imaging  showed a T2-weighted fluid-attenuated inversion recovery hyperintense lesion with heterogeneous gadolinium enhancement in the pons (Figure)

There were no signs of diffusion restriction on diffusion-weighted imaging or hemorrhages on susceptibility-weighted imaging

Sagittal gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) (A) and sagittal T2-weighted fluid-attenuated inversion recovery (FLAIR) (B) showing the extent of the lesion

The laboratory test results showed a hemoglobin level of 15.3 g/dL (to convert to grams per liter, multiply by 10.0), total leukocyte count of 10 390/uL (to convert to ×109/L, multiply by 0.001), of which 1703 (16.4%) were eosinophils, and a platelet count of 284 000/μL (to convert to ×109/L, multiply by 0.001)

The patient’s liver and kidney function test results were normal

Computed tomography of the chest revealed bilateral patchy pulmonary infiltrates

Cerebrospinal fluid (CSF) analysis showed 640 cells, of which 57% were lymphocytes, 26% were eosinophils, and 13% were monocytes

protein levels were 70 mg/dL, and glucose levels were 46 mg/dL

Her blood cultures were found to be sterile


Linear or annular lupus erythematosus panniculitis of the scalp

A man in his 50s presented to our dermatology department with an asymptomatic, arc-shaped, depressed skin groove on the left side of his forehead, frontal scalp, and vertex area

Localized linear hair loss and hair thinning on the left scalp area were observed

The patient reported that when the lesion had begun to appear, approximately 10 years earlier, he had received 2 doses of intralesional steroid via injection on a small bald patch on the vertex

Thereafter, the lesion gradually progressed to the frontal scalp and eventually made a linear furrow on the left side of his forehead

Physical examination revealed 2 long, curved-line, depressed, alopecic patches on the left side of the vertex and frontal scalp area extending to the left eyebrow (Figure, A and B)

The lesions measured (length × width) 7 × 2 cm and 6 × 1 cm, respectively

Dermoscopic examination of the alopecic area revealed several short vellus hairs, yellow dots, and honeycomb hyperpigmentation

The result of a hair pull test was negative

The patient denied any trauma history and had no history of connective tissue disease nor any evidence of systemic involvement, such as arthralgia, photosensitivity, or skin rashes

Skin biopsies were performed on the left side of the vertex and the forehead

Histopathologic findings of the 2 biopsy specimens were identical (Figure, C and D)

A, Clinical image of annular arc from a longitudinally furrowed skin lesion on the left eyebrow and forehead to an alopecic lesion

B, Clinical image of the bandlike grooved alopecic lesion on the left side of the frontal scalp and vertex

C, Scanning view shows predominant lymphocytic infiltrates in perifollicular and periappendageal regions of the dermis and lobular panniculitis (hematoxylin-eosin staining)

D, High-power view shows inflammatory infiltrates between adipocytes with hyaline fat necrosis in the subcutis (hematoxylin-eosin staining)


Paraneoplastic autoimmune multiorgan syndrome

A White man in his 50s with a clinical history of recurrent respiratory infections and diarrhea presented with painful oral erosions that began 2 years before

Results of a previous intestinal biopsy had shown unspecific findings and absence of apoptosis

He reported a 5-kg weight loss that he attributed to impaired intake owing to the oral lesions

He was also being evaluated for a mediastinal mass detected in radiography of the chest performed for pneumonia

Physical examination revealed whitish edematous lacy patches with erosions on the dorsal and lateral aspects of the tongue and buccal mucosa (Figure, A)

A lingual biopsy specimen was obtained for pathologic evaluation and direct immunofluorescence (DIF

The result of indirect immunofluorescence (IIF) testing, using monkey esophagus, salt-skin split, and rat bladder as substrates, was negative

Enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis did not detect any desmoglein-1 or -3, bullous pemphigoid-180 or -230, collagen VII, desmocollin-1 to -3, laminin-332, envoplakin, or periplakin antibodies

indicative of hypogammaglobulinemia, with a decreased immunoglobulin (Ig) G serum level of 465 mg/dL (normal, 750-1600 g/L

Positron emission tomography revealed a 10-cm hypercapturing extrapulmonary mass (Figure, D)

Surgical excision of the mediastinal mass was performed

its histopathologic features were consistent with a type AB thymoma, Masaoka-Koga stage 2A

A, Lacy, white erosive lesions on the tongue

B, Epidermis with acanthosis, parakeratosis, necrotic keratinocytes, and dermal band lymphocytic infiltrate with effacement of the dermoepidermal junction (hematoxylin-eosin)

C, Fibrogen deposition along the basement membrane

D, Hypercapturing, heterogeneous mass in the right anterior hemithorax


A 46-year-old man presented with acute-onset weakness of his bilateral lower limbs for 3 days, accompanied by ascending numbness to just below his nipples

Three weeks prior, he had developed acute urinary retention

Neurological examination revealed weakness in bilateral lower limbs (Medical Research Council grade 4 on the right and grade 3 on the left), extensor plantar responses, and a sensory level at T6. Magnetic resonance imaging of his thoracic spine was performed 10 days after the onset of weakness and did not show any signal abnormalities or restricted diffusion

Cerebrospinal fluid analysis findings were remarkable for elevated protein (0.14 g/dL [to convert to grams per liter, multiply by 10]) but white cell count (5 cells/mm3) and glucose levels (54.05 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) were normal

Cytology and flow cytometry were negative for malignancy

Antibodies to aquaporin 4 and myelin oligodendrocyte glycoprotein were not detected

The patient developed a sudden worsening of weakness in his legs 2 weeks after initial presentation

Repeated thoracic spine imaging showed an area of T2 hyperintensity in the left posterolateral cord at T7, which did not enhance with contrast or show restricted diffusion (Figure 1A)

Notably, he had a 4-year history of an asymptomatic papular skin eruption with more lesions developing in the last 4 months

These were distributed on the neck, trunk, and limbs, sparing his face, scalp, and genitalia (Figure 1B)

Findings of extensive workup for malignancy, including full-body computed tomography scan, paraneoplastic antibody panel, and systemic autoimmune diseases (antinuclear antibody, antidouble stranded DNA, and myositis antibody panel), were negative

T2-weighted magnetic resonance imaging (MRI) of the thoracic spine showing an area of hyperintensity in the left posterolateral cord at T7 (A) (arrowhead)

Multiple papules were seen on the patient’s abdomen

These consisted of hypopigmented papules with central hyperpigmented umbilication and larger papules with typical central atrophic porcelain white scarring (B)


A 65-year-old woman with locally advanced, unresectable intrahepatic cholangiocarcinoma being treated with pemigatinib, a fibroblast growth factor receptor inhibitor (FGFRi), presented with a painful eruption on the bilateral lower extremities

Pemigatinib treatment was initiated 2 months prior to the skin findings

Laboratory evaluation demonstrated a mildly elevated D-dimer level at 578 ng/mL fibrinogen-equivalent units, prolonged prothrombin time of 12.7 seconds, elevated phosphorus level at 6.8 mg/dL (of note, phosphorus was 3.1 mg/dL 1 month prior), and normal calcium level and kidney function

Other laboratory tests to note include cryoglobulin and cryofibrinogen, which both had negative results

Within weeks, there was rapid progression with skin necrosis despite treatment initiation with rivaroxaban

Physical examination revealed retiform purpura with areas of necrosis involving the bilateral lower extremities (Figure, A and B)

A punch biopsy specimen from the right calf was obtained for histopathologic analysis (Figure, C and D)

Early reticulated erythematous patches (A) that rapidly progressed to prominent retiform purpura with cutaneous necrosis (B)

Calcium deposits within wall of a blood vessel in the subcutaneous tissue (C, white arrowhead) and pseudoxanthoma elasticum–like changes with fragmented calcified elastic fibers (D, white arrowheads) in the dermis and subcutaneous tissue (hematoxylin-eosin–stained sections


A young man presented to the clinic with large, purple plaques on the left lower extremity

The plaques had been present for years, but the patient noted enlargement and darkening for the past 5 years

The lesions were asymptomatic with no associated pruritus, bleeding, or pain

No treatments or diagnostic workup had been attempted prior to presentation

The patient was otherwise healthy and was a never-smoker with no history of hypertension, atherosclerotic disease, or HIV

Physical examination revealed dark violaceous plaques, scattered subcutaneous nodules, and swelling to the mid-shin of the left lower extremity (Figure, A)

There was mild warmth noted, but no palpable bruits

Complete metabolic panel, complete blood cell count, prothrombin, and serology were negative or within normal limits

A punch biopsy was performed and submitted for histopathologic analysis (Figure, B)

A, Violaceous papules, plaques, and nodules on the left lower shin

B, Proliferation of superficial and deep vessels, with thickening of the endothelium (hematoxylin-eosin)

C, Magnetic resonance angiogram demonstrating hypervascular soft tissue mass in the left lower extremity


A man in his 30s, employed as a painter, presented with multiple painless nodules on his right cheek of 4 years’ duration

He reported episodic breathlessness, cough, and wheezing with expectoration of brownish sputum, exacerbated with exposure to hay dust, in the past 5 years

He also reported recent-onset headache while reading

Physical examination revealed a depressed plaque measuring 6 × 4 cm in the right infraorbital region, surrounded by multiple nodules of sizes ranging from 1 × 1 cm to 5 × 1 cm (Figure, A)

The nodules were firm, mobile, and nontender on palpation

There was proptosis of the right eye with mild restriction of extraocular movements on lateral gaze

Examination of the oral cavity revealed dental caries, while gingivolabial sulcus was free on bidigital examination

Respiratory system examination revealed occasional polyphonic wheeze

Chest radiography imaging showed nodular opacities in right upper zone and bronchiectasis

Punch biopsy from 1 nodule was sent for histopathological and microbiological examination (Figure, B and C)

A, Destructive depressed plaque involving the medial half of the right side of the face surrounded by multiple nodules of varying sizes

B, Hematoxylin-eosin stain of skin biopsy specimen showing inflammatory infiltrate composed of giant cells in the deeper dermis extending into the subcutaneous fat

C, High-power view showing epithelioid cell granulomas and fungal profiles within giant cells (arrowheads)

D, Periodic acid–Schiff stain highlighting septate fungal hyphae with acute-angled branching within giant cells


A 33-year-old woman with a history of hereditary bilateral retinoblastoma as an infant presented to a primary care clinic with 1 week of right lower extremity swelling

At age 8 months, she was treated with right enucleation and left eye radiotherapy (50.4 Gy)

At age 4 years, she developed a recurrence of the retinoblastoma in the nasal cavity and was treated with 4 cycles of vincristine, doxorubicin, and cyclophosphamide followed by 1 cycle of cisplatin, etoposide, and intrathecal cytarabine

Primary care evaluation was prompted by her mother, as the patient had not noticed her lower extremity edema

She had no fevers, weight loss, shortness of breath, chest pain, abdominal pain, or history of deep vein thrombosis

Her physical examination was notable for firm, nonpitting edema to the hip

She did not have any associated tenderness, inguinal lymphadenopathy, or palpable abdominal masses

Her vital signs were within normal limits and she ambulated comfortably

Laboratory work results, including a complete blood cell count with a differential, comprehensive metabolic panel, and D-dimer levels, were within normal limits

Doppler ultrasonography of her right lower extremity showed no deep vein thrombosis

A computed tomography venogram demonstrated a 4.0 × 3.5 cm mass of likely vascular origin that was extending into the right common iliac vein (Figure)

Computed tomography venogram demonstrating a 4.0 × 3.5 cm heterogeneously enhancing lobulated mass (arrowhead) extending into the right common iliac vein


A 44-year-old woman presented to the otolaryngology clinic with a 6-month history of a right neck mass with compressive symptoms

She first noticed swelling that progressed to pressure and dyspnea while supine

She reported fatigue but denied pain, voice change, weight loss, hemoptysis, and dysphagia

A physical examination revealed a visible and palpable fullness to the right neck without overlying cutaneous or sinus tract changes

Results of a complete blood cell count, a thyroid stimulating hormone test, triiodothyronine and levorotatory thyroxine testing, and a complete metabolic panel were normal

Ultrasonography showed a 7.9 × 6.3-cm septate cystic mass lateral to the right thyroid gland

A contrast-enhanced computed tomography scan of the neck demonstrated a large, nonenhancing cystic-appearing lesion abutting the lateral and posterior margins of the right thyroid lobe and extending from the level of the piriform sinus to the thoracic inlet (Figure)

Ultrasound-guided fine-needle aspiration revealed clear fluid with a parathyroid hormone (PTH) level of 67 pg/mL (reference range, <100 pg/mL

A barium swallow study showed no communication between the cyst and the piriform sinus

Excision in the operating room was performed, and right thyroid lobectomy was necessary because of the intimate association of the lesion to the thyroid lobe

Contrast-enhanced computed tomography scan of the neck with coronal (A) and axial (B) views demonstrating the right cystic neck mass


A 40-year-old man presented with a large left neck mass in the setting of recently treated mixed nonseminomatous germ cell tumor (NSGCT) of the right testicle with metastasis to the retroperitoneal and mediastinal lymph nodes

He was treated with a right radical orchiectomy and 4 cycles of etoposide, ifosfamide, and cisplatin (VIP) chemotherapy with resulting reduction in metastatic tumor burden and normalization of α-fetoprotein and β-human chorionic gonadotropin

The patient’s neck swelling, which initially decreased in size while undergoing chemotherapy, progressively enlarged shortly after concluding treatment

He underwent magnetic resonance imaging and computed tomography of the neck that showed a clearly defined, bulky supraclavicular mass confined to left neck levels 3, 4, and 5 (Figure)

A, Postcontrast coronal magnetic resonance imaging (MRI) demonstrated a bulky, cystic left neck mass at levels 3, 4, and 5. B, Axial computed tomography (CT) scan with contrast highlighted extensive septations and modularity within the mass


Extramedullary myeloid sarcoma of the larynx

A 59-year-old man presented with progressive hoarseness and dyspnea over a 2-month period

Fifteen months previously, he had undergone allogeneic stem cell transplant (allo-SCT) with a matched related donor for treatment of fms-like tyrosine kinase (FLT3) internal tandem duplication–mutated acute myeloid leukemia (AML)

The patient had been diagnosed with chronic gastrointestinal graft-vs-host disease after a workup for diarrhea

Results of a restaging bone marrow biopsy 2 weeks prior to presentation showed no evidence of leukemia

Physical examination findings revealed no neck masses or abnormalities, but the patient was noted to be severely dysphonic and stridulous

Flexible laryngoscopy findings demonstrated a right vocal fold neoplasm crossing the posterior commissure with associated bilateral vocal fold motion impairment and obstruction of the glottic airway (Figure, A)

Awake tracheostomy was performed for airway protection, and biopsy of the neoplasm was obtained via operative microlaryngoscopy (Figure, B)

Histologic findings demonstrated diffuse infiltrate of large cells with irregular nuclear contours, vesicular chromatin, and prominent nucleoli (Figure, C)

Immunohistochemical stains showed CD33, CD43, and CD117 positivity, with a subset positive for CD7 and myeloperoxidase

Stains were negative for CD3, CD20, and cytokeratin expression

Evaluation of the larynx from awake flexible laryngoscopy (A) including posterior commissure (A, inset) and operative microlaryngoscopy (B) with biopsy (C


Malignant neoplasm–associated microscopic polyangiitis

Intravascular involvement by NK/T-cell lymphoma

A woman in her 50s with a history of nasal-type natural killer (NK)/T-cell lymphoma (diagnosed 2 years prior

treated with pembrolizumab and methotrexate, ifosfamide, etoposide, dexamethasone, and pegaspargase) and chronic pulmonary coccidiomycosis being treated with fluconazole was admitted for fever, hypotension, and rash

Three months prior, pembrolizumab treatment was stopped because of a widespread morbilliform reaction, which had resolved completely 6 to 8 weeks before admission

The new widespread, asymptomatic skin eruption had been ongoing for 1 to 2 weeks and appeared different from her pembrolizumab reaction

A complete blood cell count was notable for a normal white blood cell count of 4100/μL, normal absolute neutrophil count of 2940/μL, chronic normocytic anemia (hemoglobin level of 8.2 g/dL), and chronic thrombocytopenia (platelet count of 62 ×103/μL)

Blood culture results showed no growth at 1 week

Serum β-D-glucan, galactomannan, Coccidioides antibody by complement fixation, and immunodiffusion results were negative

Respiratory viral panel and SARS-CoV-2 test results were negative

Total body skin examination findings were notable for widespread, nontender, erythematous patches and thin plaques, some with prominent overlying telangiectases and hyperpigmentation (Figure, A)

A punch biopsy of a representative lesion was performed (Figure, B-D)

A, Physical examination findings were notable for widespread erythematous patches and thin plaques, some with prominent overlying telangiectases

B and C, Hematoxylin-eosin stained section

D, CD56 immunostaining labels intravascular atypical cells


A 66-year-old man presented with multiple progressive ulcers on the right side of his face that had developed over the past 3 months (Figure, A)

He had also experienced a burning sensation on the right side of his face, but denied headache, shoulder, or jaw pain and visual disturbance

Neurological examination revealed hypoesthesia of the right side of the face, while cold-warm sensation and motor function were intact

The erythrocyte sedimentation rate was 82 mm per hour (normal value, less than 15 mm per hour) and the serum C–reactive protein concentration was 107 mg/L (normal value, less than 5 mg/L)

Chest radiography showed bilateral perihilar infiltrates consistent with pneumonia

About 2 weeks before the ulcerations developed, the patient had been admitted to the hospital for unstable angina, and coronary angiography was performed

Immediately after the angiography, the patient developed left-sided hemiplegia and hemianopsia

Magnetic resonance imaging of the brain revealed an extensive ischemic posterior circulation stroke involving the right occipital lobe, lower cerebellar peduncle, and pontomedullary boundary (Figure, B)

Clinical and radiological findings in a man aged 66 years

A, Multiple ulcers limited to the right half of the face

B, Magnetic resonance image showing brainstem involvement by the stroke (diffusion-weighted sequence)


Immune checkpoint inhibitor–induced acute interstitial nephritis

Acute tubular necrosis secondary to kidney melanoma metastasis

A 53-year-old man received a diagnosis of stage IV melanoma with metastatic disease to the spine and brain 3 months before presentation

Four weeks following receipt of immunotherapy with ipilimumab and nivolumab, he developed acute abdominal pain in the setting of a rapidly rising lactic acid dehydrogenase levels, prompting hospital admission

Imaging results showed mild disease progression (new ascites and periportal metabolic lymph node)

Splenic infarct and portal/splenic vein thrombi were identified as etiologies of his acute pain and were presumed to be secondary to hypercoagulable state of malignancy

Over the next 3 days, he had rising serum creatinine (sCr) levels (baseline, approximately 1 mg/dL [to convert to μmol/L, multiply by 88.4])

The initial workup included ultrasonography and urinalysis

Ultrasonography results showed abnormal intraparenchymal flow to both kidneys without evidence of kidney artery stenosis

Urine studies were consistent with prerenal etiology, while the presence of casts suggested acute tubular necrosis

Nephrotoxic medications (omeprazole/pantoprazole) were discontinued

The top differential diagnoses at this juncture included contrast-induced nephropathy or immune checkpoint inhibitor (ICI)–induced acute interstitial nephritis, and empirical high dose steroids were prescribed

Despite observation and steroid treatment, his sCr levels continued to increase over the next 5 days, peaking at 5.8 mg/dL, and the patient progressed into anuric kidney failure, requiring hemodialysis

This prompted a kidney biopsy for definitive diagnosis (Figure)

One week later, he received encorafenib, a BRAF inhibitor.1 Two weeks later, the patient’s kidney function began to improve, and hemodialysis was discontinued

He continued to show gradual improvement, with a return to near baseline kidney function (sCr level, 1.3 mg/dL) approximately 6 weeks after treatment initiation

Histopathology (original magnification x40) of kidney capillaries with hematoxylin and eosin stain showing atypical cells (arrowheads) (A), tubules with hematoxylin and eosin stain (B), and capillaries with melanin-A (C)


A 71-year-old man with a history of rheumatoid arthritis and type 2 diabetes presented to the otolaryngology team with 6 weeks’ history of pain and ulcers in the pharynx

He also complained of nasal regurgitation

He took linagliptin, valsartan, and 15 mg of methotrexate weekly

He was a nonsmoker and consumed very little alcohol

Clinical examination including flexible nasendoscopy revealed multiple shallow ulcers on the posterior wall of the nasopharynx

There was a large defect involving the entire soft palate on the left

There was no obvious mass or any exophytic lesion

The edges of the soft palate defect were smooth and clean (Figure 1)

There was no cervical, axillary, or inguinal lymphadenopathy

Findings of the remaining head and neck examinations were normal

Results of laboratory investigations, including lactate dehydrogenase level and autoimmune antibody tests, such as antinuclear antibody and antineutrophil cytoplasmic antibody, were negative

Screening test results for HIV and Treponema pallidum were also negative

The only positive result was immunoglobulin (Ig) G for Epstein-Barr virus (EBV)

Magnetic resonance imaging of the head and neck on short tau inversion recovery sequence confirmed the soft palate defect but also showed some thickening and hyperenhancement around the edges of the defect

There was no demonstrable nasopharyngeal mass

The hard palate was intact, and there were no significant cervical lymph nodes

The patient had biopsies taken from the ulcers and edges of the soft palate defect


A 50-year-old woman presented with a 2-month history of a neck mass that was associated with hoarseness of voice and globus sensation

Physical examination showed thyromegaly (right greater than left) with an approximately 5-cm palpable nodule in the right lobe

There was no tenderness or cervical lymphadenopathy

There was no prior radiation exposure to the head and neck area

Thyroid function test results were normal, and she did not take thyroid medications

A relative had received a diagnosis of papillary thyroid cancer at age 50 years

There was no other pertinent family history, including a history of multiple endocrine neoplasia

Ultrasonography results showed a multinodular goiter with a dominant 4.6-cm right thyroid nodule, 1.6-cm left-sided thyroid nodule, and suspect left level IV lymph node

Ultrasonography-guided fine-needle aspiration biopsy results showed papillary thyroid carcinoma (PTC) (Bethesda VI) with a BRAFV600E variation in the left nodule and lymph node, and atypia of undetermined significance (Bethesda III) with a suspicious Afirma genomic sequence classifier in the right nodule

She underwent total thyroidectomy with modified left lateral neck dissection

Gross examination of the specimen showed a 2.9-cm pale-tan, partially circumscribed, soft nodule in the right thyroid lobe

a 1.4-cm pale-tan, fibrotic, centrally brown nodule in the left lobe

and a 1.8-cm pale-tan, rubbery, partially circumscribed nodule in the isthmus

Histologic examination of the right thyroid lesion was performed (Figure), with ancillary testing

A, The right-sided nodule showed an organoid zellballen pattern, with sharp demarcation from thyroid tissue (hematoxylin-eosin)

B, At higher magnification, the tumor cells exhibited amphophilic granular cytoplasm, round to oval nuclei, and salt-and-pepper chromatin (hematoxylin-eosin)


Intralymphatic proliferation of T-cell lymphoid blasts

A woman in her 70s presented with a 3-month history of episodic fever and painless cutaneous lesions on her lower limbs

The patient otherwise felt well and denied malaise, weight loss, or any other symptoms

She did not have any known benign inflammatory conditions

Physical examination showed indurated plaques with multiple telangiectasias (Figure, A and B) on almost all the surface of the legs

Except for slightly elevated C-reactive protein levels, the results of other routine blood and urine tests were unremarkable

A skin biopsy specimen was obtained for histopathology examination (Figure, C and D)

A, Indurated violaceous plaques with multiple telangiectasias on the lower limbs

B, Prominent telangiectasia on the thigh

C, Histopathologic analysis shows large round cells proliferating within dermal blood vessels (hematoxylin-eosin)

D, Round cells with scanty cytoplasm and prominent nucleoli filling a vessel (hematoxylin-eosin)


A school-aged boy experienced generalized erythematous rashes for 4 years

Skin examination showed ichthyosiform brownish plaques on his lower extremities and multiple erythematous confluent papules and plaques on his trunk and face (Figure, A and B)

Topical steroid and pimecrolimus were administered, but their effects were limited

In addition, painful distal and proximal interphalangeal joints were noted for 2 years, and the patient could not clench his fists

Uveitis in both eyes was also diagnosed by an ophthalmologist

Microscopic examination of his hair showed no trichorrhexis invaginata or trichorrhexis nodosa

A skin biopsy specimen was obtained and submitted for further histopathologic analysis (Figure, C and D)

A, Diffuse erythematous papules and plaques with mild scaling and some confluence on the face, neck, and trunk

B, Ichthyosiform rashes predominantly distributed over the lower extremities

C, Tissue biopsy results revealed multiple circumscribed nests of granulomas that were infiltrating the dermis and subcutis (hematoxylin-eosin)

D, At higher magnification, histologic findings showed noncaseating granulomas with multinucleated giant cells and neutrophil infiltration in the dermis and subcutis (hematoxylin-eosin)


A 29-year-old man presented with a 2-month history of rapidly growing, widespread, asymptomatic skin nodules all over his body

He denied having fever, chills, fatigue, night sweats, or weight loss

He had no history of malignant neoplasm or chemical exposure

Physical examination findings demonstrated numerous erythematous, indurated nodules involving the surface of his head, neck, torso, and extremities, without ulceration or scarring (Figure, A and B)

Findings of systemic reviews were unremarkable, and there was no lymphadenopathy or peripheral nerve enlargement

Complete blood cell count with differential results were normal (white blood cell count, 6060/μL, normal range, 4500-10 000/μL

absolute neutrophils, 3070/μL, normal range, 1800-8300/μL [to convert cell counts to ×109/L, multiply by 0.001])

Serum lactate dehydrogenase level was elevated (279 U/L, normal range, 100-240 U/L [to convert to μkat/L, multiply by 0.0167])

Biopsies from skin nodules (Figure, C) and bone marrow were obtained

Skin lesions on the patient with widespread, erythematous, indurated nodules involving his head and neck (A) and trunk (B)

C, Histologic findings demonstrate diffuse dermal infiltrates, extending to the subcutis, with sparing of the upper papillary dermis (original magnification ×20)

The infiltrates are characterized by immature myeloid cells (inset, original magnification ×400)


A 9-year-old boy was referred to the pediatric otolaryngology clinic with a 3-month history of a left-sided neck mass

The mass had been slowly enlarging and he had been experiencing mild intermittent pain, but no additional symptoms were reported

His medical history was significant for several episodes of upper respiratory infection during the previous winter season, and he previously had an adenotonsillectomy several years prior and bilateral ear tubes placed 1 year before presentation

Physical examination showed a mildly tender, nonmobile, left parotid mass near the angle of the mandible with no overlying skin changes or drainage around the mass

There was no lymphadenopathy or other lesions noted in the neck area, and cranial nerve VII was fully intact

Ultrasonography results of the neck showed a left 1.5-cm preauricular nodular mass with internal and marginal vascularity

A neck magnetic resonance imaging study without contrast performed at an outside institution revealed the 1.5-cm heterogeneous intraparotid nodule that was predominantly isotense to glandular tissue on T1 images with vague hypointensity of a small irregular central region, as well as vague hyperintensity on T2 images

He subsequently underwent fine needle aspiration biopsy to assess the lesion, which demonstrated benign-appearing salivary gland tissue and clusters of myoepithelial cells

The mass was continuing to enlarge, and the patient’s pain was increasing in that area, so the decision was made to perform left superficial parotidectomy with preservation of the facial nerve

Intraoperatively, the left parotid mass was noted to be just below the lower branches of the facial nerve

The excised parotid mass was sent to the pathology department for analysis

Gross examination of the specimen demonstrated a 1.6 × 1.5 × 1.1–cm tan-white, well-circumscribed lesion that was partially surrounded by salivary gland parenchyma (Figure, A)

Histologic examination of the nodule was performed (Figure, B and C)

A, Serial sections of the intraparotid mass demonstrate a well-demarcated solid nodule with tan-white, glistening cut surfaces

B, Microscopic examination shows a multilobulated, complex lesion with prominent stromal fibrosis and collections of ductal structures with varying degrees of cystic change (hematoxylin-eosin)

C, Acinar cells with brightly eosinophilic intracytoplasmic granules (hematoxylin-eosin)


A woman in her late 30s was evaluated by the dermatology inpatient consult service for a 4-day history of perianal pain

Her medical history included systemic lupus erythematosus, antiphospholipid antibody syndrome, and external hemorrhoids

Six months before admission, she underwent a deceased donor kidney transplant

One month before presentation, she was hospitalized for acute cellular transplant rejection managed with systemic corticosteroids, belatacept, mycophenolate mofetil, and tacrolimus therapies

Her immunosuppressive regimen at the time of dermatologic evaluation consisted of prednisone, 5 mg daily, and mycophenolate mofetil, 500 mg twice daily

On admission, she was afebrile and normotensive

laboratory results were notable for an elevated creatinine level of 1.43 mg/dL (reference range, 0.40-1.30 mg/dL) (to convert to micromoles per liter, multiply by 88.4) and thrombocytopenia (platelet count, 92 × 103/μL [reference range, 140-440 × 103/μL] [conversion to ×109 per liter is 1:1)

She developed diarrhea 1 day after admission

Stool antigen test results for cryptosporidium, giardia, and rotavirus were negative

Polymerase chain reaction (PCR) test results for campylobacter, norovirus, salmonella, shigella, Shiga toxin–producing Escherichia coli 1 and 2, Vibrio cholerae, and Yersinia enterocolitica in the stool were negative

Antigen and toxin test results for Clostridium difficile in the stool were positive

Total body skin examination was notable for 1- and 3-cm tender, round perianal ulcers with a clean base

Another 4-mm round ulcer was present at the superior intergluteal cleft (Figure, A)

A biopsy specimen of a perianal ulcer border was obtained for histopathologic analysis (Figure, B-D)

Clinical and histologic images of multiple perianal ulcers

A, Two round ulcers, each with well-demarcated borders, were present perianally

A smaller, third ulcer was also noted in the intergluteal cleft

B, Microscopic examination of the punch biopsy on low magnification reveals epidermal ulceration and mixed dermal inflammation (hemoxylin-eosin

C, On higher magnification, the epidermis lacks viral cytopathic changes but there are enlarged dermal fibroblasts and endothelial cells (hemoxylin-eosin)

D, Higher magnification reveals large fibroblasts and endothelial cells with glassy cytoplasm and intranuclear inclusions (hemoxylin-eosin)


A woman in her 50s presented with an edematous, massively enlarged right auricle

The patient had immigrated to Israel 9 years before admission

She was adamant that the lesion had been present since early childhood but had gradually increased with a recent appearance of foul-smelling otorrhea

On examination, the auricle was markedly enlarged, edematous, and encircled by an erythematous, indurated plaque partially covered with a fine scale (Figure 1A)

Diascopy revealed an “apple jelly” appearance

There was no local or distant lymphadenopathy

general physical examination findings were unremarkable

A, Clinical findings at presentation in 2008 showed an enlarged and edematous auricle encircled by an indurated erythematous plaque

Bloody otorrhea from the external auditory canal was seen

B, Biopsy specimen showed superficial and deep diffuse granulomatous dermatitis (hematoxylin-eosin)

C, Higher magnification demonstrated classic tuberculoid granuloma with histiocytes and Langhans giant cells surrounded by lymphoplasmacytic infiltrate (hematoxylin-eosin)

Results of routine laboratory investigations, including complete blood cell count, biochemical profile, liver function tests, and chest radiography, were normal

An intradermal Mantoux test induced a 20-mm induration

Histopathologic evaluation of the cutaneous lesion revealed noncaseating granulomatous dermatitis involving the dermis (Figure 1B)

High magnification demonstrated tuberculoid dermal granulomas composed of histiocytes and Langhans giant cells surrounded by lymphoplasmacytic infiltrate (Figure 1C)

Results of polarized light examination and periodic acid–Schiff, Ziehl-Neelsen, Giemsa, Gram, and Grocott methenamine silver stains were negative for microorganisms


A 16-year-old boy with acute leukemia of ambiguous lineage developed tender, 1- to 2-cm erythematous plaques and nodules during treatment with chemotherapy

Previously, he had been well, with morphological remission found on a recent bone marrow biopsy

The patient had no significant dermatological history, except an allergy to cashew nuts and a prior episode (6 mo) of urticaria during a platelet transfusion that had resolved with 1 dose of oral antihistamine

The patient’s medications included ondansetron, aprepitant, prednisolone, and oxycodone (supportive care initiated with chemotherapy), and long-term posaconazole and trimethoprim/sulfamethoxazole treatment

Lesions were noted on day 2 of the fourth cycle of a chemotherapy regimen comprising fludarabine, cytarabine, and filgrastim (G-CSF)

Initially present over the distal limbs, palms, and soles, the lesions progressed to the proximal limbs and lower trunk during 24 hours (Figure, A and B)

The patient developed a fever, which we extensively investigated

Intravenous cefotaxime was commenced, but because no infectious source was identified, the fever was thought to be secondary to cytarabine

A and B, Clinical images showing erythematous plaques and nodules on patient’s palm and forearm

C, Hematoxylin-eosin–stained specimen showing leukocytoclastic neutrophilic infiltrate in deeper dermis, around appendage structures and coiled eccrine glands, and into the interstitium

The results of a complete examination of blood drawn at lesion onset demonstrated a total white cell count of 6330/μL (to convert to 109/L multiply by 0.001) with absolute neutrophil count of 6140/μL, more than the previous day’s counts of 3210/μL and 1720/μL, respectively

The blood film demonstrated increased neutrophil granulation with a left shift

A punch biopsy from the upper arm was performed (Figure, C)


A 56-year-old patient with no medical history presented spontaneously to the emergency department of our university hospital (Assistance Publique Hôpitaux de Paris) for bilateral neck swelling that had developed over 24 hours

The patient had no traumatic or iatrogenic triggers

He reported an edema of the lower lip that resolved spontaneously the day before

He had no dyspnea nor dysphagia, but did have a discrete dysphonia

Neck swelling was global, bilateral, and painless, and was most severe on the left side

There was a rash, the border of which was marked with a felt pen

Nasofibroscopy results showed a normal airway with a posterior pharyngeal wall bulging

Oropharyngeal and oral cavity examination results were normal, with no trismus

A contrast-enhanced computed tomography (CT) scan showed a large retropharyngeal fluid accumulation of 2 × 10 × 6 cm that extended laterally to the vascular spaces, especially on the left side (Figure, A and B)

This was associated with infiltration of the mediastinal fat and a thin left pleural effusion

There was no vascular thrombosis or dental abnormality

We did not have the result of the C reactive protein assay

Cervical computed tomography scan of the sagittal (A) and axial (B) planes

In the sagittal plane, there is retropharyngeal fluid accumulation, and in the axial plane, there is fluid accumulation in the retropharyngeal and vascular spaces with fat infiltration


Spontaneous airway hemorrhage with obstructive hematoma

A 71-year-old man presented to the emergency department with dyspnea, dysphonia, dysphagia, and neck swelling

He denied chills, fever, neck stiffness, new medications, otalgia, sick contacts, trismus, and use of an angiotensin-converting enzyme inhibitor

His complex medical history included factor V Leiden deficiency requiring therapeutic anticoagulation, heart failure with atrial fibrillation, and chronic obstructive pulmonary disease associated with 110-pack-year smoking history

Laboratory studies demonstrated an international normalized ratio of 16.4, a prothrombin time of 118.1 seconds, and a partial thromboplastin time of 81.4 seconds

On examination, the patient had substantial dysphonia, fullness in the left submandibular region, and ecchymosis of the lateral left neck extending toward the midline

Contrast-enhanced computed tomography performed in the emergency department revealed a large, intermediate-density, modestly enhancing, left-sided submucosal lesion extending from the nasopharynx inferiorly to the glottis with encroachment on the airway (Figure)

Flexible fiberoptic laryngoscopy demonstrated a large submucosal mass extending from the left posteroinferior nasopharyngeal wall to the left lateral and posterior pharyngeal walls, obstructing the view of the left supraglottis, glottis, and piriform sinus

The right side of the epiglottis was ecchymotic and edematous

The mass extended farther along the aryepiglottic fold to involve the arytenoid and interarytenoid space, as well as the false vocal fold on the left

The vocal cords were only partially visualized

Given the important laryngoscopy findings, the decision was made to proceed with awake fiberoptic nasotracheal intubation in the operating room to secure the patient’s airway

Contrast-enhanced computed tomography of the neck in the coronal (A) and axial (B) views demonstrating a large, predominantly left-sided, obstructive, submucosal, upper airway lesion extending from the nasopharynx to the glottis


A girl younger than 2 years presented with a 1-year history of slightly pruritic lesions involving her face

She was born after an uncomplicated pregnancy and delivery, and her growth and development were appropriate for her age

No associated symptoms such as fever, anorexia, or weight loss were noted

Physical examination revealed multiple skin-colored and erythematous follicular papules, 1 to 2 mm in diameter, distributed in a segmental pattern on the right side of the forehead, as well as the dorsum and tip of the nose

A small, excoriated plaque was also noted on the right malar area (Figure 1A)

No mucosal lesions were present, and the rest of the physical examination findings were unremarkable

A complete hematological and biochemical survey, including blood cell count, liver and renal function tests, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, disclosed no abnormalities

Representative histopathological features are shown in Figure 1B and C

Multiple skin-colored and erythematous follicular papules are seen coalescing into a linear plaque involving the patient’s forehead, as well as the dorsum and tip of the nose (A)

Two skin punch biopsies were taken from the forehead and nose (B and C)


A 17-month-old boy was referred to pediatric dermatology for evaluation of a slow-growing, nontender plaque on the lower back

The child's mother reported that, on discovery, the plaque was initially 1 × 1 cm and had since grown in size with the child

She was uncertain if the plaque was present at birth

The patient’s medical history was significant for dermal melanocytosis of the right hip and mid back, increased head circumference (97th percentile), and expressive language delay

There was no family history of congenital birthmarks or neurofibromatosis type 1 or 2.Physical examination revealed a well-appearing boy with normal vital signs and Fitzpatrick type III skin type

On the left lower back, there was a 15 × 5-cm indurated skin-colored to yellow, firm, multinodular plaque with hypertrichosis, extending from the midline to the left lower flank (Figure, A)

There were additional blue-gray patches on the back and right hip, as well as a small café au lait macule on the right lower back

Limited neurologic examination was within normal limits

A 4-mm punch biopsy was performed for further diagnostic evaluation (Figure, B-D)

A, Large, well-defined, firm yellow to skin-colored multinodular hypertrichotic plaque on the left lower back

B, Hematoxylin-eosin staining demonstrates diffuse dermal infiltration of spindle cells, predominantly encircling terminal folliculosebaceous units (original magnification ×4)

C, Higher-power magnification highlights a mix of partially fusiform melanocytes and dendritic cells with glassy, eosinophilic cytoplasm (hematoxylin-eosin, original magnification ×40)

D, Immunohistochemical staining reveals diffuse and periadnexal S100 positivity in the mid to deep dermis (original magnification ×4)


A 73-year-old man with metastatic BRAF-mutant colorectal cancer presented with a 1-month history of crusted lesions with purulent drainage on the scalp, with associated pruritus and pain

Five months earlier he began treatment with cetuximab, binimetinib, and encorafenib, complicated by a grade 1 acneiform eruption that was managed with doxycycline hyclate and topical hydrocortisone and clindamycin phosphate

Oncologic therapy was withheld pending further evaluation of the scalp eruption

He had a distant history of actinic keratoses on the scalp treated with liquid nitrogen but otherwise denied previous skin cancer

Examination of the scalp revealed male pattern baldness, diffuse actinic damage, and multiple thick, yellow-brown crusts overlying erosions with purulent drainage (Figure 1)

A wound culture was performed and grew methicillin-sensitive Staphylococcus aureus


A 16-year-old female complained of an olfactory disorder since birth

She had a history of a laryngeal tracheoesophageal fissure, intestinal hernia, and hearing loss because of an ossicular malformation

From age 10 years, she was unable to catch up with conversation of curry smell

Olfactory tests were performed, and T&T olfactometry1  results showed severe hyposmia (5.4/5.4

detection threshold/odor recognition threshold)

On the card-type odor identification test, Open Essence,2  she only identified menthol correctly

Her Self-Administered Odor Questionnaire3  score was 20%

Her visual analog scale4  score was 10 for odor but 100 for taste

There were no unusual nasal findings on endoscopy or computed tomography

Because we suspected a congenital olfactory disorder, we recommended magnetic resonance imaging (MRI), which showed olfactory bulb (OB) atrophy (Figure, A)

A, Coronal short-tau inversion recovery magnetic resonance imaging (MRI) of the olfactory bulb shows that the olfactory fissure remains aerated, but the olfactory bulb is slightly atrophied on both sides (arrowheads)

There were no dysplastic signs in the frontal gyri

B and C, An axial MRI T2-weighted image of the pelvis shows vaginal defects and bilateral 1 layer–differentiated uterine rudiments (arrowheads) that were 35 mm on the left and 37 mm on the right

Both ovaries are normal (equivalent to Mullerian duct anomaly class I)

The patient also confirmed that she had not started menstruating

After consulting the pediatric department, an endocrine test was performed

The results showed an atypical reaction to the insulin tolerance test

However, the results for adrenocorticotropic hormone/cortisol corticotropin-releasing hormone load test, diurnal variation, and urine accumulation were normal

The luteinizing hormone (LH)/follicle-stimulating hormone (FSH) values were normal as determined by LH-releasing hormone load tests

She was subsequently referred to the gynecology department

Her MRI results showed a vaginal defect and uterine rudiments

however, the bilateral ovaries were normal (Figure, B and C)


A woman in her 70s with recurrent primary peritoneal carcinoma receiving pembrolizumab and ipilimumab presented to the Division of Dermatology with a pruritic rash that had been ongoing for 2 weeks

The rash started as an erythematous papule on her right arm 2 months after initiation of a new immunotherapy regimen, then gradually enlarged and spread to involve both legs (Figure, A and B)

She denied any new systemic symptoms associated with onset of the rash

A recent trial of oral terbinafine for possible tinea corporis yielded no improvement

Physical examination revealed erythematous annular plaques without scale on her right arm and bilateral legs

A 4-mm punch biopsy was obtained from the patient’s right arm (Figure, C and D), and she was prescribed fluocinonide, 0.05%, ointment

She returned to the clinic 3 weeks later with resolution of pruritus but enlarging lesions

Her last dose of ipilimumab was 2 months prior, and she was scheduled to receive pembrolizumab with doxorubicin, carboplatin, and prednisone for treatment of her underlying malignant tumor

For management of her rash, the patient was prescribed betamethasone dipropionate, 0.05%, ointment (augmented)

A, Erythematous annular plaques without scale on the left lower leg

B, Erythematous annular plaques without scale on the right lower leg

C, Hematoxylin and eosin stain demonstrating superficial and deep perivascular and interstitial inflammation

D, Hematoxylin and eosin stain demonstrating numerous scattered eosinophils


A man in his 60s presented as a transfer from an outside hospital

The division of dermatology was consulted for evaluation of lesions on the face, chest, back, and arms that were gradually increasing in size and number over the past year

Physical examination revealed leonine facies with madarosis and an eschar on the nasal dorsum (Figure, A)

Red-to-brown dome-shaped papules coalescing into plaques were present on the upper extremities

The lesions were nontender and nonpruritic

Cervical and axillary lymph nodes were palpable

The patient had a muffled voice and reported shortness of breath with exertion

Results of laboratory investigation demonstrated marked leukocytosis with a white blood cell count of 77.5 × 103/uL with 76.5% lymphocytes

No blasts were present on peripheral smear

Computed tomography of the chest, abdomen, and pelvis demonstrated multiple enlarged mediastinal, axillary, subpectoral, abdominopelvic, and inguinal lymph nodes

Small pulmonary nodules were also detected

A punch biopsy was obtained from the right arm (Figure, B, C, and D)

A, Infiltrative plaques and nodules obscuring normal facial architecture

B and C, Histopathologic images show normal epidermis with dense diffuse dermal lymphoid infiltrate composed of small to medium cells with irregular nuclear contours (hematoxylin-eosin stain)

D, Immunohistochemistry shows diffusely positive cyclin D1 staining


A 42-year-old woman presented with clinical features of microcephaly, short stature, intellectual disability, severe degree of scoliosis, gait abnormality, and encephalopathy (Figure, A and B)

She was born in 1973 at 38th week of gestation followed by a normal delivery (weight, 3.15 kg and head circumference, 42 cm) to nonconsanguineous parents

The head size was normal at birth, and no other abnormalities were seen during her infancy

At age 2 years, her parents noticed that she had delayed motor and language milestones

She experienced a progressive developmental delay such as reduction of head growth, loss of acquired communication, and loss of motor functions between ages 9 and 12 years

The severity of scoliosis increased with age, and she became a wheelchair user at age 18 years

She was referred to us at age 40 years with the characteristic features of growth deceleration (height, 142 cm

body mass index, 11 [calculated as weight in kilograms divided by height in meters squared]), apraxia, left-sided hemiplegia, spasticity, sleep apnea, constipation, osteoporosis, hypoalgesia, and repetitive hand tapping (Video)

Blood reports showed anemia (hemoglobin level of 9.1 g/dL

to convert to grams per liter, multiply by 10) and low levels of high-density lipoprotein cholesterol (47 mg/dL

to convert to millimoles per liter, multiply by 0.0259)

There was no history of autistic behavior, vision or hearing impairments, or epilepsy

The electrocardiogram showed sinus rhythm with T wave inversion (V3-V6), and echocardiography showed mild cardiomegaly

The brain magnetic resonance imaging studies showed a diffuse reduction in the corpus callosum involving splenium and enlarged right ventricle, resulting in cerebral lateral ventricular asymmetry (Figure, C)

A, Characteristic features of a 42-year-old woman with microcephaly

C, Magnetic resonance imaging of the patient with reduced volume of corpus callosum (arrowhead), sagittal view


A female smoker in her 50s was referred for hyperparathyroidism and a multinodular goiter

The patient reported symptoms of joint and musculoskeletal pain and fatigue but denied fever, sore throat, abdominal pain, and kidney stones

Her medical history was remarkable for congestive heart failure and schizophrenia

Neck examination revealed no meaningful findings except right thyroid enlargement

Results of laboratory evaluation demonstrated normal white blood cell count, borderline hypercalcemia (10.6 mg/dL), and elevated parathyroid hormone level (208 pg/mL)

She underwent ultrasonography at an outside facility, and results demonstrated a 2.2-cm dominant right thyroid nodule with additional smaller thyroid nodules

Findings of preoperative technetium-99m (Tc-99m) sestamibi planar and single-photon emission computed tomographic/computed tomographic (SPECT/CT) imaging (Figure, A) were nonlocalizing for a parathyroid adenoma and showed increased uptake in the dominant right thyroid nodule (Figure, B)

Results of an ultrasound-guided biopsy of the thyroid nodule demonstrated a benign colloid nodule with cystic changes

Computed tomography with intravenous contrast was obtained, and findings were initially reported as negative except for right multinodular goiter

However, on additional review, a well-circumscribed fat density mass measuring 3.0 × 2.3 × 1.1-cm was identified in the right retropharyngeal space posterior to the hypopharynx (Figure, C)

A, Results of single-photon emission computed tomography/computed tomography (SPECT/CT) demonstrated relatively low radiopharmaceutical uptake superior to the expected area of the parathyroid glands

B, Findings of technetium-99m sestamibi SPECT/CT demonstrated increased radiopharmaceutical uptake in the previously identified dominant right inferior thyroid nodule (white arrowhead)

C, A CT neck scan with contrast showing a mass in the right retropharyngeal space with complex internal areas of increased attenuation (red circle)


Odontogenic keratocyst (keratocystic odontogenic tumor)

A 19-year-old woman with no noteworthy medical issues or surgical history presented to the oral and maxillofacial surgery clinic with a 3-month history of right-sided maxillary pain and swelling

The patient denied any drainage from the site but reported worsening swelling and pain over the past several weeks

On physical examination, there was noted intraoral swelling involving the buccal and palatal aspects of the posterior maxilla

The lesion was soft and fluctuant with no appreciable drainage

The patient’s history was notable for an 8-year history of right maxillary first premolar impaction

Findings from computed tomography of the head demonstrated a relatively spherical 4-cm growth of the right anterior maxilla abutting the maxillary sinus and orbital floors, and enclosing an impacted premolar at the superior margin of the growth (Figure, A)

There was no proptosis or visual field changes associated with the lesion

An incisional biopsy was performed via an intraoral approach, and results demonstrated a thickly encapsulated proliferation of odontogenic epithelial cells with pseudoglandular elements (Figure, B and C)

Following diagnostic confirmation, the patient was taken to the operating room, and a midface (Weber-Ferguson) incision was used to access the maxillary lesion for complete removal

A, Sagittal computed tomography (CT) of the head and neck demonstrating an expansile, 5.0-cm mass enclosing an impacted first maxillary premolar (white arrowhead)

B, Neoplastic proliferation of swirls and anastomosing cords of odontogenic epithelium with formation of psuedoglandular structures (black arrowheads

C, High-powered view of ductlike structures (black arrowhead


Palmar fasciitis and polyarthritis syndrome

A woman in her late 40s presented with rapidly progressive redness and stiffness of both hands, accompanied by 2 months of multiple finger joint and right shoulder pain

Results of autoimmune serology, including antinuclear antibody, C3 and C4, rheumatoid factor, and Scl-70 antibody tests, were negative

There was an absence of nailfold capillary changes and distal digital pitting

The patient was treated with nonsteroidal anti-inflammatory drugs, systemic steroid therapy, and disease-modifying antirheumatic drugs (ie, hydroxychloroquine), but symptoms persisted

Two weeks after treatment initiation, multiple tender nodules developed over the palms and interphalangeal joints, and flexion contractures continued (Figure, A)

Incisional skin biopsy of the palmar nodules (Figure, B and C) and computed tomography (CT) were performed

Results of the CT demonstrated bilateral ovarian tumors with highly suspect peritoneal metastases

A, Clinical image of erythematous and edematous changes of bilateral hands and multiple nodules on palms and interphalangeal joints

B and C, Hematoxylin-eosin–stained specimen showing increased fibroblasts with fibrosis from dermis to subcutis


An otherwise healthy man in his 50s was referred to the Department of Dermatology with a 5-year history of an asymptomatic, gradually enlarging, reddish hematomalike plaque with a brownish peripheral border in his left axilla (Figure 1)

The patient described the spontaneous onset of the lesion and reported no previous history of trauma or any other systemic symptoms

he had previously applied a topical antifungal cream but observed no lesion improvement

Physical examination revealed a nonindurated and well-defined 10 × 8-cm reddish-brown annular plaque with peripheral ecchymosis

Two biopsy specimens were obtained from different areas of the lesion for immunohistochemical studies

vascular channel endothelial cells were positive for CD31, CD34, and D2-40 and negative for human herpesvirus 8 (HHV-8) (latent nuclear antigen) and Wilms tumor 1 (WT1)

Serologic tests for HIV and hepatitis B and C were negative

Clinical image of the left axilla showing an asymptomatic, reddish hematomalike plaque with a brownish peripheral border


A 7-year-old African American girl without significant medical history presented with progressive painless right-sided neck swelling for 2 months

Initially, she experienced fever and sore throat

Physical examination findings demonstrated minimally tender and nonmobile 4-cm right submandibular space swelling

Laboratory examination findings were significant for leukocytosis with neutrophilia (white blood cell count, 19.8 K/μL

neutrophil count, 18.2 K/μL [to convert to ×109/L, multiply by 0.001]), anemia (hemoglobin level, 9.6 g/dL [to convert to g/L, multiply by 10.0]), elevated erythrocyte sedimentation rate (>130 mm/h), and elevated C-reactive protein level (3.1 mg/dL [to convert to mg/L, multiply by 10])

Ultrasonography revealed multiple enlarged hyperemic lymph nodes within the right side of the neck, the largest measuring 3.4 × 2.4 × 2.1 cm in the submandibular space

She was treated with oral antibiotics without improvement

Ultrasonography at 1-month follow-up revealed interval enlargement of the lymph nodes, which appeared rounded in shape, without preservation of internal architecture

The mother reported that the patient lost 3.2 kg in 2 months, without any chills or night sweats, difficulty swallowing or breathing, change in voice, abdominal pain, recent travel, or exposure to animals or pets

Magnetic resonance imaging (MRI) demonstrated extensive unilateral right-sided neck adenopathy, the largest nodes measuring approximately 4 cm at level IB

an approximately 2-cm destructive mass involving the left maxillary malar eminence

and additional lesions involving the T4 vertebra and upper sternum (Figure, A and B)

Fluorodeoxyglucose 18F-labeled positron emission tomography with computed tomography (FDG PET/CT) demonstrated extensive FDG-avid right-sided cervical lymphadenopathy and innumerable FDG-avid lytic foci involving the axial and appendicular skeleton (Figure, C)

A, Postcontrast T1-weighted fat-suppressed magnetic resonance imaging (MRI) of the brain demonstrated an approximately 2-cm destructive mass involving the left malar eminence of maxilla with homogeneous enhancement

B, Axial T2-weighted fat-suppressed MRI through the neck demonstrated unilateral right-sided neck adenopathy

C, Fluorodeoxyglucose F18-labeled positron emission tomography whole-body imaging demonstrated avid right cervical lymphadenopathy and innumerable avid foci involving the axial and appendicular skeleton


A 69-year-old man with a smoking history and complaints of back pain and cough for 2 weeks was found to have a right lung mass on chest radiography results

A chest computed tomography (CT) scan showed a right upper lobe lung mass with multiple lymphadenopathies (N3), and bone scan and brain magnetic resonance imaging results showed multiple metastatic foci

A biopsy was performed, and the pathologic report showed a poorly differentiated lung adenocarcinoma with ROS1 rearrangement identified by immunohistochemical staining (clone: D4D6

H-score: 280) and further confirmative fluorescence in situ hybridization

The patient received ceritinib, 450 mg/day, and his tumor and brain and bone metastatic lesions subsequently decreased in size

The ceritinib was then shifted to crizotinib, 500 mg/day, when the reimbursement of crizotinib as a first-line therapy was approved by Taiwan's National Health Insurance system

Three weeks after the first dose of crizotinib, the patient developed a dry cough without fever or purulent sputum

There was no significant finding on physical examination except mild crackles over the right lung field, although chest radiography results showed a new consolidation lesion over the right upper lobe

Meanwhile, the results of mycobacterial and bacteriologic surveys were unremarkable

The tumor marker carcinoembryonic antigen level decreased from an initial 14.76 to 0.71 ng/mL (reference range, 0-5.00 ng/mL [to convert to micrograms per liter, multiply by 1])

A CT scan was arranged, and developing lung cancer with lymphangitic carcinomatosis was highly suspected by the radiologist (Figure, A)

A bronchoscopy with bronchial brushing and biopsy was performed, and no pathogen was identified

A, The comparison of the chest computed tomographic (CT) scan of the new consolidation lesion (red arrowheads) mimicking recurrence (right panel) with the primary tumor (yellow arrowhead) in the initial CT scan (left panel)

B, Microscopic findings of a CT-guided biopsy (left panel) and CT scan after resuming ceritinib treatment (right panel)

Granulomatous inflammation or sarcoid-like reaction with predominant T-cell infiltration (hematoxylin and eosin stain, magnification ×200) and less B cell infiltration

Inset: double immunohistochemical staining showing abundant T cells (CD3, red staining

red arrowheads) and rare B cell infiltration (CD20, brown staining

The CT scan after resuming ceritinib treatment for 2 months showed decreased lung consolidation and the primary tumor (yellow arrowhead)

Treat with chemotherapy for disease recurrence because the agents available for recurrent ROS1 tumors remain limitedAdminister antibiotics with coverage for pneumonia pathogen for 7 to 10 days and a repeated CT scan in 4 weeksAdminister steroid treatment and discontinue crizotinib and other tyrosine kinase inhibitors (TKIs) permanently because TKI-induced interstitial lung disease is highly suspectedPerform a CT-guided biopsy for histological confirmation of recurrence or identification of other benign disease, such as granulomatous inflammation


A male newborn was noted to have right eye and right cheek masses at birth

His prenatal course was complicated by maternal drug use, hepatitis C, and lack of routine prenatal care

Intraocular pressure of the right eye was elevated to 31 mm Hg (normal pressure, <20 mm Hg)

Parotid ultrasonography demonstrated a lobulated solid vascular mass measuring 2.1 cm

The infant was referred to the ophthalmology and otolaryngology service

At the age of 5 weeks, a swollen right eye with a foggy cornea and conjunctival vascular anomaly were noted

A soft, mobile, right parotid mass had doubled in size

Ocular B-scan ultrasonography revealed a large subretinal lesion with multiple intralesional, hyperechoic foci extending temporally from the optic disc to the periphery

Results of magnetic resonance imaging (MRI) showed an intraocular mass in the right eye, with faint contrast enhancement thought to represent intratumoral calcification or hemorrhage, and a well-circumscribed, 3.1-cm, right superficial parotid mass with faint enhancement (Figure 1)

18F-fludeoxyglucose–positron emission tomography (FDG-PET) showed hypermetabolic masses at the posterior aspect of the right globe, the lateral aspect of the orbit, and the right parotid gland

Computed tomography of the chest, abdomen, and pelvis provided no evidence of distant metastasis

Cerebral spinal fluid analysis and examination of a bone marrow biopsy specimen showed no suspicious findings

A pathological specimen from the parotid gland featured small blue cells with a fine chromatin granular pattern and complete loss of integrase interactor 1 (INI-1)

Axial magnetic resonance image showing a right orbital mass (arrowhead) with faint contrast enhancement


The patient is a 48-year-old man with a history of a rectal adenocarcinoma (cT3N2bM0) diagnosed 9 years prior

Following neoadjuvant chemoradiotherapy, low anterior resection, and 6 cycles of adjuvant FOLFOX therapy (fluorouracil, leucovorin, and oxaliplatin), he had developed a lung metastasis (KRAS wild type) 1 year later

He subsequently developed multiple lung metastases treated with palliative local interventions (lobectomy, radiofrequency ablation) and 4 lines of chemotherapy

Owing to symptomatic lung disease, he was enrolled in a clinical trial (NCT03502733) following informed consent and achieved a confirmed partial response

After 9 months, contrast computed tomography restaging scans noted a new, 1-cm posterior subglottic lesion of unclear origin (Figure, A)

He had no shortness of breath or noisy breathing, dysphagia, voice change, or hemoptysis

A partial response was maintained without evidence of progression of lung disease

A, An axial computed tomographic image reveals a new posterior subglottic lesion (pink arrowhead) of unclear etiology

B, In the operating room, the larynx was exposed with a Lindholm laryngoscope, and a Hopkins rod-lens endoscope was used to photograph the lesion under apneic conditions

C, Photomicrograph (original magnification ×20) of a section of the mass stained for CDX2 via standard immunohistochemical techniques

Otolaryngology was consulted to assess the lesion

The differential diagnosis based on imaging included a mass vs inspissated mucus

Examination using distal-chip flexible laryngoscopy revealed a 1-cm, broad-based, exophytic mass along the posterior wall of the subglottis with prominent vasculature

No other anatomic abnormalities in the upper aerodigestive tract or cervical lymphadenopathy were noted

The decision was made to proceed to the operating room for definitive endoscopic biopsy under general anesthesia (Figure, B)

Examination revealed a subglottic mass that did not extend inferiorly beyond the caudal aspect of the cricoid cartilage

The mass was debulked and sent to pathology for analysis, including hematoxylin-eosin and immunohistochemical staining (Figure, C)


A 69-year-old woman returning from a vacation in Cuba was brought to the emergency department directly from the airport

Her medical history was unremarkable, and she had no allergies

She had been well until 2 hours before the flight home, when at the Havana airport, she developed generalized weakness, increased sweating, severe nausea, and vomiting

In flight, she had lethargy, vomiting, and urinary incontinence

On arrival to the emergency department, she was stuporous and required intubation

Initial laboratory tests showed a hemoglobin level of 10.9 g/dL (reference range, 12.0-15.2 g/dL [to convert to grams per liter, multiply by 10.0]), a creatinine level of 1.31 mg/dL (reference range, 0.51-1.08 [to convert to micromoles per liter, multiply by 88.4]), and a pH of 7.22 with a normal anion gap

levels of glucose, creatine kinase, lactic acid, and thyrotropin

and liver function tests had normal results

An electrocardiogram showed sinus bradycardia at 53 bpm and borderline QT interval prolongation (QTc

A urine toxicology screen had negative results for acetaminophen, salicylates, opiates, barbiturates, benzodiazepines, cocaine, and ethanol

Cerebrospinal fluid was clear, with normal levels of glucose, total protein, and white blood cells and negative microbiology and cytology testing results

A malaria smear and antigen test, respiratory viral assay, and cultures of cerebrospinal fluid, blood, and urine had negative results

Computed tomography of the head showed bilateral hyperdensity of the globus pallidi (Figure 1)

Within several hours, her level of consciousness improved spontaneously, and she was extubated

Involuntary facial muscle twitching was noted

Her muscle tone was normal, and she had mild proximal muscle weakness with occasional bilateral upper extremity and lower extremity fasciculations and jerky movements

Deep tendon reflexes were normal, with flexor plantar responses

Her sensations to pain and vibration were normal

Computed tomography of the head showing bilateral hyperdensity of the globus pallidi


Proliferative nodule in a congenital melanocytic nevus

A woman in her early 70s was referred to the dermatology department for evaluation of a solitary, asymptomatic lump on her scalp

She was born with the lesion but noticed some growth following a minor local trauma a couple of months prior to seeking medical evaluation

The patient denied local inflammation, purulent discharge, and systemic symptoms

Her medical history was unremarkable apart from an allegedly benign breast nodule resection in her teenage years

In addition, her father died of metastatic cutaneous melanoma at 83 years old

Clinically, there was an ill-defined, infiltrated plaque with a normochromic, exophytic nodule on her scalp vertex measuring 4.2 × 3.8 cm (Figure, A)

It had a waxy surface with irregular transverse furrows and overlying alopecia

Dermoscopic evaluation findings revealed a homogeneous yellow hue with no visible vascular or pigmented structures and absence of follicular ostia

The lesion was firm and mildly tender to the touch and seemed adherent to the underlying bone

A brain magnetic resonance imaging was performed for further elucidation (Figure, B), as well as a punch biopsy (Figure, C and D)

A, Clinical image of the lesion on the scalp

B, Paramedian sagittal gadolinium-enhanced T1-weighted brain magnetic resonance imaging (MRI)

C, Cellular infiltration in the reticular dermis (hematoxylin-eosin, original magnification ×100)

D, Monomorphic cells in a syncytial configuration surrounding collagen bundles (hematoxylin-eosin, original magnification ×400)


Drug reaction with eosinophilia and systemic symptoms

Eosinophilic dermatosis of hematologic malignancy

A woman in her 50s with a recent diagnosis of acute myeloid leukemia (subtype M5a, French-American-British classification) was admitted to the hospital for induction chemotherapy

At presentation she had a 3-week history of a striking pruritic and generalized cutaneous eruption

The patient otherwise felt well and denied fever, malaise, insect bites, or starting new drug treatments

Except for leukopenia and a slightly elevated C-reactive protein level, results of other routine blood and urine tests were unremarkable

Physical examination revealed an erythematous eruption composed of small indurated and edematous papules (Figure, A and B)

Confluent papules leading to large urticariform plaques, some with annular configuration, were present on the flanks, lower legs, breasts, and scalp

Hyperpigmented patches and focal areas of bruiselike discoloration were seen adjacent to acute lesions

Mucous membranes, palms, and soles were spared

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

A, Erythematous indurated and edematous papules and plaques on the thighs with some residual discoloration

B, Large erythematous plaques involving the scalp and ear

C, Hematoxylin-eosin–stained histologic specimen showing a superficial and deep dermal perivascular and interstitial mononuclear infiltrate with numerous eosinophils (original magnification ×40)

D, Higher magnification of C showing an abundant number of eosinophils in the infiltrate (original magnification ×400)


A 72-year-old man with recently diagnosed metastatic appendiceal adenocarcinoma undergoing chemotherapy with capecitabine plus oxaliplatin presented with lower abdominal pain and watery, large-volume diarrhea up to 15 times per day for the previous 3 weeks

His diarrhea was nonbloody, woke him up from sleep, was accompanied by crampy abdominal pain, and was not associated with nausea or vomiting

The diarrhea persisted despite treatment with combinations of loperamide, atropine/diphenoxylate, colestipol, and tincture of opium

He required repeated intravenous infusions for fluid and electrolyte repletion

His physical examination results revealed normal vital signs and a mildly tender abdomen with hyperactive bowel sounds, but no peritoneal signs

His laboratory workup results were notable for severe hypokalemia and hypomagnesemia, as well as positive fecal lactoferrin and elevated fecal calprotectin levels of 646 μg/g

His infectious workup results were unremarkable

A computed tomography scan of the abdomen/pelvis revealed diffuse long-segment wall thickening involving nearly the entire terminal ileum (Figure, A)

An ileocolonoscopy revealed erythematous and congested mucosa with scattered erosions and ulcerations throughout the examined terminal ileum (Figure, B)

Targeted biopsies were obtained (Figure, C)

Contrasted computed tomography of the abdomen and pelvis (A), colonoscopy (B), and histopathology (hematoxylin-eosin, original magnification ×100) (C)


A man in his 40s presented with mobility of the anterior mandibular dentition

A consultation with a dentist 1 year prior revealed an impacted mandibular canine (No

He denied any pain, swelling, or paresthesia, and his medical history was unremarkable

Clinical examination revealed fullness on the mentolabial fold but no gross facial asymmetry or mental nerve paresthesia

Intraorally, there was an expansile mass of the left anterior mandible with ill-defined margins, which crossed the midline and obliterated the gingivolabial sulcus

Results of dental cone beam computed tomography imaging revealed a 4.3 × 4.0-cm radiolucent mandibular lesion with an unerupted mandibular canine in the center of the lesion, cortical destruction, and root deviation of teeth Nos

An incisional biopsy was performed, and the patient underwent radical mandibular resection 2 months later

Histological sections from the resection demonstrated nests and cords of polygonal cells with clear to eosinophilic cytoplasm embedded in a dense collagenous stroma (Figure, B)

The lesion was centered in the cortical bone (Figure, C) and extended into the surrounding mucosa (Figure, D), fibroadipose tissue, and skeletal muscle

Perineural invasion was identified (Figure, E), and lymphovascular invasion was absent

Immunohistochemistry findings revealed the tumor cells were positive for p40. Fluorescence in situ hybridization  studies demonstrated an EWSR1 gene rearrangement in 60% of the tumor cells (Figure, F)

A, Dental cone beam computed tomography (CT) scan showing 4.3 × 4.0-cm radiolucent lesion in the anterior mandible with impacted mandibular canine at the center of the lesion

B, Nests and cords of polygonal cells with clear to eosinophilic cytoplasm (hematoxylin-eosin stain)

C, Lesion centered in the bone (hematoxylin-eosin stain)

D, Tumor cells extending beyond the cortex of the mandible to involve the gingival mucosa (hematoxylin-eosin stain)

E, Perineural invasion is present (hematoxylin-eosin stain)

F, Fluorescence in situ hybridization for EWSR1 gene rearrangement highlighted separation of the red and green signals in 60% of cells


A woman in her 70s presented with an enlarged and variegated plaque on her left axilla, which she had had for 4 years

The lesion started as a small eczematous, pink-to-brown plaque

As the lesion was asymptomatic and slow growing, she did not initially seek treatment

Recently, the color of the lesion had changed to an alarming dark brown color (Figure, A)

No breast mass or lymphadenopathy was observed

Her medical and family history was unremarkable

A skin biopsy specimen was obtained and submitted for further histopathologic analysis

A, Clinical presentation of pigmented plaque in the axilla with well-demarcated margins

B, Histologic findings revealed an intraepidermal neoplasm consisting of pagetoid cells, characterized by round, pale, vacuolated cytoplasm, and large pleomorphic nuclei (hematoxylin-eosin

C, Immunohistochemical findings showed positive staining for EMA (original magnification ×200)

D, The lesion was surrounded by numerous reactive dendritic HMB-45–positive melanocytes scattered among the tumor cells (original magnification ×200)


An otherwise healthy man in his 40s presented with a 3-month history of an asymptomatic nodule on his scalp

There were no systemic complaints, history of arthropod bite, immunosuppression, travel abroad, or contact with animals in the recent past

Physical examination revealed a skin-colored, firm, nontender, freely mobile 2 × 1.5-cm nodule with overlying normal skin on the right occipital region of the scalp (Figure, A)

A, Clinical photograph shows a 2 × 1.5-cm skin-colored nodule on the occiput

A nodular lesion surrounded by a fibrous capsule is seen in the dermis with cross-sections of many parasites along with pink material in the nodule (hematoxylin-eosin, original magnification ×2)

C, The parasite morphology depicts a thick cuticle, well-developed inner muscular layer, tubular structures containing microfilariae, and necrotic debris (hematoxylin-eosin, original magnification ×20)

D, Higher magnification shows spinous processes on the outer surface of the cuticle (hematoxylin-eosin, original magnification ×20)

The nodule was completely excised and sent for histopathologic examination, which revealed a nodule in the dermis with an unremarkable epidermis

Cross-sections of parasites were present, surrounded by a fibrous capsule (Figure, B)

The parasite showed an outer cuticle, muscle layer underneath, and gravid uterus filled with microfilariae (Figure, C)

The cuticle demonstrated a wavy pattern of longitudinal ridges on its outer surface (Figure, D)

The fibrous capsule contained mixed inflammatory infiltrate of lymphocytes, eosinophils, histiocytes, and plasma cells

Findings of slitlamp examination and fundoscopy of the eyes were normal

Findings of routine hematologic and biochemical investigations were normal

No microfilaria was seen in peripheral blood

Findings of chest radiography and abdomen ultrasonography were unremarkable


Eosinophilic granulomatosis with polyangiitis

A healthy 21-year-old Chinese man with no relevant medical history presented to multiple general practitioners for a recurrent sore throat associated with hoarseness of voice for 3 months’ duration

Despite having taken multiple courses of oral antibiotics, he saw no improvement in his symptoms

Over the course of 3 months, the patient went on to notice swelling and redness of his left ear (Figure 1A) that would resolve and recur every few weeks

Clinical photographs demonstrating auricular chondritis (A) and saddle nose deformity (B)

Bothered by his hoarse voice and sore throat, he consulted a private otolaryngologist, who performed a nasoendoscopy, the results of which showed severe Reinke edema and chronic laryngitis

He was treated with a short course of oral prednisolone that alleviated all his symptoms

However, on cessation of oral steroids, the patient noticed a saddle-shaped deformity on his nose (Figure 1B) that appeared without any antecedent trauma

In addition, his hoarseness of voice worsened during a 2-week span and was now associated with difficulty breathing when he laid supine

In our otolaryngology clinic, physical examination results revealed a saddle-nose deformity, left pinna perichondritis, and a soft inspiratory stridor

He was unable to speak a full sentence without drawing a deep, labored breath

Laboratory test results showed elevated C-reactive protein levels of 143 mg/L, erythrocyte sedimentation rate of 97 mm/h, and a microcytic hypochromic anemia of hemoglobin level of 12.1 g/dL (to convert to grams per liter, multiply by 10)

The results for antinuclear antibody, anti–double-stranded DNA, and antineutrophil cytoplasmic antibodies were negative


A 9-year-old, vaccinated boy with glucose-6-phosphate dehydrogenase deficiency and β-thalassemia trait presented with 1 month of progressive dyspnea, snoring, dysphagia, and weight loss

Both parents had a history of latent tuberculosis infection treated after immigrating to the US from Syria shortly after the patient’s birth

The patient’s pediatrician diagnosed him with reactive airway disease and adenotonsillar hypertrophy

He was referred to the otolaryngology clinic, where flexible laryngoscopy revealed diffuse upper airway lymphoid hyperplasia and supraglottic edema

He was sent to the emergency department, where he was stridulous and afebrile with a normal white blood cell count and an elevated erythrocyte sedimentation rate

A computed tomography scan of the neck revealed diffuse edema and contrast enhancement of the nasopharynx, oropharynx, hypopharynx, and supraglottis

The patient was taken urgently to the operating room for direct microlaryngoscopy (Figure 1A and B) and intubated

Results of biopsies and cultures of the tonsils, adenoids, and supraglottis revealed diffuse non-necrotizing granulomas (Figure 1C) and oropharyngeal flora with negative acid-fast bacilli and Grocott methenamine silver stains

He remained intubated, and treatment with systemic corticosteroids and antibiotics was initiated

During this time, he had a normal angiotensin-converting enzyme (ACE) level and normal titers for antinuclear antibody (ANA), cytoplasmic antineutrophilic cytoplasmic antibody, perinuclear antineutrophilic cytoplasmic antibody, antimyeloperoxidase antibody, antiproteinase 3 antibody, anti–double-stranded DNA antibody, Smith antibody, Sjogren antibodies, and histoplasma antibodies

He also had normal results on tuberculin purified protein derivative and interferon-γ release assay (QuantiFERON

A, View with laryngoscope blade in vallecula, revealing only a profoundly swollen epiglottis

B, View with laryngoscope blade beneath epiglottis, revealing edema and distortion of supraglottic structures that obscured the glottis (* indicates left arytenoid

C, Supraglottic biopsy specimen demonstrating non-necrotizing granulomas in a background of lymphoid tissue

hematoxylin-eosin stain, original magnification ×200.


Cancer-associated systemic lupus erythematosus

Cancer-associated pancreatitis, panniculitis, and polyarthritis syndrome (PPP) syndrome

A man in his 30s presented with a 3-month history of fourth finger right hand articular heat, pain, redness, and swelling

Similar symptoms subsequently spread to the left hallux and ankle, and he developed a fever

Despite many medical consultations and various attempts at treatment with nonsteroidal anti-inflammatories, the patient developed widespread arthritis within the following month, which was predominant in the knee, shoulder, and hip

In the month before presentation the articular symptoms worsened, the joints had become tender, and ill-defined skin nodules had appeared predominantly on the legs (Figure, A and B)

An acute abdominal pain in the left hypochondrium developed, accompanied by nausea and vomiting, which led to a diagnosis of pancreatitis

The patient was admitted to the hospital and clinical measures relieved the pain

Laboratory test results revealed strikingly high levels of lipase and amylase, as well as normal levels of cancer antigen 19-9. Bone computed tomography (CT) of the right shoulder and knee demonstrated cortical bone destruction and intraosseous medullary necrosis (Figure, C and D)

An abdominal CT was performed (Figure, E), and the patient underwent surgery


A 73-year-old woman with a history of chronic cervical neck pain presented with complaints of globus sensation, dysphagia, and localized throat swelling

On examination, she had an approximately 1.5-cm mucosally covered mass on her left lateral pharyngeal wall that was cystlike in appearance

The remainder of her examination findings were normal

The patient reported that this cyst had been drained 2 years before with resolution of her symptoms

Contrasted computed tomographic (CT) imaging of her head and neck was obtained, which revealed a pharyngeal cyst that extended to the atlantoaxial joint (Figure, A)

Further magnetic resonance imaging (MRI) of the area was obtained, which demonstrated communication of the cyst with the atlantoaxial joint (Figure, B and C)

Computed tomographic (CT) image (A) and magnetic resonance images (MRIs) (B and C) of the neck show a pharyngeal cyst (all images) that is communicating with the left atlantoaxial joint (B) at the level of the second cervical vertebra (C)


A 19-year-old White woman who was previously in good health, with no reported history of drug abuse, presented with progressive bilateral nasal airway obstruction, crusting, and saddle nose deformity over a 6-month period

The patient denied systemic symptoms, including oral ulcers, sicca, photosensitivity, dermatitis, or arthralgias

Her medical history had negative results for allergic rhinitis, asthma, chronic rhinosinusitis, epistaxis, nasal trauma, or surgery

An in-office nasal endoscopy demonstrated synechiae bridging from the septum to the lateral nasal walls, polypoid changes, and yellow crusting bilaterally

Her immune workup showed elevated complement C3 (200 mg/dL) and total hemolytic complement (CH50

>60 U/mL) levels, with otherwise unremarkable levels of C4, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, Sjögren antibodies, angiotensin-converting enzyme, antinuclear antibody, antineutrophil cytoplasmic antibody, bullous pemphigoid IgG antibodies, and quantitative immunoglobulins and IgG subclasses (IgG4, 53 mg/dL [to convert to grams per liter, multiply by 0.01])

Nasal cultures had positive results for methicillin-resistant Staphylococcus aureus and Bacteroides

Preoperative computed tomography showed no evidence of paranasal mucosal disease or bone erosion

An operative endoscopy with elevation of the mucoperichondrial flaps revealed an absence of the quadrangular cartilage caudal struts and irregular, friable tissue along the cartilage and perichondrium

Surgical pathology examination demonstrated prominent lymphoplasmacytic infiltrate (Figure, A), angiocentric fibrosis with a relative lack of eosinophils (Figure, B), and increased IgG4 absolute count (up to 50 cells per high-power field), although an IgG4-IgG ratio that was only slightly elevated (0.2) (Figure, C and D)

Histopathologic findings: A, hematoxylin-eosin (original magnification ×40)

B, hematoxylin-eosin (original magnification ×100)


Erythema gyratum repens associated with lung adenocarcinoma

A man in his 60s presented to the dermatology clinic with a widespread, intermittently pruritic eruption

Examination showed coalescing annular, arcuate, and serpiginous red scaling plaques in a concentric pattern diffusely involving the chest, back, and abdomen with extension to proximal extremities (Figure, A and B)

Punch biopsies from the chest (Figure, C and D) and back were obtained for histopathology and tissue culture

Treatment with topical corticosteroids under wet dressings was associated with partial improvement in the eruption and pruritus

A and B, Clinical images show concentric annular, arcuate, and serpiginous red scaling plaques diffusely involving the back and right flank

C, Histopathology of skin biopsy from the chest reveals epidermal hyperplasia with spongiosis and parakeratosis (hematoxylin-eosin, original magnification ×400)

There is a superficial dermal and epidermotropic infiltrate of atypical lymphocytes focally distributed along the dermal-epidermal junction and aggregated in Pautrier microabscesses

D, CD30 immunohistochemical stain (original magnification ×400) highlighting atypical lymphocytes

Erythema gyratum repens–like eruption associated with mycosis fungoidesErythema gyratum repens associated with pityriasis rubra pilaris


A 62-year-old man with a prior 10–pack-year history of smoking presented with a 3-cm right level IIa lymph node

Fine-needle aspiration results showed metastatic p16-positive squamous cell carcinoma

No mucosal primary site was identified with positron emission tomography, computed tomography, or a head and neck examination

The patient underwent direct laryngoscopy with directed biopsies and bilateral tonsillectomy

Pathology results revealed a 1.8-cm primary cancer in the right tonsil, and the patient received a stage designation of T1 N1 M0. The tumor was intracapsular, and all surgical margins were negative

Multidisciplinary tumor board discussion concluded that surgical and nonsurgical treatment options were available, and the patient elected to proceed with further surgery, which would entail additional directed biopsies at the primary site with additional resection if necessary and selective neck dissection of levels Ib to IV

In preparation for the neck dissection, computed tomography of the neck with contrast was obtained

Imaging results revealed an enhancing structure at the skull base adjacent to the carotid sheath (Figure)

Computed tomography of the neck with contrast and the axial (A) and coronal (B) views revealing an enhancing structure at the skull base along the carotid sheath (arrowheads)


A woman in her 70s presented with a week of painless, rapidly progressive, edematous, necrotic papules and plaques on the extremities, buttocks, and face with sharp demarcation at the nasolabial folds and extension into the oral mucosa (Figure, A and B)

Notable symptoms included 4 months of extreme fatigue, 20.4 kg weight loss, and a recent episode of hematochezia

Her medical history included diabetes, hyperlipidemia, and hypertension that were well controlled with simvastatin, chlorthalidone, hydralazine hydrochloride, lisinopril, and verapamil hydrochloride

She had been taking these medications for 5 years with no new exposures

Age-appropriate cancer screening was up to date

She was afebrile and hemodynamically stable, but laboratory evaluation revealed that she had leukocytosis, normocytic anemia, elevated erythrocyte sedimentation rate, hematuria, and proteinuria

On hospital day 2, she developed bright red blood per rectum, necessitating transfusion

A computed tomography of the chest, abdomen, and pelvis revealed parenchymal lung nodules

On admission, punch biopsies of the skin were performed for both histological examination and bacterial, fungal, and acid-fast bacterial cultures (Figure, C and D)

A, Edematous, ulcerated pink plaques confluent on forehead and cheeks with sharp demarcation at nasolabial fold are shown

B, Retiform purpuric plaque is shown on the left leg with overlying desquamation

C and D, Biopsy specimen findings (hematoxylin-eosin)


Blastic plasmacytoid dendritic cell neoplasm

A man in his 60s presented for evaluation of asymptomatic skin lesions on the chest that had been stable since onset 4 months prior

His medical history was significant for hyperlipidemia, familial polyposis, and acute myelogenous leukemia (AML) for which he had undergone an allogenic hematopoietic stem cell transplant 13 months earlier

Cutaneous examination revealed green-gray nodules and plaques on the left and right upper chest (Figure 1)

Bilateral cervical, axillary, and inguinal lymph node chains were negative for adenopathy

The patient had not attempted measures to alleviate the nodules and denied experiencing exacerbating factors or pain

Biopsies of the skin lesions were performed

A, Representative dusky, green-gray nodule located on the upper chest

B, A prominent green hue is present at the base of a lesion following shave biopsy


Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

A white man in his early 40s presented with dizziness and fatigue followed by tingling of both lower extremities as well as gait disturbances

The patient’s medical history was unremarkable besides mild intermittent whole-body itching starting 9 months prior

Physical examination revealed mild proximal pyramidal weakness of the left leg (Medical Research Council grade 4/5), with brisk reflexes and extensor plantar response as well as hypoesthesia below the T2 level without sphincter disturbances

In addition, mild decrement in position sense and marked decrement of vibration sense were observed in both lower extremities

No skin lesions were detected, while cervical and supraclavicular lymph nodes were enlarged

Multiple enhancing lesions were observed on brain and cervical spine magnetic resonance imaging (MRI) (Figure)

Cerebrospinal fluid (CSF) was acellular, and eosinophils and oligoclonal bands were not detected, while proteins, glucose, and angiotensin-converting enzyme (ACE) levels were within normal range

Test results for B-cell clones, viral, and fungal infections were all negative

Routine blood test results were unremarkable besides an elevated eosinophilic count (2.76 K/μL

Antibodies for AQP4, MOG, and paraneoplastic syndromes were not detected

Whole-body fluorodeoxyglucose positron emission tomography demonstrated generalized lymphadenopathy without any other pathological findings

Whole-body gallium scan, chest high-resolution computed tomography, and bone marrow biopsy results were normal, while axillary and inguinal lymph node biopsies revealed nonspecific reactive lymphadenopathy

Parasitic infections were excluded by plasma and CSF antibodies testing with enzyme-linked immunosorbent assay, stool, and lymph node microscopy

Extensive diagnostic workup for malignancies and systemic autoimmune diseases was also inconclusive

Fluid-attenuated inversion recovery (FLAIR) images presenting bilateral subcortical lesions in the brain (A) and T2-weighted images demonstrating multiple lesions and swelling of the cervical cord (C)

Presence of gadolinium (GD) enhancement of the lesions in corresponding post-GD T1-weighted images of the brain (B) and predominantly in the posterior columns of the spinal cord (D)


A 41-year-old man presented with a 7-month history of episodes of back and abdominal pain associated with nausea, vomiting, and flushing

Immediately following workup with noncontrast abdominal ultrasonography, he experienced intense flushing and vomiting

Subsequent contrast-enhanced magnetic resonance imaging identified a 5-cm thoracic paraspinal mass (Figure, A)

Computed tomography–guided biopsy of the paraspinal mass revealed a dense cellular infiltrate on histopathology composed of cells with round nuclei and abundant pale cytoplasm (Figure, B)

A, Axial postcontrast T1-weighted magnetic resonance imaging of the spine identifying a paraspinal soft-tissue mass (bracketed by white arrowheads) encasing the descending aorta with neural foramen extension (pink arrowhead)

B, Computed tomography–guided biopsy sample (original magnification ×400) showing a monomorphic infiltrate of small- to medium-sized round cells with uniform angulated nuclei and abundant amphophilic hypogranular cytoplasm


A girl younger than 2 years presented with a 7-month history of an inflammatory plaque on her left index finger (Figure, A)

This lesion had started as a light erythema a few months before, initially oriented as a bacterial paronychia or herpetic whitlow and treated with an oral antibiotic (amoxicillin) and antiviral (acyclovir) without improvement

The family reported living in a rural area on the Mediterranean coast

A, Erythematous nodule on the proximal nail fold

B, Inflammatory erythematous plaque with a central shiny orange crust on the left index

C, Diffuse dermatitis with epithelioid granulomas (hematoxylin-eosin stain)

D, Intracellular amastigotes in the dermal macrophages (hematoxylin-eosin stain)

Physical examination findings revealed an inflammatory erythematous plaque with a central shiny orange crust on the left index finger (Figure, B)

There were no systemic symptoms or family history of similar lesions

Given the chronic course, with no improvement with empiric therapy, a biopsy specimen was obtained for further evaluation (Figure, C and D)