This case involves a 68-year-old man who presented with diplopia of 2 days' duration. He had a history of granulomatosis with polyangiitis with chronic renal insufficiency, diagnosed 21 months prior to admission. Initially, he experienced diplopia that resolved when closing the right eye, accompanied by nausea, vomiting, mild headache, and unsteadiness while walking. The following day he remained fatigued and light-headed when standing, with persistent nausea but without vomiting. On the day of admission, he noted weakness and clumsiness of his left hand while buttoning his shirt. He reported continued diplopia with one image appearing above and to the right of the other, mild nausea, but denied headache, neck stiffness, photophobia, vertigo, weakness, numbness, fevers, or chills. He had a chronic decrease in vision in the right eye due to cataract. His baseline creatinine was 5.4 mg/dL. On examination, he appeared fatigued but arousable with temperature 37.2°C, blood pressure 139/91 mmHg, pulse 91 bpm, respiratory rate 18/min, and oxygen saturation 93% on room air. There was mild left-sided ptosis, subjective diplopia in primary gaze with greater vertical than horizontal separation, left-sided upper and lower facial weakness, diminished soft-palate elevation on the left, left hand held in flexion with 4/5 strength in left wrist extensors and finger abductors, normal right arm strength, dysdiadochokinesia of the left arm, fasciculations in the left calf, and flexor plantar responses with fanning of toes.

Laboratory results, including hematology, biochemistry, immunology, and initial cerebrospinal fluid analysis.

Laboratory results showed hematocrit 33.7%, hemoglobin 11.2 g/dL, white-cell count 10,400/mm³ with 74% neutrophils and 16% lymphocytes, platelet count 177,000/mm³, elevated ESR at 34 mm/hr, C-reactive protein 11.1 mg/L, creatinine 6.83 mg/dL, urea nitrogen 79 mg/dL, and other electrolytes within normal ranges. ANCA showed borderline perinuclear staining with anti-myeloperoxidase antibodies at 2.4 U (borderline), and IgG level was low at 550 mg/dL. Initial CSF analysis showed 4-6 white cells/mm³, protein 42 mg/dL, glucose 81 mg/dL, and was colorless and clear without xanthochromia.

MRI of the head, performed on day 1.

Initial MRI of the head on day 1 showed mild, scattered white-matter changes, predominantly in the periventricular and subcortical regions, as well as in the midbrain region with more changes on the right side than left, consistent with chronic microangiopathic disease.

MRI performed on day 3.

Repeat MRI on day 3 showed new, progressive, hyperintense punctate and linear cortical and subcortical foci bilaterally, with some foci showing restricted diffusion suggestive of infarction, most notable in the right cingulate, precentral, and postcentral gyri, and also in the right midbrain, thalamus, corona radiata, and putamina bilaterally.

Cerebral vasculitis due to granulomatosis with polyangiitis

isolated benign cerebral vasculitis

Granulomatosis with polyangiitis


64-year-old male exercise physiologist who had ground, machined, drilled, and sanded Corian in his garage for about 16 years. He presented with clinical features typical of idiopathic pulmonary fibrosis.

Clinical photograph of Corian dust from the patient's garage.

A: Corian dust from the patient’s garage is shown in a gross clinical photograph, illustrating the source of environmental aluminum trihydrate exposure relevant to the case.

CT of the lungs, high-resolution technique.

High-resolution computed tomographic images of the lungs showing pattern suggestive of usual interstitial pneumonia

H&E staining of surgical lung-biopsy specimen from right lower lobe.

Hematoxylin-and-eosin staining showing pattern of usual interstitial pneumonia (patchy fibrosis and fibroblast focus) in surgical lung-biopsy specimen from right lower lobe

(D) Surgical lung biopsy from the right lower lobe, H&E staining, examined with polarized light microscopy.

D: In Panel D, hematoxylin-and-eosin stained sections of a surgical lung-biopsy specimen from the patient's right lower lobe, examined with polarized light microscopy, show abundant translucent, birefringent particles located in areas of fibrosis and, to a lesser extent, in a lymphatic distribution around small vessels and airways (left image), with the birefringent nature of these particles highlighted under polarized light (right image).

Scanning electron microscopy with energy dispersive x-ray spectroscopy of the lung.

Scanning electron microscopy with energy dispersive x-ray spectroscopy showing most abundant particles in lung contained aluminum and oxygen

Raman spectroscopy of lung tissue.

Raman spectroscopy showing peaks associated with lung tissue containing aluminum oxide and aluminum trihydroxide

Pulmonary fibrosis associated with aluminum trihydrate (Corian) dust exposure, presenting with radiographic and histologic features of usual interstitial pneumonia

pulmonary fibrosis NOS

interstitial pneumonia NOS

Cardiovascular and respiratory disorders


41-year-old right-handed man with neurologic history dating to his early twenties when he presented with seizures. In 2009, he developed headaches. Initial biopsy/resection pathology showed PXA (WHO grade 2) with BRAF V600E mutation confirmed by PCR testing.

MRI of the brain.

MRI showing brain lesion with nodular enhancement and surrounding edema

Anaplastic pleomorphic xanthoastrocytoma (PXA, WHO grade 3) with BRAF V600E mutation

Pleomorphic xanthoastrocytoma of brain


41-year-old white male with history of myelofibrosis. Past medical history includes splenectomy and allogeneic peripheral hematopoietic stem cell transplantation from single-antigen mismatched unrelated donor 2 years prior. After sun exposure during sailing trip, developed nonpruritic rash on face, trunk and extremities, associated with intermittent fever, muscle pain and weakness. Only current medication is daily oral acyclovir. Vital signs normal. Physical exam showed impaired ability to dorsiflex wrists while bringing palms together ('prayer sign'). Lab results showed: AST 41 U/L, ALT 68 U/L, alkaline phosphatase 147 U/L, total bilirubin 0.7 mg/dL. Antinuclear antibody test positive (1:320) with speckled pattern.

(A) Clinical photograph of the forehead and cheeks. (B) Clinical photograph of the chest. (C) Clinical photograph of the dorsal surfaces of the hands.

Physical findings showing: (A) Well-demarcated erythematous to violaceous scaly plaques on forehead and cheeks, sparing nasolabial folds and periocular regions. (B) Diffuse areas of reticulated hyperpigmentation on chest. (C) Violaceous, thin, flat-topped papules bilaterally on dorsal surfaces of hands.

Chronic graft-versus-host disease


A 69-year-old woman presented in January 2013 with progressive fatigue, 30-pound weight loss over 2 years, and shortness of breath on exertion. She had a history of hairy cell leukemia initially diagnosed in March 2010, with multiple prior treatments including two courses of cladribine, splenectomy in January 2011, rituximab therapy, and interferon therapy without sustained response. Physical examination revealed a palpable 2-cm right-side submandibular lymph node, multiple subcentimeter lymph nodes in bilateral cervical and axillary regions, and a palpable 2-cm left axillary lymph node. Laboratory findings showed pancytopenia with hemoglobin 9.6 g/dL, white cell count 2.8 K/μL, hematocrit 28.8%, platelet count 41 K/μL, and mild neutropenia with absolute neutrophil count 1.46 K/μL. Peripheral blood smear demonstrated lymphocytes with light basophilic cytoplasm and hairy cell cytoplasmic projections. Liver enzymes were mildly elevated with AST 105 IU/L, ALT 136 IU/L, and ALP 500 IU/L. Serum β2 microglobulin was elevated at 4.7 mg/L, and serum interleukin-2 receptor levels were markedly elevated at >6,500 units/mL. Chest x-ray was normal.

Bone marrow aspirate, tartrate-resistant acid phosphatase (TRAP) staining, 1,000× magnification, lymphocytes=86%.

Bone marrow aspirate shows 86% lymphocytes with multiple hairy cells having circumferential cytoplasmic projections and kidney-shaped nuclear contours, with positive tartrate-resistant acid phosphatase (TRAP) stain at ×1,000 magnification

Bone marrow biopsy, immunohistochemical staining for DBA44 and annexinA1, 200× and 400× magnification.

Bone marrow biopsy shows diffuse and dense lymphoid infiltrates occupying approximately 40-50% of bone marrow medullary space with small lymphocytes having dense nuclear chromatin and abundant cytoplasm, with lymphocytes positive for DBA44 and annexinA1 immunohistochemical stains at ×200 and ×400 magnifications

Flow cytometry of bone marrow aspirate.

Flow cytometry studies of bone marrow aspirate show monoclonal B cells with surface immunoglobulin kappa light chain restriction, with CD19+ lymphocytes positive for CD11c, CD20, CD25 dim, CD103, and CD200 and negative for CD5 and CD10

Left axillary lymph node biopsy, H&E staining, 40× and 400× magnification.

Excisional left axillary lymph node biopsy shows diffuse effacement by hairy cells with parenchymal hemorrhage, with lymphoid infiltrates mostly large in size having abundant pale cytoplasm, kidney-shaped irregular nuclear contours, closed chromatin, and inconspicuous nucleoli at ×40 and ×400 magnifications

(A) Splenectomy specimen, ×40 and ×400 magnifications.

Splenectomy specimen shows diffuse red pulp infiltration by lymphoid cells at ×40 and ×400 magnifications with similar immunophenotypic features as bone marrow and lymph node

IGHV4-34+, BRAF negative relapsed hairy cell leukemia (HCL)

Hairy-cell leukaemia


A 42-year-old man with a history of coronary artery disease and dyslipidemia presented to the emergency department with abdominal and chest discomfort. Two days prior, he experienced sudden onset of left upper quadrant abdominal pain that radiated to his back in a bandlike pattern across the subcostal margin, associated with nausea and early satiety. The pain worsened with movement and increased from 3 to 6 on a 10-point scale over two days. He also reported substernal chest pressure consistent with his usual angina but unresponsive to one sublingual nitroglycerin tablet. He denied abdominal trauma, emesis, rectal bleeding, or black stools. His chronic history included diarrhea since coronary bypass surgery over 10 years ago, worsening to four loose stools daily after cholesterol medication dose increase 6 months prior. He experienced 16 kg unintentional weight loss over 6 months, intermittent early satiety, daily headaches, frequent nocturia, and feeling warm at night without night sweats or fevers. Physical examination revealed mild left upper quadrant tenderness without peritoneal signs. His temperature was 36°C, heart rate 80 bpm, blood pressure 100/60 mmHg right arm and 105/63 mmHg left arm, respiratory rate 16, oxygen saturation 98% on room air, weight 78 kg, height 174 cm, and BMI 25.8. Laboratory findings showed normal electrolytes and renal function, leukocyte count 4780/mm³ with normal differential, hematocrit 46.9%, platelets 217,000/mm³, calcium 8.8 mg/dL, amylase 85 U/L (elevated), lipase 114 U/L (elevated), ALT 112 U/L (elevated), AST 88 U/L (elevated), alkaline phosphatase 57 U/L, total bilirubin 0.5 mg/dL, and triglycerides 85 mg/dL. Electrocardiogram showed normal sinus rhythm without ST-segment or T-wave abnormalities, and chest radiograph was normal.

(A) Abdominal CT, cross-sectional view. (B) Abdominal CT, coronal view.

A cross-sectional view (Panel A) and a coronal view (Panel B) of the patient’s abdominal CT scan show multiple enlarged jejunal mesenteric lymph nodes (arrows), measuring up to 1.9 cm in diameter. The unenhanced hepatic veins (Panels A and B) are prominent, but the liver parenchyma is otherwise normal.

(A) Photomicrograph, hematoxylin and eosin staining, low magnification. (B) Photomicrograph, hematoxylin and eosin staining, high magnification.

A photomicrograph at low magnification (Panel A, hematoxylin and eosin) shows flattening of the villi. A photomicrograph at high magnification (Panel B, hematoxylin and eosin) shows intraepithelial lymphocytes (arrows).Images courtesy of Dr. Deborah Wayler, Beth Israel Deaconess Hospital–Needham, Needham, MA.

Coeliac disease


An 8-year-old boy presented to his general practitioner with limping and complaints of occasional leg pain. He was otherwise healthy and afebrile. On physical examination, he walked with a limp and demonstrated painful, reduced internal rotation and abduction of his right hip. Plain radiographs were obtained to evaluate his symptoms.

(Left) Radiograph at age 7. (Centre) Radiograph at age 9 following surgical pelvic osteotomy. (Right) Radiograph at age 12.

Radiographic findings and course of treatment. Left: radiograph of 7 year old boy with Perthes’ disease showing increased density of left femoral head, with early collapse and fragmentation (right side is normal). Centre: same boy at age 9, following surgical treatment with pelvic osteotomy; femoral head is reossifying and restoring its shape. Right: the same boy at age 12, with nearly full anatomic restoration of shape of femoral head

Perthes disease

Diseases of the musculoskeletal system or connective tissue

Orthopedic and connective tissue disorders


71-year-old man with acute myeloid leukemia (AML) characterized by trisomy 11 karyotypic abnormality and FLT3-tyrosine kinase domain mutation. He had Fitzpatrick phototype II skin. Initial presentation showed myeloblasts accounting for greater than 90% of peripheral blood cells and presence of FLT3-ITD mutation.

Clinical photographs of the anterior distal lower extremities taken before treatment.

Pre-treatment photographs of anterior distal lower extremities showing hyperkeratotic pink papules and plaques

(E) Skin biopsy from the left thigh, H&E staining, low-power magnification.

E: Figure 1E displays a low-power hematoxylin and eosin (H&E) stained section of a skin biopsy obtained from a representative lesion on the left thigh, showing pronounced epidermal proliferation with epidermal thickening, overlying parakeratosis, and underlying microinvasive nests of squamous cells.

High-power H&E-stained section of a skin biopsy from the left thigh.

F: High-power hematoxylin and eosin-stained section of a skin biopsy from the left thigh displaying microinvasive nests of atypical squamous cells with dyskeratosis and malignant cytological features, consistent with squamous cell carcinoma.

Extensive Squamous Cell Carcinoma of the Skin in a patient with FLT3-Mutant Acute Myeloid Leukemia

Squamous cell carcinoma of skin

Acute myeloid leukaemia, unspecified


A 44-year-old woman with a history of breast cancer presented with abnormal findings on 18-fluorodeoxyglucose positron emission tomography imaging. She had previously been diagnosed with breast cancer (T1N2M0, Stage IIIa, intraductal carcinoma, triple negative cancer) and had undergone adjuvant chemotherapy and radiation therapy after a right breast conserving surgery 2 years prior. She was a non-smoker with no specific occupational or environmental exposure to known carcinogens and had been taking tamoxifen after chemotherapy. Laboratory results revealed mild anemia (hemoglobin 11.4 mg/dL) and leucopenia (3,300/μL), with all other results within normal limits. Additional laboratory findings included an elevated angiotensin I-converting enzyme level of 101 U/L, and her purified protein derivative skin test for tuberculosis was negative. The biopsy sample was also negative for tuberculosis antigen-specific interferon gamma.

Positron emission tomography-computed tomography scan of the lungs and thoracic lymph nodes, SUV values: lung parenchyma 11.5, thoracic pleura 9.0, paratracheal lymph nodes (right 8.4, left 7.1), AP window lymph nodes 9.6, subcarinal lymph nodes 8.6, hilar lymph nodes (right 10.2, left 13.7), interlobar lymph nodes (right 10.7, left 13.2), paraesophageal lymph nodes 4.8.

Positron emission tomography-computed tomography scan demonstrated multiple new hypermetabolic lesions in the parenchyma of both lungs (SUV 11.5), both thoracic pleura (SUV 9.0), both paratracheal lymph nodes (SUV Rt. 8.4/Lt 7.1), lymph nodes in the AP window (SUV 9.6), subcarinal lymph nodes (SUV 8.6), both hilar lymph nodes (SUV Rt. 10.2/Lt. 13.7), both interlobar lymph nodes (SUV Rt. 10.7/Lt. 13.2), and paraesophageal lymph nodes (SUV 4.8).

(A) Chest computed tomography, sagittal view, mediastinal setting. (B) Chest computed tomography, axial view, mediastinal setting. (C) Chest computed tomography, lower and upper subpleural lungs.

Chest computed tomography scan. (A, B) Multiple lymphadenopathies were seen on both sagittal (A) and axial (B) sections in a mediastinal setting. (C) Faint ground-glass opacities and fine reticular densities were observed on both lower lungs. These findings were also observed on both upper subpleural lungs.

(A) Mediastinal lymph node tissue, H&E staining, 100× magnification. (B) Mediastinal lymph node tissue, H&E staining, 200× magnification. (C) Mediastinal lymph node tissue, H&E staining, 400× magnification.

Pathologic findings for the mediastinal lymph node tissue. Chronic non-caseating granulomatous inflammation was observed (H&E staining; A, ×100; B, ×200; C, ×400).

Sarcoidosis of lung


Young female European traveler presented to a medical clinic in central Australia with vaginal discharge. She reported having sex with a new partner (another European traveler) 1 week previously in Sydney.

Laboratory test results for N. gonorrhoeae strain A8806: ceftriaxone MIC 0.5 mg/liter, penicillin G MIC 1 mg/liter, ciprofloxacin MIC 32 mg/liter, azithromycin MIC 0.25 mg/liter, spectinomycin MIC ≤64 mg/liter.

Laboratory testing revealed N. gonorrhoeae strain A8806 with the following characteristics: - Ceftriaxone MIC: 0.5 mg/liter (resistant) - Penicillin G MIC: 1 mg/liter (resistant/intermediate) - Ciprofloxacin MIC: 32 mg/liter (resistant) - Azithromycin MIC: 0.25 mg/liter (susceptible) - Spectinomycin MIC: ≤64 mg/liter (susceptible)

Neisseria gonorrhoeae infection with a new multidrug-resistant strain (A8806)

Infections due to Neisseria gonorrhoeae


A 49-year-old man presented to the emergency department with acute onset pain in the right upper quadrant and epigastric pain radiating to his back. Over the past 24-36 hours, he had experienced nausea and vomiting as well as dark urine and pale stools, and he had developed several painful lumps on his abdomen and upper limbs. On examination, his abdomen was soft but notably tender in the epigastrium and right upper quadrant, with no palpable intra-abdominal masses or organomegaly. Blood tests on admission showed deranged liver function tests, as well as a raised amylase (20.8 μkat/L; reference range <1.67) and C reactive protein (1181 nmol/L; <95). His full blood count and urea and electrolytes were normal. Urine analysis was positive for bilirubin and protein.

Magnetic retrograde cholangiopancreatogram of the abdomen. Abdominal ultrasound of the gallbladder. MRCP of the abdomen, maximal common bile duct diameter 6 mm.

Magnetic retrograde cholangiopancreatogram showing the descending duodenum, gallstones within the contracted gall bladder, a cystic duct, the right hepatic duct, left hepatic duct, common hepatic duct, and common bile duct. Abdominal ultrasound showed a thick walled gallbladder containing several small calculi. MRCP showed a contracted gallbladder containing several stones, a common bile duct dilated to a maximal diameter of 6 mm with no visible stones or filling defects, and areas of likely subcutaneous fat necrosis throughout the abdominal wall and upper limbs.

Gallstone pancreatitis with pancreatic panniculitis

Gallstone pancreatitis

Pancreatic enzyme panniculitis


A 56-year-old Ethiopian male immigrant was admitted with persistent fever and chills, cough, night sweats, and weight loss. He had a past medical history significant for a type A thymoma that was resected 3 years prior to admission. He reported a history of fatigue and dyspnea on exertion, as well as recurrent sinopulmonary infections that intermittently responded to antibiotics, with these infections often recurring in the setting of irritable bowel syndrome D (IBS-D) symptoms hallmarked by diarrhea. At admission, he had a low-grade fever with otherwise normal vital signs and oxygen saturation on room air. Blood tests showed an absolute lymphocyte count of 1,000 cells/μL and hemoglobin of 11.7 g/dL, with additional abnormalities including decreases in albumin and protein levels. Cultures of blood, sputum and urine were negative for an extensive workup including HIV, cytomegalovirus, acid-fast bacillus, Histoplasma, Aspergillus and coccidioidomycosis. On the second day of hospitalization, induced sputum was positive for Pneumocystis jiroveci and Moraxella catarrhalis. Biopsy of the cavitary lesion showed ulceration with acute and chronic inflammation, with cultures from transbronchial biopsy being negative, GMS staining negative for fungal organisms, and no evidence of malignancy. He showed no antibody response to any of the 14 pneumococcal serotypes examined, and lymphocyte proliferation assay demonstrated significantly decreased response to tetanus and candida compared to normal control.

CT scan of the chest.

CT scan of the chest shows an irregular, cavitating soft-tissue right hilar mass involving the posterior segment of the right upper lobe and superior segment of the right lower lobe, with focal areas of mucous impaction and bronchiectasis with multiple diffuse scattered clusters of bronchocentric micronodules, many in a tree-in-bud nodularity

Laboratory results: lymphocyte subset enumeration and immunoglobulin levels.

Lymphocyte and immunoglobulin enumeration shows low CD3 (540/cmm, normal 841-2,402), low CD4 (250/cmm, normal 355-1,426), normal CD8 (264/cmm, normal 255-1,090), profoundly deficient CD19 (1/cmm, normal 10-590), normal CD16&56 NK cells (93/cmm, normal 71-477), severely low IgA (20 mg/dL, normal 80-400), severely low IgG (176 mg/dL, normal 690-1,660), and severely low IgM (<5 mg/dL, normal 37-318)

Good syndrome


A 47-year-old man presented to his primary care physician with a six-month history of left-sided sore throat, ipsilateral otalgia, and a six-week history of a left-sided neck mass. He had never smoked and drank less than 5 units of alcohol per week. On examination in the ENT clinic, a firm fixed lymph node was palpable in the upper anterior triangle.

Ultrasound of lymph nodes, left side. Fine needle aspiration cytology.

Ultrasound image showing a rounded hypoechoic lymph node, with multiple left-sided pathological lymph nodes identified. Fine needle aspiration cytology confirmed metastatic squamous cell carcinoma.

CT, axial view, contrast enhanced, tonsillar region.

Axial contrast enhanced computed tomography showing a left-sided tonsillar mass (red arrow) and associated ipsilateral lymphadenopathy (black arrow). The tonsil primary tumor was confirmed to be greater than 4 cm with no evidence of invasion of adjacent structures.

Fused axial positron emission tomography-computed tomography (PET-CT) of the neck, axial view.

Fused axial positron emission tomography-computed tomography image showing a metabolically active tonsillar tumor (red arrow) and ipsilateral lymph node (black arrow). The scan detected no additional disease and confirmed metabolically active disease in the neck.

Metastatic squamous cell carcinoma with primary tonsillar tumor

Squamous cell carcinoma of tonsil

Cutaneous squamous cell carcinoma


80-year-old woman with 6-month history of slowly increasing asymptomatic lumbar subcutaneous mass. History of chronic renal failure requiring dialysis three times weekly for 10 years. Poor compliance with phosphate-binding medications and dietary restrictions. Physical exam showed firm, immobile subcutaneous nodule measuring 9 cm in major axis. Laboratory findings: serum calcium 1.95 mmol/L (normal: 2.05-2.55), serum phosphorus 3.3 mmol/L (normal: 0.74-1.52), serum intact parathyroid hormone 142 ng/L (normal: 10-65), serum creatinine 787 μmol/L (normal: 53-106).

Clinical photograph of the right lumbar area at the time of physical examination.

A: An irregularly shaped subcutaneous mass with a normal surface is shown on the right lumbar area in a clinical photograph, depicting the anatomical site on the patient’s back at the time of physical examination.

(B) CT, transverse slice. (C) Three-dimensional CT, subcutis.

(B) CT transverse slice. (C) Three-dimensional CT showing lobular calcified mass with fibrous capsule in the subcutis.

^67Ga-scintigraphy of the right lumbar region.

67Ga-scintigram showed abnormal gallium accumulation corresponding to the right lumbar mass, with no other pathological uptake

tumoural calcinosis

Endocrine, nutritional or metabolic diseases


A 16-year-old male presented with bilateral breast enlargement that had been present for 4 years, causing social withdrawal and avoidance of outdoor activities. He had a history of hypospadias requiring surgical correction at 1 year of age. Physical examination revealed height of 161 cm, weight of 57.8 kg (BMI 22.3 kg/m²), and blood pressure of 120/80 mmHg. His pubertal development showed normal progression overall, but both breasts were enlarged (Tanner stage III). Pubic hair development was at Tanner stage V, bilateral testicular volume was 15 mL (Tanner stage IV). Complete blood count, biochemistry, and urinalysis were normal. Endocrine testing showed testosterone level of 50.83 nmol/L (normal 9.7-27.8), DHEA level of 15.03 nmol/L (normal 6.2-43.3), DHEA-S level of 5,120 nmol/L (normal 1,600-12,200), 17-hydroxyprogesterone level of 6.61 nmol/L (normal 1.88-10.94), LH level of 11.5 IU/L (normal 1.7-8.6), FSH level of 5.5 IU/L (normal 1.5-12.4), estradiol level of 0.191 mmol/L (normal 0.026-0.147), β-hCG level of <0.1 IU/L (normal <2.6), prolactin of 21.7 pg/L (normal 4.0-15.2), free T4 level of 18.9 pmol/L (normal 11.9-21.9), and TSH level of 2.43 mIU/L (normal 0.27-4.2). His karyotype was 46,XY.

(A) Clinical photograph, anterior view. (B) Clinical photograph, lateral view.

Shows bilateral gynecomastia from anterior and lateral views, demonstrating breast enlargement in the male patient

Clinical photograph of the external genitalia, anterior view.

Figure 2 depicts a clinical photograph of the external genitalia demonstrating a micropenis, illustrating the anatomical finding in this partial androgen insensitivity syndrome patient; the image provides a direct anterior view, and no additional imaging or staining modalities are employed.

(A) Androgen receptor gene sequencing analysis, exon 4, comparison between normal and patient sequences.

Androgen receptor gene sequencing results showing somatic mosaicism (c.2128G>A, p.Glu710Lys) in exon 4, with comparison between normal and patient sequences

Partial androgen insensitivity


A 27-year-old primigravid woman from Brazil at 25 weeks 5 days of gestation presented to the emergency department with acute respiratory distress that developed the evening before. She experienced progressively worsening cough productive of blood-tinged, frothy sputum, shortness of breath, and chest pain, but denied fevers, chills, hemoptysis, lower-extremity edema, or calf pain. She reported regular fetal movement with no uterine contractions. Her pregnancy had been uncomplicated with regular prenatal care, and she had no history of serious medical conditions. She immigrated from Brazil to Massachusetts 7 years earlier and her family history was negative for venous thrombosis and pulmonary or cardiovascular disease. On examination, she appeared in acute respiratory distress with accessory muscle use, temperature 37.4°C, pulse 144 beats per minute, blood pressure 142/80 mmHg, respiratory rate 30 breaths per minute, and oxygen saturation 76% on room air improving to 85% with 70% oxygen via nonrebreather mask. She had elevated jugular venous pressure to the angle of the jaw, diffuse bilateral rales, tachycardia, no murmurs, normal abdomen, fundal height 23 cm, fetal heart rate 130-140 bpm, closed cervix, warm extremities with 2+ pedal pulses bilaterally, and no edema.

Chest radiograph of both lungs.

Chest radiograph shows diffuse air-space opacities with butterfly-like appearance throughout both lungs, prominence of the right minor fissure, dilatation of the proximal pulmonary artery, and left atrial enlargement

Electrocardiogram.

Electrocardiogram shows sinus tachycardia with broad, notched P waves (P mitrale) in lead II and prominent negative P waves in lead V1, findings consistent with left atrial enlargement

(A) Echocardiogram, parasternal long-axis view. (B) Echocardiogram, apical four-chamber view. (C) Continuous-wave Doppler imaging, mean mitral-valve pressure gradient=20 mm Hg.

A parasternal long-axis view (Panel A) and an apical four-chamber view (Panel B) show normal left ventricular size, left atrial (LA) enlargement, and thickening of the mitral-valve leaflets (arrows) (see Videos 1 and 2). Continuous-wave Doppler imaging (Panel C) shows a mean mitral-valve pressure gradient of 20 mm Hg. The findings are consistent with severe rheumatic mitral stenosis.

Rheumatic mitral valve stenosis


An 18-year-old woman was initially well until developing headache and sore throat without fever two weeks prior to current admission. Her medical history included dysmenorrhea treated with norethindrone acetate and ethinyl estradiol oral contraceptives, and asthma. She was allergic to penicillins (caused urticaria) and possibly allergic to cephalosporins. She lived with family and attended high school, with no smoking, alcohol, or illicit drug use, and no travel exposures. She initially had a negative rapid streptococcal test, but during the subsequent days developed persistent throat pain, decreased oral intake, dehydration, weakness, and fevers up to 39.4°C. Laboratory findings showed white-cell count less than 2000 per cubic millimeter, positive IgG and IgM antibodies to EBV viral capsid antigen and EBV nuclear antigen antibodies, with negative influenza A and B, and CMV IgM and IgG antibodies. Pharyngeal culture grew group C streptococcus. Nine days before current admission, she developed trismus, jaw opening pain, and right facial/jaw swelling. Six days before admission, right parotid gland swelling and erythema persisted with fevers up to 38.3°C. Two days before current admission, right eyelid swelling and horizontal diplopia with decreased right eye abduction developed. On examination at Massachusetts Eye and Ear Infirmary, she was somnolent but arousable with normal vital signs. She had diffuse right preauricular and periorbital swelling, mild trismus, bilateral cervical lymphadenopathy (greater on right), and right-sided preauricular and postauricular lymphadenopathy. White plaque was visible on gingivobuccal sulcus and anterior tongue that was painful when scraped. The right parotid gland was tender with no fluid discharge from Stensen's duct. Neurologically, the right eye had medial deviation with inability to abduct past midline, supraduction limited by 50%, and mild tandem walking difficulty. Visual acuity was 20/30 right eye and 20/20 left eye. She had 1+ lateral clear chemosis of the right eye with minimal erythema and tenderness, and no palpable fluctuance. A grade 1/6 systolic murmur was heard at left lower sternal border.

Laboratory results. Urinalysis.

Laboratory results showed hematocrit 28.0%, hemoglobin 9.8 g/dl, white-cell count 8290 per mm³ with 80.6% neutrophils and 11.3% lymphocytes, platelet count 119,000 per mm³, prothrombin time 15.8 sec with INR 1.2, glucose 173 mg/dl, glycated hemoglobin 5.9%, total protein 5.9 g/dl, albumin 2.3 g/dl, calcium 7.9 mg/dl, and phosphorus 3.3 mg/dl. Activated partial-thromboplastin time, red-cell indexes, renal-function tests, electrolytes, magnesium, globulin, angiotensin-converting enzyme, and IgG, IgA, and IgM levels were normal. Tests for heterophile antibodies, HIV types 1 and 2 antibodies, and HIV nucleic acid were negative. Urinalysis showed trace protein, 3+ glucose, and 2+ urobilinogen with squamous epithelial cells and bacteria suggesting contamination.

(A) MRI of the head, coronal view, T1-weighted with contrast. (B) MRI of the neck, coronal view, fat-saturated sequence. (C) MRI of the neck, axial view, diffusion-weighted imaging. (D, E) MRI of the right orbit, axial and coronal views, fat-saturated sequence.

MRI Scans of the Head and Neck. T1‑weighted images of the head and neck were obtained after the administration of contrast material. A coronal image of the head shows temporal pachymeningeal enhancement and subtle leptomeningeal enhancement, findings suggestive of basilar and temporal meningitis (Panel A, arrows). A coronal fat‑saturated image (Panel B) and an axial diffusion‑weighted image (Panel C) show changes consistent with abscess formation in the right parotid gland (arrows). Axial and coronal fat‑saturated images (Panels D and E, respectively) show changes consistent with a subperiosteal abscess in the right orbit (arrows).

Clinical photographs of the right periorbital region.

Photographs showed periorbital erythema and edema surrounding the right eye, and conjunctival injection and chemosis.

Lemierre's syndrome caused by Fusobacterium necrophorum, with cavernous-sinus thrombophlebitis, carotid-artery thromboarteritis, and abscesses of the parotid gland and subperiosteal orbit

THE - [tricho-hepato-enteric] syndrome

nonpyogenic thrombophlebitis of cavernous sinus

Carotid artery syndrome

abscess of parotid gland

Orbital subperiosteal abscess


A 62-year-old male patient presented with renal cell carcinoma requiring partial nephrectomy. His past medical history included stable chronic lymphocytic leukemia treated with rituximab and hypothyroidism under substitution with L-thyroxine. Five days after nephrectomy, he developed a progressive painful ulceration at the site of incision that was deep. The left lumbar area was indurated and erythematous. The patient became febrile and his white blood cells rose from 6,100 to 56,000/mm³, while C-reactive protein levels increased from 1.4 to 259 mg/L. Despite empirical antibiotic treatment with ciprofloxacin, then imipenem and doxycycline, his condition progressed relentlessly. Ultrasound and computer tomography scans failed to identify an abscess. Surgical wound revision did not identify any sign of bacterial infection. Preoperative, intraoperative, and postoperative wound cultures remained negative, however blood culture was positive for Staphylococcus haemolyticus.

(A) Clinical photograph of the left lumbar area obtained five days after nephrectomy.

A: Figure 1 (A) depicts a clinical photograph showing extensive ulceration at the surgical incision site on the left lumbar area, following nephrectomy, characterized by a deep lesion with overhanging violaceous borders and surrounding indurated, erythematous skin that developed five days postoperatively.

Histology of the vital edge of the dermal debridement, H&E staining.

Histology with haematoxylin and eosin staining of the vital edge of the dermal debridement shows pronounced phlegmonous and granulomatous nonspecific inflammation approximating the deep dermis and the subcutaneous fat tissue

Immunohistochemistry.

Immunohistochemistry shows the inflammatory infiltrate mostly consisted of myeloperoxidase positive granulocytes with only few concomitant lymphocytes

Immunohistochemistry for CD79a.

Immunohistochemistry shows no indication of an appreciable CD79a positive B-lymphoid cell population

Postoperative pyoderma gangrenosum in association with chronic lymphocytic leukemia and renal cell carcinoma

Pyoderma gangrenosum

chronic lymphocytic leukaemia

renal cell carcinoma NOS


A 35-year-old female with a history of intermittent rhinitis presented with a 5-day history of urticaria, fever, headaches, myalgia and arthralgia. She developed pruriginous and painful wheals and erythematous maculae more than 1 cm in diameter with a burning sensation on her limbs. The lesions lasted more than 24 hours and caused alteration of skin pigmentation. Angioedema was present in hands, fingers, ankles and feet, leaving no pitting. She experienced severe headaches and myalgia that impaired her daily activities, and fever spiked as high as 39.5°C. The patient had been taking over-the-counter diet pills eighteen days before symptom onset and had previously consulted six days earlier for dehydration and violaceous hives in her palms, after which she discontinued the pills. Physical examination revealed large confluent areas of wheals and maculae on limbs, with patient-scored pruritus intensity of 6/10 and complaints of muscular pain. Laboratory findings showed normal hemoglobin concentration, lymphopenia, and elevated C-reactive protein at 7.5 mg/L (normal <5 mg/L), while complement components, liver function tests, urea, creatinine, plasma sodium, glucose, thyroid hormones and antibodies were within normal ranges, and antinuclear antibodies were not detectable. Skin biopsy revealed slight alteration of vacuolar interface, papillary dermis edema, and moderate superficial and perivascular infiltrate of lymphocytes and eosinophils with focal fibrin deposits in blood vessel walls and extravasation of erythrocytes.

Clinical photograph of the trunk, back, and abdomen.

Shows wheals and erythematous maculae found in trunk, back and abdomen

Clinical photograph of the ankle during the acute presentation.

Figure 2 depicts a clinical photograph showing the patient’s ankle with wheals and erythematous maculae, demonstrating the cutaneous manifestations of urticarial vasculitis at this anatomical site during the acute presentation.

Urticarial Vasculitis induced by OTC diet pills

Urticarial vasculitis


An 83-year-old woman with hypertension was diagnosed with biopsy-proven vaginal melanoma four months prior to admission. She had invasive loco-regional disease and a three-millimeter nodule in the left upper lung lobe on PET-CT. She had received four cycles of ipilimumab (3 mg/kg every three weeks), with the last dose administered three weeks prior to hospitalization. The patient had developed pruritus, lethargy, and malaise after the third dose and diarrhea after the fourth dose of ipilimumab. Prior to admission, she experienced two weeks of fairly continuous worsening substernal chest pain and progressive dyspnea. On admission, she denied acute emotional stress, illicit drug use, or herbal medication use. Electrocardiography revealed sinus tachycardia at 110/minute and 1 millimeter ST elevations in leads I, V2, and V3. The initial troponin-I level was 0.98 (normal <0.04) ng/ml, thyroid-stimulating hormone was 2.6 (0.4-4.0) mIU/L, and the erythrocyte sedimentation rate was 65 (<20) mm/hour. Transthoracic echocardiography showed an ejection fraction of 50% and LV outflow tract obstruction with a peak gradient of 100 mmHg with systolic anterior motion of the mitral valve. Emergent cardiac angiography demonstrated an isolated 30% proximal left anterior descending artery stenosis without evidence of a thrombus.

(A) Ventriculogram during diastole. (B) Ventriculogram during systole.

Ventriculogram during diastole (left) and systole (right). While the left ventricular apex in these two images appears nearly akinetic, the remaining left ventricle is hyperkinetic.

(A) Coronal PET/CT, left ventricular apex. (B) Axial PET/CT, chest.

Coronal (left) and axial (right) PET/CT showing a focus of mildly increased FDG uptake corresponding to ballooning of the left ventricular apex. Additional findings at the axial level through the chest include FDG-avid metastatic lung nodules in the right upper lobe, small right pleural effusion and a large hiatal hernia.

Takotsubo cardiomyopathy


39-year-old woman with renal failure secondary to congenital kidney malformation, on haemodialysis 3 days/week for 17 years. Presented with sudden onset bilateral reduction of vision occurring soon after waking. One day prior, experienced visual obscurations in left eye after waking, described as temporary episodes of blurred vision lasting ~2 minutes. No headache reported. On examination: Snellen visual acuities were 6/5 right eye and 6/9.5 left eye. Had recently been diagnosed with episodes of hypotension associated with dizziness in mornings. Haemoglobin was 7.5 mmol/L. Blood pressure had typically been 110-120/80. MRI brain was normal.

(A) Color fundus photography of the optic disc, right eye. (B) Color fundus photography of the optic disc, left eye.

Figure 1 consists of fundus photographs of the right and left eyes, demonstrating bilateral optic disc swelling. The modality is color fundus photography, and the anatomical site examined is the optic disc of both eyes. The images were acquired in the context of acute bilateral visual loss occurring shortly after a hemodialysis session, as described in Case 1. The photographs show clear disc swelling in both eyes, with more pronounced swelling in the left eye, but do not depict hemorrhages, exudates, or other retinal abnormalities.

(A) Humphrey visual field chart of the right eye. (B) Humphrey visual field chart of the left eye.

Figure 2 consists of Humphrey visual field charts for the right and left eyes, illustrating bilateral inferior altitudinal visual field loss in both eyes, consistent with the characteristic visual defect of non-arteritic anterior ischaemic optic neuropathy in the context of dialysis-induced hypotension, as described in the body text and confirmed by the figure caption on page 2.

Bilateral non-arteritic anterior ischaemic optic neuropathy (NAAION) secondary to dialysis-induced hypotension

Non-arteritic anterior ischemic optic neuropathy

drug-induced hypotension


An 8-year-old Korean boy presented with severe global developmental delay and multiple exostoses. He was born to healthy non-consanguineous Korean parents after 40 weeks gestation with a birth weight of 2,400 g (<3rd percentile) and had no perinatal problems. Developmental delay was first noted at 3 months of age due to incomplete eye contact and head control. Physical examination revealed hypotonia, ptosis, nystagmus, and microcephaly. At age 6 years, his growth was severely retarded with height 96 cm (<3rd percentile), weight 15.7 kg (<3rd percentile), and head circumference 45 cm (<3rd percentile). Facial features showed sparse eyebrows, nystagmus, prominent nasal bridge, hypoplastic nare, down-turned mouth, and high arched palate. He was hypotonic and could not sit or walk alone. At age 5 years, his full-scale Intelligence Quotient was less than 30, indicating severe intellectual disability, with a social quotient of 17.8 and social age of 0.91 years. Multiple exostoses were first noted as protrusions of the right wrist and knee at age 6 years. Peripheral blood chromosome analysis showed a normal karyotype of 46,XY.

(A) Skeletal survey of the humerus, performed at age 6 years. (B) Skeletal survey of the wrists, performed at age 6 years. (C) Skeletal survey of the proximal femora, performed at age 6 years. (D) Skeletal survey of the distal femora and proximal tibia and fibula, performed at age 6 years.

Skeletal survey of long bones at age 6 yr. Multiple exostoses (arrows) of the metadiaphyseal portion of the humerus (A), wrists (B), and proximal femora (C) and at the distal femora and proximal tibia and fibula are evident.

(A) Skull radiograph, frontal view, at age 4 months. (B) Skull radiograph, lateral view, at age 4 months. (C) Skull 3-D reconstruction image at age 4 months. (D) Skull 3-D reconstruction image at age 8 years.

Serial changes of biparietal foramena in the skull. Frontal (A) and Lateral (B) radiographs taken at age 4 months. Large biparietal foramina are noted (arrows). 3-D reconstruction image (C) of the skull at age 4 months shows enlarged biparietal foramina acrossing midline (arrows). Follow up skull 3-D reconstruction image (D) at age 8 yr shows persistent biparietal foramina (arrows).

Chromosomal microarray.

Result of chromosomal microarray. The red bar indicates an 8.6 Mb deletion at 11p11.2p12 including EXT2, ALX4, and PHF21A.

Potocki-Shaffer syndrome


A 39-year-old man with a history of current smoking and no other medical history presented with left-sided squeezing chest pain that was worse in the early morning after drinking alcohol and lasted 30 minutes. Initial vital signs showed blood pressure of 132/89 mmHg and pulse rate of 98 beats/minute. Initial laboratory findings revealed creatine kinase 118 U/L (normal 58-348), CK-MB 1.7 ug/L (normal 0-5.0), elevated highly sensitive troponin-T 0.027 ng/mL (normal 0-0.014), and microcytic hypochromic anemia with hemoglobin 9.8 g/dL. Echocardiography showed normal-sized cardiac chambers with good left ventricular systolic function (ejection fraction of 61%) and no regional wall motion abnormality.

12-lead electrocardiogram performed on admission.

Figure 1 presents a standard 12-lead electrocardiogram (ECG) obtained on admission, which demonstrates ST-segment depression in leads V3 to V5 and flattened T waves in leads II, III, and aVF, indicating the initial cardiac electrical activity at presentation.

(A) Left coronary angiography. (B) Right coronary angiography. (C) Coronary angiography after stent implantation. (D) Intravascular ultrasound after overlapping stent implantation.

Initial coronary angiography. A: left coronary angiography shows near total occlusion of the mid left anterior descending coronary artery and intermediate stenosis of the left circumflex coronary artery. B: right coronary artery shows significant stenosis at the mid portion. C: after stent implantation, coronary angiography shows a successful result. D: final intravascular ultrasound finding after overlapping stent does not show dissection, or stent malap-position, or stent underexpansion.

Acute non-ST elevation myocardial infarction


A 16-year-old adolescent male presented with a 4-week history of weakness, malaise, anorexia, nausea, fever, and vomiting. There was no history of skin rash, joint pains, oral ulcers, or native/herbal medicinal intake. Physical examination revealed pallor, pitting pedal edema in both feet, and hypertension (160/90 mmHg), while systemic examination was otherwise unremarkable. Laboratory investigations showed hemoglobin of 90 g/L, total leukocyte count of 6600/cu mm, platelet count of 2×10^9/cu mm, dipstick albumin 3+ with 24-hour urine protein of 2.4 g, 15-20 red blood cells per high power field with RBC casts, blood urea of 46.4 mmol/L (130 mg/dL), and serum creatinine of 265.2 μmol/L (3 mg/dL) which rapidly progressed to 884 μmol/L (10 mg/dL) after 7 days. Antinuclear antibody and ANCA were negative by both ELISA and immunofluorescence. The patient tested negative for HBsAg, anti-hepatitis C antibody, and HIV. Serum complement levels were normal (C3/C4=120/40 IU/mL). Ultrasonography showed normal-sized kidneys (10 cm on either side) with normal pelvicalyceal system. Contrast-enhanced CT of chest and abdomen was normal, and ocular fundus examination was unremarkable.

Light microscopy of kidney biopsy. Direct immunofluorescence and electron microscopy of kidney tissue.

Light microscopy of kidney biopsy revealed necrotizing glomerulonephritis with crescents, showing a glomerulus with cellular crescent and underlying glomerular tuft with segmental necrotising lesion with disruption of the glomerular basement membrane, fibrin exudation and presence of karyorrhectic debris indicating small vessel vasculitis. Direct immunofluorescence and electron microscopy did not reveal any immune complexes.

ANCA-negative renal-limited pauci-immune glomerulonephritis

Pauci-immune proliferative glomerulonephritis


A 14-year-old girl presented with a 3-year history of continuous pain in the parietal and occipital regions of the scalp. The pain was described as oppressive and graded 5 out of 10 on a numerical pain rate scale. The patient did not identify any trigger factors. Neurological and general examinations were unremarkable with neither sensory symptoms nor local trophic changes present within the affected regions of the head. The occipital and auriculotemporal nerves were not tender to palpation. Brain magnetic resonance imaging and routine blood work-up with erythrocyte sedimentation rate and immunological screening showed no abnormalities. The patient had previously used acetaminophen with no substantial relief of symptoms.

Table of mean pressure pain thresholds measured in kPa at 25 scalp points including 21 EEG electrode positions and 4 symptomatic areas.

Shows mean pressure pain thresholds (PPT) measured in kPa at 25 points across the scalp, including 21 standardized EEG electrode positions and 4 symptomatic areas. The symptomatic points (painful areas behind C3, C4, between O2-T4, and O1-T5) all showed identical lower PPT values of 147.1 kPa compared to surrounding areas which ranged from 106.1 to 225.6 kPa.

Topographical pressure pain sensitivity map of the scalp using pressure algometry at 21 standard EEG points and four symptomatic areas.

Figure 1 presents a topographical pressure pain sensitivity map of the scalp in a patient with multifocal nummular headache, created by assessing pressure pain thresholds (PPT) at 21 standard EEG points plus four symptomatic areas using a pressure algometer applied to the scalp; the map, depicted as a color-coded diagram on page 3, demonstrates four localized patches of reduced PPT corresponding to the painful regions, indicating discrete areas of mechanical hyperalgesia without generalized scalp involvement.

Nummular headache


A 57-year-old man with an 8-year history of HIV infection presented with a 3-week history of worsening left inguinal pain and enlarging hernia. He reported a 10-year history of bilateral inguinal hernias (left larger than right) with intermittent bulging that was previously easily reducible. Three months prior, pain associated with the bulging increased. During the 3 weeks before presentation, he developed intermittent subjective fevers with associated night sweats, and noted hard, tender lumps next to the hernia. The night before presentation, his oral temperature reached 38.1°C. He was a heterosexual white man with a well-controlled HIV infection (most recent CD4 count 250/mm³, undetectable viral load on antiretroviral therapy). Past medical history was notable for Kaposi's sarcoma 8 years prior, molluscum contagiosum, anal dysplasia, pulmonary Mycobacterium avium complex infection, pneumocystis pneumonia, thrush, preseptal cellulitis, and cryptosporidium-related diarrhea. He reported no recent sexual activity (last contact 2 years prior with condom use), smoked cigarettes for 30 years, drank 1-2 alcoholic beverages daily, and had a 22-year-old cat. Physical examination revealed temperature 36.8°C, blood pressure 155/79 mmHg, pulse 82 bpm, and normal oxygen saturation. He had easily reducible bilateral inguinal hernias with bulky, slightly tender lymphadenopathy including three large lymph nodes (maximum diameter 3 cm) in the left inguinal region.

Laboratory results on presentation.

Laboratory results on presentation showed hematocrit 37.6%, hemoglobin 12.6 g/dl (both slightly below normal range for men), white cell count 12,100/mm³ (elevated), with neutrophilia at 83.9% and lymphopenia at 8.3%. Glucose was elevated at 144 mg/dl.

(A, B) CT scans with oral and intravenous contrast, axial view, left iliac and left inguinal regions. (C) CT scan with oral and intravenous contrast, coronal view, left inguinal region and liver.

Axial (Panels A and B) and coronal (Panel C) images from CT scans that were obtained after the administration of oral and intravenous contrast material show lymphadenopathy in the left iliac and left inguinal regions. An enlarged lymph node in the left external iliac region (Panel A, arrow) measures 2.4 cm in the short‑axis dimension, and a partially visualized lymph node in the left inguinal region (Panel B, arrow) measures 2.2 cm in the short‑axis dimension. Both of these nodes contain an area of hypodensity consistent with necrosis. Other enlarged lymph nodes were also seen in the left inguinal region (Panel C, ellipse), as was enlargement of the liver (Panel C).

(A–D) Inguinal lymph node biopsy, H&E staining. (E) Inguinal lymph node biopsy, Steiner silver staining. (F) Inguinal lymph node biopsy, Warthin–Starry silver staining.

Lymph-Node–Biopsy Specimen (Hematoxylin and Eosin and Silver Stains). Hematoxylin and eosin staining of an inguinal lymph‑node–biopsy specimen reveals focal capsular thickening, follicular hyperplasia, and irregularly shaped microabscesses (Panels A through D, within black dashed lines), lined by epithelioid histiocytes (Panel D, contained by white dashed lines). Steiner silver staining (Panel E) and Warthin–Starry silver staining (Panel F) reveal black pigmented structures at the periphery of a microabscess.

(A, B) Lymph-node biopsy, immunohistochemical staining for Treponema pallidum.

Lymph-Node–Biopsy Specimen (Immunohistochemical Stain). Immunohistochemical staining specific for Treponema pallidum reveals numerous coiled microorganisms (Panels A and B, stained in brown) outside and within the abscesses (Panel A, within dashed lines).

Necrotizing lymphadenitis due to Treponema pallidum (syphilis)

Syphilis, unspecified

Histiocytic necrotising lymphadenitis of Kikuchi and Fujimoto


A 44-year-old man was admitted to the hospital with prolonged diarrhea lasting one week, fever, and anuria. On admission, his blood pressure was severely elevated at 220/150 mmHg, but retinal fundoscopy showed no signs of malignant hypertension. Blood analysis revealed hemolytic anemia with hemoglobin of 6.9 g/dL, the presence of schistocytes in the blood smear, elevated lactate dehydrogenase at 1837 U/L, and a platelet count of 111,000/dL. The direct Coombs test was negative. He had acute renal failure with creatinine levels of 20.7 mg/dL. Laboratory studies showed normal C3, C4 and CH50 levels, and ADAMTS-13 activity was normal at 57%. Anti-nuclear, antiphospholipid, anti-topoisomerase III, and anti-ADAMTS-13 antibodies were all negative. Stool analysis was negative for Shiga-like toxin. Molecular genetic studies revealed normal plasmatic factor H at 26 mg/mL (normal range 12-56), 70% plasmatic concentration of factor I (normal range 71-115), and no antibodies against factor H. The expression of MCP on leukocytes was reduced at 51% compared to control (normal range 91-109), and genetic analysis identified a heterozygous mutation of intron 2 (c.286+1G>C) of the MCP gene. The patient's condition was resistant to standard treatment with plasmapheresis.

Renal biopsy performed in the second week after admission.

Renal biopsy conducted the second week after admission showed renal arteriolar wall thickening, mild interstitial fibrosis and tubular atrophy areas, with occlusive thrombosis in several small- and medium-sized arteries with secondary ischemic glomerular changes and extensive acute tubular necrosis.

Renal biopsy performed 2.5 months after admission.

Second renal biopsy performed 2.5 months after admission showed ischemic glomeruli and artery wall thickening with thrombotic microangiopathy changes, similar to those observed at the first biopsy with persistent thrombotic microangiopathic lesions and deterioration of interstitial fibrosis and tubular atrophy.

Atypical hemolytic uremic syndrome with MCP gene mutation

Atypical haemolytic uraemic syndrome

Diseases of the blood or blood-forming organs

PANK gene mutation


A 65-year-old male retired farmer presented with an inability to fully straighten the ring finger and little finger of his right hand, which had progressed over the past two years. He had recently noticed a 'rope like' swelling in his palm with no history of trauma. His medical history was unremarkable except for smoking cessation 10 years earlier with a 90 pack-year history. His father had a similar deformity. On examination, he had palpable cords to his middle, ring, and little fingers with palpable nodules on the volar aspect of all proximal phalanges, causing flexion contractures of the proximal interphalangeal joints. The cord and nodules in the ring finger were adherent to the overlying skin.

Clinical photograph of the right hand, volar aspect, showing metacarpophalangeal and proximal interphalangeal joints of the ring and little fingers.

Shows contractures of the metacarpophalangeal and proximal interphalangeal joints of the ring finger and little finger of the right hand. The skin was affected on the volar aspect of the metacarpophalangeal joint of the ring finger.

Dupuytren's contraction or disease


52-year-old woman initially diagnosed in 2007 with breast cancer. Pre-treatment staging was cT2cN0M0. Initial diagnostic testing showed: Estrogen receptors positive (40%), progesterone receptors negative, and ERBB2 testing showed 60% positivity (2+) but was not amplified by Fluorescence in situ Hybridization (FISH) on the primary surgical sample. In May 2010, she was found to have liver and retro-pectoral muscle metastases. By May 2014, molecular screening of retro-pectoral metastasis identified ERBB2 L869Q and CDH1 R63* mutations, without ERBB2 amplification. Pre-treatment liver function tests showed elevated transaminases (AST: 329 IU/L, ALT: 298 IU/L) and CA15-3 tumor marker was 3327 U/mL.

CT of the liver, pre-treatment.

Pre-treatment liver CT scan showing metastatic disease

Metastatic pleomorphic invasive lobular breast carcinoma (ILC) with ERBB2 L869Q and CDH1 R63* mutations

Pleomorphic invasive lobular breast carcinoma

Invasive pleomorphic lobular carcinoma of breast

Metastatic breast carcinoma [primary breast carcinoma spreading elsewhere]


An 80-year-old man presented with a one-month history of cough. He had a past medical history significant for colon cancer surgery performed 10 years prior, with no evidence of recurrent or metastatic disease. He also had a 10-year history of hypertension and atrial fibrillation. Laboratory tests, including serological tests for human immunodeficiency virus (HIV), revealed no abnormalities. Physical examination findings included chest radiography showing right pleural effusion and cardiomegaly. A few enlarged lymph nodes were noted at the right cardiophrenic angle. Initial cytological examination of pleural fluid and pleural biopsy using an Abram's needle were non-diagnostic.

CT, contrast-enhanced, right hemithorax.

Contrast-enhanced CT showing pleural effusion and diffuse homogeneous pleural mass invading into extrapleural space in right hemithorax, with intercostal artery enveloped by parietal pleural and extrapleural masses demonstrating sandwich sign.

F-18-fluorodeoxyglucose positron emission tomography.

F-18-fluorodeoxyglucose positron emission tomography showing diffuse hypermetabolism in right pleural mass.

Pleural biopsy, immunohistochemistry for CD-20 antigen, Epstein-Barr virus negative.

Pleural biopsy revealing diffuse infiltration of small to medium-sized lymphoid cells with scant to moderate amount of clear cytoplasm, with monotonous infiltration of small B-cells expressing CD-20 antigen. Epstein-Barr virus was negative in the specimen.

Primary cutaneous marginal zone B-cell lymphoma


A 35-year-old woman presented with severe hypertension, oedema and renal failure. She had a medical history significant for a pregnancy 12 months earlier that was complicated by preeclampsia, requiring Caesarean delivery at 29 weeks gestation. Following delivery, she developed poorly controlled hypertension and proteinuria exceeding 1 g/day. Six months before this admission, she began experiencing fatigue, headaches, severe hypertension, and facial and pedal oedema. She denied fever, neurologic abnormalities, or diarrhoeal prodrome. Physical examination revealed a pale, hydrated woman with blood pressure of 151/103 mmHg. Laboratory investigations showed severe anemia (hemoglobin 4.65 mmol/L or 7.5 g/dL), significant renal dysfunction (urea 182 mg/dL, creatinine 65 mmol/L or 6.46 mg/dL), thrombocytopenia (platelets 46 × 10⁹/L), increased reticulocyte count, and schistocytes on peripheral blood smear. Urinalysis revealed proteinuria of 4.9 g/24h and 5-10 red blood cells per high-power field. Additional laboratory findings included elevated lactate dehydrogenase (1669 U/L), total bilirubin 14 mg/L, direct bilirubin 4.4 mg/L, low haptoglobin (<0.2 mg/dL), and negative Coombs test. Normal liver enzymes were noted. All immunologic tests, viral screening, and antiphospholipid antibodies were normal.

(A–C) Clinical photographs of leg skin lesions before plasmapheresis.

(A) Leg skin lesions with purplish colour before plasmapheresis. (B) Leg skin lesions with purplish colour before plasmapheresis. (C) Leg skin lesions with purplish colour before plasmapheresis.

(A–C) Skin biopsy.

(A) Skin biopsy showed fibrin thrombi in the small blood vessels, with discrete inflammatory infiltrate of lymphocytes and plasma cells. (B) Skin biopsy showed fibrin thrombi in the small blood vessels, with discrete inflammatory infiltrate of lymphocytes and plasma cells. (C) Skin biopsy showed fibrin thrombi in the small blood vessels, with discrete inflammatory infiltrate of lymphocytes and plasma cells.

Atypical haemolytic uraemic syndrome (aHUS)

Atypical haemolytic uraemic syndrome


A 47-year-old homeless man presented with intermittent pain and pins-and-needles sensation in his legs that had developed over one month, beginning as paresthesias in his toes and gradually spreading to his shins. He had a 33-year history of intravenous heroin use and was a current user, with hepatitis C virus infection and hypertension. He had a 52 pack-year smoking history and reported rare alcohol intake. He was not sexually active and had no family history of neuropathy. Physical examination revealed a chronically ill-appearing man who was alert and oriented, afebrile, with blood pressure of 170/110 mmHg, pulse 68 beats per minute, and respiratory rate 20 breaths per minute. Cardiac, pulmonary, abdominal, and skin examinations were normal. Neurologic examination showed no cranial nerve abnormalities, normal muscle strength (5/5 bilaterally), normal deep-tendon reflexes, but he had an unsteady gait with limited ambulation due to pain and decreased sensation to pinprick, light touch, and temperature in the lower extremities bilaterally.

Clinical photograph of the upper chest and dorsal arms taken during the chronic phase of illness.

Figure 1 on page 4 is a clinical photograph showing symmetric, photodistributed erythema with overlying hyperkeratosis affecting the patient's upper chest and dorsal aspects of the arms, as described in the figure caption and referenced in the body text. The image demonstrates dermatological findings in sun-exposed areas, consistent with a nutritional deficiency dermatosis, and corresponds to the skin manifestations observed in this patient; no special staining, imaging, or magnification is used, and the timing is during the chronic phase of the patient's illness after the persistence of a photodistributed rash.

Clinical photograph of the anterior neck.

Demonstrates a well-demarcated erythematous eruption in the distribution of a necklace on the front of the neck, representing Casal's necklace, a hallmark clinical sign of pellagra

Pellagra

niacin deficiency NOS


A previously healthy 9-year-old boy presented to the emergency department with a 6-hour history of left chest pain and increasing respiratory distress. His vital signs showed a respiratory rate of 40/min and heart rate of 105/min. Physical examination revealed unremarkable cardiac auscultation, while auscultation of lung fields showed diminished breath sounds over the left side.

(A) Chest radiograph, anteroposterior view. (B) Chest radiograph, lateral view.

Anteroposterior (a) and lateral (b) chest radiographs with large air-fluid level in left hemithorax. Note superior rim formed by stomach wall and compressed lung (arrows) and mediastinal shift to the right

Chest x-ray performed after gastric decompression.

Chest x-ray after gastric decompression showing normalization of the mediastinal shift and the gastric tube curving back into the left hemithorax, confirming the intrathoracic position of the stomach.

Tension gastrothorax due to late onset congenital diaphragmatic hernia (CDH) with a 5×5 cm posterolateral defect in the left diaphragm

high arterial tension

Congenital diaphragmatic hernia


45-year-old woman presented with syncope and severe anemia (hemoglobin 6 g/dL) with lower GI bleeding. A diagnostic colonoscopy was negative. CT scan of abdomen and pelvis revealed a 3.2 x 3 x 2.9 cm contrast-enhancing right lower-quadrant mass arising from the wall of the ileum. No evidence of metastatic disease. Subsequent laparotomy found a 3.5 cm mass that was resected with negative margins. Molecular studies showed a 42-base pair deletion in exon 11 of the KIT gene (V559_D572del) that would delete all or part of codons 558 to 572 and would change the 558-encoding amino acid from Lys to Asn (K558N).

(A) Small intestine photomicrograph, H&E staining. (B) Small intestine photomicrograph, CD117 staining. (C) Small intestine photomicrograph, DOG-1 staining. (D) Small intestine photomicrograph.

Photomicrographs of a small-intestinal GI stromal tumor (courtesy of A. Lazar, MD). (A) Hematoxylin and eosin staining show the mixed spindle and epithelioid appearance. (B) Positive staining for CD117. (C) Positive staining for DOG-1. (D) A cropped-out area showing a mitotic figure.

GI stromal tumor (GIST) with mixed spindle and epithelioid features

Gastrointestinal stromal tumour of unspecified gastrointestinal sites


A 49-year-old Asian man presented with oppressive chest pain associated with hypertensive crisis (BP 200/100 mmHg). His medical history included hypertension, smoking, and surgical mitral and aortic valve substitution with mechanical prosthesis 16 years prior, followed by re-substitution due to secondary thrombosis. He had paroxysmal atrial fibrillation previously controlled with amiodarone, which was stopped 2 weeks before admission due to thyrotoxicosis. On admission, he was oriented and alert with BP 200/100 mmHg, heart rate of 100 bpm, and normal physical examination. Laboratory tests showed elevated myocardial necrosis enzymes (troponine T-hs 133 ng/L, creatine kinase-MB 13.0 ng/L) and thyroid hormones (TSH 0.007 µIU/mL, fT3 8.3 pg/mL, fT4 44.2 pg/mL). Additional tests revealed elevated 24-h urinary epinephrine (547 μg/24h), urinary metanephrine (8,720 μg/24h), and serum calcitonin (312 pg/mL), with normal parathormon (34 pg/mL).

CT of the right adrenal region, lesion size 35 mm, density >2 HU.

CT showed a 35 mm right adrenal lesion with smooth margins and density higher than 2 HU

The thyroid sample. (A) Original histological slide, H&E staining. (B) H&E staining, 100× magnification. (C) Calcitonin staining, 200× magnification.

Medullary thyroid carcinoma: histological findings. (A) Scan of original histological slide (H&E staining, pale central area corresponded to dense fibrous tissue infiltrated by tumor). (B) Two tumor nodules in dense fibrous tissue at the top of figure (H&E staining, 100×). (C) Tumor cells are positive for Calcitonin (Calcitonin staining, 200×).

Multiple endocrine neoplasia type 2A (MEN2A) syndrome with right adrenal pheochromocytoma and medullary thyroid carcinoma, confirmed by RET gene mutation p.C634R in exon 11

Multiple endocrine neoplasia type 2A

Malignant phaeochromocytoma of adrenal gland[Right]

Medullary carcinoma of thyroid gland


32-year-old man with history of mixed germ cell tumor of testis. Previous findings included: 5-cm testicular tumor that was 95% yolk sac tumor and 5% embryonal carcinoma. Presented with acute-onset right-sided weakness and numbness. Had 2-week history of intermittent headaches. Serum alpha-fetoprotein (AFP) level was elevated at 47 ng/mL.

Histopathological section of resected brain tissue (left parietal lobe), H&E staining.

Figure 1 presents a histopathological section of resected brain tissue stained with hematoxylin and eosin (H&E), examining predominantly a yolk sac element of a metastatic germ cell tumor; the tissue was acquired following emergency surgical decompression and tumor resection from the patient's left parietal lobe due to acute neurological symptoms, and the image demonstrates characteristic histological features under light microscopy, although specific magnification is not stated.

Metastatic germ cell tumor (predominantly yolk sac tumor) with brain metastasis

Germ cell tumour of testis

Yolk sac tumour, unspecified site, female

brain metastases


An 85-year-old man presented to the emergency department with a 5-day history of headache, vomiting, and progressive visual loss in both eyes. He denied weight loss, seizures, or limb or facial weakness. His medical history included hypertension, abdominal aortic aneurysm under surveillance, hypothyroidism, and benign prostatic hypertrophy. On examination, his blood pressure was 110/75 mmHg, pulse 80 beats per minute and regular, with a Glasgow Coma Score of 15. Peripheral neurological examination was normal, but cranial nerve examination revealed bitemporal hemianopia with normal fundoscopy.

Coronal T2-weighted MRI of the head, non-contrast.

Coronal T2 weighted magnetic resonance imaging of the head without contrast shows a sellar mass compressing the optic chiasm and signal changes suggestive of haemorrhagic regions within the mass

Pituitary apoplexy


A 47-year-old woman with a known medulloblastoma diagnosed 2 years previously presented for a scheduled oncology check-up. Her existing medications included temsirolimus for her tumor and valproate for seizures she had experienced over the past year. She reported not feeling well for the previous few days with symptoms including drowsiness, lethargy and headaches. Clinical assessment revealed a fever but otherwise no apparent issues with no signs of edema, normal jugular venous pressure, and normal heart and lung auscultation. Her physician determined that her hyponatremia was most likely being caused by SIADH.

Physical examination findings and laboratory results.

Physical examination showed weight 58 kg, blood pressure 115/75 mmHg, heart rate 93 bpm, SpO₂ 98%, temperature 38.4°C. Laboratory data revealed serum sodium 123 mmol/L, serum osmolality 253 mOsm/kg, serum potassium 3.2 mmol/L, creatinine 44.2 μmol/L, urea 24 mg/dL, uric acid 125 μmol/L, urinary osmolality 599 mOsm/kg, urinary sodium 99 mmol/L, urinary potassium 39 mmol/L.

Hyponatremia secondary to SIADH caused by underlying pneumonia

hyponatraemia

Syndrome of inappropriate antidiuretic hormone secretion

Syndrome of inappropriate secretion of antidiuretic hormone

Pneumonia


A 23-year-old man was urgently referred for evaluation of rapidly enlarging cervical lymphadenopathy, progressive dyspnea, fatigue, night sweats, and an unintentional weight loss of 25 pounds. His physical examination was remarkable for bulky cervical and supraclavicular lymphadenopathy, with a normal testicular examination. A computed tomography scan of the neck performed 30 days before referral revealed bilateral cervical and supraclavicular lymphadenopathy (6×5 cm). A fine-needle aspirate of nasopharyngeal tissue demonstrated fibroadipose tissue. A core needle biopsy of a left internal jugular lymph node demonstrated a reactive lymph node but no malignancy. His lactate dehydrogenase concentration was 327 U/L (normal range, 118-225 U/L). A marrow aspirate and biopsy revealed normal trilineage hematopoiesis with no evidence of lymphoma and a normal male karyotype (46, XY). A lumbar puncture sample did not contain lymphoma cells.

(A) Cytospin preparation micrograph of mediastinal mass, 100× magnification. (B) Biopsy specimen micrograph of mediastinal mass, H&E staining, 40× magnification.

Cytospin and hematoxylin-and-eosin-stained slides from a mediastinal mass specimen containing T-lymphoblastic lymphoma. (A) Micrograph of a cytospin preparation (magnification, ×100). There are numerous lymphoblasts with a high nuclear-to-cytoplasmic ratio, irregular nuclear contours, finely dispersed chromatin, small indistinct nucleoli, and no granules. (B) Micrograph of a biopsy specimen stained with hematoxylin and eosin (magnification, ×40). Infiltrating lymphoblasts (small, round, blue cells) show marked nuclear irregularities, fine nuclear chromatin, and scant cytoplasm.

B lymphoblastic leukaemia or lymphoma with t(v;11q23); MLL rearranged


A 56-year-old woman presented with a 1-week history of shortness of breath and sore throat. Her medical history included smoking, obesity, type 2 diabetes On examination, her oxygen saturation was 81% on room air, dropping to 71% with exertion. She was afebrile with a normal white blood cell count. Chest examination revealed soft heart sounds, decreased air entry, wheeze, and aegophony at the lung bases bilaterally. Abdominal examination was normal except for obesity.

Chest radiograph.

Chest radiograph showed a large mass-like density in the right cardiophrenic angle and hyperinflation

CT scan of the thorax and diaphragm with contrast, defect measuring 22.6 cm.

Contrast-enhanced CT scan revealed a large incarcerated Morgagni hernia, characterized by a defect in the right anterior diaphragm with herniation of omentum into the thorax, measuring 22.6 cm at its widest point

Hernias, unspecified

incarcerated sliding hiatus hernia


59-year-old man with multiple nodules on his joints. Patient had history of gouty arthritis (confirmed by visualization of negative birefringent crystals in joint aspirate), hypertension, and type 2 diabetes mellitus. Physical examination showed multiple gouty nodules in the auricle, knee, ankle, and toe joints, with severe loss of flexion and extension in hands. Laboratory findings showed elevated creatine (137 μmol/L; normal range 62–115 μmol/L) and uric acid (725 μmol/L; normal range 208–428 μmol/L).

Clinical photographs of the hands taken at presentation.

Figure 1 shows clinical photographs of the hands of a 59-year-old man, depicting giant gouty tophi most prominently in the joints of the hands, as documented during physical examination on presentation.

Gout

Tophaceous gout

Gout


A-year-old female presented to the emergency department with pain in the left upper abdominal quadrant. She brought an abdominal CT scan from another hospital showing a 10 × 6.3 × 8.6 cm-sized left adrenal mass with hemorrhagic necrosis. On admission, her blood pressure was elevated (systolic 150-170 mmHg, diastolic 100-110 mmHg) with no previous history of hypertension. Her weight was 63 kg and height was 175 cm. During history taking after surgery, she revealed she had undergone breast augmentation surgery because she never developed breasts during puberty, had no menarche, and lacked secondary sexual characteristics such as pubic and axillary hair (Tanner stage I). Routine biochemical studies, urine analysis, and coagulation tests were normal. Serum electrolytes showed Na 141 mmol/L, K 3.3 mmol/L, and Cl 100 mmol/L. Chest X-ray and electrocardiography were normal. Chromosomal study showed normal karyotype 46,XX. Genetic analysis revealed compound heterozygous mutations p.Tyr329fs and p.His373Leu in exon 6 of the CYP17A1 gene.

(A) CT scan of the left adrenal gland. (B) 18F-FDG PET-CT of the left adrenal gland, FDG uptake.

(A) Computed tomography (CT) scan of the large, 7.6-cm, hemorrhagic mass in the left adrenal gland (white arrows). (B) Fluoro-deoxyglucose (FDG) uptake (black arrow) in the solid portion of the mass in 18F-FDG-positron emission tomography-CT.

Pre-surgical laboratory hormone levels. Post-surgical laboratory hormone evaluation. 24-hour urine analysis. Low-dose ACTH stimulation test.

Pre-surgical hormone levels showed cortisol 0.9 μg/dL (NR 6.7-22.6), ACTH 75.94 pg/mL (NR 7.2-63.6), aldosterone 183.31 pg/mL (NR 29.9-158.8), renin 0.80 ng/mL/hr (NR 1.31-3.95), with aldosterone-renin ratio of 22.9. Additional post-surgical hormonal evaluation revealed thyroid stimulating hormone 3.1 μIU/mL, prolactin 27.2 ng/mL, luteinizing hormone 25.0 mIU/mL, follicular stimulating hormone 51.5 mIU/mL, estradiol <20 pg/mL, progesterone 4.32 ng/mL, 17-OH-progesterone 0.21 ng/mL, DHEA 0.41 μg/mL, and testosterone <2.5 ng/dL. 24-hour urine analysis showed metanephrine 0.518 mg/day, epinephrine 2.3 μg/day, vanillylmandelic acid 4.04 mg/day (all within normal range), but reduced 17-ketosteroids 2.77 mg/day (NR 7-20) and urinary free cortisol 37.6 (NR 55.5-286). Low-dose ACTH stimulation test showed blunted response with cortisol levels at baseline 1.0 μg/dL, 1.6 μg/dL at 30 minutes, and 1.0 μg/dL at 1 hour

Gross pathological examination of the adrenal gland.

Gross pathological examination revealed adrenal cortical adenoma measuring 10 × 5 × 3 cm with degenerative cystic changes

Congenital adrenal hyperplasia with 17α-hydroxylase/17,20-lyase deficiency caused by compound heterozygous mutation of CYP17A1 gene, presenting as massive adrenocortical adenoma

Congenital adrenal hyperplasia due to 17α-hydroxylase/17,20-lyase deficiency

Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency

Adrenocortical adenoma


78-year-old woman with hepatitis C virus (HCV) history presented with abnormal liver function tests on routine examination. She had no alcohol use history. Clinical findings: Eastern Cooperative Oncology Group performance status of 1, no stigmata of chronic liver disease, no ascites or encephalopathy or other associated clinical symptoms. Laboratory findings: Child-Pugh score A6 (due to low albumin of 34 g/L), platelets slightly depressed at 121,000 mL, alpha-fetoprotein level 89 mg/L.

Computed tomography for radiation planning, with prescription dose 45 Gy in five fractions and 50% dose 22.5 Gy in five fractions.

Radiation planning computed tomography images showing target volume to be treated (gross tumor volume in red and planning target volume in blue). Prescription dose (45 Gy in five fractions) shown in green, and 50% dose (22.5 Gy in five fractions) shown in orange.

(A) CT of the liver, axial view, arterial phase, baseline. (B) CT of the liver, axial view, portal venous phase, baseline. (C) CT of the liver, coronal view, arterial phase, baseline. (D) CT of the liver, axial view, arterial phase, 9 months post radiotherapy. (E) CT of the liver, axial view, portal venous phase, 9 months post radiotherapy. (F) CT of the liver, coronal view, arterial phase, 9 months post radiotherapy.

Axial arterial and portal venous phase and coronal arterial phase computed tomography (CT) images of hepatocellular carcinoma at baseline and 9 months post stereotactic body radiotherapy (RT), showing continued shrinkage and reduction in arterial enhancement.

Hepatocellular carcinoma (HCC) - 4.1 cm lesion in liver segment 7/8 with underlying cirrhosis due to HCV

hepatocellular carcinoma, NOS

Hepatic cirrhosis

Congenital Hepatitis C virus infection

Certain conditions originating in the perinatal period


An 18-year-old male presented with fever and pain in the lower abdomen, groin, and scrotum. Four days before admission, he developed fatigue, subjective fever, and chills, followed by headaches, non-bilious nonbloody emesis, diarrhea, decreased appetite, low back pain, and dysuria. His medical history included exercise-induced asthma and childhood hospitalization for diarrhea. He was born in Central America and moved to the US at age 15. Recent testing showed negative interferon-gamma release assay for tuberculosis, and negative tests for HIV, syphilis, gonorrhea, and chlamydia. On examination, he appeared tired with temperature 39.4°C, blood pressure 125/67 mmHg, pulse 121/min, respiratory rate 36/min, and oxygen saturation 100%. The paraspinal muscles of the low back were tender.

CT scan of the abdomen and pelvis, axial view.

CT scan showed ill-defined low-density material tracking along left retroperitoneum anterior to left psoas muscle and aorta into pelvis, displacing bladder to right. Low-density material also seen in left paracolic gutter.

MRI of the paraaortic, left common iliac, and left external iliac lymph nodes.

MRI revealed several prominent paraaortic, left common iliac, and left external iliac lymph nodes, some with central necrosis.

(A) Bone marrow core biopsy, H&E staining. (B) Bone marrow core biopsy, H&E staining, higher magnification. (C) Bone marrow core biopsy, immunostaining for CD163. (D) Bone marrow aspirate smear, Wright–Giemsa staining. (E) Bone marrow aspirate smear, Wright–Giemsa staining.

Bone Marrow–Biopsy Specimen. Hematoxylin and eosin staining of a core - biopsy specimen of the bone marrow shows appropriate cellularity for the patient’s age and maturing trilineage hematopoiesis; no lymphoid aggregates are present (Panel A). At higher magnification, hematoxylin and eosin staining shows a hemophagocytic macrophage with foamy cytoplasm containing red - cell debris and intact hematopoietic elements (Panel B, circle). Immunostaining for CD163 shows numerous hemophagocytic macrophages (Panel C, circle). Wright–Giemsa staining of a smear of bone marrow aspirate shows hemophagocytic macrophages, including one with numerous platelets and red cells (Panel D, arrow) and one containing a red cell and two granulocytic forms (Panel E, arrow).

Laboratory results.

Laboratory data showed decreasing platelet count (126,000 to 75,000), elevated C-reactive protein (120.9-178.5 mg/L), markedly elevated ferritin (8343-7008 ng/ml), elevated triglycerides (341-282 mg/dl), and other abnormalities in blood counts and chemistry.

Hemophagocytic lymphohistiocytosis of an unknown cause

haemophagocytic lymphohistiocytosis NOS


38-year-old woman, asymptomatic, discovered during routine health checkup due to abnormal chest radiograph. No history of smoking. All laboratory findings were within normal limits.

CT of the right lower lobe.

CT showed 1.2 cm-sized nodule in right lower lobe with spiculated margin and needle-like projections in periphery of nodule

Dynamic contrast-enhanced CT, peak enhancement 245 HU, with subsequent decrease to 168 HU at 180 seconds.

Dynamic contrast-enhanced CT showed early strong enhancement with peak enhancement of 245 HU and gradual loss of enhancement (washout) to 168 HU through 180 seconds

18F-FDG PET/CT, SUVmax=2.0.

18F-FDG PET/CT showed nodule with mildly increased radiopharmaceutical uptake with maximum standardized uptake value (SUVmax) of 2.0

(H) Gross photograph. (I) Photomicrograph, 200× magnification. (J) Photomicrograph, 100× magnification. (K) Immunohistochemistry staining, SMA, 200× magnification. (L) Immunohistochemistry staining, CD31, 200× magnification. (M) Immunohistochemistry staining, Ki-67, 200× magnification.

H. Gross photograph indicates soft and dark-reddish nodule with hemorrhage (arrows). I. Photomicrograph reveals highly vascular tumor with prominent freely anastomosing vascular channels, papillary growth, and endothelial tufting that was absent to minimal (x 200).J. Tumor’s peripheral vasoformative features (arrows) indicate anastomosing vascular channels lined by malignant endothelium (x 100). These marginal characteristics correspond to needle-like projections in periphery of nodule seen in CT image A. K-M. Immunohistochemistry staining shows tumor cells are diffusely positive for SMA (K), and CD31 (L), and weakly positive for Ki-67 (M) (x 200). SMA = smooth muscle actin

Primary pulmonary low-grade angiosarcoma

Angiosarcoma, primary site


An 81-year-old man presented to the ICU 10 days after a 4-week cruise in New Caledonia, Vanuatu, the Solomon Islands, and New Zealand. He was reported to have been in perfect health during the cruise. On examination, he was febrile (39.1°C) and comatose with a Glasgow Coma Scale score of 6. He exhibited hemiplegia of the left side, paresis of the right upper limb, normal tendon reflexes, and a Babinski sign on the left side. A transient rash was observed within 48 hours of admission. Cerebrospinal fluid analysis showed leukocyte count of 41/mm³ (98% polymorphonuclear leukocytes), protein level of 76 mg/dL, and CSF:blood glucose ratio of 0.75.

(A, B) MRI, fluid-attenuated inversion recovery (FLAIR) imaging, 3T MRI unit, subcortical white-matter of right frontal, right parietal, right temporo-occipital, and bilateral rolandic regions. (C) MRI, diffusion-weighted imaging (DWI), 3T MRI unit. (D) Computed tomographic angiogram, right callosomarginal artery, Discovery CT750 HD scanning system.

MRI with the use of fluid-attenuated inversion recovery (FLAIR) imaging revealed subcortical white-matter hyperintensities in the right frontal region, the right parietal region (Panel A), the right temporo-occipital region (Panel B), and bilateral rolandic regions (Panel A). The slight hyperintensity of the right rolandic fissure (Panel A, arrow) is suggestive of meningitis. The multiple punctuated hyperintensities on diffusion-weighted sequences are suggestive of ischemic foci (Panel C). The MRI with FLAIR imaging and diffusion-weighted sequences were performed with the use of a 3T MRI unit (Magnetom Verio, Siemens). The computed tomographic angiogram shows an irregular narrowing of the right callosomarginal artery (Panel D, arrows). Angiography was performed with the use of a Discovery CT750 HD scanning system (GE Medical Systems).

infection NOS

Certain infectious or parasitic diseases

meningoencephalitis NOS


A 14-year-old girl with no prior medical history presented to the emergency department with severe abdominal pain for 2 days, accompanied by non-bilious vomiting. Physical examination revealed pallor, diffuse abdominal tenderness with guarding, and sluggish bowel sounds but no rigidity. Her recent history included two episodes of multiple oral ulcers that had resolved spontaneously. Laboratory findings showed hemoglobin 88 g/L, total leucocyte count 3.6 × 10⁹/L, platelets 96 × 10⁹/L, and ESR 54 mm/h. Urinalysis was normal, and blood and urine cultures were sterile. Initial ANA testing by indirect immunofluorescence with HEp-2 cell substrate was negative. Subsequent repeat ANA testing at a different laboratory remained negative, but dsDNA and anti-Ro antibodies were strongly positive with low concentrations of C3 and C4. Echocardiography showed a mild pericardial effusion.

Abdominal radiograph.

Abdominal radiograph showed dilated small and large bowel loops with no signs of intestinal obstruction or pneumoperitoneum

Contrast-enhanced CT.

Contrast-enhanced CT showed oedematous and enhancing bowel loops with target sign and bilateral hydroureteronephrosis

ANA-negative systemic lupus erythematosus with lupus enteritis and lupus cystitis

Systemic lupus erythematosus

enteritis NOS

Cystitis


A previously healthy 10-year-old boy presented with left upper quadrant abdominal pain that worsened with deep breathing or lying down, accompanied by fever. He also complained of mild cough and whitish sputum. On physical examination, the child was irritable but there were no other remarkable findings. Laboratory data showed elevated C-reactive protein (8.65 mg/dL) without leukocytosis and other findings were unremarkable.

Left posterior sagittal chest ultrasonography with 3.5 MHz convex transducer.

Left posterior sagittal chest ultrasonography using convex, low-frequency (3.5 MHz) transducer shows lentiform heterogeneous solid mass with linear structures in left lower hemithorax. Adjacent consolidated lung and large amount of left pleural effusion containing low-level echoes were also identified.

Color Doppler ultrasonography of the left lower hemithorax, convex low-frequency (3.5 MHz) transducer.

B: Color Doppler ultrasonography of the left lower hemithorax, using a convex low-frequency (3.5 MHz) transducer, demonstrates minimal vascularity within the lentiform, heterogeneously echogenic solid mass that is sharply demarcated from the adjacent atelectatic lung and partly abutting the descending aorta, in a 10-year-old boy presenting with extralobar pulmonary sequestration with hemorrhagic infarction.

Axial T2-weighted MRI.

Axial T2-weighted image shows well-defined triangular solid mass lesion with left pleural effusion. Central branching cystic structure within mass corresponded to dilated bronchiole on histopathologic examination. Hemiazygos vein appears to be mildly dilated.

Axial T1-weighted MRI of the thoracic region.

Axial T1-weighted image reveals small artery arising from descending thoracic aorta and connecting to lesion.

(E) MRI of the left lower hemithorax, axial view, dynamic contrast-enhanced T1-weighted sequence, performed preoperatively after intravenous contrast administration.

E: Dynamic contrast-enhanced axial T1-weighted MRI of the left lower hemithorax performed preoperatively demonstrates irregular central enhancement with several foci of poor enhancement in the periphery of the lesion, indicating a well-defined solid mass in the left pleural space associated with pleural enhancement; the acquisition was performed after intravenous contrast administration in a 10-year-old boy with extralobar pulmonary sequestration and hemorrhagic infarction.

Extralobar pulmonary sequestration with hemorrhagic infarction

Extralobar sequestration of lung

Pulmonary haemorrhage

Symptoms, signs or clinical findings, not elsewhere classified


A 64-year-old woman presented with intermittent bilateral knee pain for several years. She described her pain as mild, diffuse, both improved and worsened with walking, and occasionally associated with a sensation of instability. She had no history of trauma, mechanical symptoms such as locking, interference with daily activities, or pain in other joints. Her past medical history included osteoarthritis of the knee and osteoporosis. Several years earlier she had received a corticosteroid injection in her left knee but had never undergone imaging of her knees. Physical examination showed bilateral genu valgum with bilateral diffuse tenderness to palpation along her joint lines and patellar facets. Bilateral patellar movement caused considerable crepitus and discomfort. She had a small joint effusion in her left knee but not on the right. She had decreased flexion of the knees- 110° on the left and 100° on the right. Her gait was mildly antalgic bilaterally.

Plain radiograph of bilateral knees, anteroposterior view.

Anterioposterior plain radiograph of bilateral knees showing multiple calcified bodies of various sizes distributed throughout the knee joint and severe bilateral tricompartmental knee osteoarthritis.

Lateral radiograph of bilateral knees.

Lateral radiograph of bilateral knees confirming the diagnosis of severe tricompartmental osteoarthritis and extensive synovial calcification.

Sunrise radiograph of bilateral knees.

Sunrise radiograph of bilateral knees confirming the diagnosis of severe tricompartmental osteoarthritis and extensive synovial calcification.

Secondary synovial osteochondromatosis of bilateral knees in the setting of severe osteoarthritis

Osteochondromatosis syndrome

osteoarthritis NOS


This case involves a 39-year-old man from the Dominican Republic who had been well until approximately 1 month before admission when a pruritic rash developed below the waist, most prominently on the left upper thigh. He had an 8-year history of recurrent pruritic rashes predominantly around the waist and axillae that were associated with transient eosinophilia. On presentation to the emergency department, he had severe headache rated 10/10 that was unlike any previous pain, with photophobia, nausea, agitation, restlessness, and tearfulness. Physical examination revealed dry mucous membranes, pupils 4 mm and reactive to light, neck stiffness with pain on flexion and rotation, bilateral strength 4/5, and unsteady gait requiring assistance to stand. He had previous medical history of melasma, acne, hidradenitis suppurativa, and partial small-bowel obstruction with Meckel's diverticulum resection 4 years earlier. He was born in the Dominican Republic, immigrated to the US over 15 years earlier, and had visited the Dominican Republic 2 months before symptoms. Nine days before admission, he had received prednisone for contact dermatitis thought to be caused by nickel allergy.

Laboratory results: blood white-cell count 17,400 per mm³ (86.9% neutrophils, 8.5% lymphocytes, 2.1% eosinophils); cerebrospinal fluid analysis (tube 1): white-cell count 13,800 per mm³ (90% neutrophils, 3% band forms, 4% lymphocytes, 3% monocytes), protein 195 mg/dl, glucose 46 mg/dl; blood glucose 121 mg/dl; lactic acid 3.8 mmol/liter; phosphorus 1.4 mg/dl; magnesium 1.5 mg/dl.

Laboratory results showed blood white-cell count 17,400 per mm³ with 86.9% neutrophils, 8.5% lymphocytes, 2.1% eosinophils. Cerebrospinal fluid analysis revealed markedly cloudy appearance, white-cell count 13,800 per mm³ (tube 1) with 90% neutrophils, 3% band forms, 4% lymphocytes, 3% monocytes, protein 195 mg/dl, glucose 46 mg/dl. Blood glucose was 121 mg/dl, lactic acid 3.8 mmol/liter, phosphorus 1.4 mg/dl, magnesium 1.5 mg/dl.

Fecal smear, unstained preparation, rhabditiform larva measuring approximately 180–380 μm × 14–20 μm.

Fecal smear showed Strong. stercoralis rhabditiform larva in unstained preparation, approximately 180 to 380 μm in length by 14 to 20 μm in width, with short pointed tail, bulbous esophagus, conspicuous genital primordium, and short buccal canal.

(A) Biopsy specimen from cecal polyp, H&E staining. (B) Biopsy specimen from cecal polyp, H&E staining. (C) Biopsy specimen from cecal polyp, H&E staining, higher magnification. (D) Biopsy specimen from cecal polyp, H&E staining, higher magnification.

Biopsy Specimen from a Cecal Polyp (Hematoxylin and Eosin). Panel A shows polypoid colonic mucosa with expansion of the lamina propria by an inflammatory infiltrate composed of histiocytes, lymphocytes, and eosinophils. Panel B shows two profiles of nematode larvae (circles). At higher magnification, Panel C shows a cross section of the larvae and Panel D shows a longitudinal section of the larvae.

(A) Small intestine biopsy specimen, H&E staining. (B, C, D) Small intestine biopsy specimen, H&E staining.

Biopsy Specimen from a Meckel’s Diverticulum (Hematoxylin and Eosin). A specimen from a Meckel’s diverticulum resected 4 years earlier was reviewed for the presence of strongyloides larvae. The current examination of a segment of small intestine (Panel A) revealed very few ova and developing and late-stage Strong. stercoralis larvae (Panels B, C, and D, arrows).

Streptococcus bovis-associated meningitis and the Strongyloides stercoralis hyperinfection syndrome

Meningitis due to Streptococcus

Gastric strongyloides stercoralis


43-year-old woman presented with multiple lung and brain metastases.

Lung biopsy specimen, H&E staining, scale bar 100 μm.

A: Hematoxylin-eosin staining of a thoracoscopic lung biopsy specimen of the primary tumor obtained at diagnosis demonstrates an adenocarcinoma histology, with the sample originating from the lung and shown at a scale bar of 100 μm.

CT of the chest, contrast-enhanced, pre-treatment.

Pre-treatment contrast-enhanced CT of chest showing primary tumor

ALK rearrangement–positive lung adenocarcinoma with multiple lung and brain metastases (confirmed by FISH analysis showing ALK gene rearrangement)

lung adenocarcinoma

metastasis in lung

brain metastases


A 69-year-old retired nuclear engineer presented with fatigue and an unintentional weight loss of 14 kg over the preceding year. His medical history included hypertension, hyperlipidemia, gastroesophageal reflux, and adult-onset diabetes mellitus. His medications included atorvastatin, glipizide, omeprazole, lisinopril, hydrochlorothiazide, and amlodipine. He had a history of heavy tobacco use but had quit smoking 30 years earlier. His hobbies included dancing with his wife. Review of systems was negative for fevers, nausea, orthopnea, edema, or paroxysms of nocturnal dyspnea. Physical examination revealed a systolic murmur, elevated jugular venous pulse to 12 cm of water above the right atrium without Kussmaul's sign, no pulsus paradoxus, no pericardial friction rub but a soft early-peaking systolic murmur at the right upper sternal border, mild crackles at both lung bases, soft nontender abdomen without hepatosplenomegaly, no cervical/inguinal/axillary lymphadenopathy, normal neurological examination with 5/5 muscle strength and 2+ reflexes throughout, and no joint swelling or rash. Vital signs on admission showed afebrile temperature, heart rate 72 bpm, blood pressure 165/64 mmHg, respiratory rate 16, and oxygen saturation 96% on ambient air. During his second hospitalization 3 months later, he had developed cognitive impairment with difficulty maintaining conversation, word-finding problems, completing only two iterations of serial 7 subtractions, and naming only 6 animals in 1 minute on category-fluency testing.

CT of the abdomen.

CT scan of the abdomen showed perirenal inflammation manifested as soft-tissue stranding surrounding both kidneys and the infrarenal aorta, sparing the posterior aortic wall and inferior vena cava, with masslike heterogeneous thickening of the renal cortexes bilaterally and multiple soft-tissue nodules in the omentum suggestive of carcinomatosis.

MRI of the brain, T2-weighted sequence.

T2-weighted MRI of the brain revealed bilateral retro-orbital masses.

Cardiac MRI.

Cardiac MRI showed pericardial effusion and enhancing masslike involvement of the entire right atrial wall and right atrioventricular groove.

Technetium-99 whole-body bone scan.

Technetium-99 whole-body bone scan revealed increased metadiaphyseal uptake at both knees, distal tibias, and distal radii.

(A) Tibial biopsy, H&E staining. (B) Tibial biopsy, CD68 immunohistochemistry.

Tibial biopsy specimen showed sclerotic bony trabeculae with CD68+ foamy histiocytes infiltrating the bone marrow cavities, with hematoxylin and eosin staining in Panel A and CD68 staining in Panel B.

Erdheim-Chester disease