A 7-month-old female infant presented with a 2-month history of brown macules on the back and thighs, without prodromal erythema or trauma. Her birth history was unremarkable, and her growth and development were normal. Family history was unremarkable. Physical examination revealed 7 sharply marginated, irregularly shaped, polymorphic hyperpigmented macules of 10 to 15 mm in diameter, without scales, on the back and thighs. The hyperpigmented macules were of orange hue, with unevenness of the pigmentation. Vital signs were normal. There was no lymphadenopathy or hepatosplenomegaly. Laboratory test results, including complete blood cell count, liver function tests, and renal function, were normal.

Clinical photograph of the upper back and right lumbar area, performed at initial presentation.

Figure 1 is a clinical photograph depicting the upper back and right lumbar area of a 7-month-old female infant, demonstrating sharply marginated, irregularly shaped, polymorphic hyperpigmented macules measuring 10 to 15 mm in diameter, with an orange hue and uneven pigmentation, and lacking scales; the lesions were present at the time of initial presentation and physical examination.

Clinical photograph of the right lumbar skin.

Figure 2 is a clinical photograph demonstrating a positive Darier sign on the right lumbar brown macule; the image captures the skin site after it has been stroked, showing localized erythema and urticarial response consistent with mast cell degranulation, as described in the patient outcome section of the case report.

Maculopapular cutaneous mastocytosis (polymorphic variant)

Maculopapular cutaneous mastocytosis


20-year-old male with 5-year history of multiple brownish-yellow xanthoma-like papules and nodules affecting face, flexures of trunk, and limbs. No systemic symptoms. Lesions initially appeared as discrete/grouped papules, coalescing into plaques and nodules over 2 years. Lesions were painless and asymptomatic. No family history of cutaneous disorders. Physical exam showed numerous papules and nodules on eyelids, cheeks, oral commissure, neck, cubital fossae, palms, abdomen, flank, and popliteal fossa. Lesions were discrete and confluent, shiny, ranging from skin-colored to yellow and brown. Linear arrangement noted on oral commissure and abdomen, suggesting koebnerisation. Laboratory blood tests showed normal lipid levels.

(A,B) Clinical photographs of the axillae.

A: Clinical photographs demonstrate hundreds of red to brown papules and nodules distributed symmetrically in the axillae. B: Clinical photographs demonstrate hundreds of red to brown papules and nodules distributed symmetrically in the axillae.

Histopathological examination of right axilla lesion, H&E staining.

Histopathological examination of right axilla lesion showed dense, granulomatous dermal infiltrate in upper dermis consisting of histiocytes, lymphocytes, and multinucleated giant cells (H&E stain)

Xanthoma disseminatum


50-year-old woman with advanced high-grade serous ovarian cancer presented with large and painful supraclavicular erosions. Erosions appeared 4 weeks after localized palliative radiotherapy on a supraclavicular metastatic lymphadenopathy. Subsequently developed oral mucosa erosions and widespread cutaneous lesions. Clinical examination showed: polymorphic skin lesions with substantial skin confluent erosions over irradiated area, atypical targets mimicking erythema multiforme on forearms. Involvement of oral, nasal, genital, and anal mucous membranes. Histological examination showed suprabasal acantholysis, intra-epithelial blisters, eosinophilic spongiosis, and dermal inflammatory infiltrate. Indirect immunofluorescence showed antibodies against intercellular substance (titre 1:1280). ELISA tests positive for anti-desmoglein 1 and 3 antibodies. Immunoblot analysis showed presence of anti-desmoplakin I and II antibodies.

Clinical photograph of the body at the time of dermatological examination.

A: Clinical photograph showing disseminated bullae on variably inflamed skin, evolving into erosions, located on the patient's body at the time of dermatological examination.

Direct immunofluorescence analysis of skin showing immunoglobulin G deposits on keratinocyte cell surfaces and linear C3 deposits at the dermal-epidermal junction.

Direct immunofluorescence analysis showing immunoglobulin G deposits on epithelial cell surface of keratinocytes (in fishnet pattern) and linear C3 deposits on dermal-epidermal junction

Paraneoplastic pemphigus


A 54-year-old man with a history of polysubstance abuse presented with altered mental status. His past medical history was notable for treatment-naïve hepatitis C infection. Family history was notable for a sister who was diagnosed with renal failure of obscure etiology requiring dialysis at the age of 45 years. On examination, the patient was found to be afebrile, drowsy and hypertensive (172/110 mmHg). Jugular veins were distended and there were crackles at the lung bases. Blood tests revealed creatinine 16.0 mg/dL, blood urea nitrogen 99 mg/dL, hemoglobin 11.3 g/dL, platelets 222,000/mm³, LDH 907 (84-246 IU/L) and haptoglobin 171 (30-200 mg/dL). Urinalysis showed proteinuria. A blood film revealed rare schistocytes. Random urine protein-to-creatinine ratio was 1.9. Urine toxicology revealed cocaine and its metabolites. Routine blood and urine cultures showed no growth. Serologic tests showed reduced complement C3 level of 71 (90-180 mg/dL) and normal C4 level of 32 (10-40 mg/dL). C3 hypocomplementemia persisted throughout hospitalization. There were no antibodies against HIV 1/2. Ultrasonography showed echogenic kidneys measuring 9.8 cm (right) and 10.3 cm (left).

(A) Kidney artery, H&E staining. (B) Kidney artery, Verhoeff’s Van Gieson elastin staining. (C) Arteriole, periodic acid–Schiff staining.

Vascular histopathology. (A) An artery in the kidney showing luminal occlusion secondary to edematous intimal expansion (arrow) (hematoxylin and eosin stain). (B) Same artery as (A), demonstrating the absence of elastic fibers in the expanded intima (arrow) (Verhoeff’s Van Gieson elastin stain). (C) An arteriole demonstrating onion skin-like smooth muscle cell hyperplasia (hyperplastic arteriolopathy) (arrow) (periodic acid–Schiff stain).

Thrombotic microangiopathy, not elsewhere classified

Diseases of the musculoskeletal system or connective tissue

Cardiovascular and respiratory disorders


A 67-year-old woman presented with leg pain. Seven weeks prior, she developed cramping sensations in thighs and calves after walking a couple blocks, relieved by rest. Symptoms progressed to cramping after walking less than one block. Medical history included rheumatoid arthritis (in remission for >20 years), mild aortic insufficiency from thickened valve leaflets, intermittent palpitations from premature atrial contractions, and generalized anxiety disorder. She never smoked. Family history included coronary artery disease in both parents diagnosed after age 70. Physical exam showed: temperature 37.0°C, heart rate 79, blood pressure 138/90 right arm and 140/84 left arm, respiratory rate 12, oxygen saturation 100%. Clear lungs, grade 2/4 diastolic murmur at right upper sternal border, bilateral bruits over carotid/oral arteries, diminished pulses in legs (popliteal, dorsalis pedis, and posterior tibialis 1/3). Initial lab results showed normal basic metabolic panel, liver function tests, and complete blood count. HbA1c was 5.6%, LDL 95 mg/dL, HDL 83 mg/dL, triglycerides 110 mg/dL. Ankle-brachial index was 0.8 bilaterally.

(A–C) Color Doppler ultrasonography of the arterial wall.

Panels A, B, and C show edema of the vasculitic wall with a “halo” sign (blue arrows), a finding of a dark halo around the arterial lumen on color Doppler ultrasonography.

(A) Temporal artery biopsy, H&E staining. (B) Temporal artery biopsy, H&E staining.

Figure 2 consists of histopathological images of temporal artery biopsy specimens, with Hematoxylin and Eosin (H&E) staining. Panel A demonstrates a normal segment of the temporal artery showing a "skip" lesion—an area of normal tissue frequently observed between inflamed segments in giant-cell arteritis. Panel B displays pathologic features including disruption of the internal elastic lamina, thinning of the media, and scarring of the intima, corresponding to histologic evidence of giant-cell arteritis.

Giant-cell arteritis (large-vessel variant)

Giant cell arteritis


A 44-year-old woman with cerebral palsy and multiple sclerosis (diagnosed at age 16) presented to the emergency department with four days of acute constipation and vomiting. She had a history of chronic constipation due to neurogenic bowel dysfunction secondary to her underlying conditions, initially managed with laxatives. Her constipation had become severe enough to warrant insertion of a sacral anterior root stimulator in the last year. On examination, her abdomen was markedly distended, diffusely tender, with absent bowel sounds. There was no guarding, rigidity, or previous incisions, and all hernia orifices were intact. Vital signs showed tachycardia (140 beats/min), tachypnea, normal blood pressure (130/60 mmHg), and oxygen saturation of 98% on room air. Laboratory findings revealed normal pH of 7.36, hypocapnea (PCO2 29mmHg), hyperlactataemia (20 mg/dL), normal PO2 (), white blood cell count of 10,500 cells/mm3 (73% neutrophils), and elevated C-reactive protein of 3.25 mg/dL.

Abdominal radiograph, anteroposterior view.

Plain abdominal radiograph (anteroposterior view) showing hugely distended colon with classic 'coffee-bean' sign

Plain abdominal radiograph, lateral decubitus view.

Plain abdominal radiograph (lateral decubitus view) showing grossly distended colon with air-fluid levels

CT scan of the colon and liver regions.

CT scan showing complex colonic volvulus with hugely distended bowel, small amount of free fluid around the liver, and severe fecal impaction in sigmoid colon

CT of the colon, axial view.

Axial CT showing pneumatosis within the colonic wall and air-fluid levels, indicating bowel obstruction

Sigmoid volvulus

gangrenous enteritis[Large bowel, NOS]

Certain infectious or parasitic diseases


A 20-year-old man presented to the emergency department with palpitations lasting half an hour, accompanied by dizziness and near-fainting symptoms. He denied chest pain and had no known cardiac history. Physical examination revealed low blood pressure of 70/50 mm Hg and oxygen saturation of 91% on room air. No murmur was detected on chest auscultation.

ECG on presentation, ventricular rate 212 beats/min.

ECG on presentation showed irregular wide complex tachycardia at an average ventricular rate of 212 beats/min with beat-to-beat variation in QRS morphology

Resting 12-lead electrocardiogram performed during emergency department evaluation.

Figure 2 is a resting electrocardiogram (ECG) demonstrating pre-excitation, as shown on page 1 of the document. The image depicts a 12-lead ECG acquired during the patient's evaluation in the emergency department, revealing features consistent with pre-excited atrial fibrillation, including irregular wide complex tachycardia and beat-to-beat variation in QRS morphology, which is attributed to antegrade conduction through an accessory pathway.

Atrial fibrillation with very fast ventricular response as a result of antegrade conduction through an accessory pathway (pre-excited atrial fibrillation)

Atrial fibrillation

Preexcited atrial fibrillation

Accessory pathway


24-year-old man presented with a 2-day history of swelling on the left side of neck and fever. Past medical history included two similar neck abscesses 2 years and 6 years ago, which were treated with antibiotics and drainage. Physical examination showed a 2 cm diameter swelling at the level of thyroid cartilage.

Clinical photograph of the left side of the neck at the level of the thyroid cartilage, taken on admission.

A: Clinical photograph demonstrating a 2-cm swelling at the level of the thyroid cartilage on the left side of the neck, representing a neck abscess present on admission.

Barium esophagography and CT of the neck.

Barium esophagography and CT revealed a sinus tract extending from the region of the superior pole of the left thyroid lobe to the neck abscess

Branchial-cleft sinus presenting as recurrent neck abscess

first branchial cleft fistula

abscess NOS


A 58-year-old overweight African American male presented with a 5-year history of a slightly pruritic and painful rash that worsened during summers, and blisters sometimes developed. Emollients were unhelpful. The patient was otherwise healthy, performed indoor manual labor as a maintenance engineer, and had no significant sun exposure. His sister had diabetes mellitus and a similar rash in her axillae. Physical examination revealed irregularly thickened skin containing hyperpigmentation, hypopigmentation, multiple acrochordons (skin tags), malodorous crust, and areas of maceration and erosion. Further examination showed pseudofolliculitis barbae in the submental and mandibular regions bilaterally. The nails, oral cavity, and mucosal membranes appeared normal.

(A) Clinical photograph of right axilla, global view. (B) Clinical photograph of right lateral neck, global view. (C) Clinical photograph of right axilla, close-up view. (D) Clinical photograph of right lateral neck, close-up view.

Shows rash of right axilla and right lateral area of neck with global and close-up views

Biopsy, H&E staining.

Biopsy showing epidermal acantholysis causing separation of keratinocytes into dilapidated brick wall appearance (hematoxylin-eosin staining)

Hailey-Hailey disease (benign familial pemphigus)

Hailey-Hailey disease

Benign familial pemphigus


21-year-old woman with history of cardiac transplant in 2007 for right ventricular failure following Mustard surgery for transposition of great arteries. Last follow-up (Nov 2016) showed normal biventricular function. Prior to current presentation, patient had an angry debate. Presenting with reduced tolerance to activity and fatigue. Physical exam showed borderline tachycardia (HR 100 bpm), oxygen saturation 98%, blood pressure 130/87 mmHg.

Electrocardiogram, 12-lead tracing, performed at the time of admission.

Figure 1 presents an electrocardiogram tracing performed at the time of admission, depicting a 12-lead ECG from the patient in the acute phase; the assessment reveals a right bundle branch block, which was present previously, with new negative T waves in all precordial leads, consistent with the initial clinical findings in this episode of takotsubo cardiomyopathy.

Echocardiography of the left ventricle, ejection fraction=34%.

Echocardiography revealed dilated left ventricle with severely depressed ejection fraction (34%), akinetic mid-to-apical segments and normally contracting basal segments

Coronary angiography of the epicardial coronary arteries performed during acute hospital admission.

Figure 3 presents coronary angiography images demonstrating the absence of coronary artery obstruction in the examined patient during the acute episode. The modality is coronary angiography, focused on the epicardial coronary arteries, acquired during the acute hospital admission for suspected ischemic cardiomyopathy in a young heart transplant recipient, with the key finding being negative angiographic evidence for coronary obstruction.

Takotsubo cardiomyopathy in transplanted heart

Takotsubo cardiomyopathy

heart transplant status

Factors influencing health status or contact with health services


A 32-year-old woman presented with severe headache and loss of peripheral vision. Four weeks prior, she underwent elective pregnancy termination with methotrexate after an intrauterine device failure. Three weeks later, she developed left upper quadrant pain, vaginal bleeding, and headache. She had a history of chronic back pain from vertebral disk herniation requiring spinal fusion surgery 4 years prior, and two episodes of self-limited thrombocytopenia associated with methotrexate treatment for an unknown skin disorder. Physical examination revealed temperature 38.3°C, blood pressure 126/72 mmHg, pulse 54/min, respiratory rate 20/min, and oxygen saturation 96% on room air. She had left homonymous hemianopia but otherwise normal cranial nerve function. Strength, sensation, and reflexes were normal.

Laboratory results. Peripheral blood smear, high-power field.

Laboratory results showed: hematocrit 27.5%, hemoglobin 9.0 g/dL, platelets 80,000/mm3, elevated d-dimer 9377 ng/mL, undetectable haptoglobin <6 mg/dL, elevated LDH 487 U/L, and elevated alkaline phosphatase 165 U/L. Peripheral blood smear showed 0-2 schistocytes per high-power field, teardrop and pencil cells.

CT of the abdomen, splenic size 15.6 cm.

CT scan of abdomen showed splenomegaly (15.6 cm) and central filling defect in splenic vein compatible with acute splenic-vein thrombosis

(A) CT of the head, pre-contrast. (B) CT venogram of the head, frontal projection, post-contrast. (C) MRI of the head, fluid-attenuated inversion recovery sequence. (D) MRI of the head, diffusion-weighted imaging. (E) MRI of the head, gradient-echo sequence. (F) Transfemoral cerebral angiogram, lateral projection, venous phase, post-contrast in the right internal carotid artery.

Imaging Studies of the Head. A CT scan of the head (Panel A), obtained before the administration of contrast material, shows an area of hypodensity and sulcal effacement involving the right parietal lobe that extends into the right aspect of the splenium of the corpus callosum, a finding suggestive of edema and a recent infarct. Also shown are small, focal areas of hyperdensity, findings consistent with hemorrhagic conversion. A CT venogram (Panel B), obtained in frontal projection after the administration of contrast material, shows no evidence of filling in at least one right cortical vein that drains into the superior sagittal sinus. MRI of the head was performed, and fluid-attenuated inversion recovery, diffusion-weighted, and gradient-echo images (Panels C, D, and E, respectively) show evidence of edema, ischemia, and hemorrhage involving the right parietal lobe. A transfemoral cerebral angiogram (Panel F), obtained in lateral projection during the venous phase after the administration of contrast material in the right internal carotid artery, shows multiple filling defects in cerebral veins (arrows), findings that indicate thrombosis of the right frontal and parietal cortical veins, with no involvement of the major dural sinuses.

(A) Peripheral-blood flow cytometry, CD59 expression in glycophorin A+ erythrocytes, approximately 1% partial CD59 deficiency, approximately 5% complete CD59 deficiency. (B) Peripheral-blood flow cytometry, CD24 expression and FLAER staining in CD15+ neutrophils, 57% with loss of CD24 expression and no FLAER staining. (C) Peripheral-blood flow cytometry, CD14 expression and FLAER staining in CD64+ monocytes, 60% with loss of CD14 expression and no FLAER staining.

Results of Peripheral-Blood Flow Cytometry. Panel A shows the level of CD59 expression in glycophorin A+ erythrocytes; approximately 1% of the glycophorin A+ erythrocytes show a partial CD59 deficiency (these are known as type II cells), and approximately 5% show a complete CD59 deficiency (type III cells). Panel B shows the level of CD24 expression and fluorescein-labeled proaerolysin (FLAER) staining in CD15+ neutrophils, which have a high level of side scatter of light (SSC, a marker of cytoplasmic complexity and granulation) (top graph); approximately 57% of the CD15+ neutrophils show loss of CD24 expression and no FLAER staining, a finding consistent with a paroxysmal nocturnal hemoglobinuria (PNH) clone (bottom graph). Panel C shows the level of CD14 expression and FLAER staining in CD64+ monocytes, which have a low level of SSC (top graph); approximately 60% of the CD64+ monocytes show loss of CD14 expression and no FLAER staining, a finding consistent with a PNH clone (bottom graph).

Paroxysmal nocturnal haemoglobinuria

Diseases of the blood or blood-forming organs


A 41-year-old woman presented with chest pain. One year prior, she had experienced transient left-sided chest and shoulder tightness. Five days before presentation, she developed acute substernal chest pain radiating to jaw and shoulders with dyspnea while packing for a flight. The pain lasted 1 hour and resolved spontaneously. The day before presentation, similar pain recurred after walkingd with light-headedness and dyspnea. Medical history included laparoscopy for ovarian cyst and miscarriage 1 month prior. She exercised regularly, did not smoke, and consumed two alcoholic drinks weekly. Family history included hypermobile Ehlers-Danlos syndrome in mother, brother, and sister, and a maternal second cousin died from cerebral aneurysm at age 51. On examination, she was diaphoretic with temperature 36.6°C, heart rate 68, BP 143/87 mmHg bilaterally, respiratory rate 18, and oxygen saturation 100ensible digits but no cardiac murmurs, rubs, or gallops.

Laboratory results for troponin T at initial presentation and after 8 hours; hemoglobin, blood counts, electrolytes, renal function, glucose, and lipid panel.

Laboratory results showed initial troponin T of 0.03 ng/dl rising to 0.21 ng/dl after 8 hours. Other results within normal ranges included hemoglobin, blood counts, electrolytes, renal function, glucose, and lipid panel.

ECG.

ECG showed normal sinus rhythm and submillimeter down-sloping ST-segment depressions in leads V3, V4, and V5.

(A) Coronary angiogram of the left coronary artery, right anterior oblique caudal view. (B) Coronary angiogram of the left coronary artery, left anterior oblique caudal view.

Coronary Angiogram. An angiogram of the left coronary artery was obtained in the right anterior oblique caudal view (Panel A). Diffuse narrowing of the vessel lumen (arrow) and a filling defect (oval) are visible in the first obtuse marginal branch of the left circumflex coronary artery; these findings are consistent with an intimal tear and type 1 coronary-artery dissection. An angiogram of the left coronary artery was also obtained in the left anterior oblique caudal view (Panel B). Evidence of initiation of a coronary-artery dissection is visible in the first obtuse marginal branch, including narrowing of the vessel lumen (arrow) and staining of the vessel wall (circle); tortuosity of the coronary arteries is also shown.

(A) CT angiogram of the right kidney, oblique coronal reformatted multiplanar image, delayed phase. (B) CT angiogram of the left kidney, oblique coronal reformatted multiplanar image, delayed phase. (C) CT angiogram of the right renal artery, oblique coronal maximum-intensity-projection image, arterial phase. (D) CT angiogram of the left renal artery, oblique coronal maximum-intensity-projection image, arterial phase.

CT Angiogram. Oblique coronal reformatted multiplanar images showing the long axis of the right and left kidney (Panels A and B, respectively) were obtained during the delayed phase. Bilateral, wedge-shaped cortical defects are visible (arrows); these findings are consistent with small, remote infarctions. Oblique coronal maximum-intensity-projection images showing the right and left renal arteries (Panels C and D, respectively) were obtained during the arterial phase. Paired right and single left renal arteries have subtle luminal irregularities (arrowheads).

spontaneous coronary artery dissection


44-year-old male nurse who was working alone at a nursing post in Coral Bay, Australia (>1000 km from Perth, 150 km from nearest medical facility). Presented with severe chest pain and dizziness while on duty.

ECG.

First ECG showed complete heart block, right bundle-branch block, hyperacute T waves in the inferior leads, and reciprocal ST-segment depression in the anterolateral leads

Electrocardiogram performed 50 minutes later.

Second ECG (50 minutes later) showed sinus tachycardia with 2 mm of inferior ST-segment elevation and reciprocal ST-segment depression in the anterolateral leads

Inferior ST-segment elevation myocardial infarction (STEMI)

Acute ST segment elevation myocardial infarction[inferior wall NOS]


A 44-year-old woman presented to her optometrist with a 10-week history of progressive blurred vision. She had no headaches or nausea. On examination, funduscopy showed bilateral papilloedema.

MRI of the brain, sagittal view, T1-weighted sequence post gadolinium.

Sagittal T1 volume post gadolinium MRI shows a large, avidly enhancing, left frontal convexity extra axial mass with a broad dural base and bony hyperostosis. Mass effect with sulcal effacement and compression of left frontal lobe and distortion of the anterior body and genu of the corpus callosum is noted.

MRI, axial view, T1-weighted sequence with gadolinium.

Axial T1 volume post gadolinium MRI reconstruction shows the mass

Coronal T1-weighted MRI with gadolinium contrast.

Coronal T1 volume post gadolinium MRI reconstruction shows the mass

Meningioma - WHO grade I lesion infiltrating the dura but not the brain

Meningiomas


A previously healthy 44-year-old Chinese woman presented with a seven-week history of progressively worsening nausea and vomiting associated with 13 kg weight loss. She denied abdominal pain, distension, or diarrhea. Her symptoms had been initially treated as a functional gastrointestinal disorder with antidepressants (flupentixol, melitracen tablets, and olanzapine), prokinetics (domperidone), and anti-emetics (domperidone and ondansetron) for three weeks without response. Eight days after admission, she developed metabolic alkalosis, acute respiratory failure, and neurological deficits. On examination, she had paralysis of the right limbs, horizontal nystagmus, loss of pharyngeal reflex, loss of tendon reflex on the right side, and positive Babinski sign bilaterally. Laboratory studies showed normal liver, kidney, and thyroid function, normal basic autoimmune antibodies, normal fasting blood glucose and glycated hemoglobin. Serum AQP4-IgG antibodies were negative, but cerebrospinal fluid was positive for AQP4-IgG. Previous gastroscopy and abdominal CT scan showed no abnormalities.

MRI of the head, sagittal view, performed three weeks after the first episode.

Initial sagittal MRI of the head taken three weeks after first episode showed a very small hyperintense lesion in the medulla oblongata, which was initially considered normal

Sagittal T2-weighted MRI of the head and cervical spinal cord performed two months later.

Follow-up sagittal T2-weighted MRI of the head two months later showed progression of the lesion to an extensive longitudinal hyperintense lesion involving the medulla oblongata and spinal cord at C1-C2

Neuromyelitis optica spectrum disorder


A 28-year-old healthy woman presented with a 2-week history of dyspnea, cough, wheezing, and lithoptysis (expectoration of calcific material). She had no significant past medical history and did not smoke, drink alcohol, or use illicit drugs. The patient was living in New England but had previously lived in Nebraska, Colorado, Mississippi, and Florida. Recent travel included visits to Uganda, Afghanistan, Albania, and Croatia, with frequent hiking and camping trips. Physical examination findings are not specifically detailed in the case report. A chest radiograph was unremarkable.

(A) Chest computed tomography (CT). (B) Three-dimensional reconstruction of chest CT (Slicer version 4.6.2).

Left, Chest computed tomography (CT) scan. Right, Three-dimensional reconstruction of the chest CT (Slicer version 4.6.2, Brigham and Women’s Hospital).

Broncholithiasis


38-year-old male motorcyclist presented to emergency department after colliding with a car at high speed. Landed on outstretched right hand. Presented with painful, swollen right wrist. Motor and sensory neurological function of right radial, ulnar, and median nerves was intact. Radial pulse was palpable.

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

Anteroposterior and lateral radiographs of the wrist showing volar dislocation of the lunate. Break in Gilula's arcs visible on anteroposterior view, indicating bony or ligamentous injury.

dislocation NOS

Injury, poisoning or certain other consequences of external causes

Orthopedic and connective tissue disorders


A 39-year-old male with no prior history of heart disease presented with symptoms of palpitations and weakness lasting for several hours. He had no family history of sudden cardiac death or arrhythmias. Initial ECG showed a wide complex tachycardia with left bundle branch block morphology, consistent with sustained ventricular tachycardia of right ventricular origin. The patient was experiencing hemodynamic instability.

ECG performed post-cardioversion; QRS complex duration 112 ms; S-waves upstroke 55 ms; leads V1–V3.

Post-cardioversion ECG demonstrated inverted T-waves in leads V1-V3, with QRS complex duration of 112 ms, and prolonged S-waves upstroke of 55 ms

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

arrhythmogenic right ventricular cardiomyopathy


A 74-year-old woman presented with general edema and macrohaematuria. Physical examination revealed mucocutaneous paleness, high arterial blood pressure (199/73 mmHg), and general edema. Laboratory findings showed acute renal failure (serum creatinine 1.8 mg/dL, urea 183 mg/dL), low total protein and albumin levels, and anemia. A monoclonal IgG-k was detected in the serum. The patient had nephrotic range proteinuria (5.26 g per 24h) with Bence Jones and hematuria (30-50 red blood cells per field). Bone marrow aspirate showed 9% plasma cells and cryoglobulins were negative. Complement studies showed normal immunoglobulin and C4 levels but reduced C3, suggesting complement alternative pathway activation. Factor H measurement revealed reduced levels, and anti-factor H autoantibodies were detected in the patient's serum.

Electron microscopy of the kidney.

Electron microscopy showed irregular and discontinuous thickening of glomerular basement membranes with electron-dense and homogeneous deposits. Fibrillar deposits of approximately 27 nm in diameter were found in the mesangium and capillary walls.

(B) Western blot following SDS–PAGE using IgG-depleted normal human serum in lanes 1 and 3 and purified factor H in lane 2; lanes 1 and 2 probed with patient-purified IgG, lane 3 probed with polyclonal anti–factor H antibody.

B: Figure 1 (B) presents a western blot in which SDS–PAGE was performed using IgG-depleted normal human serum (NHS) in lanes 1 and 3 and purified factor H in lane 2; after transfer, lanes 1 and 2 were probed with IgG purified from the patient, while lane 3 was probed with a polyclonal anti–factor H antibody that identifies factor H and some complement factor H–related proteins in NHS, with molecular weight markers and distinct protein bands identified on the blot.

ELISA assay.

ELISA assay showed anti-FH activity was associated mainly with monoclonal IgG-k

Dense Deposit Disease (DDD) with fibrillar glomerulonephritis and anti-factor H autoantibodies associated with monoclonal gammopathy

Glomerular disease with dense deposit disease

acute glomerulonephritis

autoimmune disease NOS

monoclonal gammopathy NOS


A 25-year-old man was referred to the oncology unit with a three-week history of a progressively enlarging neck lump and atypical lymphoid cells found on fine needle aspiration cytology. He reported mild exertional dyspnea and drenching night sweats, but denied weight loss, occupational exposure to harmful substances, recent travel, or high-risk sexual behavior. He had a smoking history since age 16. On physical examination, a palpable right supraclavicular lymph node measuring 3 cm in diameter was found. Chest radiography revealed a widened mediastinum but no lung lesions. Core biopsy of the lymph node showed partial effacement of nodal architecture by scattered large cells in a background of reactive lymphocytes, eosinophils, and plasma cells with some collagen fibrosis. These large cells stained positive for CD15 and CD30 and negative for CD45.

CT of the thorax, axial view, contrast enhanced.

Axial contrast enhanced computed tomography of the thorax showing an anterior mediastinal mass, with a central hypodense area suggestive of necrosis.

Classical Hodgkin lymphoma


A 69-year-old man presented after slipping in the snow with swelling and pain in the left knee. On physical examination, he was unable to extend his knee and had a palpable, visible indentation on the surface of his distal anterior thigh, above the patella. The injury was not open and he did not have substantial tension in the overlying skin. There was no neurovascular deficit.

Lateral radiograph of the left knee.

Lateral radiograph of the left knee shows the left patella has dislocated around its horizontal axis with its articular surface facing inferiorly, and the upper pole of the patella is engaged in the intercondylar groove of the femur.

Sagittal MRI of the left knee.

Figure 3 is a sagittal magnetic resonance image of the left knee demonstrating an intra-articular dislocation of the patella (indicated by a blue arrow), a tear of the left quadriceps tendon (white arrow), and an intact patellar tendon (red arrow).

Intra-articular patella dislocation with quadriceps tendon rupture

Dislocation of patella

Rupture of quadriceps muscle or tendon


A 58-year-old man presented with a six-week history of muscle weakness, dysphagia, and a symmetrical widespread rash on the face, torso, and limbs. Laboratory testing revealed elevated creatine kinase of 7070 u/L (reference range 30-175). An oesophagogastroduodenoscopy was performed and showed abnormal findings, and a PET CT scan was arranged.

Clinical photograph of the dorsum of the right hand at presentation.

Figure 1 depicts a clinical photograph of the dorsum of the patient’s right hand, showing symmetrical erythematous papules and a rash consistent with Gottron's papules, which are characteristic cutaneous manifestations of dermatomyositis; the image demonstrates the anatomical site as the hand, but no specific technical modality or timing is described beyond this being on presentation.

PET CT of the mid esophagus.

PET CT image shows high uptake of fluorodeoxyglucose in the mid esophagus

Acute dermatomyositis with oesophageal cancer

acute myocarditis NOS[Dermatomyositis, unspecified]

Malignant neoplasms of oesophagus


60-year-old Japanese woman presented with a black nodule on the right postauricular area. Initial staging after radical resection and sentinel node biopsy was pT3aN0M0 stage IIA. At 19 months post-surgery, imaging detected right jugular lymph node and lung metastases. Seven courses of pembrolizumab treatment later, evaluation showed further lung metastasis and new liver metastasis. Tumor harbored BRAF V600E mutation. Thirteen days after starting dabrafenib/trametinib, patient developed fever and hepatosplenomegaly. Laboratory findings showed pancytopenia, hyperferritinemia, increased liver enzyme levels, and coagulation abnormalities.

Clinical photograph of the arm taken during an acute febrile episode.

A: Target-like (erythema multiforme-like) skin lesions are present on the patient’s arm, documented with a clinical photograph during the acute febrile episode following dabrafenib and trametinib therapy after anti-PD-1 treatment.

Skin biopsy.

Skin biopsy showed vacuolization of basal cell layer and lymphocytic infiltration into dermoepidermal junction, consistent with erythema multiforme

Bone marrow smear.

Bone marrow smear showed erythrocytes, myelocytes, and platelets being phagocytosed by macrophages, without evidence of hematologic malignancies

Hemophagocytic lymphohistiocytosis (HLH) during dabrafenib and trametinib combination therapy following pembrolizumab administration for advanced melanoma

haemophagocytic lymphohistiocytosis NOS

melanoma NOS[Locally advanced]


51-year-old woman with history of rheumatic heart disease (diagnosed 10 years ago). Presented with recent onset reduced level of consciousness and right-sided weakness. Neurological exam showed right-sided hemiplegia. Cardiovascular exam revealed atrial fibrillation with ventricular rate of 110 beats/min and diastolic murmur heard at apex.

CT of the chest, non-contrast.

Non-contrast chest CT showed 6 cm diameter high attenuation circle in the left atrium

Transthoracic echocardiography of the heart, left atrium.

Transthoracic echocardiography revealed a mobile left atrial mass with concentric circles around periphery, severe mitral stenosis with dilated left atrium filled with dense spontaneous echo contrast, no left atrial appendage thrombus

Left atrial ball thrombus with severe mitral stenosis

coronary thrombus

mitral stenosis[Severe]


A 50-year-old postmenopausal woman (gravida 1, para 1) presented with abdominal distention, anorexia, and exertional dyspnoea. She had been in good health and was postmenopausal for 1 year. Physical examination revealed a markedly distended abdomen. CT of the abdomen and pelvis showed gross ascites extending under the diaphragm and a heterogeneous mass in the left adnexa, with part of the solid component having strong enhancement, plus small calcifications along the cystic wall. No lymphadenopathy or peritoneal dissemination was observed. Pelvic MRI showed the left pelvic mass with homogeneous low intensity on T1-weighted images and the solid parts including thick septa were uniformly low intensity on T2-weighted images and well enhanced on contrast-enhanced MRI, with no fatty components identified. Laboratory results showed serum CA 125 level of 1237 U/ml (normal <35 U/ml), while serum CEA, CA 19-9, and SCC levels were within normal ranges. Abdominal paracentesis performed multiple times showed benign mesothelial cells without malignant cells on cytological examination. ¹³¹I scintigraphy demonstrated strong uptake in the normal thyroid. The patient had no symptoms or clinical signs of thyroid hormone imbalance, with free-T3, free-T4, and thyroid stimulating hormone levels within normal ranges.

Transvaginal ultrasound of the pelvis.

Transvaginal ultrasound showing marked ascites and a large solid and cystic mass with a diameter of 8 cm in the left ovary

Chest X-ray.

Chest X-ray showing a massive right-sided pleural effusion

CT scan.

CT scans showing a solid component of the tumor with a higher attenuation lesion

T2-weighted MRI.

T2-weighted MRI showing the cystic lesions with various intensities separated by the septa

FDG PET/CT of the pelvis.

Pelvic FDG PET/CT shows lesions in the tumor without strong uptake of FDG

131I scintigraphy of the pelvic region.

¹³¹I scintigraphy shows strong uptake in the pelvic mass

Struma ovarii with pseudo-Meigs' syndrome

Struma ovarii

Endocrine, nutritional or metabolic diseases

Meige syndrome


A 40-year-old black woman presented with progressive edema of the legs, abdominal distention and pain. Her symptoms began 10 months prior with episodes of pain and swelling in feet and ankles, initially occurring in evenings after prolonged standing. The swelling progressed to involve lower legs and thighs. Five months before evaluation, she developed left back and flank pain. Her medical history included hypothyroidism, latent tuberculosis with previous negative chest radiograph, two spontaneous vaginal deliveries, ectopic pregnancy, hysterectomy for fibroid uterus, and appendectomy. Physical examination revealed temperature 36.8°C, pulse 76/min, blood pressure 131/70 mmHg, respiratory rate 20/min, oxygen saturation 97% on room air. Weight was 88.5 kg with BMI 29.7. She had 2+ edema of lower and upper legs, jugular venous pressure 8 cm water, distended and mildly tender abdomen with well-healed surgical scars.

Laboratory results. Urinalysis.

Laboratory findings showed hemoglobin 12.4 g/dL, WBC 5920/mm3, platelets 295,000/mm3, normal electrolytes, creatinine 0.95 mg/dL, markedly low albumin 1.4 g/dL, calcium 7.0 mg/dL. Urinalysis showed 3+ protein, 1+ blood, pH 5.0.

(A) CT of the abdomen and pelvis, coronal reconstruction. (B) CT of the abdomen and pelvis, coronal reconstruction, different plane. (C) CT of the abdomen and pelvis, axial view.

CT Scan of the Abdomen and Pelvis.  A coronal reconstruction image (Panel A) shows a filling defect in the right renal vein near the confluence with the inferior vena cava, a finding consistent with a nonocclusive thrombus (arrowhead), as well as mild perinephric fat stranding on the right side, a finding suggestive of edema (arrows). An image obtained on a different coronal plane (Panel B) shows wall thickening of the proximal small bowel and mild surrounding edema (arrowheads), as well as multiple enlarged mesenteric lymph nodes and mesenteric edema extending into the lower abdomen (arrows). An axial image (Panel C) shows findings consistent with small-volume ascites in the pelvis (arrowhead) and mild, symmetric soft-tissue edema bilaterally (arrows).

Glomerular disease associated with thin basement membrane nephropathy


A 31-year-old man with a background of sleep apnea was referred to the endocrine clinic for newly diagnosed hypertension. He had documented blood pressure readings of 170/128 mm Hg initially, with persistent hypertension on repeat measurements (164/110 mm Hg and 173/110 mm Hg). He complained of lethargy for the past six months and reported intermittent headaches. He was an ex-smoker with a 20 pack-year history. On examination, his heart rate was 106 beats per minute and body mass index was 34. There was no evidence of cushingoid features, hyperpigmentation, renal bruits, carotid bruits, or fine tremors. Apart from elevated blood pressure and raised BMI, physical examination was unremarkable. His full blood count, urea, and electrolyte levels were normal. Renal artery Doppler showed no evidence of renal artery stenosis.

Laboratory investigations including serum aldosterone, plasma direct renin concentration, aldosterone-to-renin ratio, 24-hour fractionated urinary metanephrine, 24-hour fractionated urinary normetanephrine, 24-hour urinary cortisol test, and low dose dexamethasone suppression test with adrenocorticotropic hormone.

Laboratory investigations showed serum aldosterone 278 pmol/L (reference range 30-400 pmol/L), plasma direct renin concentration 1.8 mu/L (reference range 2-29 mu/L), aldosterone-to-renin ratio 157 (reference <55), 24 hour fractionated urinary metanephrine 0.03 mmol/mol (reference <0.10 mmol/mol), 24 hour fractionated urinary normetanephrine 0.19 mmol/mol (reference <0.25 mmol/mol), 24 hour urinary cortisol test 227 nmol/24 hour (reference <150 nmol/24 hour), and low dose dexamethasone suppression test showing post-dexamethasone cortisol 30 nmol/L (reference <50 nmol/L) with adrenocorticotropic hormone <10 ng/L (reference 10-50 ng/L).

primary aldosteronism


An 18-year-old male college student from the United States presented with a 6-month history of fatigue, dry cough, dyspnea, and unintentional weight loss of 18 kg (from 100 to 82 kg). He had been previously healthy with no travel history outside the US. Four months prior, he was treated for presumed pneumonia with azithromycin without improvement. He did not smoke, drink alcohol, or use intravenous drugs and took no medications. On examination, his vital signs showed temperature 37°C, heart rate 110/min, blood pressure 123/72 mmHg, and respiratory rate 20/min. Physical examination revealed a palpable 2×2-cm firm, nontender, right supraclavicular lymph node and decreased breath sounds with dullness to percussion in the right lower lung field. No hepatosplenomegaly or leg edema was noted. Routine laboratory tests, including complete blood cell counts, renal function, electrolytes, and hepatic function, were within normal limits.

CT of the chest, abdomen, and pelvis.

Computed tomography scans of the chest, abdomen, and pelvis revealed a 15 × 11-cm centrally necrotic mass in the right anterior mediastinum displacing the trachea to the left, a large right pleural effusion, and compression of the superior vena cava

Lymph node biopsy, hematoxylin-eosin staining, 50× magnification. Immunostaining.

Lymph node biopsy sample showing binucleated Reed-Sternberg cells with prominent eosinophilic nucleolus, in a background of inflammatory cells (hematoxylin-eosin, ×50). Immunostaining confirmed the diagnosis

Hodgkin lymphoma


A 3-year-old boy presented with a 3-week history of painless nail alterations. The changes were first noticed by his mother and included nail discoloration and brittle nails with cracks. The child was otherwise healthy but had been diagnosed with hand, foot, and mouth disease five weeks before the nail presentations. No toenails were involved. All nail changes moved distally with nail growth.

Clinical photograph of the dorsal aspect of both hands.

Figure 1 is a clinical photograph showing the dorsal aspect of both hands of a 3-year-old boy, focusing on the thumbnails and fingernails. The image demonstrates proximal nail plate separation from the nail matrix on the right thumbnail and left index fingernail, a white transverse furrow in the right third fingernail, and a transverse, whitish, non-palpable, non-blanching line on the right fourth fingernail. This figure represents clinical documentation rather than imaging or laboratory analysis, illustrating nail changes consistent with onychomadesis, Beau’s line, and Mees’ line. The photograph was taken following a three-week history of painless nail alterations that appeared after a recent episode of hand, foot, and mouth disease.

Onychomadesis (complete nail plate separation), Beau's lines (white transverse depression), and Mees' lines (transverse leukonychia) secondary to hand, foot, and mouth disease

Onychomadesis

Beau lines

Harris lines

Hand, foot and mouth disease


A 12-year-old boy from Sri Lanka was admitted with fever (38-39°C) of 4 days' duration and bilateral cervical lymphadenopathy. He had a significant medical history of being diagnosed with Kikuchi-Fujimoto disease (KFD) five years earlier while living in Sri Lanka, where he presented with intermittent fever of 12 days' duration, mild cough, abdominal pain, and significant bilateral cervical lymphadenopathy. On examination, he was febrile with painful lymphadenopathy (3 cm in diameter) on the right side of the neck and normal physical development. Initial investigations revealed mild increase in CRP (1.79 mg/dL) and hepatic enzymes (AST 51 IU, ALT 81 IU). Viral markers showed past CMV infection while markers for EBV, Toxoplasma gondii, Adenovirus and Parvovirus were negative. Angiotensin-converting enzyme levels were normal. A tuberculin intradermal reaction was negative. Blood tests confirmed increased hepatic enzymes, and hepatitis B, C and HIV viral markers were negative. Hepatic autoantibodies and LKM were negative, ANA and ASMA were mildly positive (ANA 1:80 homogeneous pattern, ASMA 1:80 vascular pattern), anti ds-DNA and complement fractions (C3 and C4) were normal. Due to persistence of intermittent fever, lymphadenopathy and appearance of a diffuse erythematous and itchy rash on the trunk, arms, and legs, an excisional lymph node biopsy was performed. The cytometric investigation showed B lymphocytes with non-malignant features, with just a reduced CD4 to CD8 lymphocyte ratio.

Lymph node biopsy, laterocervical region, 20× magnification.

lymph node biopsy shows 3rd level laterocervical lesion with lymph node (1 cm in diameter) and tissue fragments (0.3 cm in largest). The lymph node shows only small subcapsular necrotic focus with karyorrhectic debris and several large immunoblastic cells at 20× magnification.

Tissue fragment, CD3 immunohistochemical staining.

tissue fragment shows plasmacytoid histiocytes and large immunoblastic cells in a necrotic and karyorrhectic background, devoid of granulocytes. CD3 immunohistochemical stain demonstrates that most of the large cells have a T-cell phenotype.

Recurrent Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis)

Kikuchi-Fujimoto disease

Histiocytic necrotising lymphadenitis of Kikuchi and Fujimoto


28-year-old male who suddenly went into coma for 9 hours preceded by tonic-clonic seizures lasting 10 minutes. No fever, vomiting or micturition. No focal neurological signs. Past medical history was unremarkable. Neurological examination revealed normal cranial nerves, normal power and reflexes. Routine laboratory tests were normal.

CT of the brain, left frontoparietal lobe, frontal horn of left ventricle.

Referral CT scans showed acute cerebral hemorrhage near the left frontoparietal lobe extending to frontal horn of left ventricle, with brain edema around hemorrhagic lesion and midline shift to the right

(A–C) Brain MRI performed 1 week later, left frontoparietal lobe, axial, coronal, and sagittal T1-weighted images. (D, E) Brain MRI, axial T2-weighted images. (F) Brain MRI, FLAIR sequence.

MRI done 1 week later revealed cerebral ring enhancing lesion (4.6×3.4×4.0 cm) at left frontoparietal lobe, appearing hypo-dense on T1 and hyper-dense on T2. FLAIR showed slightly mixed signals with no significant enhancement after contrast. Significant peripheral edema and swelling of adjacent brain tissue, with small blood clot at right side of falx. Left frontal horn compressed, right ventricle normal, slight midline shift to right. A-C) are axial, coronal and sagittal T1 image respectively. D,E) are axial T2 images while 2F is FLAIR.

CT-angiography of the intracranial arteries.

CT-angiography revealed stenosis of main intracranial arteries with no obvious signs of ectasia or vascular abnormalities

(A) Evacuated hematoma. (B) H&E staining, 400× magnification. (C) GFAP immunohistochemical staining, 400× magnification. (D) Oligo2 immunohistochemical staining, 400× magnification. (E) IDH-1 immunohistochemical staining, 400× magnification. (F) ATRX immunohistochemical staining, 400× magnification. (G) P53 immunohistochemical staining, 400× magnification. (H) MIB-1 immunohistochemical staining, 400× magnification, Ki-67=40%.

Immunohistochemical staining showed tumor cells that were GAFP (+), Oligo2 (+), EMA (-), IDH-1 (+), ATRX (+), P53 (+) and 40% Ki-67(+) rate. A) Is the evacuated hematoma, while B-H) are images of varies immunohistochemical staining. B) HE 400×, C) GFAP 400×, D) Oligo2 400×, E) IDH-1 400×, F) ATRX 400×, G) P53 400×, H) MIB-1 400×.

Glioblastoma Multiforme (GBM) WHO grade 4, confirmed by immunohistochemical staining

Glioblastoma multiforme of brain


51-year-old female with confirmed Birt-Hogg-Dubé syndrome (BHD), diagnosed 3 years prior through genetic testing showing a 4 bp deletion in one copy of FLCN gene. Initially asymptomatic regarding laryngeal mass, which was incidentally discovered during intubation for an open partial nephrectomy. No cervical lymphadenopathy. Had a brother recently diagnosed with renal tumor. No other significant past medical history. Physical examination via flexible nasendoscopy showed smooth mass around right aryepiglottic fold and right arytenoid, with reduced movement of right vocal cord.

MRI of the neck with contrast, right piriform fossa and right supraglottis, mass diameter 28 mm.

MRI neck with contrast showed 28 mm diameter mass centered on right piriform fossa and extending into right supraglottis without associated lymphadenopathy

(A) MRI, coronal view, T1-weighted sequence. (B) MRI, sagittal view, T1-weighted sequence. (C) MRI, axial view, T2-weighted sequence.

Endoscopic image showing laryngeal mass in the right piriform fossa. a T1-weighted coronal, b T1-weighted sagittal, c T2-weighted axial

(A) H&E staining of rhabdomyoma, 200× magnification. (B) H&E staining of rhabdomyoma, 400× magnification. (C) Immunohistochemistry of rhabdomyoma for desmin, 400× magnification. (D) Immunohistochemistry of rhabdomyoma for S100, 100× magnification. (E) Immunohistochemistry of rhabdomyoma for myogenin, 200× magnification. (F) Immunohistochemistry of rhabdomyoma for MyoD1, 400× magnification.

a Rhabdomyoma composed of polygonal cells with abundant eosinophilic cytoplasm, bland nuclei and scanty nucleation. Haematoxylin and Eosin ×200. b Rhabdomyoma with cells demonstrating cross striations (arrow). Haematoxylin and Eosin ×400. c Rhabdomyoma, with immunohistochemistry confirming expression of desmin with evidence of cross striations (arrow) ×400. d Rhabdomyoma, with a few scattered nuclei expressing S100×100. e Rhabdomyoma showing patchy expression of myogenin ×200. f Rhabdomyoma stained for MyoD1 expression ×400

Adult-type rhabdomyoma of the larynx in a patient with Birt-Hogg-Dubé syndrome

Adult rhabdomyoma

Birt-Hogg-Dubé syndrome


A 70-year-old female patient presented with lower abdominal pain persisting for 5 months. The pain was initially intermittent but progressively worsened, requiring narcotic management. She reported constipation without rectal bleeding, and developed urinary retention requiring a Foley catheter, which revealed hematuria. Associated symptoms included anorexia, nausea, abdominal bloating, and worsening bilateral leg edema. She denied vomiting, hematemesis, chest pain, melena, jaundice, fever, chills, night sweats, or weight loss. The patient had no history of heart disease, rheumatic fever, neurological disorder, diabetes, ulcers, asthma, tuberculosis, kidney, liver, or thyroid disease, and had no suspicious skin lesions.

CT of the pelvis.

CT scan showed a large heterogeneous but predominantly fatty pelvic mass compressing the bowel and bladder.

(A) Pelvic MRI, axial view, nonfat saturated T2-weighted sequence. (B) Pelvic MRI, axial view, fat saturated T2-weighted sequence.

Axial nonfat saturated (A) and fat saturated (B) T2-weighted MRI images of the pelvis also demonstrates a large fat containing mass within the presacral region (arrowheads). Bright fat on nonfat saturated image (A) saturates out on the fat saturated image (B) (arrows).

FISH analysis of 200 interphase cells per probe using 4 DNA probes.

FISH analysis summary showed examination of 200 interphase cells per probe with 4 DNA probes.

MDM2 FISH analysis.

MDM2 FISH analysis showed MDM2/CEP 12 ratio of 1.0, indicating no amplification of the MDM2 gene.

Adrenal myelolipoma in the presacral region

Lipoma


A 55-year-old man, born and raised in Pakistan who immigrated to the US mid-Atlantic region in his 30s, presented with a 3-month history of intermittent fevers and fatigue after returning from a 5-month visit to Pakistan. His medical history included coronary artery disease, stroke, hypertension, hyperlipidemia, and gastroesophageal reflux disease. He was a retired restaurant owner with a 60 pack-year smoking history but quit 12 years prior. Initial symptoms evolved to include daily fevers, drenching night sweats, nonproductive cough, and myalgias. Physical examination revealed temperature 38.4°C, pulse 116/min, BP 124/88 mmHg, respiratory rate 16/min, and oxygen saturation 97% on room air. Laboratory findings showed pancytopenia with WBC 3bin 13.1 g/dL, platelets 127,000/mm³, elevated liver enzymes (AST 119 U/L, ALT 48 U/L), elevated ESR (37 mm/hr) and CRP (2.9 mg/dL). The patient later developed confusion, early satiety, nausea, and abdominal distention.

(A) CT of the abdomen and pelvis, axial view. (B) CT of the abdomen and pelvis, coronal view.

CT images of abdomen and pelvis showing splenomegaly in both axial (A) and coronal (B) views

(A) Skin biopsy, H&E staining. (B) Skin biopsy, immunostaining for CD20.

Skin biopsy showing malignant large B cells within small-vessel lumen (H&E staining) (A) and CD20-positive (B) malignant cells (immunostaining)

Intravascular large B-cell lymphoma


A 36-year-old man, sexually active with men, presented to the emergency department with a 2-week history of fever, headache, drowsiness, and photophobia. He was previously healthy. Physical examination revealed a temperature of 38.3°C and neck stiffness. CT of the head was normal. Lumbar puncture showed an opening pressure of 29 cm of water (ref: <20 cm). CSF analysis revealed: cell count 340 cells/µL (90% mononuclear cells, predominantly lymphocytes), glucose 46 mg/dL, and protein 0.80 g/L. HIV antibody test was positive with viral load 300,000 copies/mL and CD4+ count of 7 cells/µL.

Gram stain of cerebrospinal fluid obtained on admission, light microscopy.

A: Gram’s stain of cerebrospinal fluid obtained on admission demonstrates abundant encapsulated, round yeasts, some with budding forms, consistent with Cryptococcus neoformans seen under light microscopy.

India ink stain.

India ink stain showed abundant encapsulated, round yeasts, with some budding forms

Cryptococcal meningoencephalitis


69-year-old man with type 2 diabetes mellitus, obesity, hypertension, and coronary artery disease. Patient experienced dizziness and intermittent weakness in the left hand over past six months. Visual acuities and intra-ocular pressures were normal, and slit lamp examination of anterior segment of both eyes was unremarkable.

Ultrawide field colour fundus image of the retina, left eye, acquired during ophthalmic evaluation.

Figure 1 is an ultrawide field colour fundus image of the left eye demonstrating diffuse intraretinal haemorrhages in the retinal midperiphery, arterial narrowing, and venous dilation; the anatomical site examined is the retina of the left eye, and the imaging modality is ultrawide field colour photography, with the scan acquired during ophthalmic evaluation for unilateral retinopathy.

Autofluorescence imaging of the retinal midperiphery.

Autofluorescence image showing diffuse intraretinal hemorrhages in retinal midperiphery, arterial narrowing, and venous dilation

Wide field fluorescein angiography of the left eye.

Wide field fluorescein angiography of left eye shows delayed and patchy choroidal filling, delayed retinal arteriovenous filling, peripheral areas of retinal capillary non-perfusion, and blocked fluorescence from intraretinal hemorrhages

Doppler carotid ultrasonography of the left internal carotid artery.

Doppler carotid ultrasonography reveals complete occlusion of the left internal carotid artery with calcific, heterogenous plaques

Ocular ischemic syndrome due to unilateral retinopathy with ipsilateral carotid occlusive disease

THE - [tricho-hepato-enteric] syndrome

Retinopathy

occlusive disease NOS


A 67-year-old previously healthy male presented with a 4-month history of dry cough, wheezing, and mild dyspnea that had initially been diagnosed as eosinophilic asthma at another hospital, with symptoms worsening despite treatment with inhaled bronchodilators and corticosteroids. He had no smoking history and unremarkable medical history. On examination, he required 1L nasal cannula oxygen with SaO2 of 96%, had decreased breath sounds in the right lower lung field with fine crackles, and no raised JVP, murmurs, gallop, or peripheral edema. Chest x-ray showed right ground glass opacities, and high-resolution CT revealed ground glass opacities surrounded by consolidation in the right lower lung field.

Laboratory test results.

Laboratory findings showed WBC 7,770/μL with 53.5% eosinophils, RBC 366×10⁴/μL, hemoglobin 8.6 g/dL, platelets 25.5×10⁴/μL, C-reactive protein 2.66 mg/dL (elevated), LDH 243 IU/L (slightly elevated), IgE 254 IU/mL (normal), and soluble IL-2 receptor 495 U/mL (normal). Infectious markers for HBs-Ag, HBs-Ab, HCV-Ab, and HIV-Ab were all negative. Autoimmune markers including ANA, Jo-1-Ab, RF, PR3-ANCA, and MPO-ANCA were all negative. TARC was 119 pg/mL. Arterial blood gas analysis showed pH 7.549, pCO2 27.1 mmHg, pO2 68.2 mmHg, and HCO3 23.1 mmol/L.

(A) Bone marrow aspirate smear, Wright-Giemsa staining, 400× magnification. (B) Bone marrow aspirate smear, Wright-Giemsa staining, 400× magnification.

Bone marrow eosinophilia. A representative Wright-Giemsa stain, (×400) of bone marrow aspirate smears of the patient. Notice the presence of various immature eosinophils, including eosinophilic band and Polymorphonuclear eosinophils (A), as well as eosinophilic myelocyte and eosinophilic metamyelocyte (B).

Genetic analysis of bone marrow cells.

Chromosomal analysis of bone marrow cells revealed 46,XY,+1,der(1;7)(q10;p10) in 13 of 20 metaphases, showing allelic imbalance of trisomy 1q and monosomy 7q. The patient was negative for PDGFRA, PDGFRB rearrangement, FGFR1, and JAK2 mutations.

Myelodysplastic syndrome (refractory cytopenias with multilineage dysplasia type)

Myelodysplastic syndromes, unspecified

Refractory cytopenias with multilineage dysplasia

Refractory cytopenia with multi-lineage dysplasia


A 13-month-old male infant presented to the Department of Dermatology with a single asymptomatic plaque on the lower back that was first noticed by parents at approximately 4 months of age. During observation, the lesion gradually became larger and firmer, and intermittent sweating on the surface was noticed.

Clinical photograph of the lumbar area at 6 months of age.

Shows a 4×2-cm normal skin-colored soft nodule on the lumbar area with hypertrichosis on the surface at 6 months of age.

T2-weighted MRI of the lumbar spine at L3-4 level.

T2-weighted MRI showed an abnormal mass in the subcutaneous fat layer at the L3-4 level, not connected to the spinal cord.

Ultrasonography of the subcutaneous fat layer at the L3-4 level.

Ultrasonography showed a 4×2-cm abnormal echogenicity in the subcutaneous fat layer at the L3-4 level.

Clinical photograph of the lumbar area at 13 months of age.

Shows a 5×3-cm normal skin-colored nodule on the lumbar area with localized prominent hypertrichosis at 13 months of age.

Punch biopsy of lumbar skin lesion, H&E staining.

A: Hematoxylin and eosin (H&E) stained section of a punch biopsy specimen from the lumbar skin lesion demonstrates mature hair follicular structures and fat tissue in the dermis, without specification of magnification, representing the histopathological findings characteristic of fibrous hamartoma of infancy.

Histopathological section of the skin, punch biopsy, H&E staining.

B: Histopathological section of the skin obtained by punch biopsy, stained with hematoxylin and eosin, showing well-defined fibrous trabeculae composed of spindle cells and an increased number of eccrine glands admixed with mature adipose tissue in the lower reticular dermis.

Skin punch biopsy from lumbar region, H&E staining, intermediate magnification.

C: Histopathological examination of a skin punch biopsy from the lumbar plaque demonstrates primitive mesenchymal tissue in the lower reticular dermis, visualized using hematoxylin and eosin (H&E) staining at intermediate magnification.

Immunohistochemical staining for smooth muscle actin on a skin biopsy specimen.

D: Immunohistochemical staining for smooth muscle actin on a skin biopsy specimen from the lesion, demonstrating positive staining of spindle cells, as shown in the lower reticular dermis, supporting the identification of myofibroblastic differentiation in the examined tissue (as seen in Figure 4D on page 3).

Fibrous hamartoma of infancy with eccrine hyperplasia

Fibrous hamartoma of infancy

Bone hyperplasias


A 19-year-old previously healthy gravida 3 para 2002 female presented at 28 weeks' gestation after emigrating to the U.S. at 25 weeks of gestation. During the 20th week of gestation, she experienced a maculopapular rash, conjunctivitis, fever, and headache. She and her spouse had unprotected intercourse through the first and second trimester. The patient's initial fetal ultrasound with neurosonography revealed cerebral ventriculomegaly (20-25 mm) with dangling choroid, prominent 3rd ventricle, and a widened cavum septum pellucidum. Amniocentesis showed negative NAT for ZIKV with no evidence of chromosomal variations by CMA; TORCH panel was negative.

Timeline summarizing exposure risk, clinical findings, laboratory testing (nucleic acid testing and serologic IgM), estimated date of delivery, gestational age, and timing of prenatal ultrasound and/or MRI, for four subjects.

Figure 1 presents a timeline summarizing the exposure risk, clinical findings, and standard clinical laboratory testing for ZIKV among four subjects, with the gestational period outlined by a checked box and possible windows of endemic exposure (orange bar) as well as the timing of maternal ZIKV screening by nucleic acid testing (NAT) or serologic IgM, distinguished by type and fluid tested (blue/purple legend); the estimated date of delivery and gestational age are indicated, and key prenatal imaging findings by ultrasound (US) and/or MRI, as well as timing of delivery, are annotated for each case.

Fetal neurosonography at 31 weeks and 1 day.

Fetal neurosonography at 31w1d showed thinning of the cortex, reduced subarachnoid space, bilateral ventriculomegaly, punctiform calcifications within basal ganglia, and dysplastic cavum septum pellucidum

(A) MRI at 31 weeks 1 day, axial view. (B) MRI at 31 weeks 1 day, sagittal view.

Axial (i) and sagittal (ii) MRI at 31w1d revealed bilateral ventriculomegaly, abnormal sulcation pattern in Sylvian fissure, absent dorsal cavum septum pellucidum leaflets, and thin corpus callosum near the splenium

Congenital Zika Syndrome with prenatal evidence of brain malformations

Zika virus disease

Malformations of brain


A 64-year-old man presented with neutropenia, bilateral symmetrical joint pain, and morning stiffness in multiple joints, along with weight loss, fevers, increased sweating, and fatigue for 2 months. Physical examination revealed bilateral synovitis in the elbow, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints, with no lymphadenopathy or splenomegaly. Laboratory findings showed hemoglobin 12.1 g/dL, platelets 272 × 10⁹/L, and white blood cell count 1.7 × 10⁹/L (21% neutrophils, 55% lymphocytes, 17% monocytes, 3% basophils, 4% eosinophils). T-cell large granular lymphocyte count was 0.53 × 10⁹/L. C-reactive protein was 80.4 mg/L with elevated erythrocyte sedimentation rate of 129 mm/h. Rheumatoid factor (23 IU/mL) and anti-cyclic citrullinated peptide antibodies (>25 U/mL) were markedly elevated. Flow cytometry showed 61.76% of lymphocytes positive for CD3 and CD8, with 2% atypical T-cell populations showing loss of CD5 and CD7. PCR analysis revealed clonal T-cell receptor γ and β chain gene rearrangements.

Peripheral blood smear, Wright-Giemsa stain, 100× magnification.

A: Peripheral blood smear showing a T-cell large granular lymphocyte using Wright-Giemsa stain at an original magnification of ×100.

Bone marrow biopsy, histopathological examination, 100× magnification.

B: Hypercellular bone marrow is shown under histopathological examination of a biopsy sample, with original magnification ×100.

Immunohistochemical staining of bone marrow biopsy.

Linear arrays of cytotoxic T cells seen with immunohistochemical staining of bone marrow biopsy

T-cell large granular lymphocytic leukaemia (T-LGL) in the context of rheumatoid arthritis

Rheumatoid arthritis


A 51-year-old female presented to the emergency room with general weakness and hyperglycemia. She had been diagnosed with type 2 diabetes in March 2014, with initial fasting plasma glucose of 140 mg/dL. Three days before admission, her blood glucose levels gradually increased to over 400 mg/dL, with worsening polydipsia and general weakness. On admission, she was alert with blood pressure 100/60 mmHg, respiratory rate 18 breaths/min, heart rate 103 beats/min, and temperature 36.2°C. Her height was 155.4 cm, weight 60.5 kg, and BMI 25.05 kg/m2, with no recent weight changes. Chest X-rays and abdominal CT showed no abnormal findings except for moderately fatty liver.

Laboratory results. Arterial blood gas analysis. Urinalysis.

Initial laboratory findings showed: WBC 8,300/μL, hemoglobin 12.3 g/dL, platelets 201x10³/μL, glucose 431 mg/dL, elevated urea/creatinine (25.0/1.09 mg/dL), sodium/potassium/chloride 132.1/4.6/100 mEq/L, osmolarity 309 mOsmol/kg, amylase/lipase 69/120 U/L, CRP 4.1 mg/dL. Arterial blood gas showed metabolic acidosis with pH 7.17, PaCO2 22 mmHg, PaO2 109 mmHg, HCO3- 8.0 mmol/L, SaO2 97%. Urinalysis was positive for glucose (3+) and ketones (3+). Additional tests showed HbA1c 7.0%, very low fasting C-peptide (0.01 pmol/mL), and negative results for GAD-Ab, ICA, and IAA.

Fulminant type 1 diabetes occurring in a patient previously diagnosed with type 2 diabetes mellitus

Fulminant type 1 diabetes mellitus

Type 2 diabetes mellitus


A 46-year-old Chinesed with bilateral tumor-like nodules over his neck that had been present for 6 months and developed edema for 15 days. The neck nodules were painless without pruritus or dermatitis and had enlarged over the 6-month period. He experienced a 10 kg weight loss during the past 6 months without symptoms such as fever, cough, diarrhea, or oliguria. Physical examination revealed blood pressure of 145/90 mmHg, multiple 1×1 cm hard and movable masses over bilateral post-auricular and submandibular areas with intact overlying skin and sharp boundaries, and trace edema of the lower extremities. Laboratory findings showed markedly increased peripheral eosinophil count at 3.66×10⁹/L (50% of total leukocytes), normal serum creatinine, 24-hour urine total protein of 8 g, serum albumin of 19 g/L (normal 40-55 g/L), elevated serum IgE of 2930 IU/ml (normal <100 IU/ml), decreased IgG at 3.61 g/L (normal 7.0-16.0 g/L), and decreased C3 at 0.75 g/L (normal 0.9-1.8 g/L). IgG4 was within normal range, anti-nuclear antibody and anti-neutrophil cellular antibody were normal, and hepatitis B surface antigen, hepatitis C virus, and HIV serology were all negative. Ultrasound examination revealed swelling lymph nodes over bilateral neck and supraclavicular areas, while renal ultrasound, chest X-ray, and electrocardiogram were normal.

(A) Renal specimen, PAS staining, 400× magnification. (B) Renal specimen, Masson staining, 400× magnification. (C) Renal specimen, PASM + Masson staining, 400× magnification. (D) Renal specimen, HE staining, 400× magnification. (E, F) Renal specimen, electron microscopy, 10000× magnification.

Renal specimen showed membranoproliferative glomerulonephritis (A, B, C) along with eosinophils infiltration in the interstitium (D: arrow). Electron microscope showed electron dense deposit in endodermic (E: arrow) and subepithelial (F: arrow) region. (A: PAS × 400; B: Masson × 400; C: PASM + MASSON × 400; D: HE × 400; E&F: EM × 10000).

(A) Lymph node specimen, H&E staining, 4× magnification. (B) Lymph node specimen, H&E staining, 20× magnification. (C) Lymph node specimen, H&E staining, 40× magnification.

Lymph node specimen showed eosinophilic lymphoid follicular granuloma with abundant eosinophil infiltration. Immunohistochemical staining showed positive S-100 and CD1a, but negative CD68, lysozyme, CD15, CD20, CD3, CD138, CD30, CD117, and EB virus-encoded small RNA.  (A: HE 4; B: HE 20; C: HE 40).

Kimura's disease with membranoproliferative glomerulonephritis

Kimura disease


A 7-year-old girl with no past medical history presented with interm pain for approximately 1 month that was not relieved with anti-inflammatory treatment. A subsequent abdominal computed tomography (CT) scan at a local hospital showed peritoneal effusion and retroperitoneal lymphadenopathy. Her serum AFP level was elevated at 1,210 ng/mL (normal range: <25 ng/mL). Ultrasonography examination showed multiple enlarged abdominal and retroperitoneal hypoechoic lymph nodes. The bilateral ovaries and fallopian tubes as well as the uterus, cervix, and vagina were unremarkable. Upon surgical resection, the jejunal mass measured 4 cm in the largest dimension and involved the full thickness of the jejunum. The cut surface of the tumor was grey-white in color. Histologically, the tumor cells showed multiple patterns including microcystic, reticular, macrocystic, papillary, solid, and tubule-glandular structures. The tumor cells had large, irregular, pleomorphic nuclei with vesicular chromatin and variably prominent nucleoli, with moderate to abundant cytoplasm that was clear, mixed clear, or eosinophilic. Mitotic figures were abundant (highest, 18-20/10 high power fields). Pathologically, the lymph nodes showed reactive hyperplasia, including two ileocecal lymph nodes and one small mesenteric lymph node.

(A) CT plain scan of the lower right abdomen, jejunum region, CT value 40 HU, size 1.7 cm × 2.2 cm. (B) PET scan of the right lower abdomen, SUVmax=7.8. (C) PET/CT fusion image. (D) Whole body PET maximum intensity projection.

18F-FDG PET/CT imagings of the patient. (A) CT plain scan shows the soft tissue shadow of jejunum in the lower right abdomen. The CT value is 40 Hu, the size is about 1.7 cm x 2.2 cm. (B) PET shows the abnormal concentration nodules of 18F-FDG uptake in the right lower abdominal. SUVmax is 7.8. (C) The PET/CT image is the fusion of CT (A) and PET (B), showing the lesions. (D) MIP of patient's whole body, showing abnormal accumulation of 18F-FDG uptake in the right lower abdomen (arrows).

(A) SP staining, 200× magnification. (B) SP staining, 200× magnification, AFP positive. (C) SP staining, 200× magnification, glypican-3 positive. (D) SP staining, 200× magnification, SALL4 positive. (E) SP staining, 200× magnification, SATB2 positive (focal). (F) SP staining, 200× magnification, EMA negative.

The YST of the patient does not involve the mucosa and shows solid and glandular pattern with myxoid stroma (A, SP staining, 200 ×). Immunohistochemically the tumor cells are diffusely positive for AFP (B, SP staining, 200 ×), glypican-3 (C, SP staining, 200 ×) and SALL4 (D, SP staining, 200 ×). The tumor cells are focally positive for SATB2 (E, SP staining, 200 ×) and negative for EMA (F, SP staining, 200 ×).

Immunohistochemical analysis of the jejunum.

Immunohistochemical profile shows Case 1 (Jejunum) positive for pan-CK, CK8/18, CDX-2 (partial), SATB2 (partial), AFP, GPC-3, and SALL4, while negative for CK7, CK20, EMA, and OCT4.

Yolk sac tumour, unspecified site, female


A previously healthy 58-year-old male presented with two weeks of lumbar pain and fever, accompanied by asthenia, anorexia, and recent weight loss of 3kg. He was a non-smoker with no drug abuse, recent travel, or animal contact history. On examination, he had a fever of 39.3°C with hemodynamic stability, bilateral painless swollen legs, and respiratory crackles on the right side. Laboratory tests showed hemoglobin 116 g/l, leukocyte count 33.3*109 cells/l, C-reactive protein 114.6mg/l, creatinine 56 μmol/l, elevated liver enzymes (AST 174 U/l, ALT 209 U/l, ALP 406 U/l, GGT 517 U/l), total bilirubin 76 μmol/l, conjugated bilirubin 66 μmol/l, and INR 1.38. Serology for hepatitis B, hepatitis C, and HIV were negative. Urinary sediment was unremarkable.

CT scan of the pelvis and lumbar spine.

CT scan showed thromboses of both iliac veins, abscesses in the right iliac muscle (2.3 × 2.0 cm) and left psoas muscle (6.0 × 4.8 cm), right pleural effusion with pneumonia, and L4-L5 spondylodiscitis. The yellow arrow indicates L4-L5 spondylodiscitis, red arrow shows left iliac abscess, and blue arrow shows left iliac thrombosis.

Atypical Lemierre's syndrome caused by Fusobacterium nucleatum, presenting with iliac vein thromboses, muscle abscesses, pneumonia with pleural effusion, and L4-L5 spondylodiscitis

THE - [tricho-hepato-enteric] syndrome


A 51-year-old woman was hospitalized for bilateral painful skin ulcers in the mammary region that had begun 6 months prior and rapidly developed from pustular lesions. The skin lesions were refractory to antiseptic and antibiotic therapies. During hospitalization, chest computerized tomography revealed a multinodular goiter. Neck ultrasound disclosed a 12.4 mm solid hypoechoic nodule in the upper pole of the left thyroid lobe and an 8.5 mm hypoechoic nodule in the lower pole of the same lobe. Fine-needle aspiration of the dominant nodule resulted in Tir4 category according to 2014 SIAPEC classification, equivalent to 'suspicious for thyroid carcinoma'. Fine-needle aspiration of the thyroid bed lesions revealed numerous neutrophils, together with scattered erythrocytes, lymphocytes, histiocytes, and few thyrocytes without cytological alterations.

(A,B) Clinical photographs of the right and left breast. (C) Skin biopsy, H&E staining, 100× magnification. (D,E) Clinical photographs after therapy. (F,G) Clinical photographs after complete healing.

Dermatological and histopathological characteristics of pyoderma gangrenosum. (a,b) Ulcerative lesions showing necrotic base and erythematous-violaceous undermined borders on the right and left breast, respectively; (c) Skin histology revealing epidermal necrosis and a dermal-hypodermal inflammatory infiltrate mainly consisting of neutrophils (haematoxylin-eosin, original magnification ×100) (in the box, a magnified detail of the inflammatory infiltrate); (d,e) Partial healing after therapy with pulsed intravenous methylprednisolone, followed by the combination of prednisone and cyclosporine given orally; (f,g) Complete healing with hypertrophic aspects.

(A) Neck ultrasonography, transversal scan, performed at 12-month follow-up after thyroidectomy. (B) Neck ultrasonography, longitudinal scan, performed at 12-month follow-up after thyroidectomy.

Neck ultrasonography performed at 12-month follow-up visit after thyroidectomy. (a) Transversal scan shows two adjacent left paratracheal lesions (arrows). These marked hypoechoic areas have ill-defined margins but not microcalcifications; (b) Longitudinal scan depicts the elongated shape of the paratracheal lesion (lateral one) and its parallel orientation to the dermis without deformation of surrounding tissues, unlike true focal masses.

Laboratory tests at 12 months after radioiodine ablation.

Laboratory tests show that at 12 months after radioiodine ablation: TSH 0.89 mIU/L, undetectable Tg <0.04 ng/mL, anti-Tg antibodies <12 IU/mL, elevated ESR 60 mm (normal <20), elevated CRP 1.17 mg/dL (normal <0.5), and elevated absolute neutrophil count 3.22 × 10⁸/L

Post-surgical thyroid bed pyoderma gangrenosum mimicking recurrent papillary thyroid carcinoma

Pyoderma gangrenosum

Papillary carcinoma of thyroid gland


A 38-year-old male patient was investigated for slowly progressive difficulty in walking and climbing stairs that began at age 35 years. No family history of neuromuscular disorders or consanguinity was reported. On neurological examination, scapular, anterior and posterior thigh muscle atrophy were observed. Muscle strength assessment using the MRC scale showed weakness of shoulder girdle muscles (with arm flexion and abduction possible against gravity until 90°) without scapular winging, inferior trapezius (2/5), arm extensors (2/5), elbow flexors (3/5), hip flexors (3/5), hip extensors (2/5), knee flexors and extensors (4/5), and dorsal foot extensors (4/5). No cranial nerve involvement was observed. Joint contractures and skeletal deformities were absent. The patient presented a waddling gait with increased lumbar lordosis and was unable to get up from the floor. Functional ability was 3 on the Brooke scale for upper limbs and 3 on the Vignos scale for lower limbs. CK was only slightly increased at 253 UI/l. EMG showed myopathic findings in all tested muscles with fibrillation potentials and positive sharp waves. Respiratory and cardiac functions were normal.

(A) T1-weighted muscle MRI of the leg. (B) T1-weighted muscle MRI of the thigh.

T1-weighted muscle MRI at leg (a) and thigh (b) level. In the leg symmetrical fatty changes are more evident in medial and lateral gastrocnemius and, to a lesser degree, in tibialis anterior muscles (a). In the thigh a diffuse fatty substitution is present, with relative sparing of gracilis and rectus femoris muscles (b)

Muscle biopsy from left quadriceps at age 38, H&E staining.

H&E staining of muscle biopsy from left quadriceps taken at age 38 showed fiber size variability, a few central nuclei, scattered degenerative fibers.

Muscle biopsy, Gomori Trichrome staining.

Gomori Trichrome staining showed few cytochrome oxidase-negative fibers and ragged red appearing fibers that were rare (about 1%) but above the expected number in a 38-year-old man.

Electron microscopy of first biopsy.

Electron microscopy of first biopsy showed mitochondria of abnormally large size containing densely packed cristae.

Western blot analysis of transportin 3.

Western blot analysis showed greatly reduced intensity of the transportin 3 band in the patient compared to control subject.

(I) Bar graph of Real Time PCR results quantifying TNPO3 transcript levels in muscle biopsy samples.

I: Figure 2 (I) presents a bar graph of Real Time PCR results quantifying TNPO3 transcript levels in muscle tissue, demonstrating a marked reduction of TNPO3 mRNA copy number in the patient (Pt) compared to control (Ctrl). This analysis was performed on muscle biopsy samples, and the finding indicates decreased TNPO3 transcript abundance in the patient.

LGMD1F (Limb Girdle Muscular Dystrophy 1F) with heterozygous G>A transition (c.G2453A) in exon 20 of the TNPO3 gene

Limb-girdle muscular dystrophy


22-year-old athletic male presented with swelling and locking of the left knee. He had no recent trauma but had several football injuries as a child. Two years prior, he had experienced disabling knee pain.

Plain radiograph of the left knee, lateral view, at current presentation.

Plain radiograph (lateral view of left knee) at current presentation shows a loose body at the medial aspect of the patellar pouch with anterior displacement of the patella, and a deformity in the articular surface of the posterior aspect of the lateral condyle

Plain radiograph of the left knee, lateral view, performed two years prior.

Plain radiograph (lateral view of left knee) from two years prior shows a large area of osteochondritis bordered by a crescent of radiolucency

Displaced osteochondral body (a dislodged fragment of subchondral bone) resulting from osteochondritis dissecans (OCD)

osteochondral lesion

Osteochondritis dissecans


A 64-year-old immunocompetent woman presented with cerebral hemorrhage in the left temporal-parietal region. CT angiography detected an aneurysm in the distal segment of left middle cerebral artery. Immunohistochemistry showed the cells were positive for CD30 with partial expression of CD79α and CD20. The cells expressed LMP-1. Clonal immunoglobulin heavy chain (IGH) rearrangement was detected. Staging procedures including CT scan and bone marrow biopsy were negative.

(A) Artery histology, low power view. (Inset) Thrombus histology, high power view.

Low power view of artery with interrupted wall containing thrombotic material; inset shows rare atypical lymphoid cells lying within the thrombus at high power view

High power microscopic view of lymphoid cells; left inset: PAX5 immunohistochemistry; right inset: MUM1 immunohistochemistry.

High power detail of large lymphoid cells; inset left shows PAX5 positivity; inset right shows MUM1 expression

(A) Ki-67 immunostaining. (B) In situ hybridization for EBV-encoded RNA (EBER).

Subfig A shows high proliferative index (Ki67); Subfig B shows Epstein-Barr virus positivity in large-sized cells by in situ hybridization for EBV-encoded RNA (EBER)

Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) within a cerebral artery aneurysm

Diffuse large B-cell lymphomas

Cerebral aneurysm NOS[Cerebral artery]


54-year-old woman without comorbidities presented to emergency department with 12-hour history of redness and painful swelling in left gluteal region. Denied trauma. At admission: afebrile (36.2°C), normal blood pressure (109/65 mmHg), heart rate 89 bpm, mild peripheral oxygen desaturation (92% on room air) without respiratory distress. Rest of physical exam normal.

(A) Clinical photograph of the left gluteus at admission. (B) Clinical photograph of the left gluteus 3 hours after admission.

Shows macroscopic aspect of left gluteus with signs of cutaneous infection at admission and rapid progression of redness around central area of induration 3 hours after admission. (a) at admission. (b) 3 h after admission,

(A) Point-of-care ultrasound of the left gluteal soft tissue, 15–6 MHz linear probe. (B) Point-of-care ultrasound of the contralateral gluteal soft tissue, 15–6 MHz linear probe.

Point-of-care ultrasound scan of the affected left gluteal soft tissue (a) and normal soft tissue on the contralateral side (b) using a 15–6 MHz linear probe. In the affected tissue, there is loss of the normal subcutaneous architecture, diffuse increased echogenicity, hypoechoic regions that correspond to little fluid accumulations (arrow) and an hyperechoic focus with posterior dirty acoustic shadowing, corresponding to gas in the soft tissue (arrowhead)

infection NOS


A 71-year-old woman presented with hematuria and underwent an abdominal CT scan. Her past medical history included nephrolithiasis at age 41, a long history of easy skin bruising that worsened at age 66, and osteoporosis with a T-score of -2.6 at the left femoral neck. Physical examination was notable only for bruising on her lower extremities. Serial testing at a tertiary center showed late-night serum cortisol of 70 ng/mL, and a Dex-CRH test with cortisol levels of 1.8 μg/dL at 0 minutes and 2 μg/dL at 15 minutes.

CT of the adrenal glands.

CT images show an enlarged right adrenal gland and a 1.7-cm left adrenal nodule with nodular hyperplasia

Laboratory results.

Laboratory findings show fasting plasma glucose of 253 mg/dL, HbA1c of 7.9%, blood pressure of 129/70 mm Hg, cortisol after 1-mg DST of 18 μg/dL, multiple LNSC values of 5.075 and 2.43 ng/mL (ULN <1.56 ng/mL), multiple UFC values ranging from 32-116 μg/d, ACTH levels ranging from undetectable to 14.6 pg/mL, and DHEA-S of 82 μg/dL

Primary bilateral macronodular adrenal hyperplasia (BMAH) with hypercortisolism

ACTH-independent macronodular adrenal hyperplasia

Hypercortisolism


Patient 1 is a 15-year-old Ukrainian male who was the only child of a healthy non-consanguineous family (family 1). His mother had a full-term first pregnancy without miscarriages or health concerns. At the time of examination, his weight was 45 kg (Z score -1.32, 9% centile). He suffers from headaches, urolithiasis, and pyelonephritis. Within 2 months, sarcoma-like ossification measuring 5×4 cm without clear contour developed, enlarging to 7×5 cm after 1.5 months with some thickening and clearer contour line. By 2017, extreme hyperplastic callus formation was present with lower limb inflammatory symptoms including redness, fever, and enlargement. He developed deformities of the spine and combined deformities of lower limbs, upper limbs, and chest. Due to severe callus formation in the hips, he was immobile and unable to sit. His bone mineral density Z-score was -5.9 for the spine and -3.6 for the lower arm.

(A) Clinical photograph of the femur during the period of extreme hyperplastic callus formation.

A: Figure 1 (a) on page 5 shows a clinical photograph depicting hyperplastic callus formation in the femur of Patient 1, a 15-year-old male with osteogenesis imperfecta type V, at a stage when the callus appeared markedly enlarged, with visible swelling and redness as described after inflammatory symptoms developed. This image documents the anatomical site as the femur and represents a gross clinical photograph rather than a radiological or histopathological modality; the timing corresponds to the period during which extreme hyperplastic callus was present and inflammatory signs were observed.

(C) Conventional X-rays performed in 2017, right humerus, both femurs, and right forearm.

Figure 1 (c) displays radiographic images demonstrating the radiological features of Patient 1, a 15-year-old male with osteogenesis imperfecta type V, highlighting severe hyperplastic callus formation involving the right humerus and both femurs, congenital synostosis of the right forearm with calcification of the radioulnar interosseous membrane, and contracture with radial head dislocation of the right elbow; the images are conventional X-rays taken after symptoms became extreme in 2017, clearly visualizing cortical thickening and extensive ossifications in multiple long bones, and also showing postsurgical changes following osteosynthesis.

Table summarizing clinical, radiological, and genetic data for five patients with osteogenesis imperfecta type V with the IFITM5 c.-14C>T variant.

Table 1, found on page 4 of the document, summarizes the phenotype characteristics of five patients with osteogenesis imperfecta type V confirmed to have the IFITM5 c.-14C>T pathogenic variant. The table presents individual data for each patient, including age, sex, country, phenotype severity, mimicked classic OI type, family history, presence of hyperplastic callus, interosseous membrane calcification, radial head dislocation, metaphyseal radiodense band, hearing loss, presence of dentinogenesis imperfecta or teeth brittleness, sclera hue, number and annual rate of fractures, timing and anatomical site of first fracture, most frequently fractured bone, presence of chest deformity and scoliosis, upper and lower limb long-bone deformities, mobility status, height Z-score, birthweight and length, and joint laxity. This table provides a comparative overview of clinical, radiological, and genetic features across the cohort, highlighting the phenotypic variability in OI type V.

Osteogenesis imperfecta type V caused by c.-14C > T pathogenic variant in the IFITM5 gene

Osteogenesis imperfecta


A 28-year-old man presented with an 8-year history of recurrent urticaria, arthralgia, and fever induced by cold stimuli. His father had exhibited the same symptoms since childhood but died without knowing the source of these symptoms. The patient had been previously diagnosed with cold urticaria and received symptomatic treatment at other hospitals, but his arthralgia, fever, and familial history were not explained by this initial diagnosis. The urticaria developed repeatedly and worsened upon exposure to cold environments, typically appearing and worsening in winter, and sometimes appearing in summer upon exposure to air conditioning. Arthralgia particularly affected the knee joint and accompanied the presentation of urticaria. Symptomatic treatment including anti-inflammatory agents had minimal effect on his symptoms. Laboratory findings showed elevated C-reactive protein (5.2 mg/dL) and erythrocyte sedimentation rate (62 mm/h), while other lab tests were within normal ranges. Antinuclear antibodies were positive with a titer of 1:80 and a cytoplastic pattern.

(A) Clinical photograph of the trunk. (B) Clinical photograph of the hand. (C) Clinical photograph of the leg.

Shows urticaria on the trunk (A), hand (B) and leg with joint swelling (C)

Genetic analysis chromatogram of the NLPR3 gene.

Chromatogram showing p.Gly303Asp variant of the NLPR3 gene

Cryopyrin-associated periodic syndrome (CAPS), specifically familial cold autoinflammatory syndrome (FCAS)

Cryopyrin-associated periodic syndromes

Familial cold autoinflammatory syndrome


54-year-old female with hypertension and hyperlipidemia presented to cardiology clinic for follow-up 20 months since her most recent office visit. She was being evaluated for follow-up of cardiac risk factors and medication management. The patient was in her usual state of health and asymptomatic without changes in her exercise tolerance, weight, or energy levels. She did not have any gross hematuria or flank pain.

(A) Point-of-care ultrasound of the right kidney. (B) Renal ultrasonography of the right kidney, largest mass measuring 4.6 cm in the inferior pole. (C) Contrast-enhanced CT of the abdomen and pelvis, coronal view, right kidney.

(a) Point-of-care ultrasound image of the right kidney in an asymptomatic 54-year-old woman shows a peripherally located isoechoic solid mass (arrow) causing distortion of the renal border. (b) Formal renal ultrasonography image of 1 (arrow) of 2 solid masses found in the inferior pole of the right kidney, the largest measuring 4.6 cm in its biggest dimension. (c) Contrast-enhanced computed tomography imaging of the abdomen and pelvis, coronal view shows a peripheral, likely multifocal renal cell carcinoma (arrow) in the inferior pole of the right kidney.

Clear cell renal cell carcinoma, stage pT2a

renal cell carcinoma NOS


A 60-year-old female patient initially presented with atrial premature beats and paroxysmal atrial fibrillation. An initial transesophageal echocardiogram (TEE) showed a small, localized thickening of the interatrial septum that was considered as a structural variant. Three months after radiofrequency catheter ablation (RFCA), she was readmitted with sudden onset of chest tightness, dyspnea, transient palpitation, and recurrent pericardial effusion. Chest x-ray examination revealed moderate cardiomegaly and T-wave abnormalities in precordial leads were found in electrocardiogram. The mass did not extend into the superior vena cava and did not cause stenosis of the tricuspid valve annulus. The mass exhibited central cavitation suggesting poor blood flow in this region. No malignant or atypical cells were found in the bloody pericardial effusion.

(A) Transesophageal echocardiography (TEE) of the interatrial septum, performed before RFCA. (B) Transthoracic echocardiography (TTE) of the interatrial septum, performed 3 months after RFCA. (C) Transesophageal echocardiography (TEE) of the right atrial walls, performed 3 months after RFCA.

Echocardiography revealed the changes of the mass before and after RFCA. a Before RFCA, transesophageal echocardiography (TEE) revealed a local thickening of the interatrial septum (*) near the root of aorta. b Transthoracic echocardiography (TTE) detected a large immobile, non-pedunculated mass (*) involving the interatrial septum 3 months after RFCA. c TEE revealed a large polymorphic tumor (*) infiltrating the right atrial walls with hypoechoic area (arrow) 3 months after RFCA

(A) Positron emission tomography scan of the heart, SUVmax=21.2. (B) 18F-FDG PET-CT fusion image of the heart.

PET-CT assessed the metabolic activity of the cardiac mass. a Positron emission tomography scan showed hypermetabolic activity (*) in the RA with a standard uptake value SUVmax of 21.2. b 18F-FDG PET-CT fusion image illustrates high FDG uptake of the cardiac mass (*). 18F-FDG PET-CT: F18-fluorodeoxy glucose-positron emission tomography

(A) Heart tumor, H&E staining. (B) Immunohistochemical staining for CD31, heart tumor, 200× magnification.

Pathological analysis identified the tumor as a primary cardiac angiosarcoma. a Malignant cells are frankly atypical with hyperchromatic nuclei (arrow). They line poorly formed immature vessels containing red blood cells (H&E stain). b Immunohistochemical stain for CD31 (blue) revealed the endothelial nature of the tumor cells (original magnification × 200)

Primary cardiac angiosarcoma of the right atrium

Angiosarcoma of heart


8-month-old male from non-consanguineous family with no relevant prior family history. Born at term. Previously admitted twice for bronchitis at 3 and 6 months of age, with severe neutropenia during one episode that resolved without treatment. Presented with respiratory distress, fever, and fatigue. Physical examination revealed no palpable lymph nodes or tonsillar tissue, bilateral lung crackles and diminished breath sounds. Chest X-ray showed bilateral infiltrates with no pleural effusion, establishing diagnosis of acute bilateral pneumonia.

Laboratory results: complete blood count, lymphocyte subset analysis, immunoglobulin levels.

Complete blood count showed normal leukocytes (10.79 × 10⁹/L), decreased neutrophils (19.6%), increased lymphocytes (55.1%). T cells CD3+ were elevated (89.97%). CD19+ B cells were profoundly decreased (1%, 0.05 × 10⁹/L). Immunoglobulin levels were very low: IgA <10 mg/dl, IgM 12 mg/dl, IgG 135 mg/dl. CD56+CD16+ NK cells were normal (5.78%).

(A) Sanger sequencing of BTK gene, exon 6. (B) Massive parallel sequencing of BTK gene, variant p.C165Y, blood (5.4%), urine (4.6%), buccal swab (2.3%), vaginal swab (4.7%), coverage 2,454× to 107,374×.

Sanger sequencing identified hemizygous missense mutation c.494G>A/p.C165Y in exon 6 of BTK gene in the patient. Mother's Sanger sequencing showed very small adenine peaks at c.494 position in both sense and antisense strands with two different primer pairs. Massive parallel sequencing detected the BTK p.C165Y mutation in mother's samples at low frequencies: blood (5.4%), urine (4.6%), buccal swab (2.3%), and vaginal swab (4.7%) with high coverage ranging from 2,454× to 107,374×.

Flow cytometry of monocytes and B cells.

Flow cytometry showed complete absence of BTK protein expression in patient's monocytes, confirming BTK deficiency. Mother's BTK expression was within normal range in both monocytes and B cells, indicating low-level mosaicism did not significantly impact protein expression and could not be reliably detected by flow cytometry.

X-linked agammaglobulinemia (XLA) caused by BTK gene mutation c.494G>A/p.C165Y

X-linked agammaglobulinaemia