A 30-year-old male baker from South India presented with 6 weeks of low-grade fever, fatigue, and progressive polyarthritis affecting large joints of arms and legs, without small joint involvement or diurnal variation. He had no relevant medical history and denied tuberculosis contact or high-risk sexual behavior. Physical examination revealed fever (38.9°C), multiple dull red tender nodules on forehead, left cheek, and sternum, and a solitary 1x1 cm firm right cervical lymph node. Musculoskeletal examination showed active arthritis of knee, hip, and elbow joints bilaterally. The liver was palpable 4 cm below right costal margin (liver span 16 cm). Laboratory findings showed normal full blood count and erythrocyte sedimentation rate (6 mm/h protein (131 mg/L). Tests were negative for antinuclear antibodies, IgM-rheumatoid factor, anti-neutrophil cytoplasmic antibodies, antistreptolysin O, and antiDNase B antibodies. Four blood cultures were sterile, and tests for Gonococci and syphilis were negative. Serum calcium and angiotensin converting enzyme were normal.

Chest radiograph.

Chest radiograph showed bilateral upper-zone and mid-zone parenchymal infiltrates with nodular lesions, worse on the left side

Lymph node biopsy, Ziehl-Neelsen staining.

Lymph node biopsy showed large areas of necrosis rimmed by epithelioid cell granulomas with occasional Langhans' multinucleated giant cells. Ziehl-Neelsen staining was positive for acid-fast bacilli

Tuberculous lymphadenitis with Poncet's disease (tubercular rheumatism)

tuberculous lymphadenitis

Poncet's disease


A 15-year-old female with only a history of an ovarian cyst presented initially with left arm pain, frontal headaches, and conjunctival hyperaemia, without fever or neurological deficits. Seven days later, she developed acute lower back pain, paraesthesia on the left side of her body, and left arm weakness. On admission, she showed slight left-sided weakness, proximal pain of left arm and leg (worse with movement), no fever, no signs of meningism, and Glasgow Coma Score of 15. Laboratory analysis revealed elevated leucocytes (11.5 × 10⁹/L) and polymorphonuclear leucocytes (9.2 × 10⁹/L). By day 2, she developed dysuria and urinary retention, worsening left-sided hemiparesis and pain, loss of temperature sensation below T2 dermatome on left and T4 on right, and bilateral Hoffman signs. Cerebrospinal fluid examination and electromyography were normal. PCR detected high concentrations of Zika virus in serum, urine, and cerebrospinal fluid. All other viral, bacterial and autoimmune tests were negative.

MRI T2-weighted sequence of the thoracic and cervical spinal cord.

T2 sequences showed hypersignal in the thoracic cord T5-T8 and enlargement of the cervical spinal cord

Sagittal STIR MRI of the cervical spinal cord (C4–C7).

Sagittal STIR sequences showed hypersignal in the cervical spinal cord C4-C7

Acute myelitis due to Zika virus infection

acute myelitis

Zika virus infection

Certain infectious or parasitic diseases


This is a 56-year-old woman who underwent radical nephrectomy and lymph-node resection for clear-cell renal-cell carcinoma in February 2012. During subsequent follow-up, a single metastasis to the body of the left mandible was detected. She was referred in October 2012 for resection of the mandibular metastasis and fibular free-flap reconstruction. Two months later, bone scintigraphy revealed good vascularization of the flap, though additional bone metastases to the right humerus and pelvis were detected. In January 2014, the patient presented with visible bone exposure in the area of the graft with inflammation of surrounding tissues. Over days, there was an increase in bone exposure and necrosis without evidence of acute secondary infection.

(A) CT, April 2013. (B) Intraoral clinical photograph, January 2014. (C) CT, March 2014.

Occurrence of Osteonecrosis in a Patient over a Period of a Few Months. Panel A shows complete bone healing on computed tomography (CT) (April 2013). Panel B shows intraoral exposure of the bone graft (January 2014). Panel C shows bone sequestration and osteonecrosis on CT (March 2014).

Osteochemonecrosis of fibular bone graft

aseptic necrosis of bone

Diseases of the musculoskeletal system or connective tissue


A 73-year-old man presented with abdominal distention and maldigestion for 1 month. The patient had a medical history of diabetes and hypertension. On physical examination, an intraabdominal mass was palpated in the epigastric area, and the patient did not complain of pain and tenderness. Laboratory findings showed no abnormalities except an elevated fasting glucose level.

CT of the stomach, anterior wall.

Computed tomography shows an 18.0 × 15.0 cm irregular enhancing soft tissue mass with exophytic growth on the anterior wall of the stomach without regional enlarged lymph nodes

Gross photograph of the resected stomach.

Figure 2 presents gross photographs of the resected gastric specimen, revealing a multi-lobulated, yellow, soft, and fleshy mass with focal involvement of adjacent adipose tissue, consistent with a large exophytic tumor from the anterior wall of the stomach.

(A) Tumor section, H&E staining, 100× magnification. (B) Tumor section, H&E staining, 100× magnification. (C) Tumor section, H&E staining, 400× magnification. (D) Tumor section, H&E staining, 400× magnification.

Microscopic features. (A) At lower magnification, a hypercellular tumor lesion with diffuse sheet-like growth pattern is identified (H&E, ×100). (B) There are focal areas of hyalinized stroma with slit-like vessels and some capillaries (H&E, ×100). (C) At higher magnification, epithelioid tumor cells with prominent cytoplasmic vacuoles and moderately pleomorphic nuclei are identified (H&E, ×400). (D) Frequent mitotic figures (arrows) are observed (H&E, ×400).

(A) Immunohistochemical staining, 200× magnification, CD117. (B) Immunohistochemical staining, 200× magnification, CD34. (C) Immunohistochemical staining, 200× magnification, DOG1.

Immunohistochemical staining (×200). Tumor cells are negative for CD117 (A) and CD34 (B). (C) The membrane and cytoplasm of tumor cells are stained for DOG1.

C-kit negative GIST with a high risk of malignant behavior

Gastrointestinal stromal tumour of unspecified gastrointestinal sites

Malignant gastrointestinal stromal tumor

Malignant GIST - [gastrointestinal stromal tumour] of large intestine


A 52-year-old man was brought to the emergency department with acute onset shortness of breath and confusion. On physical examination, he was agitated and taking deep breaths at a rate of 28/min. Initial venous blood gas on ambient air showed pH 7.02, partial pressure of carbon dioxide 3.4 kPa, and partial pressure of oxygen 4.1 kPa. Laboratory studies revealed blood glucose 7.1 mmol/L (reference range 4.4-6.1), lactic acid 6.6 mmol/L (0.5-2.2), serum anion gap 19 mmol/L (8-16), serum osmolality 318 mmol/kg (275-295), serum osmolal gap 20 mmol/kg (<10), and acute kidney injury with creatinine 141 μmol/L (70-120). Blood ethanol was undetectable and urine drug screen was negative. Urinalysis showed haematuria and no ketones.

Light microscopy of urine sample.

Light microscopy of urine sample shows elongated crystals of calcium oxalate monohydrate

poisoning NOS

Injury, poisoning or certain other consequences of external causes


A man in his 70s with a history of coronary artery disease, hypertension, and mild aortic stenosis presented with altered mental status, acute kidney injury requiring dialysis, and painful, dusky skin discoloration on his distal extremities. Three weeks prior to presentation, he had undergone coronary angiography and coronary artery bypass graft surgery after myocardial infarction. Laboratory examination revealed a white blood cell count of 9100/μL with 22% eosinophils, blood urea nitrogen level of 70 mg/dL (25 mmol/L), and creatinine level of 6.1 mg/dL (539.2 μmol/L). Urinalysis showed 1+ blood and 2+ protein.

(A) Clinical photograph of the plantar aspect of the toes, performed three weeks after coronary angiography and coronary artery bypass graft surgery.

A: Figure 1 (A) is a clinical photograph depicting the plantar aspect of several toes of a patient, showing blue macules, patches, and papules with associated skin changes over the lower extremity; this image was taken during the physical examination in the context of recent postprocedural complications, specifically three weeks after coronary angiography and coronary artery bypass graft surgery.

Clinical photograph of the right hand, palmar surface.

Shows pink papules scattered over the palmar surface of the right hand, with painful red macules over fingertips

cholesterol embolisation syndrome

Cardiovascular and respiratory disorders


A 29-year-old intravenous drug user presented to the acute medical unit feeling generally unwell. On clinical examination, he was found to be in septic shock with a fever of 39.2°C. Blood cultures grew Staphylococcus aureus in both bottles after one day. An echocardiogram showed a large irregular mass on the tricuspid valve.

CT of the thorax.

Computed tomogram of the thorax shows multiple solid and cavitating lesions throughout both lung fields consistent with pulmonary septic emboli, along with bilateral pleural effusions and consolidation.

Infective endocarditis of the tricuspid valve with pulmonary septic emboli

infective endocarditis NOS

pulmonary embolism NOS


A previously healthy 2½-year-old boy presented with a 6-week history of progressive inability to bear weight on his right leg. His mother noted no recent trauma and reported that his medical history was notable only for speech delay. He had received all recommended vaccinations and took no medications. He had a slight cough and his mother thought he felt warm, but review of systems was otherwise unremarkable. His mother described him as a 'picky eater' with no changes in eating or drinking patterns. Initially evaluated after 1 week of limping, he continued to worsen over 4 weeks, developing pain in the left leg, began crawling instead of walking, and cried when either leg was touched. Two days before hospital presentation, his mother noted diffusely swollen gums with a black spot on the gingiva between his front teeth that bled when she attempted to wipe it away. On examination at the community hospital, he was afebrile with blood pressure 128/51 mmHg and pulse 164 beats per minute. He was an agitated toddler without spontaneous movement in the legs, with both legs diffusely tender to palpation and no evidence of bruising or joint swelling. On transfer to the university hospital, his temperature was 37.4°C, blood pressure 112/62 mmHg, and pulse 174 beats per minute. He was pale but did not appear ill, crying throughout examination. He had gingival hypertrophy with purplish discoloration of the mucosa between teeth and a diffuse petechial rash. He held his legs in a frog-legged position with diffuse tenderness, mild nonpitting edema, and no joint swelling. Tone was diminished in arms and legs, he could wiggle toes but did not actively move legs or withdraw from painful stimuli. Biceps and brachioradialis reflexes were normal, patellar reflexes were brisk, no ankle clonus, and toes went up bilaterally on plantar stimulation.

(A) Frontal radiograph of the left femur. (B) CT of the left femur, sagittal view.

A frontal radiograph of the left femur (Panel A) shows lucent metaphyseal bands (arrows) and subtle cortical thinning. A CT image in the sagittal view (Panel B) confirms the radiographic finding of submetaphyseal band (arrow). There is suggestion of subperiosteal fullness in the femoral metaphysis (arrowhead).

Axial T2-weighted fat-saturated MRI of the distal femurs.

An axial T2-weighted fat-saturated MRI at the level of the distal femurs shows bilateral elevated periosteum (arrows) and a heterogeneous subperiosteal signal, possibly representing hematoma (arrowheads).

Scurvy

Endocrine, nutritional or metabolic diseases

Vitamin C deficiency


An 80-year-old man with type 2 diabetes mellitus, peripheral arterial disease, hypertension, coronary arteriosclerosis, congestive heart failure, hyperlipidemia, and gout was admitted to this hospital because of anorexia, weight loss, abdominal pain, and diarrhea. The patient had emigrated from Southeast Asia 22 years earlier and now lived in an area of New England with his wife and daughter. His family history was negative for gastrointestinal, renal, and immunodeficiency diseases. He drank alcohol rarely and did not smoke cigarettes or use illicit drugs. On examination, he appeared thin and chronically ill. The temperature was 36.7°C, pulse 104 beats per minute, blood pressure 114/65 mm Hg, respiratory rate 16 breaths per minute, and oxygen saturation 97% while breathing ambient air. Crackles were heard in the posterior lower lung fields on auscultation. The abdomen was mildly tender, and the legs were edematous.

(A) FDG–PET scan. (B) CT scan, axial view, left upper lobe. (C) CT scan, coronal view, terminal ileum and ileocecal valve.

Positron-Emission Tomographic and CT Scans. An 18F‑fluorodeoxyglucose–positron‑emission tomographic (FDG‑PET) scan (Panel A) shows increased FDG uptake in a nodule in the left upper lobe (arrow‑head) and in the region of the ileocecal valve (arrow). A corresponding axial CT scan (Panel B) shows a 1‑cm nodule in the left upper lobe (arrowhead). A corresponding coronal CT scan (Panel C) shows wall thickening of the terminal ileum and ileocecal valve (arrow) and adjacent fat stranding, as well as an infrarenal aortic aneurysm (asterisk).

(A–E) Coronal CT scans of the abdomen obtained over a 30-month period.

Serial CT Scans Obtained over a 30-Month Period. Coronal CT scans that were obtained over a 30‑month period (Panels A through E) show persistent thickening of the terminal ileum and ileocecal valve (arrows in all panels) and adjacent fat stranding. There is high‑attenuation fluid in the retroperitoneum (Panel A, asterisk), a finding consistent with hemorrhage due to a right renal subcapsu lar hematoma (not shown). There is also an infrarenal aortic aneurysm (Panel B, asterisk), which shows endovascular repair on follow‑up images (Panels C and D).

Colonoscopy of the ileocecal valve.

Colonoscopic image shows a nonobstructive fungating mass (4 cm by 2 cm) visualized at the ileocecal valve.

Laboratory results.

Laboratory data showing progressive anemia with hemoglobin decreasing from 12.9 g/dl to 8.8 g/dl over time, elevated white-cell count on admission of 11,460 per mm³ with neutrophilia (82.7%), consistently elevated erythrocyte sedimentation rate (65-96 mm/hr), elevated C-reactive protein (52.5-220.6 mg/liter), elevated creatinine (4.13-8.09 mg/dl) consistent with end-stage renal disease, and positive enzyme-linked immunospot test for cell-mediated immune response to Mycobacterium tuberculosis (interferon-γ release assay).

Tuberculous enteritis


A 79-year-old man with a history of hypertension, stroke, and glaucoma was brought to the emergency department after being found unresponsive by a caregiver. He was cold to the touch with vital signs showing blood pressure of 85/55 mm Hg, heart rate of 36/min, respiratory rate of 14/min, and pulse oximetry of 100% on ambient air. Multiple temperature measurements, including core temperature assessment via rectal method, did not yield a detectable temperature. Physical examination revealed clear bilateral chest auscultation. Chest radiographs and computed tomography of the head were negative for any acute pathology.

Electrocardiogram at presentation.

Initial electrocardiogram on presentation showing severe sinus bradycardia with attenuated P waves and classic Osborn waves pathognomonic of hypothermia

ECG, lead V3.

Osborn wave best seen in lead V3, characterized by a 'delta' or 'camel's hump' elevation in the terminal portion of the QRS deflection

Hypothermia


12-year-old Saudi boy presented with severe spontaneous dental pain for 3 days. He was the fourth of five siblings. Parents were not related. His mother had 5 previous spontaneous abortions in first trimester. Mother took acetazolamide 1000mg/day for idiopathic intracranial hypertension before and throughout pregnancy. Patient was born at full term via spontaneous vaginal delivery, weighing 2,270g (below 5th percentile). He presented without major dysmorphic features, was intelligent with good behavior, and had normal skin, hair and nails. Intraoral exam showed mixed dentition with retained primary lower central incisors, hypocalcified permanent upper incisors, and multiple carious teeth. Tongue, floor of mouth, upper lip, hard and soft palate were normal.

Clinical photograph of both hands.

A: Clinical photograph showing ectrodactyly of the index and middle fingers in both hands.

Clinical photograph of the feet.

B: Clinical photograph of the feet showing syndactyly between the third and fourth toes of the left foot, as well as ectrodactyly of the second toe and a deformed second toe of the right foot with a surgical scar.

Panoramic radiograph of the jaws.

Panoramic radiograph shows oligodontia of 16 permanent teeth

Isolated ectrodactyly with possible teratogenic cause, as diagnosed by genetic consultant after normal skeletal survey, chromosomal study, abdominal ultrasound and cardiology evaluation

ectrodactyly


A 62-year-old woman presented with a 10-day history of left-sided headache. Two days after headache onset, she developed a painful and pruritic left-sided rash. In the 24 hours before presentation, her left eye became painful and photophobic. On examination, she had discrete tender scabbed lesions extending into the hairline. No lesions were present on the tip of her nose or auditory canal. Ocular examination revealed unaided visual acuity of 6/6 in the right eye and 6/9 in the left eye, with full ocular motility. Intraocular pressures were 10 mm Hg (right) and 12 mm Hg (left). The left cornea was clear without fluorescein staining. Slit lamp examination showed 1+ cells and flare in the left anterior chamber. Dilated funduscopy showed a clear vitreous and healthy fundus. Right ocular examination was normal.

Clinical photograph of the face.

Figure 1 is a clinical photograph showing the patient's face with left-sided scabbed skin lesions that respect the midline, associated with swelling of the left upper eyelid and conjunctival injection. The image documents the dermatological manifestation over the upper lid and forehead, extending into the hairline, and visually demonstrates the unilateral distribution without crossing to the contralateral side, which is consistent with the ophthalmic dermatome (V1) involvement on presentation.

Left herpes zoster ophthalmicus (HZO) with associated anterior uveitis

Herpes zoster ophthalmicus

Anterior uveitis


A 22-year-old male patient with known Crohn's disease presented to the emergency room with massive hematochezia and hypovolemic shock. He was severely malnourished with a BMI of 17.8 kg/m2. Initial laboratory findings showed WBC count 22,850/µL, hemoglobin 8.8 g/dL, platelets 157,000/µL, CRP 0.03 mg/dL, protein 3.0 g/dL, albumin 1.8 g/dL, triglyceride 73 mg/dL, cholesterol 119 mg/dL, BUN 6 mg/dL, creatinine 1.09 mg/dL, and prothrombin time/international normalized ratio 20.6 s (1.78). After a period of treatment and fasting, he developed progressive blurred vision, cognitive dysfunction, intermittent confused speech, dizziness, and experienced a brief generalized tonic-clonic seizure lasting 10 minutes. Neurologic examination found slight latent nystagmus in the lateral gaze.

(A) Abdominal CT, horizontal section, ileocecal valve and terminal ileum. (B) Abdominal CT, horizontal section, small bowel. (C) Abdominal CT, coronal view, right perianal area. (D) Abdominal CT, coronal view, small bowel.

Abdominal CT findings. (A) In the horizontal section, CD involvement of the ileocecal valve and terminal ileum is seen. (B) In the horizontal section, multisegmental small bowel wall thickening is found. (C) In the coronal view, a rim-enhancing low-density lesion in the right-side perianal area is seen. (D) In the coronal view, multifocal small bowel wall thickening is also noticed.

(A) Brain MRI, horizontal section, T2-weighted image, mammillary body region. (B) Brain MRI, horizontal section, T2-weighted image, tectum region. (C) Brain MRI, horizontal section, T2-weighted image, 4th ventricle floor. (D) Brain MRI, T2-weighted image, medial thalamus.

Brain MRI findings. (A) In the horizontal section of a T2-weighed image (T2WI), a high signal intensity lesion is seen at both the right and left sides of the mammillary body. (B) In same scene of the T2WI, a high signal intensity lesion is present at both the right and left tectum. (C) In the horizontal section of the T2WI, the 4th ventricle floor showing a high signal intensity lesion. (D) At the medial thalamus, a high signal intensity lesion is noted.

Wernicke's encephalopathy in a patient with Crohn's disease

Wernicke encephalopathy

Crohn disease


25-year-old previously healthy European woman who lived and worked as a volunteer in Natal, Brazil. At 13 weeks gestation, she developed high fever followed by severe musculoskeletal pain, retroocular pain, and itching generalized maculopapular rash. Reduced fetal movements noticed at 28 weeks gestation. Physical exam showed only microcephaly as external anomaly. Fetal body weight was 1470g (5th percentile), length 42cm (10th percentile), head circumference 26cm (1st percentile).

Ultrasonography at 32 weeks, brain and placenta.

Ultrasonography at 32 weeks showed numerous calcifications in brain and placenta, dilated occipital horn of lateral ventricle

(C) Gross photograph of fetal brain, coronal slice, autopsy. (D) Gross photograph of fetal brain, coronal slice, autopsy.

C: This panel presents a gross photograph of a coronal slice of fetal brain obtained at autopsy, showing multifocal cortical and subcortical white matter calcifications and almost complete absence of cortical gyration, with poorly delineated but developed basal ganglia and widely open sylvian fissures bilaterally; the third ventricle is not dilated. D: This panel shows another gross brain coronal slice demonstrating markedly dilated bodies of the lateral ventricles (with the left side collapsed), dilated temporal horns, well-developed thalami and left hippocampus, while the contralateral hippocampal structure is unrecognizable due to autolysis. (Source: Figure 1, panels C and D, page 3, with caption for technical context on acquisition.)

(A) Brain tissue, H&E staining, low magnification. (B) Brain tissue, H&E staining, higher magnification. (C) Brain tissue, immunohistochemistry for glial fibrillary acid protein (clone 6F2 [Dako]). (D) Brain tissue, immunohistochemistry for HLA-DR (clone TAL 1B5 [Dako]). (E) Lumbar spinal cord, neurofilament immunohistochemical staining (clone 2F11 [Dako]), cross-section. (F) Fetal brain tissue, indirect immunofluorescence.

Microscopic Analysis of Brain Tissue. Panel A shows thickened leptomeninges (black arrowhead) and irregular cortical and subcortical calcifications (asterisks) associated with cortical displacement (arrows), with preserved germinative matrix (white arrowhead); gyration is absent. Panel B shows higher magnification of calcifications with filamentous structures (arrow), possibly representing encrusted, damaged axons and dendrites, and oval and polygonal structures (arrowheads), possibly representing encrusted, damaged neuronal-cell bodies (hematoxylin and eosin staining in Panels A and B). Panel C shows immunohistochemical labeling of proliferated reactive astrocytes that extend into the subarachnoid space (asterisk) (glial fibrillary acid protein, clone 6F2 [Dako]). Panel D shows immunohistochemical labeling of numerous activated microglial cells and macrophages in the cortex (full thickness marked with a line) and subcortical white matter (lower part of the figure). Nonspecific staining of the calcifications is present (arrow). Focal leptomeningeal infiltrates of macrophages are seen (arrowhead) (HLA-DR, clone TAL 1B5 [Dako]). Panel E shows neurofilament immunohistochemical staining of axons in a cross-section of the lumbar spinal cord with severe Wallerian degeneration of the lateral corticospinal tracts (black asterisks), moderate involvement of other descending tracts (arrows), and well-preserved ascending tracts in the dorsal columns (white asterisk) (neurofilament, clone 2F11 [Dako]). Panel F shows indirect immunofluorescence of fetal brain tissue, revealing a green granular intracytoplasmic reaction (see also inset). The yellow signals adjacent to the green granules indicate auto- fluorescence of lipofuscin, suggesting that viral particles are located in the cytoplasm of neurons.

(A) Electron microscopy of ultrathin section of fetal brain. (B) Electron microscopy of ultrathin section of fetal brain, magnified view. (C) Electron microscopy of ultrathin section of fetal brain. (D) Electron microscopy, negative staining.

Electron Microscopy of Ultrathin Sections of Fetal Brain and Staining of a Flavivirus-like Particle. Panel A shows a damaged brain cell with a cluster of dense virions located in the disrupted endoplasmic reticulum. Remains of membranes derived from different cellular compartments and filamentous structures are also seen. A magnified view of the boxed area with virions clearly visible (arrows) is shown in Panel B. Panel C shows a group of enveloped structures with a bright interior, presumably indicating viral replication (arrow). Panel D shows a negatively stained viral particle with morphologic characteristics consistent with those of Flaviviridae viruses (arrow).

Vertical transmission of Zika virus infection causing severe fetal brain injury and microcephaly

Congenital Zika virus infection

Certain conditions originating in the perinatal period

brain haemorrhage in fetus or newborn due to birth injury

Microcephaly


A 65-year-old man with a history of hypertension and laminectomy presented for evaluation. He had never smoked. His family history was notable for prostate cancer in his father. His prostate-specific antigen and digital rectal examination results were normal.

Urine dipstick test.

Urine dipstick results showed: negative for glucose, protein, ketones, nitrite, leukocytes, and bilirubin; trace blood; specific gravity 1.015; pH 7.5; urobilinogen 1 EU/dL; clear yellow appearance

False positive dipstick hematuria (confirmed by subsequent negative microscopic urinalysis showing absence of RBCs)

Haematuria

Symptoms, signs or clinical findings, not elsewhere classified


24-year-old male with quadriplegia from a car accident 5 years prior that required cervical spine stabilization with metal plates. Presented with dysphagia, odynophagia, neck pain, fever, and chills. Medical history significant for quadriplegia requiring cervical spine stabilization with metal plates. CT and MRI showed large paraspinal abscess extending from cervical spine 4 to thoracic spine 11.

(A) Endoscopy of the posterior pharyngeal wall and anterior cervical spine. (B) Oesophagram of the region of the upper oesophageal sphincter.

(A) Endoscopy showed a destroyed posterior pharyngeal wall, with the anterior cervical spine metal plate eroding into the pharynx (arrow). (B) An oesophagram showed substantial leakage into the mediastinum past the region of the upper oesophageal sphincter. No distinct upper oesophageal structure could be identifi ed.

(A) Endoscopic image of the hypopharynx at the level of the upper oesophageal sphincter. (B) Endoscopic image of the mediastinum. (C) Endoscopic image using an ultrathin endoscope retrogradely advanced via the gastro-oesophageal junction through the mediastinum into the oral cavity. (D) Endoscopic placement of serially aligned, telescoped self-expanding metal stents (18 mm diameter) across the mediastinal cavity. (E) Endoscopic image showing upper end of the proximal stent at the level of the interarytenoid folds.

Figure 2 consists of a series of endoscopic images depicting the disrupted oesophagus and the process of stent placement. A: Endoscopic image at the hypopharynx at the level of the upper oesophageal sphincter (UOS) shows pus within the mediastinal cavity, indicating disruption of the oesophageal wall. B: On entering the mediastinum, copious pus is observed and no oesophageal structure is identifiable. C: After failed attempts to access the remnant oesophagus, an ultrathin endoscope is retrogradely advanced via the gastro-oesophageal junction into the remnant oesophagus, through the mediastinum, and into the oral cavity, demonstrating the continuity of the disrupted luminal path. D: Serially aligned, telescoped self-expanding metal stents (18 mm diameter) are positioned endoscopically across the mediastinal cavity to bridge the defect, with the lower end placed in the remnant oesophagus. E: The upper end of the proximal stent is precisely positioned at the level of the interarytenoid folds to avoid interference with the movements of the epiglottis during swallowing, with the vocal cords monitored for potential compression during stent expansion. These images collectively document the endoscopic and procedural details of the management of a full-thickness oesophageal defect with copious mediastinal pus and the technical aspects of self-expanding metal stent placement at the hypopharyngo-oesophageal junction and mediastinum.

Full-thickness oesophageal segment destruction (5 cm) by mediastinal abscess leading to direct communication between hypopharynx and mediastinum

Abscess of mediastinum

disorder of oesophagus

Perforation of oesophagus


57-year-old postmenopausal woman presented with progressive low abdominal pain and urinary frequency for 4 months duration. No significant gynecological, medical, surgical, or family history. No bowel complaints. Physical examination revealed an enlarged, relatively nodular pelvic mass.

(A) Pelvic MRI, axial view, T2-weighted sequence. (B) Pelvic MRI, contrast-enhanced fat-suppressed T1-weighted sequence. (C) Pelvic MRI, sagittal view, T2-weighted sequence. (D) Pelvic MRI, coronal view, T2-weighted sequence.

Pelvic magnetic resonance image of the pedunculated subserosal leiomyosarcoma of the uterus. a Axial T2 - weighted image showing a large pelvic mass (arrows) with heterogeneous signal intensity. b Contrast - enhanced fat - suppressed T1 - weighted image showing marked heterogeneous enhancement (arrow) of the mass. c, d On sagittal (c) and coronal (d) T2 - weighted images, the mass (arrows) abutted the uterus (U). Note the bridging vessels (arrowheads) between the uterus and the juxta - uterine mass.

(A) Gross specimen of the uterus, pedunculated subserosal mass. (B) Gross cut section of the uterus and tumor.

(a) Gross appearance of pedunculated subserosal leiomyosarcoma of the uterus. The mass was bilobed rather than bilateral. Both ovaries were normal in appearance. (b) Cut section of the uterus and tumor

Microscopic examination, mitotic activity ≥28/10 high-power fields.

Microscopic examination showed highly atypical spindle cells with brisk mitotic activity (≥28/10 high-power fields) and necrosis

(A) Immunohistochemistry for SMA, 400× magnification. (B) Immunohistochemistry for desmin, 400× magnification. (C) Immunohistochemistry for h-caldesmon, 400× magnification.

Immunohistochemistry revealed diffuse strong positivity for SMA (a), desmin (b), and h-caldesmon (c) (×400). SMA: smooth muscle actin

Pedunculated subserosal leiomyosarcoma of the uterus

Leiomyosarcoma of uterus


A 57-year-old man presented to the emergency department with a 12-hour history of hematuria. Several hours after intravenous urography was performed with iodinated contrast material, generalized pustular eruptions developed, with multiple coalescing vesicles and pus-filled bullae observed on the trunk, arms, and legs. Laboratory studies revealed neutrophilia and mild eosinophilia with 55% neutrophils and 8% eosinophils, and a white-cell count of 6500 per cubic millimeter. Histopathological examination of the lesions showed pseudoepitheliomatous hyperplasia, full-thickness epidermal necrosis, and a diffuse neutrophilic dermal infiltrate. Microbiologic studies were negative.

Clinical photograph of the face.

A: Clinical photograph showing multiple coalescing vesicles and pus-filled bullae on the patient’s face following intravenous administration of iodinated contrast material, indicative of a generalized pustular eruption associated with iododerma.

Clinical photograph of the ear.

Shows generalized pustular eruptions with multiple coalescing vesicles and pus-filled bullae on the patient's ear

Iododerma


A 9-year-old female presented in May 2013 with a 3-month history of occasional seizure-like movements in the early morning and 6-month history of dizziness and difficulty waking up in the morning, with symptoms disappearing after eating. She had gained 10 kg in the previous year due to increased eating. On the day of hospital visit, she experienced a generalized tonic-clonic seizure lasting 5 minutes in the early morning. She also complained of dizziness, occasional palpitation, weakness, hunger, and sweating. Physical examination revealed a well-nourished girl with normal vital signs, weighing 41 kg with BMI of 22.5 kg/m². Her abdomen was soft and non-tender without palpable masses or organomegaly, and neurologic examinations were normal. Laboratory evaluation showed severe hypoglycemia with serum glucose of 34 mg/dL, markedly elevated insulin of 142.7 μIU/mL, and elevated C-peptide of 5.88 ng/mL. Other endocrine markers were within normal ranges: serum PTH 15 pg/mL (normal 11-62), serum IGF-1 298 ng/mL (normal 78-517), serum prolactin 7.5 ng/mL (normal 2.7-19.7), and serum calcium 9.3 mg/dL (normal 8.8-10.8). She was not taking any prescription medications at the time of evaluation.

(A) MRI of the pancreas, T1-weighted sequence, mass measuring 1.3 × 1.5 cm. (B) MRI of the pancreas, T2-weighted sequence, head region.

MR study of the pancreas. (A) A mass with hyposignal intensity on T1 weighted images, 1.3 × 1.5 cm. (B) High signal intensity on T2 weighted images at the head of the pancreas.

Genetic analysis of MEN1 gene, exon 8, c.1121_1126delACCTGCinsGGGGA.

Pedigree analysis showed familial MEN1 mutation (c.1121_1126delACCTGCinsGGGGA) found in the patient, patient's father, and younger sister. DNA sequencing analysis confirmed the heterozygous mutation in exon 8 of the MEN1 gene.

Multiple Endocrine Neoplasia Type 1 (MEN1) presenting as hypoglycemia due to insulinoma

Multiple endocrine neoplasia type 1

hypoglycaemia NOS

Insulinoma


A 47-year-old man with a history of hypertension presented to an urgent care clinic with a 3-day history of swelling around his left eye and a sensation of tightness in his throat. He reported hoarseness but no pruritus, photophobia, diplopia, headache, changes in visual acuity, or pain. He had no wheezing or shortness of breath but experienced difficulty swallowing solids with a sensation of food sticking in his throat. He denied fevers, fatigue, gastrointestinal symptoms, or recent illness. On examination, his vital signs showed temperature 37.3°C, heart rate 95 beats per minute, blood pressure 130/80 mmHg, respiratory rate 18 breaths per minute, and oxygen saturation 100% on room air. He appeared comfortable, speaking in full sentences with a hoarse, muffled voice. Physical findings included edema surrounding the entire left eye with faint erythema, no ptosis, intact extraocular movements, equal and reactive pupils, and a mildly and diffusely enlarged tongue. Lungs were clear with no stridor. Two weeks later, he developed additional symptoms including worsening dysphonia, increased throat swelling sensation, nasal regurgitation of liquids, shoulder and hip pain, and loss of ability to jump while playing basketball. Re-examination revealed tenderness over anterior and lateral neck musculature, subcutaneous edema in both upper arms, normal arm strength (5/5), but reduced hip strength (4/5) and difficulty rising from seated position. Laboratory studies showed normal thyrotropin (0.708 mIU/L), elevated liver enzymes (ALT 298 U/L, AST 857 U/L), markedly elevated creatine kinase (33,950 U/L), mildly elevated inflammatory markers (ESR 16 mm/hr, CRP 24.1 mg/L), and positive antinuclear antibodies (1:160) with negative myositis-specific antibody panel including anti-Jo-1. Muscle biopsy from the left deltoid showed mild fiber size variability without perifascicular atrophy, inflammatory infiltrate around epimysial blood vessels, positive MHC class I staining with patchy distribution on nonnecrotic fibers.

Clinical photograph of the left periorbital region.

Periorbital swelling and discoloration showing violaceous discoloration and swelling in the left periorbital region

(A) Transverse imaging of the head. (B) Coronal imaging of the neck.

Transverse images of the head (Panel A) and coronal images of the neck (Panel B) reveal increased focal signaling that is consistent with edema in multiple muscles.

Muscle biopsy, membrane-attack complex (MAC) staining.

Muscle biopsy specimen shows membrane-attack complex (MAC) deposition on the endothelium of capillaries, resulting from complement cascade activation

Dermatomyositis

Orthopedic and connective tissue disorders


A 12-year-old boy presented with a 1-month history of malaise, fevers, abdominal pain, and worsening pallor. His symptoms began with headache and abdominal pain, with an initial temperature of 38.6°C and pale skin. He experienced persistent upper abdominal pain and recurrent fevers. The patient reported nausea, occasional diarrhea, headache, myalgias, fatigue, and occasional dizziness. He described nearly constant periumbilical pain radiating to the left lower quadrant, with occasional blood in stools. His height was 132 cm (1st percentile), weight 26.8 kg (1st percentile), with recent 1 kg weight loss. Physical examination revealed pale skin and mucosa, distended abdomen with mild tenderness in right upper and left lower quadrants, and ecchymoses on the shins. He had visited the Dominican Republic 3 months prior. Laboratory tests showed severe microcytic anemia (hemoglobin 6.7 g/dL), elevated inflammatory markers (ESR >140 mm/hr, CRP 143.2 mg/liter), and elevated ferritin (320 μg/L).

Abdominal radiograph.

Abdominal radiograph showed moderate amount of fecal matter in the colon without dilated bowel loops, free air, or skeletal abnormality

Ultrasound of the abdomen.

Ultrasound revealed multiple enlarged retroperitoneal and mesenteric lymph nodes, thick-walled small-bowel loops, a 2-cm hypoechoic liver lesion, and mild right kidney hydronephrosis

(B) CT, coronal reformatted image, chest, abdomen, and pelvis. (C) CT, axial image, abdomen.

A coronal reformatted CT image (Panel B) shows extensive lymphadenopathy in the chest, abdomen, and pelvis (arrowheads) and a hypodense lesion in the liver (arrow). An axial CT image (Panel C) shows retroperitoneal lymphadenopathy (arrows), thick‑walled small‑bowel loops (arrowheads), and a solitary right kidney.

PET-CT, chest, abdomen, and pelvis.

PET-CT demonstrated extensive FDG-avid lymphadenopathy in chest, abdomen, and pelvis, with intense uptake in thick-walled small bowel loops and right liver

(A,B) Lymph node biopsy, H&E staining, (B) higher magnification. (C) Immunohistochemical staining for CD30. (D) Immunohistochemical staining for CD15. (E) Immunohistochemical staining for PAX5. (F) In situ hybridization for Epstein–Barr virus–encoded RNA.

Retroperitoneal Lymph Node–Biopsy Specimen. Hematoxylin and eosin staining of the lymph node–biopsy specimen (Panels A and B) shows that the tissue is replaced by a mixed cellular infiltrate containing eosinophils, lymphocytes, histiocytes, and scattered large cells (Panel A), which are seen better at higher magnification (Panel B, arrows). Immunohistochemical staining of the large cells shows strong staining for CD30 (Panel C), weak granular staining for CD15 (Panel D), and faint nuclear staining for PAX5 (Panel E); in situ hybridization with the use of Epstein–Barr virus–encoded RNA shows strong nuclear staining (Panel F). Admixed granulocytes show strong staining for CD15 (Panel D), and B lymphocytes show strong staining for PAX5 (Panel E).

Mixed-cellularity subtype of classic Hodgkin's lymphoma and Epstein-Barr virus infection

Mixed cellularity classical Hodgkin lymphoma

Epstein-Barr virus infection NOS


A 65-year-old Haitian man with end-stage renal disease requiring hemodialysis presented with a leg injury and diffuse pruritic rash. His medical history included hypertension, bicuspid aortic valve, ascending and aortic-root aneurysm, and a positive tuberculin skin test 13 years prior with negative chest radiograph. He had secondary syphilis 11 years ago treated with penicillin, and recent HTLV-1 positive testing. He experienced 12 kg unintentional weight loss over 2 years. On examination, he had wrinkling of axillary plaques present bilaterally. Multiple thin, brown macules and patches with collarette of scale were present on palms and some on soles. He had bilateral inguinal lymphadenopathy.

Laboratory results.

Laboratory findings showed mild anemia (Hct 33.9%, Hb 10.8 g/dL), leukocytosis (13,800/mm3), elevated BUN (45 mg/dL) and creatinine (8.16 mg/dL), positive RPR at 1:1 dilution, positive treponemal antibody test, positive HTLV-1 antibody test, and elevated ferritin (1351 ng/mL)

(A) Clinical photograph of the neck, arms, wrists, and hands at initial evaluation. (B) Clinical photograph of the thighs, legs, and feet at initial evaluation. (C) Clinical photograph of the bilateral axillae at initial evaluation.

On initial evaluation, the patient had diffuse large, brown papules that coalesced into polygonal plaques, and he had a powdery, thick scale on the neck, arms, wrists, and hands (Panel A), as well as on the thighs, legs, and feet (Panel B). The bilateral axillae had scaly gray‑to‑brown plaques overlying slack skin (Panel C). The photographs are courtesy of Dr. Daniel Sugai.

(A) Biopsy specimen of the right anterior forearm, superficial dermis and epidermis, no staining method or magnification specified. (B) Biopsy specimen of the right anterior forearm, no staining method or magnification specified.

A 3‑mm biopsy specimen of a lesion on the right anterior forearm was obtained. Monomorphic clusters of atypical lymphoid cells involving the superficial dermis and epidermis (Pautrier’s microabscesses) are shown (Panel A). The cells are small to medium‑sized and have irregular nuclear contours, clumped chromatin, small nucleoli, and eosinophilic cytoplasm (Panel B).

(A) Immunohistochemical staining for CD3. (B) Immunohistochemical staining for CD4. (C) Immunohistochemical staining for CD30. (D) Immunohistochemical staining for CD8. (E) Immunohistochemical staining for CD2. (F) Immunohistochemical staining for CD25.

The atypical lymphoid cells were positive for CD3 (Panel A) and CD4 (Panel B), negative for CD30 (Panel C) and CD8 (Panel D), faintly positive for CD2 (Panel E), and positive for CD25 (Panel F).

adult t cell leukaemia lymphoma


A 28-year-old woman of Jewish descent with a history of sickle β-thalassaemia disorder presented with a 2-week history of frank haematuria. She had been taking paracetamol daily for persistent headaches. On examination, she was pale and tachycardic with a palpable spleen. Laboratory findings showed hemoglobin of 60 g/L and creatinine of 97 μmol/L.

Intravenous urogram.

Intravenous urogram revealed: laterally displaced distal ureters, pyelotubular reflux (backflow of contrast from renal calyces), displacement and compression of the left kidney inferiorly, coarsening of bone trabeculations throughout the pelvic girdle and spine, and gallstones. Additional findings included splenomegaly and uterine fibroids.

Sickle β-thalassaemia with acute renal papillary necrosis secondary to chronic anemia and paracetamol use

sickle-cell thalassaemia

Diseases of the blood or blood-forming organs

Acute renal papillary necrosis

chronic anaemia


A 33-year-old bisexual Brazilian man presented with a 4-month history of painful bowel movements and rectal bleeding. He had one bowel movement daily with bright red blood on toilet paper but not mixed in stool. He had no abdominal pain or weight loss. He reported a sexual encounter with a man approximately 6 weeks before initial presentation. Physical examination showed a tender external hemorrhoid initially, with vital signs normal. Tests were negative for hepatitis B surface antigen and antibodies to hepatitis B virus, hepatitis C virus, and HIV. At follow-up examination 10 weeks later, bleeding hemorrhoids were noted around the anal opening. In the surgery clinic, examination revealed large superficial anal fissures at the anterior and posterior midline anal verge with small-to-moderate distal sentinel skin tags. Digital rectal examination showed moderate tenderness. Anoscopy revealed fissures and small internal hemorrhoids. Flexible sigmoidoscopy showed mild-to-moderate mucosal inflammation of the distal 10 cm of rectum with edema and patchy erythema.

(A,B) Sigmoid colon biopsy, H&E staining. (C) Sigmoid colon biopsy, H&E staining. (D) Sigmoid colon biopsy, immunohistochemical staining.

Biopsy specimens of sigmoid colon showed: (A,B) Colonic mucosa with surface erosion, separation of colonic crypts by lymphohistiocytic infiltrate, and lymphoid hyperplasia; (C) Regenerative colonic crypts with crypt-cell apoptosis, numerous histiocytes expanding the lamina propria, and acute inflammation; (D) Immunohistochemical stain revealed numerous spirochetes in the lamina propria

proctitis NOS


A 66-year-old man presented with a 2-day history of fevers, lethargy, polyarticular arthralgias, and a painful rash. His medical history included hypertension, poorly controlled type 2 diabetes, hypercholesterolemia, and biopsy-proven autoimmune hepatitis. He had started azathioprine 75 mg 10 days prior after normal thiopurine methyltransferase activity was confirmed. Other medications included aspirin, metformin, verapamil, and pravastatin. On examination, he had a temperature of 38°C, and bilaterally tender knees with a patellar tap. Laboratory findings showed WBC 10,500/μL (neutrophils 9900/μL [94%]), CRP 76 mg/L, ESR 69 mm/h, slightly elevated rheumatoid factor at 16 IU/mL, negative anti-CCP antibody, negative tests for double-stranded DNA, extractable nuclear antibodies, and anti-ASO. Renal function was normal, with no abnormalities in urinalysis. Chest radiograph was normal. Synovial fluid analysis showed noninflammatory picture with leukocyte count of 700 cells/L, with no bacteria or crystals seen.

(A) Clinical photograph of the lower extremity. (B) Clinical photograph of the upper extremity.

Figure 1 presents clinical photographs showing tender erythematous papulonodular lesions on the extensor surfaces of the lower extremity (left image) and upper extremity (right image) of a patient, demonstrating the cutaneous manifestations observed at presentation; these are standard gross clinical images depicting the distribution and morphology of the skin lesions without magnification or specific staining.

Erythema nodosum


A 24-year-old woman with no significant medical history presented to the emergency department with left leg pain. She had been training for a 5-km race when, 2 days before presentation, she experienced crampy pain in her left leg extending to the left lower abdomen and buttock, along with generalized leg swelling and exertional dyspnea. She denied fever, chest pain, dyspnea at rest, or antecedent trauma. Her vital signs showed pulse of 102 beats per minute with other vitals normal. Physical examination revealed pitting edema and erythema in the left leg from thigh to calf with increased warmth. Her medical history included oral contraceptive use since age 15, previous smoking history of 3 cigarettes per day (quit 2 years prior), and family history of DVT in her father after knee surgery. Laboratory results showed white blood cell count 12,000/mm3 with normal differential, hemoglobin 12.4 g/dL, platelet count 269,000/mm3, prothrombin time 11.4 seconds, INR 1.05, and partial-thromboplastin time 27.0 seconds. Levels of troponin T and N-terminal pro-BNP were normal.

CT angiography of the chest.

CT angiography of the chest revealed multiple pulmonary emboli in the pulmonary arteries in the left lower lobe and right lower lobe, and a small wedge-shaped infarction at the left lung base

CT scan of the abdomen and pelvis.

CT scan of abdomen and pelvis showed deep-vein thrombosis in the left common, external, and internal iliac veins extending into the common femoral vein

May-Thurner syndrome (iliac vein compression syndrome) with associated deep vein thrombosis and pulmonary embolism

THE - [tricho-hepato-enteric] syndrome

Deep vein thrombosis

pulmonary embolism NOS


A 55-year-old Japanese woman with malignant melanoma was receiving nivolumab (2 mg/kg, once every 3 weeks) for 12 months when she was referred for hyperglycemia. She had no history of diabetes and no evidence of pancreatic metastases. Blood glucose levels had been normal until 3 weeks before referral. She had previously received 1 year of chemotherapy with dacarbazine, nimustine, cisplatin and tamoxifen before starting nivolumab. She had no blood examination findings or symptoms suggesting acute viral infection before onset. Physical examination revealed mild pancreatic atrophy on computed tomography and endoscopic ultrasonography showed hyperechoic foci and strands, lobularity, and cysts consistent with early chronic pancreatitis changes, though she had no history of alcohol use.

Laboratory results and time-series serum C-peptide levels (days 0, 2, 7, and 17).

Laboratory results showed glucagon 134 pg/mL (normal 70-174), amylase 36 U/L (normal 37-125), elastase1 93 ng/dL (normal <300), lipase 31 IU/L (normal 11-53), thyroid-stimulating hormone receptor antibody <1.0 IU/L (normal <2.0), thyroglobulin antibody 10.9 IU/mL (normal <28), thyroid peroxidase antibody 5.9 IU/mL (normal <16), negative antipituitary antibody, negative antinuclear antibody. Time-series serum C-peptide levels (normal 0.61-2.09 ng/mL) showed progressive decline: Day 0: 1.0 ng/mL, Day 2: 0.7 ng/mL, Day 7: 0.3 ng/mL, Day 17: <0.1 ng/mL.

Laboratory results (urine ketones, blood glucose, HbA1c, C-peptide, islet cell autoantibodies, HLA typing).

Case 1 in Table 2 summarizes a 55-year-old Japanese female with malignant melanoma and pertinent history of dyslipidemia and gastric ulcer, who developed abrupt-onset ketonuria and marked hyperglycemia (580 mg/dL, HbA1c 7.0%, C-peptide 1.0 ng/dL with simultaneous glucose 580 mg/dL) 12 months after commencing nivolumab therapy (also receiving dacarbazine, nimustine, cisplatin, and tamoxifen without preceding viral infection); all islet cell autoantibodies (GAD, ICA, IA-2, ZnT8) were negative, and HLA typing revealed DRB1*04:05 and DQB1*04:01 alleles.

Fulminant type 1 diabetes mellitus


A 65-year-old man presented to his general practitioner with a three-day history of bright red, painless macroscopic haematuria and was found to have acute kidney injury with a raised serum creatinine of 461 μmol/L (reference range 60-105) and estimated glomerular filtration rate of 11 mL/min/1.73 m². His baseline serum creatinine had been stable around 120 μmol/L for five years until one month earlier when he had an episode of acute kidney injury during hospitalization for cellulitis of the right leg, after which his serum creatinine had remained raised at 252 μmol/L. He denied recent respiratory infections, weight loss, night sweats, lethargy, or previous haematuria. His medical history included hypertension, type 2 diabetes, chronic kidney disease stage 3, coronary artery bypass grafting, atrial fibrillation, ischaemic stroke, benign prostatic hypertrophy, and tobacco use. His regular medications included digoxin 125 μg, atorvastatin 80 mg, tamsulosin 400 μg, metoprolol 95 mg, aspirin 100 mg, and warfarin, all once daily. On physical examination his blood pressure was 116/70 mm Hg and he had mild pedal oedema. Urine analysis showed gross haematuria and proteinuria with protein:creatinine ratio of 51.2 mg/mmol (reference <23). His international normalised ratio (INR) was markedly raised at 5.7.

(A) Kidney biopsy, light microscopy, Jones’s methenamine silver staining. (B) Kidney biopsy, light microscopy, trichrome staining. (C) Kidney biopsy, direct immunofluorescence for IgA. (D) Kidney biopsy, direct immunofluorescence for C3.

Light microscopy of kidney biopsy stained with Jones’s methenamine silver (A) and trichrome (B). Direct immunofluorescence of kidney biopsy for IgA (C) and C3 (D)

Kidney biopsy, light microscopy, Trichrome stain.

Light microscopy of kidney biopsy with Trichrome stain showing numerous red cell casts obstructing the tubular lumina and a glomerulus containing red blood cells in Bowman's space.

Kidney biopsy, light microscopy, silver stain.

Light microscopy of kidney biopsy with silver stain showing a glomerulus with diffuse mesangial proliferation.

(A) Direct immunofluorescence of the kidney, 400× magnification, IgA staining, positivity 4+ on a semi-quantitative scale (0–5+). (B) Direct immunofluorescence of the kidney, 400× magnification, C3 staining, positivity 2–3+ on a semi-quantitative scale (0–5+).

Direct immunofluorescence (original magnification ×400) showing (A) IgA positivity (4+) (on a semi-quantitative visual scale ranging from 0 to 5+) within the mesangium and along some capillary loops, and (B) C3 positivity (2-3+) mainly within the mesangium

Chronic IgA nephropathy with acute glomerular haematuria, probably precipitated by excessive anticoagulation with warfarin causing acute anticoagulant nephropathy

IgA nephropathy

Recurrent or persistent glomerular haematuria

Nephropathy NOS


A 32-year-old woman presented with a 2-week history of back and loin pain, heaviness in thighs, intermittent fever and rigors. Her medical history included trigeminal neuralgia and pervasive anxiety, for which she had recently started quetiapine. On examination, her temperature was 39°C with no other abnormal physical findings. Initial blood tests showed elevated C-reactive protein (118 mg/L), with normal blood count and biochemical profile including liver and renal function. Further testing revealed elevated serum creatine kinase (30.51 μkat/L), decreased hemoglobin (93 g/L from initial 126 g/L), mild neutropenia (0.9 × 10⁹/L), thrombocytopenia (110 × 10⁹/L), markedly elevated and fluctuating serum ferritin (range: 494-45,301 pmol/L), and elevated lactate dehydrogenase (10.55 μkat/L). Blood cultures, urine cultures, throat swabs, and cerebrospinal fluid showed no microorganisms. Autoantibody screens were negative with unremarkable serum complement levels.

PET-CT, bone marrow at T10, sternum, and right anterior superior iliac spine.

PET-CT showed widespread non-homogeneous increase in tracer uptake within bone marrow at T10 and sternum, and in the right anterior superior iliac spine. No abnormalities were found in muscles or organs including lymph nodes, liver, or spleen.

Bone marrow biopsy, immunohistochemistry for CD3.

Bone marrow biopsy showed extensive infiltration with high-grade tumor, with immunohistochemical expression of CD3 showing T-cell malignancy.

peripheral t-cell lymphoma unspecified


63-year-old man with 32-year history of reddish-brown skin lesions, which worsened over previous year. Presenting symptoms included daily abdominal pain, pruritus, flushing, joint pain, and fatigue. Physical examination showed brown patches covering >90% of body, sparing only soles and head. Laboratory findings showed serum tryptase of 70.5 μg/L (6x upper limit of normal). Skin biopsy showed multiple mast cells. Bone marrow aspirate and biopsy revealed spindle-shaped mast cells co-expressing CD2 and CD25 involving 10% of bone marrow biopsy cells, and presence of KIT D816V mutation specific for mastocytosis.

(A) Clinical photograph of the anterior body surface. (B) Clinical photograph of the posterior body surface. (C) Clinical photograph of the palms.

Shows severe skin involvement with reddish-brown lesions affecting front (Subfig A) and back (Subfig B) of body, with sparing of palms (Subfig C)

Systemic mastocytosis with severe skin involvement

Systemic mastocytosis

Cutaneous mastocytosis


A 60-year-old white Caucasian woman presented with a 4-year history of worsening gait and sensory disturbance accompanied by urinary urgency and nocturia. She reported slow deterioration in vision from age 50, though she could still drive. Her mother was registered blind and had Parkinson's disease with dementia. On examination, she had a spastic gait with normal power in lower limbs but increased tone and sustained ankle clonus. Reflexes were brisk with flexor plantar responses. She had mild reduction in visual acuity and dyschromatopsia, but no detectable visual field defect and preserved pupillary light reflexes. CSF analysis showed presence of oligoclonal bands. Routine hematological, biochemical and immunological blood tests were normal, including folate and vitamin B12. Anti-aquaporin 4 antibodies were negative in serum.

(A) Fundoscopic examination of both eyes. (B) Optical coherence tomography of both eyes, average peripapillary retinal nerve fiber layer thickness: right eye 63 μm, left eye 62 μm.

Bilateral optic atrophy observed on fundoscopic examination (A). OCT showed average peripapillary retinal nerve fiber layer thickness of 63 μm in right eye and 62 μm in left eye (B)

MRI of the brain and cervical spinal cord, T2-weighted sequence.

MRI revealed multiple foci of T2 hyperintensity in periventricular and pericallosal white matter regions, with discrete areas of signal abnormalities in cervical spinal cord. Findings met MRI diagnostic criteria for multiple sclerosis

Multiple sclerosis-like disorder with OPA1 mutation (specifically, a novel heterozygous splice site mutation, c.2356-1G>T)

Multiple sclerosis-like disorder

CNS1 - [Crigler-Najjar syndrome type 1]


A previously well 57-year-old woman presented with a 1-week history of generalized aches, malaise, anorexia, and fevers (temperatures between 37.7°C and 38.3°C). She reported a cough and persistent pain in the right upper quadrant but had no nausea, vomiting, or diarrhea. She had a history of migraines and was taking only acetaminophen and naproxen. Her family history was notable for giant-cell arteritis in her mother and prostate and colon cancer in her father. She worked for a nonprofit organization, lived in New England, had not traveled recently, and had no pets. On physical examination, she was in no distress with blood pressure 120/70 mm Hg, pulse 72 beats per minute, and temperature 38.9°C. The remainder of the physical examination was normal with no abdominal tenderness. Initial laboratory tests showed hematocrit 38%, normal white-cell and platelet counts, normal other blood tests, and elevated ESR of 68 mm per hour (normal 0-18). Tests for antibodies to Lyme disease, babesia, and ehrlichia species were negative. One month later, she had lost approximately 2 kg, had temperature of 38.3°C, and mild right upper quadrant tenderness. Follow-up labs showed hematocrit 34%, normal white-cell and platelet counts, ESR 104 mm per hour, and negative blood cultures. Three months after onset, she had lost a total of 7 kg, blood pressure was 100/70 mm Hg with conjunctival pallor. Laboratory results showed hematocrit 27%, normal white-cell count, platelet count 455,000 per cubic millimeter, ESR greater than 120 mm per hour, alkaline phosphatase 354 U per liter (normal 35-130), alanine aminotransferase 71 U per liter (normal 7-52), aspartate aminotransferase 57 U per liter (normal 9-30), and ferritin 828 μg per liter (normal 10-170). Multiple infectious serologies were negative, antinuclear antibodies were less than 1:40, ANCAs and other autoantibodies were negative, and complement levels were normal. CT chest was normal, abdominal-pelvic CT showed enlarged heterogeneous uterus with ill-defined enhancement consistent with fibroids. Pelvic ultrasonography confirmed enlarged uterus consistent with fibroids and thickened endometrial stripe. Gynecologic examination revealed smooth, firm uterus consistent with uterine fibroid, and endometrial biopsy showed benign endometrial polyp. Indium-111-labeled leukocyte scintigraphy was normal. Liver biopsy showed normal parenchyma with no abnormalities, and temporal artery biopsy was negative. Physical examination showed no temporal-artery tenderness, synovitis, or proximal muscle weakness, and no rash or joint symptoms were present.

(A) FDG-PET of the uterus. (B) FDG-PET/CT of the uterus.

18Ffluorodeoxyglucose–positronemission tomography (FDGPET) (Panel A) shows the FDG avidity of the uterine mass (arrow), and FDGPET with computed tomography (CT) (Panel B) shows the uterine abnormality with a necrotic center, findings that are consistent with leiomyosarcoma

Gross specimen of the uterus.

Gross appearance shows a variegated and fleshy uterine mass measuring 9.5 cm in largest diameter that had subtotally replaced the anterior myometrium.

Leiomyosarcoma of uterus[Differentiated, NOS]


A 32-year-old incarcerated male presented after being found unresponsive in his jail cell. Two days prior, he had nausea and vomiting. He had a history of substance use disorder (alcohol, opiates, cocaine), traumatic brain injuries, seizures, anemia, and possible paranoid schizophrenia. Six years prior, he tested negative for HIV and HCV. Eight months before admission, he had been admitted for altered behavior with hyperammonemia and echogenic liver on ultrasound. On examination, he was unresponsive with grunting respirations. Vital signs showed temperature 36.9°C, pulse 112/min, blood pressure 170/119 mmHg. He had jaundiced skin, icteric sclerae, asymmetric pupillary responses, diffuse hypertonicity, extensor posturing of arms, myoclonic jerking of legs, and clonus. The abdomen was mildly distended. Initial blood glucose was <10 mg/dL.

Chest radiograph.

Chest radiograph showed discoid atelectasis at the left lung base

Abdominal ultrasound of the gallbladder.

Abdominal ultrasound showed thick, hypoechoic gallbladder wall consistent with hepatitis

(A, B) Fluid-attenuated inversion recovery MRI, cortex and thalami. (C, D) Diffusion-weighted MRI, cortex and thalami. (E, F) Apparent diffusion coefficient MRI, cortex and thalami.

Fluid‑attenuated inversion recovery images (Panels A and B) show swelling of the cortex and thalami with increased signal, findings consistent with edema. On diffusion‑weighted images (Panels C and D), the cortex and thalami have increased signal, and on apparent diffusion coefficient maps (Panels E and F), the cortex and thalami have decreased signal; these findings are consistent with decreased diffusion due to cytotoxic edema.

Laboratory test results.

Laboratory tests showed elevated liver enzymes (AST 3944 U/L, ALT 3767 U/L), elevated total bilirubin (10.8 mg/dL), prolonged coagulation times (PT 110.8 sec, INR 11.6), elevated ammonia (306 μmol/L), and metabolic derangements

Serologic testing for hepatitis B virus.

Serologic testing showed positive results for HBV surface antigen, HBV surface antibodies, total HBV core antibodies, HBV core IgM antibodies, and HBV DNA (39,200 IU/mL)

Fulminant liver failure associated with hepatitis B virus infection

fulminant hepatic failure

Congenital Hepatitis B virus infection


16-year-old girl presented with left wrist deformity present since birth. She had progressively increasing pain in the left wrist with limited dorsiflexion. Physical examination revealed loss of grip strength, decreased extension, and supination. No other external congenital deformities were noted.

(A) Anteroposterior radiograph of the left wrist. (B) Lateral radiograph of the left wrist.

Anteroposterior and lateral radiographs of left wrist showing Madelung deformity

Madelung deformity


A 45-year-old man presented to the haematology ward with fever, nausea, vomiting, diarrhea and severe prostration lasting several days. He had mantle cell lymphoma and was on day 45 post-allogeneic haematopoietic stem cell transplantation from a related donor. Physical examination revealed tachycardia, hypotension, high inflammatory markers, and marked dehydration. Laboratory tests showed acute renal insufficiency with symptoms of thrombotic thrombocytopenic purpura (TTP) and kidney damage from cyclosporine nephrotoxicity. High-resolution computed tomography (HR-CT) of the chest showed typical radiological signs of pulmonary mycosis. Galactomannan was detected in the patient's serum. Mycological cultures of BAL and sputum were negative, though oral mucous membrane cultures yielded Pichia kluyveri and Candida albicans.

Lung tissue. (H&E 40x)

Lung tissue showing necrosis within Aspergillus spp. mycelium

Heart histopathological section, H&E staining, 40× magnification.

Figure 2 depicts a histopathological section of the heart showing a spherical mycelium of Aspergillus spp. surrounded by cardiomyocytes, stained with haematoxylin and eosin at a magnification of ×40, as described in the figure caption and confirmed by the image on page 3.

Histopathological section of the heart, interventricular septum, H&E staining, 100× magnification, post-mortem autopsy sample.

Figure 3 shows a histopathological section of the heart demonstrating Aspergillus spp. mycelium with branching hyphae and small mixed inflammatory infiltrations in the surrounding tissue, stained with hematoxylin and eosin at a magnification of ×100, with the anatomical site being the interventricular septum and the sample acquired post-mortem during autopsy.

Histological section of heart tissue.

Heart tissue showing radial arrangement of Aspergillus spp. hyphae

Invasive aspergillosis involving both the heart septum and lungs in an allogeneic haematopoietic stem cell transplant recipient

Invasive aspergillosis

Invasive cardiac aspergillosis

Chronic pulmonary aspergillosis

Allogeneic haematopoietic stem cell transplant recipient

Presence of transplanted stem cell

Factors influencing health status or contact with health services


A 48-year-old woman presented with severe occipital headache. Two months prior, she had developed bilateral auricular swelling, scleral injection, and fever which had responded to oral glucocorticoid. The current headache started 3 days prior and was accompanied by nausea, vomiting, and neck stiffness. Cerebrospinal fluid examination showed WBC count of 71/mm3 (lymphocyte 58%, PMN 28%), total protein of 86.6 mg/dL, and glucose of 62.9 mg/dL. Stains and cultures for microorganisms were negative. Serologic tests including antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA), and rheumatoid factor (RF) were all negative.

(A) Brain MRI, T2-weighted image, cerebellum. (B) Brain MRI, T2-weighted image, basal ganglia. (C) Brain MR angiography, left distal internal carotid artery, left proximal middle cerebral artery, and left anterior cerebral artery.

Brain MRI and MR angiography. T2 weighted image showed edema of brain cortex and some high signals (arrows) in parenchyma of bilateral cerebellum (A) and basal ganglia (B). MR angiography showed near complete occlusion (arrow heads) of left distal internal carotid artery, left proximal middle cerebral artery, and left anterior cerebral artery (C).

Meningoencephalitis from Relapsing Polychondritis (RP)

Relapsing polychondritis

meningoencephalitis NOS


A 52-year-old perimenopausal Caucasian woman, gravida 3 para 3, presented with a 10-week history of vaginal bleeding, bloating, fatigue, weight gain (>7 kg), and hypogastric mass. She was admitted to the emergency room for epigastric pain and mild dyspnea, and had observed breast tenderness for the past 3 months. Her personal history included appendectomy, amiodarone-induced hypothyroidism, chronic atrial fibrillation, and breast abscess but no hypertension. Her last delivery was 23 years ago, she discontinued oral contraceptive pills at least 18 months prior, and her last menses occurred 4 months ago. Initial examination revealed a fundal height of 18 cm. When referred to the cancer center ten days later, she developed signs of early onset preeclampsia including new onset severe hypertension (170/100 mmHg), proteinuria, oliguria, headache, hyperreflexivity in lower limbs, and growing epigastric pain radiating to both hypochondria. Laboratory tests at the cancer center showed rapidly deteriorating results with hemolytic anemia (hemoglobin 97 g/L, haptoglobin <0.06 g/L), thrombocytopenia (75 G/L), elevated liver enzymes (ALT 120 IU/L, AST 252 IU/L), and severe proteinuria (1.85 g/24 h), presenting a complete form of HELLP syndrome. Her serum hCG level was initially 0.96 × 10⁶ IU/L, rising to 1.266 × 10⁶ IU/L.

(A) Contrast-enhanced CT of the abdominopelvic region, mid sagittal plane. (B) Contrast-enhanced CT of the abdominopelvic region, transverse plane. (C) Chest CT, axial view, lung window.

Abdominopelvic contrast-enhanced CT scans showing an enlarged uterus with focal areas of hypoattenuation; (a) mid sagittal plane; (b) transverse plan. (c) Axial chest CT scan (lung window) showing at least one left pulmonary metastase

(a) Photograph of the specimen with scale in centimeters. (b) Photograph of the specimen with longitudinal incision. (c) Micrograph of uterine tissue, hematoxylin and eosin staining, low magnification. (d) Micrograph of uterine tissue, hematoxylin and eosin staining, high magnification.

(a) Photograph of the specimen with scale (cm); (b) Photograph of the specimen with longitudinal incision exposing vesicles; (c) Low magnification micrograph of the invasive complete hydatiform mole component (hematoxylin and eosin): two enlarged chorionic villi associated with a trophoblastic proliferation invading the vessels and the muscular wall of the uterus (bottom left); (d) high magnification micrograph of a suspected choriocarcinomatous component (hematoxylin and eosin): large syncitiotrophoblasts associated with a proliferation of atypical intermediate cytotrophoblasts

Complete and invasive hydatidiform mole with post-molar high-risk gestational trophoblastic neoplasia, FIGO stage/score III:7, complicated by early onset preeclampsia and HELLP syndrome

Complete hydatidiform mole

Invasive hydatidiform mole

High-risk gestational trophoblastic neoplasia

neoplasia

Pre-eclampsia

HELLP syndrome


43-year-old woman presented to surgical assessment unit with increasing abdominal pain 36 hours after colonoscopy and polypectomy. Physical examination revealed tender and mildly distended abdomen.

CT scan of abdomen.

CT scan of abdomen shows free air, with visible polypectomy clips in ascending colon. Air bubbles seen adjacent to clips, towards anterior intra-abdominal wall, anterior to aorta, posterior to transverse colon, and adjacent to splenic flexure. Free intraperitoneal air visible anterior to transverse colon.

Perforated bowel following colonoscopy and polypectomy, with perforation likely at the site of polypectomy clips in ascending colon

bowel perforation NOS

Polyp of colon


A 53-year-old woman with a history of seropositive rheumatoid arthritis (RA) and stage IIIC, BRAFV600 mutant unresectable melanoma. She had multiple skin metastases in the left lower limb. After initial treatment with pembrolizumab, she presented with bilateral paresthesia in glove and stocking distribution that rapidly progressed to severe weakness in her lower limbs and diplopia (6th cranial nerve palsy). Electromiography and nerve conduction study showed a moderate sensory peripheral polyneuropathy.

(A) Muscle biopsy, esterase staining. (B) Sural nerve biopsy, low-power field.

Figure 1 displays histopathological images from muscle and sural nerve biopsies: the left panel shows an angulated atrophic muscle cell positive for esterase stain (indicated by arrows), while the right panel demonstrates a low-power field of sural nerve with mononuclear inflammatory infiltrate surrounding two endoneural small vessels, consistent with vasculitis.

Peripheral neuropathy due to histologically induced by pembrolizumab

peripheral neuropathy NOS


A 62-year-old woman presented with a 6-month history of hair thinning, itchy scalp, and cold sensitivity. She denied fatigue, depression, memory problems, dry skin, or constipation. Her medical history included hyperlipidemia, for which she took fish oil and red yeast rice extract. Physical examination revealed a heart rate of 80/min, body mass index of 31, thyroid gland of normal size and consistency without palpable nodules, and normal deep tendon reflexes.

Laboratory results.

Laboratory values showed: TSH 4.88 mIU/L (ref: 0.4-4.5), total cholesterol 257 mg/dL (ref: 125-200), triglycerides 59 mg/dL (ref: <150), HDL 90 mg/dL (ref: ≥46), and LDL 155 mg/dL (ref: <130)

Subclinical hypothyroidism


A 51-year-old male surgeon presente progressive hand infection following a laceration to his left ring finger near the volar distal interphalangeal joint from a fillet knife while cleaning fish in coastal New England seawaters. The injury occurred during late summer, and 12 hours later he developed throbbing pain that progressively worsened. He had been well prior to this injury and was receiving adalimumab every other week for psoriatic arthritis, with his last dose administered 6 days before presentation. On examination at the Hand Clinic, he was alert but in moderate distress with a temperature of 38.1°C (100.5°F). There was exquisite tenderness over the entire flexor tendon sheath extending proximal to the metacarpophalangeal joint, and both active and passive motions were painful and markedly limited. No angular or rotational deformity was present, but capillary refill was less than 1 second with distal dysesthesias. All four Kanavel signs for infectious flexor tenosynovitis were present. His temperature subsequently rose to 38.5°C (101.3°F) with development of rigors, sinus tachycardia, progressive lethargy, lack of focus and alertness. Laboratory studies showed a white-cell count of 15.6 × 10^9 per liter (compared to 7.2 × 10^9 per liter six weeks previously) with 91% polymorphonuclear leukocytes, while hematocrit, chemical values, and coagulation studies were normal.

(A) Clinical photograph of the left ring finger, volar view. (B) Clinical photograph of the left ring finger, lateral view from the ulnar side.

Shows circumferential swelling of the left ring finger with tracking erythema extending to the metacarpophalangeal joint, with Panel A showing the volar view and Panel B the lateral view from the ulnar side, displaying the original traumatic puncture wounds

Vibrio vulnificus infectious flexor tenosynovitis

Infectious tenosynovitis


A 60-year-old woman presented to healthcare with acute left-sided pleuritic chest pain and dyspnoea without sputum production. She had been experiencing malaise, intermittent fever, and rigors for four weeks. She had a known patent ductus arteriosus (PDA) that was identified 10 years earlier after a murmur was detected during routine medical examination and confirmed by transthoracic echocardiography with no other signs of haemodynamic importance. On presentation, she had a fever of 39.0°C with left-sided pleural rub. Precordial examination identified a continuous 'machinery' murmur. She also had a purpuric rash. Electrocardiographic findings were within normal limits. Laboratory investigations confirmed normocytic anaemia, leucocytosis, and preserved renal function. Group B streptococcus was isolated from all three separate blood cultures.

Chest X-ray at the time of clinical presentation.

Figure 1 on page 1 is a chest radiograph (plain X-ray) taken at the time of clinical presentation, demonstrating a peripheral wedge-shaped opacity in the left mid zone of the lung, corresponding anatomically to the area associated with the patient’s pleural rub; this radiographic finding, known as Hampton’s hump, is a classical sign indicative of pulmonary infarction secondary to embolism, as described in both the figure legend and the associated body text.

Chest radiograph.

Chest radiograph shows a peripheral wedge-shaped opacity in the left mid zone (Hampton's hump)

CT pulmonary angiogram, coronal view.

Coronal computed tomographic pulmonary angiogram shows septic pulmonary emboli with filling defect within a branch of the left pulmonary artery, distal lung infarction, and the calcified patent ductus arteriosus between the distal aortic arch and the roof of the pulmonary artery

Parasternal short axis transthoracic echocardiogram at the level of the pulmonary valve.

Parasternal short axis transthoracic echocardiogram at the level of the pulmonary valve shows the vegetation within the main pulmonary artery beside the ascending aorta

Patent ductus arteriosus associated streptococcal endocarditis and endarteritis with septic pulmonary emboli

patent ductus arteriosus NOS

Streptococcal endocarditis

coronary endarteritis

pulmonary embolism NOS


A previously healthy 50-year-old man presented with acute-onset dysarthria and was found to be febrile with respiratory distress and lethargy. He performed poorly in the right hand alternating movement test. Physical examination revealed a blood pressure of 130/90 mmHg and heart rate of 116 beats per minute. The apex beat was located in the sixth intercostal space, 1.5 cm outside the midclavicular line. Cardiac auscultation revealed a grade 4/6 systolic murmur that was most prominent at the apex. Laboratory findings showed normal troponin T, creatine kinase (CK), and CK-myoglobin (CK-MB) levels, but elevated N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) levels at 3277 pg/ml. The leukocyte count was 10,620/mm³ with neutrophils at 10,350/mm³, and the erythrocyte sedimentation rate was 68 mm/h. Blood culture was positive for group A β-hemolytic streptococcus. Electrocardiography revealed sinus tachycardia without evidence of ischemia.

Cranial MRI, T2-weighted sequence.

Cranial T2-magnetic resonance image showing high signal intensity in the left hemisphere, indicating cerebral infarction

Echocardiography of the heart.

Echocardiograph clearly shows a sizeable vegetation on the mitral valve measuring 40 × 30 mm

Abdominal ultrasound of the spleen.

Abdominal ultrasound showing multiple echo-free areas in the spleen, indicating liquefactive necrosis and abscess formation

Color Doppler echocardiography of the heart.

Color Doppler showing severe mitral regurgitation

Left-sided native valve infective endocarditis with multiple systemic embolism underlying Barlow's disease (mucoid degeneration and mitral valve prolapse)

Barlow syndrome

Mitral valve prolapse

infective endocarditis NOS

systemic fat embolism


66-year-old man who fell down 14 steps. Unable to weight bear due to ankle pain. Physical examination showed swollen and deformed foot.

Lateral radiograph of the left ankle.

Lateral radiograph of left ankle showed no ankle fracture but appeared abnormal

Fracture dislocation of the talus with disruption of the subtalar and talonavicular joints

foot fracture dislocation[Talus]

joint fluid[Subtalar joint]

Disruptive behaviour


60-year-old male with family history suggestive of hereditary cancer. Genetic testing revealed a deleterious germline BRCA2 mutation, which was later confirmed in the primary tumor by targeted next generation sequencing. Next generation sequencing of the primary tumor also revealed a pathogenic somatic mutation in the AKT1 gene (E17K; allele frequency 25.6%).

Timeline graph of pre-treatment PSA values, June 2013.

Pre-treatment PSA values shown in timeline graph indicating initial disease presentation in June 2013

(B) Coronal and sagittal CT images of the axial skeleton, performed before initiation of olaparib therapy. (C) Coronal and sagittal CT images of the axial skeleton, performed after 12 weeks of olaparib therapy, bone window settings.

B: Coronal (left) and sagittal (right) computed tomography (CT) images of the axial skeleton acquired before initiation of olaparib therapy demonstrate sclerotic bone metastases. C: Coronal (left) and sagittal (right) CT images of the axial skeleton obtained after 12 weeks of olaparib treatment using bone window settings reveal a marked increase in sclerotic bone metastases, with nearly complete involvement of the entire axial skeleton on follow-up.

68Ga-PSMA PET/CT scan.

Initial 68Ga-PSMA PET/CT scan showed PSMA-positive lymph node metastasis

Primary metastatic prostate cancer with skeletal involvement and germline BRCA2 mutation

Malignant neoplasms of prostate

Metastatic prostate cancer [primary prostate cancer spreading elsewhere]

bone metastasis

AQP2 mutation


15-year-old boy presented with a painless palpable lump in his right upper arm. The patient reported having the lump for 'many years' but was now conscious about it.

Anteroposterior radiograph of the right upper arm.

Anteroposterior radiograph of right upper arm showed multiple bony lesions

Anteroposterior radiograph of right upper arm demonstrated osteochondromas that were both sessile and pedunculated, growing in the metaphyseal region projecting away from the epiphysis

Lateral radiograph of the left femur.

Lateral radiograph of left femur showing additional lesions

Anteroposterior radiograph of the left femur.

Figure 4 is an anteroposterior radiograph of the left femur, as shown on page 3. The image demonstrates multiple bony outgrowths arising from the metaphyseal regions of the femur, consistent with osteochondromas seen in hereditary multiple exostoses.

Chest radiograph, posteroanterior view.

Posteroanterior radiograph of chest showing osteochondromas growing in flat bones such as ribs

Hereditary multiple exostoses (also known as diaphyseal aclasis)

Multiple congenital exostoses


A 76-year-old woman with a 20-pack-year history of smoking presented to the hospital with back pain. Pleural disseminations were resected using video-assisted thoracic surgery for diagnostic purposes, and molecular analysis identified an epidermal growth factor receptor (EGFR) mutation in exon 21 (L858R) using ScorpionARMS analysis. Immunohistochemistry showed that the tumor expressed TTF-1 but did not express NCAM, synaptophysin, or CD56.

CT of the chest performed before gefitinib therapy.

CT before gefitinib therapy shows a primary lesion in the left upper lobe with pleural disseminations.

Pleural histology, H&E staining, 400× magnification.

Histologic features of pleural dissemination obtained before treatment show adenocarcinoma (hematoxylin and eosin stain, magnification ×400).

PD-L1 immunohistochemical staining, 400× magnification, PD-L1 expression in 30% of tumor cells.

PD-L1 immunohistochemical staining shows expression in 30% of tumor cells (magnification ×400).

Adenocarcinoma of the lung with EGFR mutation in exon 21 (L858R)

lung adenocarcinoma


A 28-year-old man initially presented with abdominal pain and diarrhea consisting of 10-12 Bristol type 7 (watery) stools per day after completing a course of azithromycin for pneumonia. Six weeks later, after successful treatment and return to baseline bowel patterns, he presented again with abdominal discomfort for 3 weeks that was relieved by bowel movements and associated with increased stool frequency of 4-5 Bristol type 4 stools per day. At the second presentation, his vital signs and physical examination were unremarkable.

Laboratory studies at initial presentation.

Laboratory studies at initial presentation showed a positive Clostridium difficile polymerase chain reaction, white blood cell count 7.1 × 10³/μL (reference 3.5-10.5), hemoglobin 15.0 g/dL (reference 13.5-17.5 for men), hematocrit 43.7% (reference 38.8-50.0), mean corpuscular volume 82.8 μm³ (reference 81.2-95.1), platelets 252 × 10³/μL (reference 150-450), and albumin 4.5 g/dL (reference 3.5-5.0). All values except the C. difficile PCR were within normal ranges.

Postinfectious altered bowel habits with C difficile colonization

altered bowel habit

Intestinal infections due to Clostridioides difficile


A male newborn born at 36 weeks' gestation who died 20 hours after birth. His 26-year-old mother developed fever and rash during the first trimester of pregnancy, with no laboratory studies performed and no reported drug or chemical exposures. Ultrasonography in the second trimester revealed genital malformations. At birth, the infant presented with genital malformations. Autopsy findings showed bodyweight of 2740 g, length of 41 cm, head circumference of 29 cm, thoracic circumference of 34 cm, and abdominal circumference of 31 cm. External examination revealed subcutaneous edema, craniofacial malformations including hypertelorism, severe arthrogryposis, craniosynostosis, and cryptorchidism. CNS examination showed lissencephaly, alobar holoprosencephaly, and cerebellar hypoplasia. Chest examination revealed bilateral pulmonary hypoplasia confirmed by radial alveolar counts. Histopathological changes were restricted to the brain and included parenchymal calcification, microglial nodules, gliosis, neuronal and glial cell degeneration, and necrosis.

(A) Clinical photograph at autopsy. (B) Clinical photograph.

A: Gross clinical photograph of case 1, a newborn at autopsy, showing craniofacial malformations, including microcephaly, flat nasal bridge, anteverted nares, and additional features of fetal akinesia deformation sequence, such as upper and lower limb contractures and valgus deformities. B: Clinical photograph of the same case highlighting limb contractures and morphological limb abnormalities, consistent with severe arthrogryposis.

Congenital Zika syndrome with microcephaly, lissencephaly, alobar holoprosencephaly, cerebellar hypoplasia, severe arthrogryposis, and multiple congenital malformations

Zika virus disease


A 32-year-old man with a 14-year history of ulcerative colitis presented with a 2-month history of a purulent paronychial lesion of his right big toe. He had previously been diagnosed with bacterial paronychia (Pseudomonas aeruginosa and Enterobacter cloacae). The patient developed vegetative lesions in the groin and tender erosions of the hard palate, along with worsening diarrhea and abdominal cramping, complicated by Clostridium difficile. Physical examination revealed vegetating plaques over inner thighs, scrotum, and perineum, corrugated plaques bilaterally over the dorsal hard palate, shallow erosions on the nares and lower lip. Biopsy samples from oral mucosa, toe, and groin showed dense eosinophilic spongiotic infiltrate, and the patient had peripheral eosinophilia. Direct immunofluorescence studies showed no significant immunoglobulin, complement, or fibrinogen deposition.

Clinical photograph of the right hallux.

Shows mildly tender, ulcerating, and macerated lesion on the right hallux

Clinical photograph of the oral cavity.

B: The image presents an intraoral clinical photograph depicting asymptomatic pustular lesions arranged in a characteristic snail-track pattern along the gingiva within the oral mucosa, consistent with pyodermatitis-pyostomatitis vegetans; the modality is gross clinical photography, focusing on the oral cavity at the time of diagnosis.

Pyodermatitis vegetans

Pyostomatitis vegetans


A male infant born at term to nonconsanguineous, healthy parents with no known family history of immune deficiency presented with profound T-cell lymphopenia detected through newborn screening which revealed no detectable TRECs at 20 days of age. Physical examination revealed neonatal teeth, hypotonia, umbilical hernia, and erythematous psoriaform dermatitis. Imaging studies revealed wormian skull bones, mild pulmonary artery stenosis, and absence of corpus callosum. The patient showed no evidence of maternal engraftment.

Laboratory immunologic analysis.

Complete immunologic findings showing TRECs 0 per microliter (normal >25), CD3+ T-cell count 182 cells/μl (normal 2250-5500), CD4+ helper T-cell count 130 cells/μl (normal >1600), CD8+ cytotoxic T-cell count 26 cells/μl (normal >560), CD19+ B-cell count 1326 cells/μl (normal 300-2000), CD16+/CD56+ NK cell count 468 cells/μl (normal 170-1100), undetectable CD3+/CD4+/CD45RA+ naive cells (normal >50%), and lymphocyte proliferation to PHA 18% (normal >50%)

Clinical photographs of the face.

Clinical photographs showing increased intraorbital distance, short palpebral fissures, abnormal nasal creases, micrognathia, ear tag, loose skin folds, and hirsutism

Severe combined immunodeficiency (SCID) with multisystem anomalies caused by a heterozygous de novo missense mutation p.N441K in BCL11B

Severe combined immunodeficiencies

multi system failure


A 65-year-old woman with HIV infection, hypertension, and hyperlipidemia presented with a 1-week history of cough productive of pink sputum and mild shortness of breath on exertion. She developed slurred speech, difficulty swallowing, headache, and gait imbalance 4 days prior to presentation. Her HIV was diagnosed 17 years ago with a nadir CD4+ count of 21 cells/mm3. Recent CD4+ count was 198 cells/mm3. She was a current smoker with 25-pack-year history. On examination, vital signs were normal. She had decreased breath sounds, dullness to percussion, and increased tactile fremitus in the lower right hemithorax. Neurologic exam showed tongue deviation to the left without fasciculations or atrophy, slowed speech with decreased prosodic variation, and unsteady gait on tandem toe walking. Laboratory results showed CD4+ count of 265 cells/mm copies/mL, and normal basic labs. CSF analysis showed elevated protein (94 mg/dL), lymphocytic pleocytosis, positive EBV PCR.

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

Posteroanterior (Panel A) and lateral (Panel B) chest radiographs show a well-defined homogeneous opacity in the right lower lobe.

CT of the chest.

CT chest showed consolidation within right lower lobe

PET of the chest, 18F-fluorodeoxyglucose (FDG) tracer.

B: Positron emission tomography (PET) of the chest demonstrates intense 18F-fluorodeoxyglucose uptake within a right lower-lobe pulmonary mass, indicating a hypermetabolic lesion consistent with a primary lung neoplasm.

Contrast-enhanced MRI of the brain.

Contrast-enhanced MRI showed multiple foci of leptomeningeal enhancement around both frontal lobes, posterior fossa, and brain stem

(A) Cytopathological examination of cerebrospinal fluid sample. (B) Immunohistochemistry for keratins AE1/AE3. (C) Immunohistochemistry for thyroid transcription factor 1 (TTF-1).

Cytopathological examination of a sample of cerebrospinal fluid obtained from the patient shows metastatic adenocarcinoma. Abnormal large cells are present (Panel A). These cells show strong immunoreactivity (brown) for keratins AE1/AE3 (Panel B); this identifies the cells as being carcinomatous in origin. The cells are also positive for thyroid transcription factor 1 (TTF-1), a marker of lung adenocarcinomas (as well as thyroid carcinomas) (Panel C). Adjacent lymphocytes in Panels B and C are negative for AE1/AE3 and TTF-1.

Leptomeningeal carcinomatosis due to metastatic spread from a primary lung adenocarcinoma

lung adenocarcinoma

meninges carcinomatosis

metastatic tumour in bone


A 20-year-old male college student presented with bilateral breast enlargement of 3-year duration without nipple discharge. He reported occasional morning erections but had never been sexually active. Four years prior, he developed increased thirst, fluid consumption, and frequent urination (4-5 times daily, up to 3 times nightly), which had recently improved. He had blurred vision corrected with glasses, occasional post-exertion headaches, and decreased facial hair growth requiring shaving every 2 weeks instead of weekly. His medical history included generalized nocturnal tonic-clonic seizures and focal seizures in right leg between ages 6-13, treated with carbamazepine until age 14. He had recent constipation and chronic pilonidal cyst. Physical examination revealed a young-appearing male with minimal facial hair, blood pressure 98/62 mmHg, height 179 cm, weight 85 kg, BMI 26.5. Both breasts were enlarged without nipple retraction, masses, or discharge. Testicles were small (approximately 2.5 cm length). He had a small posterior anal fissure and small lump over coccyx with central punctum.

Laboratory results.

Laboratory findings showed elevated sodium (164 mmol/L), elevated serum osmolality (334 mOsm/kg), low testosterone (23 ng/dL), very low luteinizing hormone (<0.1 U/L), elevated prolactin (68.7 ng/mL), and low estradiol (<20 pg/mL)

Additional laboratory results.

Additional tests showed low free thyroxine (0.5 ng/dL), low cortisol (2.2 μg/dL at 8:45 PM), low insulin-like growth factor 1 (83 ng/mL), and normal cerebrospinal fluid studies except for slightly elevated protein (96 mg/dL)

Automated (Humphrey) visual-field testing performed during admission, visual fields of both eyes.

Figure 1 in this document is titled "Results of Visual-Field Testing" and, according to the image and the caption on page 4, presents the results of automated (Humphrey) visual-field testing. The figure displays two visual-field plots showing bitemporal visual-field defects with predominant involvement of the temporal inferior quadrants. The modality is automated perimetry, the anatomical site examined is the visual fields of both eyes, the data acquisition timing appears to be during the patient’s diagnostic workup on admission, and the key technical finding is bitemporal, predominantly inferior, visual-field loss consistent with chiasmal involvement.

(A) MRI of the head, performed on admission, sagittal view, gadolinium-enhanced T1-weighted sequence. (B) MRI of the head, performed on admission, coronal view, gadolinium-enhanced T1-weighted sequence. (C) MRI of the head, performed on admission, axial view, gadolinium-enhanced T1-weighted sequence. (D) MRI of the head, performed on admission, axial view, T2-weighted sequence. (E) MRI of the head, performed on admission, coronal view, T2-weighted sequence.

MRI Scan of the Head, Obtained on Admission. Shown are gadolinium-enhanced sagittal, coronal, and axial T₁-weighted images (Panels A, B, and C, respectively), as well as axial and coronal T₂-weighted images obtained before the administration of contrast material (Panels D and E, respectively). Abnormal, ill-defined enhancement is seen in the sellar and suprasellar regions (Panel A, arrows) and extending anteriorly into the suprachiasmatic and lamina terminalis regions. Additional foci of abnormal enhancement are present in the pineal region, posterior third ventricle, left thalamus, subependymal regions around the foramina of Monro, and left aspect of the genu of the corpus callosum (Panel C, arrows). Ill-defined areas of T₂ hyperintensity in the brain parenchyma are also shown around these enhancing foci.

Intracranial germ-cell tumor (germinoma)

intracranial lesion

germinoma of unspecified site


A 90-year-old man presented with a 1-month history of progressive edema in both legs and several episodes of malaise and dizziness associated with hypoglycemia. Physical examination revealed a n palpation.

Chest radiograph.

Plain chest radiograph showed a round, irregular opacity inside the gastric chamber and a colonic segment below the right hemidiaphragm

Upper gastrointestinal endoscopy of the subcardial area. Histologic examination of gastric tissue.

Upper gastrointestinal endoscopy revealed a diffusely eroded, exophytic mass arising from the subcardial area. Histologic features were consistent with a high-grade, poorly differentiated gastric adenocarcinoma

Malignant neoplasms of stomach


31-year-old male ski freerider with no significant medical history. Buried under snow for 3-5 minutes at 2500m above sea level, with hand visible. Head buried ~0.5m deep. Never lost consciousness. Presenting symptoms: unable to breathe due to compacted snow blocking airways. When uncovered: cyanotic but conscious, fully oriented, with peripheral and central cyanosis, tachypnea, and frank hemoptysis. Physical exam showed bilateral rales and crackles on pulmonary auscultation, no pain on thoracic compression, no oral bleeding wounds. Vital signs at admission: O2 saturation 93% on 100% oxygen, normal heart rate and blood pressure. Laboratory results: normal hemoglobin (168 g/L), normal B-type natriuretic peptide, normal troponin.

(A) Chest CT, apical region. (B) Chest CT, basal region.

CT scan shows impressive bilateral diffuse pulmonary edema with extensive macular alveolar infiltrations throughout both lungs, visible in both apical (Subfig: A) and basal (Subfig: B) regions. No signs of trauma.

Negative pressure pulmonary edema with pulmonary hemorrhage

Pulmonary oedema

Pulmonary haemorrhage


A 60-year-old woman presented after sustaining direct trauma to the anterior neck from a fall. She developed progressively worsening hoarse voice, difficulty swallowing, and pain with neck movement. Physical examination revealed visible neck swelling with bruising tracking onto the anterior chest wall. There was no tenderness on palpation of the cervical spine. On flexible nasal endoscopy, swelling of the posterior pharyngeal wall was observed, indicating potential airway compromise.

Lateral radiograph of the cervical region.

Lateral radiograph showed massive retropharyngeal hematoma with distortion of the upper aerodigestive tract and loss of normal cervical lordosis.

retropharyngeal haematoma