A 48-year-old man presented in April 2012 with an enlarging left supraclavicular mass that had been increasing in size for 3 weeks, with associated pain in the area. He denied respiratory or constitutional symptoms. Physical examination revealed a 6-cm left supraclavicular mass without appreciable changes of the overlying skin and no thyromegaly. Complete blood count showed a white blood cell count of 18.3 × 10⁹/L with lymphocytic predominance (54.3%), hemoglobin of 13.5 g/dL, and platelet count of 285 × 10³/μL. His lactate dehydrogenase level was 208 U/L. HIV test was nonreactive.

Biopsy of neck mass, immunohistochemistry staining for CD4, CD15, CD30, CD38, CD45, CD79a, CD138, MUM-1, CD3, CD7, and cyclin D1.

Biopsy of the neck mass revealed large atypical cells expressing CD4, CD15, CD30, CD38, CD45, CD79a, CD138, and MUM-1, with focal reactivity for CD3, CD7, and cyclin D1, with findings consistent with plasmablastic lymphoma arising from a background of chronic lymphocytic leukemia (insert shows small lymphocytic lymphoma/CLL component of the same tumor in adjacent area).

Positron emission tomography/computed tomography scan of the supraclavicular area and duodenal wall using [¹⁸F] fluorodeoxyglucose.

Positron emission tomography/computed tomography scan showed intense [¹⁸F] fluorodeoxyglucose avidity in the supraclavicular area corresponding to the palpable mass and in the duodenal wall, findings that were highly suggestive of serosal implants of lymphoma.

Immunohistochemical staining for CD30 in lymphoma tissue section.

Figure 3 demonstrates an immunohistochemical analysis of a tissue section from the patient’s lymphoma, showing strong membranous and cytoplasmic expression of CD30 in tumor cells. The specimen is derived from the lymphoma site and highlights the immunophenotype relevant to the diagnosis of plasmablastic lymphoma; no specific magnification or exact anatomical location within the figure is stated in the caption or body text, but the context indicates it is from the patient’s diagnosed lesion.

Plasmablastic lymphoma arising from a background of chronic lymphocytic leukemia

Plasmablastic lymphoma

chronic lymphocytic leukaemia


47-year-old female patient with Karnofsky performance status of 70% who developed mild gait ataxia.

(A) H&E staining of cerebellar tumor specimen. (B) Immunohistochemical analysis of tumor section for HMB45 antigen. (C) H&E staining of tumor specimen, higher magnification.

A: Hematoxylin and eosin staining of a resected tumor specimen from the cerebellar lesion shows high cellularity. B: Immunohistochemical analysis of the tumor section demonstrates strong positivity for the HMB45 antigen. C: Hematoxylin and eosin staining at higher magnification highlights the presence of mitotic figures, indicated by an arrowhead.

(D) Cytological image of cerebrospinal fluid sample acquired during therapy, Melan A staining.

D: Cytological image of a cerebrospinal fluid (CSF) sample acquired during therapy, demonstrating a Melan A-positive melanoma cell cluster.

T1-weighted contrast-enhanced MRI.

T1-weighted contrast-enhanced MRI showed widespread subependymal and occipital leptomeningeal enhancement

Cerebrospinal fluid laboratory analysis.

Initial CSF parameters showed presence of melanoma cells, elevated cell count (10-53/μL), elevated protein (623-873 mg/L), and elevated lactate (3.3-3.7 mmol/L)

V600E BRAF-mutated melanoma with leptomeningeal melanomatosis (LM), hemorrhagic left cerebellar lesion, and right parieto-occipital lesion

melanoma NOS

Leptomeningitis

Cerebellar haemorrhage

Lesion of greater occipital nerve


An 86-year-old female patient presented with lip lesions and numerous cutaneous warty growths that had been present for 6 months. She experienced mild dysphagia but had no systemic symptoms including weight loss. Her medical history included osteoporosis treated with risedronate, and she was otherwise healthy. Several wart-like papules were present on the skin of her face, neck, and extremities. There was no cutaneous hyperpigmentation or velvety thickening. Histologic examination of cutaneous and mucosal lesions showed hyperkeratosis, acanthosis, and papillomatosis but no viral inclusion or vacuolar degeneration of keratinocytes, with no evidence of human papillomavirus by polymerase chain reaction.

Clinical photograph of the lip vermillion, oral cavity, and oropharynx at initial assessment.

Figure 1 presents a clinical photograph depicting confluent fine papillomatosis across the lip vermillion, diffusely affecting the mucosa of the oral cavity and oropharynx; this image documents the gross, mucocutaneous appearance of the lesions on initial patient assessment, without use of specialized imaging or histopathological techniques.

Clinical photograph of the hand.

Shows wart-like papules on the extremities, specifically the hand

Florid cutaneous papillomatosis associated with gastric adenocarcinoma (poorly differentiated carcinoma)

Florid cutaneous papillomatosis

Adenocarcinoma of stomach


A previously healthy 27-year-old man presented with cough, hemoptysis, and low-grade fever that had persisted for a few days. He denied night sweats and unexplained weight loss. He had a notable history of left supraclavicular lymph node enlargement that had been spontaneously enlarging and shrinking since age 15. On physical examination, he appeared thin with height of 168 cm and weight of 48 kg. His vital signs were mostly normal except for low-grade fever of 37.6°C and mild hypoxemia with arterial oxygen saturation of 94% on ambient air. Physical examination revealed crackles in the left upper lung field and left supraclavicular lymphadenopathy measuring 2 cm in diameter, which was nontender, firm, nonfixed, circumscribed, and rubbery. Laboratory findings showed increased WBC count of 20,000/μL with neutrophilic predominance (88.5%), erythrocyte sedimentation rate of 66 mm/h, and C-reactive protein level of 10.5 mg/dL. Secretory interleukin-2 receptor was elevated at 4,140 U/μL. Blood and sputum cultures for bacteria, acid-fast organisms, and fungi were negative. Serum titers for antimyeloperoxidase antineutrophil cytoplasmic antibody, antiproteinase 3 antineutrophil cytoplasmic antibody, rheumatoid factor, HIV antibody, and tumor markers were all negative. Otologic evaluation showed no apparent evidence of vasculitis or other diseases. Transbronchial lung biopsy showed granulomatous inflammation but no pathogens accounting for destructive lung disease.

Chest x-ray performed on admission to the local hospital.

The chest x-ray taken on admission to the local hospital showed infiltration involving the left upper lung field.

Chest x-ray on admission, left upper lung field.

The chest x-ray taken on admission to the hospital 2 weeks later showed that the infiltration had spread throughout the patient's entire left upper lung field with cavity formation.

CT of the thorax, nonenhanced, left upper lobe.

Nonenhanced thoracic computed tomography demonstrated thick-walled, multiple cavities in various sizes up to 4 cm in diameter that were distributed throughout the left upper lobe, some of which were coalescent, but no enlargement of either the mediastinum or hilar lymph nodes was observed.

Histological section, CD3 and CD30 immunohistochemical staining, negative for CD15, CD20, and CD79α.

Histologically, scattered large atypical lymphoid cells were detected in areas of granulomatous inflammation with abundant neutrophils, which mimicked abscess formation. These atypical lymphoid cells were positively stained with both CD3 and CD30, but were negative for CD15, CD20, and CD79α.

Left supraclavicular lymph node section, H&E staining, low-power magnification.

A: Low-power field hematoxylin and eosin (H&E)-stained section of the left supraclavicular lymph node showing destructive lymphoid follicles with a nodular component delineated by collagenous fibers.

H&E staining, CD30 and CD15 immunohistochemistry.

Typical Hodgkin cells (white arrows) and Reed-Sternberg cells (black arrowheads) with abundant lymphocyte infiltration or a small number of eosinophils in their background were contained. These atypical cells were positively stained with not only CD30 but also CD15 antibodies.

Nodular sclerosis classical Hodgkin lymphoma, stage IVA, according to the Ann Arbor staging classification


A 44-year-old woman was diagnosed with diffuse large B-cell lymphoma in August 2011. At primary staging, she presented with cervical, mediastinal, axillary, and inguinal lymphadenopathy, accompanied by approximately 60% infiltration of the bone marrow by malignant B cells. Her peripheral blood count revealed thrombocytopenia and leucocytopenia. During clinical examination, the spleen was not palpable in the left upper quadrant, but resistance was detected in the lower abdomen with distinguishable bruits. The patient weighed 140 kg with a body mass index of 51.4 kg/m², having lost several kilograms in recent months. Her medical history included delivery of twins by Caesarian section in 2002.

Lymph node biopsy, CD79a staining, 250× magnification.

Lymph node biopsy showed dense infiltration by CD79a+ centroblasts at ×250 magnification.

CT scan of the spleen, performed in 2006, maximum diameter 10 cm.

CT scan from 2006 showed normal spleen extension with maximum diameter of 10 cm.

CT scan of the abdomen, performed in 2010.

CT scan from 2010 first recognized spleen dislocation with normal extension within 10 cm.

CT scan at time of B-cell lymphoma diagnosis.

CT scan at time of B-cell lymphoma diagnosis documented hepatosplenomegaly with spleen measuring about 25 cm, prolapsing into a wide abdominal hernia.

Diffuse large B-cell lymphoma with dislocated spleen

Diffuse large B-cell lymphomas

dislocation NOS

Injury, poisoning or certain other consequences of external causes


An 18-year-old woman presented with a 3-week history of fever and cough productive of white, nonbloody sputum. Over the following week, she developed night sweats, extremely painful pharyngitis, pleuritic chest pain, increasing shortness of breath, nausea, vomiting, and diarrhea. She had a history of tonsillitis and hand surgery, lived with her family and a cat, worked outdoors, and had a bedroom that was reportedly damp and moldy. She smoked cigarettes and marijuana and had a new boyfriend. She had removed a tick from her abdomen approximately 1 week before presentation. On examination at the second hospital, she was in mild respiratory distress with blood pressure 140/74 mm Hg, pulse 127 beats per minute, temperature 37.3°C, respiratory rate 20 breaths per minute, and oxygen saturation 94% on ambient air. Her lips were dry, and coughing and scattered wheezing were heard. There was mild tenderness at the costovertebral angles and in all quadrants of the abdomen, without rebound. On examination at this hospital, she was sedated, intubated, and ventilated with a crusted lesion on her lip. Blood pressure was 112/64 mm Hg, pulse 65 beats per minute, temperature 37.0°C, and oxygen saturation 95% while breathing 60% oxygen. Expiratory breath sounds were louder in the right lung than in the left lung, and there was prominent physiologic splitting of the second cardiac sound with accentuation of the pulmonic-valve closure sound.

Laboratory results, including complete blood count, erythrocyte sedimentation rate, lactate dehydrogenase, galactomannan index, 1,3-β-D-glucan, Anaplasma and Ehrlichia DNA, Giemsa-stained peripheral-blood smears, blood gases, serology for Borrelia burgdorferi, Anaplasma phagocytophilum, HIV, and legionella urinary antigen testing.

Laboratory results showed leukocytosis with white-cell count of 17,200 per mm³ on second hospital admission progressing to 21,600 per mm³ on admission to this hospital, with neutrophilia (82% neutrophils initially, 61% on final admission). Hematocrit decreased from 38.9% to 30.5% and hemoglobin from 13.3 to 10.8 g/dl. Platelet count was markedly elevated at 752,000 per mm³. Erythrocyte sedimentation rate was elevated at 55 mm/hr. Thick and thin Giemsa-stained peripheral-blood smears showed no organisms. Lactate dehydrogenase was elevated at 346 U/liter. Galactomannan index was <0.5, 1,3-β-D-glucan was <31 pg/ml, and Anaplasma and Ehrlichia DNA were negative. Blood gases showed pH 7.41, partial pressure of oxygen 41 mm Hg, and partial pressure of carbon dioxide 43 mm Hg on venous blood. Testing for serum antibodies to Borrelia burgdorferi, Anaplasma phagocytophilum, and HIV were negative, as was legionella urinary antigen testing.

(A) Chest radiograph of the chest obtained on admission to the second hospital. (B, C) Chest CT, lung window, obtained 4 days later. (D) Portable chest radiograph of the chest obtained on admission to this hospital.

A chest radiograph obtained on admission to the second hospital (Panel A) shows patchy opacities in the left middle and lower lung zones and in the right lung base, a finding suggestive of pneumonia. Lung windows from a CT study of the chest obtained 4 days later (Panels B and C) show multifocal segmental and subsegmental consolidations and ground-glass opacities, with air bronchograms. A portable chest radiograph obtained on admission to this hospital (Panel D) shows persistent but improved bilateral multifocal pneumonia.

(A) Bronchoalveolar-lavage fluid specimen, Papanicolaou staining. (B) Bronchoalveolar-lavage fluid cell block, hematoxylin and eosin staining. (C) Bronchoalveolar-lavage fluid specimen, immunoperoxidase staining.

A specimen from the bronchoalveolar-lavage fluid shows numerous Tzanck cells (Panel A, arrows; Papanicolaou stain) with cytopathological changes that are typical of herpes simplex virus (HSV) infection. Cells from a cell block prepared from the broncho alveolar-lavage fluid show the typical cytopathological effect of HSV (Panel B, hematoxylin and eosin); both HSV-1 and HSV-2 antigens are detected with immunohistochemical staining (Panel C, immunoperoxidase).

Viral pneumonia


A 48-year-old male patient (height 165 cm, weight 76 kg) presented with abdominal pain in the right upper abdomen. He had a history of exploratory laparotomy for abdominal abscess 25 years prior without acute complications. The patient had been experiencing localized pain and allodynia around the surgical scar for 4 years. The pain was continuous, throbbing, and pulsatile in nature, aggravated by overwork or alcohol consumption, and relieved by compression of the scar. Pain intensity was 4 out of 10 at rest and up to 8 out of 10 when aggravated on an 11-point numeric rating scale. When aggravated, the pain radiated to his right upper arm once every 2-3 seconds with similar nature and intensity as the original pain, accompanied by a heated sensation in both the abdomen and right upper arm. The patient had diabetes mellitus and was taking aspirin and hypoglycemic medications. Previous investigations including two abdominal CT scans and cervical spine MRI showed no abnormal conditions. Physical examination revealed a 3 cm long surgical scar on the right upper abdomen with focal tenderness, allodynia, and hyperesthesia around the scar, while the right upper arm showed no abnormal findings.

Color Doppler ultrasound of the subcutaneous layer at the mid-surgical scar, mass size 0.62 × 0.27 × 0.69 cm.

Color Doppler ultrasound demonstrates a vascular mass with turbulent blood flow measuring 0.62 × 0.27 × 0.69 cm in the subcutaneous layer of the mid-surgical scar, showing active blood flow in the pseudoaneurysm.

Fluoroscopy of the right upper abdomen, anteroposterior view.

Fluoroscopy shows an oval mass filled with contrast media at the right upper abdomen on the anteroposterior view.

Pseudoaneurysm of the abdominal wall with referred pain to the right arm

pseudoaneurysm

Cardiovascular and respiratory disorders


55-year-old white man with history of stage III colon adenocarcinoma diagnosed in 2010. In November 2011, presented with right shoulder pain. Laboratory tests showed elevated carcinoembryonic antigen level of 13.9 ng/mL (normal level, ≤ 5 ng/mL)

MRI of the right scapula.

MRI showed expansive lesion with cortical involvement in the right scapula (48 x 35 x 64 mm)

MRI of the inferior left lung lobe.

MRI showed solitary lung nodule measuring 2 cm in diameter in the posterior segment of the inferior left lung lobe

Bone scan of the right scapula.

Bone scan showed increased uptake in the right scapula

Bone biopsy, histopathology.

Bone biopsy histopathology showed proliferation of atypical cells with basophilic cytoplasm and hyperchromatic and macrocariotic nuclei arranged in complex architectural pattern with glandular differentiation

Immunohistochemical analysis, cytokeratin 20 positive, cytokeratin 7 negative.

Immunohistochemical profile was cytokeratin 20 positive/cytokeratin 7 negative, consistent with colonic origin

Colon cancer recurrence with skeletal (right scapula) and lung metastases, with VEGF-positive lesions

Malignant neoplasms of colon

bone metastasis

metastasis in lung


27-year-old female, 162cm tall, 30kg weight. Born after normal pregnancy/delivery. No family history of neurological diseases. Normal early development. At age 6, developed general muscle weakness and gait disturbance with decreased muscle tone/strength and atrophic muscle mass. At age 8, muscle biopsy showed mitochondrial myopathy of pleoconial type. At age 24, had sudden syncope. At age 26, had stroke with general weakness, aphagia, and dysarthria. Current presentation at age 27 with left hemiplegia and aphasia. Lab findings: plasma lactate 21.8 mg/dL (elevated), normal CBC/electrolytes/BUN/creatinine, free T4 1.76 ng/dL, TSH 0.04 μIU/mL, C3 13 mg/dL (low), C4 18 mg/dL (normal). Negative for ASO antibody, rheumatoid factor, anti-dsDNA, lupus anticoagulants, and anti-cytoplasmic antibody. DNA sequencing showed m.3303C>T mutation in mitochondrial tRNA leucine 1 gene.

Brain MRI.

Brain MRI shows restricted diffusion involving right front-temporal lobe, right insula and right basal ganglia, indicating acute infarction in right middle cerebral artery territory

MR angiography of the head and neck.

MR angiography shows non-visible flow at right distal internal carotid artery and right middle cerebral artery

(A) Echocardiography, left ventricular apex, short axis view. (B) Echocardiography, left ventricular apex, two chamber view.

Echocardiography detected a mobile small thrombus (arrow) with length of 2.2 cm attached to left ventricular apex at short axis view (A) and two chamber view (B).

MELAS (Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like Episodes) syndrome with intracardiac thrombus

MELAS - [Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes] syndrome

intracardiac thrombus


66-year-old male with diabetes presenting with acute onset visual loss in left eye 6 hours before emergency service visit. History includes episodes of palpitation and dizziness, previously diagnosed with non-valvular atrial fibrillation.

Visual field examination.

Visual field examination shows visual field defect in right superior nasal quadrant and left superior temporal quadrant, indicating left homonymous superior quadrantanopia

(A) Brain MRI, diffusion weighted imaging. (B) Brain MRI, apparent diffusion coefficient map. (C) Brain MRI, susceptibility weighted imaging.

Brain MRI findings: (A) Diffusion weighted imaging shows hyperintense signal in right inferior occipital region; (B) Apparent diffusion coefficient map shows dark signal in right inferior occipital region; (C) Susceptibility weighted imaging shows areas of hypointensity indicating petechial hemorrhage. Findings indicate acute infarction with mild hemorrhagic transformation in inferior occipital cortex

ECG recordings.

ECG recordings showing: First recording with P waves and regular RR interval; Middle recording showing P waves replaced by fibrillation waves with irregular RR intervals and faster heart rate; Last recording showing return of P waves and regular RR intervals - indicating paroxysmal atrial fibrillation

Acute ischemic stroke with hemorrhagic transformation in right inferior occipital region due to cardioembolism from paroxysmal atrial fibrillation

Cerebral ischaemic stroke in association with subarachnoid haemorrhage[acute subarachnoid haemorrhage NOS]

Hemorrhagic transformation of ischemic stroke

haemorrhagic stroke NOS

Cardiac embolism

Paroxysmal atrial fibrillation


A 35-year-old man presented with a two-day history of melena and syncope. His medical history included systemic mastocytosis (SM) diagnosed in childhood when he presented with a diffuse, blistering rash, and type II diabetes mellitus. A previous liver biopsy had shown multiple mast cells in the portal tracts with individual mast cells in the liver sinusoids. At presentation, his SM manifested with chronic diarrhea and a pruritic rash despite combined histamine blockade with ranitidine and cetirizine. In the emergency unit, he experienced additional gastrointestinal hemorrhage. Upper and lower gastrointestinal endoscopies revealed only mild gastritis with a normal colon. A capsule enteroscopy revealed an intraluminal mass in the proximal small bowel. The patient underwent laparoscopic excision of one of the small bowel lesions, which was found to be a 40-mm spindle cell tumor. Immunohistochemistry was negative for cytokeratin AE1/AE3, cytokeratin 20, epithelial membrane antigen, synaptophysin, S100, desmin, and smooth muscle actin. The Fletcher/Miettenen risk stratification was low based on the single excised lesion (<5-cm diameter tumor, 0 mitosis/50 hpf), but he had multiple lesions throughout the duodenum and jejunum.

(A, B) Computed tomography with oral contrast, duodenum and jejunum.

Oral contrast computed tomography demonstrated multiple soft tissue lesions throughout the duodenum and jejunum (arrows shown in subfigures A and B)

(A) Intraoperative clinical photograph of the small bowel obtained during laparoscopy. (B) Intraoperative clinical photograph of the small bowel obtained during laparoscopy.

Figure 2 demonstrates two intraoperative clinical photographs of the small bowel obtained during laparoscopy, showing distinct exophytic lesions on the bowel surface indicative of gastrointestinal stromal tumors; panel A displays a single lesion being manipulated with forceps, and panel B presents a broader view of an additional lesion on the small bowel, confirming the presence of multiple tumors within the operative field.

The excised lesion. Immunohistochemistry for CD117.

Tumor with strong diffuse membrane staining for CD117

The excised lesion. Hematoxylin and eosin staining.

Hematoxylin and eosin stain demonstrating a collection of mast cells in the submucosa

Genetic sequence analysis of exon 9 of KIT at nucleotide c1526 in tumor, peripheral blood, bone marrow aspirate, and cell lineages (CD117+, CD19+, CD3+), showing single base substitution (A>T) with 1:1 heterozygous pattern.

Genetic sequence analysis showing a single base substitution (A>T) in exon 9 of KIT at nucleotide c1526, resulting in a missense mutation K509I, found in tumor, peripheral blood, bone marrow aspirate samples, and various cell lineages (CD117+, CD19+, CD3+) with a 1:1 heterozygous pattern

Multiple gastrointestinal stromal tumors with systemic mastocytosis associated with germline KIT exon 9 mutation (K509I)

Gastrointestinal stromal tumour of unspecified gastrointestinal sites

Systemic mastocytosis

Harris lines

Diseases of the musculoskeletal system or connective tissue


A 52-year-old man from the Azores who immigrated to the United States at age 10 presented to the emergency department with acute onset of palpitations and chest pressure. Two days prior to presentation, he had developed epigastric burning, fatigue, weakness, and emesis, which improved partially with antacids. He denied antecedent fevers, chills, or other localizing symptoms. His medical history was notable for hypertension, benign prostatic hypertrophy with obstructive nephropathy, chronic renal insufficiency of unknown cause requiring dialysis until receiving a renal transplant from a living related donor one year prior, and hyperparathyroidism with bilateral cataract surgery. He had excellent adherence to his medications including mycophenolate, tacrolimus, aspirin, metoprolol, furosemide, omeprazole, and tamsulosin. His blood pressure had been well controlled for years before transplantation. On presentation, his heart rate was 200 beats per minute with atrial fibrillation and rapid ventricular response. After cardioversion, vital signs showed regular pulse of 53 beats per minute and blood pressure of 128/90 mmHg. Physical examination revealed a diffuse and laterally displaced apical impulse, prominent second heart sound, audible fourth heart sound, but no murmurs or jugular venous distention. Laboratory results showed normal electrolytes, creatinine 1.5 mg/dL, elevated troponin T at 1.04 ng/mL, normal liver function tests, white cell count 6100 per cubic millimeter with 72% neutrophils, hematocrit 37.9%, platelet count 148,000 per cubic millimeter, normal thyrotropin level, tacrolimus level 8.2 ng/mL, and urinalysis notable for 2+ proteinuria. Serum protein electrophoresis and free light-chain ratio were unremarkable. Leukocyte α-galactosidase activity was markedly reduced at 0.4 nmol per hour per milligram (reference >23.1).

12-lead electrocardiogram obtained after electrical cardioversion; PR interval=108 ms, prolonged QRS duration, increased R-wave amplitude in precordial leads (V3 and V4), ST-segment and T-wave abnormalities, presence of delta waves.

Figure 1 shows a 12-lead electrocardiogram obtained after electrical cardioversion, demonstrating sinus rhythm with frequent premature atrial depolarizations, a shortened PR interval of 108 milliseconds, prolonged QRS duration, markedly increased R-wave amplitude in the precordial leads (particularly V3 and V4), associated ST-segment and T-wave abnormalities, and the presence of delta waves as indicated by arrows, collectively suggestive of left ventricular hypertrophy and ventricular preexcitation.

(A-C) Echocardiography. (D) Doppler study.

The echocardiographic images in Panels A, B, and C show biventricular hypertrophy and left atrial enlargement, and the Doppler study in Panel D shows impaired myocardial relaxation.

Fabry's disease with nonsense mutation in the second exon of GLA gene encoding α-galactosidase

Fabry disease

Endocrine, nutritional or metabolic diseases


A 53-year-old man initially diagnosed with seminoma in 2007 presented with painful right testicular swelling. At initial diagnosis, preoperative tumor markers showed β-human chorionic gonadotropin (β-hCG) level of 1 mIU/mL, α-fetoprotein level of 3.6 ng/mL, and minimally elevated lactate dehydrogenase level of 213 U/L. The orchiectomy pathology revealed a 4.1-cm pure classical seminoma contained by the tunica albuginea with focal extension into rete testis and perivesicular soft tissue, with no lymphovascular invasion and uninvolved spermatic cord. Initial computed tomography scans were negative for metastases. His medical history included remote right shoulder surgery for rotator cuff tear and frozen shoulder. During surveillance in December 2011, he developed elevated β-hCG (86 mIU/mL) that was rapidly increasing, while lactate dehydrogenase and α-fetoprotein levels remained normal. Physical examination, CT of chest/abdomen/pelvis, and left testicular ultrasound showed no evidence of recurrence or new primary tumor.

MRI of the right shoulder, proximal humerus, bone lesion size 3 cm.

MRI of the right shoulder confirmed a 3-cm enhancing bone lesion in the proximal right humerus

FDG-PET of the right proximal humerus, SUVmax=4.9.

FDG-PET revealed a hypermetabolic focus in the right proximal humerus with a standardized uptake value of 4.9, suggestive of a metastatic lesion and clearly distinct from the tendinous structures

CT-guided core needle biopsy of the humerus.

CT-guided core needle biopsy of the humeral lesion revealed sheets of large cells with clear cytoplasm, distinct cytoplasmic borders, and vesicular nuclei consistent with metastatic classical seminoma

Immunohistochemical staining for placental alkaline phosphatase, CD117, CD30, pankeratin, and epithelial membrane antigen.

Neoplastic cells were positive for placental alkaline phosphatase and CD117 but were negative for CD30, pankeratin, and epithelial membrane antigen

Solitary bony metastasis in seminoma (metastatic classical seminoma to the right proximal humerus)

seminoma; anaplastic, unspecified site

bone metastasis


76-year-old man from the Indian subcontinent presented with fever and priapism. Physical exam showed painful, engorged penis with intact skin, no lymphadenopathy, hepatomegaly, or splenomegaly. No skin rash or nodules were found.

(D–F) PET scan, prostate and left acetabulum. (J–O) PET scan, pubis, prostate, and penis. (P–R) PET scan, sacrum and penis.

PET scan showed abnormal FDG uptake in prostate, penis, and several bones (right humerus, sacrum, pubis, left acetabulum). Subfigs D-F show prostate and acetabulum involvement; J-O show pubis, prostate, and penis involvement; P-R show sacral and extensive penile involvement.

(A) Penile biopsy. (B) Prostate biopsy. (C-D) Prostate biopsy, immunohistochemical staining for CD45, CD20, CD3, and Congo red.

Penile biopsy (Subfig A) and prostate biopsy (Subfig B) showed large abnormal lymphoid cells partially occluding small blood vessels. Immunohistochemical staining of prostate biopsy showed CD45+, CD20+, CD3-, and Congo red negative cells (Subfigs C-D).

Intravascular large B-cell lymphoma (IVLBCL) with involvement of the penis, prostate, and bones

Intravascular large B-cell lymphoma

Lymphoma NOS

prostatism

Lymphoma NOS


52-year-old woman presented with a one-month history of daily temperatures exceeding 38.5°C, night sweats, fatigue, and intermittent productive cough. She had no significant medical comorbidities. Physical examination revealed obesity with a BMI of 38.2 kg/m², but was otherwise unremarkable with no other notable findings. Laboratory analysis showed normocytic anemia with hemoglobin of 93 g/L, thrombocytopenia with platelet count of 88 × 10⁹/L, and normal white blood cell count. Biochemical analysis demonstrated elevated inflammatory markers including erythrocyte sedimentation rate of 93 mm/h, C-reactive protein of 79 mg/L, lactate dehydrogenase of 1,252 U/L, and beta-2 microglobulin of 9.0 mg/L. Immunoglobulin levels, autoantibodies, and serum angiotensin-converting enzyme were normal. Extensive infectious workup was negative, including chest radiography, CT chest and abdomen with contrast, blood/urine/sputum cultures for bacteria, mycobacteria, viruses (HIV, hepatitis B and C), peripheral blood smears for parasites, and bone marrow biopsy which showed normal findings.

Whole-body PET/CT with [18F]FDG.

Whole-body positron emission tomography/CT (PET/CT) with [18F]fluorodeoxyglucose (FDG) was performed, revealing multiple hypermetabolic nodules of various sizes distributed throughout subcutaneous adipose tissue.

H&E-stained histopathological section of skin tissue, 50× magnification.

Figure 2 in this article shows a hematoxylin and eosin (H&E)-stained histopathological section of skin tissue at 50x magnification, illustrating a diffuse, nonepidermotropic infiltrate of large lymphoid cells present in the papillary and deep reticular dermis.

section of skin tissue. Immunohistochemistry for CD20.

Immunohistochemistry demonstrated neoplastic cells positive for CD20

section of skin tissue. Immunohistochemistry.

Immunohistochemistry showed neoplastic cells positive for BCL-2

section of skin tissue. Immunohistochemistry for immunoglobulin M.

Immunohistochemistry revealed neoplastic cells positive for immunoglobulin M

section of skin tissue. Immunohistochemistry, Ki-67=70%, CD79a positive, MUM-1 positive, CD3 negative, CD5 negative, BCL-6 negative, CD10 negative.

Immunohistochemistry demonstrated Ki-67 positivity in 70% of cells, with additional positive staining for CD79a and MUM-1, but negative for CD3, CD5, BCL-6, and CD10

Primary cutaneous diffuse large B-cell lymphoma (PCLBCL), leg type (LT)

Primary cutaneous diffuse large B-cell lymphoma, leg type


26-year-old previously healthy woman presented to emergency department immediately after being involved in a road traffic incident. Clinical examination led to suspicion of scaphoid injury.

Wrist radiograph, posteroanterior view.

Posteroanterior radiograph of wrist showing an incomplete lucency at the waist of scaphoid suspicious for a fracture but not definitive

MRI of the wrist, coronal T1-weighted sequence with fat saturation.

Magnetic resonance imaging of the wrist using coronal T1 with fat saturation showing a clear, non-displaced scaphoid waist fracture

MRI of the wrist, coronal view, T2-weighted sequence with fat saturation.

Magnetic resonance imaging of the wrist using coronal T2 with fat saturation showing a clear, non-displaced scaphoid waist fracture

Scaphoid waist fracture (confirmed by MRI)

fracture of scaphoid

Orthopedic and connective tissue disorders


A 70-year-old woman presented to the gynecologic cancer center with postmenopausal vaginal bleeding. Approximately one month prior, she had noted brown vaginal discharge, and vaginal bleeding developed 18 days before her evaluation. She reported no pelvic pain, change in appetite or weight, nausea, or vomiting. Her obstetric history was gravida 3, para 3, with normal spontaneous vaginal deliveries. Her last menstrual period was 20 years earlier. Eleven years earlier, she had uterine bleeding that resolved after endometrial polypectomy. Ten years earlier, she was diagnosed with infiltrating ductal carcinoma of the right breast (T2N0) with positive estrogen and progesterone receptor testing and HER2 overexpression, treated with lumpectomy, sentinel lymph node mapping, adjuvant chemotherapy, radiation therapy, and hormonal therapy (tamoxifen for 4 years followed by anastrozole). Her medical history also included osteoporosis, hypercholesterolemia, and hypothyroidism. Her family history was significant for heart disease in both parents who died in their 90s, maternal grandfather who died of pancreatic cancer at age 70, and maternal uncle who died of liver cancer at age 60. Physical examination revealed an obese patient with normal vital signs; the uterus was small and mobile with no vulvar, vaginal, or cervical lesions. The remainder of the examination was unremarkable.

(A) Hysterectomy specimen, H&E staining. (B) Hysterectomy specimen, H&E staining. (C) Hysterectomy specimen, H&E staining. (D) Hysterectomy specimen, H&E staining.

Hysterectomy specimen (Hematoxylin and Eosin) showing malignant mixed müllerian tumor composed of high-grade serous carcinoma with pseudoglandular architecture and high-grade homologous sarcoma (Panel A), heterologous sarcomatous elements represented by chondrosarcoma (Panel B), epithelial component that has invaded the myometrium (Panel C), and lymphatic spaces (Panel D).

Malignant mixed müllerian tumor (carcinosarcoma) of the uterus, with a PIK3CA mutation

Malignant mixed müllerian tumor of the uterus

Malignant mixed Mullerian tumours[Uterine ligament]

Carcinosarcoma of uterus


A 38-year-old white Scottish man with mild learning difficulties (able to read and write but not maintain employment) presented with a three-day history of diplopia and agitation, following seven days of presumed viral gastroenteritis. On examination, he was agitated, mildly confused, tachycardic (115 beats/min, regular), and tachypnoeic (18 breaths/min). He had horizontal nystagmus, with dilated, slowly reacting pupils. Limb movements were clumsy with moderate cerebellar signs and dysdiadochokinesis, but no tremor. He was clinically jaundiced. He gave a history of lifelong alcohol avoidance and had experienced 34 kg weight loss over the preceding three months (from initial weight of 127 kg, BMI 42.4, dropping from 123 kg at four weeks to 110 kg at eight weeks). He reported excluding all identifiable sources of carbohydrate and eating virtually no solid food other than occasional rice crispies and chicken nuggets during his extreme dietary restriction.

(A) Clinical photograph of the eyes, left lateral gaze, obtained on admission. (B) Clinical photograph of the eyes, right lateral gaze, obtained on admission.

Figure 1 consists of paired clinical photographs of the patient's eyes taken during an examination in which the patient was asked to gaze to the extreme left and right. Image A shows the left lateral gaze, and image B shows the right lateral gaze. These photographs demonstrate bilateral sixth cranial (abducent) nerve palsies, resulting in complete paralysis of the lateral rectus muscles, as evidenced by the failure of both eyes to abduct appropriately. The images were obtained on admission during the acute neurological presentation.

Laboratory results after admission

Laboratory results on day 1 showed red cell thiamin diphosphate of 132 ng/g haemoglobin (reference 275-675), vitamin C of 3 μmol/L (reference 15-90), vitamin A of 0.5 μmol/L (reference 1-3), red blood cell vitamin B6 of 139 pmol/g haemoglobin (reference 250-680), selenium of 0.66 μmol/L (reference 0.8-2.0), and folate of 1.4 ng/mL (reference 3.1-20.0). Liver function tests showed bilirubin 48 μmol/L (reference <20), alkaline phosphatase 140 U/L (reference 40-150), alanine aminotransferase 70 U/L (reference <50), and γ-glutamyltransferase 111 U/L (reference <70)

Wernicke's encephalopathy as a result of acute thiamin deficiency

Wernicke encephalopathy

thiamine deficiency


A 61-year-old white man presented to the emergency department with complaints of severe back pain. He had a previous medical history of hypertension and had undergone an open small bowel resection for an idiopathic small bowel obstruction at age 52 years. He was an otherwise healthy married shoe salesman with two healthy children and no significant family or social history. Initial radiographs demonstrated multiple lumbar fractures, and bone surveys revealed osteolytic lesions involving vertebral segments L4 through T11. Protein electrophoresis and urine assays revealed elevated κ light chains. Physical examination revealed an ill-appearing, slightly malnourished man with moderate abdominal tenderness, temporal wasting, and diffuse muscle atrophy. He presented later with complaints of profound fatigue, malaise, and acute diarrhea accompanied by diffuse abdominal pain. Routine laboratory work revealed amylase >10,000 μ/L, lipase 26 μ/L, lactate dehydrogenase 1,526 μ/L, serum creatinine 1.39, blood urea nitrogen 19, total bilirubin 3.7, direct bilirubin 0.4, AST 56, ALT 66, alkaline phosphatase 121 μ/L, platelets 32,000/mm², WBC 3,200/mm³, hemoglobin 10.4 g/dL, and mean cell volume 91 fL. Additional serologic investigation revealed s-amylase 10,448 μ/L, pancreatic amylase 357 μ/L, urine amylase total 38,832 μ/L, amylase/creatine clearance ratio 4%, ferritin 11,628 ng/mL, iron 78 μg/dL, IgG total 401 mg/dL, IgA 10 mg/dL, IgM 18 mg/dL, quantified serum and urine kappa light chain 110 mg/dL and 1,450 mg/dL respectively, with negative SS-ro antibody, SS-la antibody, antinuclear antibody, double-stranded DNA antibody, rheumatoid factor (7 IU/mL), and prealbumin (14 mg/dL).

(A) Bone marrow aspirate, ×10 magnification. (B) Bone marrow aspirate, ×40 magnification. (C, D) Bone marrow aspirate, ×100 magnification. (E) Cytochemical analysis by fluorescent in situ hybridization.

Bone marrow aspirates at ×10 (A), ×40 (B), ×100 (C), and ×100 (D) revealed a complete replacement of normal marrow architecture with plasma cell infiltrates. Note the eccentric nuclei (white arrows), perinuclear hof (black arrow), and clumped chromogranin. Cytochemical analysis by fluorescent in situ hybridization demonstrated monosomy of chromosome 13q, a frequently encountered genetic abnormality in multiple myelomas that is known to be an adverse finding.

s-amylase-producing κ light chain multiple myeloma

multiple myeloma


A 22-year-old female presented with a gradually increasing pelvic mass with tenderness for 1 month. There was no evidence of previous trauma or fever, and no history of other medical or surgical disease and no evidence of pregnancy. On physical examination, there was a palpable mass with tenderness in her left pelvic area.

Plain radiograph of pelvis.

Plain radiograph of pelvis shows huge, geographic osteolytic lesion with thick, irregular sclerotic rim in left ilium.

(B) Precontrast CT of the left ilium. (C) Contrast-enhanced CT of the left ilium.

On precontrast CT image (B), there is irregular, large osteolytic lesion in left ilium with exophytic soft tissue mass and stippled calcifications. On contrast-enhanced CT (C), mass shows heterogeneous enhancement with irregular, rim and septal enhancement.

(D) MRI, T1-weighted sequence. (E) MRI, fat-suppressed T2-weighted sequence. (F) MRI after gadolinium enhancement.

On MRI, mass has heterogeneous intermediate signal on T1-weighted image (D), heterogeneous high signal on fat suppressed T2-weighted image (E), and thick irregular low signal septa on T1 and T2-weighted images. After enhancement with gadolinium, mass shows heterogeneous enhancement and non-enhanced septa (F).

99mTc hydroxymethane diphosphonate bone scan, anterior view.

99mTc hydroxymethane diphosphonate bone scan. Anterior view shows increased peripheral isotope uptake of left iliac bone lesion.

(H) 18F-FDG PET maximum intensity projection. (I) 18F-FDG PET, axial view, maximum SUV=5.1. (J) 18F-FDG PET/CT fusion, axial view, maximum SUV=5.1.

18F-FDG PET MIP (H), PET axial (I), and PET/CT fusion axial (J) images show heterogeneously increased FDG uptake of left iliac bone lesion (maximum SUV = 5.1).  18F-FDG = 2-fluoro [fluroine-18]-2-deoxy-D-glucose

Photomicrograph, H&E staining, 200× magnification.

Photomicrograph shows dilated blood-filled vessels lined by flattened endothelial cells (H/E, x 200).

Cavernous haemangioma of unspecified site


Patient 1 (P1) is a 6-year-3-month-old female of Indian origin from Andhra Pradesh, born to first cousin parents in a multiply consanguineous family. She was born at term via normal vaginal delivery with birth weight of 3.2 kg (25th centile) following a pregnancy complicated by maternal hypertension. She presented with mild neonatal hypotonia and slender, generally hypermobile fingers with bilateral contractures of the fifth digits preventing full extension. Skin hyperelasticity was reported in infancy. Motor milestones were achieved slightly later than average due to hypotonia, while language and social milestones were appropriate. At age 4, she experienced spontaneous vertical Descemet's membrane splitting in the right cornea resulting in corneal edema, and the left cornea was noted to be thin. She subsequently sustained a corneal rupture in her left eye at age 4 years 3 months with subsequent total visual loss, and has very little residual vision in her right eye. Pure tone audiometry at 4.5 years showed bilateral mild hearing loss. Tympanometry was consistent with hypercompliant tympanic membranes with hypermobility of the ossicular chain. Physical examination at age 4 showed height and weight above average (75th and 95th centiles respectively), soft but not hyperextensible skin with no abnormal bruising or scarring, prominent fetal fingertip pads, and pes planus. No fractures, joint dislocations, or developmental hip dysplasia were present. An echocardiogram at age 3 showed mitral valve prolapse and mild mitral regurgitation with normal aortic root diameter.

Table summarizing clinical, genetic, and phenotypic features of three individuals with brittle cornea syndrome.

Table 1, found on page 3, summarizes the salient clinical findings of three novel affected individuals (P1, P2, and P3) with brittle cornea syndrome from unrelated families, presenting data on features such as age at diagnosis, gender, origin, consanguinity, specific ZNF469 mutations, and presence or absence (with degree indicated as ++, +, or −) of major clinical manifestations including bluish sclera, corneal rupture, keratoconus or keratoglobus, skin and joint involvement, Beighton score, developmental delays, hearing impairment, fractures, and cardiovascular abnormalities; the table serves as a concise comparative overview of the genotype and phenotype correlations in these cases.

Brittle cornea syndrome (BCS) caused by homozygous ZNF469 mutation

Brittle cornea syndrome


A 75-year-old man was found to have lymphocytosis incidentally on a preoperative complete blood count that showed normal hemoglobin and platelet count, with total white blood cell count of 11.9 × 10^9/L and absolute B-cell lymphocyte count of 5.67 × 10^9/L. Peripheral blood flow cytometry revealed a kappa light chain restricted B-cell clone that was CD5+, CD23+, CD19+, CD20 (dim), ZAP-70+, and CD38+. Immunoglobulin variable region heavy chain gene sequencing did not detect a functional gene. Bone marrow biopsy was hypercellular (40%) with a nodular interstitial infiltrate of CLL cells (30% to 40%). Conventional cytogenetics and interphase fluorescent in situ hybridization showed trisomy 12. Physical examination revealed no palpable lymphadenopathy or hepatosplenomegaly, corresponding to clinical stage Rai 0. Approximately one year after diagnosis, he developed right eye pain associated with blurry vision, floaters, and bright halos. When evaluated at Mayo Hematology Clinic, his white blood cell count had increased to 48.7 × 10^9/L with an absolute lymphocyte count of 34.9 × 10^9/L. Initial MRI of his orbits was reported as normal. CSF analysis revealed lymphocytosis but was not initially characterized by flow cytometry. Later repeat CSF analysis demonstrated 29 total nucleated cells per μL with 96% lymphocytes, normal CSF glucose and protein levels, and flow cytometry showed 50% of lymphocytes were clonal (kappa light chain restricted) with immunophenotype compatible with CLL. No oligoclonal bands were seen in CSF, and CSF immunoglobulin G index was 0.6 (normal <0.85). After corticosteroid taper, he developed marked visual field loss in the right eye. Subsequent CSF analysis showed 20 total nucleated cells per μL with 87% lymphocytes (35% clonal). Serum and CSF testing were negative for Cryptococcus, toxoplasmosis, herpes zoster, John Cunningham virus, human herpesvirus 6, herpes simplex, Epstein-Barr virus, and cytomegalovirus infections. Serum angiotensin-converting enzyme was not elevated.

Funduscopic examination of the right eye.

Funduscopic examination shows persistent right eye disc edema, blurring, and peripapillary hemorrhages.

Funduscopic color photograph of the right eye optic disc.

B: Funduscopic color photograph of the right eye optic disc demonstrating progressive chronic changes including papilledema and blurring, consistent with either perioptic nerve infiltration or chronic papilledema, acquired during the course of visual field loss after corticosteroid dose taper in a patient with chronic lymphocytic leukemia.

MRI T1-weighted images of the right optic nerve.

MRI T1-weighted images show abnormal enhancement of the right optic nerve (indicated by red circle).

chronic lymphocytic leukaemia

Disorder of the optic nerve


A 29-year-old right-hand dominant male chef presented to the emergency department with a four-day history of feeling "not normal." He experienced gradual onset of dull pain on the left side of his neck radiating up into his head that was progressively worsening, along with diplopia ("seeing two of everything"). The pain was not influenced by changes in posture. He also reported right-sided numbness, dropping things at work, and feeling unsteady on his feet. He denied recent alcohol consumption, illicit drug use, seizure activity, head injury, or loss of consciousness. His medical history included hypothyroidism treated with thyroxine. On examination, he was alert and oriented with blood pressure of 141/94 mmHg and normal other vital signs. He had moderate weakness on the right side (Medical Research Council grade 4), mainly in the upper limb, with pronator drift, and reduced sensation to pinprick, light touch, and proprioception on the same side. There was evidence of resting and intention tremor with dysdiadochokinesia of the upper limbs, more evident on the right side. He had a broad-based gait consistent with cerebellar ataxia. He had an upgoing plantar response on the right and downgoing on the left. His pupils were equal and reactive to light, but he had diplopia on both extremes of gaze without clinical evidence of ocular palsy. No papilloedema was detected on fundoscopy.

CT head scan, initial examination.

Initial computed tomography head scan performed to rule out serious disease.

CT of the head, performed during initial imaging.

Additional computed tomography head scan performed as part of initial imaging.

CT of the brain, brainstem region, dorsal pons, adjacent to the fourth ventricle.

Computed tomography shows hyperdensity within the brainstem in the area of the dorsal pons, adjacent to the fourth ventricle, representing an acute parenchymal haematoma within the posterior midline of the pons.

CT of the foramen magnum.

Computed tomography shows evidence of tonsillar herniation, with effacement of the cerebrospinal fluid space at the foramen magnum where cerebrospinal fluid space has been replaced by cerebral parenchymal tissue.

CT of the brain.

Computed tomography shows large prominent lateral ventricles, indicative of hydrocephalus.

T1-weighted sagittal FLAIR MRI scan of the brain (pons and cerebellar region), without gadolinium.

T1 weighted sagittal FLAIR magnetic resonance imaging scan (without gadolinium) shows a well circumscribed heterogeneous lesion within the pons and descent of the cerebellar tonsils through the foramen magnum by 12 mm, consistent with Chiari I malformation.

T2-weighted axial MRI of the brain, without gadolinium.

T2 weighted axial magnetic resonance imaging scan (without gadolinium) shows the typical "popcorn" appearance of a cerebral cavernous malformation and a peripheral rim of hypointensity consisting of surrounding oedema and deposition of haemosiderin.

Pontine cavernous malformation with acute hemorrhage

pontine haemorrhage[Cerebral cavernous malformation]

Hepatic haemorrhage[Acute]


A 6-year-old girl presented with a 1-year history of intermittent bone and joint pain and recent onset of fever and abdominal distention. The patient had been well until 1 year before admission when she fell on her left hand and experienced migratory joint pain. Over the following year, she developed intermittent rib pain, right knee pain with limping, and left flank pain that radiated to her left leg. Six days before admission, she developed back pain, limping, and intermittent fever up to 39.8°C. The day before admission, she developed periorbital swelling, abdominal distention, and periumbilical discoloration. On examination, she was febrile (38.7°C), had bilateral periorbital discoloration, and a soft, nontender abdomen. She exhibited slight limping and flinching with external rotation of the right hip. Her height was 123.8 cm and weight 27.2 kg. Past medical history included gastroesophageal reflux as an infant and pollen allergy with allergic rhinitis. Family history was notable for paternal grandmother with rheumatoid arthritis and breast cancer, and no family history of childhood arthritis or other autoimmune conditions.

Laboratory results over time.

Laboratory values over time showed progressive anemia (hematocrit declining from 35.6% to 30.9%, hemoglobin from 12.0 to 10.6 g/dl), persistently elevated erythrocyte sedimentation rate (41-66 mm/hr), elevated C-reactive protein (3.0-8.3 mg/dl), reticulocytes 3.0%, prolonged prothrombin time 14.4 sec with INR 1.2, elevated lactate dehydrogenase 517 U/liter, and elevated ferritin 470 ng/ml. Lyme disease antibodies were negative on multiple occasions.

(A) CT of the left axilla and left humerus. (B) CT of the abdomen, liver, and kidneys. (C) CT of the retroperitoneum and kidneys. (D) CT of the abdomen and pelvis.

CT images show left axillary lymphadenopathy (Panel A, arrow) and retroperitoneal lymphadenopathy (Panel C, arrow). Multiple soft-tissue hypodense lesions in the liver (Panel B) and kidneys (Panels B and C) and a large dominant abdominal–pelvic mass (Panel D, arrow) are apparent. There are lytic lesions in the left humerus (Panel A, arrowhead).

(A) FDG-PET/CT of the chest, left axillary lymph node. (B) FDG-PET/CT of the abdomen and pelvis, abdominal–pelvic mass. (C) FDG-PET/CT of the abdomen, liver lesions. (D) FDG-PET/CT of the skeleton, left humerus.

Images from an 18F-fluorodeoxyglucose–positron-emission tomographic (FDG-PET) scan were fused with CT images of the chest and abdomen with color overlay. There is increased FDG avidity in the left axillary lymph node (Panel A, arrow), the abdominal–pelvic mass (Panel B, arrow), and the liver lesions (Panel C, arrow). There are scattered foci of increased FDG avidity in the skeleton, most prominently in the left humerus (Panel D, arrowhead).

(A) Biopsy of abdominal–pelvic mass, H&E staining. (A, inset) Immunoperoxidase staining for TdT. (B) Bone marrow aspirate smear, Wright–Giemsa staining. (C) Flow-cytometric analysis of bone marrow aspirate, CD10-positive, CD19-positive cells. (D) Flow-cytometric analysis of bone marrow aspirate, weak CD45-positive, CD33-positive cells.

Examination of a biopsy specimen from the abdominal–pelvic mass shows a monotonous population of cells with finely dispersed chromatin and scant cytoplasm (Panel A, hematoxylin and eosin). Immunohistochemical studies of these primitive-appearing cells show coexpression of terminal deoxynucleotidyl transferase (TdT), a marker of lymphoid blasts (Panel A, inset; immunoperoxidase), and CD10 (not shown), as well as positivity for the B-cell marker PAX5 (not shown). The morphologic and immunophenotypic findings are consistent with B lymphoblasts. A bone marrow aspirate smear (Panel B, Wright–Giemsa) shows a predominant population of small and medium-size lymphoid blasts with dispersed chromatin, small distinct nucleoli, scant cytoplasm, and occasional cytoplasmic vacuoles. Flow-cytometric analysis of the bone marrow aspirate confirmed the presence of a population of CD10-
positive, CD19-positive cells (Panel C, circle) that were also positive for TdT and negative for the mature B-cell marker CD20 (not shown). The B lymphoblasts showed weak CD45-positivity and aberrantly expressed the myeloid marker CD33 (Panel D, circle).

acute lymphoblastic leukaemia

Lymphoblastic B-cell lymphoma


A 76-year-old man with chronic renal disease, renal obstruction, and a 10-year history of recurrent urinary tract infections presented with fever, worsening renal function, and confusion. He had been well until approximately 1 week before admission when subjective fevers and increasing urinary frequency developed. Two days before admission, fatigue and increasing somnolence developed, followed by confusion and difficulty placing a thermometer in his mouth. On examination, he was warm, diaphoretic, and obtunded with nonverbal moaning. The conjunctivae were injected, he was unable to follow commands or track his eyes, had a possible tongue bite, neck stiffness without pain, bronchial breath sounds throughout all lung fields, right lower quadrant tenderness with wincing, and neurologic findings including 4 mm pupils constricting to 3 mm with light, increased tone in arms with cogwheel rigidity and myoclonus. His medical history included hypercholesterolemia, hypertension, paroxysmal atrial fibrillation, premature ventricular contractions, allergic rhinitis, basal-cell carcinoma, and orthopedic injuries from a motor vehicle accident. He had recent bilateral hydronephrosis with worsening chronic renal failure and had undergone photoselective vaporization of the prostate 2 months prior. He recently visited a forested region of New England with heavy tick and mosquito burdens.

Laboratory blood test results. Cerebrospinal fluid analysis including opening pressure, cell counts, glucose, protein, and Gram's stain.

Blood tests showed white-cell count 11,500/mm³ with 86% neutrophils and 8% lymphocytes, platelet count 59,000/mm³, sodium 134 mmol/L, potassium 4.6 mmol/L, urea nitrogen 34 mg/dL, creatinine 2.26 mg/dL, estimated GFR 28 mL/min/1.73m², and haptoglobin 345 mg/dL. Cerebrospinal fluid showed opening pressure 21.5 cm H2O, pink to faint yellow color with xanthochromia, red cells 1660/mm³ (tube 1) to 116/mm³ (tube 4), white cells 159/mm³ (tube 1) to 170/mm³ (tube 4) with 47% neutrophils and 40% lymphocytes, protein 130 mg/dL, glucose 56 mg/dL, and Gram's stain showing abundant polymorphonuclear leukocytes with no organisms.

(A) MRI of the brain performed on the third hospital day, diffusion-weighted imaging. (B) MRI of the brain performed on the third hospital day, apparent-diffusion-coefficient imaging.

MRI of the brain performed on the third hospital day revealed an abnormal signal in the occipital horns of the lateral ventricles that was hyperintense on the dif-
fusion-weighted images (Panel A, arrow) and hypointense on the apparent-diffusion-coefficient images (Panel B, arrow), findings consistent with material with reduced diffusion.

Cerebrospinal fluid and serum laboratory testing for arbovirus infection, including IgM and IgG assays and plaque-reduction neutralization test.

Cerebrospinal fluid and serum testing for arbovirus infection showed West Nile virus IgM positive in CSF, IgG negative in CSF, serum IgM positive, serum IgG positive, and plaque-reduction neutralization test positive. St. Louis encephalitis virus IgG was positive in CSF but IgM was negative. Eastern equine encephalitis virus testing was negative overall.

viral meningoencephalitis NOS

Certain infectious or parasitic diseases


A 72-year-old woman with non-small-cell lung cancer (NSCLC) and bone metastasis presented with a 5-month history of severe scalp involvement. She had been receiving gefitinib 250 mg per day and ficlatuzumab 20 mg/kg once every 2 weeks for 9 months at the time of presentation. Her symptoms began with a papulopustular rash over the face and trunk in the first month of treatment, followed by severe paronychia beginning in the second month. Bacterial culture from the scalp lesions yielded Staphylococcus aureus, while fungal and mycobacterial cultures were negative. The scalp lesions persisted despite 3 months of strong topical therapies including fluocinonide cream and fusidic acid cream, as well as oral doxycycline for 1 month.

Clinical photograph of the scalp.

Clinical photograph showing severe pustules, crusts, and dramatic hair loss over the scalp with inflammatory changes

Skin biopsy.

Skin biopsy showing upper dermal perivascular and perifollicular lymphoplasmacytic infiltration with fibrosis and vascular ectasia, compatible with late-stage scarring alopecia

Immunohistochemical examination of hair follicle outer root sheath. current patient marked as Case 1.

Immunohistochemical examination showing decreased expression of epidermal growth factor receptor (EGFR), phosphorylated acutely transforming retrovirus AKT8 in rodent T-cell lymphoma (p-Akt), and phosphorylated signal transducer and activator of transcription 3 (p-Stat3) in the outer root sheath of the patient's hair follicles compared with positive controls. p-MET expression was not detected in the patient's hair follicles

Severe refractory scarring alopecia associated with combinational use of ficlatuzumab (AV-299) and gefitinib

Scarring alopecia


Patient 1 is a 64-year-old man who visited Dubai from April 9 to April 17, 2013. He has a medical history significant for hypertension, diabetes, and underwent renal transplantation in 1998 for diabetic nephropathy. He was on immunosuppressive therapy including mycophenolate mofetil, ciclosporin, and prednisone. He also had a previous episode of sigmoiditis treated 6 months prior. On April 22, he developed fever and chills with diarrhea (three to four bowel movements per day). He was admitted to Valenciennes hospital on April 23. At admission, he had no respiratory symptoms such as cough or dyspnea. On April 26, he developed dyspnea and cough.

Laboratory results on April 23 and April 29, including leucocyte counts, neutrophil and lymphocyte percentages, creatinine, blood urea nitrogen, C-reactive protein, platelet count, and arterial blood gas analysis.

Laboratory values showed initial leucopenia (8240 cells/μL on April 23) progressing to normal leucocyte counts with neutrophilia (87% neutrophils, 7% lymphocytes on April 29). Elevated creatinine levels ranged from 177-318.6 μmol/L (normal 40-130), and blood urea nitrogen was markedly elevated at 23.7-41.6 mmol/L (normal 1.2-3.3). C-reactive protein was significantly elevated at 152.30-206.40 mg/L (normal <5). Platelet counts varied from 55,000-309,000 cells/μL. Arterial blood gas analysis showed progressive respiratory failure with declining oxygenation despite increasing oxygen support.

(A) Chest CT, performed on April 24. (B) Chest radiograph, performed on April 30. (C) Chest radiograph, performed on May 8. (D) Chest CT, performed on May 17.

(A) CT scans of the chest obtained on April 24. Substantial bilateral ground-glass opacity and consolidation can be seen. (B, C) Chest radiographs. Groundglass opacity and condensation, mainly on the lower right lobe, were noted on April 30 (B). Bilateral ground-glass opacity and consolidation were noted on May 8 (C). (D) On May 17, the CT scan of the chest showed a bilateral consolidation of the lung.

Bronchoalveolar lavage on April 26, viral testing (Ct values: upE 22.9, Orf1a 24). Nasopharyngeal swabs on April 30, viral testing (Ct values: 37.2-40). Sputum on May 7, viral testing (Ct values: upE 28.8, Orf1a 27.2). Whole blood, plasma, and serum viral testing on May 7 and 9 (whole blood Ct 35.9).

Viral testing results showed MERS-CoV detection with high viral loads in lower respiratory tract specimens. Bronchoalveolar lavage from April 26 showed cycle threshold (Ct) values of 22.9 for upE and 24 for Orf1a. Nasopharyngeal swabs from April 30 showed much higher Ct values (37.2-40), indicating lower viral loads. Sputum from May 7 showed Ct values of 28.8 for upE and 27.2 for Orf1a. Blood specimens from May 7 and 9 showed detectable virus in whole blood (Ct 35.9) with weaker detection in plasma and serum.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection

Middle East Respiratory Syndrome coronavirus infection

Middle East respiratory syndrome


77-year-old man with history of ischemic heart disease presented with a hard lump in the chest wall. Four years prior, he had undergone right hemicolectomy for pT3 pN1 moderately differentiated cecal adenocarcinoma (KRAS and BRAF wild type). He had developed multiple bilobar liver metastases 22 months after the initial surgery. Physical examination revealed several hard nodules and a 2.4-cm hard, nontender lump in the tenth right intercostal space, fixed to intercostal muscles and serratus anterior. Total area of chest wall involvement measured 7.1 cm in diameter. Blood tests were normal, including serum carcinoembryonic antigen.

PET/CT scan of the liver and chest wall, standardized uptake value provided.

PET/CT scan showed tumor recurrence adjacent to previous RFA site in liver segment 5 and uptake in chest wall with similar standardized uptake value activity

CT with portal venous contrast of chest wall and liver.

Portal venous contrast-enhanced CT showed areas of local recurrence in both chest wall and liver

Tract seeding of colorectal cancer metastases following thermal ablation, with recurrence in chest wall and liver

colorectal cancer NOS

Malignant neoplasm metastasis in rectum

Malignant neoplasm metastasis in chest wall

hepatic metastasis


A 55-year-old woman with a 13-year history of invasive ductal carcinoma of the right breast presented with stage IV breast cancer (estrogen receptor positive, progesterone receptor negative, human epidermal growth factor receptor 2/neu negative) metastatic to bone, lungs, and liver. She had undergone mastectomy and multiple systemic therapies, including stem-cell transplantation 8 years prior. Her most recent treatment prior to admission was anastrozole for 3 months, along with paracetamol for pain control. She presented with progressive generalized weakness and episodic confusion that rapidly progressed over several days to unresponsiveness. On the day of admission, she was found by her husband lying on the floor, was disoriented, had lower leg weakness, and was unable to understand basic instructions. Physical examination revealed she was awake but unresponsive and uncooperative, with no other focal neurologic findings initially. Vital signs showed normal blood pressure with mild tachycardia but no fever. Her past medical history was otherwise unremarkable, and she had a normal baseline brain MRI scan 2 weeks before presentation.

(A) Brain MRI, axial view, fluid-attenuated inversion recovery (FLAIR) sequence. (B) Brain MRI, diffusion-weighted imaging (DWI). (C) Brain MRI, susceptibility-weighted imaging (SWI).

Axial fluid-attenuated inversion recovery brain MRI (A) demonstrated areas of vasogenic edema within the subcortical white matter and cortex of the parietal lobes and within the deep white matter of the mid and posterior frontal lobes consistent with posterior reversible encephalopathy syndrome (PRES). Diffusion-weighted imaging (B) showed diffusion restriction with associated apparent diffusion coefficient dropout in the areas of vasogenic edema consistent with superimposed infarction. Susceptibility-weighted imaging (C) demonstrated multiple tiny foci of dark signal intensity within areas of PRES-related vasogenic edema consistent with superimposed microhemorrhage. There were no metastatic brain lesions, no hydrocephalus or herniation.

Posterior reversible encephalopathy syndrome (PRES)

Posterior reversible encephalopathy


A 12-year-old girl with a known history of celiac disease presented with an 8-month progression of severe irritability, hypersomnia, and multiple somatic symptoms. She experienced daily stomachaches, tingling and pain in her arms and legs, dizziness, anorexia, severe fatigue, and increased somnolence with sleeping up to 13 hours per night. She had frequent angry outbursts and became increasingly isolated from friends, lost interest in activities, had deteriorating school performance, and failed mathematics. She had a prior history of anxiety and depression, previously treated with escitalopram and cognitive behavioral therapy. Three episodes of severe vomiting requiring IV hydration occurred in the 16 months before evaluation, each preceded by fever and viral symptoms. On physical examination, she appeared exhausted with blood pressure 83/52 mmHg, pulse 102 bpm, weight 35.4 kg, height 149.9 cm, and BMI 15.8 (12th percentile). She had freckled skin with multiple dark nevi and slight axillary hyperpigmentation. Neurological examination showed brisk reflexes with 2-3 beats of unsustained clonus on the right foot. Mental status examination revealed withdrawn and disengaged presentation with sad and apathetic affect, sparse and slow speech, limited eye contact, and she fell asleep in the waiting area.

Laboratory results at initial and subsequent time points.

Laboratory results showed normal red-cell indices and thyroid function tests initially, with negative heterophile antibody. At 4.5 months before evaluation: hematocrit 35.3%, hemoglobin 11.9 g/dl, white cell count 3600/mm³, free thyroxine 0.9 ng/dl, thyrotropin 3.43 μU/ml. Later testing revealed hyponatremia (133 mmol/L), hyperkalemia (5.2 mmol/L), hypochloremia (93 mmol/L), elevated urea nitrogen (22 mg/dl), hypercalcemia (10.6 mg/dl), elevated alkaline phosphatase (235 U/L), and elevated aspartate aminotransferase (63 U/L).

(A) Duodenal mucosa, histological examination. (B) Duodenal mucosa, histological examination.

The duodenal mucosa shows subtotal villous atrophy and crypt hyperplasia (Panel A). The number of intra-epithelial lymphocytes is markedly increased (Panel B, arrows).

Celiac disease, Addison's disease, and major depressive disorder

Coeliac disease

Addison disease

major depressive disorder

Mental, behavioural or neurodevelopmental disorders


A 65-year-old man presented with a 4-month history of daily fevers, sweats, fatigue, impaired concentration, and progressive weakness that had developed after being previously well. His strength had gradually diminished over several weeks, preventing him from hiking, with fatigue on chewing, difficulty buttoning his shirt, and requiring a rigid foot brace for his right ankle. He reported pain in his feet and calves that was sufficiently distracting to prevent reading, but denied jaw pain, headaches, joint swelling, rash, or weight loss. His medical history included coronary artery bypass grafting 15 months prior complicated by upper abdominal hernia repair with surgical mesh, hepatitis B virus infection, gout, hyperlipidemia, hypertension, gastroesophageal reflux, and hypothyroidism. He had received a diagnosis of HBV infection 4 months before symptom onset during evaluation of elevated aminotransferases (six times upper normal limit) discovered during hernia repair, with positive IgM anti-HBc and HBsAg. On physical examination, he was afebrile with vital signs showing pulse 76 bpm, blood pressure 140/88 mmHg, and BMI 27.1. He appeared comfortable with no lymphadenopathy or temporal artery tenderness. Neurologic examination revealed normal proximal arm strength but decreased strength in bilateral wrists (4/5), fingers (2/5 left, 4/5 right), right hip flexion (4/5), right foot dorsiflexion (0/5), and bilateral great toes. There was interosseous muscle wasting in the left hand, decreased right calf circumference compared to left, symmetric arm reflexes but absent knee and ankle reflexes, no fasciculations, diminished sensation in hands (ulnar distribution right, median distribution left), and diminished vibration sense and nociception in feet with profound right foot drop on ambulation.

(A) Nerve biopsy, hematoxylin and eosin staining. (B) Nerve biopsy, immunohistochemical staining with CD3. (C) Nerve biopsy, immunohistochemical staining with CD20. (D) Nerve biopsy, toluidine blue staining, semithin section.

Specimens from a nerve biopsy show vasculitis and nerve-fiber loss. A marked inflammatory infiltrate is present in the wall of a medium-size vessel in the epineurium (Panel A, hematoxylin and eosin). The infiltrate consists predominantly of CD3-positive T cells (Panel B, immunohistochemical staining with CD3), with fewer CD20-positive B cells (Panel C, immunohistochemical staining with CD20). Semithin sections show destruction of nerve fibers in the endoneurial compartment, with acute and chronic breakdown of myelin (Panel D, toluidine blue).

Hepatitis B virus-associated polyarteritis nodosa

Congenital Hepatitis B virus infection

Certain conditions originating in the perinatal period

Polyarteritis nodosa


72-year-old white woman with 10-year history of recurrent cystitis. No systemic symptoms. Physical exam showed slight anemia. Urine cultures were positive for Escherichia coli. No hepatosplenomegaly or lymphadenopathy detected by CT and ultrasound. Esophagogastroduodenoscopy and subsequent biopsies were negative for both pathologic lymphoid infiltrate and Helicobacter pylori. Otolaryngologic examination and bone marrow biopsy were negative. Serology for hepatitis C virus and hepatitis B virus was negative. No monoclonal component found in serum protein electrophoresis.

Cystoscopy of the bladder, anterior wall.

Cystoscopy revealed several nodular lesions in anterior wall of bladder (largest measuring 2.5 cm in diameter) covered by hyperemic mucosa and sparing ureteral meatus

Histopathological section of the urinary bladder wall, H&E staining, low magnification.

Figure 3 shows a hematoxylin and eosin–stained histopathological section of the urinary bladder wall at low magnification, demonstrating an intense mucosal lymphoid infiltrate that extends throughout the lamina propria while sparing the underlying muscle; frequent lymphoepithelial lesions are evident in the tissue, consistent with the diagnosis of MALT lymphoma.

H&E-stained histopathological section of the urinary bladder, high-power magnification.

Figure 4 on page 2 is a high-power photomicrograph of a hematoxylin and eosin (H&E)–stained histopathological section of the urinary bladder, demonstrating the cytological features of the marginal zone lymphoma infiltrate with a spectrum of small to medium-sized and larger monocytoid-like cells exhibiting abundant often clear cytoplasm; the image illustrates the morphological heterogeneity of the lymphoma cells within the lamina propria.

FISH analysis, MALT1 gene translocation in approximately 16% of nuclei, API2 partner gene identified, t(11;18)(q21;q21), chromosome 3 trisomy in 15% of cells, chromosome 18 trisomy in 4% of cells.

FISH analysis showed MALT1 gene translocation in ~16% of nuclei and identified API2 as partner gene, proving presence of t(11;18)(q21;q21). Chromosome 3 and 18 trisomies detected in 15% and 4% of cells respectively

Primary urinary bladder MALT (mucosa-associated lymphoid tissue) lymphoma harboring the balanced translocation t(11;18)(q21;q21)

MALT - [mucosa associated lymphoid tissue] lymphoma


30-year-old Hispanic male with history of heavy NSAID use. Presented with melena and severe abdominal pain for 3 weeks, with similar but milder symptoms over prior 4-5 months. Initial hemoglobin 7.8 g/dL and mean corpuscular volume 78 fL. Later endorsed having a right swollen testicle (initially missed on previous exams). Physical exam revealed nontender enlarged right testicle. Laboratory markers showed: human chorionic gonadotropin 50 mIU/mL (normal <10), α-fetoprotein 1,990 ng/mL (normal <8), lactate dehydrogenase 534 IU/L (range 25-175).

(A) Esophagogastroduodenoscopy, gastric antrum. (B) Esophagogastroduodenoscopy, second portion of the duodenum.

A: Figure 1A on page 1 is an endoscopic image obtained during esophagogastroduodenoscopy, demonstrating a small ulcer with erosions located in the gastric antrum. B: Figure 1B on page 1 is an endoscopic image from the same procedure, showing a large ulcer with heaped-up edges and an overlying clot localized in the second portion of the duodenum. Both images are upper gastrointestinal endoscopic views acquired during evaluation for GI bleeding, with no specific mention of staining methods or magnification as they are clinical endoscopy photographs.

Endoscopic examination of the second portion of the duodenum.

Large ulcer with heaped up edges and overlying clot in second portion of duodenum

Biopsy specimen, H&E staining, 100× magnification.

Biopsy revealed malignant germ cell tumor, consistent with embryonal carcinoma (H&E stain, 100x magnification)

CT of the abdomen and pelvis.

CT abdomen/pelvis showed invasion of transverse colon and right renal hydronephrosis due to right ureter encasement

Metastatic testicular germ cell tumor (embryonal carcinoma) presenting with GI bleeding

Germ cell tumour of testis

infantile embryonal carcinoma

Gastrointestinal bleeding

Symptoms, signs or clinical findings, not elsewhere classified

metastatic tumour in bone


A 62-year-old white man with a history of hypertension and diabetes mellitus presented with a three-month history of fatigue, anorexia, weight loss, and vague upper abdominal pain that had intensified over time. He had a 40-pack year smoking history but quit 2 years prior to illness, consumed alcohol in moderation, and denied high-risk sexual behavior. His mother died of smoking-related lung cancer. Physical examination at presentation revealed renal insufficiency with serum creatinine of 3.2 mg/dL, severe anemia with hemoglobin of 7 g/dL, thrombocytopenia with platelets at 77,000/μL, hypercalcemia with calcium of 12.7 g/dL, and elevated total protein greater than 10 g/dL. He also demonstrated biochemical evidence of tumor lysis syndrome with LDH of 1,157 U/L and uric acid of 20.8 mg/dL, and clinically overt coagulopathy consistent with disseminated intravascular clotting including prolonged prothrombin time, activated partial thromboplastin time, reduced fibrinogen with elevated D-dimer and fibrin split products.

CT of the abdomen.

CT scan demonstrated a 16-cm pancreatic mass, two large (>5 cm) liver masses, a 1.8-cm right adrenal gland nodule, retroperitoneal lymphadenopathy, multiple peritoneal nodules, and moderate volume ascites.

(A) Bone marrow biopsy, H&E staining, high-power field.

A: Figure 2 (A) on page 2 shows a bone marrow biopsy section stained with hematoxylin and eosin (H&E), displaying a high-power field view with sheets of monotonous plasma cells extensively infiltrating the bone marrow, consistent with massive marrow involvement by neoplastic plasma cells in the context of multiple myeloma.

(D) Kidney section, H&E staining, intermediate magnification.

D: Microscopic section of kidney showing severe cast nephropathy with arrows indicating intratubular casts, stained with hematoxylin and eosin (H&E), at intermediate magnification.

(E) Ascites fluid cytology, H&E staining, obtained during hospitalization.

E: Microscopic image of ascites fluid cytology analyzed with hematoxylin and eosin (H&E) staining showing clusters of neoplastic plasma cells, consistent with CD138-positive kappa-restricted clonal plasma cells with plasmablastic morphology, obtained during the patient’s hospitalization for paracentesis and analysis of peritoneal fluid.

Immunohistochemical staining for CD138 of cytologic material from ascites fluid, high magnification.

F: Immunohistochemical staining for CD138 of cytologic material from ascites fluid at high magnification demonstrates diffuse, strong membranous positivity in clusters of plasma cells.

PET scan.

PET scan showed mediastinal and intra-abdominal structural involvement.

Highly proliferative, ISS (International Staging System) stage IIIB immunoglobulin A kappa multiple myeloma with hyperdiploid karyotype and multiple chromosomal abnormalities including multiple rearrangements involving chromosome 1, with extensive extramedullary disease

multiple myeloma

medullary cystic disease


A 26-year-old woman with no significant medical history was admitted to the hospital through the emergency department after having several syncopal episodes. Laboratory evaluation revealed positive antinuclear antibodies at a titer of 1:320 with a speckled pattern, and specificity for extractable nuclear antigens including antibodies against Ro52 confirmed by immunoblot and enzyme-linked immunosorbent assays (first measurement of antibodies, 1.2 U per milliliter). No clinical manifestations of rheumatologic disease were present. Other causes of reversible atrioventricular block were ruled out, including cardiac surgery, ablation procedures, drug use, infiltrative diseases, myocardial ischemia, and infectious diseases. Electrolyte levels and thyrotropin levels were normal. During the first 4 days after admission, the patient had varying degrees of atrioventricular block.

(A) Surface electrocardiography at rest; ladder diagram depicting cardiac conduction routes. (B) Surface electrocardiography (precordial leads V1 and V6) and endocavitary His bundle recordings during electrophysiological study with continuous stimulation in the superior right atrium at a cycle length of 490 msec; bipolar catheter recording from the superior third of the tricuspid annulus.

In Panel A, surface electrocardiography (ECG) conducted while the patient was at rest shows complete atrioventricular block and ventricular escape rhythm associated with left bundle-branch block. Beneath the surface ECG is a ladder diagram showing the proposed routes of cardiac conduction, with cardiac location represented vertically from the atrium to ventricle and time represented horizontally. Atrial depolarization originates in the sinus node (upper row of black dots) and is conducted into the atrioventricular node but is blocked there and does not continue into the ventricles. At the same time, ventricular escape beats originate in the ventricles (lower row of black dots) at a slower rate and are conducted retrograde but likewise are blocked in the atrioventricular node and do not continue into the atria. Panel B shows surface ECG (precordial leads V1 and V6) and endocavitary (His) recordings during an electrophysiological study. Continuous stimulation (S) was performed in the superior right atrium at a cycle length of 490 msec. The resulting electrograms show normal conduction (from the atria [A] through the bundle of His [H] to the ventricles [V]) in the first, third, and fourth stimulated beats, with infra-Hisian atrioventricular block (conduction block below the H) after the second stimulated beat. The third ECG shows the recording of a bipolar catheter located in the superior third of the tricuspid annulus.

Reversible atrioventricular block associated with anti-Ro antibodies

Complete atrioventricular block

Anti-nuclear antibody positive


A 28-year-old woman with no clinically significant medical history presented to the emergency department with fatigue and migratory joint pain. She initially developed pain and swelling in her right foot and ankle that limited walking, which persisted for several days then resolved, followed by pain in her knees and hips with swelling and pain in her right elbow. She reported intermittent low-grade fevers but denied recent cough or sore throat. Physical examination revealed temperature of 38.3°C (101.0°F), diffuse joint tenderness on palpation without swelling or erythema with normal range of motion, tachycardia without murmurs, and no chest infiltrate on radiograph. She returned 5 days later with progressive shortness of breath worse when supine, though joint pain had lessened except for continued right knee pain and stiffness. On repeat examination, she had temperature 37.5°C (99.5°F), heart rate 106 bpm, blood pressure 126/63 mmHg, respiratory rate 22/min, oxygen saturation 96% on 3L oxygen, elevated jugular venous pressure at 12 cm water, bilateral lung crackles, tachycardia with holosystolic murmur at apex radiating to axilla, warm left knee without effusion or erythema but with limited range of motion and severe pain with flexion. The patient was born in Brazil and moved to northeastern United States 10 years prior, worked as a preschool teacher, had never been sexually active, denied alcohol or IV drug use, took no medications, had no drug allergies, and had never previously sought medical care. On further questioning, she recalled becoming short of breath easily as a child in Brazil and being unable to play with other children.

(A) Echocardiogram, parasternal long-axis view, heart. (B) Echocardiogram, apical four-chamber view, heart. (C) Color Doppler echocardiogram, heart. (D) Continuous-wave Doppler flow study, mitral valve.

A parasternal long-axis view of the heart (Panel A) and an apical four-chamber view (Panel B) show normal chamber dimensions and wall thickness, with thickening of the mitral-valve leaflets and restriction of the posterior leaflet. Mitral regurgitation is shown on a color Doppler echocardiogram (Panel C), and the mitral stenosis gradient is shown in a continuous-wave Doppler flow study (Panel D).

acute active rheumatic fever


5-year-old right-hand dominant boy presented with painful and deformed left forearm after slipping in the snow and landing on his outstretched left hand. No relevant medical history. On examination, he was stable with an isolated deformed arm injury. No signs of neurovascular compromise, no skin compromise or breach.

(A) Anteroposterior radiograph of the forearm and elbow. (B) Lateral radiograph of the forearm and elbow.

Anteroposterior and lateral radiographs of the forearm and elbow showing minimally displaced proximal third ulna diaphyseal fracture and radial head dislocation

Monteggia fracture of the forearm (minimally displaced proximal third ulna diaphyseal fracture and radial head dislocation)

Monteggia fracture-dislocation

Diaphysitis

Dislocation of radial head


76-year-old woman, asymptomatic, with history of rheumatoid arthritis treated with methotrexate for 5.5 years (4 mg/week for 4 years and 8 mg/week for 1.5 years). Presented with lung mass found on chest radiography.

CT of the chest, contrast-enhanced.

Contrast-enhanced chest CT revealed lung tumors with angiogram sign in right middle lobe

Flexible bronchoscopy of right upper lobe orifice.

Flexible bronchoscopy showed ulcerative erosion surrounded by pale mucosa in right upper lobe orifice

Biopsy, H&E staining.

Biopsy with H&E staining showed bronchus epithelium and subcutaneous infiltration of small lymphocytes with necrosis

(C) Immunohistochemical staining of lung lesion, CD20 antibody, 40× magnification. (D) Immunohistochemical staining of lung tissue, CD79a antibody, 40× magnification. (E) Immunohistochemical staining of lung lesion, latent membrane protein 1, 100× magnification. (F) In situ hybridization of lung tissue, EBV-encoded small RNA-1, 200× magnification.

C: Immunohistochemical staining of the lung lesion using the CD20 antibody at 40× magnification demonstrates B-cell infiltration. D: Immunohistochemical staining with the CD79a antibody at 40× magnification shows B-cell lineage confirmation in the lung tissue. E: Immunohistochemical staining for latent membrane protein 1 at 100× magnification reveals the presence of latent Epstein-Barr virus infection in the sampled lung lesion. F: In situ hybridization for EBV-encoded small RNA-1 at 200× magnification identifies Epstein-Barr virus–positive cells within the lung tissue.

Methotrexate-induced lymphoproliferative disease: Epstein-Barr virus-associated lymphomatoid granulomatosis (LYG) grade 2 according to WHO classification

Methotrexate-associated lymphoproliferative disorders

Lymphomatoid granulomatosis


A 48-year-old man initially presented in 1999 with a mass on his right thumb, which was found to be a 1.5-cm aggressive digital papillary adenocarcinoma. Eleven years later, he presented with substernal chest pain and was found to have widespread metastatic disease. The patient reported difficulty walking due to pain in his left buttock extending into his left thigh, pain in the right hand extending from the area of initial amputation to a new mass at the base of the first finger, and exquisite point tenderness in the anterolateral sole of each foot associated with subcentimeter nodules. These lesions grew rapidly over 2 weeks, and he had decreased appetite with 20-pound weight loss over 3 months. His medical history included recent treatment for pneumonia and non-ST elevation myocardial infarction. He was a former printer with 18 years of chemical exposure and had a 20 pack-year smoking history. Physical examination revealed multiple subcutaneous nodules measuring 1-3 cm along thoracic and abdominal walls, bilateral foot sole lesions, and induration of the left gluteus maximus musculature, all tender to palpation. He had an Eastern Cooperative Oncology Group performance status of 3 and was minimally able to ambulate with crutches.

Clinical photograph of the palmar aspect of the right hand acquired two weeks after starting treatment.

Figure 1 is a clinical photograph depicting the palmar aspect of the right hand showing a large, erythematous, subcutaneous mass at the base of the first finger and thenar eminence, acquired two weeks after starting treatment for metastatic digital papillary adenocarcinoma. This image documents the anatomical site of recurrence and local progression at the original location of tumor involvement, providing visual evidence of tumor burden following initiation of therapy.

Clinical photograph of the right hand, acquired after palliative treatment initiation.

Figure 2, as depicted on page 2, is a clinical photograph showing the dorsum of the patient's right hand, illustrating multiple subcutaneous nodules associated with metastatic digital papillary adenocarcinoma; the image documents the anatomical site (right hand), demonstrates the gross morphology of subcutaneous metastatic lesions, and appears to have been acquired during the course of symptomatic disease progression, specifically after palliative treatment initiation.

CT of the left gluteus maximus musculature.

CT imaging shows induration and enhancement of left gluteus maximus musculature (indicated by arrow)

Diffusely metastatic digital papillary adenocarcinoma, 11 years after initial presentation

Aggressive digital papillary adenocarcinoma

Metastatic adenocarcinoma in colon


59-year-old man with history of prostate cancer metastatic to lumbar spine and periaortic lymph nodes diagnosed in 2001, with initial PSA of 11.3 ng/mL. In August 2011, presented to emergency room with abdominal pain. Lab tests showed elevated lipase (874 U/L), alkaline phosphatase (289 IU/L), and ALT (222 IU/L), with normal bilirubin. Later returned with right upper quadrant abdominal pain, tachycardia but afebrile. Physical exam showed positive Murphy's sign and palpable gallbladder. Labs showed elevated alkaline phosphatase of 357 IU/L and normal serum lipase.

MRI of the abdomen, coronal view, performed after the onset of jaundice.

Figure 1 on page 1 is a magnetic resonance imaging (MRI) scan of the abdomen performed after the patient developed jaundice, showing an infiltrating soft tissue process in the porta hepatis with intrahepatic bile duct dilation; the scan is presented in a coronal view, and the imaging was obtained after the onset of obstructive symptoms during the disease course.

Endoscopic ultrasound of the hilar region, liver, portal and peripancreatic lymph nodes, and tail of pancreas, lesion size 20 × 28 mm.

Endoscopic ultrasound showed cystic hypoechoic process in hilar region contiguous to liver, multiple portal and peripancreatic lymph nodes, and a 20 x 28-mm hypoechoic lesion with heterogenicity in tail of pancreas.

Fine needle aspiration biopsy of pancreatic mass, immunostaining for PSA, prostate-specific acid phosphatase, and androgen receptor.

Fine needle aspiration biopsy of pancreatic mass revealed adenocarcinoma that matched patient's previous metastases morphologically. Immunostaining was positive for PSA, prostate-specific acid phosphatase, and androgen receptor.

Metastatic prostatic adenocarcinoma to the pancreas

Adenocarcinoma of prostate

pancreas metastasis


Patient 1 was a 46-year-old man with a history of stage III melanoma who developed symptomatic pulmonary and osseous metastatic disease. Tumor mutation testing identified a BRAF V600E mutation. Prior to treatment, his lactate dehydrogenase was elevated at 3,190 IU/L. After beginning vemurafenib treatment and experiencing initial improvement, he presented after 6 weeks with acute onset dyspnea and fever. Physical examination revealed diffuse concave 1 mm ST segment elevations on electrocardiogram. Transthoracic echocardiogram revealed a small pericardial effusion initially. Following recurrent symptoms, physical exam revealed hypotension, a 12 mmHg pulsus paradoxus, and jugular venous distension. Two liters of serosanguinous pericardial fluid was drained via pericardiocentesis, with cytology negative for melanoma.

Transthoracic echocardiogram of the heart.

Transthoracic echocardiogram demonstrates a large circumferential pericardial effusion with cardiac tamponade (effusion bounded by arrowheads)

Vemurafenib-induced cardiac tamponade secondary to pericarditis with pericardial effusion

Cardiac tamponade

Pericarditis, unspecified

Pericardial effusion


A 65-year-old man with a history of immunoglobulin G (IgG) lambda monoclonal gammopathy of undetermined significance that developed into multiple myeloma in July 2003, initially diagnosed during emergency decompressive surgery for symptomatic epiduritis of the fifth cervical vertebra. In October 2010, after the eleventh chemotherapy session, the patient presented with a rapidly enlarging anterior cervical mass accompanied by dysphonia and dysphagia. Physical examination revealed a firm tumefaction in the anterior cervical region. The patient's general condition began to deteriorate in November 2010 with onset of respiratory distress related to superior vena cava syndrome resulting from tumoral compression.

Ultrasonography of the thyroid isthmus and left lobe, nodule measuring 75 × 60 × 35 mm.

Ultrasonography showed a large nodule in the isthmus and left lobe of the thyroid measuring 75 × 60 × 35 mm, with unusual and dishomogeneous echogenicity, featuring a multilobed hyperechoic central component surrounded by a hypoechoic area. No lymph node abnormalities were found in the lateral neck compartments.

Shear wave elastography analysis, maximal pressure=89.77 kPa.

Shear wave elastography analysis demonstrated a high elastography index with maximal pressure of 89.77 kPa, indicating malignancy.

Doppler ultrasonography of the thyroid, transverse section, performed after rapid enlargement of anterior cervical mass during diagnostic assessment following chemotherapy.

B: Doppler ultrasonography of the thyroid performed after the rapid enlargement of the anterior cervical mass demonstrates a large nodule in the isthmus and left lobe, showing marked internal and peripheral vascularization; the image corresponds to a transverse section acquired during the diagnostic assessment following chemotherapy, with color Doppler highlighting increased blood flow in and around the nodule.

Fine-needle aspiration. Immunocytochemical study.

Fine-needle aspiration displayed dispersed plasmacytoid cells of malignant appearance, some binucleated, with eccentric nuclei, prominent nucleoli, and chromatin enhancement. Cell morphology suggested either medullary carcinoma, myelomatous localization, or lymphoid origin. Immunocytochemical study failed to define precise cell origin, but absence of calcitonin expression ruled out medullary carcinoma, favoring plasma cell neoplasm hypothesis.

multiple myeloma

multiple myeloma


A 57-year-old woman with a history of metastatic (pulmonary, bone) left renal cell carcinoma was referred to nephrology for acute renal failure. Her cancer was previously treated with nephrectomy in March 2005, followed by interferon, and sunitinib until 2011 when she developed progressive disease. She was started on everolimus, with the dose later reduced due to rising creatinine levels. On physical examination, her blood pressure was 140/85 mmHg, she weighed 45 kg (having lost 5 kg), and the remainder of her examination was normal. Laboratory studies showed hemoglobin of 9.1 g/dl, platelet count of 390,000/mm³, and haptoglobin of 4.39 g/l. Urinalysis revealed daily protein excretion of 0.4 g and 18 red cells per high-power field. Imaging showed the right kidney was normal on non-contrast computed tomography scan and renal sonography. Immunological workup was negative, including circulating immune complexes, antinuclear antibody, rheumatoid arthritis hemagglutinin titer, anti-tubular basement membrane antibody, and anti-neutrophil cytoplasmic antibody. No monoclonal component was detected in the blood.

Table 1. Summary of clinical and laboratory parameters for biopsy-proven acute tubular necrosis cases associated with mTOR inhibitor therapy.

Table 1 in this article presents a summary of biopsy-proven acute tubular necrosis cases associated with mTOR inhibitor therapy, detailing for each patient the case number, age, sex, cancer type, concomitant nephrotoxic factors, specific mTOR inhibitor and dosage, duration of therapy before renal disturbance, baseline and peak serum creatinine levels during treatment, and outcome after drug withdrawal. This table allows direct comparison of clinical and laboratory parameters, timelines of renal injury development, and subsequent renal recovery or progression based on the type of mTOR inhibitor used and patient comorbidities.

Kidney biopsy. Immunofluorescence study of the kidney.

Kidney biopsy showed severe tubular necrosis with denudation of tubular basement membranes, cell fragments and red cells in the tubular lumen, and cellular dysmorphy. In the interstitium, mild edema was observed within non-cellular fibrosis. Most of the glomeruli are ischemic. Immunofluorescence study did not show specific deposits.

Acute tubular necrosis (ATN) associated with mTOR inhibitor therapy

Acute tubular necrosis

adverse effects, unspecified


28-year-old man initially presented in 2007 with headache and central ataxia with gait instability. No dysarthria, dysphagia, facial asymmetry, or other focal neurological deficits were present. In February 2010, he presented with increasing cervical lymphadenopathy associated with his posterior occipital surgical scar over several months.

Diff-Quik–stained smear of right neck mass aspirate, 20× magnification.

Diff-Quik–stained smear of right neck mass aspirate showing sheets of small round blue cell tumor (20x magnification)

H&E staining of right neck mass, 20× magnification.

H&E stain of right neck mass showing small round blue cell tumor cells infiltrating skeletal muscle (20x magnification)

Immunoperoxidase staining of the right neck mass, 20× magnification.

Immunoperoxidase stain positive for antibodies against neuron-specific enolase within tumor cells (20x magnification)

(A) [18F]FDG PET/CT, axial view, obtained prior to induction chemotherapy.

A: Figure 4 (A) on page 2 presents a [18F]fluorodeoxyglucose (FDG) PET/CT image in the axial view, obtained prior to induction chemotherapy, demonstrating prominent extracranial metastatic disease as indicated by the arrow, specifically localizing FDG-avid metastasis at the right occipital region.

(A) MRI of the brain, sagittal view, T1-weighted sequence, obtained before induction chemotherapy.

A: Figure 5 (A), located on page 3, presents a sagittal T1-weighted MRI of the brain obtained before induction chemotherapy, displaying an extracranial metastatic lesion indicated by an arrow adjacent to the posterior fossa region; this image was acquired prior to systemic therapy and serves to demonstrate the anatomical extent and location of the metastatic disease before treatment initiation.

Recurrent extraneural metastatic medulloblastoma

medulloblastoma of unspecified site

metastasis