This case involves a 48-year-old man with a body mass index of 44.7 and weight of 153 kg who was admitted to the hospital 71 minutes after experiencing a right hemispheric stroke. His medical history included long-standing hypertension, hypertrophic cardiomyopathy, congestive heart failure, and paroxysmal atrial fibrillation. He was also a smoker. The patient had switched from phenprocoumon to dabigatran (150 mg twice daily) 4 weeks before presentation and reported good medication compliance, with the last dose received 9 hours before stroke onset. His creatinine clearance was 163 ml per minute (reference range 76 to 120). He was also receiving a proton-pump inhibitor. Initial plasma dabigatran level measured using Hemoclot test system was 0 ng per milliliter.

CT scan performed on admission, noncontrast.

Noncontrast CT scan obtained on admission shows no early ischemic changes

CT scan of the brain performed 24 hours after initial examination.

Follow-up CT scan after 24 hours shows an embolic ischemic infarction in the territory of the right middle cerebral artery

Laboratory measurement of plasma dabigatran levels on day 4, maximum 50 ng/mL, trough 0 ng/mL, peak at 4 hours after administration.

Measurements of diurnal plasma levels of dabigatran on day 4 show a maximum plasma level of 50 ng per milliliter and a trough level of 0 ng per milliliter, with peak level reached 4 hours after drug administration

Right hemispheric ischemic stroke with embolic infarction in the territory of the right middle cerebral artery

ischaemic stroke NOS[Right]

Embolic infarction of middle cerebral artery

Middle cerebral artery syndrome[cerebral infarction due to embolic occlusion]


A 26-year-old woman presented with 5 weeks of vulvar swelling, pruritus, and progressively enlarging vulvar plaque, accompanied by 2 months of occasional constipation and recurrent bloody, mucoid diarrhea. She had no history of anogenital warts and was monogamous with her husband, with no history of blood transfusions or contact with toxic agents or irritants. Physical examination revealed bilateral purple swelling of the labium majora and a 2-mm ulcer was observed inside the right labium minus. Digital rectal examination showed bloody mucus mixed with loose stool. Laboratory results showed normal white blood cell count (4 × 10⁹/L) and neutrophil count (2.07 × 10⁹/L), slightly decreased hemoglobin level (10.2 g/dL), elevated erythrocyte sedimentation rate (71 mm/h; reference range 0-20 mm/h), and elevated C-reactive protein level (28 mg/L; reference range 0-5 mg/L). Bacterial and fungal swab cultures from the ulceration were negative, and vaginal and urethral swabs were negative with moderately increased polymorphonuclear leukocytes. Serologic testing for Treponema pallidum and human immunodeficiency virus were negative.

Clinical photograph of the vulva and perineal region, obtained during the physical examination on admission.

Figure 1 is a clinical photograph depicting bilateral purple swelling of the labium majora and multiple moist, edematous, wart-like nodules ranging from 1 to 8 mm on the perineal and perianal regions of the patient's vulva, observed during the physical examination upon admission. The image documents the gross anatomical appearance of these lesions, without specification of a particular orientation or magnification, and serves to illustrate the extent and nature of vulvar and perianal involvement in this case of suspected vulvar Crohn disease.

(A) Vulvar nodule histopathology, H&E staining, 20× magnification. (B) Vulvar nodule histopathology, H&E staining, 400× magnification.

Histopathology of the vulvar nodule. A, Noncaseating epithelioid granulomas in the dermis (hematoxylin-eosin, original magnification 20). B, The granulomas were composed of
multinucleated giant cells and a cellular infiltrate of lymphocytes and plasma cells (hematoxylin-eosin, original magnification 400).

Crohn disease


A 60-year-old female presented to the cardiology department with stable angina pectoris that she had experienced for one year. She had been diagnosed with portal vein thrombosis due to protein C deficiency, hypertension and hyperlipidemia. She was taking perindopril and warfarin at the time of presentation. An electrocardiography (ECG) showed Q waves in the inferior leads. Cardiac catheterization revealed spiral dissection of the proximal right coronary artery (RCA), extending downwards to just below the right ventricle branch, with distal TIMI-3 antegrade flow. Ventriculography showed hypokinesis of the inferior wall, and the left ventricle ejection fraction (LVEF) was 45%.

Right coronary angiogram, left anterior oblique projection.

Right coronary angiogram demonstrating spontaneous dissection in left anterior oblique projection

Spontaneous coronary artery dissection (SCAD)

spontaneous coronary artery dissection

Cardiovascular and respiratory disorders


46-year-old woman who experienced chest pain before having an out-of-hospital cardiac arrest. Pre-arrest rhythm strip showed sinus tachycardia. Initial troponin I was 5.9 μg/L (normal: 0-0.04 μg/L). Medical history included similar chest pain episode one year prior after taking sumatriptan for migraine, with transient inferior and lateral ST elevation on ECG but negative troponin at that time. Previous coronary angiography showed normal left coronary system and dominant right coronary artery with minor ostial spasm and slow flow. Negative bubble study for right to left shunting. Current medications: oral diltiazem, nicorandil, lansoprazole, and beclometasone inhaler. Patient was a former smoker.

ECG performed immediately prior to onset of pulseless electrical activity arrest.

ECG immediately prior to onset of pulseless electrical activity arrest showing ST elevation

Coronary vasospastic disease with angina


A 31-year-old man presented with chronic abdominal pain persisting for approximately one year. He was 170 centimeters tall, weighed 53 kilograms, and worked as a car mechanic. He had no specific medical history or trauma history, and no history of sports activities. The pain initially started after taking a late-night snack and was described as severe squeezing in nature, located on the right side of the periumbilical area, persisting all day long. The pain intensity on visual analogue scale (VAS) was about 60-70 out of 100. He had been on gastrointestinal medications with nonsteroidal anti-inflammatory drugs at another hospital for over two months with no effect. Extensive evaluations including abdominal ultrasonography, abdominal computed tomography, contrast media study of small and large intestine, endoscopy, colonoscopy, laboratory tests, and simple x-rays of chest, abdomen, and lumbar spine showed no specific abnormal findings. Physical examination revealed that he had greater tenderness with continuous local palpation when asked to fold his arms across the upper chest and sit halfway up, indicating a positive Carnett test, which implies that the pain originated from the abdominal wall.

Clinical photograph of ultrasound transducer and needle placement over the lateral end of the rectus abdominis muscle using a 12–5 Hz linear ultrasound probe.

Figure 1 depicts a clinical photograph showing the placement of the ultrasound transducer and needle over the lateral end of the rectus abdominis muscle in a patient positioned supine for an ultrasound-guided nerve block procedure; the image illustrates the use of a 12-5 Hz linear ultrasound probe configured to localize the target area for injection at the lateral border of the rectus abdominis for abdominal cutaneous nerve entrapment treatment.

Ultrasound, transverse scan of rectus abdominis muscle, abdominal region.

Demonstrates ultrasound guided block of the abdominal cutaneous nerve using transverse scan of rectus abdominis muscle, showing anatomical structures including rectus abdominis (1), linea semilunaris (2), internal oblique (3), transversus abdominis (4), and abdominal cutaneous nerve (*), with white arrows marking the needle trajectory.

Abdominal cutaneous nerve entrapment syndrome

entrapment syndrome NOS


A 23-year-old female presented to the hospital in April 2009 with months of increasing facial and truncal hair growth and acne. She had been amenorrheic for 2 years prior to the onset of her virilizing symptoms. Physical examination revealed a 56 kg normotensive female with obvious facial hair, breast atrophy, excessive hair on her lower abdomen and thighs, and an enlarged clitoris. Pelvic examination revealed a 5 cm right adnexal mass. The patient had been treated as having Polycystic Ovary Syndrome (PCOS) at a local hospital for one year, but symptoms worsened. Abdominal ultrasound identified a 64×52×51 mm solid left ovarian mass with Doppler evaluation showing low resistance to intratumoral blood flow. CT scan of the pelvis confirmed the ultrasound findings and detected no adrenal gland enlargement or tumor. No ascites or other abnormalities were present. The preoperative diagnosis was testosterone-producing sex-cord stromal cell tumor.

Laboratory results before surgery.

Laboratory values showed FSH 6.2 U/L, LH 4.5 U/L, E2 57 pg/ml, PRL 21.84 ng/ml, testosterone 3.68 ng/ml, DHEA-S 403.1 μg/dl, SHBG 21.16 nmol/L, and cortisol 22.59 μg/dl before surgery

Microscopic section of ovarian tissue, H&E staining, 20× magnification.

B: Microscopic appearance of a benign ovarian steroid cell tumor, not otherwise specified, demonstrating cells with small round nuclei, mild atypia, and no mitosis, arranged in a diffuse pattern of columns or nests separated by a rich vascular network; the cells display abundant pale cytoplasm and absence of Reinke crystals, visualized by hematoxylin and eosin staining at 20× magnification (as shown in the figure and its caption on page 3).

Benign ovarian steroid cell tumor, not otherwise specified (NOS)

Benign neoplasm of ovary


A 13-year-old Caucasian boy of Italian ancestry presented with Addison's disease, dysphagia, muscle weakness, excessive fatigue, and recent onset gait ataxia. His parents were apparently healthy individuals from the same small village in southern Italy, with no recognized consanguinity. He was born after an uneventful 40-week gestation with normal birth parameters and had bilateral cryptorchidism, inguinal hernia, and hypospadias noted at birth. Early developmental milestones appeared normal initially, but global developmental delay became evident later, with mild mental retardation confirmed at age 9. He had a history of deficient tear production dating back to early infancy, with his mother noting he had always 'cried without tears.' At age 2, he developed recurrent vomiting, failure to thrive, and progressive skin pigmentation, initially misdiagnosed as gastroesophageal reflux. At age 4, he presented with recurrent episodes of hypotonia, hypoglycemia, and hypothermia, leading to diagnosis of Addison's disease. Physical examination revealed height 160 cm (0.42 SDS), weight 71 kg (3.55 SDS), pubertal stage II, severe hyperpigmentation and hyperkeratosis of elbows and knuckles, facial dysmorphism with malar hypoplasia and prognathism, dysarthria, nasal speech, saccadic eye movements with horizontal gaze nystagmus, bilaterally dilated pupils with poor light response, mild bilateral optic atrophy, distal muscle weakness and wasting in arms, milder pyramidal weakness in legs, unsteady gait, hyperactive deep tendon reflexes, and extensor plantar responses bilaterally. Laboratory studies showed markedly elevated plasma ACTH levels (1494 pg/ml; normal 5-46), normal serum electrolytes, aldosterone (184 pg/ml; normal 75-455), and plasma renin (16 pg/ml; normal 5-90), confirming isolated glucocorticoid deficiency. Very long chain fatty acids were normal. Bone mineral density was normal (Z score -0.6). Severe progressive dysphagia starting at age 11 prevented normal swallowing without liquids.

Genetic analysis, family pedigree. I:3, thoracic syringomyelia with spastic diplegia at the age of 60 years, II:4, heterozygous adrenoleukodystrophy, spastic paraparesis, III:3, childhood cerebral adrenoleukodystrophy, III:1, the current patient

Family pedigree showing the proband (III:1), with family history significant for thoracic syringomyelia with spastic diplegia in a great-aunt (I:3) at age 60, and X-linked adrenoleukodystrophy in a maternal cousin (III:3).

(A) Cervical spine MRI, axial view, T2-weighted sequence. (B) Spine MRI, sagittal view, T2-weighted sequence.

A: axial T2-weighed MRI of the cervical spine showing syrinx formation at the level of 6th cervical vertebra (arrow). B: sagittal T2-weghed MRI of the spine demonstrating type 1 Chiari malformation and associated cervico-dorsal (C6-T1) syringomyelia.

Triple A (Allgrove) syndrome with type 1 Chiari malformation and syringomyelia

Triple A syndrome

Endocrine, nutritional or metabolic diseases

Chiari malformation type I

Syringomyelia


32-year-old male with history of recurrent sinusitis, bronchitis, and tonsillitis since age 12. Patient presented with diarrhea lasting more than 2 weeks. Had been diagnosed with common variable immunodeficiency (CVID) 6 years prior.

(A–D) Gastrointestinal transit radiographs of the small bowel following oral contrast administration.

The figure on page 1 presents four gastrointestinal transit radiographs, demonstrating multiple repletion defects consistent with nodular lymphoid hyperplasia in the terminal ileum. These images utilize gastrointestinal transit imaging of the small bowel and were acquired following oral contrast administration as part of the diagnostic evaluation in a patient with common variable immunodeficiency and recent-onset diarrhoea. The findings highlight accelerated transit and several well-defined nodular filling defects, without further specification of view orientation or acquisition timing beyond the context of the clinical presentation.

Nodular lymphoid hyperplasia in common variable immunodeficiency (CVID)

Common variable immunodeficiency

lymphoid hyperplasia

Symptoms, signs or clinical findings, not elsewhere classified


A 56-year-old man presented with chronic low back and intermittent hip pain with worsening symptoms. He reported no constitutional symptoms on presentation. Physical examination revealed tenderness on percussion of the lower dorsal and lumbar spine. Complete blood count showed hemoglobin 143 g/L, white blood cell count 6.5 × 10⁹/L with normal differential, and platelets 112 × 10⁹/L. Serum lactate dehydrogenase, calcium, PO4, albumin, uric acid, β₂-microglobulin, and paraprotein levels were all normal. Plain radiographs of the dorsal/lumbar spine, pelvis, and femora showed only mild wedge compression of the D9 vertebral body. Blood film and initial bone marrow aspirate with flow cytometric immunophenotyping were interpreted as essentially normal, with retrospective review confirming absence of hairy cells on blood film and only rare cells suggestive of hairy cell leukemia in the bone marrow aspirate and touch imprints. Abdominal ultrasound revealed hepatic steatosis but no splenomegaly.

Bone marrow biopsy, H&E staining.

Hematoxylin and eosin slides of bone marrow biopsy appeared free of disease.

CD20 immunohistochemistry of bone marrow biopsy, low to intermediate power field.

B: CD20 immunohistochemistry of a bone marrow biopsy showing a sparse interstitial infiltrate suggestive of hairy cell leukemia, performed on bone marrow tissue, with immunohistochemical staining for CD20 on a low to intermediate power field; the timing of sample acquisition is not explicitly stated in the figure but corresponds to the patient’s diagnostic evaluation.

H&E staining of open biopsy of left iliac crest. Immunohistochemistry for CD20, CD10, BCL2, cyclin D1, CD3, CD5, CD138. Flow cytometry for CD19, CD20, CD10, CD11c, CD25, CD103. Enzyme cytochemistry for tartrate-resistant acid phosphatase. Special staining for reticulin fibrosis. PCR for immunoglobulin heavy chain gene rearrangement. FISH for t(11;14) and t(14;18). Annexin A1 immunocytochemistry.

Hematoxylin and eosin staining of open biopsy of left iliac crest revealed diffuse infiltrate of lymphocytes with cleaved nuclei and abundant cytoplasm, with immunohistochemistry positive for CD20, CD10, BCL2, and cyclin D1, and negative for CD3, CD5, and CD138. Flow cytometry revealed coexpression of CD19, CD20, CD10, CD11c, CD25, and CD103. Enzyme cytochemistry confirmed tartrate-resistant acid phosphatase positivity, special stains confirmed reticulin fibrosis, and polymerase chain reaction confirmed clonal immunoglobulin heavy chain gene rearrangement. Fluorescent in situ hybridization was negative for translocations t(11;14) and t(14;18). Annexin A1 immunocytochemistry was positive.

Genetic analysis of BRAF gene by shifted termination assay and capillary electrophoresis.

BRAF gene analysis by shifted termination assay and capillary electrophoresis determined the V600E (GTG > GAG) mutation to be present in biopsy samples, with right peak showing wild type and left peak showing mutated BRAF.

Hairy-cell leukaemia


85-year-old man with stage IV lung adenocarcinoma who developed skin manifestations. Initially presented with erythematous follicular papules with focal scaling on scalp after 1 month of gefitinib treatment. Later developed increased scalp lesions with hair loss after switching to erlotinib. Also had paronychia, pruritus, and dry skin. No fever or constitutional symptoms. Potassium hydroxide (KOH) preparation of scalp lesions was negative.

Clinical photograph of the scalp vertex.

Shows numerous pustules with an erythematous base on the scalp vertex

Skin biopsy, H&E staining.

Skin biopsy showing diffuse inflammatory cell infiltration around hair follicles and in the dermis, with predominant lymphoplasmacytic cells and focal neutrophils (hematoxylin-eosin staining)

Acneiform drug eruption


A 30-month-old boy presented with sudden cardiac arrest during anesthesia induction with sevoflurane and nitric oxide before plastic surgery on June 7, 2004. The patient had never undergone ECG before the operation. Physical examination revealed distinctive facial features including a round face, small upper jaw and teeth, and nearly bald head. He had normal toes, with no history of seizure or syncope, and normal neurodevelopment. The patient was born via vaginal delivery without complications. Echocardiogram showed no intracardiac anomaly with normal ventricular function. Preoperative biochemical analysis and electrolyte levels were normal. Family history was notable for his older sister showing paradoxical QT interval prolongation on epinephrine stress test (QTc baseline 0.4 → peak 0.53 sec), though she was asymptomatic. The QT intervals of parents and sister were not significantly prolonged on ECG, and there was no family history of syncope, seizure, or sudden death.

(A) Clinical photograph of the hands, dorsal view, preoperative. (B) Plain radiograph of the hands, dorsal view, preoperative.

Figure 1 consists of two clinical photographs and corresponding radiographs demonstrating bilateral cutaneous syndactyly involving the third, fourth, and fifth fingers in a pediatric patient, as shown on page 2; the images depict the anatomical site (hands) at an unspecified preoperative time point, with the modality for the left panel being a gross clinical photograph and for the right panel being plain radiographs, both acquired in a dorsal (top-down) view, with no additional imaging or staining modalities used, and the key finding is the presence of fused soft tissue connecting the specified digits on both hands.

(A) 12-lead ECG after resuscitation. (B) ECG. (C) ECG.

ECG characteristics of long QT syndrome showing (A) 12-lead ECG after resuscitation with markedly prolonged QT interval, (B) markedly prolonged ventricular repolarization period resulting in functional 2:1 atrioventricular block, and (C) T-wave alternans with severe QT interval prolongation

Genetic analysis of the CACNA1C gene, sequencing, identified c.1216G>A (p.Gly406Arg) in exon 9.

Sequencing of the CACNA1C gene indicating the point mutation c.1216G>A (p.Gly406Arg) in exon 9

Timothy syndrome (genetically proven with CACNA1C mutation p.Gly406Arg)

Timothy syndrome


71-year-old man presented with gross painless hematuria and passage of clots. Medical history included: lower urinary tract symptoms, urinary retention (with transurethral resection of prostate 12 years prior), erectile dysfunction, hypertrophic cardiomyopathy, hypertension, hyperlipidemia, diverticulosis, mild obstructive sleep apnea, and nephrolithiasis. PSA was 13.0 ng/mL. Physical exam showed pulse 50 bpm, normal blood pressure/temperature/respiratory rate/oxygen saturation, BMI 30.0. Lab results showed potassium 3.3 mmol/L (low), creatinine 1.3 mg/dL, urea nitrogen 15 mg/dL, estimated GFR 59 mL/min/1.73m2. Complete blood count and other electrolytes were normal.

(A, B) Axial CT images of the bladder. (C) Sagittal reformatted CT image of the bladder. (D) Coronal reformatted CT image of the bladder.

Axial images (Panels A and B) show the presence of lobular, high-density material in the bladder (arrows), a finding consistent with blood clot. Sagittal (Panel C) and coronal (Panel D) reformatted images show that the high-density area (arrows) projects beyond the outline of the bladder, most likely representing hemorrhage in a bladder diverticulum.

(A) Bladder mass histology. (B) High magnification bladder mass histology. (C) Prostate core biopsy, Gleason score 6 (3+3).

A glandular mass (Panel A, arrows) appears underneath normal urothelium (arrowhead). In a view at high magnification (Panel B), neoplastic columnar cells form papillary (arrow) and tubular (arrowheads) structures. In addition to the ductal-type adenocarcinoma in the bladder neck, acinar-type prostatic adenocarcinoma (Panel C), Gleason score 6 (3+3), with a well-formed lumen (arrows) is seen in cores from the trans rectal biopsy of the prostate; the arrowhead shows a normal gland.

Adenocarcinoma of prostate


A 68-year-old man presented to the cancer center with metastatic melanoma. Five weeks before presentation, he developed pain and swelling in the right leg and groin, with subsequent resolution of pain and erythema following cephalexin treatment, though the mass persisted. He reported feeling well with no pain, fatigue, nausea, weight loss, headaches, cough, or dyspnea. His medical history included hypertension, gastroesophageal reflux disease, diverticulitis, cardiomyopathy, coronary artery disease with stent placement one year prior, and hearing loss. He had extensive sun exposure history and worked as a landscaper and mechanic. He smoked three packs daily for 20 years but stopped 20 years earlier. On examination, his blood pressure was 151/87 mm Hg, with decreased hearing and a hearing aid in the right ear. Physical examination revealed masses in the right groin and right medial thigh measuring 6 cm and 5 cm in maximal dimension respectively, with mild erythema and swelling of the right thigh and a well-healed scar on the right calf. No cervical, supraclavicular, submental, occipital, or axillary adenopathy was present. Laboratory studies showed blood glucose of 56 mg per deciliter (reference 70-110 mg/dL), while complete blood count, prothrombin time, renal and liver function tests, and levels of electrolytes, total protein, albumin, and globulin were all normal.

CT of the chest, abdomen, and pelvis.

CT of the chest, abdomen, and pelvis revealed enlarged retroperitoneal, pelvic sidewall, and inguinal lymph nodes on the right side, with the largest lymph node (4 cm in diameter) in the right groin.

Skin biopsy specimen of the metastasis in the right groin before treatment, H&E staining.

A skin-biopsy specimen of the metastasis in the right groin before treatment (hematoxylin and eosin) shows malignant epithelioid cells with hyperchromatic nuclei. Many of the cells also show dusty-brown cytoplasmic pigmentation that is consistent with malignant melanoma.

Biopsy specimen, Melan-A (MART1) staining, high magnification.

The pretreatment biopsy specimen at high magnification with staining for Melan-A (melanocyte antigen, also known as MART1 [melanoma antigen recognized by T cells 1]) shows diffuse cytoplasmic staining of the malignant epithelioid cells.

Metastatic melanoma with a BRAF V600E mutation

Metastatic melanoma of unspecified site


A 17-year-old boy presented to the hospital with a wound infection that developed 5 days after undergoing urological surgery. The patient came for evaluation and management of this post-surgical complication.

CT scan of the pelvis, proximal femurs included.

CT scan of the pelvis performed to assess the depth of the wound infection revealed multiple well circumscribed, ovoid, radiodense bony lesions in the pelvis and proximal femurs. These lesions showed the characteristic appearance of osteopoikilosis with symmetric distribution and sclerotic bone changes without bone destruction.

Osteopoikilosis

Diseases of the musculoskeletal system or connective tissue

Orthopedic and connective tissue disorders


A 64-year-old man presented to the Accident and Emergency Department with an area of erythema over his right hand associated with fevers and rigors. Upon examination, he showed fevers and rigors.

Bone marrow trephine biopsy.

Bone marrow trephine biopsy demonstrated a hypercellular bone marrow showing replacement of normal hematopoietic cells by sheets of primitive blast cells.

Bone marrow immunohistochemical staining, CD34, CD33, TdT, MPO, CD10, and Pax-5.

Immunohistochemical staining of the bone marrow showed CD34 positive blast cells as well as CD33, terminal deoxynucleotidyl transferase (TdT), MPO, CD10, and Pax-5 positive blast cells.

(A) Clinical photograph of the right hand acquired several days after admission.

A: Figure 2 (A) depicts a clinical photograph of the patient's right hand showing a large, well-demarcated area of necrosis involving the dorsal and volar aspects, with bandages partially removed to reveal extensive tissue loss, acquired several days after admission during the acute phase of rapidly progressing hand cellulitis and necrosis.

(B) Clinical photograph of the palmar aspect of the right hand acquired during hospital admission.

B: Figure 2 (B) presents a clinical photograph showing the palmar (volar) aspect of the right hand following dramatic progression of necrosis, demonstrating a large, well-demarcated necrotic area with evidence of surgical debridement; the image was acquired during hospital admission as part of the diagnostic and clinical course in a patient with acute myeloid leukemia complicated by extensive cutaneous and subcutaneous necrosis.

Skin biopsy.

Skin biopsy showed widespread erosion and ulceration of the epidermis with dermis extensively infiltrated by monomorphic pink cells with large nuclei showing irregular grooved margins and a small rim of cytoplasm.

Histopathological section of skin from the affected hand, H&E staining, intermediate magnification.

B: Figure 3B demonstrates a histopathological section of skin obtained from the affected hand, stained with hematoxylin and eosin (H&E) at an intermediate magnification, showing extensive dermal infiltration by monomorphic pink cells with large nuclei and irregular grooved margins, features indicative of eosinophilic precursors.

Skin biopsy, immunohistochemistry, CD34-negative, TdT-negative, MPO-positive.

Immunohistochemistry of skin biopsy showed CD34-, TdT-, and MPO-positive cells matching the findings of the bone marrow specimen.

High-count acute myeloid leukemia with acute infiltrative leukemia cutis

Acute myeloid leukaemia, unspecified

Leukaemia cutis


63-year-old male, former smoker. Medical history: Left lower lobectomy with systematic lymph node dissection for pulmonary adenocarcinoma in October 2004 (papillary adenocarcinoma, moderately differentiated with micropapillary component, pT1aN2M0 stage IIIA). Four years later had tumor recurrence in subcarinal lymph node (#7). After two years, lymph node grew and new lesion detected in right lower lobe (S10). Molecular testing showed EML4-ALK rearrangement. Current presentation: Pyrexia (38°C), progressive dyspnea, cough with hemoptysis. Vital signs: temperature 38.1°C, BP 115/55 mmHg, pulse 86/min, respiratory rate 24/min. Physical exam showed inspiratory crackles in right lung fields. Arterial blood gases (on 10L/min O2): PaO2 50.5 torr, PaCO2 61.7 torr, pH 7.42. Lab results: WBC 10,590/μL (85% neutrophils, 0.2% eosinophils, 8% lymphocytes), Hb 13.1 g/dL, INR 1.9, CRP 15.2 mg/dL, creatinine 1.68 mg/dL, AST 70 IU/L, ALT 77 IU/L, LDH 480 IU/L, CK 269 U/L, surfactant protein-D 179 ng/mL, KL-6 934 U/mL. Normal ECG and echocardiography. Negative serologic tests for collagen vascular diseases. Negative sputum and blood cultures.

Chest x-ray.

Chest x-ray showed extensive bilateral diffuse pulmonary infiltration

CT of the lungs.

CT revealed bilateral, predominantly dependent and diffuse ground-glass attenuation

(C) Chest CT, coronal view, performed on admission.

C: Coronal chest computed tomography obtained on admission demonstrates bilateral, predominantly dependent and diffuse ground-glass attenuation with a "reverse butterfly" shadow pattern, indicative of acute lung injury; image modality is CT, anatomical site is the lungs, and timing corresponds to the acute presentation following crizotinib therapy.

Fiberoptic bronchoscopy of the right bronchus intermedius, performed during the acute phase following onset of respiratory symptoms.

Figure 2 shows a fiberoptic bronchoscopy image of the right bronchus intermedius, demonstrating bronchial hemorrhage (as indicated by the asterisk), with no evidence of Pneumocystis carinii pneumonia, acid-fast bacilli, fungi, or malignancy; the specimen was obtained during the acute phase following the onset of respiratory symptoms.

Drug-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and diffuse alveolar hemorrhage (DAH) related to crizotinib therapy

acute lung injury NOS

Injury, poisoning or certain other consequences of external causes

Acute respiratory distress syndrome

alveolar haemorrhage


A 45-year-old white man was found dead at home and underwent autopsy as the cause of death was not apparent. He had recently been under review by the respiratory team for poor respiratory function and patchy fibronodular lung changes. His medical history included osteomyelitis of the elbow, congenital kyphoscoliosis, and testicular seminoma, which had been treated with orchidectomy and chemotherapy. At postmortem examination, the abdominal cavity contained copious pus covering the serosal aspect of the small bowel. There was an obvious perforation at the level of the mid-ileum, as well as three ulcers on the mucosal aspect of the ileum, one of which had perforated. Widespread pale nodules measuring up to 5 mm each were noted throughout the parenchyma of both lungs and a small pale lesion was present in the left kidney. No abnormalities were seen in the cardiovascular, endocrine, or central nervous systems.

Histological section of the small bowel.

Histological section of the small bowel shows widespread granulomatous inflammation within the submucosa and muscularis propria of the bowel, with a Langhans giant cell visible. Small bowel villi are not easily visible due to autolysis from decomposition, and caseous necrosis characteristic of tuberculosis is seen focally.

Higher power histological section of small bowel.

Higher power view of histological section of small bowel shows almost confluent granulomas and associated Langhans giant cells.

Histological section of the lung.

Histological section of the lung shows granulomas, Langhans giant cells, and prominent caseous necrosis similar to findings in the kidney and lung.

Ziehl-Neelsen staining of bowel, kidney, and lung.

Ziehl-Neelsen staining shows abundant acid fast bacilli within the bowel, kidney, and lung, indicating disseminated tuberculosis.

disseminated tuberculosis

Certain infectious or parasitic diseases


A 45-year-old man presented with dry cough and breathlessness. During the investigation, he was found to be infected with HIV. Physical examination and other baseline clinical details were not specifically described in this brief case report.

Chest X-ray of the lungs.

Chest X-ray shows bilateral pulmonary infiltrates with a diffuse, ground-glass appearance affecting both lungs

HIV infection with pulmonary manifestations (specific pulmonary diagnosis not explicitly stated in the provided text)

HIV infection

Lung disease NOS


34-year-old white male presented with an indurated plaque on the forehead that extended onto the scalp over approximately 1 year. Initial laboratory findings showed positive antinuclear antibodies (1:200) and slightly increased C3d complement; other laboratory tests were normal.

Clinical photograph of the forehead and scalp.

Shows linear erythematous, non-scaling plaque on the forehead and non-scarring alopecia, following lines of Blaschko

Skin biopsy, Alcian-PAS staining.

Skin biopsy shows normal epidermis, dermal and subcutaneous mucin accumulation, and predominantly lobular lymphocytic panniculitis (Alcian-PAS staining)

Lupus profundus


70-year-old man with history of Gleason 9 (4+5) adenocarcinoma treated with radical prostatectomy 10 years ago. Presented to primary care with rectal pain persisting for several weeks. Patient had lost 20 lbs over 3-4 weeks and complained of progressive fatigue, poor appetite, severe tenesmus, and rectal pain. Patient had been living independently on West Coast but relocated to East Coast to be closer to adult children.

CT scan of the lungs, axial view.

A: Computed tomography (CT) scan image showing bilateral lung metastases, with an axial view demonstrating multiple metastatic lesions present within both lung fields.

CT scan of the liver.

CT scan of the prostatectomy bed.

CT scan shows soft tissue mass arising from the prostatectomy bed

Recurrent metastatic prostate adenocarcinoma with small-cell transformation, with metastases to lungs, liver, and perirectal area

Adenocarcinoma of prostate


A 52-year-old man with a medical history of hypertension, dyslipidemia, and coronary artery disease presented with chest pain and ST-segment elevations on electrocardiography. His coronary artery disease history was significant, including a bare-metal stent placement in the middle portion of the left anterior descending coronary artery 12 years prior and two drug-eluting stents placed in the left circumflex artery 5 years later due to obstructing lesions. On the morning of admission, his girlfriend found him unresponsive on the floor at home, after which he regained consciousness and reported chest pain and dizziness. He took two nitroglycerin tablets sublingually and had taken his regular 325 mg aspirin earlier. EMS examination revealed he was alert and oriented but appeared uncomfortable, with pale and diaphoretic skin. His vital signs showed blood pressure 110/90 mm Hg, pulse 51 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 98%. He reported chest pain rated 7/10. Nausea and vomiting developed during transport. In the ambulance, he became increasingly pale and diaphoretic and was unresponsive to voice. Upon arrival at the emergency department, he was initially alert and oriented, but within seconds his pulse decreased to 36 beats per minute and QRS complexes widened on the cardiac monitor. External pacing was attempted without mechanical capture. Brief seizure activity occurred, followed by runs of ventricular tachycardia with wide ventricular complexes. He became unresponsive with unobtainable blood pressure and carotid pulses, and the cardiac monitor revealed ventricular fibrillation. Laboratory results showed plasma total carbon dioxide 19.5 mmol/L, anion gap 17 mmol/L, phosphorus 2.3 mg/dL, and glucose 145 mg/dL; other electrolytes, complete blood count, liver and renal function tests were normal, and troponin I screening was negative.

Coronary angiogram of the right coronary artery.

Coronary angiogram showing thrombotic occlusion in the middle portion of the right coronary artery (marked with arrowhead).

Coronary angiogram showing restored flow in the right coronary artery after placement of a bare-metal stent (marked with arrows), with a temporary pacing wire visible (arrowhead).

Cardiac arrest due to ventricular fibrillation caused by acute myocardial infarction with ST-segment elevation (STEMI)

Cardiac arrest

Ventricular fibrillation

Acute myocardial infarction with ST-segment elevation

Acute ST segment elevation myocardial infarction


Dr T is an 85-year-old male physician with a history of hypertension and aortic stenosis who was in his usual state of health until 2 months prior to presentation, when he noticed mild shortness of breath while walking up an incline. Symptoms were inconsistent and did not progress. He was able to walk on level surfaces and pursue normal daily activities without difficulty. He denied chest pain, orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, lightheadedness, or syncope, and had no history of coronary artery disease. His past medical history included recurrent skin cancers, restless leg syndrome, chronic constipation, and hyperlipidemia. Current medications included hydrochlorothiazide 50 mg, lisinopril 40 mg, pramipexole 0.25 mg, simvastatin 20 mg daily, and metoprolol tartrate 50 mg twice daily. He was a semiretired allergist-immunologist, married, living with his wife, with 2 grown children. He consumed 1-2 glasses of wine per week and had no history of cigarette smoking. Physical examination revealed blood pressure 124/78 mm Hg, regular pulse 64/min, jugular venous pressure 6 cm, palpable carotid arteries with slightly delayed upstroke and no bruits, regular heart rhythm with normal S1, fixed split S2, no S3 or S4, grade 3/4 systolic ejection murmur loudest at right upper sternal border radiating toward the carotids, and point of maximal impulse was not displaced.

Transthoracic echocardiogram, continuous wave color Doppler of the aortic valve, performed in August 2008 and January 2009, aortic valve area 0.9 cm² (August 2008), 0.7 cm² (January 2009); peak velocity 4.1 m/s (August 2008), 4.9 m/s (January 2009); peak gradient 67 mm Hg (August 2008), 97 mm Hg (January 2009); mean gradient 43 mm Hg (August 2008), 68 mm Hg (January 2009).

Transthoracic echocardiogram continuous wave color Doppler results showing progression of aortic stenosis from August 2008 to January 2009, with aortic valve area decreasing from 0.9 cm² to 0.7 cm², peak velocity increasing from 4.1 m/s to 4.9 m/s, peak gradient increasing from 67 mm Hg to 97 mm Hg, and mean gradient increasing from 43 mm Hg to 68 mm Hg

Serial echocardiographic studies from March 2003 to January 2009.

Serial echocardiographic studies from March 2003 to January 2009 showing progression of aortic stenosis with peak velocity increasing from 3.4 m/s to 4.9 m/s, peak gradient increasing from 46 mm Hg to 97 mm Hg, mean gradient increasing from 26 mm Hg to 68 mm Hg, and valve area decreasing from 1.0 cm² to 0.7 cm² over this period

stenosis of aorta


42-year-old white female, previously healthy, referred by optician with subjective loss of visual field, particularly in right eye. Recently lost confidence to drive. Central vision unaffected. No family history of eye problems. Best corrected distance visual acuity (Snellen) 6/6 bilaterally, near acuity N5 bilaterally. Mild relative afferent pupillary defect in right eye. Normal anterior segment examination bilaterally. Goldmann applanation tonometry showed pressures of 12 mm Hg in each eye. Dilated fundal examination showed unremarkable maculas and retinas. B-scan ultrasonography showed highly echogenic bodies in both optic nerve heads.

(A) Color photograph of the right eye, optic nerve head. (B) Color photograph of the left eye, optic nerve head. (C) Autofluorescence imaging of the right optic disc. (D) Autofluorescence imaging of the left optic disc.

Color photographs showing irregular disc margins and multiple excrescences over entire optic nerve head in both right (A) and left (B) eyes. Autofluorescent emissions visible from both right (C) and left (D) optic discs

(A) Goldmann visual field plot, right eye. (B) Goldmann visual field plot, left eye.

Goldmann visual field plots showing bilateral advanced constriction, worse on the right (A) than the left (B)

Drusen of optic disc


A 62-year-old fit and well Romanian man presented with a two-week history of worsening acute localized pain in the upper abdomen and vomiting. His surgical history included an open appendectomy as a child and laparoscopic cholecystectomy 20 years ago. On presentation, he had fever (39°C) and tachycardia (104 beats/min), with blood pressure of 125/73 mm Hg. Physical examination revealed generalized abdominal tenderness, worse in the right upper quadrant, with localized guarding in the right upper quadrant. Blood tests showed a raised white cell count of 16 × 10⁹/L (reference range 4-10 × 10⁹/L) and a C reactive protein concentration of 277 mg/L (reference value <9 mg/L). A frontal projection erect chest radiograph was initially reported as showing pneumoperitoneum, but showed a normal bowel gas pattern under the left hemidiaphragm.

Chest radiograph, frontal (erect) projection.

Frontal projection erect chest radiograph showing elevated right hemidiaphragm with ill-defined area of lucency and small pleural effusion on the right

CT of the liver, transverse view.

Computed tomography transverse image shows air/fluid level within the liver abscess

(A) Coronal imaging of the retroperitoneum. (B) Coronal imaging of the retroperitoneum.

Patient lying supine during the examination. Left coronal image through the retroperitoneum showing that the fluid has in the abscess gravitated posteriorly as a result of the patient’s position (arrow). The right coronal image shows air displaced anteriorly within the contained abscess (arrow)

Pyogenic liver abscess (intrahepatic abscess)

Pyogenic liver abscess

Abscess of liver


A 56-year-old retired administrator was referred to dermatology for a second opinion on lifelong atopic dermatitis management. She had a history of allergic asthma controlled with beclomethasone dipropionate inhaler and had received multiple courses of oral prednisolone for flare-ups of both eczema and asthma. On examination, she presented with generalized atopic dermatitis, truncal obesity, and striae in the groins with cutaneous atrophy and spontaneous bruising. Laboratory investigations revealed severely suppressed adrenal function with baseline cortisol of 9 nmol/L (reference range 171-536 nmol/L), undetectable baseline ACTH <5 pmol/L (<46 pmol/L at 9 am), and inadequate response to synacthen stimulation test with peak cortisol of only 137 nmol/L (expected ≥500 nmol/L). Additional findings included impaired glucose tolerance and osteopenia with spinal T-score of -1.9.

(A) Clinical photograph of axillary folds acquired at the time of dermatological examination. (B) Clinical photograph of antecubital fossae acquired at the time of dermatological examination.

Figure 1 consists of clinical photographs illustrating cutaneous adverse effects of steroid treatment, with subfigure A showing striae in the axillary folds and subfigure B depicting striae in the antecubital fossae; both images are gross clinical photographs acquired at the time of dermatological examination, documenting the anatomical sites affected and the morphological appearance of steroid-induced striae, without any staining or magnification technique involved.

Clinical photograph of the facial region.

Figure 2 presents a clinical photograph of the patient's face demonstrating steroid-associated adverse effects, specifically showing telangiectasias and moon facies, with no mention of imaging modality or sample timing, and the anatomical site examined being the facial region.

Iatrogenic Cushing syndrome


A 68-year-old woman with a longstanding history of non-specific inflammatory arthritis presented with a three-month history of flashing lights and blurred vision. She had been taking 400 mg hydroxychloroquine daily for 15 years, along with meloxicam, omeprazole, and amitriptyline. She was of normal body weight. Ophthalmological assessment revealed reduced visual acuity at 6/18 in the right eye and 6/12 in the left eye, with mild depression in color vision on Ishihara plate testing. Early cataracts were present.

Color fundus photography of both maculas.

Color fundus photography shows bilateral disturbance of retinal pigments at both maculas giving a 'bull's eye' appearance

Automated perimetry visual field testing of both eyes.

Figure 2 presents the results of formal visual field testing using automated perimetry, demonstrating bilateral annular scotomas characteristic of toxic retinopathy; the modality is automated visual field assessment, examining both eyes, with the key finding being ring-shaped visual field deficits consistent with macular involvement.

Fluorescein angiography of both eyes.

Fluorescein angiography shows bilateral bull's eye maculopathy with parafoveal hyperfluorescence

Toxic retinopathy secondary to hydroxychloroquine

Retinopathy


A 33-year-old white man was admitted to the coronary care unit with chest pain. Two hours prior to admission, he developed epigastric pain which evolved into central chest pain. He experienced one episode of vomiting accompanied by dizziness, dyspnea, sweating, and distal paresthesias. The pain had resolved by the time of admission. Later that day, he became nauseated, diaphoretic, and visibly pale, with blurred vision, muffled hearing, and tingling in both hands. His systolic blood pressure dropped to 89 mm Hg and cardiac monitoring showed a pause of 3-4 seconds with no P wave activity. His medical history included syncope with phlebotomy but no other vasovagal-type events. He had been experiencing flu-like symptoms and his daughter currently had gastroenteritis. His family history was significant for a sister diagnosed with drug-resistant epilepsy with multiple seizures. Physical examination on admission was normal, and subsequent examination after the hypotensive episode was also normal.

Twelve-lead electrocardiograph on admission.

Twelve lead electrocardiograph on admission shows ST elevation that gradually descends into inverted T waves in leads V1 and V2, representing a 'coved' type 1 Brugada pattern

Twelve-lead electrocardiograph performed three days after admission.

Twelve lead electrocardiograph three days after admission shows a type 2 Brugada pattern

Brugada syndrome


A 53-year-old woman born in Puerto Rico presented with progressive erythroderma and lymphadenopathy. Her symptoms began approximatelyuse, pruritic rash that progressed to total-body erythema over the next year. Initial physical examination revealed diffuse confluent erythroderma with superficial scaling and erosions, focal lichenification, palmoplantar hyperkeratosis, follicular prominence, madarosis (loss of eyelashes/eyebrows), bilateral small ectropion of eyelids, and painful pitting edema of legs. She had axillary and inguinal lymphadenopathy. Temperature was 37.3°C, pulse 126 beats per minute, and blood pressure 110/58 mm Hg. She reported progressive alopecia, weight gain of approximately 9 kg in 2 weeks, diffuse pruritus, and recurrent infections. She had no history of blood transfusions and was allergic to aspirin. Family history included two nieces with systemic lupus erythematosus. Testing for syphilis, HIV, and HTLV-1 was negative.

Laboratory results over multiple hospitalizations. Flow cytometry.

Laboratory results over multiple hospitalizations showing persistent eosinophilia (ranging from 1% to 29%), elevated IgE levels reaching 26,260 IU/L, low total protein levels, anemia with hemoglobin as low as 10.8 g/dL, lymphocytosis, and other abnormalities including low iron, elevated LDH, and low albumin. Flow cytometry revealed elevated CD4:CD8 ratio of 10 and 7% CD3+CD7- cells expressing CD4.

(A) Chest CT. (B) Pelvis CT.

Selected images from CT scans of the chest (Panel A) and pelvis (Panel B) show axillary and inguinal lymphadenopathy (arrows), as well as subcutaneous edema of the pelvis (arrowhead).

Clinical photograph.

Clinical photographs demonstrating diffuse erythroderma, alopecia, and edema before treatment.

Skin biopsy of the left forearm.

Skin biopsy from left forearm showing hyperplastic epithelium with pityriasiform scale, spongiosis, and moderately dense dermal lymphoid infiltrate composed of small-to-medium-size atypical lymphoid cells with cerebriform, convoluted nuclei and epidermotropism.

Immunohistochemical staining of skin biopsy for CD3, CD4, CD5, CD7, and CD2.

Immunohistochemical staining of skin biopsy revealing CD3+, CD4+, and CD5+ T cells with loss of CD7 and CD2 expression in the atypical lymphoid infiltrate.

Bone marrow biopsy, no staining method or magnification specified, CD3+, CD4+, CD2–, CD7–.

Bone marrow biopsy showing hypercellular marrow with increased eosinophils and atypical lymphohistiocytic infiltrate composed of convoluted lymphoid cells expressing CD3 and CD4 with loss of CD2 and CD7.

Sézary syndrome


A 1-year and 4-month-old girl was admitted for evaluation of psychomotor retardation and an operation for exotropia. She was born at term (gestational age: 40 weeks) by cesarean delivery after an uneventful pregnancy, and was the first child of healthy, unrelated parents. The family history was unremarkable. On admission, she presented with a characteristic high-pitched cry and microcephaly. She showed delayed motor functions and crawling, was able to sit unassisted but unable to stand, with developmental characteristics lagging behind for normal chronologic age. On neurologic examination, she had left leg hypotonia, with normal tendon reflexes and normal cranial nerve signs. When she was 6 months old, ventricular septal defect was detected by echocardiography. Chromosome analysis revealed 46,XX,del (5) (p15.2) one month after delivery.

(A) Brain MRI, sagittal view, T1-weighted sequence. (B-D) Brain MRI, axial view, T2-weighted sequence.

Sagittal T1-weighted (A) and axial T2-weighted (B-D) images show hypoplasia of brainstem, most prominently in pons, with normal cerebellum, thinning of corpus callosum and mega cisterna magna (A, C). Mild atrophy of both frontal and temporal lobes and decreased myelination in both anterior limbs of internal capsules (arrows) are seen (D).

Cri-du-chat syndrome


43-year-old female with chronic back pain and depression who attempted suicide by overdosing on diazepam (40-50 tablets of 5mg) and an unknown quantity of methadone. Found unresponsive with respiratory rate of 4 breaths per minute. Initial labs showed elevated potassium of 7.6 and leukocytosis due to mild aspiration pneumonia.

CT scan performed 3 weeks after initial event.

CT scan showed marked and diffuse hypointensity throughout the subcortical white matter when patient deteriorated 3 weeks after initial event

MRI, brain, FLAIR and T2-weighted sequences.

MRI revealed confluent changes throughout the entire white matter, appearing diffusely hyperintense on both FLAIR and T2 weighted sequences

Axial T2-weighted MRI of the brain.

Axial T2 weighted image showed extensive confluent hyperintense signal abnormality throughout subcortical white matter with spared cerebellar white matter and no obvious cortical signal change

MR spectroscopy of subcortical white matter.

MR spectroscopy of subcortical white matter showed abnormally high peaks for creatinine and choline, with small lactic acid peak present

Delayed post-hypoxic leukoencephalopathy (DPHLE) following benzodiazepine and methadone overdose

leukoencephalopathy

Intentional overdose of benzodiazepines

External causes of morbidity or mortality

Intentional overdose of methadone


51-year-old man undergoing venesection for haemochromatosis. During procedure, experienced sudden gurgling sensation up his arm, followed by severe central crushing chest pain with radiation to jaw and left arm, severe dyspnoea, and left sided hemiparesis and dysphasia. On arrival to hospital: hypoxic (oxygen saturation 88% on room air), left hemiplegia (resolved within 15 minutes). Initial ECG showed T-wave inversion inferiorly. Troponin I was raised at 0.14 μg/L (ref 0-0.08 μg/L). Transthoracic echocardiography with bubble study showed right-to-left shunting during normal respiration and Valsalva. Baseline right heart pressures were normal. Transoesophageal echocardiogram confirmed patent foramen ovale with passage of bubbles.

CT pulmonary angiogram of the lung.

CT pulmonary angiogram showed filling defect in a subsegmental branch of the lingula, suggestive of pulmonary embolism

Peripheral air embolism with paradoxical embolism through patent foramen ovale, causing pulmonary embolism and transient cerebral and myocardial ischemia

air embolism

pulmonary embolism NOS

Transient cerebral ischemia

Transient myocardial ischaemia of newborn

Certain conditions originating in the perinatal period


A 29-year-old man from Central America, who had been living in the United States for 4 years and worked in agriculture, presented with a 6-week history of unintentional weight loss (10 kg loss from his usual weight of 64.4 kg), followed by severe upper abdominal pain (rated 8/10) that radiated to his throat and worsened with eating. Three weeks before presentation, he developed nausea, occasional vomiting, decreased food intake, and later experienced one episode of hematemesis and sore throat with fever. He had a history of respiratory illness approximately 2 years earlier and was a heterosexual male who reported having no more than eight partners in his lifetime with consistent condom use. On physical examination, he appeared cachectic with a temperature of 37.3°C initially, later rising to 38.3°C, blood pressure 101/68 mm Hg, pulse 114-119 beats per minute, and respiratory rate 18-20 breaths per minute. He weighed 47.6 kg with a BMI of 18.6. Physical findings included soft abdomen without tenderness initially, later becoming firm without distention, coarse breath sounds at both lung bases with scattered fine rales, white exudate on the underside of the tongue, and multiple nontender, mobile lymph nodes in the submandibular, submental, and cervical regions measuring 1-2 cm. He also had macular hyperpigmentation of the feet and legs that had been present for 10 years.

Laboratory results

Laboratory results showed hematocrit 33.2%, hemoglobin 10.7 g/dl, white-cell count 3100 per mm³ with 79.2% neutrophils and 11.4% lymphocytes, platelet count 345,000 per mm³, sodium 131 mmol/liter, potassium 3.5 mmol/liter, chloride 96 mmol/liter, carbon dioxide 19.8 mmol/liter, total protein 8.4 g/dl, albumin 3.2 g/dl, globulin 5.2 g/dl. Helicobacter pylori immune ratio was 1.56 (positive). HIV-1 and HIV-2 antibodies and p24 antigen were reactive, with positive HIV-1 antibodies confirmed by Western blot analysis.
Laboratory results on admission showed worsening anemia with hematocrit 26.7%, hemoglobin 8.6 g/dl, white-cell count 4100 per mm³ with 88.8% neutrophils and 5.6% lymphocytes, HIV-1 RNA 172,000 copies per ml, lactate dehydrogenase 283 U/liter, absolute lymphocyte count 190 per mm³, CD4 count 10 per mm³ (5.4% of total lymphocytes), CD8 count 114 per mm³ (59.8% of total lymphocytes), and CD4:CD8 ratio 0.09.

Frontal chest radiograph of the lungs.

Frontal chest radiograph showed multiple tiny nodules throughout both lungs without focal consolidation, and no evidence of mediastinal or hilar lymphadenopathy.

CT of the chest, axial view.

Axial CT scan of the chest showed numerous nodules, 1 to 3 mm in diameter, randomly distributed in a miliary pattern in both lungs.

CT, axial view, magnified.

Magnified axial CT image showed the miliary nodules more clearly.

Contrast-enhanced CT of the abdomen and pelvis, coronal view.

Contrast-enhanced coronal CT scan of the abdomen and pelvis showed multiple enlarged mesenteric lymph nodes with low-attenuation centers suggestive of central necrosis.

Gastrointestinal and disseminated histoplasmosis with acquired immunodeficiency syndrome (AIDS)

Histoplasmosis

Disseminated classical histoplasmosis

AIDS - [acquired immunodeficiency syndrome]


An 18-year-old adopted white woman presented at age 15 years with absent breast development, primary amenorrhea, and intermittent lower abdominal pain. At age 17 years 9 months, she measured 162.6 cm in height, weighed 44 kg, and had a body-mass index of 16.6. She had severe facial acne. Her bone age was 11-12 years at chronologic age of 15 years 5 months. She had a normal female karyotype (46,XX). Fasting glucose metabolism showed normal insulin sensitivity with HOMA-IR of 0.8.

Clinical examination at 17 years 8 months. Total-body dual-energy x-ray absorptiometry at 17 years 5 months, total body fat 11,834 g, total lean mass 30,459 g.

Shows absence of breast development (Tanner stage 1) and presence of pubic hair (Tanner stage 4) when examined at age 17 years 8 months, with total-body dual-energy x-ray absorptiometry at 17 years 5 months showing total body fat of 11,834 g and total lean mass of 30,459 g.

Ultrasonography at age 17 years 9 months of the pelvis. Right ovary: 8.4 × 4.7 × 8.3 cm. Left ovary: 2.9 × 2.7 × 3.1 cm. Uterus present; endometrial stripe not clearly identifiable.

Ultrasonography shows enlarged cystic ovaries, with the right ovary measuring 8.4 by 4.7 by 8.3 cm and the left ovary measuring 2.9 by 2.7 by 3.1 cm at age 17 years 9 months, along with a small uterus with no clearly identifiable endometrial stripe.

(C) Growth velocity chart, height velocity (cm/year) versus age (2–19 years), based on serial measurements.

C: Panel C of Figure 1 presents a growth velocity chart, displaying the patient's height velocity (in cm/year) plotted against age from 2 to 19 years, based on serial measurements; the data show the absence of the normal steroid-induced growth spurt at the time of puberty.

Growth chart for height and weight percentiles by age.

Shows linear percentiles for height and weight, with both measures initially at approximately 75th and 50th percentiles respectively until age 6, then dropping with height consistently below 50th percentile and weight consistently below 25th percentile.

Laboratory results.

Laboratory values show persistently elevated estradiol levels (750-3500 pg/mL by immunoassay, 2340 pg/mL by LC-MS), elevated estrone (1040 pg/mL), mildly elevated gonadotropins (LH 5.8-13.2 mIU/mL, FSH 6.7-19.1 mIU/mL), elevated inhibin A (184-319 pg/mL), normal AMH (2.8 ng/mL), and normal levels of estrogen-responsive proteins including SHBG, CBG, and TBG.

Genetic analysis, DNA sequencing electropherogram.

DNA sequencing electropherogram shows the homozygous ESR1 mutation c.1125G→T resulting in p.Gln375His.

Genetic analysis: ESR1 gene, amino acid sequence alignment at position Gln375 across 21 species.

B: This panel presents an alignment of the affected Gln375 residue of the ESR1 gene across 21 different species, demonstrating complete conservation of this amino acid position; the analysis confirms that the neutral polar glutamine at position 375 is invariant among humans, several mammals, birds, amphibians, and fish, underscoring its functional importance.

Transactivation assay in transfected COS-7 cells, EC50=5 nM for mutated receptor, EC50=20.51 pM for wild-type receptor.

Transactivation assays in transfected COS-7 cells show greatly reduced estrogen receptor activity in the mutated receptor compared to wild-type, with EC50 values of 5 nM for mutated versus 20.51 pM for non-mutated receptor (240-fold difference).

Delayed puberty and estrogen resistance caused by a homozygous loss-of-function ESR1 mutation

Delayed puberty

Disorder of puberty due to oestrogen resistance

raised ESR - [erythrocyte sedimentation rate]


54-year-old male smoker (60 pack-year history, current smoker) presented with chest pain and ST elevation myocardial infarction. No other medical history. Initial symptoms progressed to ventricular tachycardia. Initial oxygen saturation was 88% on room air. Physical exam showed low-grade fever with mild dyspnea. Lab results showed leukocyte count of 15800/mm3 and serum creatinine of 1.2 mg/dL. Blood and sputum cultures were negative. Gram stain, tuberculosis smear, serologic tests for Legionella and Chlamydia trachomatis were negative. Mycoplasma pneumoniae PCR was negative. Antinuclear antibody, double-stranded DNA antibodies, rheumatoid factor, C3 and C4 were within normal limits. Pulmonary function tests showed mild obstructive impairment with DLCO of 16.1 L (79%). Bronchoalveolar lavage showed cell count of 200 cells/μL with 8% eosinophilia and foamy macrophages. No bacteria or fungi were found in lavage fluid.

Chest X-ray.

Initial chest X-ray showed no active lung lesion

Chest X-ray, performed after two days of intravenous amiodarone therapy.

B: The follow-up chest X-ray shows bilateral alveolar and interstitial infiltration, demonstrating new diffuse pulmonary opacities after two days of intravenous amiodarone therapy in a 54-year-old man with recent myocardial infarction.

High-resolution CT scan of the chest.

High resolution CT scan showed bilateral diffuse consolidation, ground glass opacity and underlying emphysema

Amiodarone-induced pulmonary toxicity (APT)

disorder of lung


A 57-year-old female without any medical history was admitted for evaluation of a left ventricular tumor that was discovered incidentally. The patient was asymptomatic and had no relevant past medical history. Physical examination findings were not specifically described in the case report.

(A) MRI, T1-weighted sequence. (B) MRI, T2-weighted sequence. (C) MRI, phase-sensitive inversion recovery sequence, delayed enhancement. (D) Transthoracic echocardiography, four chamber view.

A: T1 weighted image shows high signal intensity (arrow). B: T2 weighted image shows high signal intensity (arrow). C: delayed enhancement (phase-sensitive inversion recovery MR image) shows stong enhancement with central sparing (arrow). D: transthoracic echocardiographic images: four chamber view shown. It shows round shaped and echogenic mass attached at the left ventricular apex (arrow).

Gd-DTPA first pass perfusion MRI, short axis view.

Gd-DTPA first pass perfusion MRI in short axis view. The lesion shows centripetal enhancement pattern (clockwise from top left).

Gross examination of the heart.

On gross examination, a whitish, solid mass was detached from the base of the anterolateral papillary muscle.

(A) Myocardial tissue, H&E staining, 12× magnification. (B) H&E staining, 100× magnification; inset: CD31 immunohistochemical staining, 400× magnification. (C) Desmin immunohistochemical staining, 100× magnification. (D) Trichrome staining, 100× magnification.

A: on lower power view, the mass is somewhat well demarcated. And the mass seems to be originated from myocardium (arrows) (H-E, ×12). B: high power view shows multiple irregular vascular spaces (arrows) with intervening wavy eosinophilic collagen deposition (H-E, ×100). The vascular spaces express CD31 immunoreactivity (CD31 ×400 inlet). C: desmin immunohistochemical staining reveals that most of stroma do not express desmin except smooth muscles around vessel (arrows) (Desmin ×100). D: most of the stroma shows bluish staining on trichrome (trichrome ×100). Desmin and trichrome staining confirms that most of stroma consists of collagen, not smooth muscle.

Angiofibroma of unspecified site


A 30-year-old female at 22 weeks gestation with her third child presented in February 2008 with a 10-day history of episodic imbalance with left-sided tonic-clonic activity without loss of consciousness, followed by progressive frontal headache. Initial physical examination was unremarkable, but as evaluation progressed, she developed new weakness of the left arm and leg. Following biopsy at week 24, her neurologic examination demonstrated significant deficits including 1 of 5 strength of the left hip and knee flexors, 2 of 5 of the left lower extremity dorsiflexors and plantar flexors, and 2 of 5 of the left deltoids, rendering her unable to ambulate.

MRI of the head, T2-weighted sequence.

Noncontrast MRI of the head demonstrated a large region of T2 hyperintensity in the white matter extending from the anterior right lateral ventricle to the right frontal lobe, and a second region of T2 hyperintensity with mild mass effect extending from the superior-posterior right ventricle to the right frontal lobe

(A) Right frontal lobe biopsy, H&E staining, low to intermediate magnification. (B) Right frontal lobe biopsy, H&E staining, higher magnification.

A: Figure 2 (A) on page 2 shows a hematoxylin and eosin (H&E)-stained histopathological section of the right frontal lobe biopsy, demonstrating a dense infiltrate of atypical lymphoid cells consistent with diffuse large B-cell lymphoma at low to intermediate magnification. B: Figure 2 (B) presents an H&E-stained section from the same biopsy at higher magnification, highlighting the large, atypical lymphoid cells with prominent nucleoli characteristic of diffuse large B-cell lymphoma.

Primary CNS lymphoma (diffuse large B-cell lymphoma)

Lymphoma NOS

Diffuse large B-cell lymphomas


32-year-old woman admitted to emergency department with somnolence, presumably after attempted suicide. History of dissociative and depressive disorders treated as outpatient at psychiatric facility. Multiple psychiatric medications prescribed including tranylcypromine, quetiapine, temazepam, clonazepam, cyproheptadine, melatonin, oxazepam, levomepromazine, and pipamperone. On initial assessment: Glasgow Coma Scale 11/15, hemodynamically stable (BP 140/85 mmHg, regular heart rate 90/min), temperature 37.3°C, oxygen saturation normal with respiratory rate 16/min. Physical exam showed somnolence but no other abnormalities.

Laboratory results at admission.

Laboratory findings at admission showed: pH 7.22, PaCO2 22 mmHg, PaO2 133 mmHg, bicarbonate 9.1 mmol/L, sodium 142 mmol/L, potassium 3.8 mmol/L, calcium 2.15 mmol/L, chloride 110 mmol/L, creatinine 100 μmol/L, BUN 5.2 mmol/L, glucose 6.8 mmol/L, lactate 25.9 mmol/L, plasma osmolality 380 mmol/kg, hemoglobin 7.4 mmol/L, WBC 5.2×109/L, platelets 240×109/L

Laboratory results.

Calculated values showed: anion gap 23 mmol/L (elevated), osmolality gap 84 mmol/kg (markedly elevated)

Ethylene glycol poisoning with level of 5.3 g/L

poisoning NOS


A 19-year-old woman presented with a 4-day history of right upper quadrant and epigastric abdominal pain that was intermittent and variable in intensity, associated with nausea, and radiating occasionally to her back. She reported profound fatigue and a significant 13.6-kg (30-lb) weight loss over the preceding months, which she attributed to stress from her parents' recent divorce. She had a history of hereditary spherocytosis and had undergone laparoscopic splenectomy and cholecystectomy 10 years earlier for chronic hemolytic anemia with symptomatic gallstones. Her medications included folic acid and an oral contraceptive, and she smoked one pack of cigarettes per day. On initial examination, she was afebrile with focal right-upper-quadrant abdominal tenderness without Murphy's sign. Initial laboratory studies showed elevated alanine aminotransferase (275 U/L) and aspartate aminotransferase (275 U/L), while alkaline phosphatase, total bilirubin, albumin, amylase, and iron levels were normal. Serologic tests for hepatitis A, B, and C were negative, and serum alpha-fetoprotein and human chorionic gonadotropin levels were normal. Upon re-evaluation at the university hospital, she had developed a low-grade fever (38.0°C), sore throat, and generalized lymphadenopathy involving cervical, supraclavicular, and inguinal regions with nodes up to 2 cm in diameter. Laboratory studies revealed a white cell count of 11,500/mm³ with 28% atypical lymphocytes, elevated lactate dehydrogenase (428 U/L), hyperuricemia (8.1 mg/dL), and reactive thrombocytosis (553,000/mm³).

Abdominal MRI of the liver, T1-weighted and T2-weighted sequences, segment VI, mass diameter 4.5 cm.

Abdominal MRI scan shows an exophytic mass within segment VI of the liver, measuring 4.5 cm in diameter, characterized by hypointensity on T1-weighted images and isointensity to slight hyperintensity on T2-weighted images, with no fat content, no arterial phase enhancement, and no delayed uptake of gadoxetate disodium.

(A) Peripheral blood smear, low magnification. (B) Peripheral blood smear, high magnification. (C) Peripheral blood smear, high magnification.

Several large atypical lymphocytes are evident in a background of spherocytes lacking central pallor (Panel A, low magnification; Panel B, high magnification), in addition to scattered Howell–Jolly bodies (Panel C, high magnification).

18F-FDG-PET-CT scan of lymph nodes in cervical, axillary, hilar, mediastinal, periportal, peripancreatic, mesenteric, and retroperitoneal regions.

18F-FDG-PET-CT scan demonstrates intense 18F-FDG uptake in multiple lymph nodes including bilateral cervical and left axillary regions, with additional uptake in hilar, mediastinal, periportal, peripancreatic, mesenteric, and retroperitoneal lymph nodes, while the hepatic mass was not hypermetabolic.

(A) Lymph node specimen, H&E staining. (B) Lymph node specimen, CD20 immunostaining. (C) Lymph node specimen, in situ hybridization for EBV-encoded small RNA.

The specimen shows reactive lymphoid hyperplasia with reactive follicles (Panel A, hematoxylin and eosin). Paracortical expansion by small lymphocytes and scattered large immunoblasts were also observed (not shown). CD20 immuno-staining highlights intact B-cell follicles (Panel B). In situ hybridization for Epstein–Barr virus (EBV)–encoded small RNA shows scattered EBV-positive cells (Panel C, darkly stained cells), a finding consistent with EBV infection.

(A) Planar scintigraphy of the abdomen, anterior view, performed 2 hours after intravenous administration of 99mTc-labeled, heat-denatured red cells. (B) Planar scintigraphy of the abdomen, posterior view, performed 2 hours after intravenous administration of 99mTc-labeled, heat-denatured red cells.

Anterior (Panel A) and posterior (Panel B) planar images of the abdomen, obtained 2 hours after intravenous ad- ministration of 99mTc-labeled, heat-denatured red cells, show focal uptake of red cells in the inferior right (RT) hepatic lobe, corresponding to the mass seen on MRI scanning, and in the left (LT) side of the upper abdomen, interpreted as indicating the presence of a splenule. Diffuse, mild hepatic red-cell uptake is also evident.

Excisional Biopsy Specimen of a Left Axillary Lymph Node.(A) Hematoxylin and eosin staining, microscopy. (B, C) Electron microscopy.

Panel A (hematoxylin and eosin) shows pleomorphic cells that are small to intermediate in size with round to slightly irregular nuclei, condensed chromatin, indistinct nuclei, and a moderate amount of cytoplasm. There are intermittent fibrous bands and numerous interwoven small vessels and capillaries, with no hepatic tissue or metastatic tumor evident. On staining with CD45, CD20, myeloperoxidase, and glycophorin A, the majority of cells were of hematopoietic origin (not shown); in situ hybridization for EBV-encoded early RNA showed strong, diffuse positivity
(not shown). The electron micrographs in Panels B and C show reticulocytes (green), red cells (red), myeloid cells (blue), lymphocytes (black), and nucleated red cells (purple).

Infectious mononucleosis due to Epstein-Barr virus infection with concurrent intrahepatic splenosis and residual splenule following previous splenectomy

Infectious mononucleosis

Epstein-Barr virus infection NOS

Splenosis

Diseases of the blood or blood-forming organs

Residual urine

status post asthmaticus


20-year-old previously healthy man presented with a mildly pruritic, progressive rash. The eruption began in his scalp and spread over 9 days to neck, back, and chest. No improvement with oral cephalexin prescribed in ED. Denies any medication use (prescription, OTC, herbal, vitamins) prior to onset. No travel or illicit drug use history. No fever, chills, or systemic symptoms. Appropriate immunizations, no relevant family history, never experienced similar episodes. Patient was afebrile and appeared well.

(A) Clinical photograph of the trunk and extremities, dermatologic examination at presentation.

A: Figure 1 (A) is a clinical photograph depicting grouped vesicles and tense bullae in a generalized distribution on the trunk and extremities of the patient, demonstrating a symmetric annular vesiculobullous eruption primarily affecting the torso, consistent with a dermatologic examination at presentation.

Clinical photograph of the trunk.

B: Closer view clinical photograph of the trunk showing vesicles and tense bullae arranged in an annular configuration with central erythema and scale, demonstrating the cutaneous lesions characteristic of this patient's progressive eruption.

Direct immunofluorescence of skin, 40× magnification.

Direct immunofluorescence showing linear IgA deposits along the basement membrane zone of the skin (40x magnification)

Linear IgA bullous dermatosis


A 35-year-old woman presented to the emergency room with a clinically incarcerated umbilical hernia. Fourteen days after the initial hernia repair surgery, she developed strong pain in the right lower abdomen and complained of umbilical secretion. Physical examination revealed the patient was afebrile. Blood analysis showed a slight elevation in leukocyte count at 11.05 × 10^9/L, while other parameters were unexceptional. Ultrasound of the abdominal wall detected a semisolid infraumbilical mass with a diameter of 5.5 cm. Initial histologic examination of the resected omental fat from the hernia repair revealed malignant cells with neuroendocrine differentiation. Immunohistochemical analysis was positive for synaptophysin and protein gene product 9.5. Fluorescent in situ hybridization revealed a rearrangement of the EWSR1 gene.

CT scan, infraumbilical region.

CT scan shows an infraumbilical mass (indicated by red circle) that was initially considered as a possible hematoma due to the postoperative chronology

an infraumbilical mass was sected by an open procedure. Immunohistochemical staining for CD99.

Immunohistochemical staining shows positivity for CD99

an infraumbilical mass was sected by an open procedure.Immunohistochemical staining for neuron-specific enolase.

Immunohistochemical staining shows positivity for neuron-specific enolase

an infraumbilical mass was sected by an open procedure. Histologic examination, MIB1 staining, proliferation fraction=60%.

Histologic appearance shows malignant, small, round, blue-cell tumor of the Ewing type with high proliferation fraction (MIB1) of 60%

Central primitive neuroectodermal tumour


An 80-year-old male smoker was referred with a 1.5-month history of chest pain and breathlessness, diagnosed with right-sided pleural effusion and left lower lobe mass. He had an Eastern Cooperative Oncology Group performance status of 2. On physical examination, he had right supraclavicular lymphadenopathy and decreased breath sounds on the right side of the chest. Fine needle aspiration cytology of the lung lesion was consistent with adenocarcinoma, while FNAC from the supraclavicular lymph node revealed necrotizing granulomatous lymphadenitis suggestive of tuberculosis. AFB stain was negative, and AFB culture or DNA tests were not performed on the FNAC specimen. Pleural fluid analysis showed straw-colored fluid with glucose of 106 mg/dL, protein 5.4 g/dL, LDH 279 U/L, and adenosine deaminase of 98.16 U/L (range for tubercular pleurisy being >40 U/L). The fluid was cytologically negative for malignancy and showed many lymphocytes, making it a lymphocyte-rich effusion.

PET scan, lower lobe of left lung mass, size 2.8 × 3.0 cm, SUV=7.15; right pleural deposits, SUV=12.8; cervical lymph nodes, SUV=5.03; bilateral supraclavicular lymph nodes, SUV=7.9; bilateral axillary lymph nodes, SUV=13.9; mediastinal lymph nodes, SUV=14.2; periportal lymph nodes, SUV=13.4; bilateral external iliac lymph nodes, SUV=3.7; right inguinal lymph nodes, SUV=12.9; peritoneal deposits, SUV=18.6; multiple hypermetabolic skeletal lesions; right loculated pleural effusion.

PET scan revealed a spiculated 2.8 × 3.0 cm mass with standardized uptake value (SUV) of 7.15 in the lower lobe of left lung, right loculated pleural effusion, multiple right pleural deposits (SUV, 12.8) and multiple lymph nodes in cervical (SUV, 5.03), bilateral supraclavicular (SUV, 7.9), bilateral axillary (SUV, 13.9), mediastinal (SUV, 14.2), periportal (SUV, 13.4), bilateral external iliac (SUV, 3.7) and right inguinal (SUV, 12.9) areas. There were also multiple discrete peritoneal deposits (SUV, 18.6) and multiple hypermetabolic skeletal lesions.

Adenocarcinoma of the lung with concurrent tuberculosis

lung adenocarcinoma

Tuberculosis, unspecified


An 82-year-old woman presented with a skin change on her chest wall, specifically about 2 weeks of pain associated with a small lump located on the right anterior chest on the lower aspect of her rib cage, 2 cm below her breast. Her medical history was significant for resected left cheek malignant melanoma at age 56 and left breast cancer at age 62 treated with modified radical mastectomy. The previous breast cancer pathology revealed grade 4 infiltrating ductal adenocarcinoma measuring 1.0 × 1.0 × 0.8 cm, positive for both progesterone and estrogen receptors, with all 13 removed lymph nodes being negative. On physical examination, a 6 to 7 mm slightly mobile lesion was noted, initially appearing most consistent with a sebaceous cyst, fibroma, or lipoma. The patient also recalled that approximately 60 years previously, she had a small skin lesion in that same area that was excised after it lactated while she was breastfeeding.

Histopathological section of ectopic breast tissue from the right anterior chest wall, H&E staining.

Figure 1 presents a histopathological section of the resected chest wall lesion stained with hematoxylin and eosin (H&E), demonstrating infiltrating ductal carcinoma with associated high-grade ductal carcinoma in situ; the anatomical site examined is ectopic breast tissue from the right anterior chest wall, though no specific magnification or field orientation is provided.

Second primary infiltrating ductal carcinoma in an extra mammary breast tissue (ectopic milk line breast cancer)

Infiltrating ductal carcinoma of breast

breast cancer


A 42-year-old white man was diagnosed with multiple myeloma (IIIA immunoglobulin G [IgG], International Staging System II) in June 2009. At diagnosis, his hemoglobin was 8.2 g/dL, protein electrophoresis showed monoclonal gamma globulin spike (4.46 g/dL), the IgG was 6,350 mg/dL, the bone marrow contained 32% abnormal plasmocytes, the serum albumin was 2.7 g/dL, and the results of blood and urine immunoelectrophoresis were compatible with monoclonal IgG-kappa gammopathy. There were no severe osteolytic lesions. Following chemotherapy and being prepared for autologous hematopoietic stem-cell transplantation, he was given cyclophosphamide 3 g/m² and G-CSF 10 μg/kg per day starting on day 9 when the WBC count was 0.8 × 10⁹/L. His WBC was 3.9 × 10¹⁰/L on day 16. After the second peripheral blood stem cell harvest on day 16, he developed fever (38.7°C). The patient complained of a severe stinging sensation.

Clinical photograph of the anterior trunk and upper and lower extremities, taken after the onset of symptoms.

Figure 1 on page 1 is a clinical photograph showing the anterior aspect of a male patient's upper and lower extremities and trunk, depicting extensive erythematous nodular and plaque-like skin lesions distributed over the arms, chest, abdomen, and legs; the image was taken after the onset of symptoms, which began following peripheral blood stem cell harvesting and discontinuation of granulocyte colony-stimulating factor in a patient with multiple myeloma.

Clinical photograph of the torso, upper arm, shoulder, and upper chest.

Figure 2 is a clinical photograph showing the patient’s torso, illustrating extensive erythematous cutaneous lesions in the form of nodules and plaques on the upper arm, shoulder, and upper chest, acquired following peripheral blood stem cell harvesting and onset after granulocyte colony-stimulating factor administration.

Clinical photograph of the lower limbs taken after stem cell harvesting.

Figure 3 is a clinical photograph taken after stem cell harvesting, depicting extensive erythematous cutaneous lesions in the form of nodules and plaques involving the patient's lower limbs, illustrating the severe, widespread skin involvement characteristic of acute neutrophilic dermatosis (Sweet’s syndrome) following granulocyte colony-stimulating factor administration.

Skin biopsy of the arm, histological examination.

Histological examination of arm skin biopsy showing edema and a predominantly inflammatory neutrophilic infiltrate of the upper half of the dermis, with tumescent endothelium but not characteristic of leukocytosis or vasculitis, and epidermis exhibiting areas of hydropic degeneration of basal keratinocytes with patches of spongiosis permeated with neutrophils, features characteristic of neutrophilic dermatitis consistent with Sweet's syndrome

Severe, extensive, granulocyte colony-stimulating factor-induced, corticosteroid-resistant Sweet's syndrome

Sweet syndrome


A 37-year-old male presented to the emergency department with dyspnea that had begun one week prior, initially characterized by fever and chills, followed by progressive respiratory difficulty. He appeared acutely ill with crackling sounds on chest examination, regular heartbeat without murmur, and purplish discoloration of the right ankle without local heat or tenderness. Initial vital signs showed blood pressure of 163/91 mmHg, pulse rate of 114 beats/min, respiratory rate of 24 breaths/min, and body temperature of 38°C. Oxygen saturation was initially 87% and increased to 95% with nasal cannula oxygen at 5 L/min. Laboratory tests revealed profound peripheral eosinophilia and thrombocytopenia with white blood cell count of 22,580/μL (50% neutrophils, 31% eosinophils, 10% lymphocytes), hemoglobin of 13.7 g/dL, and platelet count of 26,000/μL. Additional laboratory findings showed prothrombin time of 15 seconds, activated partial thromboplastin time of 35.4 seconds, normal fibrinogen levels, and markedly elevated D-dimer at 26.69 μg/mL. Serum total IgE and ECP levels were elevated at 939.4 IU/mL and 201.0 ng/mL respectively. Tests for anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, and parasites in stool and serum were negative. Bone marrow biopsy showed normal cellularity with increased eosinophils, and FIP1L1-PDGFRA gene fusion was not detected. The patient became progressively tachypneic requiring mechanical ventilation due to ARDS, with PaO2 levels remaining low at 49.9 mmHg despite supplementation.

Chest radiograph.

Initial chest radiograph shows patchy areas of consolidation with ground-glass opacity in both lower lung zones.

Skin biopsy of the right ankle.

Skin biopsy of the purpuric lesions of the right ankle shows diffuse eosinophilic perivascular infiltration in the dermis.

Skin biopsy of the right ankle, H&E staining, 40× magnification.

B: Skin biopsy of the purpuric lesion on the right ankle shows an eosinophilic abscess in the subcutaneous fat, demonstrated using hematoxylin and eosin (H&E) staining at 40× magnification.

Idiopathic hypereosinophilic syndrome (IHES) based on the presence of peripheral and tissue eosinophilia, along with the exclusion of other causes of eosinophilia

Idiopathic hypereosinophilic syndrome


A 67-year-old man presented to the emergency department with chest pain. He felt well until 10 days prior when nausea, nonbloody emesis, bloating, and epigastric pain developed, initially treated as gastroesophageal reflux with omeprazole without relief. On the day of presentation, substernal, nonradiating chest heaviness developed on exertion and progressed to rest pain accompanied by diaphoresis and dyspnea, rated 8/10 in severity. Medical history included mild asthma and hemicolectomy for dysplastic polyps with ventral abdominal hernia. Current medications included omeprazole, inhaled glucocorticoids, bronchodilators, montelukast, and zolpidem. He had a remote 20 pack-year smoking history. Physical examination revealed tachycardia (125 bpm), hypotension (84/62 mmHg), tachypnea (22 breaths/min), oxygen saturation 94% on 6L oxygen, BMI 30, uncomfortable appearance with pallor, diaphoresis, and accessory muscle use. Jugular venous pressure was 18 cm H2O, cardiac exam showed regular tachycardia with grade 2/6 holosystolic apical murmur, lung exam revealed rales at left base, abdomen was soft with palpable liver edge 4 cm below costal margin, and extremities were cool and clammy with thready pulses.

12-lead electrocardiogram.

12-lead electrocardiogram showed sinus tachycardia, low limb-lead voltage, left atrial enlargement, septal Q waves, poor R-wave progression, and diffuse T-wave flattening

(A) Chest X-ray, posteroanterior view. (B) Chest X-ray, lateral view.

A posteroanterior view of the chest (Panel A) reveals an enlarged cardiac silhouette, small pleural effusions in both lungs, and evidence of mildtomoderate pulmonary edema. A lateral view (Panel B) shows small pleural effusions.

(A) Cardiac tissue biopsy, hematoxylin and eosin staining, low magnification. (B) Cardiac tissue biopsy, hematoxylin and eosin staining, high magnification.

A photomicrograph at low magnification (Panel A, hematoxylin and eosin) shows a patchy, dense inflammatory infiltrate with destruction of cardiac myocytes. All four of the biopsy specimens obtained revealed this pattern of injury. Occasional giant cells can be identified within the infiltrate even at low power (arrows). A photomicrograph at highpower magnification (Panel B, hematoxylin and eosin) reveals an infiltrate consisting of a mixed population of lymphocytes, macrophages, eosinophils, and prominent multinucleated giant cells (black arrows). Ongoing myocyte necrosis (yellow arrows) is associated with the infiltrate.

Giant cell myocarditis


A 44-year-old man presented with a 6-month history of a lesion on the penis that began as a small, dark area following a sports-related groin injury while visiting another country. Initially diagnosed as a hematoma, the lesion persisted and developed into a small, firm nodule after 2 months, which enlarged over the next 2.5 months with eventual ulceration of the overlying skin. He noted a lump in the right inguinal region one week before seeking evaluation. He was born in a Caribbean country, immigrated to the United States 20 years earlier, was married with children, currently unemployed, and had no history of sexually transmitted diseases. His mother died of lung cancer. Physical examination revealed blood pressure of 155/83 mmHg, pulse 131 beats per minute, with normal temperature, respiratory rate, and oxygen saturation. A firm, erythematous nodule (4 mm diameter) was present on the right scrotum, and an erythematous, nontender, nonmobile mass (approximately 1 cm diameter) was evident in the right inguinal region. Routine laboratory tests were normal. Cultures of the penile lesion grew moderate amounts of Pseudomonas aeruginosa and Proteus mirabilis and a few colonies of enterococcus, while urine culture grew pseudomonas and blood culture was sterile.

CT of the pelvis, axial view, contrast-enhanced.

Axial contrast-enhanced CT of the pelvis shows a superficial necrotic penile mass measuring 5.6 cm by 1.0 cm on the right side, suspicious for squamous-cell carcinoma with possible invasion of the corpora cavernosa and corpus spongiosum.

CT, axial view, inguinal and pelvic regions.

Axial CT at a higher level shows necrotic right inguinal lymphadenopathy and an enlarged right external iliac lymph node.

MRI of the pelvis, axial view, T1-weighted gadolinium-enhanced and T2-weighted sequences.

Axial T1-weighted gadolinium-enhanced MRI of the pelvis shows signal abnormality on T2-weighted images with enhancement surrounding the penile shaft, thickening of the overlying skin, and nonenhancing, hypointense material surrounding the penile shaft without discrete signal abnormality within the shaft, with foreshortening of the shaft and the glans not visible.

Axial T1-weighted MRI of the right inguinal region.

Axial T1-weighted MRI at a higher level shows two peripherally enhancing lymph nodes measuring 2.8 cm by 2.8 cm and 1.4 cm by 1.2 cm in the right inguinal region, with stranding of the adjacent fat associated with the dominant node.

Fine-needle aspiration biopsy of the right inguinal mass.

Fine-needle aspiration biopsy of the right inguinal mass reveals clusters of keratinized squamous epithelial cells with cytologic features consistent with metastatic squamous-cell carcinoma.

Squamous-cell carcinoma of the penis, moderately to poorly differentiated, involving the glans and distal shaft, invading the corpora cavernosa and corpus spongiosum, and metastatic to inguinal lymph nodes (pathologic stage, pT2N2MX)

Squamous cell carcinoma of penis

Metastatic carcinoma of inguinal lymph nodes

Inguinal lymph node enlargement


30-year-old man with history of right radical nephrectomy 5 years prior for a 9.5-cm kidney mass. No family history of tuberous sclerosis. Patient was lost to follow-up in May 2009 but returned in June 2011 with newly found lung nodules.

Kidney biopsy, H&E staining, 400× magnification.

Nephrectomy biopsy showed sheets of large, oval tumor cells with high degree of nuclear pleomorphism and macronucleoli (H&E stain, x400)

Immunohistochemistry using HMB-45, 200× magnification.

Neoplastic cells showed diffuse and strong HMB-45 immunoreactivity (x200)

CT scan of the lungs.

CT scan showed two lung nodules in left upper lobe (3.5-cm LUL lingular nodule; 1.9-cm LUL apicoposterior nodule) and one subpleural nodule in right lower lobe (<0.5 cm)

(C) Percutaneous needle biopsy of left upper lobe lingular nodule, H&E staining, 400× magnification. (D) Percutaneous needle biopsy of left upper lobe lingular nodule, HMB-45 staining, 400× magnification.

Percutaneous needle biopsy of left upper lobe lingular nodule showed epithelioid angiomyolipoma with strong HMB-45 expression. (C: H&E, 400 magnification; D: HMB-45, 400 magnification)

Metastatic epithelioid angiomyolipoma (E-AML) of the kidney with lung metastases

Angiomyolipoma of kidney

metastasis in lung


52-year-old woman with exertional right buttock and thigh pain that resolves within 2 minutes of rest. Exercise tolerance worsened over past year, now limited to several blocks. Previously able to run 5-6 miles per day. Recently diagnosed hypertension controlled with lisinopril (5 mg daily). No other cardiovascular risk factors. Physical exam shows blood pressure 124/76 mm Hg bilaterally, high-pitched systolic bruit over right subcostal region and umbilicus, normal peripheral pulses. Ankle brachial index (ABI) at rest borderline normal (0.91) on right and normal (1.03) on left. Remainder of examination normal.

Selective renal arteriogram of the right renal artery.

Selective renal arteriogram shows 'beaded appearance' in the right renal artery

Catheter-based angiogram of the right external iliac artery.

Catheter-based angiogram shows long-segment stenosis of the right external iliac artery without atherosclerosis

Fibromuscular dysplasia (FMD) of the right renal artery and dissection of the right external iliac artery

fibromuscular dysplasia

Renal artery fibromuscular dysplasia

Aneurysm or dissection of iliac artery[External iliac artery]


57-year-old white male with history of AML in remission after allogeneic stem-cell transplantation from HLA-identical sister. Three years post-transplant, developed worsening sore throat over several months with associated progressive shortness of breath. Went into acute respiratory distress one morning after showering, requiring hospitalization and tracheotomy. Examination under anesthesia revealed right-sided laryngeal mass involving true vocal cord and false vocal fold.

Biopsy, H&E staining. Inset: high-power magnification.

Biopsy with H&E staining showed large atypical cells with high nuclear to cytoplasmic ratio, fine chromatin with prominent nucleoli, and high mitotic activity. Inset shows high power magnification of myeloid blasts

Immunohistochemical staining for CD117 on laryngeal biopsy specimen, high-power field.

B: Immunohistochemical staining for CD117 on a biopsy specimen of the laryngeal mass demonstrates strong positive labeling of neoplastic cells, confirming myeloid lineage; this image represents a high-power field of the laryngeal tissue section.

Immunohistochemical staining for myeloperoxidase of laryngeal tissue, high magnification.

C: This panel presents an immunohistochemically stained section of the laryngeal mass for myeloperoxidase, demonstrating cytoplasmic positivity in neoplastic myeloid blasts, thereby confirming the myeloid lineage of the tumor cells; the tissue sample was obtained from the larynx and is shown at relatively high magnification.

Contrast-enhanced CT scan of the neck.

Contrast-enhanced CT scan showed 2.7 x 2.7 x 2.8 cm mass arising from right true vocal cord and extending to supraglottis and anterior portion of left true vocal cord

Extramedullary AML (granulocytic sarcoma) of the larynx

Acute myeloid leukaemia, unspecified

Granulocytic sarcoma


76-year-old man with extremely high serum ferritin concentration (33,790 μg/L). Carrier of haemochromatosis-associated allele (H63D/heterozygous). Laboratory tests showed renal insufficiency and liver damage, with bilirubin concentration of 730 μmol/L and unconjugated bilirubin concentration of 272 μmol/L.

(A) Light microscopy smear, 40× magnification. (B) Scanning electron microscopy. (C) Scanning electron microscopy.

Abnormal red blood cell morphology shown in: (A) Light microscopy smear at 40x magnification showing changed morphology in most red blood cells, (B) Scanning electron microscopy showing red blood cells with pointed extensions and large membrane pores, contrasting with (C) normal discoid shape in healthy individuals

Iron overload with abnormal red blood cell morphology associated with H63D haemochromatosis allele

Iron overload diseases

Red blood cell morphology abnormal

Haemochromatosis


An 80-year-old man presented with melena and fresh red blood per rectum, associated with lightheadedness, but no other symptoms. His past medical history included metastatic Merkel cell carcinoma diagnosed eleven months earlier. During the current presentation, the patient remained hemodynamically stable but was dyspneic on exertion, though he denied any other cardiorespiratory symptoms. On examination, his jugular venous pressure was not elevated, pulsus paradoxus was not present, and there was no pedal edema. The chest was clear on auscultation and heart sounds were normal. Despite multiple investigations including two CT mesenteric angiograms, a definitive cause for the bleeding was not identified.

Cardiac MRI, axial orientation, performed during current clinical admission.

Figure 1 on page 1 is a cardiac magnetic resonance imaging (MRI) scan in an axial orientation, depicting a lobulated right atrial mass located along the posterior aspect of the right atrium, as indicated by the arrow; the scan was performed during the current clinical admission to assess a newly identified cardiac lesion.

FDG-PET/CT scan, left axillary lymph node, SUVmax=13.7; right atrial mass, SUVmax=8.8.

[18F]-fluorodeoxyglucose (FDG)-PET/CT scan demonstrated an intensely FDG-avid, enlarged left axillary lymph node (standardized uptake value, 13.7), and moderate to intense uptake in the right atrial mass (standardized uptake value, 8.8), but no evidence of metastatic disease elsewhere.

Metastatic Merkel cell carcinoma with cardiac metastasis to the right atrium

Merkel cell carcinoma of unspecified site

heart metastasis


A 41-year-old man presented to the emergency department with excruciating and sudden-onset abdominal pain originating in his right lower quadrant and radiating to his right groin and flank. The pain was slightly reduced when lying down but otherwise unaffected by position. He reported nausea and one episode of nonbloody, nonbilious emesis shortly after pain onset. Two weeks prior, he had experienced a less severe episode of similar pain in his left lower quadrant with radiation to his left flank, which resolved spontaneously. He reported several months of fatigue preceding these episodes but denied fevers, weight loss, chest pain, diarrhea, or urinary symptoms. He worked as a bartender in Massachusetts, had no medical problems or prescription medications, drank 1-2 alcoholic beverages 2-3 times weekly, and smoked one pack of cigarettes daily for 26 years. Family history included coronary artery disease and arrhythmias. Physical examination revealed an uncomfortable-appearing man with temperature 37.4°C, pulse 78 bpm, blood pressure 188/116 mmHg, respiratory rate 18/min, and oxygen saturation 96% on room air. Abdominal examination showed soft abdomen with diffuse, nonfocal tenderness on deep palpation in all quadrants without rebound tenderness or guarding. Bilateral costovertebral angle tenderness was present, more pronounced on the right side. Laboratory results showed white cell count 14,280/mm³ with 78% neutrophils, hemoglobin 12.6 g/dL, creatinine 1.5 mg/dL, and lactate dehydrogenase 440 U/L. Urinalysis revealed 1+ protein, specific gravity 1.043, and bland sediment. Erythrocyte sedimentation rate was 31 mm/hour and C-reactive protein 193 mg/dL. Various serologic tests including ANCAs, hepatitis B and C, HIV, antinuclear antibodies, and hypercoagulability panel were negative or normal.

CT of the abdomen after intravenous contrast administration.

Computed tomographic scan of the abdomen after intravenous contrast administration shows infarcts in both kidneys with focal volume loss in the left kidney suggestive of scarring.

(A) Angiogram of the left kidney vasculature. (B) Angiogram of the superior mesenteric artery vasculature.

Angiographic studies reveal numerous microaneurysms in multiple vascular territories. Panel A shows angiogram of left kidney vasculature with a single large aneurysm and multiple small aneurysms. Panel B shows angiogram of superior mesenteric artery vasculature with many small aneurysms. Additional microaneurysms were found in both kidneys and hepatic arteries.

Polyarteritis nodosa