32-year-old man presented with progressive vision loss. History of hypertension, alcohol and illicit inhalational drug use (stopped 3 months prior). Symptoms began 3 weeks prior with painless conjunctival injection and dryness in left eye. One week before admission developed bilateral eye discharge with crusting. Three days before admission noted vision loss on awakening. Additional symptoms included 1-week hip pain, 3-week acneiform facial rash, and 4-week leg rash. Father had 'spine fusion disease'. Physical exam showed: temporal wasting, pale and thin appearance, BMI 19.4. Eyes showed punctate epithelial erosions on right cornea, perforated descemetocele on left cornea. Visual acuity 20/200 right eye, light perception only left eye. Other findings: petechiae on soft palate, follicular horny papules, perifollicular erythema, corkscrew hairs, nonscarring alopecia on arms, purpuric macules/papules on legs. Mental status showed flat affect and poor insight. Lab tests showed low sodium (124-127), low potassium (2.4-3.4), low total protein (5.2), low albumin (2.6), low calcium (7.8).

Clinical photograph of the left eye.

Photograph shows left eye with conjunctival injection and purulent crusting/discharge on eyelashes

(A) Head CT with contrast. (B) Head CT with contrast.

A CT scan of the head obtained with the administration of contrast material shows multiple rim-enhancing cystic lesions in the submental subcutaneous tissue (Panel A, arrow). Fat stranding and swelling of the preseptal soft tissues of the left ocular globe (Panel B, arrow) are noted. The left sclera shows thickening and enhancement (arrowhead), which most likely indicate scleritis.

(A) Skin biopsy. (B) Skin biopsy.(Hematoxylin and Eosin).

Skin biopsy shows: A) Follicular keratotic plug suggestive of vitamin A deficiency B) Extravasated erythrocytes in superficial dermis suggestive of vitamin C deficiency

Vitamin A deficiency

Vitamin C deficiency

Vitamin D deficiency


A 50-year-old woman presented to her primary care physician with right nasal congestion and right parotid swelling. She had no significant past medical history but was a current smoker with a 35 pack-year history. Her symptoms did not respond to antibiotics or steroids. Physical examination and nasal endoscopy demonstrated swelling in the adenoid pad, more prominent on the right. CT scan confirmed the presence of a nasopharyngeal soft tissue density measuring 4.1 cm in diameter. Initial biopsy revealed atypical lymphoid hyperplasia with scattered large atypical cells with prominent nuclei that were positive for CD30, focally positive for CD15, and negative for CD20, CD45, CD56, and EBV latent membrane protein 1. Flow cytometry showed no clonal B cells. Following adenoidectomy, repeat MRI at 3 months showed recurrence of the mass. Subsequent nasal endoscopy with excision revealed a nodular infiltrate of small lymphocytes. The lymphoma cells were negative for CD20, CD45, and EBV latent membrane protein 1, with no clonal IGH gene arrangement identified. Additional workup included PET-CT scan showing fluorodeoxyglucose avidity only in the nasopharynx with standard uptake value maximum of 7.4 and no lymphadenopathy. Bone marrow biopsy was negative for lymphoma, establishing stage IEA disease.

Histopathological section of nasopharyngeal tissue, H&E staining.

Figure 1 presents a histopathological section of nasopharyngeal tissue obtained during excision of a mass, stained with hematoxylin and eosin (H&E); the image demonstrates a nodular infiltrate of small lymphocytes with scattered classical Reed-Sternberg cells, as described in the figure legend and referenced in the body text on page 1, with no further details regarding magnification or specific view provided.

Immunohistochemical staining for CD30 of nasopharyngeal tissue, high magnification.

A: Immunohistochemical staining of a nasopharyngeal tissue section for CD30 demonstrates classic Hodgkin lymphoma cells exhibiting characteristic Golgi staining; the section is shown at high magnification, confirming the presence of CD30-positive large atypical cells within the lymphoid infiltrate.

Immunohistochemistry for CD15.

Shows CD15 positive staining in lymphoma cells with characteristic Golgi pattern

Lymphocyte-rich classical Hodgkin lymphoma of the nasopharynx


A 46-year-old woman presented with a 2-month history of myasthenia gravis, having initially developed ptosis, weakness in the neck, and dyspnea. She was diagnosed with acetylcholine receptor-positive myasthenia gravis. During her clinical course, she developed a myasthenic crisis requiring ventilator care. A mediastinal mass was incidentally discovered on chest radiography. The mass was clinically suspected to be a thymoma given the association with myasthenia gravis.

CT of the anterior mediastinum.

Computed tomography reveals an anterior mediastinal mass with calcifications

Gross pathological photograph of the resected anterior mediastinal mass.

Figure 2 depicts a gross pathological photograph of the resected anterior mediastinal mass, showing a hard, lobulated nodule with a cut surface that is yellow to gray in color and exhibits calcification, consistent with the macroscopic appearance of the localized thymic amyloid deposit.

(A) Histopathology of the mass, H&E staining, 40× magnification. (B, C) Histopathology of the mass, H&E staining, 40× magnification.

Histopathology of the mass, HE stained. (A) The mass consists of amorphous eosinophilic hyaline substances that surround islands of thymic tissues, × 40. (B, C) Calcification and ossification are present in the amyloid deposits, × 40.

Polarized light microscopy after Congo red staining.

Apple-green birefringence is noted under polarized light microscopy after Congo red staining

Primary localized thymic amyloidosis with myasthenia gravis

localised primary amyloidosis

Endocrine, nutritional or metabolic diseases

Myasthenia gravis


78-year-old woman presented with asymptomatic, dome-shaped nodules on her left leg that appeared over a 1-year period. The lesions had pink-red surface; some were eroded and covered by necrotic crusts or fibrinous induit. Nodule diameters varied from 0.2 to 6 cm, with small satellite lesions around the largest nodule. Clinical examination showed bilaterally enlarged inguinal lymph nodes.

Clinical photograph of the left leg obtained after a one-year history of lesion appearance.

Figure 1 is a clinical photograph depicting multiple dome-shaped, pink-red nodules with some areas of erosion, necrotic crust, or fibrinous coating on the left leg, illustrating the cutaneous presentation of Merkel cell carcinoma on the extremity of a 78-year-old woman as observed on clinical examination after a one-year history of gradual lesion appearance.

Clinical photograph of the left leg.

Figure 2 is a clinical photograph demonstrating multiple, clustered, dome-shaped nodules with a pink-red surface and areas of erosion and necrotic crust on the left leg; the image highlights lesions ranging from 0.2 to 6 cm in diameter, including small satellite nodules surrounding the largest lesion, consistent with the clinical presentation of Merkel cell carcinoma.

Histologic examination, H&E staining. Immunohistochemistry, cytokeratin (CK) 20 and neuron-specific enolase.

Histologic examination showed dermal-based lesion composed of strands of small, uniform, round cells with scanty cytoplasm and round to oval nucleoli with powdery chromatin. Immunohistochemistry showed characteristic paranuclear dot-like positivity with cytokeratin (CK) 20 and neuron-specific enolase positivity

Multiple lesions of Merkel cell carcinoma (MCC)

Merkel cell carcinoma of unspecified site


12-year-old Hispanic girl initially presented with proteinuria detected at a well-child visit. Blood urea nitrogen and serum creatinine levels were normal. Urinalysis showed trace blood with urinary protein-to-creatinine ratio of 1.5. Renal ultrasonography showed normal-size kidneys. C3 and C4 serum levels were normal. By age 17, she had developed hypertension and urinary protein-to-creatinine ratio increased to 5.2. She was otherwise asymptomatic.

(A) Light microscopy, high-power view, Periodic acid–Schiff (PAS) staining. (B, C) Immunofluorescence microscopy for C3. (D) Immunofluorescence microscopy for C4d. (E, F) Electron microscopy, medium power.

Panel A shows findings on light microscopy (high-power view). Periodic acid–Schiff staining shows a proliferative glomerulonephritis with dense ribbonlike material (white arrows) along the capillary wall. In Panels B and C, immunofluorescence microscopy was negative for C3 (the yellow arrows indicate the glomerulus). C3 staining (internal positive control) in the tubules indicates reabsorption granules (white arrows in Panel B) and segmental staining in one capillary tuft (white arrow in Panel C). In Panel D, immunofluorescence microscopy shows bright staining for C4d. In Panels E and F, electron microscopy at medium power shows large osmiophilic subendothelial dense deposits lining the glomerular basement membrane (white arrow in Panel E). Panel F shows a double-contour formation (black arrows indicate the basement membrane). The deposits line the glomerular basement membrane and do not infiltrate the glomerular basement membrane.

C4 dense-deposit disease characterized by C3-negative proliferative glomerulonephritis with C4 deposition associated with large osmiophilic subendothelial dense deposits, driven by overactivation of the lectin pathway

C syndrome

Proliferative glomerulonephritis NOS


A 56-year-old man presented to the emergency room with shortness of breath, cough, fever, and chest pain. He had a history of mild essential hypertension but no history of significant cardiovascular disease. Five years prior to this acute presentation, he was diagnosed with immunoglobulin A myeloma and had undergone multiple treatment cycles including idarubicin and dexamethasone, thalidomide maintenance, autologous hematopoietic stem-cell transplantation, and subsequent relapses treated with bortezomib/dexamethasone and most recently lenalidomide starting 2 months before his emergency presentation. On presentation, cardiac enzymes were slightly elevated, his initial electrocardiogram and chest radiograph were normal, but he subsequently became acutely tachycardic with a second electrocardiogram demonstrating atrial flutter and an echocardiogram identifying a small pericardial effusion.

Laboratory results for total IgA and IgA kappa paraprotein levels; bone marrow infiltration percentages at presentation, first relapse, and second relapse; skeletal survey for lytic lesions at T10/T11 initially and L3/L5 at second relapse.

Shows disease course from initial presentation to second relapse with total IgA levels ranging from 80.8 g/L at presentation to 4.33 g/L at second relapse, IgA kappa paraprotein levels from 40 g/L initially to detectable but unsuitable for analysis at relapses, bone marrow infiltration of 65% at presentation, 25% at first relapse, and 30% at second relapse, with lytic lesions identified on skeletal surveys at T10/T11 initially and L3/L5 at second relapse.

Low-power microscopic examination of myocardium sections.

Low-power magnification microscopic examination of myocardium sections revealing diffuse infiltrate of pleomorphic plasma cells.

High-power microscopic examination of myocardium sections.

High-power magnification microscopic examination of myocardium sections showing diffuse infiltrate of pleomorphic plasma cells.

Congestive cardiac failure secondary to myocardial infiltration from multiple myeloma relapse

Congestive heart failure

glycogenic myocardial infiltration

multiple myeloma


A 29-year-old female former smoker was diagnosed with stage IV signet-ring cell carcinoma of the lung with multiple pulmonary metastases. Fluorescent in situ hybridization analysis of biopsied tumor tissue revealed the presence of an anaplastic lymphoma kinase gene (ALK) rearrangement. After 10 months of crizotinib therapy, the patient showed no symptoms of infection such as fever or weight loss, helping to rule out differential diagnoses of abscess, tuberculosis, and parasitic infection for the cystic brain masses.

CT of the brain performed over a two-month period.

CT imaging revealed multiple cystic lesions in the brain that increased in size and number over a two-month period, suggesting brain metastases.

MRI of the brain, T1-weighted and T2-weighted sequences.

Cranial MRI revealed multiple cystic masses that were predominantly centrally hypointense in T1-weighted images and hyperintense in T2-weighted images with an extremely thin cyst wall.

Cystic brain metastasis in non-small-cell lung cancer with ALK rearrangement

Non small cell lung cancer

brain metastases

brain metastases

Balanced rearrangements or structural rearrangements


23-year-old white female initially diagnosed with stage IIB melanoma of the upper extremity after wide resection and sentinel lymph node biopsy. Ten months later, she developed metastatic disease with a large chest wall mass and axillary lymph node involvement. Initial imaging showed bilateral pulmonary nodules and bilateral hilar adenopathy. Five months after that, she developed lower extremity neurologic deficits.

Sagittal T1-weighted MRI with contrast of the spinal cord and conus medullaris.

Sagittal T1 image with contrast shows diffuse enhancement of the pial surface of the cord and conus medullaris, indicating melanomatous meningitis, as well as medullary deposits in the cord

Sagittal T2-weighted MRI.

Sagittal T2 image shows diffuse cord edema secondary to these deposits

Melanomatous meningitis (MM) with concurrent spinal cord metastases, confirmed by presence of malignant cells consistent with melanoma in spinal fluid

meningitis NOS

Malignant neoplasm metastasis in spinal cord

melanoma NOS


A 61-year-old woman presented with a 3-4 week history of gastrointestinal symptoms including epigastric pain, vomiting, and diarrhea, along with fever and arthralgias that she initially attributed to viral gastroenteritis. She had a medical history of labile hypertension, hypercholesterolemia, allergic rhinitis, and possible GERD. Physical examination revealed mild epigastric tenderness, blood pressure of 160/77 mmHg, pulse of 89 bpm, and temperature of 37.7°C. Stool was positive for occult blood. Upper endoscopy showed only a small hiatal hernia. Testing for ANA and anti-dsDNA antibodies was negative.

Laboratory results.

Laboratory data showing progressive anemia (hemoglobin declining from 13.4 to 8.9 g/dL), acute kidney injury (creatinine rising from 0.88 to 1.66 mg/dL), elevated inflammatory markers (ESR 28 mm/hr, CRP 47.2 mg/L), abnormal free light chain ratio (kappa:lambda 3.1), low immunoglobulins (IgA 67, IgG 523, IgM 80 mg/dL), very low complement C4 (<2 mg/dL), low C3 (77 mg/dL), positive rheumatoid factor (41 IU/mL), and active urinary sediment with proteinuria, hematuria, numerous casts including red cell casts, and high urine protein content

(A) Kidney tissue, H&E staining. (B) Kidney tissue, PAS staining. (C) Vessel, H&E staining. (D) Kidney immunofluorescence for IgM. (E) Kidney electron microscopy.

Glomeruli have pseudothrombi (arrows), swollen endothelial cells, and endocapillary inflammatory cells (Panel A, hematoxylin and eosin; and Panel B, periodic acid–Schiff). Vessels with reactive endothelial cells, mural cryoglobulin deposits (Panel C, arrow; hematoxylin and eosin), extravasated red cells (arrowhead), and karyorrhectic debris are present. IgM immunofluorescence (Panel D) revealed granular staining of capillary loops and positive pseudothrombi. An electron micrograph (Panel E) shows a subendothelial deposit with a tubular substructure. (In all images, the Smart Sharpen filter [Photoshop CS] was used for white balance and sharpening, with identical settings for each image.)

(A) Cryocrit tube. (B) Gel electrophoresis of washed cryoprecipitate. (C) Bone marrow aspirate flow cytometry. (D) Bone marrow aspirate flow cytometry.

The left cryocrit tube (Panel A) shows a negative sample, and the right tube shows a sample from the patient, with 3% of the total serum volume consisting of a cryoprecipitate (cryo). Gel electrophoresis (Panel B) performed on the washed cryoprecipitate shows a band at the origin (arrowhead) and a cathodal band (arrow). In replicate lanes probed with isotype-specific antiserums, IgM and kappa antiserums show similar banding patterns, whereas IgG shows a polyclonal smear. Flow cytometry of a bone marrow aspirate (Panel C) shows a small population of CD20+ B cells with expression of kappa light chain. This population is negative for lambda light chain (Panel D). FITC denotes fluorescein isothiocyanate, PE phycoerythrin, and PERCP peridinin chlorophyll protein. Panels C and D courtesy of Frederic I. Preffer, Ph.D., Flow Cytometry Laboratory.

Type II cryoglobulinemia with acute glomerulonephritis and renal vasculitis

Cryoglobulinaemia Type II

acute glomerulonephritis

Renal vasculitis


A 15-year-old boy with congenital neutropenia due to an ELA2 gene mutation and refractory anemia with excess blasts 2 (WHO Myelodysplastic Syndrome Classification) was referred to the hospital for bone marrow transplantation. He had a history of low absolute neutrophil count ranging from 200 to 1,000/μL and frequently required granulocyte colony-stimulating factor and antimicrobial therapy for multiple bacterial skin and lung infections since infancy. On physical examination, he presented with multiple nonpruritic skin ulcerations on the right side of his abdomen, scalp, and left ankle. According to patient and family history, these skin lesions had been present for several weeks and were initially thought to be of fungal origin. Laboratory studies showed normal absolute neutrophil count while receiving granulocyte colony-stimulating factor, normal absolute lymphocyte and eosinophil counts, significantly elevated immunoglobulin G levels (3× the upper normal level for his age), and normal immunoglobulin E levels.

(A) Clinical photograph of the scalp at hospital admission.

A: Figure 1 (A) on page 1 is a clinical photograph showing the patient's scalp with numerous discrete, coalescing, erythematous, crusted, variably alopecic, and eroded plaques measuring 10 by 15 centimeters in aggregate, representing nonpruritic ulcerative skin lesions present for several weeks at the time of hospital admission.

(B) Clinical photograph of the right flank.

B: Figure 1 (B) is a clinical photograph depicting the patient's right flank, showing two large, well-defined, round and oval, focally eroded erythematous and hyperpigmented plaques, with a total aggregate size of 30 cm, representing nonpruritic ulcerative skin lesions that had been present for several weeks.

Skin section, H&E staining.

Hematoxylin and eosin-stained section shows skin with focal epidermal ulceration at the edge of the biopsy, hyperkeratosis, parakeratosis, and a mite burrowing into the stratum corneum. The superficial/papillary dermis demonstrates chronic inflammation, increased fibrosis, and a haphazard arrangement of skin adnexal structures

Longitudinal section of a scabies mite.

Shows a longitudinal section of a scabies mite with a chitin exoskeleton, with spines on its dorsal surface allowing it to anchor to the stratum corneum and internal organs

Crusted scabies

Certain infectious or parasitic diseases


A 78-year-old white woman was referred by her general practitioner for anemia with a high erythrocyte sedimentation rate. Her main complaints were lethargy and easy fatigue that had persisted for 2 months. Her past medical history included hypertension and high cholesterol, for which she was receiving perindopril and atorvastatin tablets. Clinical examination revealed normal cardiac, respiratory, and neurologic statuses, with no organomegaly or lymphadenopathy. Her Eastern Cooperative Oncology Group performance status was 1. Initial blood tests showed low hemoglobin (99 g/L; normal range 120-160 g/L), normal white cell and platelet counts, high erythrocyte sedimentation rate (120 mm per hour; normal range 5-20 mm per hour), mildly elevated creatinine level (110 mmol/L; normal range 50-100 mmol/L), and high calcium level (2.81 mmol/L; normal range 2.10-2.60 mmol/L). Lactate dehydrogenase was mildly elevated (333 U/L; normal range 125-243 U/L). Additional blood investigations revealed high levels of immunoglobulin G (IgG) kappa paraprotein quantified at 32 g/L, high β₂-microglobulin (6.3 mg/L; normal level <3.0 mg/L), high free kappa light chains of 1,400 mg/L (normal level <19 mg/L), and a high kappa/lambda ratio of 280. Bence-Jones protein (kappa) was detected in urine, and 24-hour urine protein excretion was within normal limits. Serum vitamin D, parathyroid hormone, and alkaline phosphatase levels were within normal ranges.

Bone marrow histopathology, trephine section, 16× magnification.

Histopathologic examination of bone marrow trephine showed a marked increase in trabecular bone mass with scanty marrow. The thickened trabeculae were covered by osteoid seams showing active mineralization, indicating increased osteoblastic activity (×16 magnification).

(A) Bone marrow biopsy, 400× magnification, CD138 immunohistochemical staining. (B) Bone marrow biopsy, reticulin fibers, silver nitrate staining.

Marrow spaces appeared as small islands within thickened trabeculae and were markedly hypercellular. Approximately 80% of the marrow was infiltrated with abnormal plasma cells (×400 magnification), confirmed by positive CD138 immunohistochemical stain. Reticulin fibers were markedly increased as evidenced by silver nitrate staining.

Skeletal survey with x-rays, anteroposterior view, axial bones including skull, ribs, vertebrae, and pelvis.

Skeletal survey with x-rays showed sclerotic dense bones causing diffuse increase in radio-opacity throughout the axial bones, including skull, ribs, vertebrae, and pelvis (anteroposterior view), and to a lesser extent in upper and lower limb bones.

Bone mass densitometry of the lumbar spine (L2-L4) and femoral neck performed before treatment.

Pretreatment bone mass densitometry showed markedly increased bone mineral density: lumbar spine (L2-L4) was 2.192 g/cm², T-score 7.1, representing 178% of young adult values and 226% of age-matched values; femoral neck was 1.661 g/cm², T-score 5.1, representing 163% of young adult values and 228% of age-matched values.

Multiple myeloma with diffuse osteosclerosis

multiple myeloma

Osteosclerosis

Diseases of the musculoskeletal system or connective tissue


A 21-year-old man presented to his general practitioner with intermittent left-sided pain in the anterior chest wall associated with neck discomfort. The pain was described as 'stabbing' in nature and had arisen suddenly while watching television, with no history of trauma before onset. The pain was not exacerbated by inspiration or effort. His medical history and physical examination were initially unremarkable. Several days later, he attended the emergency department with worsening chest pain and dyspnea. On examination, chest expansion was equal and breath sounds were normal, although there was crepitus on auscultation of the precordium. Palpation of the neck and supraclavicular fossae detected subcutaneous emphysema. His respiratory rate was 25 breaths per minute and oxygen saturations were 100%. His full blood count and inflammatory markers were within normal limits.

Chest radiograph on admission.

Chest radiograph on admission showing linear lucencies in the suprasternal region and superior mediastinum projected parallel to the trachea, with changes most prominent to the left of the trachea, consistent with paratracheal free air and gas in the soft tissues at the base of the neck extending into the superior mediastinum.

CT of the superior mediastinum, axial view, contrast-enhanced.

Contrast enhanced axial CT image at the level of the superior mediastinum showing areas of decreased attenuation lying posterior to the sternum, adjacent to the left brachiocephalic vein and to the right of the trachea, with attenuation values consistent with gas and no parenchymal lung disease, confirming pneumomediastinum.

Spontaneous pneumomediastinum (Hamman's syndrome)

pneumomediastinum

Hamman-Rich syndrome

Cardiovascular and respiratory disorders


14-year-old boy presented to trauma unit with gunshot wound to left eye. Alert and hemodynamically stable, blind in left eye, no CSF rhinorrhea. Pubertal status: Tanner stage S3, height: 1.7m (75th percentile). Laboratory findings: 8am serum cortisol 28 nmol/L (normal 171-536), thyroid-stimulating hormone 0.63 mIU/L (normal 0.27-4.20), free thyroxine 13.5 pmol/L (normal 13.6-23.2), luteinising hormone 0.7 IU/L (normal 1.3-9.8), insulin-like growth factor 1 19.4 nmol/L (normal 28.8-127.3), prolactin 13.04 pmol/L (normal 174-660.9), testosterone undetectable <0.1 nmol/L (normal 1-38.5).

Plain radiograph.

Plain radiograph shows 9mm bullet partly located in the sphenoid sinus

CT scan of the clivus and pituitary fossa.

CT scan shows fracture of the clivus with bullet partially located in pituitary fossa, with associated artifact

Hypopituitarism


A 35-day-old male infant, born at 37.5 weeks gestation as a fraternal twin via cesarean section for breech presentation, presented with fever, vomiting, mottled skin, and severe anemia. The patient was previously healthy, consuming both breast milk and formula. His mother had uncomplicated prenatal care with negative screening tests for various infections. Two days before admission, he was well at a routine examination. The day before admission, his mother noted increased fussiness, pale and warm skin, and one episode of vomiting. On the morning of admission, tachycardia was noted with increased vomiting. At presentation, the patient was pale with mottled skin and showed signs of respiratory distress. Physical examination revealed a temperature of 39.1°C, blood pressure 101/69 mmHg, pulse 176 beats per minute, respiratory rate 68 breaths per minute with supraclavicular, intercostal, and subcostal retractions, and oxygen saturation 97% on 1 liter of oxygen via nasal cannula. He was pale, listless, and fussy with a holosystolic-flow murmur grade 2/6. The spleen was palpated 2-3 cm below the costal margin. His arms and legs were mottled and slightly cool. The family lived in a suburban, forested neighborhood where the mother frequently walked, and they had a pet dog. The mother had vacationed on an island off the coast of Massachusetts approximately 2.5 months before admission. Urinalysis showed dark red, cloudy urine with large amounts of blood, protein, and granular casts.

Laboratory results from the other hospital and this hospital. Blood smear examination, Wright's stain. Cerebrospinal fluid analysis, Wright's stain.

Laboratory results showed severe anemia with hematocrit of 16.9% at the other hospital and 20.9% at this hospital, hemoglobin 6.1 g/dl and 7.6 g/dl respectively. Severe thrombocytopenia with platelet count of 23,000 and 36,000 per mm³. White cell count was normal at 8000 and 6500 per mm³, but neutropenia was present (6% and 9% neutrophils). Blood smear showed moderate stippling and polychromasia with 35-40% erythrocytes containing multiple ring forms at the other hospital, and 18% erythrocytes with intracellular parasites including multiple ring forms at this hospital. Elevated D-dimer at 5906 ng/ml, elevated aspartate aminotransferase at 121 and 134 U/liter, and markedly elevated lactate dehydrogenase at 2254 U/liter. Cerebrospinal fluid showed normal cell counts and chemistry with Wright's stain revealing intraerythrocytic ring forms.

Chest and abdominal radiograph.

Chest and abdominal radiograph showed perihilar vascular congestion consistent with mild pulmonary edema, normal cardiac and mediastinal silhouette, and homogeneous haziness overlying the left upper abdomen consistent with splenomegaly.

(A) Peripheral blood smear. (B) Peripheral blood smear.

A thin peripheral-blood smear shows erythrocytes containing organisms characterized by a ring (stained pale purple) with central clearing and a peripheral purple chromatin dot (Panel A). Several erythrocytes contain four organisms (Panel B), which represent the stages that occur after the breakdown of the classic tetrad (“Maltese cross”) configuration, a feature characteristic of babesia.

Laboratory testing for B. microti antibody titer, PCR for Anaplasma phagocytophilum, ehrlichia, and babesia, antibody testing for borrelia, immunohistochemical staining and PCR for babesia on placental tissue, and PCR for babesia on dried blood spots.

Additional testing showed the patient had B. microti antibody titer positive at 1:1024 after partial exchange transfusion. PCR tests for Anaplasma phagocytophilum and ehrlichia were negative, as were IgM and IgG antibodies against borrelia. The patient's twin and mother both had high B. microti antibody titers of 1:4096 but negative PCR tests for babesia. Dried blood spots from both infants collected at birth were negative for babesia by PCR. Placental tissue was negative for babesia by both immunohistochemical staining and PCR.

Babesiosis, most likely congenitally acquired

Babesiosis

Babesiosis


A 22-year-old African American/Asian college-age woman presented with a 3-month history of mild exertional dyspnea that progressively worsened despite treatment with inhalers for suspected reactive airway disease. She reported shortness of breath with mild exertion, nonproductive cough for several weeks, and a 5-lb weight loss. She denied fever, chills, headaches, syncope, dizziness, bone pain, nausea, or vomiting. Physical examination was unremarkable except for decreased breath sounds and slight dullness to percussion on the left. Routine laboratory work-up was unremarkable. Initially, chest x-ray showed mediastinal widening, which led to further imaging and biopsy. An open mediastinal biopsy was performed after CT-guided biopsy failed, revealing a poorly differentiated carcinoma initially thought to be thymic carcinoma. Flow cytometry from tissue showed T cells and polyclonal B cells with no immunophenotypic evidence of malignancy.

Chest CT scan. Staging CT scan.

Chest CT scan showed a mediastinal mass that had significantly increased in size over 1 month, with bulky confluent pretracheal and subcarinal lymphadenopathy causing compression of the distal carina and left main stem bronchus. Staging CT scan showed no evidence of metastatic disease.

carcinoma NOS


A 49-year-old HIV-negative woman with relapsing-remitting multiple sclerosis and an EDSS score of 2.5 had received 43 infusions of natalizumab monotherapy over 3.6 years. She presented with an episode of aphasia and seizure, leading to a diagnosis of progressive multifocal leukoencephalopathy (PML). She was considered at high risk for severe immune reconstitution inflammatory syndrome (IRIS) due to elevated JC viral load in cerebrospinal fluid. Her condition remained stable without clinical or imaging evidence of overt IRIS initially. Approximately 2 months after plasmapheresis, she inadvertently stopped taking maraviroc for 5 days and subsequently presented with cognitive and behavioral changes.

MRI, axial fluid-attenuated inversion recovery (FLAIR) sequence.

Axial fluid-attenuated inversion recovery images showed multilobar progressive multifocal leukoencephalopathy at presentation

T1-weighted MRI of the brain, axial view, obtained approximately two months after plasmapheresis and five days after discontinuation of maraviroc, post-gadolinium infusion.

C: A T1-weighted axial magnetic resonance image of the brain obtained after gadolinium infusion approximately two months after plasmapheresis, following a five-day discontinuation of maraviroc, demonstrates frank immune reconstitution inflammatory syndrome (IRIS) involving all visible progressive multifocal leukoencephalopathy (PML) lesions.

Natalizumab-associated progressive multifocal leukoencephalopathy with subsequent JC virus-associated immune reconstitution inflammatory syndrome

Progressive multifocal leukoencephalopathy

Immune reconstitution inflammatory syndrome


A 60-year-old woman originally from Greece was admitted after burning herself while trying to warm her legs on an electric heater. She had rheumatoid arthritis treated with methotrexate and adalimumab. Four months prior to admission, she developed pain and stiffness in her metacarpophalangeal and interphalangeal joints, right ankle, and both knees. Six weeks before admission, she presented with severe arthralgia, temperature of 37.6°C, a net-like rash on her legs compatible with livedo reticularis, and purpuric lesions around the malleoli. Laboratory examinations at that time showed hemoglobin 109 g/L, leukocytes 2.9 × 10⁹/L, neutrophils 1.2 × 10⁹/L, platelets 170 × 10⁹/L, rheumatoid factor 183 IU/mL, hypergammaglobulinemia, antinuclear antibodies 1:640, complement C4 0.04 g/L, anti-double stranded DNA antibody 8.6 IU/mL, negative antibodies to extractable nuclear antigens, and a positive test for cryoglobulins. Serological tests for HIV, hepatitis B, and hepatitis C viruses were negative. On admission, fever (38.7°C) and pancytopenia (leukocytes 1.8 × 10⁹/L, neutrophils 0.5 × 10⁹/L, hemoglobin 90 g/L, platelets 126 × 10⁹/L) were noted. She had no hepatosplenomegaly or lymphadenopathy. A blood film was unremarkable. Cultures of blood, urine, and sputum; computed tomography of the chest, abdomen, and pelvis; a polymerase chain reaction assay of the peripheral blood for cytomegalovirus, and a tuberculin skin test were negative. History revealed she had traveled to Athens seven months earlier and had stayed with relatives who kept several dogs.

Bone marrow smear, Giemsa stain, 400× magnification.

Bone marrow smear (Giemsa stain, original magnification ×400) shows large numbers of intracellular and extracellular amastigotes consistent with visceral leishmaniasis

Serum analysis after storage at 4°C for five days, cryocrit=4%.

Comparison of patient's serum with control serum after storage at 4°C for five days shows cloudy cryoprecipitate in the patient's serum with a cryocrit of 4%

Visceral leishmaniasis


A 67-year-old man presented with elevated white blood cell count that had persisted for several years. In April 2008, he was referred for evaluation of marked leukocytosis. He was slightly anemic with tear drop cells, hematocrit of 40.2%, and elevated platelet count. Physical examination revealed a gradually enlarging spleen. Bone marrow trephine biopsy showed megakaryocytic hyperplasia with marked fibrosis, and a repeat biopsy in April 2011 again revealed prominent myelofibrosis with increased megakaryocytes.

(A) Laboratory values over time, including WBC count, platelet count, and hemoglobin level. (B) FISH analysis. (C) Spleen size over time.

Shows clinical course with laboratory values over time, including WBC count rising to peak levels around 2011, platelet counts, hemoglobin levels, FISH analyses photographs showing BCR and ABL transcripts (white arrows) and BCR-ABL fusion transcript (white arrowhead), and spleen size progression indicated by red arrows of increasing thickness

(A,B) JAK2 sequence analysis. (C) JAK2 sequence analysis after treatment.

JAK2 sequence analysis showing heterozygous G→T transversion in JAK2 (arrows in panels A and B), and demonstrates persistence of JAK2V617F mutation level after treatment (panel C, arrow)

Karyotype analysis.

Shows karyotype analysis revealing three-way variant Philadelphia translocation (9;22;21)(q34;q11;q22) with arrows indicating the translocation

Primary myelofibrosis (PMF) with JAK2V617F mutation that subsequently developed chronic-phase chronic myeloid leukemia (CML) with BCR-ABL translocation

Primary myelofibrosis

chronic myeloid leukaemia


11-year-old boy who received his first black henna tattoo while on holiday in Portugal in August 2013. One week after getting the tattoo, the area became hot, red, raised and itchy. Physical exam showed bullae with clear yellow-orange discharge and golden crusting on a background of erythematous plaque.

Clinical photograph of the upper arm, performed approximately two weeks after initial black henna tattoo exposure.

The figure displays a clinical photograph of the upper arm of an 11-year-old boy showing an impetigo-like lesion confined within the pattern of a recent black henna tattoo; the image reveals bullae with clear yellow-orange discharge and golden crusting on a background of erythematous plaque, representing allergic contact dermatitis to black henna, with sample acquisition timing approximately two weeks after initial tattoo exposure.

Allergic contact dermatitis to black henna

Allergic contact dermatitis


A 67-year-old man with advanced alcoholic cirrhosis presented with progressive dyspnea. Physical examination after thoracentesis revealed right lung crackles, and the patient developed coughing, tachypnea, and tachycardia. His oxygen saturation was 82% while breathing ambient air.

Chest radiography.

Chest radiography showed findings suggestive of a large right pleural effusion

CT of the chest, right lung.

Computed tomography of the chest showed diffuse areas of consolidation and ground-glass opacity in the right lung (arrows), suggestive of reexpansion pulmonary edema

Reexpansion pulmonary edema after thoracentesis

Pulmonary oedema


A 78-year-old man presented with an eight-week history of left-sided abdominal pain and back pain, associated with anorexia, 3 kg weight loss, and night sweats. He was previously well with no significant medical history, taking no regular medications, and was an ex-smoker. On physical examination, he was afebrile with normal baseline vital signs and present peripheral pulses. Cardiorespiratory assessment was unremarkable, and his abdomen was soft but revealed a tender, non-pulsatile palpable central mass at the level of the umbilicus. Blood results showed normochromic, normocytic anemia with hemoglobin 92 g/L (reference range 130-180), elevated erythrocyte sedimentation rate of 75 mm in the first hour (0-22), and elevated C-reactive protein of 15 mg/L (<3). Initial chest and abdominal radiographs showed no abnormalities.

CT of the abdomen at the level of the iliac crest, axial contrast-enhanced.

Axial contrast enhanced computed tomogram at the level of the iliac crest shows aneurysmal dilation of the abdominal aorta with a thickened wall and a cuff of enhancing periaortic fibrotic tissue.

Inflammatory abdominal aortic aneurysm


A 29-year-old man presented with a 3-week history of headaches, blurred vision, nausea, vomiting, anorexia, and weight loss of 7.3 kg. Three days before admission, he developed photophobia, diplopia, neck stiffness, tremulousness of the left hand, and somnolence, becoming mute on the day of admission. He was born in a refugee camp in Southeast Asia, immigrated to the northwestern United States at age 5, and had possibly received BCG vaccination. His history included surgery for eustachian-tube dysfunction at age 11 and a possible head injury during snowboarding 2 months prior. He had recent travel to Texas 3 weeks before admission. On examination, he was somnolent but arousable, with neck rigidity, normal pupils, inability to fully abduct the right eye on lateral gaze, right-sided lower facial weakness, and normal limb strength. Blood tests showed normal renal function, electrolytes, and C-reactive protein, with negative HIV antibodies. Chest radiograph was normal, and electrocardiogram showed sinus rhythm with non-significant ST elevations.

Laboratory results for cerebrospinal fluid and blood.

Laboratory results showing progressive CSF abnormalities with persistently elevated protein levels (419-870 mg/dl), low glucose levels (15-41 mg/dl), elevated opening pressures, and negative microbiologic studies including PCR for various viruses, cryptococcal antigen, and mycobacterial DNA. Blood tests showed declining hematocrit and hemoglobin over time, with elevated liver enzymes by hospital day 24.

(A) Brain MRI, obtained on the first admission, gadolinium-enhanced T1-weighted sequence, sagittal view. (B–D) Brain MRI, obtained on the first admission, gadolinium-enhanced T1-weighted sequence, axial view. (E) Brain MRI, obtained on the first admission, FLAIR sequence. (F) Brain MRI, obtained on the first admission, diffusion-weighted sequence.

MRI Images of the Brain Obtained on the First Admission. Gadolinium-enhanced, T1-weighted sagittal (Panel A) and axial (Panels B, C, and D) images show diffuse leptomeningeal enhancement that is most pronounced in the left frontal region and the basal cisterns. A fluid-attenuated inversion recovery (FLAIR) image (Panel E) and a diffusion-weighted image (Panel F) show a hyperintense lesion (arrows) in the left precentral gyrus that is consistent with a subacute ischemic focus.

(A) MRI of the brain performed on the second admission, gadolinium-enhanced T1-weighted axial view. (B) MRI of the brain performed on the second admission, gadolinium-enhanced T1-weighted coronal view. (C) MRI of the brain performed on the second admission, gadolinium-enhanced T1-weighted sagittal view. (D) MRI of the brain performed on the second admission, diffusion-weighted image. (E) MRI of the brain performed on the second admission, gradient-echo image. (F) MRI of the brain performed on the second admission, FLAIR image.

MRI Images of the Brain Obtained on the Second Admission. There is a 3.6-cm mass in the left inferior frontal lobe. Gadolinium-enhanced, T1-weighted axial (Panel A), coronal (Panel B), and sagittal (Panel C) images show that the mass has thick, irregular rim enhancement. A diffusion-weighted image (Panel D) shows restricted diffusion in the rim. A gradient-echo image (Panel E) shows foci of susceptibility, a feature consistent with hemorrhage, neovascularity, or both. A FLAIR image (Panel F) shows a moderate amount of associated edema.

Glioblastoma, WHO grade IV of IV, involving the leptomeninges and consistent with primary leptomeningeal gliomatosis

glioblastoma NOS

Leptomeningitis


A 27-year-old man of Indian origin with a history of ulcerative colitis presented with diarrhea, fatigue, and significant eosinophilia. He had been in good health until 2 weeks before admission when fatigue developed. Eleven days prior to presentation, he moved to the United States from Indonesia. After arrival, he experienced bloating and nonbloody, loose bowel movements without fever, chills, vomiting, cramping, or abdominal pain, with persistent diarrhea and sharply decreased exercise tolerance. He reported weight loss of approximately 4.5 kg in recent weeks. Two years earlier, he had been diagnosed with ulcerative colitis confirmed by colonoscopy and biopsy, which responded to mesalamine treatment. His medications included mesalamine 1.2 g daily and acetaminophen as needed. He had traveled to a rural area in India in the previous month. On physical examination, vital signs were normal, the spleen tip was palpable, and an erythematous papular rash was seen on the anterior thorax. The remainder of the examination was normal.

Laboratory test results on admission.

Laboratory findings showed marked leukocytosis with white-cell count of 145,400 per mm³ on admission (146,700 the day before), with 83% eosinophils representing an absolute eosinophil count of 120,690 per mm³. Other findings included prolonged prothrombin time (16.3 sec), low sodium (133 mmol/liter), low glucose (44 mg/dl), low albumin (3.2 g/dl), elevated alkaline phosphatase (232 U/liter), elevated aspartate aminotransferase (163 U/liter), elevated lactate dehydrogenase (322 U/liter), markedly elevated total IgG (3240 mg/dl) with elevated IgG subclasses, elevated IgE (428 U/ml), and positive antinuclear antibody at 1:1280 dilution with homogeneous pattern.

Peripheral-blood smear.

Peripheral-blood smear shows marked leukocytosis with a preponderance of mature eosinophils, including forms with three or four nuclear lobes and some with sparse or uneven granulation.

Bone marrow biopsy.

Bone marrow-biopsy specimen shows markedly hypercellular marrow (95% cells, 5% fat) with numerous mature and immature eosinophilic forms. Megakaryocytes had normal morphologic features.

Bone marrow aspirate smear.

Smear of the bone marrow aspirate shows a preponderance of maturing eosinophils among normally granulated myeloid elements and a relative paucity of erythroid forms.

Rectal biopsy, no staining method specified, no magnification specified.

Rectal-biopsy specimen shows mild gland distortion and foreshortening consistent with the patient's history of chronic inflammatory bowel disease; there is an increase in eosinophil numbers in the lamina propria but no evidence of active colitis or crypt injury.

(E) Gastric biopsy, H&E staining.

E: The gastric biopsy, as shown in subfigure E of Figure 1 on page 5, is a histopathological section demonstrating foci of eosinophilic infiltration in the lamina propria without evidence of active gastritis; the specimen was obtained using routine biopsy and is stained with hematoxylin and eosin (H&E), and no specific magnification is indicated in the caption or text.

Idiopathic hypereosinophilic syndrome


43-year-old, previously healthy Hispanic woman presented with a 2-week history of ataxia, diplopia, and headaches. Neurologic examination failed to show any focal deficit.

MRI of the brain, pineal gland region, mass size 3.4 cm × 2.1 cm × 2.4 cm.

MRI of the brain showed a homogeneous, brightly enhancing, 3.4 cm × 2.1 cm × 2.4 cm lobulated mass within the pineal gland

(A) Pineal gland tumor section, H&E staining, 100× magnification. (B) Pineal gland tumor section, H&E staining, 400× magnification. (C) Immunohistochemical staining for desmin, pineal gland tumor section. (D) Immunohistochemical staining for muscle-specific actin, pineal gland tumor section.

A: Hematoxylin and eosin-stained section of the pineal gland tumor at 100× magnification demonstrates a malignant neoplasm with spindle cell proliferation and frequent large polygonal tumor cells with rhabdomyoblastic differentiation. B: Hematoxylin and eosin-stained section at 400× magnification reveals greater cellular detail, highlighting the pleomorphic nature of tumor cells. C: Immunohistochemical staining for desmin shows strong cytoplasmic positivity in tumor cells, supporting myogenic differentiation. D: Immunohistochemical staining for muscle-specific actin demonstrates positive cytoplasmic staining in tumor cells, further confirming skeletal muscle lineage.

Rhabdomyosarcoma, primary site


A 68-year-old woman presented to the ENT clinic with gradually worsening bilateral hearing loss over at least the past five years. She experienced some non-intrusive tinnitus but had no other otological symptoms, no history of vertigo, and no associated systemic problems. She found herself increasing the TV volume to uncomfortable levels for her family and had begun avoiding social situations due to difficulty hearing conversation among background noise. Her medical history was unremarkable except for well-controlled hypertension treated with amlodipine. She had no history of excessive noise exposure, previous otological problems, or relevant family history. Physical examination revealed normal ear canals and tympanic membranes bilaterally, and tympanometry was normal in both ears.

Pure tone audiogram.

Pure tone audiogram showing bilateral symmetrical sensorineural hearing loss with air conduction thresholds marked by 'x' for left ear and 'o' for right ear, and unmasked bone conduction thresholds marked by triangles. The hearing loss demonstrates a characteristic 'ski slope' pattern with gradual deterioration as frequency increases, showing mild hearing loss at lower frequencies progressing to severe-to-profound hearing loss at higher frequencies. The lack of significant air-bone gap indicates sensorineural rather than conductive hearing loss.

age-related hearing loss


A 61-year-old obese woman (BMI 53 kg/m²) with a history of benign breast mass and lumpectomy 15 years prior presented to her primary care physician with a breast lump beneath the left breast, described as dime-sized, mobile, non-tender, and not warm. She reported several months of fatigue but denied fevers, chills, sweats, weight loss, appetite changes, bruising, bleeding, breast pain, or nipple discharge or inversion. Her gynecologic history included menarche at age 14, single pregnancy at age 30, and menopause at age 49. She had a 20-pack-year smoking history but had quit many years prior. Her last mammogram 7 years earlier was normal. Physical examination revealed a 2×3-cm nontender, firm mass under the left breast at 5 o'clock position, approximately 3 cm from the areola, and a 2-cm lymph node in the anterior left axilla. Her CBC was unremarkable.

Hematoxylin and eosin staining, histology.

Histology shows areas of geographic necrosis and tingible body macrophages creating a starry sky appearance, with diffuse infiltrate of immature cells having round oval nuclei, vesicular chromatin, visible nucleoli, and scant cytoplasm on hematoxylin and eosin staining.

Tumor tissue, lysozyme staining.

Shows positive lysozyme staining of the tumor tissue.

(A) PET-CT. (B) PET-CT, left axillary node. (C) PET-CT, subcutaneous masses beneath left breast and right abdominal wall.

PET-CT imaging shows three soft tissue masses with moderately increased fluorodeoxyglucose avidity (A), a left axillary node (B), and subcutaneous masses beneath the left breast and on the right abdominal wall (C).

Myeloid sarcoma with myelomonocytic differentiation

Myeloid sarcoma


72-year-old woman with increased peripheral WBC count (15.6 × 109/L) found during routine medical examination in early 2012. History of lung cancer operation in 2007. WBC differential showed: blasts (1%), myelocytes (12%), metamyelocytes (3%), band-form neutrophils (2%), segmented neutrophils (63%), basophils (1%), eosinophils (1%), monocytes (4%), and lymphocytes (13%). Hemoglobin 14.8 g/dL and platelet count 170 × 109/L were normal. Elevated serum lactate dehydrogenase (818 U/L). No splenomegaly or lung cancer recurrence on systemic CT. Bone marrow showed myeloid cell proliferation (72.0%) with promyelocytes 8.4%, myelocytes 12.0%, metamyelocytes 8.0%, band-form neutrophils 35.6%, segmented neutrophils 5.6%, increased eosinophils (8.0%), blasts 2.4%, and basophils 1.6%.

Fluorescent in situ hybridization (FISH) of peripheral interphase neutrophils, BCR-ABL1 fusion: single fusion in 14%, dual fusions in 82%.

Fluorescent in situ hybridization showed single BCR-ABL1 fusion (14%) and dual BCR-ABL1 fusions (82%) in peripheral interphase neutrophils

Genetic analysis of bone marrow chromosomal karyotype: 47,XX, t(9;22)(q34;q11.2), +der(22)(9;22).

Bone marrow chromosomal analysis revealed 47,XX, t(9;22)(q34;q11.2), +der(22)(9;22) in all 20 analyzed mitotic cells

Chronic-phase Chronic Myeloid Leukemia (CML) with e19a2 BCR-ABL1 transcript and double Philadelphia chromosome

chronic myeloid leukaemia

Double vision


27-year-old woman with history of emergency caesarean section 3 weeks prior and post-operative wound infection treated with 7-day course of cefuroxime and metronidazole (completed 12 days before current admission). Presented with 3-day history of fever, diarrhea, and vomiting. On examination, patient was clinically septic. Stool culture confirmed Clostridium difficile toxin.

(A) CT, axial view, colon. (B) CT, coronal view, colon.

Axial (A) and coronal (B) CT images showing marked submucosal oedema of the entire colon, and intramural air locules (arrows)

pancolitis NOS


A 92-year-old man presented with iron-deficiency anemia. During evaluation, guaiac-positive stools were discovered and subsequent colonoscopy revealed an invasive adenocarcinoma of the cecum. He was scheduled for laparoscopic right hemicolectomy. Preoperative stress echocardiogram showed no significant cardiac dysfunction. On the third postoperative day, he developed paroxysmal tachycardia without chest pain or mental status changes. Physical examination revealed a pulse of 130/min that was irregularly irregular, blood pressure of 126/59 mm Hg, and diminished breath sounds in bibasilar lung fields. The abdomen was soft with clean laparoscopy port sites free of erythema, blood, or exudate. A bedside 12-lead electrocardiogram showed atrial fibrillation with rapid ventricular response and no ST-segment elevation. Portable chest x-ray demonstrated pulmonary edema.

Laboratory results.

Laboratory values showed hemoglobin 7.4 g/dL (reference 13.5-17.1), serum creatinine 1.4 mg/dL (reference 0.5-1.3), serum troponin I 1500 ng/L (reference <100), and B-type natriuretic peptide 311 pg/mL (reference <100).

Congestive heart failure with volume overload

Congestive heart failure

Fluid overload


This case a 45-year-old man who presented with acute illness after dog bites. The patient was well until 2 p.m. the day before admission when he developed nausea, epigastric pain, and vomiting. Three days before presentation, he had been bitten on his hands and forearms while bathing his dog. He also had head trauma from a rusty nail a few days before presentation and dental extractions 1-2 weeks prior. His medical history included asthma, mild chronic obstructive pulmonary disease, anxiety, depression, chronic back pain, and alcohol abuse with recent consumption up to 18 beers daily (stopped 3 days before admission). Physical examination revealed an ill-appearing, anxious, diaphoretic man with temperature 35.6°C, blood pressure 154/102 mmHg, pulse 110 bpm, respiratory rate 28 breaths per minute, and oxygen saturation 100% on room air. Numerous lacerations with necrotic edges and scratch marks were present on his hands and forearms, with the largest mark on his right forearm (3-4 cm in length) having a surrounding border (5-7 cm in diameter) with a purplish tinge. Capillary refill occurred in 5 seconds.

Clinical photographs of the fingers, abdomen, flank, arms, and legs.

Photographs show the patient's fingers appeared slightly blue, there was mottling of skin on abdomen and flank, and diffuse, purple, blanching livedo extended over his arms and legs.

Laboratory results over 3 days.

Laboratory results show progressive changes over 3 days including leukocytosis with increasing bandemia, anemia, thrombocytopenia, coagulopathy with elevated D-dimer, markedly elevated aminotransferases, lactic acidosis, acute kidney injury with rising creatinine, and elevated troponin T levels.

Chest radiograph, frontal view.

Frontal chest radiograph shows interstitial opacities and bilateral hilar fullness consistent with pulmonary edema, with new blunting of left costophrenic angle and hazy opacity in left lower lobe consistent with pleural effusion.

Radiographs of the right hand and forearm.

Radiographs of right hand and forearm show soft-tissue reticulation consistent with edema but no soft-tissue gas.

Gram staining of organism isolated from blood cultures.

Gram's staining of organism isolated from blood cultures reveals long, thin, gram-negative bacilli with tapered ends, characteristic of Capnocytophaga canimorsus.

Bacteremia and purpura fulminans due to Capnocytophaga canimorsus

Bacteraemia

Symptoms, signs or clinical findings, not elsewhere classified

Purpura fulminans


A previously healthy 62-year-old man presented to his primary care physician with a 3-month history of fatigue and unremitting back pain. Physical examination revealed mucosal pallor and point tenderness at T10-T12, with a normal neurologic examination including preserved lower extremity strength and sphincter tone. Laboratory work-up disclosed hemoglobin 10.1 g/dL with mean corpuscular volume of 101 fL and otherwise normal blood cell counts, reticulocytes 0.98%, stable creatinine 1.1 mg/dL, calcium 9.1 mg/dL, albumin 3.4 g/dL, β₂-microglobulin 5.7 mg/L, lactate dehydrogenase (LDH) 397 IU/L, and normal liver function tests. Serum protein electrophoresis (SPEP) demonstrated a 3.5 g/dL monoclonal peak in the gamma region, with monoclonal immunoglobulin G and lambda light chain detected on immunofixation. Serum free light chain (sFLC) ratio was 0.0001. Twenty-four-hour urine protein electrophoresis (UPEP) was normal. Congo red stain on bone marrow biopsy and fat pad aspirate was negative for amyloid light-chain deposition.

(A) Bone marrow biopsy, H&E staining, 20× magnification. (B) Bone marrow aspirate, Wright-Giemsa staining, 100× magnification. (C) Bone marrow aspirate, interphase FISH.

(A) Low-power ( 20) magnification of a hematoxylin-eosin bone marrow biopsy from a patient with newly diagnosed multiple myeloma (MM). (B) High-power magnification ( 100) of a Wright-Giemsa stain of bone marrow aspirate from the same patient showing typical features of MM cells, including clumped chromatin and perinuclear pallor corresponding to Golgi apparatus (images courtesy of Dr Andrew Evans). (C) Interphase fluorescent in situ hybridization of a bone marrow aspirate from a patient with t(4;14) MM (arrows; image courtesy of Dr Paola Dal Cin and Cynthia J. McLaughlin).

High-risk, International Staging System stage III immunoglobulin G lambda multiple myeloma (MM) with t(4;14) translocation

multiple myeloma


patient is a 51-year-old man who presented with a general seizure. The patient was initially diagnosed with a mixed diffuse glioma and underwent subtotal resection with postoperative radiochemotherapy. Five years after diagnosis, he underwent contrast-enhanced fluorescence imaging-guided tumor reresection, which led to a subsequent diagnosis of glioblastoma multiforme (GBM). Two years later, follow-up MRI revealed recurrent tumor. After completing radiochemotherapy, the patient was hospitalized for progressive dyspnea. A chest X-ray revealed pleural effusion requiring thoracic drainage.

Coronal T1-weighted postcontrast cranial MRI.

Coronal T1-weighted postcontrast cranial MRI demonstrated an enhancing left parietal mass involving small venules from the superior sagittal sinus

Axial cranial MRI, T2-weighted sequence.

Axial T2-weighted cranial MRI demonstrated an enhancing left parietal mass involving small venules from the superior sagittal sinus

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

Axial contrast-enhanced computed tomography demonstrated an ill-defined 4-cm mass in the left lower lung lobe and pleural metastases with infiltration of the chest wall

Pleural biopsy, H&E staining, 200× magnification.

Histologic examination of the pleural biopsy sample with hematoxylin and eosin staining (×200 original magnification) revealed a malignant astrocytic glioma

CT scan.

CT imaging showed pleural metastases and destruction of a ventrolateral left rib

Glioblastoma multiforme with pleural and pulmonary metastases

Glioblastoma multiforme of brain

pleura metastasis

metastasis in lung


An 83-year-old woman presented to the acute stroke unit with sudden onset double vision that had lasted for three hours. She had a medical history of monoclonal gammopathy of uncertain significance and atrial fibrillation, for which she was not receiving anticoagulation because of an adverse reaction to warfarin. She had no history of transient ischaemic attack or stroke. She had diplopia only when looking through her right eye. On examination, she was unable to adduct her left eye, with nystagmus in her right eye when she attempted to do this. Her neurological examination was otherwise normal.

T2-weighted MRI at the level of the upper pons.

T2 weighted sequence at the level of the upper pons showing normal appearance

Diffusion weighted MRI of the brain, axial view at the level of the upper pons.

Diffusion weighted sequence at the level of the upper pons showing a small hyperintense lesion in the left upper pons, in the region of the medial longitudinal fasciculus, representing a small area of restricted diffusion in the left upper pontine tegmentum

Left internuclear ophthalmoplegia caused by acute posterior circulation infarct

Internuclear ophthalmoplegia[Left]

acute intestinal infarction NOS


A 34-year-old woman presented with a 4-month history of progressive dyspnea. Prior to admission, she had been well until 4 months ago when shortness of breath developed, followed by nocturnal awakening with chest tightness, fever, cough, and dyspnea on exertion 3 months before admission. She reported significant weight fluctuations - an intentional loss of more than 45 kg over 14 months, followed by 10 kg weight gain over the past 4.5 months. She had a 3-year history of symmetric joint pains affecting knees, elbows, metacarpal and proximal interphalangeal joints that were worse in the morning, along with Raynaud's phenomenon for 1.5 years and eczema since age 14. Additional symptoms included productive cough with white mucus, dry mouth for 3 months, heartburn, mild dysphagia, intermittent abdominal pain, diarrhea, hair thinning, early satiety, decreased appetite, hoarseness, and leg swelling. She was married with children, lived in various regions of the US, and had no substance use. Family history included maternal hyperlipidemia and thyroid disease. On examination, she appeared uncomfortable with persistent cough, blood pressure 158/120 mmHg and later 201/147 mmHg, pulse 115 beats per minute, oxygen saturation 98-99% on ambient air, height 171.5 cm, weight 91.6 kg, BMI 31. Physical findings included jugular venous distension to 10 cm above right atrium, distant heart sounds without murmur, cervical and supraclavicular lymphadenopathy, swollen left proximal interphalangeal joint, leg edema to knees, and a 1x1 cm violaceous macule on left inner thigh. Normal complete blood count except for red-cell distribution width of 18.1%, peripheral blood smear showed 2+ anisocytosis and hypochromasia, and normal coagulation, liver function, electrolytes, and various vitamin levels.

(A) Echocardiography, parasternal long-axis view. (B) Echocardiography, M-mode tracing in the parasternal short-axis view at the base of the heart. (C) Echocardiography, parasternal short-axis view at the midventricular level. (D) Echocardiography, apical four-chamber view.

The parasternal long-axis view shows a mild-to-moderate pericardial effusion (Panel A, arrow) and thickened left ventricular (LV) walls, features suggestive of left ventricular hypertrophy. An M-mode tracing of the posterior pulmonary valve leaflet in the parasternal short-axis view at the base of the heart (Panel B) shows systolic notching (arrow), known as the “flying W sign,” which indicates pulmonary hypertension. In the parasternal short-axis view at the midventricular level (Panel C), interventricular septal flattening (arrow) during systole, known as the “D sign,” is a finding consistent with increased pressure in the right ventricle (RV); pericardial effusion is also evident (arrow-head). The apical four-chamber view (Panel D) shows an enlarged right atrium (RA) and right ventricle relative to the left heart chambers. LA denotes left atrium.

Laboratory results.

Laboratory results showed elevated C-reactive protein at 14.0 mg/liter (normal <8.0), low C3 at 45 mg/dl (normal 86-184), low C4 at 5 mg/dl (normal 16-38), elevated N-terminal pro-B-type natriuretic peptide at 2509 pg/ml (normal 0-450 for age <50), positive antinuclear antibody at >1:5120 dilution with speckled nuclear pattern (normal negative at 1:40 and 1:60), negative anti-cyclic citrullinated peptide IgG antibodies at 6 U (normal 0-19), and negative anti-double-stranded DNA antibodies at 1:10 dilution.

(A) Chest radiograph. (B) Pulmonary CT angiogram, axial view, main pulmonary artery diameter=3.8 cm. (C) Pulmonary CT angiogram, axial view. (D) Pulmonary CT angiogram, coronal view.

A chest radiograph (Panel A) shows enlargement of the main pulmonary artery and of the right and left pulmonary arteries. There is peripheral pruning of the pulmonary vessels, with enlargement of the right atrium. An axial image from a pulmonary CT angiogram (CTA) confirms enlargement of the main pulmonary artery, which measures 3.8 cm just proximal to its bifurcation (Panel B). In another axial image from the CTA, hypertrophy of the right ventricular wall, flattening of the interventricular septum, and right atrial enlargement (Panel C) are seen. A coronal image from the CTA (Panel D) shows reflux of contrast material into the inferior vena cava and hepatic veins (black arrow), with a small pericardial effusion (arrowhead); multiple enlarged left axillary lymph nodes are present (white arrow). There is no mediastinal or hilar lymphadenopathy.

Right heart catheterization, hemodynamic measurements.

Right heart catheterization demonstrated severe pulmonary hypertension with elevated right atrial pressure at 18 mmHg (normal 1-6), pulmonary artery pressure 74/33 mmHg with mean 52 mmHg (normal 15-25/4-12 with mean <25), normal pulmonary capillary wedge pressure at 5 mmHg (normal 4-12), severely reduced mixed venous oxygen saturation at 32%, markedly reduced cardiac output at 2.93 liters/min (normal 4-6), and elevated pulmonary vascular resistance at 1283 dyn·sec·cm⁻⁵ (normal <240).

Systemic inflammatory rheumatic disease identified as U1-ribonucleoprotein-associated mixed connective-tissue disease

Rheumatism, unspecified

Mixed connective tissue disease

Orthopedic and connective tissue disorders


A 25-year-old woman with type 2 diabetes mellitus presented to the emergency department for evaluation of a hyperpigmented lesion on the shin. The lesion appeared as a small reddish-brown macule 3 years ago and has gradually increased in size. During the past several months, the lesion has become indented and increasingly tender. The patient denies systemic symptoms, including fevers and chills, and is primarily concerned about the changing appearance of the lesion and the new-onset tenderness. Laboratory evaluation shows a random blood glucose level of 217 mg/dL (12 mmol/L).

Clinical photograph of the shin during emergency department presentation.

Figure 1 is a clinical photograph depicting a 3-cm sclerotic reddish brown macular lesion with central yellow deposits located on the shin, as seen during cutaneous examination at the time of emergency department presentation.

(A) Skin biopsy, H&E staining, 4× magnification. (B) Skin biopsy, H&E staining, 40× magnification.

Skin biopsy. A: Layered dermal necrobiosis and inflammatory infiltrate extending to the deep dermis (hematoxylin-eosin, original magnification x4). B: Dermal necrobiosis (hematoxylin-eosin, original magnification x40).

Necrobiosis lipoidica


A 72-year-old man with a 23-year history of polycythemia vera presented with a 2-week history of left upper quadrant pain. Three years earlier, red cell scintigraphy had documented a splenic hemangioma, which remained stable on periodic computed tomography scans. He had no history of abdominal trauma, melena, or hematochezia. The patient had lost 6.75 kg (15 lb) and experienced increasing fatigue during a period of 1 month. On physical examination, vital signs were normal. The spleen edge was palpable 6 cm below the left costal margin (increased from 1 month prior). There was no hepatomegaly or lymphadenopathy. On rectal examination there was no gross blood, and no stool was available to perform a guaiac test. Laboratory studies showed a hemoglobin level of 6.8 g/dL (from 12 g/dL 2 months earlier and 8 g/dL 1 week earlier), white blood cell count of 15.76 × 10^9/L, and platelet count of 266 × 10^9/L.

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

Computed tomography scan of the abdomen. A, Axial view. B, Coronal view.

Spontaneous atraumatic splenic rupture with subcapsular hematoma and hemorrhage in the left pericolic and perihepatic areas, secondary to splenic angiosarcoma

Cutaneous angiosarcoma

traumatic spontaneous spleen rupture

Injury, poisoning or certain other consequences of external causes

subcapsular liver hematoma

haemorrhagic colitis

Haemorrhage NOS


A 52-year-old woman was referred to the hospital with abnormal chest radiographs. She was completely asymptomatic and denied having any cough, wheezing, or hemoptysis. Her past medical history was unremarkable and physical examination findings were normal. Laboratory examination revealed hemoglobin 14.1 g/dL, white blood cell count 8160/μL (61.7% neutrophils, 31.1% lymphocytes, 2.6% eosinophils, 4.4% monocytes, 0.2% basophils), and platelet count 209,000/μL. Urine analysis findings, blood chemistry findings, and erythrocyte sedimentation rates were normal. Pulmonary function test showed mild restrictive patterns. Bronchoscopy revealed no endobronchial lesion, and bronchoalveolar lavage results were negative for malignant cells. Transbronchial lung biopsy identified thick varicose septal veins and intraalveolar macrophages.

Chest radiograph, posteroanterior view.

Posteroanterior chest radiograph showed increased interstitial markings in both lungs.

CT scan.

Initial CT scan demonstrated diffuse, smooth, and nodular interlobular septal thickening, and minimal amounts of bilateral pleural effusion.

CT of the mediastinum.

CT showed low-density infiltration of mediastinal fat and lymph node enlargement in the right anterior diaphragmatic area.

CT of the chest performed seven months after initial examination.

Follow-up chest CT scan taken seven months later revealed increased interstitial septal thickening.

CT.

Follow-up CT showed new peribronchovascular cuffing and small amounts of bilateral pleural effusion.

Clinical photograph of the lung taken intra-operatively.

Intra-operative photograph showing abnormal hypervascularity noted on the lung surface.

Hematoxylin and eosin-stained section of lung tissue, 200× magnification.

I: Hematoxylin and eosin-stained section of lung tissue showing proliferation of thin-walled, anastomosing lymphatic vessels lined by a single layer of endothelial cells lacking cytological atypia, located along the lymphatic distribution, at 200x magnification.

(J) Immunohistochemical staining with D2-40 of lung tissue, 200× magnification.

J: Immunohistochemical staining with D2-40 of lung tissue at 200x magnification demonstrates proliferative lymphatic channels characteristic of diffuse pulmonary lymphangiomatosis, with the anatomical site being the lung and the stain specifically highlighting lymphatic vessels.

Diffuse pulmonary lymphangiomatosis (DPL)

Pulmonary lymphangiomatosis


A 52-year-old female presented with an abdominal lump of 6-month duration. She had a history of left eye surgery five years prior following sudden onset loss of vision, resulting in permanent vision loss in the left eye. Her younger son (age 28) had undergone similar eye surgery for unilateral vision loss. On examination, she was normotensive with no perception of light in the left eye while right eye visual acuity was normal. A secondary cataract prevented evaluation of the left posterior chamber. No cerebellar signs were present. Abdominal examination revealed a large lump in the right upper and lower quadrant. Complete hemogram, renal function tests, and liver function tests were normal. Serum and urinary catecholamine levels were normal.

(A) Contrast-enhanced CT of the abdomen, transaxial view, pancreatic body and tail region, mass size 9.6 × 7.4 × 5.4 cm. (D) Contrast-enhanced CT of the abdomen, transaxial view, left renal interpolar region, mass size 7.8 × 5.8 × 5.1 cm.

Transaxial contrast enhanced CT (A) of abdomen show large (9.6 x 7.4 x 5.4 cm) mass lesion in region of body and tail of pancreas with intense post contrast enhancement (arrow). Multiple cysts of varying sizes are noted in rest of pancreas (asterix). Also, note tortuous blood vessels in peripancreatic and perisplenic location. Transaxial contrast enhanced CT (D) of abdomen also shows another mass (7.8 x 5.8 x 5.1 cm) arising from interpolar region of left kidney and showing intense post contrast enhancement (arrow). Multiple feeding vessels are seen to arise from left renal artery and supply mass. Also noted are bilateral multiple renal cortical cysts (asterix).

(B) PET transaxial image of the pancreas and liver with 68Ga-DOTANOC, SUVmax=18.6 in pancreatic mass, SUVmax=13.2 in liver segment III. (C) PET-CT transaxial image of the pancreas and liver with 68Ga-DOTANOC, SUVmax=18.6 in pancreatic mass, SUVmax=13.2 in liver segment III. (E) PET image of the kidney with 68Ga-DOTANOC, SUVmax=3.1 in renal mass. (F) PET-CT image of the kidney with 68Ga-DOTANOC, SUVmax=3.1 in renal mass.

Transaxial PET (B) and PET-CT (C) images show intense heterogeneous uptake of 68Ga-labelled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-Nal3-Octreotide (68Ga-DOTANOC) (SUVmax = 18.6) in pancreatic mass (arrow), thus confirming it to be NET. Focal 68Ga-DOTANOC uptake (SUVmax = 13.2) was also seen in segment III of liver (B, C, broken arrow) suggesting liver metastasis from pancreatic NET. PET (E) and PET-CT (F) images reveal mild 68Ga-DOTANOC uptake (SUVmax = 3.1) in renal mass (arrow).

(G) PET of the brain, transaxial view, 68Ga-DOTANOC, SUVmax=9.9. (H) PET-CT of the brain, transaxial view, 68Ga-DOTANOC, SUVmax=9.9. (I) MRI of the brain, transaxial view, T2-weighted, gadolinium enhanced.

Transaxial PET (G) and PET-CT (H) images of brain show focal area of 68Ga-DOTANOC uptake (SUVmax = 9.9) in hypodense lesion (2 x 2 cm) in left cerebellum (arrow). Transaxial T2 weighted gadolinium enhanced MRI (I) of brain reveals nodular lesion in lateral half of left cerebellar hemisphere with intense post contrast enhancement (arrow), suggesting hemangioblastoma.

(J) PET, transaxial view, 68Ga-DOTANOC, SUVmax=8.3, left globe. (K) PET-CT, transaxial view, 68Ga-DOTANOC, SUVmax=8.3, left globe. (L) MRI, transaxial view, T2-weighted, gadolinium-enhanced, left globe.

Transaxial PET (J) and PET-CT (K) images also revealed focal 68Ga-DOTANOC uptake (SUVmax = 8.3) in lateral part of left globe, corresponding to heterogeneous nodular lesion (arrow). Transaxial T2 weighted gadolinium enhanced MRI (L) showed eccentric nodule in lateral part of left globe with intense post contrast enhancement, suggesting retinal hemangioblastoma (arrow).

Von Hippel-Lindau syndrome with cerebellar hemangioblastoma, retinal hemangioblastoma, renal cell carcinoma, metastatic pancreatic neuroendocrine tumor, pancreatic cysts and renal cysts

Von Hippel-Lindau syndrome


46-year-old woman presented with frequent collapse. Medical history included carotid endarterectomy in 2005 following a small right hemispheric stroke, and hypercholesterolaemia. No previous dermatological or scalp problems. Current medications: clopidogrel 75mg, aspirin 80mg, and simvastatin 40mg daily.

Clinical photograph of the scalp at the time of presentation.

A: Clinical photograph of the scalp demonstrating ischaemic ulceration and hair loss, depicting the anatomical site of the lesion on the patient's head at the time of presentation.

Magnetic resonance angiography of the head and neck.

Magnetic resonance angiography revealed occlusion of both common carotid arteries, the innominate artery, and the right vertebral artery, and 80% stenosis of the orifice of the left subclavian artery. The circle of Willis was perfused by the left vertebral artery, and the right vertebral artery was filled retrograde from the left side. Blood supply to the head was maintained by the stenosed left subclavian artery.

Ischaemic scalp lesions due to insufficient tissue perfusion caused by multiple arterial occlusions and stenosis

Laceration of scalp

Acute arterial occlusion

arterial stenosis


22-year-old male presented with infertility. Seven years prior, he had developed diabetes insipidus and seborrheic dermatitis without specific diagnosis. Later developed partial complex seizures, bilateral hemianopsia, bilateral parotitis, oozing of both ears, ulcerative axillary lymphadenopathy, and rectal proctitis.

MRI of the brain, suprasellar and prepontine cistern, with measurement 3.3 × 3.4 × 4.2 cm.

MRI showed hypothalamic mass (3.3 × 3.4 × 4.2 cm) in the suprasellar and prepontine cistern, with posterior displacement of the brainstem and mass effect on optic chiasm. Two small foci noted at medial aspect of both temporal lobes.

Rectal biopsy, immunohistochemistry staining, 100× magnification, CD68+, CD1a+, CD201+, S100+.

Rectal biopsy showed Langerhans cell histiocytosis positive for CD68, CD1a, CD201, and S100 (×100 magnification)

(A) Chest radiograph, posteroanterior view, performed in October 2010. (B) Chest CT, axial view, performed in October 2010.

A: A posteroanterior chest radiograph from October 2010 demonstrates bilateral cystic changes and bullae in both lung bases, consistent with regressed pulmonary Langerhans cell histiocytosis. B: An axial chest CT image from October 2010 shows multiple bilateral thin-walled cystic lesions predominantly in the lung bases, further confirming cystic pulmonary involvement.

Multisystem Langerhans Cell Histiocytosis (LCH)

Langerhans cell histiocytosis


A 56-year-old man presented with a seven-day history of worsening epigastric pain associated with nausea and belching. He had a medical history of splenectomy following trauma, hyperlipidaemia, obesity, and Bell's palsy. Abdominal computed tomography performed in 2007 had shown multiple abdominal nodules consistent with splenunculi but nothing else of note. He had recently been prescribed orlistat to facilitate weight loss and had been taking the drug for about 10 days before the onset of symptoms. On examination, he was haemodynamically stable with a temperature of 37.5°C, and his abdomen was soft but tender in the epigastric region and left iliac fossa. Digital rectal examination did not identify blood, masses, or melaena. Blood tests revealed mild neutrophilia (8.4 × 10^9/L; reference range 1.7-8.0) and raised C reactive protein (102.4 mg/L; reference range 0-7.5), but normal liver biochemistry, renal function, and concentrations of amylase and lipase. While awaiting inpatient oesophagogastroduodenoscopy, his inflammatory markers deteriorated and his abdominal pain persisted despite appropriate analgesia and high-dose proton pump inhibitor therapy.

CT with contrast of the abdomen.

Contrast enhanced computed tomography shows non-occlusive acute venous thrombosis in the portal and mesenteric veins with associated mesenteric venous congestion

Contrast-enhanced computed tomography of the portal and mesenteric veins.

Acute portal vein thrombosis with superior mesenteric vein thrombosis

Portal vein thrombosis

thrombosis of mesenteric vein


An 84-year-old woman presented with a five-month history of central, recurrent, severe epigastric pain occurring about 20 minutes after eating. The pain was associated with nausea, occasional diarrhea, and vomiting. She experienced early satiety and weight loss over the last few months. Her medical history included myocardial infarction two years earlier and a 40 pack-year history of smoking. On examination, she was cachectic, but physical examination and digital rectal examination were otherwise unremarkable. Blood tests including full blood count, liver function tests, amylase, and renal function were normal. Chest and abdominal radiographs, abdominal ultrasound, and computed tomography of the abdomen were unremarkable.

CT angiogram of the abdominal aorta.

Computed tomography angiogram showing atherosclerotic disease of the abdominal aorta with wall calcification, severe stenotic disease of the proximal segments of both the coeliac axis and superior mesenteric artery with large calcified plaques narrowing the origins of these vessels, and occlusion of the inferior mesenteric artery, indicating severe splanchnic arterial stenotic disease.

Mesenteric angina (chronic mesenteric ischaemia)

mesenteric angina

Chronic mesenteric ischaemia


A 16-year-old girl presented with acute left shoulder pain, left-sided chest pain, and shortness of breath. She had a 4-month history of intermittent left shoulder and left-sided chest pain following a dance recital, which had been treated with analgesia and physiotherapy. She denied fever, cough, orthopnea, weight loss, and appetite change. Physical examination revealed tenderness at the location of the left fifth rib and reduced left chest expansion.

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

Anteroposterior and left lateral chest radiographs show left lower lobe opacification obscuring the left hemidiaphragm and blunting of the left costophrenic angle.

Chest CT, axial view.

Chest computed tomography axial view demonstrates a mixed lytic/sclerotic destructive lesion of the left fifth rib associated with a 5.5 × 5.1-cm heterogenous extrapleural mass with extensive intrathoracic involvement.

Chest CT, sagittal view.

Chest computed tomography sagittal view shows the mixed lytic/sclerotic destructive lesion of the left fifth rib with associated extrapleural mass and intrathoracic involvement.

Hematoxylin-eosin slide of biopsied rib lesion.

Hematoxylin-eosin slide of biopsied rib lesion demonstrates histology featuring round to oval pleomorphic osteoblasts with irregular hyperchromatic nuclei and frequent mitoses and intervening lace-like osteoid matrix, consistent with osteosarcoma.

Osteosarcoma of bone or articular cartilage of ribs, sternum or clavicle


A 32-year-old man presented with a 10-week history of skin rash and muscle weakness. Ten weeks before admission, he developed a violaceous rash involving the eyelids, elbows, metacarpophalangeal and proximal interphalangeal joints, and knees. One week later, intense generalized muscle pain and weakness developed, including difficulty walking, arising from a squat, and climbing stairs. Physical examination at another hospital revealed a heliotrope rash on the eyelids, periungual edema, erythematous papules on the fingertips, and moderate-to-severe weakness of the deltoids, triceps, hip flexors, hamstrings, and quadriceps bilaterally. Muscle bulk and tone, deep-tendon reflexes, and the sensory examination were normal. On examination at this hospital, he was alert, oriented, and afebrile with blood pressure 175/90 mmHg, pulse 128 beats per minute, respiratory rate 40 breaths per minute, and oxygen saturation 93% on 10 liters oxygen via nonrebreather mask. He had diminished breath sounds at both lung bases, hypoactive bowel sounds, erythematous papules on the extensor surfaces of fingers, elbows, and knees, heliotrope rash bilaterally, nontender periungual erythema, and pitting edema of arms and legs. Grip strength and strength of foot dorsiflexion and plantar flexion were 4-/5, and he was unable to lift his arms, legs, or head against gravity (2+/5). The patient had a history of meniscal repair 10 years earlier, worked in a service industry, did not smoke or use illicit drugs, and had a family history of hypertension in his father and hypothyroidism in two aunts.

Column: 1st Hospital, 24 Days before Admission to MGH

Laboratory results.

Laboratory results showed hematocrit 46.8%, hemoglobin 16.3 g/dl, white-cell count 24,000 per mm³ with 93.8% neutrophils, 2.7% lymphocytes, platelet count 288,000 per mm³, sodium 124 mmol/liter, potassium 6.0 mmol/liter, chloride 87 mmol/liter, carbon dioxide 24 mmol/liter, urea nitrogen 30 mg/dl, creatinine 1.09 mg/dl, glucose 158 mg/dl, total protein 5.4 g/dl, albumin 2.5 g/dl, alkaline phosphatase 62 U/liter, aspartate aminotransferase 440 U/liter, alanine aminotransferase 128 U/liter, creatine kinase 12,511 U/liter, creatine kinase MB isoenzyme 109.5 ng/ml, and troponin I 0.05 ng/ml.

Laboratory results on admission.

Laboratory results on admission showed hematocrit 31.0%, hemoglobin 10.5 g/dl, white-cell count 17,000 per mm³ with 85% neutrophils, 2% lymphocytes, platelet count 728,000 per mm³, red-cell distribution width 16.1%, erythrocyte count 3,650,000 per mm³, activated partial-thromboplastin time 30.0 sec, prothrombin time 13.9 sec, international normalized ratio 1.2, sodium 135 mmol/liter, potassium 3.6 mmol/liter, chloride 97 mmol/liter, carbon dioxide 30.2 mmol/liter, urea nitrogen 17 mg/dl, creatinine 0.38 mg/dl, glucose 155 mg/dl, total protein 6.3 g/dl, albumin 3.0 g/dl, alkaline phosphatase 74 U/liter, aspartate aminotransferase 225 U/liter, alanine aminotransferase 63 U/liter, lactate dehydrogenase 468 U/liter, creatine kinase 1915 U/liter, creatine kinase MB isoenzyme 19.7 ng/ml, troponin T 0.72 ng/ml, fibrinogen 473 mg/dl, ferritin 2324 ng/ml, iron 24 μg/dl, total iron-binding capacity 108 μg/dl, soluble interleukin-2 receptor α chain 3172 U/ml, glucose-6-phosphate dehydrogenase 14.9 IU/g hemoglobin, and arterial blood gases showing pH 7.15, partial pressure of carbon dioxide 88 mmHg, partial pressure of oxygen 45 mmHg, base excess -0.9 mmol/liter on 100% inspired oxygen.

Dermatomyositis and malignant atrophic papulosis (Degos's disease)

Dermatomyositis

Malignant atrophic papulosis


3-year-old boy, born at 41 weeks gestation without perinatal problems, birth weight 3.4kg. Parents were not consanguineous and had no medical history. History of 3 prior hospitalizations for viral pneumonia at 12, 18, and 27 months. Presented with recurrent and persistent pneumonia. Current symptoms included cough, sputum and fever. Physical exam showed: temperature 39.5°C, pulse 129/min, respiration 28/min, BP 95/55 mmHg. Weight 15.3kg (50-75th percentile), height 96.5cm (50-75th percentile). Two 3mm ulcers in uvula, fine crackles in both lung fields, palpable liver 1 finger-breadth below right costal margin, palpable spleen tip.

(A) Chest X-ray. (B) Chest CT.

(A) Chest X-ray showed patchy consolidation in the right middle lobe and increased peribronchial opacity in the bilateral lower lung fields. (B) Chest CT showed air bronchogram and consolidation in the left lower lobe and atelectasis with pleural effusion in the right lower lobe.

(A) Dihydrorhodamine (DHR) assay of granulocytes from the patient, stimulation index (SI)=1.4. (B) DHR assay of granulocytes from the patient's mother, SI=25. (C) DHR assay of granulocytes from a normal subject, SI=127.9.

Histograms of the dihydrorhodamine (DHR) assay of granulocytes from the patient, his mother and a normal subject. DHR assay of the patient’s granulocyte (A) revealed the near absence of fluorescence upon granulocyte stimulation. The stimulation index (SI) was 1.4 which was compatible with X-CGD. The DHR assay of granulocytes from the patient’s mother (B) and a normal subject (C) showed a histogram with SI 25 and 127.9, respectively.

(A) Genetic analysis of CYBB gene exon from the patient. (B) Genetic analysis of CYBB gene exon from the patient's mother. (C) Genetic analysis of CYBB gene exon from a normal subject.

Analysis of a CYBB gene exon of the patient (A), his mother (B) and a normal subject (C). Chromatogram of a CYBB exon of the patient showed a novel complex mutation, c.1133A>G (p.Asp378Gly).

X-linked Chronic Granulomatous Disease (CGD) with novel CYBB gene mutation c.1133A>G (p.Asp378Gly)

Chronic granulomatous disease


92-year-old woman with BMI 14.2 kg/m². Past history: no abdominal surgery, five children by normal vaginal delivery. Presenting with: 2-day history of sudden onset right knee pain, 1-day history of nausea and vomiting. Physical exam: no knee swelling/tenderness, patient frequently flexed right knee for pain relief, abdominal distension present, tenderness to deep palpation but no peritoneal irritation signs, no abdominal mass. Rectal exam revealed small extraluminal mass on right side. Initial abdominal radiograph showed small-bowel obstruction.

CT of the pelvis, coronal(A)  and sagittal (B) views.

CT of pelvis (coronal and sagittal views) showed small intestine herniating into right obturator canal. The incarcerated bowel loop showed prominent wall enhancement consistent with early vascular compromise.

Obturator hernia


A 52-year-old man presented to the emergency department with complete inability to swallow (absolute dysphagia) and throat pain that began acutely while eating a piece of steak three hours earlier. He described pain in the middle of his throat and inability to swallow fluids without regurgitation. He arrived carrying a bowl and was spitting out his own saliva. He reported no voice changes or breathing difficulty. He was otherwise fit and well with no recent trauma, weight loss, or history of similar presentations. Physical examination of the neck was unremarkable except that he regurgitated test drinks of water.

Lateral soft tissue radiograph of the neck, showing a 2 cm soft tissue opacity at the level of C5-C6 vertebrae within the distal pharynx-proximal oesophagus.

Lateral soft tissue radiograph of the neck shows a soft tissue opacity measuring 2 cm in width at the level of C5-C6 vertebrae within the distal pharynx-proximal oesophagus, consistent with a wedged food bolus at the level of the cricopharyngeus muscle, with air below the mass in the oesophagus and mild loss of lordosis due to muscular spasm. No prevertebral soft tissue swelling or surgical emphysema suggestive of perforation is visible.

Soft food bolus in the proximal oesophagus

Oesophageal obstruction


A 55-year-old man with a history of heart failure presented to the emergency department with pain and swelling in his right foot and leg. Three days prior to presentation, he developed sudden onset of swelling in the right foot and calf without trauma, which progressively worsened and extended to the upper leg, accompanied by pain in the foot and calf. On the day of presentation, he noted new dusky discoloration of the toes on his right foot. His medical history included obesity, paroxysmal atrial fibrillation, hypertension, and heart failure with preserved ejection fraction. He had a 30-pack-year smoking history but quit 5 years prior, consumed about four beers weekly, and reported intentional weight loss of 22.7 kg over the preceding 6 months. Current medications included warfarin, sotalol, torsemide, and lisinopril. Physical examination revealed temperature of 36.1°C, heart rate 80 beats per minute, blood pressure 96/50 mmHg, and oxygen saturation 95% on ambient air. Notable findings included poor dentition, clear lungs, regular heart sounds, jugular venous pressure of 8 cm water, and markedly asymmetric legs with 4+ pitting edema of the right upper thigh and 2+ pitting edema of the left calf. The right leg and foot were dusky and cold with distal pulses detectable only on Doppler ultrasonography.

Clinical photograph of the dorsal and plantar surfaces of the right foot.

Shows discrete hemorrhagic bullae on a purpuric base with central, dusky discoloration suggestive of epidermal necrosis on both dorsal and plantar surfaces of the right foot, with confluent bullae particularly over the dorsomedial aspect of the foot and toes.

Venogram of the right femoral vein obtained before treatment.

Venogram obtained before treatment shows contrast material staining the wall of the right femoral vein, but occlusion prevents it from filling the lumen.

CT of the abdomen without contrast.

Abdominal CT scan without contrast shows heterogeneous liver texture, ascites, diffuse omental nodularity, and a solid mass extending along the greater curvature of the stomach with papillary fronds.

(A) Endoscopic examination of the stomach, greater curvature. (B) Endoscopic examination of the stomach, greater curvature.

Endoscopic images show thickened, erythematous, poorly distensible gastric folds along the greater curvature (Panel A). Closer inspection reveals a centrally ulcerated mass in this area (Panel B).

(A) Gastric mucosa biopsy, H&E staining. (B) Gastric mucosa biopsy, H&E staining.

Panel A shows a transition from non-neoplastic gastric mucosa at the left (arrows) to infiltrative glands with irregular gland profiles and enlarged hyperchromatic nuclei at the right; the latter is a finding consistent with adenocarcinoma. Panel B shows biopsy-specimen fragments completely replaced with neoplastic epithelium that shows focal-gland formation (arrows) and solid areas with central necrosis (arrowhead). The overall findings are consistent with a poorly differentiated adenocarcinoma.

Phlegmasia cerulea dolens secondary to poorly differentiated, invasive adenocarcinoma of gastric origin

phlegmasia alba dolens

Poorly differentiated invasive adenocarcinoma of gastric origin

Adenocarcinoma of stomach


58-year-old woman with history of hypertension presented to emergency department with seizures. Initial symptoms included mild frontal headache, blurry vision, and disorientation, followed by two witnessed episodes of tonic left side stiffening, left head turn, and bilateral lower extremity shaking. No prior history of seizures. On examination: blood pressure 178/84 mmHg, alert but not oriented to time, had left-right confusion, simultanagnosia, prominent ocular apraxia, no visual field loss, brisk reflexes throughout with bilateral Babinski signs, and diminished sensation to vibration, temperature, and light touch in both feet. Laboratory testing showed normal liver and renal function, normal blood glucose, ammonia, and electrolytes.

CT of the head, occipital and parietal lobes.

Head CT showed patchy areas of hypoattenuation in bilateral occipital and parietal lobes with obscuration of cortical gray-white matter differentiation and sulcal effacement

MRI of the brain, T2-weighted sequence, bilateral occipital, parietal, and minimal frontal lobe involvement, diffusion-weighted imaging.

Brain MRI revealed patchy areas of abnormal T2 hyperintensity in bilateral occipital and parietal lobes with minimal involvement of frontal lobes. Several punctate foci of reduced diffusivity were detected in occipital lobes

Posterior Reversible Encephalopathy Syndrome (PRES)

Posterior reversible encephalopathy


50-year-old man presented with 2-week history of constant worsening headache affecting the whole head. No history of head trauma, but reported headbanging at a Motörhead concert 4 weeks prior to presentation. Medical history was unremarkable and patient denied substance misuse. Neurological examination and laboratory studies, including coagulation screening, were normal.

CT of the head, preoperative, maximum hematoma width 20 mm.

Preoperative CT showed right-sided chronic subdural hematoma (maximum width 20 mm) with pronounced midline shift and a clot at the tip of the right temporal lobe

Chronic subdural haematoma secondary to headbanging, with an underlying arachnoidal cyst in the right middle cranial fossa

chronic subdural haematoma

arachnoid cyst


A 52-year-old woman presented with complaints of anal pain, constipation, and tenesmus for 3 months before being referred to the hospital. There were no relevant prior illnesses. Rectal digital examination revealed a 6-cm smooth elastic mass on the rectal posterior left side 2 cm from the anal verge. Colonoscopy showed a rectal submucosal bulging. Computed tomography scan and magnetic resonance imaging confirmed the presence of a single 6-cm well-delimited mass, compressing and infiltrating the wall of the medium to low rectum.

Histopathological examination of the rectal wall, H&E staining, 50× high-power fields, mitoses=80/50 HPF. Immunohistochemical staining: CD117 positive, DOG1 positive, CD34 positive, S100 positive (patchy cytoplasmic pattern), desmin negative, melan-A negative, HMB45 negative.

Histopathological examination showed tumor composed of spindle cells with perinuclear vacuolization and several mitoses (80/50 high-power fields), with scarce rectal wall smooth muscle present. The tumor stained positive for CD117, DOG1, CD34, and S100 (patchy cytoplasmic pattern), while desmin, melan-A, and HMB45 were negative.

(A) Polymerase chain reaction direct sequencing of tumor DNA. (B) Polymerase chain reaction direct sequencing of rectal wall smooth muscle DNA.

Polymerase chain reaction direct sequencing on independent DNA templates from four different tumor fragments revealed two mutations: a 6-nucleotide insertion GCCTAT between 1509-1510 nucleotides causing an insertion of two amino acids alanine and tyrosine (p.Y503_F504insAY) in KIT exon 9, and a point mutation (A→T at 2525) determining a Val for Asp substitution at 842 (D842V) of exon 18 of PDGFRA. KIT and PDGFRA were wild type in the rectal wall smooth muscle.

Gastrointestinal stromal tumour of unspecified gastrointestinal sites


4-year-old healthy girl presented with left eye noticed by parents for past 2 months. Visual acuity: right eye 6/7.5 (20/25), left eye did not follow objects. No family history of childhood cancers. No other pertinent medical history. Physical examination otherwise unremarkable.

Clinical photograph of the left eye at presentation.

Figure 1 is a clinical photograph demonstrating the left eye of a 4-year-old girl at presentation, showing leukocoria, characterized by an abnormal white pupillary reflection.

Funduscopic examination of the eye.

Funduscopic examination revealed subretinal white tumor and retinal detachment

Axial T2-weighted MRI of the retina.

Axial T2-weighted MRI showed total retinal detachment with subretinal hemorrhage. Retina diffusely infiltrated by retinoblastoma

Retinoblastoma[Unilateral, unspecified]