53-year-old male presented with right chest pain. Physical examination and laboratory studies were unremarkable.

Chest radiograph of the thorax.

Chest radiographs showed a well marginated anterior mediastinal mass in the entire right lung zone, compressing the lower trachea, right bronchus, and heart toward the left side

At surgery, after aspiration of fluid within the cystic mass, pericardial invasion was noted. Thus, partial resection of the mass was done.Photomicrograph (H-E stain, ×40)

Photomicrograph (H-E stain, ×40) shows tumor cells forming cords or solid sheets within the fibrous stroma. Three cellular compositions; intermediate, squamous, and mucous cells are noted. Small spaces filled with mucus are also present.

(A) Chest CT scan at the level of aortic origin. (B) Contrast-enhanced chest CT scan.

(A) Chest CT scan at the level of aortic origin demonstrates a huge, low attenuating, cystic mass in anterior mediastinum with internal septa and heterogeneous solid area anteromedially.(B) Contrast enhanced CT scan shows the focal solid mass area with heterogeneous enhancement anteromedially and irregular margin between the mass and anterior chest wall and pericardium.

Poorly differentiated mucoepidermoid carcinoma of the thymus

Mucoepidermoid carcinoma of thymus


A 41-year-old man presented in September 2003 with unexp weight gain, facial plethora, tremor, sweating, newly-diagnosed hypertension, hypokalemia, and diabetes mellitus. Physical examination revealed blood pressure of 170/110 mm Hg, pulse of 88 bpm, thyroid enlargement, and cushingoid features including striae, moon face, central obesity, and a buffalo hump. Laboratory testing showed hyperthyroidism with undetectable TSH, free T4 of 32 pmol/L (normal: 12-22), and free T3 of 9 pmol/L (normal: 3.95-6.80). Hypercortisolism was evident with 24-hour urinary free cortisol of 7579 nmol per day (normal: 22-212), elevated basal serum cortisol of 1307 nmol/l (normal: 187-724), and elevated plasma ACTH of 22.51 pmol/l (normal: 1.98-11.4). Midnight cortisol was elevated at 847 nmol/l. After a 2-mg overnight dexamethasone suppression test, serum cortisol remained elevated at 1132 nmol/l (normal <80). After an 8-mg dexamethasone suppression test, serum cortisol decreased by only 38% suggesting ectopic ACTH secretion. CRH stimulation resulted in less than 4% increase in serum cortisol and plasma ACTH. Inferior petrosal sinus sampling did not show significant central-to-peripheral ACTH gradients. Thyroid ultrasound showed multinodular goiter, and Tc-99m-pertechnetate thyroid scan revealed increased uptake corresponding to an autonomous adenoma. Serum calcitonin was normal, and thyroid antibodies were negative. Twenty-four hour urinary catecholamines including fractionated metanephrines were negative.

T1-weighted gadolinium-enhanced MRI of the pituitary. A hypointense lesion of the neurohypophysis is indicated.

^111In-pentetreotide scintigraphy of the thyroid region

111In-pentetreotide scintigraphy. Radiotracer accumulation in the left thyroid in 10/2003 (arrow). The mesenterial neuroendocrine tumor became clearly visible in 4/2005 (arrow).

(upper) CT of the abdomen. (lower) MRI of the abdomen, fat-saturated and T1-weighted sequences after gadolinium, mesentery.

CT and MRI scans of the abdomen. In 4/2005, a mass (circle) is shown which has also been there in earlier scans but had been interpreted as normal intestine. Fat-saturated and T1-weighted MRI scanning after gadolinium shows a mass in the mesentery outside the intestine.

Ectopic Cushing syndrome caused by a neuroendocrine carcinoma of the mesentery

Ectopic Cushing syndrome

Endocrine, nutritional or metabolic diseases

Neuroendocrine carcinoma of the mesentery

neuroendocrine carcinoma of unspecified site


A 29-year-old woman presented to the emergency room in September 2001 with low abdominal pain. Laboratory examination revealed severe anemia. Both direct and indirect Coomb's tests were positive, confirming autoimmune hemolytic anemia. The erythrocyte sedimentation rate was 30 mm/hr, while C-reactive protein was not increased. Anti-nuclear antibody and anti-double-stranded DNA antibody were absent, and complement levels were normal. Peripheral blood smear showed normocytic normochromic anemia with red blood cell agglutination. Physical examination during exploratory laparotomy in November 2001 revealed a multinodular mass involving the right ovary that was not adherent to adjacent organs. The left Fallopian tube, ovary, uterus, and kidneys were normal, and the liver, diaphragm, and omentum were not involved. No enlarged lymph nodes greater than 1 cm were identified in the abdomen. Additional diagnostic workup including chest, abdomen, and neck CT scans, Gallium-67 scan, endoscopy, bone marrow biopsy, and serum protein electrophoresis showed no abnormalities.

Pelvis MRI.

Pelvis MRI showing a well-marginated large mass in the pelvic cavity

Gross pathological photograph of the cut surface of the right ovarian lesion.

Figure 2 depicts a gross pathological photograph of the cut surface of the right ovarian lesion, demonstrating a solid, gray-white to yellow, multilobulated tumor.

Gross examination of the right ovarian mass measuring 14 × 10 × 9 cm.

Gross examination of the right ovarian mass measuring 14 × 10 × 9 cm with cut surface revealing a solid, gray-white to yellow, multilobulated tumor

Laboratory results at time of diagnosis.

Serial laboratory findings showing initial hemoglobin of 6.7 g/dL, reticulocyte count of 7.2%, lactate dehydrogenase of 2450 U/L, and total/direct bilirubin of 3.2/1.0 mg/dL at time of diagnosis

Primary ovarian non-Hodgkin's lymphoma, diffuse large B-cell type, accompanied by autoimmune hemolytic anemia

Diffuse large B-cell lymphomas

autoimmune haemolytic anaemia

Diseases of the blood or blood-forming organs


A 32-year-old woman, gravida 1 para 0, presented during her first pregnancy with a medical history significant for cervical intraepithelial neoplasia (CIN II) treated 2 years prior by loop excision and bilateral breast reduction with complicated but spontaneous wound healing 13 years earlier. At 18 weeks of gestation, she was diagnosed with chronic hypertension with maximum diastolic blood pressure of 95 mm Hg. At 31 weeks and 4 days of gestation, she presented with lower abdominal pain and fever, having experienced flu-like symptoms, headache, and sore throat two weeks prior. Physical examination revealed body temperature of 38.3°C, uterine contractions, and fundal height corresponding to 29 weeks of gestation. The cervix was 1 cm dilated and completely effaced with intact amniotic membranes. Ultrasound showed fetal growth corresponding to the fifth percentile and oligohydramnios. Fetal cardiotocogram showed variable fetal heart rate of 160 beats per minute with late decelerations, and external tocodynamometry registered uterine contractions. Blood tests revealed high white blood cell count of 24.4 × 10.9/L with neutrophilia and elevated C-reactive protein of 170 mg/L. Following cesarean section for suspected fetal distress, she developed postoperative complications including persistent fever, rising inflammatory markers, and ultimately a non-healing surgical wound despite standard wound care and antibiotic treatment.

Clinical photograph of the surgical wound 23 days after cesarean delivery.

Shows the surgical wound 23 days after cesarean delivery, displaying violaceous colored wound borders with an expanding ulcerative defect, measuring approximately 15-20 cm in length with purulent appearance and characteristic features of pyoderma gangrenosum

Pyoderma gangrenosum


A 5-year-old male patient presented with inflammation and swelling in his left mandible and wrist without a history of trauma. He had a past medical history of several episodes of pneumonia starting at age seven months. During his second admission eight months later, his major complaints were severe dyspnea, persistent cough, and chest and abdominal pain in the epigastric area that had started 10 days prior. Initial laboratory findings showed erythrocyte sedimentation rate (ESR) 84 mm/h, WBC count 12,100/mm³ (61% neutrophils, 39% lymphocytes), hemoglobin 11.3 g/dl, and thrombocyte count 386,000/mm³. CRP was elevated at 20 mg/dl. Roentgenogram revealed osteolytic lesions in the distal metaphysis of hand and maxillary bone. Bone biopsy showed non-necrotizing granulomatoid lesions. The purified protein derivative reaction showed 10 mm diameter induration. HIV, hepatitis B surface antigen, rheumatoid factor, and brucella agglutination tests were all negative. Serum IgG level was elevated at 1650 mg/dl (normal: 441-1135 mg/dl), while IgM and IgA were in high normal range at 250 and 175 mg/dl, respectively. The nitroblue-tetrazolium (NBT) slide test result was 0, confirming chronic granulomatous disease (CGD) as the underlying condition.

Clinical photograph of the right upper abdominal region, performed at readmission eight months after initial treatment.

Figure 1 presents a clinical photograph depicting subcutaneous swelling and granuloma formation in the right upper quadrant of the abdomen, corresponding to a tender mass observed on admission during the patient’s readmission eight months after initial treatment; this image documents the anatomical site and gross pathological findings, without the use of specialized imaging modality or staining, at the time of acute symptoms.

CT of the liver, right lobe, with adjacent lower right ribs and soft tissue.

Computerized tomography showed a hypodense area in right lobe of liver with peripheral enhancement, with adjacent involvement of lower right ribs and reaction to soft tissue, indicating rib osteomyelitis

KOH 10% preparation of hepatic abscess, microscopic examination.

KOH 10% preparation of hepatic abscess showing dichotomous septated hyaline hyphae, with microscopic examination revealing branched, septated, and dichotomous mycelia that was identified as Aspergillus fumigatus based on microscopic and macroscopic findings including rapid growth, bluish green colonies, and characteristic morphology

Invasive aspergillosis with Aspergillus osteomyelitis of the ribs and hepatic abscess in a CGD patient, with Aspergillus fumigatus identified as the causative agent

Chronic granulomatous disease

Invasive aspergillosis

Certain infectious or parasitic diseases

Aspergillus osteomyelitis

Abscess of liver


A 47-year-old male patient presented with tenesmus and mucoid stool and was admitted to the hospital via a local clinic. He had a 20-year smoking history of one pack of cigarettes daily and did not drink alcohol. His past medical history was significant for pulmonary tuberculosis 20 years ago, which was treated with anti-tuberculosis medication for 9 months. On admission, he appeared in good health without complaints of weight loss, fever, or night sweats. His vital signs showed blood pressure of 110/90 mmHg, pulse rate of 78/min, body temperature of 36.2°C, and respirations of 18/min. Physical examination revealed a normal appearance with no remarkable findings except a depressed anterior chest wall, no lymphadenopathy, clear breath sounds, and regular heart sounds without murmurs. Laboratory findings showed hemoglobin 13.4 g/dL, white blood cells 4,600/μL, platelets 305,000/μL, AST 22 IU/L, ALT 35 IU/L, ALP 47 IU/L, GGT 42 IU/L, LDH 393 U/L, BUN 14.8 mg/dL, creatinine 1.0 mg/dL, uric acid 6.2 mg/dL, and calcium 3.6 mg/dL. Chest radiograph showed a white lesion in the right upper lung field thought to be a healed scar from pulmonary tuberculosis. Upper gastrointestinal endoscopy revealed a healed ulcer in the duodenal bulb with negative rapid urease test for Helicobacter pylori. Additional staging evaluation revealed β2-microglobulin titer of 1,770 μg/L (normal range), serum protein electrophoresis showing polyclonal gammopathy pattern, abdominal CT showing no lymphadenopathy, and bone marrow aspiration and biopsy showing no remarkable findings.

(A) Colonoscopy at admission, rectum. (B) Colonoscopy at admission, appendiceal orifice.

Colonoscopic findings at admission. (A) Colonoscopy showing granular & reddish mucosal thickening in the rectum just above anus.(B) Colonoscopy showing reddish inflammatory mucosal swelling in the appendiceal orifice.

(A) Colon biopsy, H&E staining, 200× magnification. (B) Colon biopsy, immunohistochemical staining for CD20, 200× magnification.

Histologic findings of biopsy specimens. (A) Neoplastic lymphoid cells infiltrated colonic gland resembling a lymphoepithelial lesion (H&E, ×200). (B) Immunohistochemical stain for CD 20 showing diffuse reaction in the cell membrane. Lymphoepithelial lesions (arrow heads) are also positive for CD20 (×200).

Low grade MALT lymphoma of stage IE (using Ann-Arbor staging) and stage II (using St. Jude Children's Research Hospital staging)

MALT - [mucosa associated lymphoid tissue] lymphoma


Patient 1: One-year-old Navajo male, appeared well until 5 months when skull and thorax deformities were noted. At 7 months, skeletal abnormalities were discovered during chest radiography for pneumonia. History includes streptococcal pneumonia with meningitis at 10 months. Physical exam showed: small stature (below 3rd percentile for length, 5th percentile for weight), deafness, tachypnea, weakness, short humeri, markedly delayed gross motor skills, and poor muscle tone. Laboratory findings: hypercalciuria (401 mg calcium/g creatinine), elevated serum alkaline phosphatase (2716 U/L; normal 133-347), excessive urinary deoxypyridinoline (173 nmol/mmol creatinine; normal 2-41).

(A) Clinical photograph of Patient 1 at initial evaluation.

A: Figure 1 (A) is a clinical photograph depicting Patient 1, a one-year-old male proband with juvenile Paget’s disease, demonstrating a disproportionately large head, deformed chest, curvature of the limbs, and marked weakness, with the image serving as a gross clinical representation of the phenotypic manifestations at the time of initial evaluation.

Radiograph of right proximal femur, anteroposterior view.

Anteroposterior radiograph of right proximal femur shows markedly widened, poorly modeled and osteopenic bone, with cortical thinning and coarse trabecular pattern

Juvenile Paget's disease caused by homozygous deletion of TNFRSF11B (the gene encoding osteoprotegerin)

Juvenile Paget disease

Diseases of the musculoskeletal system or connective tissue

Orthopedic and connective tissue disorders


27-year-old male presented with sudden loss of central vision in right eye in March 2002, followed by vision loss in left eye within 18 days. Patient was a light occasional drinker and moderate smoker (15 cigarettes/day for 5 years). History of chronic headaches responsive to painkillers. Previously worked as electrician, then in glue factory since 1998. Headaches worsened after starting work in glue factory, particularly after transfer to glue preparation department. Initial fundus examination showed microangiopathy and pseudoedema of optic disc in both eyes. One month after onset, visual acuity was 1/100 in right eye and 7/10 in left eye. By June 2002, had bilateral paleness of optic discs and inability to count fingers with either eye, with complaints of disturbing photopsias. Blood test positive for homoplasmic 11778G → A/ND4 mutation. mtDNA belonged to haplogroup H. Pre-treatment lab results showed increased urinary 2,5-hexandione (4.1 mg/L) and hippuric acid (1,040 mg/L).

(A) Optical coherence tomography of the right eye, RNFL thickness in each quadrant, at 9, 10, or 15 months of follow-up. (B) Optical coherence tomography of the left eye, RNFL thickness in each quadrant, at 9, 10, or 15 months of follow-up.

RNFL thickness in each quadrant of the eye, as measured by optical coherence tomography. (A ) Right eye. (B ) Left eye. Solid lines refer to the patient’s eyes at 9, 10, or 15 months of follow-up; dashed and dotted lines refer to historical groups of healthy subjects (control) and of patients in an advanced stage of LHON with atrophy of the optic nerve

Pedigree analysis with mtDNA analysis of the maternal line. mtDNA analysis of the patient and his mother and siblings (asterisks) revealed the homoplasmic 11778/ND4 LHON muta- tion in all four of them

Figure 2 on page 2 presents a three-generation pedigree reconstruction of the patient’s maternal line, showing the results of mtDNA analysis which detected the homoplasmic 11778/ND4 LHON mutation in the patient, his mother, and his siblings (indicated with asterisks); the pedigree diagram displays gender, affected status, and deceased individuals, demonstrating that although all tested maternal relatives carry the mutation, only the reported patient developed Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON) with homoplasmic 11778G → A/ND4 mutation

Leber hereditary optic neuropathy


63-year-old man with well-controlled hypertension and diabetes was referred from primary clinic due to hepatic mass found on ultrasonography. Physical examination was unremarkable. Laboratory findings showed normal hematological indexes, liver function tests, and renal functions. Patient was negative for viral markers with normal α-fetoprotein levels. Bone marrow biopsy showed 30% marrow cellularity but was otherwise normal. Serum calcium, β-2 microglobulin, and serum/urine protein immunoelectrophoresis were normal. Skeletal radiography revealed no abnormalities.

(A) Contrast-enhanced CT of the liver, arterial phase, segment VI, 2×2 cm mass. (B) Contrast-enhanced CT of the liver, portal venous phase, hypodense mass. (C) MRI of the liver, T1-weighted image. (D) MRI of the liver, T2-weighted image.

Contrast-enhanced CT showed: (A) 2×2 cm well-enhanced mass in segment VI of liver during arterial phase, (B) hypodense mass in portal venous phase. MRI revealed: (C) well-defined mass with low signal intensity on T1-weighted image, (D) high signal intensity on T2-weighted image

(A) Liver, H&E staining, 100× magnification. (B) Liver, H&E staining, 400× magnification. (C) Liver, ABC immunohistochemical staining, 200× magnification, IgG heavy chain. (D) Liver, ABC immunohistochemical staining, 200× magnification, kappa light chain.

The liver shows diffuse solid proliferation of monotonous small round to ovoid cells (A: H&E, ×100). They have eccentric cytoplasm and round nuclei with peripheral condensation of chromatin (B: H&E, ×400). Immunohistochemical stains of the hepatic mass exhibit monoclonality for IgG heavy chain (C: ABC, ×200) and kappa light chain (D: ABC, ×200).

Solitary extramedullary plasmacytoma of the liver without systemic monoclonal gammopathy

Extramedullary plasmacytoma


A 36-year-old obese woman with a 5-year history of type 2 diabetes presented to the emergency department with a 5-day history of fever, chills, cough with yellowish phlegm, and sharp right lower chest pain that worsened with deep breathing. Physical examination was initially unremarkable with the patient being afebrile and having clear lungs. She had a positive Mantoux test from 1976, smoked one pack per day, and consumed alcohol socially. There was a history of visiting her sister's cottage at a local lake a week prior to symptom onset, where she slept at the gazebo for two nights. When she returned to the hospital five days later due to persistent symptoms, she had a temperature of 39 degrees Celsius, mild tachycardia with heart rate of 104 beats per minute, normal blood pressure of 125/74 mmHg, respiratory rate of 18, and oxygen saturation of 96% on room air. Physical examination revealed decreased air entry with bronchial breath sounds in the right lower chest.

Table of demographics, timing of symptom onset and diagnosis relative to exposure, and clinical outcomes for five patients with acute blastomycosis pneumonia.

Table 1 summarizes the demographics, timing of symptom onset and diagnosis relative to cottage or lake exposure, and outcomes for five patients with overwhelming acute blastomycosis pneumonia. It includes data on month of presentation to hospital, age, gender, weight in pounds, number of days from exposure to symptom onset, number of days to diagnosis after onset of symptoms and after hospitalization, and clinical outcome (death or recovery). Key findings are that all patients were obese, symptoms began within 6–10 days after exposure (except one unclear case), time to diagnosis ranged from 19 to 40 days after onset, and two patients died while three recovered.

Chest X-ray, posteroanterior (PA) view, initial examination.

Initial chest X-ray (PA view) showed early right lower lobe consolidation

Chest X-ray, posteroanterior view, performed 5 days later.

Follow-up chest X-ray (PA view) 5 days later showed progression of disease with infiltrates in right and left lower lobes

CT scan of the chest performed 8 days after hospitalization.

CT scan of chest performed 8 days after hospitalization showed bilateral consolidation of lungs, mainly of lower lung fields

Chest X-ray, posteroanterior (PA) view, performed after 8 days of intravenous antibiotic therapy.

Chest X-ray (PA view) after 8 days of intravenous antibiotic therapy showed further worsening of bilateral lower lung disease with nodular pattern, raising suspicion of metastatic disease

Wet preparation of sputum, 25% NaOH with 5% Glycerol mounting medium, 40× magnification.

Wet preparation of sputum (25% NaOH with 5% Glycerol mounting medium, 40× magnification) showed budding yeast (blastocyst) consistent with Blastomyces dermatitidis

Acute blastomycosis pneumonia caused by Blastomyces dermatitidis

Blastomycosis


A 44-year-old man was hospitalized because of jaundice. Physical examination revealed normal findings except jaundice, and his past medical history was unremarkable. Complete blood count showed hemoglobin of 15 g/dL, white blood cell count of 8,200/μL with differential of 79% segmented neutrophils, 15% lymphocytes, 5% monocytes, and 1% eosinophils, and platelet count of 248,000/μL. Liver function test showed elevation of total bilirubin (15.3 mg/dL), direct bilirubin (9.4 mg/dL), and alkaline phosphatase (298 IU/L). Immunohistochemical stains showed tumor cells positive for leukocyte common antigen (CD 45) and negative for CD 3,4,5,8,10,21,23,56 and terminal deoxynucleotidyl transferase. Bone marrow aspirate and biopsy showed neither significant abnormalities nor evidence of myelodysplasia or leukemic infiltration.

(A) Abdominal CT, common hepatic duct level. (B) Abdominal CT, intrahepatic duct.

Abdominal computed tomography demonstrating thickening of common bile duct wall, luminal narrowing at common hepatic duct level (A), and mild, diffuse dilatation of intrahepatic duct (B).

Magnetic resonance cholangiography.

Magnetic resonance cholangiography showing dilatation of both intrahepatic duct and right posterior duct

Histopathological section of bile duct tumor, H&E staining, 400× magnification.

Figure 3 presents a high-power histopathological section of the bile duct tumor stained with hematoxylin and eosin at 400× magnification, demonstrating that the majority of infiltrating cells are myeloid precursors characterized by large round to oval cells with slightly eosinophilic cytoplasm and round to oval vesicular nuclei, admixed with a minor population of more mature myeloid forms including eosinophils.

Immunohistochemical staining for myeloperoxidase.

Immunohistochemical stain for myeloperoxidase reveals positive granular cytoplasmic staining of most of the myeloid cells except for the most immature precursors, and the epithelial cells of the bile ducts

Granulocytic sarcoma


A 46-year-old man with a history of radical extirpated melanoma presented with spontaneous acute severe headache occurring one week prior, followed a few days later by progressive confusion and mild left-sided hemiparesis. The patient did not use any medication but smoked 20 cigarettes and 3-4 times cannabis daily. On admission, his blood pressure was 184/89 mmHg and the following day 154/90 mmHg. Neurological examination revealed confusion with a score of 15 out of 30 on the mini-mental state examination and left-sided hemiparesis with MRC grade 4 strength. Brain MRI showed ischemic lesions bilateral occipital and right parietal. Initial MR angiography showed no abnormality, however on second review the examination was without gadolinium and of poor quality, therefore not reliable. Ancillary laboratory investigations in serum (including blood count, serum electrolytes, liver, renal and thyroid function tests, erythrocyte sedimentation rate, C-reactive protein level, antinuclear and antineutrophil cytoplasmic antibody tests, complement C1q, C3 and C4, lupus anticoagulant, rheumatoid factor) and cerebrospinal fluid showed no abnormalities. Transcranial Doppler ultrasonography examination showed increased intracranial blood flow velocities in the medial cerebral artery (154 cm/s) and anterior cerebral artery (168 cm/s).

Cerebral angiography.

Cerebral angiography showed multiple caliber changes in the intracranial blood vessels

Reversible cerebral vasoconstriction syndrome (RCVS)


75-year-old right-handed woman presented with a three year history of word-finding difficulties. Her speech showed frequent use of 'thing' in place of specific words and confusion of related words (e.g., 'door' for 'window'). She had difficulties with arithmetic, writing, spelling, and speech comprehension for 2 years. No significant memory problems or getting lost. No behavioral symptoms or appetite changes. No family history of dementia. Initial assessment showed fluent aphasia with circumlocutory speech. Single word repetition preserved but sentence repetition impaired. Bilateral limb apraxia present. General neurological examination normal. Neuropsychological assessment revealed severe anomia (only able to produce 'train' on naming task), impaired comprehension (13/50 on British Picture Vocabulary Scale), poor reading (2/50 on National Adult Reading Test), dyscalculia (0/24 on Graded Difficulty Calculation Test), poor spelling, decreased digit span (four digits forwards, unable to repeat two digits backwards), and executive dysfunction.

(A) Coronal T1-weighted MRI of the brain through frontal, mid-temporal, posterior temporo-parietal, and posterior parietal regions, performed 5 years after symptom onset; sagittal MRI of the left temporo-parietal region with voxel-compression-mapping overlay, showing changes from 3.5 to 5 years after symptom onset.

Coronal T1-weighted MR images (with left hemisphere shown on the right of the images) through the frontal, mid-temporal, posterior temporo-parietal and posterior parietal
regions and a sagittal MR image through the left temporo-parietal region with a voxel-compression-mapping overlay to show the progression of regional atrophy (degree of volume
loss and expansion coded in the colour scale: red represents 20% or greater expansion of voxels and blue represents 20% or greater contraction of voxels.): A) — coronal images
5 years after symptom onset; sagittal image shows change over time period 3.5 to 5 years from symptom onset.

Atypical semantic dementia (SD) with features suggestive of logopenic/phonological aphasia (LPA) variant of primary progressive aphasia, characterized by fluent, empty speech with profound anomia, loss of word meaning, impaired single word comprehension and surface dyslexia, along with early dominant parietal lobe deficits

Semantic dementia

Mental, behavioural or neurodevelopmental disorders

Logopenic variant primary progressive aphasia

Non-amnestic Alzheimer’s disease, logopenic variant with primary progressive aphasia

Dyslexia

Symptoms, signs or clinical findings, not elsewhere classified

Parietal lobe injury

Injury, poisoning or certain other consequences of external causes


10-month-old male admitted with fever. Born at 38 weeks gestation after unremarkable pregnancy, birth weight 2,960g. History of cephalhematoma over parietooccipital region at birth, bilateral inguinal hernia repair at 2 months, recurrent pneumonia and urinary tract infection. Growth parameters below 3rd percentile (weight: 7,500g, length: 73.7cm). Physical exam showed pale skin, sparse/light/curly hair with pili torti on microscopy. Neurologic exam revealed diffuse hypotonia with poor head/trunk support, no visual fixing/following, hyperreflexic deep tendon reflexes bilaterally with ankle clonus, bilateral Babinski extension. Lab results: serum copper 27 μg/dL (normal 70-130), ceruloplasmin 9.07 μg/dL (normal 20-60).

(A) Brain MRI at 10 months, T2-weighted imaging. (B,C) Brain MRI at 10 months, diffusion-weighted imaging and ADC map. (D) Brain MR angiography at 10 months.

Initial MRI at 10 months showed: (A) T2-weighted imaging revealed symmetric hyperintense lesions in deep periventricular white matter, mild atrophy of cerebellum and brainstem without prominent cerebral hemisphere atrophy; (B,C) Diffusion-weighted imaging showed high signal intensity with decreased ADC; (D) MR angiography demonstrated markedly tortuous intracranial and extracranial vessels

(A,B) MRI at 13 months, white matter and corpus callosum. (C,D) MRI at 13 months, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC), white matter.

Follow-up MRI at 13 months showed: (A,B) Marked progression of white matter lesions extending to deep white matter and corpus callosum; (C,D) Extended lesions showing high signal intensity on DWI with decreased ADC

Menkes disease


37-year-old woman presented with a 3-month history of exertional dyspnea, cough and one recent episode of hemoptysis. At admission, she showed no hypertension or systemic symptoms.

Chest radiograph.

Chest radiograph showed a left hilar mass with a lobulated margin

CT, contrast-enhanced, axial view.

Contrast-enhanced CT axial images showed a left hilar mass with an endobronchial protrusion extending along the bronchial lumen, with mild homogeneous enhancement

CT of the left lung, lung window, axial view.

D: The lung window axial CT image demonstrates localized emphysema distal to the endobronchial lesion in the left lung.

Bronchoscopy of the lingular segmental bronchus.

E: Bronchoscopy reveals a hypervascular bulging mass with a lobulated surface located in the lingular segmental bronchus.

Histopathology with immunohistochemical staining for chromogranin.

Histopathology showed tumor consisting of nests of epitheloid cells in an organoid/alveolar pattern, surrounded by vascular reticulin network ('zellballen' pattern). Cells showed marked nuclear pleomorphism and up to 1-2 mitotic figures/10 high power fields. Microscopic necrotic foci present. Immunohistochemical staining for chromogranin was strongly positive.

Primary pulmonary paraganglioma with malignant potential

paraganglioma NOS


A 66-year-old man without smoking history presented with a one-month history of progressively worsening cough and dyspnea along with febrile symptoms. He had been previously healthy until diagnosed with gastroesophageal reflux disease (GERD) a month prior and began treatment with lansoprazole. He had a history of working at a dusty place several weeks before hospitalization but did not experience any respiratory symptoms at that time. The symptoms developed a few days after initiation of lansoprazole treatment. On examination, vital signs were stable and laboratory studies including eosinophil count were all within normal ranges.

Posteroanterior chest radiograph of the lungs.

Posteroanterior chest radiograph shows diffuse ground-glass opacities in both lungs, which are predominant in upper lung zones.

(B) High-resolution CT, axial view, lungs. (C) High-resolution CT, coronal view, lungs.

Axial (B) and coronal (C) reconstruction high-resolution CT images show areas of diffuse ground-glass opacity in both lungs with upper lung predominance.

Lung histopathological specimen.

Histopathological specimen shows mixed interstitial infiltration of lymphocytes and plasma cells, suggestive of nonspecific interstitial pneumonia pattern. Note active hyperplasia of type II pneumocytes (arrows) and Massons’ body (arrowheads).

Lansoprazole-induced interstitial lung disease

interstitial lung disease NOS

Cardiovascular and respiratory disorders


A previously well 34-year-old man presented with generalized tonic-clonic seizure and transient right side weakness. He also had recurrent hemoptysis of one month's duration. Physical examination findings included normal kidney size, shape and echogenicity on renal ultrasound. Laboratory results showed hemoglobin level of 10.5 g/dL, white blood cell count of 6.3 × 10³/mm³, normal complement levels, normal serum creatine level (1.04 mg/ml, normal range: 0.6-1.2 mg/ml), and urinalysis showing no protein but a few old form RBCs. The patient was anti-GBM antibody negative, with no anti-neutrophil cytoplasmic antibodies (ANCA), double-stranded DNA or anti-smooth muscle antibody. Bacterial cultures obtained during bronchoscopy and virus serology were negative. Echocardiography was negative. An immunofluorescence study revealed a large amount of total linear and granular IgG deposits in the lung and renal tissues. Other possible causes such as septicemia, thrombogenic hematologic disorder, cardiogenic embolism and bacterial endocarditis were excluded.

CT of the lungs.

Lung CT showing multifocal ground-glass opacities in both lungs, consistent with diffuse alveolar hemorrhage.

Brain MRI, T2-weighted sequence, axial view.

Brain MR T2-weighted axial images showing multiple small nodular, high signal intensities in the bilateral cerebellar hemispheres, right frontal and left parietal cortices.

MRI, T1-weighted, axial view, contrast enhanced.

Contrast enhanced T1-weighted axial images showing leptomeningeal enhancement along both parasagittal regions and cerebellar hemispheres, consistent with multiple small vascular infarcts.

CNS vasculitis associated with Goodpasture's syndrome

CNS pseudovasculitis

Goodpasture syndrome


A 26-year-old man presented with a firm, nontender palpable lymph node in his left cervical area. The patient had no specific past medical history. On admission, his vital signs were stable with blood pressure 120/80 mmHg, pulse rate 80/min, respiratory rate 24/min, and body temperature 36.5°C. Routine laboratory investigations showed a normal complete blood count, serum chemical tests, and erythrocyte sedimentation rate (ESR). Serologic tests for cytomegalovirus, human immunodeficiency virus (HIV) and polymerase chain reaction (PCR) analysis of mycobacteria yielded negative results. Serum immunoglobulin levels were within normal ranges: IgG 1,680 mg/dL (normal 700-1,700 mg/dL), IgA 117 mg/dL (normal 70-400 mg/dL), IgM 129 mg/dL (normal 40-230 mg/dL), and IgE 33.8 IU/mL (normal 0-100 IU/mL). The patient had no history of fever during the clinical course.

CT of the chest.

Chest CT revealed pleural effusion and mediastinal lymphadenopathies with calcification.

H&E staining of cervical lymph node excisional biopsy, 400× magnification.

Figure 2 presents a high-power hematoxylin and eosin (H&E) stained histopathological section (magnification ×400) from an excisional biopsy of the cervical lymph node, demonstrating dilated sinuses filled with histiocytes possessing abundant pale eosinophilic cytoplasm, as indicated by arrows.

(A) Immunohistochemical staining for CD68, 400× magnification. (B) Immunohistochemical staining for S-100, 400× magnification.

Immunohistochemical staining for CD68 and S-100 protein. Histiocytes show positive immunoreactivity with brown color for CD 68 (A, ×400) and S-100 (B, ×400).

Sinus histiocytosis with massive lymphadenopathy (SHML)


A 49-year-old nonsmoking female with acute myeloid leukemia (AML) had been treated with one course of induction chemotherapy using daunorubicin and cytosine arabinoside. After AML relapse, she received a second course consisting of 10 mg/m² IV mitoxantrone daily for six days and 3 g/m² IV ARA-C daily for six days. On day six after completion of chemotherapy, she developed flu-like symptoms including fever and cough. Physical examination revealed elevated temperature (38.5°C), tachypnea, and diffuse bilateral inspiratory crackles on chest auscultation. Despite empirical antibiotic therapy, fever and cough persisted over the following days.

Chest radiograph, posteroanterior view.

Posteroanterior chest radiograph showing diffuse nodular opacities scattered throughout both lungs

(B) CT of the lung, axial view. (C) CT of the lung, coronal view.

Axial CT (B) and reformatted coronal (C) images of lung show numerous 1-mm to 5-mm nodules (arrow) in diffuse distribution and along bronchovascular structure. Patchy infiltration is present in left lower lobe.

(D) Lung biopsy, Hematoxylin & Eosin staining, 200× magnification. (E) Lung biopsy, Hematoxylin & Eosin staining, 40× magnification.

Pathological examination of lung biopsy specimen (D) (Hematoxylin & Eosin staining, ×200) shows aggregates of fibrous plugs within small airways and alveoli around interstitial inflammation, consistent with cryptogenic organizing pneumonia. (E) Parenchymal nodules show localized areas of organizing pneumonia (open arrow) surrounding bronchiolitis obliterans (black arrow) that are separated from other involved areas by zone of relative normal parenchyma (Hematoxylin & Eosin staining, ×40).

Pneumonia


A 41-year-old female with neurofibromatosis type I presented with a 3-year history of recurrent epigastric soreness, heartburn, and diarrhea. Repeated end recurrent duodenal ulcers that improved with proton-pump inhibitors but recurred when medication was withdrawn. She had been previously diagnosed with NF1 based on clinical features and family history, with first-degree relatives also affected. Physical examination revealed several café-au-lait spots and multiple small nodules on the anterior chest and areolar area, plus multiple axillary freckles. Upper gastrointestinal endoscopy revealed multiple shallow ulcers in the descending duodenum. Both rapid urease test and urea breath test for Helicobacter pylori were negative. The serum fasting gastrin level was >1,000 pg/mL and 837 pg/mL in two consecutive measurements. Evaluation for MEN1 association through hormonal and radiologic investigations of the parathyroid, pituitary, pancreas, and adrenal gland proved negative.

CT of the abdomen.

Abdominal CT scan showing a 3×2 cm, well-defined, uniformly enhanced mass adjacent to the duodenal loop

Histopathology of solid mass, H&E staining, 40× magnification.

The pathologic findings were of a well-encapsulated solid mass containing cells with a diffuse, trabecular growth pattern. (×40, H&E).

Immunohistochemical staining for gastrin, avidin-biotin-peroxidase method, 250× magnification.

The tumor cells were strongly immunopositive for gastrin. (×250, avidin-biotin-peroxidase).

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

Biopsy of the multiple small nodules revealed the haphazard arrangement of uniform spindle cells in a collagenous stroma. (×100, H &E).

Liver tissue section, H&E staining, 100× magnification.

The tumor cells were immunopositive for C-kit (CD117). (× 100, H &E).

Zollinger-Ellison syndrome associated with neurofibromatosis type I; gastrinoma confirmed by immunohistochemical staining

Zollinger-Ellison syndrome

Neurofibromatosis, unspecified

Gastrinoma


A 62-year-old woman with known neurofibromatosis type 1 (NF-1) presented to the Emergency Department with a painful and suddenly enlarging mass on the left back area. She had no family history of NF-1 but had a medical history of operation and skin graft of a large hematoma on the right back area 30 years prior, with biopsy findings indicative of neurofibroma. On initial physical examination, her vital signs were blood pressure 160/90 mmHg, heart rate 120 beats/min, respiratory rate 20 breaths/min, and axillary temperature 36.5°C. Physical examination revealed a soft mass with tenderness on palpation on the left back area. The mass was scarlet-colored, non-pulsating, and had a well-demarcated border. Multiple areas of hyperpigmentation (café-au-lait spots) were present on her torso and extremities, and axillary frecklings were also noted. During the next 3 hours, the mass expanded and she became hemodynamically unstable with blood pressure 73/50 mmHg and heart rate 100 beats/min, with hemoglobin falling from 12.4 g/dL to 8.1 g/dL.

CT of the abdomen and pelvis.

Abdomen and pelvis CT showing a huge, subcutaneous, 13×7.6 cm-sized hematoma, along with fluid collection in the posterior and left lateral subcutaneous layer of the thoracolumbar and left lower back area

Neurofibromatosis type 1 with recurrent, massive, subcutaneous hemorrhage on the back region combined with hypovolemic shock; diffuse neurofibroma

Neurofibromatosis type 1

subcutaneous haemorrhage

Hypovolaemic shock

Neurofibroma


A 66-year-old man was admitted because of dysphagia with repeated aspirations in March 2007. His illness began around 2000 with several episodes of falling while riding a motorcycle that were not associated with dizziness or faintness and were independent of specific situation or body position. In October 2003, he was evaluated for blurred vision, dislike of bright lights, and easy falls. He had undergone bilateral lens implantation in 2000 for bilateral cataracts and presbyopia but did not benefit from the surgery. His symptoms progressively worsened with imbalance and unsteadiness when walking. Pupils were irregularly shaped with sluggish bilateral direct light reflexes. Vertical ocular movements for willed gaze and following objects were slow and limited, though full ocular movements were elicited during passive head motions. Volitional horizontal gaze and pursuit were slow with bilateral adduction paresis, but convergence was normal. He was slow and made errors when performing distal rapid alternating movements and tended to topple backwards. There was no resting or action tremor initially. His condition continued to deteriorate with frequent falls requiring a cane, retracted head, slurred voice, inability to look down, and swallowing difficulties. By March 2007 admission, his eyes deviated up and lateral with absent vertical and medial eye movements. When attempting lateral gaze, only brisk quick lateral movements occurred on the same side with no medial movement of the opposite eye. He could not converge his eyes, had no Bell's phenomenon or optokinetic nystagmus, and caloric stimulations with warm and cold water did not evoke nystagmus bilaterally. Doll's eye maneuver evoked no eyeball movements. He had severe nuchal rigidity and retrocollis, could not sit independently, repeatedly fell backward without support, and had axial rigidity making distal movements appear ataxic. Reflexes were symmetrical and minimally brisk with bilateral flexor plantar responses and no resting tremor.

(A) Clinical photograph in mid-forties. (B) Clinical photograph at age 62. (C) Clinical photograph at age 64. (D) Clinical photograph at age 66. (E) MRI, T2-weighted, midsagittal view of the brain. (F) MRI, T2-weighted, axial view of the brain. (G) MRI, T1-weighted, coronal view of the brain.

Serial photographs showing progressive eyeball deviation from normal binocular vision in mid-forties (A), beginning exodeviation at age 62 (B), more pronounced exodeviation at age 64 (C), to full exodeviation at age 66 (D). MRI images show moderate atrophy of the whole cerebrum and brainstem, as well as mild bihippocampal atrophy with T2-weighted midsagittal and axial images demonstrating midbrain atrophy and T1-weighted coronal images showing bilateral hippocampus and mesial frontal lobe atrophy (E-G).

Progressive supranuclear palsy (PSP) with nuclear level involvement causing complete ophthalmoplegia with exodeviation

Progressive supranuclear palsy

Complete ophthalmoplegia

divergent strabismus


A 63-year-old woman presented with abdominal pain and diarrhea for two weeks. The patient had no personal or family history of pancreatic disease. Physical examination revealed no unusual findings. Laboratory tests showed no elevation of serum amylase and lipase levels, and tumor markers including carbohydrate antigen 19-9 (CA 19-9) were within normal limits.

Contrast-enhanced pancreas CT, arterial phase.

Contrast-enhanced pancreas CT scan obtained at arterial phase shows only moderate dilatation of main pancreatic duct (arrow) in tail of pancreas, and there is no evidence of obstructive mass. Atrophy with decreased enhancement of pancreatic tail is due to chronic pancreatitis.

(B) Pancreas MRI, T2-weighted sequence. (C) Pancreas MRI, gadolinium-enhanced sequence.

T2-weighted (B) and gadolinium-enhanced (C) pancreas MR images show enhancing intraductal mass (short arrows) of main pancreatic duct in pancreatic body with dilatation of upstream main pancreatic duct (long arrow).

MR cholangiopancreatography, pancreas.

MR cholangiopancretography shows filling defect (short arrows) that is due to intraductal mass with dilatation of upstream main pancreatic duct (long arrow) and there is no dilatation of downstream main pancreatic duct.

Endoscopic retrograde pancreatogram of the pancreatic body.

Endoscopic retrograde pancreatogram shows filling defect (arrows) of contrast media that is due to mass in main pancreatic duct in pancreatic body.

Photograph of resected specimen of pancreas.

Photograph of resected specimen shows mass (arrow) in dilated main pancreatic duct.

T1N0M0 stage intraductal tubular carcinoma (ITC)

intraductal carcinoma of unspecified site


A previously healthy 33-month-old girl presented with a 10-day history of high fever, sore throat, and non-productive cough, followed by worsening lower respiratory tract symptoms including severe cough, acute onset hematochezia, and numerous ecchymoses. She had no prior illness or family history of bleeding problems. On admission, she appeared febrile with diminished breath sounds and rales over the left lower lung field, multiple ecchymotic skin lesions over the upper and lower extremities, but no evidence of hemarthroses, soft tissue hematomas, hepatosplenomegaly, or sensorimotor deficits. Her cardiac examination was unremarkable. Initial laboratory studies showed normal red and white blood cell counts, normal liver and renal function studies, normal urinalysis, negative Widal test, and normal anti-streptolysin O titer. Fecal occult blood testing was positive but no stool leukocytes were present. Latex agglutination test for rotavirus was negative. C-reactive protein was elevated at 8.3 mg/L. IgM antibody titer to M. pneumoniae was 1:1,280 on admission day. Coagulation studies revealed normal prothrombin time of 12.7 sec but prolonged activated partial thromboplastin time of 94.0 sec. Plasma mixing studies failed to correct the aPTT (77.3 sec). The patient had normal bleeding time, FVIII activity of 3%, factor IX activity of 61%, von Willebrand factor antigen of 146.2%, ristocetin cofactor activity of 110.1%, and FVIII inhibitor of 2.5 Bethesda Units/mL. Additional tests showed no evidence of disseminated intravascular coagulopathy with normal fibrinogen, fibrin degradation products, and anti-thrombin 3 levels. Tests for anti-nuclear, anti-phospholipid, lupus anticoagulant, and anti-smooth muscle cell antibodies were all negative.

PCR testing of oropharyngeal swab collected on 4th hospital day.

PCR testing of oropharyngeal swab collected on 4th hospital day was positive for M. pneumoniae DNA amplification

Chest radiograph on admission.

Chest radiograph on admission shows consolidation in left lower lung field and blunting of the costophrenic angle

Transient acquired hemophilia associated with Mycoplasma pneumoniae pneumonia

Acquired haemophilia

Pneumonia due to Mycoplasma pneumoniae


A 52-year-old man with no prior medical history presented with a 3-month history of fever and progressive fatigue. On physical examination, he appeared chronically ill but alert, with vital signs showing blood pressure 100/70 mmHg, pulse rate 102 bpm, respiratory rate 22 bpm, and body temperature 38.5°C. Examination revealed no abnormalities in head, neck, or chest, no hepatosplenomegaly or abdominal mass, and no evidence of lymphadenopathy or abnormal skin lesions. Laboratory findings showed hemoglobin 10.4 g/dL, hematocrit 30.0%, white blood cell count 5,000/μL, platelet count 104,000/μL, sodium level 126 mM/L (low), elevated β₂-microglobulin 4.7 μg/mL, elevated LDH 476 IU/L, low serum cortisol 2.9 μg/dL at 8 AM, elevated plasma ACTH 210 pg/mL at 8 AM, and normal aldosterone 56.2 pg/mL. Urinalysis showed slightly elevated epinephrine 21.5 μg/day and norepinephrine 202.1 μg/day, while vanillylmandelic acid and total metanephrine were normal. Rapid cosyntropin stimulation test demonstrated inadequate cortisol response (9.5, 10.0, 10.5 μg/dL at 0, 30, 60 minutes respectively), strongly suggesting adrenal insufficiency. Chest radiography was normal without hilar lymphadenopathy. Bone marrow biopsy was negative for lymphomatous involvement.

CT scan of the abdomen and pelvis, bilateral adrenal masses, right adrenal gland 5.8 × 2.7 cm, left adrenal gland 3.7 × 2.0 cm.

Abdominal pelvic CT scan showing bilateral adrenal masses, with the right adrenal gland measuring 5.8 × 2.7 cm and the left adrenal gland measuring 3.7 × 2.0 cm in greatest dimension.

F-18 FDG PET scan of the adrenal glands.

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scan showing intense FDG accumulation in both adrenal glands. There was no abnormal FDG uptake in the rest of the body.

CT-guided core needle biopsy of the left adrenal mass, immunohistochemistry positive for CD20, negative for CD3 and CD30, Ki-67=90%.

CT-guided core needle biopsy of the left adrenal mass showing a tumor comprised of large cells, immunohistochemically positive for CD20 but negative for CD3 and CD30. The Ki-67 labeling index was about 90%. The tumor was diagnosed as a diffuse large B-cell lymphoma.

Primary bilateral adrenal diffuse large B-cell lymphoma

Diffuse large B-cell lymphomas


A healthy 20-year-old male nonsmoker began working at a beryllium production plant on 12 March 1979. After working in ceramics and alloy fabrication departments, he was transferred on 31 December 1979 to the metal production department to operate the reduction furnace. On 12 January 1980, he presented with a new rash on both forearms and was seen multiple times over the next month for this rash. On 29 March 1980, he complained of shortness of breath, chest pain, and nonproductive cough that had begun several weeks earlier, with a 2.7 kg weight loss over the preceding month. Physical examination on 1 April 1980 revealed scattered rales on chest examination. Following work restriction and a period away from work, symptoms improved, but when he returned to work on 28 April 1980 in the same department, he developed recurrent symptoms including rash and skin ulcers on the wrist and hand in July and August, followed by productive cough and progressive weight loss of 7.7 kg by October 1980, along with exertional dyspnea.

Chest radiograph performed on 2 March 1979.

Preemployment chest radiograph taken on 2 March 1979 showing normal lung fields

Chest radiograph performed on 17 March 1981.

Chest radiograph taken during the second episode of acute work-related illness on 17 March 1981 showing a mild diffuse nodular infiltrate

Pulmonary function tests with FVC and DLCO measurements

Preemployment pulmonary function tests were normal with forced vital capacity (FVC) of 6.34 L (120% predicted) and carbon monoxide diffusing capacity (DLCO) of 39.5 mL/min/mmHg (119% predicted). During acute illness on 29 March 1980, substantial decline in FVC to 3.41 L (64% predicted) and decrease in DLCO to 8.9 mL/min/mmHg (27% predicted). FVC reached nadir of 2.84 L (54% predicted) on 4 April 1980. By 11 October 1980, FVC was 4.33 L (83% predicted) with DLCO of 24.8 mL/min/mmHg (78% predicted). On 2 December 1980, further decline in FVC to 3.61 L (68% predicted) and DLCO to 20.0 mL/min/mmHg (62% predicted). By 2 February 1981, FVC had fallen to 2.83 L (52% predicted)

TWA airborne beryllium exposures in patient’s departments during this time period

Air sampling data showed that none of the measured beryllium air samples exceeded 100 μg/m³ and most were <10 μg/m³. During a specific exposure event on 2 March 1980, when patient entered the cooling bay twice for 45 minutes total wearing a negative-pressure half-face respirator during heavy fumes, the 8-hour time-weighted average was 5.9 μg/m³

Acute beryllium disease progressing to chronic beryllium disease

beryllium disease

beryllium disease


A 41-year-old woman presented with a three-year history of a painless mass in the region of the right parotid gland. Physical examination revealed a non-tender, firm and slightly mobile mass without clear borders that was palpable in the right parotid region. The overlying skin was indurated and warm. Clinical examination of the neck revealed no lymphadenopathy, and facial nerve function was normal on both sides. No evidence of abnormality was found by chest radiograph and abdominal ultrasonography.

CT scan, unenhanced, right parotid gland.

Unenhanced CT scan shows 5-cm round mass with lower central density and poorly defined margin in superficial lobe of right parotid gland (white arrow). Also note enlarged lymph nodes (arrowheads).

Contrast-enhanced CT scan of the head and neck.

Contrast-enhanced CT scan shows peripheral enhancement (white arrow) and irregular central non-enhanced attenuation of mass. Multiple reactive lymph nodes with similar CT features are also demonstrated in subcutaneous fat of right cheek and parapharyngeal spaces (arrowheads).

Clinical photograph of the gross specimen, right parotid gland, acquired at the time of surgical excision.

C: The gross specimen photograph shows an encapsulated, tan-colored, lobulated solid tumor mass measuring approximately 5.6 × 5.5 × 3 cm, resected from the right parotid gland of a 41-year-old woman, with the tumor (indicated by a straight arrow) surrounded by parotid glandular tissue (curved arrow), as acquired at the time of surgical excision.

Histology specimen, H&E staining, 200× magnification.

Photomicrograph of histology specimen shows numerous thin-waled vessels surrounded concentricaly by proliferative spindle-shaped to oval-shaped myoid tumor cels in peripheral zone, as wel as hyaline degeneration (E in black asterisks) in central zone (Hematoxylin & Eosin staining, original magnification, ×200).

Immunohistochemical staining for smooth muscle actin, CD34, and desmin.

Immunohistochemical staining shows positive reactivity for smooth muscle actin in tumor cells, but negative for CD34 and desmin.

Benign myopericytoma that arose from the parotid gland

benign tumour NOS


A 68-year-old Asian woman on haemodialysis presented with a history of high grade fever, diarrhea and nausea. Her symptoms began one day after eating grilled chicken and beef at a restaurant, though she denied abdominal pain, vomiting, or hematochezia. She had diabetes mellitus diagnosed at age 50, had undergone haemodialysis for diabetic nephropathy for the past 2 years with three times weekly sessions, and had an aortic mechanical valve replacement for aortic stenosis 7 months prior to admission. On examination, her temperature was 106°F, blood pressure 150/90 mmHg, heart rate 152/min, and respiratory rate 24/min. Physical examination revealed a Levine IV/VI systolic murmur at the right second intercostal space, slightly hypoactive bowel sounds, but no abdominal tenderness, rebound, or evidence of embolization including Osler node, Janeway lesion, or petechiae.

Blood culture on admission.

Blood culture on admission revealed Salmonella enterica serotype Enteritidis (O9, Hg) sensitive to ceftriaxone (MIC ≤1) and ciprofloxacin (MIC ≤0.25), with resistance to cefazolin, amikacin, tobramycin, and gentamicin, but sensitivity to aztreonam, ceftazidime, ampicillin, piperacillin, sulfamethoxazole-trimethoprim, ampicillin sulbactam, meropenem, cefepime, and piperacillin-tazobactam.

Diffusion-weighted MRI of the brain, performed on day 9.

Diffusion-weighted MRI of the brain taken on day 9 showed high intensity areas in the left middle cerebral artery region indicating acute cerebral infarction.

(A) Transthoracic echocardiogram performed on day 13. (B) Transesophageal echocardiogram performed on day 13.

Transthoracic echocardiogram (A) and transesophageal echocardiogram (B) performed on day 13 revealed vegetation on the mitral valve.

Infective endocarditis caused by Salmonella enteritidis

infective endocarditis NOS


A 25-year-old female in her third trimester of pregnancy presented with paroxysmal headache, palpitations, sweating, and hypertension up to 230/130 for three weeks. Her medical history was negative for previous hypertension, and physical examination was unremarkable. Initial work-up excluded pre-eclampsia. Her urine catecholamines were markedly elevated: Dopamine 607 μg/24 hours (range 65-400), Norepinephrine 978 μg/24 hours (range 15-80), Metanephrine 108 μg/24 hours (range 24-96), Normetanephrine 4067 μg/24 hours (range 75-375), and Vanillyl mandelic acid 13.6 mg/24 hours (range 2-7). Epinephrine level was normal at 0.8 μg/24 hours (range 0.0-20.0). Initial abdominal MRI showed a 28×19 mm left juxta-adrenal mass that was later found to be brown fat.

PET-CT scan of the posterior mediastinum near the left atrium, mass size 4.5×2.7×3.9 cm, F18 Levo-DOPA tracer.

PET-CT scan demonstrates a large hypermetabolic soft tissue mass measuring 4.5×2.7×3.9 cm in the region of posterior mediastinum near the left atrium with intense uptake of F18 Levo-DOPA consistent with paraganglioma.

CMR SSFP cine imaging, horizontal long axis view, posterior mediastinum.

Horizontal long axis CMR SSFP cine imaging shows a round, well-defined hypo-intense soft tissue mass in the posterior mediastinum with smooth extrinsic compression of left atrial wall and no apparent fat plane between the lesion and the posterior wall of the left atrium.

T2-weighted dark blood turbo spin-echo imaging.

T2-weighted dark blood turbo spin-echo imaging demonstrates the mass shows homogeneously high signal intensity.

T1-weighted inversion recovery gradient-echo myocardial perfusion imaging.

T1-weighted inversion recovery gradient-echo myocardial perfusion imaging demonstrates heterogeneous, mostly peripheral, dynamic contrast filling of the mass suggesting vascularity.

(D) Cardiovascular magnetic resonance image, T1-weighted, fat-saturated, inversion recovery sequence, horizontal long axis orientation, late gadolinium enhancement, posterior mediastinum, acquired 10 minutes after intravenous administration of 0.2 mmol/kg gadopentetate dimeglumine.

D: T1-weighted, fat-saturated, inversion recovery late gadolinium enhancement cardiovascular magnetic resonance image obtained in the horizontal long axis orientation shows a round, well-defined posterior mediastinal mass adjacent to the left atrium, demonstrating peripheral rim enhancement without central enhancement, suggestive of central tissue necrosis; the image was acquired 10 minutes after intravenous administration of 0.2 mmol/kg gadopentetate dimeglumine.

paraganglioma NOS


A 52-year-old Korean man presented with a 1-month history of general weakness that was aggravated three days before his emergency room visit. Initial neurologic examination revealed disorientation of time, place, and person, attention deficit, immediate memory disturbance, dysarthria, weakness of bilateral upper extremities with increased deep tendon reflexes, and right hemiparetic gait. Blood work showed an elevated eosinophil count of 5,500/μL, representing 41% of total white blood cells. The patient's clinical history and basic examinations did not reveal any identifiable cause of hypereosinophilia, including parasitic infection, neoplasm, vasculitis, or allergy. Additionally, the patient had no prior clinical symptoms or signs suggesting Churg-Strauss syndrome, such as sinusitis or asthma. Cardiac enzymes were elevated with creatine kinase-MB at 7.3 ng/ml and troponin-I at 4.78 ng/ml. An echocardiogram revealed mild left ventricular inferior wall hypokinesia.

Diffusion-weighted brain MRI.

Diffusion-weighted brain MRI revealed multiple acute infarcts in bilateral border zones as well as randomly distributed cortices.

(B) T2-weighted MRI of the brain. (C) Gradient echo MRI of the brain.

T2-weighted image (B) and gradient echo image (C) reveal focal intracerebral hemorrhaging (arrows) at left frontal white matter.

Chest CT.

Chest CT revealed multiple nodules in both lungs.

(E) Cerebral MR angiography. (F–H) Digital subtraction angiography.

Cerebral MR angiography (E) and digital subtraction angiography (F-H) shows no evidence of arterial or venous sinus abnormalities.

Hypereosinophilic syndrome


An 80-year-old white man with a medical history of hypertension presented with progressive left-sided weakness and dysphagia. He had begun dragging his left leg at least one month prior to presentation and started using a walker 5 days before admission. The dysphagia initially occurred with fast eating but progressed to occur with regular eating rate. He had lost 35 pounds over the preceding 3 months and experienced monthly falls requiring emergency visits. On physical examination, his vital signs were: blood pressure 158/81 mmHg, respiratory rate 12/min, heart rate 90/min, and temperature 37°C. He appeared cachectic but was alert, awake, and oriented. Speech was fluent with intact comprehension, naming, and repetition. Cranial nerve examination showed mild left facial drooping. He had left hemiparesis with motor strength 4+/5 on the left in upper and lower extremities and 5-/5 on the right. Deep tendon reflexes were hyperactive with no extensor plantar responses. His neurological status progressively worsened during hospitalization, with eventual left-sided weakness of 1/5 in upper extremity and 2/5 in lower extremity, along with decreased sensation on the left side.

(A) Head CT without contrast. (B) Head MRI, T1-weighted sequence. (C, D) Head MRI, T2-weighted sequence.

A, computed tomography of the head without contrast. B, T1-weighted magnetic resonance imaging of the head. C and D, T2-weighted magnetic resonance imaging of the head. The arrows indicate the subcortical lesion in the left frontal lobe; the block arrows indicate the lesion in the right posterior limb of the internal capsule and thalamus extending along the corticospinal tract (solid arrow, image D)

Brain biopsy, deep white matter, H&E staining.

Brain biopsy revealed infiltrating foamy macrophages and reactive astrocytes on hematoxylin and eosin staining of deep white matter.

Brain biopsy, immunohistochemical staining with anti-simian virus 40 antibody.

Brain biopsy showed positive immunohistochemical staining with anti-simian virus 40 antibody which stains polyomavirus in humans.

Progressive multifocal leukoencephalopathy (PML)


A 19-year-old Korean male presented with a history of abnormal gait since the age of 2 years. His symptoms included wide-based waddling gait, proximal muscle weakness, pain in the extremities, and easy fatigability. He had no history of trauma, infection, or systemic illness. Physical examination showed no abnormalities in his reflexes and he was able to walk independently. Other family members, including the proband's father and 2 younger brothers, did not show any symptoms of muscle weakness. Laboratory findings showed normal serum levels of electrolytes, calcium, and phosphate, with mildly elevated serum alkaline phosphatase (139 IU/L; reference range 42-117 IU/L) and slight increase in ESR level (24 mm/hr; reference range 0-15 mm/hr). Muscle biopsy performed at the patient's right vastus lateralis showed no pathologic findings, with no degenerating or regenerating fibers seen and normal immunohistochemical staining for dystrophin along the membranes of the muscle fibers.

Genetic analysis, family pedigree.

Family pedigree showing the proband (indicated by arrow) and affected family members in an autosomal dominant inheritance pattern.

Radiographs of the femur, tibia, fibula, ulna, radius, humerus, thoracic spine, lumbar spine, knees, and skull.

Radiographs of the proband show cortical, periosteal, and endosteal bony thickening with narrowing of the medullary spaces confined to the diaphyses of the femur, tibia, and fibula, with epiphyses and metaphyses relatively spared. In the upper extremity, the ulna is more severely affected than the radius, and the humerus showed only mild cortical thickening. Some curvature changes were seen in both tibias with genu valgus changes of both knees. Scoliosis of the thoracic and lumbar spines with mild kyphosis of the thoracic spines was observed. No gross bony abnormality was seen in the skull.

(A) Standing AP radiograph of the lower limbs. (B) Scannogram of the right upper limb. (C) Scannogram of the left upper limb. (D) Skull radiograph, right lateral view.

Standing AP radiograph of the lower limbs (A), scannograms of the right (B) and left (C) upper limb, and right lateral view of the skull (D) of the proband. Cortical and periosteal thickenings confined to the diaphyses are seen in all long bones. Gross bony abnormalities were not seen in the skull.

Genetic analysis of exon 4 of the TGFB1 gene.

Direct sequencing of exon 4 of the TGFB1 gene shows a heterozygous G to A transition at cDNA position +653 (R218H) detected in both the proband and his mother.

Camurati-Engelmann disease (progressive diaphyseal dysplasia) confirmed by TGFB1 gene mutation analysis

Camurati-Engelmann disease

Progressive diaphyseal dysplasia


An 8-month-old Korean boy presented at the dermatologic outpatient clinic with skin lesions on his inguinal area and knees that had been present since 7 months of age. His body weight was 8.4 kg (25-50 percentile) and height was 69.2 cm (10-25 percentile), with no evidence of growth delay. He had experienced loose stool 3-4 times per day one month prior to presentation, described as waxing and waning diarrhea with total stool amount less than 10 g/kg/day. He had been breast-fed up to 2 months of age and was being weaned at the time of visit. Despite initial treatment for presumed atopic dermatitis, the skin lesions progressed with accompanying oozing. After a trial of zinc replacement which temporarily improved the lesions, cessation of zinc supplementation led to recurrence and progression to erosion and eczematous changes. His plasma zinc level was markedly decreased at 18.8 μg/dL (normal 66-110 μg/dL). His parents are not consanguineous and have no family history of zinc deficiency.

Clinical photographs of knees, feet, perioral, and inguinal areas.

Shows erythematous and desquamated skin lesions around knees, feet, and perioral and inguinal areas in the 8-month-old boy

Genetic analysis of the SLC39A4 gene showing compound heterozygous mutations; Family study demonstrating heterozygous carrier status in parents.

Direct sequencing analyses revealed the patient was compound heterozygous for two mutations in SLC39A4: a missense mutation c.283C>T (p.Arg95Cys) and a novel splicing mutation c.1287+2T>C in the donor site of intron 7. Family study showed the parents were heterozygous carriers of each mutation

Acrodermatitis enteropathica (AE) from congenital zinc deficiency caused by mutations of the SLC39A4 gene

Acrodermatitis enteropathica

Zinc deficiency


A 17-year-old female with no previous medical history presented to the emergency room with deterioration of her general condition, fever, dyspnea, and paroxysmal severe cough. Two weeks prior to admission, she had acute pharyngitis treated with amoxicillin for 8 days. At initial presentation, she had persistent lateral cervical pain, hyperleukocytosis with a leukocyte count of 13,300/mm³ including 90% neutrophils, and elevated CRP at 450 mg/L. After 48 hours, blood cultures were positive for anaerobic Gram negative bacilli. She subsequently developed pain in both hypochondria, body temperature of 39.7°C, respiratory failure with hypotension, and awareness disorders. Physical examination at ICU admission revealed severe ARDS with PaO₂/FiO₂ ratio of 65 mmHg, bilateral alveolo-interstitial syndrome, and septic shock. Laboratory findings showed CRP of 475 mg/L and procalcitonin of 92 mg/L. The anaerobic Gram negative bacillus was identified as Fusobacterium necrophorum sensitive to penicillin.

CT scan of the thorax.

Initial thoracic CT-scan showed voluminous buildup of air and fluid in the left thorax

Chest X-ray.

CT of the thorax performed after chest tube placement and under mechanical ventilation.

Thoracic CT-scan after chest tube and under mechanical ventilation revealed large number of small abscesses of the upper and median lobes of the right lung, in addition to the abscess of the lingula and the drained pyopneumothorax

Genetic analysis of TLR5, TF, and PAI-1 genes.

Genotype findings showed functional variations in TLR5 gene (TLR5-R392 heterozygous and TLR5-F616L homozygous mutant), heterozygous TF p603 mutation, and PAI-1 4G-4G homozygous genotype associated with thrombotic events

Lemierre's syndrome with septic shock, acute respiratory distress syndrome, and partial thrombosis of the left internal jugular vein, caused by Fusobacterium necrophorum

THE - [tricho-hepato-enteric] syndrome

septic shock NOS

Acute respiratory distress syndrome

Partial thrombosis of internal jugular vein

incomplete transection of internal jugular vein


A 20-year-old male patient presented with a past medical history of bleeding tendency during the neonatal period and visited the otorhinolaryngology department for preoperative evaluation for chronic maxillary sinusitis surgery. He reported a family history of easy bruisability in his father and had conductive hearing difficulty following childhood meningitis. No laboratory abnormalities indicating coagulation defects had been detected after birth. In the preoperative evaluation, he had normal blood counts and serum chemistry test results. However, initial coagulation screening revealed prolonged prothrombin time (24.5 sec; normal 10.4-12.5 sec) and activated partial thromboplastin time (47.3 sec; normal 26.0-41.0 sec). The bleeding time was normal (2 min 30 sec; normal 1-5 min). PT and aPTT mixing test results indicated factor deficiency. Plasma fibrinogen activity examined using the Clauss method was lower than the detection limit (<25 mg/dL; normal 140-460 mg/dL), while the antigen level measured by fibrinogen ELISA was normal (437 mg/dL). He had no mutations in the FGA or FGB genes. His parents showed normal plasma fibrinogen activities (309 and 254 mg/dL respectively) and normal coagulation tests, and molecular genetic study confirmed both parents were homozygous for the wild-type allele, indicating a de novo mutation.

Laboratory coagulation test results.

Coagulation test results showed FDP <10 μg/mL (normal >40), D-dimer 0.45 μg/mL, plasminogen 130.4% (normal 75-150%), antithrombin 93.4% (normal 75-125%), vWF:Ag >200% (normal 48-151%), vWF:RCo 152% (normal 46-164%), negative anti-factor IX and VIII antibodies, protein C antigen 113% (normal 72-160%), protein C activity 80% (normal 70-130%), protein S antigen (free) 101% (normal 50-150%), and various coagulation factors within or near normal ranges: Factor II 79%, Factor V 63%, Factor VII 90%, Factor VIII 87%, Factor IX 97%, Factor X 88%, Factor XI 108%, Factor XII 58%, and Factor XIII normal.

Laboratory test, fibrinogen mixing test.

Fibrinogen mixing test results showed measured fibrinogen levels consistently lower than expected values across multiple mixing combinations, with control samples showing 250 mg/dL and 233 mg/dL, while patient sample was not checkable (NC), and various mixing combinations yielding significantly lower measured values than expected, suggesting presence of inhibitors.

(A) DNA sequencing chromatogram of FGG. (B) DNA sequencing chromatogram of FGG. (C) DNA sequencing chromatogram of FGG.

DNA sequencing chromatograms of fibrinogen γ-chain gene (FGG) showing the patient (A) with heterozygous FGG mutation c.1007T>C (p.Met336Thr), while father (B) and mother (C) samples showed normal wild-type sequences.

Congenital dysfibrinogenemia with gamma methionine-310 to threonine substitution (fibrinogen Yecheon)

congenital dysfibrinogenaemia


A 31-year-old woman underwent barium enema examination as part of a medical checkup. She had been healthy without specific complaints and had no significant past medical or family history. The patient was 161 cm in height and weighed 44 kg, appeared well, and the physical examination showed no abnormalities. Complete blood cell count and biochemical analysis of the blood for hepatic and renal function, urine analysis, and fecal occult blood test were all within normal limits. The tumor markers for CEA and CA 19-9 were also normal. No lesions were observed on the upper endoscopy and the abdominal ultrasound.

Air contrast barium enema of the colon.

Air contrast barium enema showed multiple thumbprintlike lesions ranging from 7 to 20 mm in diameter from the cecum to the hepatic flexure, mainly in the ascending colon.

(A, B) Endoscopy of the ascending colon.

Endoscopic views of a cluster of elevated lesions, with a smooth surface and gentle slope, in the ascending colon. (A, B) The overlying mucosa was intact and appeared thin, and the lesion was soft and compressible.

(A,B) Endoscopic ultrasound (EUS) images of the colon obtained with a catheter EUS probe, frequency 12 MHz.

EUS images of the colon, obtained with a catheter EUS probe (frequency 12 MHz). (A) The EUS image depicting elevated lesions as echo-free cysts (arrowheads) in the submucosal layer. (B) Some submucosal cysts had septal walls (arrows).

(A) Endoscopic biopsy of the submucosa, H&E staining, 20× magnification; inset: H&E staining, 400× magnification. (B) D2-40 immunostaining of endothelial cells of lymphatic spaces, Polymer method, 200× magnification.

Microscopic findings. (A) Endoscopic biopsy revealed submucosal cyst with occasional multinucleated cells (inset), however, there were no fat or blood cell components (H&E, ×20; inset: H&E, ×400). (B) D2-40 immunostaining showed positive reactivity (arrows) for lining endothelial cells of lymphatic spaces (Polymer method, ×200).

diffuse lymphangiomatosis


19-year-old female born full-term to non-consanguineous parents. At birth she was hypotonic with weak breathing and crying. During first month experienced respiratory failure requiring tracheotomy and mechanical ventilation. Had patent ductus arteriosus requiring surgery at age 2. At age 4, nerve stimulation showed 36% decrement of compound muscle action potential area. No repetitive CMAPs after single nerve stimulation. Serum antibodies against AChR and MuSK were negative. Had recurrent respiratory infections and scoliosis surgery at age 12. Recent exam showed normal cognition, bilateral ptosis, mild reduction of upward gaze, facial/bulbar/neck/proximal limb weakness with intact deep tendon reflexes.

(A) Electron microscopy of the neuromuscular junction. (B) Electron microscopy of the neuromuscular junction (control).

Ultrastructural findings at the NMJ. (A) An example of a NMJ from the patient demonstrating marked simplification of postsynaptic folds and underdeveloped secondary synaptic clefts (black arrows). In contrast the size of the nerve terminal (asterisk) and the width of the primary synaptic cleft (white arrow) are normal. (B) An example of a NMJ from a control showing normal secondary synaptic clefts (black arrows), nerve terminal (asterisk) and width of the primary synaptic cleft (white arrow). Calibration marks represent 1 mm.

Microelectrode recordings.

Microelectrode recordings showing: Reduced MEPP amplitude (0.43±0.05 mV vs control 1.24±0.15 mV), reduced MEPC amplitude (1.29±0.05 nA vs control 4.55±0.28 nA), normal MEPC time constant, reduced EPP quantal content at 1Hz (6.79±1.48 vs control 12.71±1.60)

Table comparing morphometric parameters of neuromuscular junctions between patient and controls.

Table 2, located on page 3 of the document, presents morphometric data comparing the neuromuscular junctions of the patient and controls. The parameters measured include the EI ratio (length of the presynaptic membrane/length of the postsynaptic membrane), the number of secondary clefts per micron of primary cleft length, nerve terminal area (µm²), and the number of synaptic vesicles per µm². The patient's EI ratio is markedly reduced (4.99 ± 0.34, n = 18) compared to controls (11.71 ± 2.36, n = 12), with a statistically significant difference (P < 0.05, Student t-test). The number of secondary clefts per primary cleft length (1.45 ± 0.1, n = 20 vs 1.79 ± 0.14, n = 12), nerve terminal area (7.28 ± 1.06 µm², n = 24 vs 7.34 ± 0.93 µm², n = 12), and synaptic vesicles per area (13.48 ± 4.62, n = 17 vs 16.77 ± 2.77, n = 12) are also reported, although only the EI ratio shows statistical significance, reflecting a marked reduction in postsynaptic membrane complexity in the patient compared to age-matched controls.

Severe congenital myasthenic syndrome (CMS) caused by two missense mutations (M605I and A727V) in the gene encoding the muscle specific receptor tyrosine kinase (MUSK)

Congenital myasthenic syndromes


32-month-old Korean boy presented with irritability and fever. Born at 40 weeks gestation with 2.9kg birth weight via normal vaginal delivery to a healthy 28-year-old G3P2 mother. Had flexion deformity of both middle fingers at birth. Showed mild general hypotonia in early infancy with weak cry and poor sucking. History of epileptic seizures 6 times since age 15 months. Developmental delay: raised head at 7 months, sat at 26 months, not yet standing. Physical exam showed prognathism, low-set ears, small crashed nose, widely spaced incisors, round back. Demonstrated repeated stereotyped behavior like hitting chin with palm. Neurologic exam showed decreased muscle tone (grade IV/IV bilaterally) but normal deep tendon reflexes, no spasticity or pathologic reflexes, normal sensory function, and no meningeal signs.

(A) Clinical photograph of the face at age 6 months. (B) Clinical photograph of the face at age 3 years.

Patient's facial features showing typical phenotype including epicanthus, midface hypoplasia, flat nasal bridge, small triangular nose with anteverted nostrils, carp-shaped mouth with full lips, and dental diastema at age 6 months (A) and 3 years (B)

(A) Peripheral blood photomicrograph of the patient. (B) Peripheral blood photomicrograph of the mother. (C) Peripheral blood photomicrograph of the eldest sister.

Photomicrograph of the peripheral blood of our case with ATR-X syndrome. It shows cells containing HbH inclusions in our patient (A), and also his mother (B) and eldest sister (C).

X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome, confirmed by presence of HbH inclusions and genetic testing showing a point mutation on the 9th exon in the ATRX gene (thymine to cytosine mutation causing Trp220Ser amino acid change)

X-linked alpha-thalassemia/mental retardation syndrome

X-linked alpha thalassaemia with mental retardation


A 35-year-old man presented to the outpatient clinic with constant pain in the right hip for 2 months that worsened while walking. He had no history of systemic disease, regular medication use, trauma, morning stiffness, weight loss, or fever. On musculoskeletal examination, range of motion of all joints was within normal limits, with the right hip showing pain at the end of range. Neurological examination was normal, and no skin lesions were detected. Complete blood count, erythrocyte sedimentation rate, rheumatoid factor, C-reactive protein, thyroid, kidney and liver function tests, serum calcium, phosphorus, magnesium, alkaline phosphatase, 25[OH] vitamin D and parathyroid hormone levels were all normal.

Pelvis radiograph, anteroposterior view.

Anteroposterior radiograph of the pelvis showing multiple, small, ovoid sclerotic lesions in both femoral heads, ileum and around the acetabulum of the pelvis, without narrowing the joint spaces

CT scan of the pelvis.

Computed tomography image showing multiple round sclerotic nodular lesions at iliac wings and sacrum which are mimicking metastases

Tc-99m bone scintigraphy. Urinary system ultrasonography.

Tc-99m bone scintigraphy revealed normal findings but incidentally showed kidney fusion anomaly, which was confirmed with urinary system ultrasonography

Anteroposterior radiograph of the hands.

Anteroposterior radiograph of the hands demonstrating multiple sclerotic foci in the distal radius and ulna, carpal, metacarpal and proximal phalangeal bones

Shoulder radiograph, anteroposterior view, bilateral.

Bilateral anteroposterior radiograph of the shoulder showing multiple radiodense sclerotic foci of the proximal humerus

Osteopoikilosis


A 48-year-old Korean woman presented with an incidentally found neck mass in July 2006. Her past history was nonspecific and she had been well without weight loss or hoarseness until admission. There was no familial history of autoimmune diseases. On thyroid sonography, a 3.0 cm solid and cystic mass was detected in the right lobe of thyroid gland. Laboratory tests showed mild leukocytosis (12,430/μL) and normal thyroid function tests (free T4: 0.9 ng/dL, T3: 119 ng/dL, TSH: 5.16 μg/mL) with increased anti-thyroglobulin antibodies (11.25 unit/mL, reference: 0-0.3). She was serologically negative to human T-cell leukemia virus type I and human immunodeficiency virus. 99Tc nuclear medicine scans showed a large cold nodule in the right lobe. Fine needle aspiration of the thyroid was performed but was not informative due to drying artifact. Staging work-up including computed tomography scan (neck, chest and abdomen), bone marrow examination, and positron emission tomography were negative, indicating stage I tumor. The excised specimen from right lobectomy measured 5.3 × 4.0 × 2.0 cm and weighed 12.7 grams, with an ill-defined firm lesion measuring 2.5 × 1.5 × 0.6 cm on the cut surface.

Histopathological image of the thyroid gland, H&E staining, ×100 and ×400 magnification.

Figure 1 is a histopathological image of the thyroid gland, stained with hematoxylin and eosin (H&E), demonstrating at low magnification (original magnification ×100) a diffuse effacement of normal thyroid architecture by lymphoid infiltrates; the inset at higher magnification (original magnification ×400) shows small atypical lymphocytes invading thyroid follicles and forming lymphoepithelial lesions.

(A) Immunohistochemical staining with CD3, peroxidase method, 400× magnification. (B) Immunohistochemical staining with CD8, peroxidase method, 400× magnification. (C) Immunohistochemical staining for cytoplasmic TIA-1, peroxidase method, 400× magnification. (D) Immunohistochemical staining with CD20, peroxidase method, 400× magnification.

Atypical small lymphocytes are stained with CD3 (Peroxidase. Original magnification ×400, A), CD8 (Peroxidase. Original magnification ×400, B), and cytoplasmic TIA-1-immunoreactivity (Peroxidase. Original magnification ×400, C). They are not stained with CD20 (Peroxidase. Original magnification ×400, D).

PCR-SSCP analysis for TCR-γ gene rearrangement, Vγ11 gene.

PCR-SSCP analysis for TCR-γ gene rearrangement showed a monoclonal rearranged band for Vγ11 gene, confirming T-cell monoclonality.

summary table of the current case of primary thyroid T-cell lymphomas with lymphoepithelial lesions, including patient age and sex, pathology type, genetic analysis method and result, presence of Hashimoto’s thyroiditis, treatment types, and clinical outcome at follow-up.

Table 1, titled "Summary of the primary thyroid T-cell lymphomas showing lymphoepithelial lesions," is a comparative summary table listing four reported cases of primary thyroid T-cell lymphomas with lymphoepithelial lesions, presenting patient age and sex, pathology type, genetic analysis method and result, presence of concomitant Hashimoto’s thyroiditis, treatment types used (including surgery, chemotherapy, and radiation), and the clinical outcome at follow-up, with all cases associated with Hashimoto’s thyroiditis and all patients being alive and disease-free at the indicated months of follow-up.

Peripheral T-cell lymphoma of TCR α/β+ inactivated cytotoxic phenotype associated with Hashimoto's thyroiditis

peripheral t-cell lymphoma unspecified

Hashimoto thyroiditis


A 40-year-old housewife woman presented with a 6-month history of increasing proximal muscle weakness that rapidly exacerbated one month prior to admission. She had been an athlete during high school and remained healthy until 3 years earlier when she developed weight loss and fatigue with diagnosis of Graves' disease and thyrotoxicosis. At that time, her serum liver enzymes (ALT 184 IU/mL, AST 94 IU/mL) were elevated without serologic evidence of viral hepatitis. After treatment with methimazole for one and a half years, remission of hyperthyroidism was achieved, but liver enzymes continued to fluctuate. Eighteen months before admission, she experienced persistent fatigue and weakness despite euthyroid status, with continued mild liver enzyme elevation. One year before admission, weight loss and myalgia developed with AST elevation to 187 IU/mL. Six months before admission, recurrent myalgia, muscle weakness, and anorexia developed. Three months prior to admission, proximal muscle weakness became evident with difficulty climbing upstairs. On examination, she appeared chronically ill but had normal vital signs. She could walk but complained of difficulty climbing upstairs or raising arms, with no specific skin lesions. Family history revealed that her two sons had been diagnosed with Duchenne muscular dystrophy in childhood and were bed-ridden, while her two brothers and parents were healthy, suggesting de novo mutation. Laboratory results showed serum CK level of 2,436 IU/mL, aldolase 11.9 IU/mL, LDH 312 IU/L, with normal TSH and free T4. Antinuclear antibody, anti-Jo-1 antibody, and anti-PM-SCL antibody were all negative.

(A) Muscle biopsy of the right vastus lateralis, low-power view. (B) Muscle biopsy of the right vastus lateralis, high-power view. (C) Muscle biopsy of the right vastus lateralis. (D, E) Muscle biopsy of the right vastus lateralis. (F) Muscle biopsy of the right vastus lateralis, dystrophin staining. (G) Muscle biopsy of the right vastus lateralis, LCA staining. (H) Muscle biopsy of the right vastus lateralis, CD68 staining.

Muscle biopsy specimen of right vastus lateralis muscle. It shows variable sized muscle fiber, fatty infiltration, perimysial fibrosis, focal inflammatory infiltrates with the suspicious area of perifascicular atrophy in low power (A) and high power view (B). Perimysial atrophy mimicking dermatomyositis are also shown (C). Also regenerating fibers with inflammatory infiltration was shown (D, E). Dystrophin staining showed variable different staining pattern from normal to interruped mosaic pattern (F). Inflammatory cells are mainly macrophage-lineages on LCA (G), CD 68 (H) special staining with rarety of CD 4 and CD 8 positive cells (not shown).

X chromosome inactivation analysis after HpaII digestion

X chromosome inactivation analysis showed highly skewed X chromosome inactivation with ratio of 19:81 after HpaII digestion compared to positive control with ratio 32:68.

Manifesting carrier of Duchenne muscular dystrophy with deletion mutation in exon 44 and highly skewed X chromosome inactivation

Duchenne muscular dystrophy


A 36-year-old woman presented with paroxysmal orbito-temporal pain as the primary symptom. Beginning in August 2009, she experienced attacks of pulsating and stabbing pain in the right orbital to temporal region with sudden onset and duration of about 30 seconds, occurring 8-12 times almost daily without particular timing or identified triggers. During attacks, she experienced photophobia and phonophobia, but denied nausea, vomiting, conjunctival injection, or tearing. Nasal congestion was the only autonomic symptom present. She was previously healthy with no familial history of migraine. Physical examination during an attack-free period revealed no swelling or reddening of scalp arteries, no herpetic rash on face or head, and no particular neurological abnormalities except hypoesthesia in the first and second right trigeminal branch territories and tinnitus. Blood tests showed no abnormality in peripheral blood or general biochemical analysis, no signs of inflammatory reaction, and no abnormalities related to collagen disease or hypothalamo-hypophyseal hormones including prolactin or thyroid hormones. Previous treatment with carbamazepine and ibuprofen showed no improvement, and ophthalmologic consultation revealed no ocular pathology.

Brain MRI, axial plane, T1-weighted, T2-weighted, and FLAIR sequences, right cerebellopontine angle.

Brain MRI in axial plane and T2 sequences showed an extraaxial lesion at the right cerebellopontine angle that was heterogeneous, hyperintense with well-defined edges. The lesion was hypointense on T1 (relative to cerebral cortex), hyperintense on T2, heterogeneous in FLAIR sequences, and did not capture contrast. The lesion displaced the VII and VIII cranial nerves and produced imprint on the brain stem and adjacent right cerebellar hemisphere without signs of infiltration. All features were suggestive of an epidermoid cyst.

Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) secondary to epidermoid cyst in the right cerebellopontine angle

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection or tearing

Epidermoid cyst


A 52-year-old female patient presented with a 1-year history of intermittent dysphagia and chest pain occurring specifically when swallowing large amounts of water. Her symptoms were localized to the lower substernal area and were accompanied by sharp, non-radiating chest pain that was relieved when the swallowed water reached the stomach. Notably, symptoms only occurred when guzzling water and not when taking small sips or eating, with no correlation to water temperature. Her past medical history was unremarkable with no family history of similar symptoms. Physical examination revealed normal body weight with no abnormalities on chest and abdominal examination. Upper gastrointestinal endoscopy performed at other hospitals showed no abnormal mucosal lesions. Barium esophagogram showed no abnormalities, and 24-hour esophageal impedance-pH monitoring revealed no pathologic regurgitation.

(A) High-resolution manometry spatio-temporal plot and concurrent 8 channel conventional manometry line plot on first swallow of 5 mL water. (B) High-resolution manometry spatio-temporal plot and concurrent 8 channel conventional manometry line plot on second swallow of 5 mL water. (C) High-resolution manometry spatio-temporal plot and concurrent 8 channel conventional manometry line plot on 13th swallow of 50 mL water. (D) High-resolution manometry spatio-temporal plot and concurrent 8 channel conventional manometry line plot on 14th swallow of 25 mL water.

High-resolution manometry (HRM) spatio-temporal plots and concurrent 8 channel conventional ma- nometry line plots (from the same recording). (A) On the first swallow of 5 mL water, HRM shows a normal peristalsis and the patient has no chest pain and dysphagia. (B) On the second swallow of 5 mL water, HRM shows no spasm. (C) Normal peristalsis with impaired deglutitive inhibition is seen (asterisk) on 13th swallow of 50 mL water. The patient felt chest pain and dysphagia with this swallow. (D) On the 14th swallow of 25 mL, she complains symptoms and HRM shows esophageal spasm and normal deglutitive inhibition.

Diffuse oesophageal spasm


A 37-year-old woman presented with a 4-month history of right facial pain and a 3-month history of progressive painful swelling beneath the right ear lobe. Physical examination revealed a soft swelling in the anteroinferior auricular area that was smooth, elastic, mobile and painful on pressure, but not fluctuant. The facial nerve function was normal and the cervical lymph node was not palpable. There were no systemic symptoms. The patient was screened for metastases, and no lung or abdomen lesions were detected.

CT scan of the right deep parotid lobe, contrast-enhanced.

CT scan shows a contrast-enhanced computed tomography revealing a well-defined soft tissue mass (40 mm × 25 mm) in the right deep parotid lobe.

Intraoperative gross photograph of the right parotid region.

Figure 2 shows an intraoperative gross photograph depicting the relationship between the tumor and the facial nerve during surgery; the image demonstrates a grayish-red collagenous mass representing the tumor (indicated by a black arrow) and direct involvement of the main stem of the facial nerve (indicated by a yellow arrow), identified in the right parotid region.

Photomicrograph of the parotid gland tumor, H&E staining, 100× magnification, specimen obtained post-parotidectomy.

Figure 3 is a photomicrograph of the tumor using hematoxylin and eosin (H&E) staining at 100x magnification, displaying myxoid areas in association with spindle cells exhibiting a pleomorphic storiform pattern; the anatomical site is the tumor arising from the parotid gland, and the specimen was obtained during pathological assessment post-parotidectomy.

(A) Immunohistochemical staining (immunoperoxidase technique), 200× magnification, ACT positive. (B) Immunohistochemical staining (immunoperoxidase technique), 200× magnification, VIM positive. (C) Immunohistochemical staining (immunoperoxidase technique), 200× magnification, Ki-67 labeling index=35%.

Positive immunohistochemical findings (immunoperoxidase technique; ×200). The tumor cells are positive for ACT (a) and VIM (b). Labeling index of Ki-67 (c) is 35%.

(A) Immunohistochemistry, immunoperoxidase technique, CD34 staining, 200× magnification. (B) Immunohistochemistry, immunoperoxidase technique, DES staining, 200× magnification. (C) Immunohistochemistry, immunoperoxidase technique, MG staining, 200× magnification. (D) Immunohistochemistry, immunoperoxidase technique, SMA staining, 200× magnification.

Negative immunohistochemical findings (immunoperoxidase technique; ×200). The tumor cells are negative for CD34 (a), DES (b), MG (c) and SMA (d).

T3N0M0 (AJCC 2002) parotid myxofibrosarcoma of low histological grade

Myxofibrosarcoma, primary site


A 37-year-old woman without known medical history presented two weeks after a tick bite with fever of 38.5°C, chills, headaches, and arthromyalgia. Physical examination findings were normal. Laboratory findings included leukopenia (3,300 leukocytes/μL, 45% polymorphonuclear cells, 37% lymphocytes), elevated liver enzymes with aspartate aminotransferase 136 IU/L and alanine aminotransferase 160 IU/L, γ-glutamyl transpeptidase 135 IU/L, alkaline phosphatase 131 IU/L, and elevated C-reactive protein at 48 mg/L. Serologic tests for Lyme disease, tick-borne encephalitis virus, tularemia, Anaplasma spp., Coxiella burnetii, and Rickettsia spp. were negative, as were blood cultures. A thin peripheral blood smear stained with May-Grünwald-Giemsa initially did not show ehrlichial morulae but retrospective examination revealed pear forms and trophozoites of intraerythrocytic parasites with parasitemia level of 0.29%. PCR testing was positive for Babesia spp., and sequencing showed 100% homology with B. divergens human strains.

Blood smear, May-Grünwald-Giemsa stain, original magnification ×1,000.

Shows two pear-shaped trophozoites of Babesia divergens in erythrocytes from the patient (original magnification ×1,000, May-Grünwald-Giemsa stain)

Babesiosis


A 10-year-old boy born at term in Morocco from non-consanguineous parents after an uncomplicated pregnancy presented with occipital headache lasting three months and height growth arrest, having grown only 1 cm in the previous 2 years while declining from the 75-90th percentile to the 25th percentile for height, and his weight increased from the 50th to 75th percentile in the last year. He denied vomiting, tiredness, or other symptoms. His past and family history were unremarkable with normal cognitive development. Physical examination revealed height 136 cm (25th percentile), weight 42 kg (75th percentile), prepubertal status, blood pressure 120/67 mmHg, pulse rate 72 bpm, and non-palpable thyroid gland. Neurological examination was normal, as were fundus oculi and visual fields. Blood tests showed full blood count, erythrocyte sedimentation rate, renal and liver function, and anti-coeliac screening were all normal. Thyroid ultrasound revealed normal thyroid size with markedly heterogeneous echo texture, hypo-echoic areas, and diffuse hypervascularization consistent with late-stage chronic thyroiditis.

(A, B) Sagittal T1-weighted MRI of the pituitary gland, pretreatment. (C-E) Coronal T1-weighted MRI of the pituitary gland, pretreatment. (B, D) Post-contrast intravenous Gadolinium administration.

Pretreatment sagittal (A, B) and coronal (C-E) T1-weighted MR images show diffuse enlagement of the pituitary gland, that extends into the suprasellar cystern with mild compression of the optic chiasm and of the posterior neurohypophyseal lobe, which keeps its normal bright signal. After intravenous Gadolinum administration (B, D) the mass demonstrate homogeneous enhancement; the pituitary stalk (E) is raised but still along the midline.

Laboratory results before therapy.

Before therapy, laboratory values showed TSH 589 mU/L (normal 0.20-4.50), Free T4 1.5 pmol/L (normal 12-22), Free T3 2.2 pmol/L (normal 3.8-8.6), IGF-I 8.6 nmol/L (normal 11.64-34.1), and PRL 1.23 nmol/L (normal 0.17-0.64).

Pituitary hyperplasia secondary to primary autoimmune hypothyroidism (chronic autoimmune Hashimoto's thyroiditis)

pituitary disease

Autoimmune hypothyroidism

Chronic autoimmune Hashimoto's thyroiditis

Autoimmune thyroiditis