A 34-year-old woman presented with hypercortisolism in the context of a metastatic pancreatic neuroendocrine tumor. She had been well until 4 years before presentation, when abdominal pain, diarrhea, and ascites developed, leading to the diagnosis of a pancreatic neuroendocrine tumor with metastases to the liver and spleen. Seven months before presentation, she was evaluated for weight gain, hyperglycemia, and changes in mood, and was found to have elevated blood levels of corticotropin and elevated salivary and urinary levels of cortisol. MRI of the head revealed a pituitary lesion measuring 1.3 cm in greatest dimension, and blood obtained from the inferior petrosal sinus identified a pituitary source of corticotropin secretion. Two transsphenoidal resections of the pituitary lesion were performed, but cortisol and corticotropin levels remained elevated. Ten days before presentation, the patient began to have confusion, urinary incontinence, and recurrent falls, with atypical impulsive behaviors. On examination at this hospital, the temperature was 36.9°C, blood pressure 152/87 mm Hg, pulse 77 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 97% while breathing ambient air. The patient was alert and oriented with a rounded face, acne, hair thinning, increased abdominal adiposity with palpable striae, and several bruises on her arms and legs.

(A) CT of the chest, axial view, lung windows. (B) CT of the chest, axial view, soft-tissue windows. (C) CT of the chest, coronal view, lung windows. (D) CT of the chest, sagittal view, lung windows.

(A) CT chest axial view with lung windows showing patchy consolidation in the right upper lobe with areas of cavitation (black arrow) and associated tree-in-bud opacities (black arrowheads). (B) CT chest axial view with soft-tissue windows showing small bilateral pleural effusions (white arrows). (C) CT chest coronal view with lung windows showing areas of cavitation (black arrows) and small bilateral pleural effusions (white arrows). (D) CT chest sagittal view with lung windows showing areas of cavitation (black arrows) and small bilateral pleural effusions (white arrow).

(A) Papanicolaou staining of a bronchoalveolar-lavage cytologic smear. (B) Culture of bronchoalveolar-lavage sample after incubation at 30°C. (C) Microscopic examination of mold colonies with lactophenol cotton-blue stain.

(A) Papanicolaou staining of a cytologic smear from bronchoalveolar-lavage (BAL) sample showing large (8 to 12 microns in diameter) thick-walled yeast cells with broad-based budding. (B) Culture of BAL sample after incubation at 30°C showing slowly growing mold colonies that became white and cottony as they matured. (C) Microscopic examination of mold colonies with lactophenol cotton-blue stain showing septate hyphae with short or long conidiophores topped by round-to-pear-shaped reproductive structures known as conidia.

Laboratory results on presentation.

Laboratory data on presentation at this hospital showed hematocrit 30.9%, hemoglobin 9.2 g/dl, white-cell count 2240 per μl with 83.5% neutrophils, 7.6% lymphocytes, platelet count 117,000 per μl, and mean corpuscular volume 78.2 fl.

Blastomycosis


A 43-year-old man from Panama was evaluated at the multidisciplinary Pulmonary Nodule Clinic because of an incidentally found pulmonary nodule. The patient was in his usual state of good health but requested imaging due to a family history of cancer. He had no fever, shortness of breath, cough, wheezing, hemoptysis, headache, vision changes, oral ulcers, nausea, vomiting, abdominal pain, arthralgias, or rash. He had a history of gastroesophageal reflux disease. The patient worked in the finance industry and had previously been a health care worker. He was born in northern South America and had moved to southern Central America 5 years earlier. He had extensive travel history throughout the Americas, Europe, Africa, Mediterranean, and Pacific Islands. He had smoked two cigarettes daily and one cigar every 3 months for 2 years. His family history included breast cancer in his mother, prostate and pancreatic cancers in his father, cancer of unknown primary origin in his maternal grandfather, and ovarian cancer in his paternal grandmother. On evaluation, he appeared well with normal vital signs and clear lungs on auscultation. Laboratory results showed hemoglobin level 12.7 g/dL (reference range 13.5-17.5), white cell count 6970/μL, and platelet count 213,000/μL. The 5-hydroxyindoleacetic acid level in a 24-hour urine specimen and the chromogranin A level in blood were normal, as were pulmonary function testing and colonoscopy results.

CT of the neck, chest, and abdomen with intravenous contrast.

CT of the neck, chest, and abdomen performed after administration of intravenous contrast material revealed a pulmonary nodule (measuring 12 mm by 13 mm) in the right middle lobe. The nodule has low attenuation and does not have calcification, macroscopic fat, or intense enhancement. Normal-sized lymph nodes are present in the right hilum, subcarinal area, and right paratracheal region.

PET-CT scan of the chest, FDG modality, right middle lobe nodule (14 mm, SUVmax=3.8), right hilar lymph node (8 mm, SUVmax=6.7).

18F-fluorodeoxyglucose (FDG)–positron-emission tomography (PET) and CT revealed FDG uptake in the right-middle-lobe nodule (measuring 14 mm in diameter), with a maximum standardized uptake value of 3.8. There was also FDG uptake in multiple normal-sized right inferior paratracheal, subcarinal, and hilar lymph nodes. A right hilar lymph node (measuring 8 mm in diameter) had a maximum standardized uptake value of 6.7.

(A) Lymph node, H&E staining. (B) Lymph node, H&E staining, higher magnification. (C) Lymph node, Grocott–Gomori methenamine silver staining.

(A) Hematoxylin and eosin staining shows necrotizing granulomatous inflammation effacing the residual lymph node. (B) At higher magnification, palisading histiocytic inflammation with rare giant cells and central necrosis is shown. (C) Grocott–Gomori methenamine silver special staining highlights numerous fungal forms that are round to ovoid, measure 3 to 4 μm in greatest dimension, and have focal narrow-based budding.

Histoplasmosis

Certain infectious or parasitic diseases


A 47-year-old female patient presented with a right adrenal mass discovered incidentally during physical examination 3 years ago. The mass was initially approximately 2.2 cm × 3.1 cm and remained untreated. A recent enhanced CT scan performed 10 days prior at a local hospital showed the right adrenal mass had increased in size to approximately 5.8 cm × 4.7 cm, suggesting a possible adrenal adenoma. The patient reported no symptoms throughout the disease course. She had no history of hypertension, diabetes, cardiac, pulmonary, or cerebrovascular diseases, denied smoking or alcohol use, and reported reduced menstrual flow. Physical examination revealed: temperature 36.5°C, pulse 72 beats/min, respiration 18 breaths/min, blood pressure 125/78 mmHg, height 163 cm, weight 63 kg, BMI 23 kg/m². The patient appeared well with clear consciousness and no signs of illness. Cardiopulmonary examination was normal. The abdomen was soft without distension, no palpable masses or tenderness, and no renal percussion pain bilaterally.

(A) Pre-operative CT plain scan, hepatorenal space. (B) Pre-operative CT, sagittal view. (C) Pre-operative enhanced CT, right adrenal gland region, lesion size approximately 5.83 cm × 5.15 cm.

(A) Pre-operative CT plain scan showing a round soft tissue mass in the hepatorenal space with heterogeneous density. (B) Pre-operative sagittal view. (C) Pre-operative enhanced CT showing heterogeneous enhancement of the lesion closely related to the right adrenal gland, measuring approximately 5.83 cm × 5.15 cm, with unclear boundaries from the upper pole of the right kidney in some sections.

Pre-operative adrenal ultrasound with contrast, right adrenal region.

Pre-operative adrenal ultrasound contrast imaging showing a solid mass in the right adrenal region with unclear boundaries from the renal parenchyma. Based on contrast-enhanced ultrasound features, an adrenal tumor (likely malignant) was considered.

Adrenal tumor pathological examination, H&E staining, 400× magnification, tumor size 5.2 cm × 4.0 cm × 2.2 cm.

Pathological examination of the adrenal tumor (HE staining, 400× magnification) showing tumor cells arranged in nests and sheets with vascular-rich stroma, acidophilic cytoplasm, mitotic figures >5/50HPF in hot spots, pathological mitotic figures, tumor necrosis, and capsular invasion. Tumor size: 5.2 cm × 4.0 cm × 2.2 cm.

Adrenocortical carcinoma


A 12-year-old male patient presented with progressive weakness of all four limbs for over 1 day. He had a history of back trauma 6 hours before symptom onset when his shoulder and back hit a table corner while standing, causing severe pain. The patient first developed left hand grip weakness, which progressively evolved to right leg weakness, right hand grip weakness, and bilateral lower limb weakness, accompanied by urinary and fecal retention. He was admitted to the pediatric ICU with suspected spinal cord injury. The patient had normal birth and developmental history with no clear history of infection. On physical examination, he was conscious but in poor spirits with normal communication. A scratch scab was visible on the left shoulder near the midline. Upper limb muscle strength was grade 2 with reduced muscle tone, lower limb muscle strength was grade 0 with absent muscle tone. Superficial sensation and reflexes were absent below the T4 level, while deep sensation was preserved. All limb tendon reflexes could not be elicited, bilateral abdominal and cremasteric reflexes were absent, and pathological signs were negative.

Thoracic spine vascular angiography performed on day 5 of illness.

Thoracic spine vascular angiography performed on day 5 of illness showing abnormal vessels on the right side of the lower thoracic segment (indicated in circle), suggesting high possibility of spinal vascular malformation

(A) Cervical and thoracic spine MRI, sagittal T2-weighted sequence, performed on day 12 of illness. (B) Cervical and thoracic spine MRI, sagittal T2-weighted sequence, performed on day 61 of illness.

Cervical and thoracic spine MR sagittal T2 sequence. (A) Day 12 of illness showing strip-like high signal intensity from C5-T2 level within the spinal cord. (B) Day 61 of illness showing linear high signal from C5-T1 level within the spinal cord, appearing somewhat reduced compared to previous

(A) Cervical and thoracic spine MRI, axial T2-weighted sequence, performed on day 12 of illness. (B) Cervical and thoracic spine MRI, axial T2-weighted sequence, performed on day 61 of illness.

Cervical and thoracic spine MR axial T2 sequence. (A) Day 12 of illness showing typical 'owl's eye sign'. (B) Day 61 of illness, lesion appears somewhat reduced

Acute venous infarction of the spinal cord


A 38-year-old man was evaluated at the cardiology clinic because of exertional chest discomfort. He had been a competitive athlete in the past and had remained an avid runner. Approximately 15 years before the current evaluation, while he was running, he had episodes of flushing with diffuse cutaneous swelling involving the face, lips, hands, and trunk, along with hives on the abdomen and legs and associated dyspnea. The first episode occurred in autumn and the second episode the following summer. After the second episode, he lost consciousness while sitting on a bench. The next day, he was evaluated at an urgent care center. A Holter monitor was placed, and a transthoracic echocardiogram (TTE) was reportedly normal. The patient consulted with an allergist, who made a diagnosis of food-related exercise-induced anaphylaxis with reactions to soybeans, chickpeas, and tahini, on the basis of the foods he had eaten before these episodes and the results of radioallergosorbent testing. An epinephrine autoinjector was prescribed for use during future episodes, but the anaphylaxis symptoms did not recur. Approximately 4 months before the current evaluation, during a routine 5-mile jog, the patient had a new sensation that he described as 'my heart beating out of my chest.' He rested, and the symptom subsided; he completed his run. One month later, during a bicycle ride, he had 'crampy' discomfort in the anterior chest, which abated when he stopped cycling. Two weeks before the current evaluation, during a jog of several miles, he had cramping pain in the anterior chest on the left side that gradually escalated over a 5-minute period. He started walking, and the pain abated; he ran for an additional 20 minutes without a recurrence of pain. He sought an evaluation in the cardiology clinic of this hospital to determine the cause of his symptoms and the safety of continued vigorous exercise. On evaluation in the cardiology clinic, a review of systems was negative for dyspnea, recent syncope, orthopnea, edema, cough, hemoptysis, and recent allergic symptoms. The patient ran or cycled four times per week and had previously completed a marathon. His medical history included attention deficit–hyperactivity disorder. Five years earlier, an episode of syncope had occurred in the context of multiple episodes of nonbloody diarrhea, abdominal discomfort, and chills. His surgical history included two colonic polypectomies, one 6 years before this evaluation and the other 1 month before this evaluation; pathological examination of the polyps had revealed lymphoid aggregates and hyperplastic polyps. The patient took no medications and reported no adverse reactions to medications. The patient worked in the financial sector and lived with his wife and children. He did not use tobacco, alcohol, or other substances. Multiple maternal relatives had had colon cancer, and an older brother had had colonic polyps removed in his fourth decade of life. There was a family history of hypertension. On examination, the blood pressure was 122/84 mm Hg (measured in both arms), the heart rate 54 beats per minute, and the oxygen saturation 99% while the patient was breathing ambient air. There were mild expiratory wheezes; the remainder of the examination was normal. An electrocardiogram (ECG) showed sinus bradycardia and anterior T-wave abnormalities, findings that had been observed on tracings obtained 5 years earlier during an evaluation for presyncope; a TTE obtained at that time had been normal. Sinus bradycardia and anterior T-wave abnormalities had not been observed on tracings obtained 15 years earlier. The white-cell count and platelet count were normal, as were blood levels of hemoglobin, electrolytes, calcium, and thyrotropin and results of renal-function tests. The high-sensitivity troponin level was 10 ng per liter (reference range, 0 to 14). Plasma metanephrines were undetectable, and the normetanephrine level was normal. The next day, a TTE showed no abnormalities of cardiac chamber size and function and no evidence of valvular dysfunction. An ambulatory patch heart monitor, applied to evaluate cardiac rhythm over a 2-week period, revealed sinus rhythm without arrhythmia. A cardiopulmonary exercise stress test was performed; the patient exercised for 19 minutes 17 seconds according to a treadmill protocol that increased incrementally to maximal effort with a respiratory exchange ratio of 1.12 and a maximum heart rate of 181 beats per minute (99% of the age-predicted maximum). At peak effort, the stress test did not reproduce symptoms, and he stopped because of leg fatigue. An ECG showed 0.5-mm horizontal ST-segment depression in leads III, aVF, V3, and V6, along with isolated premature ventricular contractions. The ventilatory efficiency was normal.

(A) Electrocardiogram obtained 15 years before the current presentation. (B) Electrocardiogram obtained 5 years before the current presentation. (C) Electrocardiogram obtained at the time of the current presentation. (D) Transthoracic echocardiogram, parasternal short-axis view of the heart. (E) Transthoracic echocardiogram. (F) Transthoracic echocardiogram.

(A) Electrocardiogram obtained 15 years before the current presentation. (B) Electrocardiogram obtained 5 years before the current presentation. (C) Electrocardiogram obtained at the time of the current presentation. Anterior T-wave abnormalities from V1 to V3 are present on the ECG obtained at the time of the current presentation and on the ECG obtained 5 years earlier but not on the ECG obtained 15 years earlier. (D) Transthoracic echocardiogram obtained in the parasternal short-axis view of the heart showing normal origins of the left coronary artery (arrowheads). (E) Transthoracic echocardiogram showing normal origin of the right coronary artery (arrowheads). (F) Transthoracic echocardiogram showing another vessel anterior to the aorta with an unclear origin (arrows).

(A) Coronary CT angiogram, axial view, arterial phase, attenuation level of 218 Hounsfield units. (B) Pre-contrast CT, attenuation level of 50 Hounsfield units. (C) Delayed phase CT, attenuation level of 111 Hounsfield units. (D) CT, sagittal view. (E) Volume-rendered CT image. (F) 123I-metaiodobenzylguanidine (123I-MIBG) single-photon-emission CT (SPECT).

(A) Coronary CT angiogram, axial view during the arterial phase, showing an intrapericardial mass (arrow), anterior to the heart and within the aortopulmonary groove, with heterogeneous enhancement and an attenuation level of 218 Hounsfield units (HU). (B) Pre-contrast CT image showing the mass with an attenuation level of 50 HU (arrow). (C) Delayed phase CT image showing the mass with an attenuation level of 111 HU (arrow). (D) Sagittal CT image showing that the proximal right coronary artery is encased by the mass (arrow). (E) Volume-rendered image showing the relationship of the mass (in purple) with the chambers on the right side (in blue) and on the left side (in red) and with the coronary arteries; there is evidence of narrowing of the left anterior descending coronary artery (black arrow), prominent venous drainage (white arrow), and feeding vessels arising from the right coronary artery (arrowheads). (F) 123I-metaiodobenzylguanidine (123I-MIBG) single-photon-emission CT (SPECT) showing moderate tracer uptake in the mass (arrow).

(A) Cardiac MRI, T1-weighted sequence. (B) Cardiac MRI, T2-weighted sequence. (C) Cardiac MRI, first-pass perfusion after gadolinium-based contrast administration.

(A) Cardiac MRI, T1-weighted image showing the heterogeneous mass is predominantly isointense (arrow). (B) T2-weighted image showing the mass is hyperintense with punctate foci of hypointensity, which results in a 'salt and pepper' appearance (arrow). (C) First-pass perfusion image obtained after the administration of gadolinium-based contrast material showing enhancement is intense and brisk (arrow).

Cardiac paraganglioma with a germline mutation in the gene encoding succinate dehydrogenase subunit C (SDHC)

paraganglioma NOS

Germline mutation in succinate dehydrogenase subunit C

C syndrome


A 72-year-old man presented with a history of gastroesophageal reflux disease that had been well controlled with daily omeprazole therapy until 11 months before admission, when heartburn recurred despite treatment. He also noticed nausea after eating and early satiation. During the next 9 months, symptoms slowly increased in severity, and he adjusted his diet from solid food to soft solid food. Two months before admission, he sought evaluation at the gastroenterology clinic of another hospital. The glycated hemoglobin level was 6.1%. He had not eaten food for 24 hours before esophagogastroduodenoscopy (EGD), but the stomach could not be adequately visualized because there was a large amount of residual food; no intraluminal masses were seen. During the 2 months after evaluation, he adjusted his diet from soft solid food to blended solid food. Two weeks before admission, he adjusted his diet to primarily liquid food, such as nutritional supplement drinks, protein shakes, and ice cream. When he was no longer able to drink liquids, he sought evaluation at the emergency department. On examination, the temperature was 37.7°C, blood pressure 128/76 mm Hg, pulse 105 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 97% while breathing ambient air. He was thin and had a nasogastric tube in place. The abdomen was flat, soft, and nondistended, with mild tenderness in the epigastrium on palpation.

(A) CT scan with intravenous contrast, axial view. (B) CT scan with intravenous contrast, axial view. (C) CT scan with intravenous contrast, coronal view.

(A) CT scan performed after administration of intravenous contrast material, axial view, shows wall thickening at the antrum (arrowhead) and secondary distention of the stomach (arrow). (B) Additional axial image shows circumferential wall thickening at the incisura and pyloric canal (arrowhead). (C) Coronal image shows the antral thickening (arrowhead) and gastric distention (arrow).

Laboratory test results on transfer.

Laboratory test results on transfer showed sodium 138 mmol/liter, potassium 3.4 mmol/liter, chloride 93 mmol/liter, carbon dioxide 33 mmol/liter, urea nitrogen 27 mg/dl, creatinine 0.93 mg/dl, glucose 110 mg/dl, calcium 9.6 mg/dl, magnesium 2.1 mg/dl, phosphorus 3.3 mg/dl, prealbumin 22 mg/dl, albumin 3.8 g/dl, globulin 3.6 g/dl, total protein 7.4 g/dl, direct bilirubin 0.2 mg/dl, total bilirubin 0.5 mg/dl, alanine aminotransferase 25 U/liter, aspartate aminotransferase 19 U/liter, alkaline phosphatase 86 U/liter, glycated hemoglobin 6.7%, hemoglobin 14.4 g/dl, hematocrit 42.8%, platelet count 197,000 per μl, white-cell count 7890 per μl.

(A) Endoscopic image of the stomach, prepyloric region. (B) Endoscopic ultrasound of the stomach, wall thickness ≤15 mm, involving deep mucosal, submucosal, and muscularis propria layers.

(A) Endoscopic image of the stomach shows diffuse nodular mucosa in the prepyloric region. (B) Endoscopic ultrasound image shows patchy wall thickening (≤15 mm) involving the deep mucosal, submucosal, and muscularis propria layers.

(A) Hematoxylin and eosin staining of gastric biopsy specimen. (B) Cytokeratin AE1-AE3 and CAM5.2 staining of peritoneal biopsy specimen. (C) Hematoxylin and eosin staining of gastric resection specimen. (D) Hematoxylin and eosin staining of unspecified tissue.

(A) Hematoxylin and eosin staining of biopsy specimen from the stomach obtained during endoscopic ultrasonography shows fragments of muscularis propria with an associated infiltrative, poorly differentiated adenocarcinoma. (B) Cytokeratin AE1-AE3 and CAM5.2 staining of biopsy specimen from the peritoneum obtained during laparoscopic evaluation shows infiltrative, poorly cohesive tumor cells in a background of fibroadipose tissue with marked fibrosis and inflammation. (C) Hematoxylin and eosin staining of the gastric-resection specimen shows scattered clusters of poorly differentiated adenocarcinoma. (D) Hematoxylin and eosin staining shows extension to the subserosa and serosa.

Linitis plastica (invasive gastric adenocarcinoma)

Linitis plastica of stomach

Adenocarcinoma of stomach


A 38-year-old female patient presented with status epilepticus 2 hours before admission, manifesting as generalized tonic-clonic seizures, loss of consciousness, upward eye deviation, and trismus with urinary and fecal incontinence. She had her first seizure at age 17, with poor control despite intermittent medication, experiencing 10 seizures in the past 2 years. She had recurrent stroke-like episodes for 5 years, cognitive impairment for over 10 years, and cerebellar atrophy for over 10 years. On examination, she was in a light coma state (under diazepam infusion), with pupils equal and round at 2.0 mm diameter with preserved light reflexes, negative doll's eye test, symmetric nasolabial folds, and uncooperative for tongue protrusion. Muscle strength examination was uncooperative, with decreased muscle tone and tendon reflexes, negative bilateral pathological signs. Sensory and coordination examinations were uncooperative. Neck was soft with negative Kernig's sign. Family history revealed her mother was short with kyphosis and hearing loss, developing cognitive decline in middle age and dying of stroke at 60. The patient's elder daughter (17 years old) had mild cognitive impairment and mild visual impairment, while her younger daughter (13 years old) had intellectual disability and could not attend school normally.

(A) Optical coherence tomography of the right eye, performed on March 28, 2024. (B) Optical coherence tomography of the left eye, performed on March 28, 2024.

Optical coherence tomography performed on March 28, 2024. (A) Right eye showing mild atrophy of outer retinal layer. (B) Left eye showing no obvious abnormalities.

(A-L) Brain MRI performed 1 day after onset on March 18: (A) T1FLAIR sequence, left frontal and parietal lobes. (B) T1FLAIR sequence, left temporal and occipital lobes. (C) Cerebellum, structural MRI. (D) Magnetic resonance angiography (MRA). (E) T2-weighted sequence, left frontoparietal region. (F) T2-weighted sequence, left temporal and occipital lobes. (G) T2FLAIR sequence, left frontal and bilateral parietal lobes. (H) T2FLAIR sequence, left temporal and bilateral occipital lobes. (I) DWI sequence, left parietal and bilateral temporal lobes. (J) ADC map, left frontal and parietal lobes. (K) DWI sequence, left occipital and bilateral temporal lobes. (L) ADC map, left temporal and occipital lobes. (M-P) Brain MRI performed 1 month after onset on April 18: (M) DWI sequence, left parietal lobe. (N) ADC map, left frontal and parietal lobes. (O) DWI sequence, left occipital lobe. (P) ADC map, left occipital and temporal lobes.

Brain MRI findings. (A-L) Performed 1 day after onset on March 18. (A) Left frontal and parietal lobes showing T1FLAIR low signal. (B) Left temporal and occipital lobes showing T1FLAIR low signal. (C) Cerebellar atrophy with widened sulci. (D) MRA showing fenestration deformity of left anterior cerebral artery and slightly thin right vertebral artery. (E) Left frontoparietal T2 patchy high signal. (F) Left temporal and occipital T2 high signal. (G) Left frontal and bilateral parietal T2FLAIR high signal. (H) Left temporal and bilateral occipital T2FLAIR high signal. (I) Left parietal DWI high signal, bilateral temporal lobes without obvious high signal. (J) Left frontal and parietal ADC high signal. (K) Left occipital DWI high signal, bilateral temporal lobes without obvious high signal. (L) Left temporal and occipital ADC high signal. (M-P) Performed 1 month after onset on April 18. (M) Left parietal DWI high signal disappeared compared to previous. (N) Left frontal and parietal ADC high signal disappeared compared to previous. (O) Left occipital DWI high signal disappeared compared to previous. (P) Left occipital and temporal ADC high signal disappeared compared to previous.

Brain MR spectroscopy performed on March 28, 2024, left temporal lobe lesion area. Shows elevated Cho peak, slightly decreased NAA peak, decreased NAA/Cr ratio, elevated Cho/Cr ratio, elevated Glu peak, slightly elevated MI peak, presence of Lip and Lac peaks with inverted double Lac peak.

(A) Genetic analysis. (B) Genetic analysis. (C) Genetic analysis.

Genetic testing results. (A) Patient showing T10191C mutation. (B) Patient's younger daughter without this mutation. (C) Patient's elder daughter with T10191C mutation.

(A, E) Muscle biopsy, H&E staining, 400× magnification. (B, F) Muscle biopsy, COX staining, 400× magnification. (C, G) Muscle biopsy, modified Gomori staining, 400× magnification. (D, H) Muscle biopsy, SDH staining, 400× magnification.

Muscle pathology findings. (A) Mild variation in muscle fiber size, small fibers elongated, no ragged red fibers, HE×400. (B) No enzyme activity deficient fibers, COX staining×400. (C) No ragged red fibers, modified Gomori stain×400. (D) Atypical SSV (strongly SDH reactive blood vessels), SDH staining×400. (E) Elder daughter's muscle fibers with mild size variation, small fibers elongated, no ragged red fibers, HE×400. (F) Elder daughter without enzyme activity deficient fibers, COX staining×400. (G) Elder daughter without ragged red fibers, modified Gomori stain×400. (H) Elder daughter showing atypical SSV, SDH staining×400.

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) caused by mitochondrial gene T10191C mutation

Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes

lactic acidosis

Endocrine, nutritional or metabolic diseases


An 82-year-old woman was admitted to the hospital because of difficulty walking, falls, and cognitive decline. The patient had been in her usual state of health, living independently with her husband and participating in a walking club, until 8 months before the current presentation, when generalized weakness developed. She began to walk more slowly and was no longer active with her walking club; she felt limited by pain in her feet. Five months before the current presentation, the patient began to have difficulty with climbing stairs and with rising from a seated position. Four months before the current presentation, she began to have falls at home. Three months before the current presentation, the patient fell and her husband was not able to lift her up from the floor. Emergency medical services were called, and she was admitted to another hospital for evaluation. During that hospitalization, a urinary tract infection and hyponatremia were diagnosed. The urinary tract infection was treated with trimethoprim–sulfamethoxazole. The hyponatremia was attributed to the syndrome of inappropriate antidiuretic hormone and was treated with fluid restriction and salt tablets. Eight weeks before the current presentation, the patient was discharged from the rehabilitation facility, and she and her husband moved to an assisted-living facility. Fatigue developed, along with loss of appetite and a reduced intake of food. The patient began to need one-person assistance to walk. She also noticed that she had been having difficulty with math associated with the family finances, which she had always done with ease. Her family noticed that she had been having trouble carrying on a conversation and that she seemed less attentive than usual. Two weeks before the current presentation, the patient had another fall and was admitted to a second hospital, where she was found to have hyponatremia, hypokalemia, and hypomagnesemia. After discharge from the hospital, the patient had a progressive loss of independence. She noted worsening generalized weakness and low back pain, and she needed two-person assistance to walk. Her family brought her to the emergency department of this hospital for evaluation. In the emergency department, the patient reported urinary incontinence, which she attributed to not having enough time to get to the toilet because of her physical limitations with movement; she had no dysuria or urinary urgency. There was no fecal incontinence. The patient had a history of hypertension, dyslipidemia, and hypothyroidism. Surgical history included hemiarthroplasty of the right shoulder and arthroplasty of both knees. She had chronic pain in the shoulders, knees, wrists, and hands, which had been attributed to osteoarthritis. On examination, the temporal temperature was 36.6°C, the heart rate 88 beats per minute, the blood pressure 108/54 mm Hg, the respiratory rate 17 breaths per minute, and the oxygen saturation 100% while the patient was breathing ambient air. The body-mass index was 25.8. She appeared tired but was oriented to person and place. Pitting edema was present in the legs to the level of the mid-shins. A detailed strength examination was limited because of pain, with minimal movement of the shoulders, wrists, fingers, ankles, and knees. The patient could wiggle her toes but had weak plantar flexion and dorsiflexion of both feet. She could easily wiggle her fingers and lift her arms against gravity at the elbows. Light touch of the dorsum of the right hand caused pain, as did light touch of the right knee and the soles of both feet. Recognition of sensation to light touch and to vibration were normal. Cerebellar testing, gait testing, and reflex testing were limited by severe pain with movement and touch. The patient had symmetric erythema, swelling, and tenderness of the metacarpophalangeal and proximal interphalangeal joints. She had limited range of motion in the wrists and elbows, along with symmetric tenderness in the subtalar joints and swelling and pain with squeezing of the metatarsophalangeal joints.

Laboratory results on admission. Urinalysis.

Laboratory data on admission showed hemoglobin 9.2 g/dl, hematocrit 28.7%, mean corpuscular volume 73 fl, white-cell count 7470 per μl, platelet count 481,000 per μl, erythrocyte sedimentation rate 28 mm/hr, C-reactive protein 143.8 mg/liter, sodium 124 mmol/liter, potassium 4.3 mmol/liter, chloride 90 mmol/liter, carbon dioxide 23 mmol/liter, urea nitrogen 14 mg/dl, creatinine 0.56 mg/dl, glucose 118 mg/dl, calcium 8.4 mg/dl, magnesium 1.7 mg/dl, total protein 5.1 g/dl, albumin 2.6 g/dl, osmolality 255 mOsm/kg of water. Urinalysis showed 3+ leukocyte esterase, presence of nitrates, and more than 100 white cells per high-power field.

CT of the head, performed without intravenous contrast.

CT of the head, performed without the administration of intravenous contrast material, revealed moderate ventriculomegaly that was out of proportion to the enlargement of the cerebral sulci.

Laboratory results from hospital day 6.

Additional laboratory data on hospital day 6 showed antinuclear antibody positive at 1:1280 with a speckled pattern, anti-dsDNA antibody positive at 1:20, rheumatoid factor 636 IU/ml, anti–cyclic citrullinated peptide antibody 317 IU/ml, C3 76 mg/dl, C4 <6 mg/dl, cryoglobulins not present, antineutrophil cytoplasmic antibody negative.

(A) Sural nerve biopsy, H&E staining. (B) Sural nerve biopsy, H&E staining. (C) Sural nerve biopsy, H&E staining. (D) Sural nerve biopsy, toluidine blue staining. (E) Muscle biopsy, H&E staining. (F) Muscle biopsy, immunohistochemical staining for fast myosin heavy chain.

(A) Hematoxylin and eosin staining of sural nerve biopsy specimen shows a dense inflammatory infiltrate involving small and medium-sized blood vessels. (B) Focal fibrinoid necrosis is present. (C) The nerve fascicles contain numerous myelin ovoids with rare intact myelinated axons. (D) Toluidine blue staining of the sural nerve specimen shows severe loss of myelinated axons. (E) Hematoxylin and eosin staining of muscle biopsy specimen shows moderate neurogenic changes, including scattered angulated atrophic fibers. (F) Immunohistochemical staining of the muscle specimen for fast myosin heavy chain shows extensive fiber-type grouping.

(A) Radiograph of the hands. (B) Radiograph of the wrists and proximal phalanges of the hands. (C) Radiograph of the feet. (D) Radiograph of the first metatarsophalangeal joints.

(A) Radiograph of the hands shows periarticular osteopenia — decreased mineralization that is more pronounced at the carpal, metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints than at the shafts of the metacarpal and phalangeal bones. (B) Enlarged view of the wrists and proximal phalanges of the hands shows representative erosions of the radiocarpal joints and distal ulnas and the metacarpophalangeal joints. (C) Radiograph of the feet shows periarticular osteopenia — decreased mineralization that is more pronounced at the tarsal and metatarsophalangeal joints than at the metatarsal shafts. (D) Enlarged view of the first metatarsophalangeal joints shows numerous erosions.

Rheumatoid arthritis with vasculitis causing a confluent mononeuritis multiplex

Rheumatoid arthritis

Diseases of the musculoskeletal system or connective tissue

Vasculitis

Mononeuritis multiplex

Orthopedic and connective tissue disorders


A 72-year-old Korean woman presented in February 2003 with recent enlargement of inguinal lymph nodes associated with fatigue and weight loss of 2 kg over 3 months. She had a medical history significant for microscopic hematuria 20 years prior, hyperthyroidism 15 years prior, iron deficiency anemia refractory to iron supplementation discovered in February 2001, and polyclonal gammopathy. She was diagnosed with primary Sjögren's syndrome in October 2001 based on 30 years of ocular and oral sicca symptoms, positive Schirmer test, salivary gland involvement on salivary scintigraphy, FANA positivity (1:160+, speckled pattern), and rheumatoid factor positivity (26.7 IU/mL), though anti-SSA/SSB were negative. Physical examination revealed a cachexic woman with pale conjunctiva and multiple inguinal lymph node enlargement. Laboratory investigations showed hemoglobin 7.9 g/dL, white cell count 6,800/μL, platelet count 399,000/μL, MCV 73.3 fL, ESR 56 mm/hr, C-reactive protein 13.0 mg/dL, total protein 10 g/dL with globulin 7.1 g/dL, and elevated β2-microglobulin at 3,490 ng/dL. Serum electrophoresis demonstrated a polyclonal pattern with increased IgG (4,610 mg/dL) and IgA (681 mg/dL).

Bone marrow biopsy, H&E staining, 400× magnification.

Bone marrow biopsy revealed normocellular marrow with multifocal increase of plasma cells that were normal in morphology and maturation (H&E stain, ×400).

Lymph node biopsy, H&E staining, 400× magnification.

Lymph node biopsy revealed extensive infiltration of plasma cells showing profound germinal center reaction. The lymph node plasma cells were normal in morphology and maturation, and immunostaining stained equally for both kappa and lambda light chains (H&E stain, ×400).

Immunofluorescence staining of CD27 on CD19+ peripheral blood B cells revealed marked increase of CD19+/CD27high plasma cells (24.8%) and significant reduction of CD19+/CD27+ memory B cells (16.1%), with naive B cells comprising 59.0%.

Reactive plasmacytosis in association with primary Sjögren's syndrome

Plasmacytosis

Symptoms, signs or clinical findings, not elsewhere classified

Primary Sjögren syndrome