An 85-year-old obese white female presented to the emergency department with a 2-week history of constipation accompanied by intermittent crampy abdominal pain. She denied nausea, vomiting, fever, weight loss, or blood in stools. She had a remote history of endometriosis requiring total abdominal hysterectomy with bilateral salpingo-oophorectomy and had been taking estrogen 0.625 mg daily for 40 years. She had no known family history of cancer. On examination, she was not in distress with stable vital signs, BMI of 30.2 (weight 75 kg, height 62 inches), non-tender abdomen with a soft, large, palpable anterior pelvic mass. Pelvic examination revealed no vaginal lesions, bleeding, or discharge, and no signs of fecal impaction or rectal bleeding.

CT of the abdomen and pelvis.

CT scan of the abdomen and pelvis revealed a 13 × 10 × 11-cm solid and cystic mass in close proximity with the sigmoid colon causing obstruction. The uterus and ovaries were not visualized and there were no noticeable signs of metastasis.

Colonic histopathological section, CD10 immunohistochemistry.

Figure 2 is a histopathological section from the colonic segment showing areas composed of sieve-like channels with abortive glandular arrangements and round-cell stroma, representing the endometrial stroma-like element of the tumor; the specimen was stained for CD10 immunohistochemistry, which highlights this stroma, and demonstrates the morphological biphasic pattern characteristic of Müllerian carcinosarcoma arising from intestinal endometriosis, as described in the text on page 1 and visually depicted in the image on page 1.

a histopathological image showing section of the bowel wall

Figure 3 is a histopathological image found on page 2, showing a section of the bowel wall containing foci of endometriosis intimately associated with a malignant Müllerian carcinosarcoma. The image demonstrates the anatomical site as the bowel wall, the analysis modality as histology, and likely employs hematoxylin and eosin (H&E) staining, as is standard for such diagnostic pathology slides, although the specific stain and magnification are not explicitly stated in the text. The figure highlights the presence of endometriotic tissue within the bowel wall adjacent to or involved by the malignant tumor, supporting the diagnosis of Müllerian carcinosarcoma arising from intestinal endometriosis.

Carcinosarcoma of unspecified site

Endometriosis of intestine


A 19-year-old woman presented with respiratory failure. Three weeks before presentation, she developed pain in the right shoulder and right flank and was evaluated at another hospital where testing for kidney stones and appendicitis was reportedly negative. Two weeks before presentation, dyspnea with exertion and nonproductive cough developed. She went on an 8-day vacation cruise with her family, during which her symptoms progressively worsened, preventing her from participating in activities. By the end of the cruise, she had severe dyspnea with walking and required a wheelchair. Upon presentation to the emergency department, she appeared ill with increased work of breathing, temporal temperature 37.1°C, heart rate 132 beats per minute, blood pressure 133/47 mm Hg, respiratory rate more than 40 breaths per minute, and oxygen saturation 88% on ambient air. A murmur was heard on cardiac examination. She had intermittent back pain beginning 6 months before presentation, asymptomatic SARS-CoV-2 infection 2 months before presentation, and a dental cleaning 5 weeks before presentation. During the cruise, she had two episodes of diarrhea without fever. She had visible chest pulsations during the 2 weeks before presentation and labored breathing while sleeping. Medical history included anxiety and anemia. She took supplemental iron and had no known drug allergies.

Laboratory test results on presentation at another hospital. And laboratory test results and arterial blood gas analysis on presentation at this hospital.

Laboratory data on presentation at other hospital showed hemoglobin 9.1 g/dl, hematocrit 31.5%, mean corpuscular volume 66.7 fl, white-cell count 15,540 per μl with 72% neutrophils, platelet count 745,000 per μl, albumin 2.9 g/dl, lactate 0.2 mmol/liter, and N-terminal pro-B-type natriuretic peptide 24,913 pg per milliliter. On presentation at this hospital: hemoglobin 8.4 g/dl, hematocrit 28.4%, mean corpuscular volume 66.8 fl, white-cell count 15,690 per μl, platelet count 620,000 per μl, albumin 3.1 g/dl, lactate 1.3 mmol/liter, erythrocyte sedimentation rate 77 mm/hr, C-reactive protein 147.8 mg/liter. Arterial blood gases on fraction of inspired oxygen 0.70 showed pH 7.51, partial pressure of carbon dioxide 31 mm Hg, partial pressure of oxygen 206 mm Hg.

(A) ECG. (B) Transthoracic echocardiography, parasternal long-axis view. (C) Transthoracic echocardiography, parasternal short-axis view. (D) Transthoracic echocardiography, apical five-chamber view. (E) Transthoracic echocardiography, suprasternal notch view, color Doppler. (F) Transthoracic echocardiography, continuous-wave Doppler tracing.

(A) ECG showed sinus tachycardia, borderline rightward axis, poor R-wave progression in leads V1 through V4, and nonspecific ST-segment and T-wave abnormalities. (B) Transthoracic echocardiography parasternal long-axis view showed dilated left ventricle and thickening of aortic-root walls. (C) Parasternal short-axis view showed tricuspid aortic valve and thickening of aortic-root walls. (D) Apical five-chamber view showed very large jet of severe aortic regurgitation. (E) Suprasternal notch view with color Doppler showed holodiastolic flow reversal in descending thoracic aorta. (F) Continuous-wave Doppler tracing confirmed holodiastolic flow reversal.

(A) CT angiography, curved planar reformatted image, arterial phase, descending aorta. (B-C) CT angiography, maximum-intensity-projection images, aortic arch and innominate artery, bilateral common carotid arteries, and right renal artery. (D-F) CT angiography, axial images, arterial phase, aortic root and ascending aorta, aortic arch vessels. (G) CT angiography, axial image, venous phase, abdominal aorta.

(A) CT angiography curved planar reformatted image during arterial phase showed irregular contour of descending aorta. (B-C) Maximum-intensity-projection images showed luminal narrowing of partially visualized vessels of aortic arch including mild focal stenosis of innominate artery, diffuse narrowing of proximal bilateral common carotid arteries (severe on right, mild to moderate on left), and severe focal stenosis in right renal artery. (D-F) Axial images during arterial phase showed circumferential wall thickening in aorta at root and ascending segment, and in partially visualized proximal vessels of aortic arch. (G) Axial image during venous phase showed circumferential wall thickening in abdominal aorta with corresponding mural enhancement.

Takayasu arteritis

Diseases of the musculoskeletal system or connective tissue

Cardiovascular and respiratory disorders


A 15-year-old girl presented with lower abdominal pain that began 6 weeks prior along the midline, was sharp and crampy, increased with movement, and decreased with lying down. The pain shifted from midline to the right side within 24 hours. On examination at the initial presentation, she had mild bilateral lower abdominal tenderness (greater on the right), a soft nondistended abdomen, normal bowel sounds, and no rebound or guarding. Laboratory findings showed leukocytosis (white-cell count 14,270 per microliter), anemia (hemoglobin 10.9 g/dl), and elevated C-reactive protein (5.9 mg/liter). The patient was discharged with a presumptive diagnosis of ruptured ovarian cyst. Six weeks later, she returned with recurrent similar abdominal pain and inability to attend school. She reported increased waist size over 2 weeks and difficulty fitting into pants. She had no fever, chills, night sweats, nausea, vomiting, anorexia, dysuria, hematuria, frequent urination, or vaginal bleeding/discharge. She had no notable medical history, took no medications, had no allergies, and had normal growth and development. Menarche had not occurred. Physical examination revealed a firm, distended right lower abdomen with mild tenderness. Development of pubic hair and breasts was Tanner stage 4. Laboratory findings showed worsening leukocytosis (16,120 per microliter) and anemia (hemoglobin 10.1 g/dl), with elevated C-reactive protein (27.7 mg/liter).

(A) MRI pelvis, coronal T2-weighted image. (B) MRI pelvis, sagittal T2-weighted image, endometrial thickness=22 mm. (C) CT abdomen and pelvis with intravenous contrast, coronal reconstruction. (D) CT abdomen and pelvis with intravenous contrast, sagittal reconstruction.

(A) MRI pelvis, coronal T2-weighted image showing a large, heterogeneous, round lesion with internal solid, mixed hypointense and hyperintense signal intensity and multiple internal cystic foci. (B) MRI pelvis, sagittal T2-weighted image showing endometrial hypertrophy (22 mm in thickness) and large-volume ascites. (C) CT abdomen and pelvis with intravenous contrast, coronal reconstruction showing the full extent of the large heterogeneous lesion with areas of nodular, solid enhancement and large-volume ascites. (D) CT abdomen and pelvis with intravenous contrast, sagittal reconstruction showing the lesion, ascites, and endometrial hypertrophy.

Laboratory results at 6 weeks before presentation and on current presentation.

Laboratory data showing elevated white-cell count (14,270 at 6 weeks before current presentation, 16,120 on current presentation), neutrophilia (10,130 and 12,280 respectively), anemia (hemoglobin 10.9 and 10.1 g/dl respectively), elevated C-reactive protein (5.9 and 27.7 mg/liter respectively), and elevated erythrocyte sedimentation rate (19 mm/hr on current presentation).

(A) Gross pathology of resected ovarian mass, size 18.0 cm. (B-D) H&E staining.

(A) Gross pathology showing resected ovarian mass measuring 18.0 cm with tan-white, multilobulated cut surface and cystic cavity filled with blood. (B) H&E staining showing multinodular architecture with diffuse growth of tumor cells within nodules. (C) H&E staining showing variably sized and shaped follicles with secretions. (D) H&E staining showing tumor cells with abundant, eosinophilic, variably vacuolated cytoplasm and primitive-appearing nuclei, with abundant mitoses and apoptosis.

Juvenile granulosa cell tumour unknown behaviour of unspecified site


A 12-year-old boy presented with episodes of seizures for the past 10 months. The seizures were generalized tonic clonic for the first 3 months, then developed into recurrent episodes of myoclonic jerks (7-8 episodes per day) with frequent falls. Six months after seizure onset, he developed disruptive and aggressive behavior along with poor scholastic performance. Subsequently, he developed progressive visual loss in the left eye six weeks prior to presentation. On examination, the child had multiple scar marks on the forehead due to recurrent falls. He was oriented with normal speech but had poor memory and insight. Visual acuity with pinhole was 6/9 in the right eye and 3/60 in the left eye. A left relative afferent pupillary defect was present. Further inquiry revealed he was unvaccinated and had a history of measles at two years of age in the form of exanthematous fever. The provisional diagnosis by the pediatric neurologist was a neurodegenerative disease with myoclonic epilepsy under investigation.

Color fundus photography of the right eye at initial presentation.

A: Color fundus photography of the right eye at initial presentation demonstrates mild temporal pallor of the optic disc, documenting the posterior pole with no significant macular or peripheral pathology noted at this time.

Fundus examination of the left eye at first ophthalmic evaluation.

The left eye at the first ophthalmic evaluation showed macular scar with pigment splinters. Small irregular whitish lesions with some pigmentation around the macular scar suggest distinct areas of chorioretinal atrophy.

(D) Electroencephalogram (EEG), compressed image format, paper speed 10 mm/s.

D: The electroencephalogram (EEG) presented as Figure 2 (D) on page 3 demonstrates generalized pseudo-periodic epileptiform discharges occurring at variable intervals of 6–30 seconds, shown in a compressed image format at a paper speed of 10 mm/s, reflecting the characteristic electrophysiological findings associated with subacute sclerosing panencephalitis.

B: Optical coherence tomography (OCT) of the left eye showed severe retinal thinning at the posterior pole.

Subacute sclerosing panencephalitis (SSPE) confirmed by positive measles ELISA-IgG antibody in both cerebrospinal fluid and serum, with anti-measles antibody titer of 1:256 in serum and 1:16 in CSF

Subacute sclerosing panencephalitis

ear infection[Measles]


An 11-year-old girl presented with redness of the eyes that had persisted for 8 weeks. She had been well until the onset of mild eye redness, which was worse in the right eye than in the left eye. There was intermittent swelling of the eyelids but no photophobia, itching, pain, tearing, or discharge. The patient had emigrated from West Africa to the United States 6 years earlier. Physical examination revealed visual acuity with correction of 20/20 in the right eye and 20/25 in the left eye. Slit-lamp examination showed abundant white cells in the anterior chamber of both eyes (greater in the right eye), keratic precipitates, posterior synechiae, and rare iris nodules in the right eye. Funduscopic examination revealed optic-disk swelling and peripheral retinal hemorrhages in both eyes, as well as perivascular exudates in the right eye. Laboratory tests showed hemoglobin 10.2 g/dl, hematocrit 31.3%, platelet count 233,000 per μl, white-cell count 4690 per μl, creatinine 0.75 mg/dl, erythrocyte sedimentation rate 90 mm/hr, lysozyme 3.83 μg/ml (elevated), and normal angiotensin-converting enzyme level. Screening tests for HIV, syphilis, and Lyme disease were negative. An interferon-γ release assay for M. tuberculosis was indeterminate. Chest radiography revealed hilar fullness.

(A) CT of the chest, coronal view, performed after administration of intravenous contrast material. (B) CT of the abdomen, axial view. (C) MRI of the head, axial T1-weighted fat-suppressed image of the orbits, performed after administration of intravenous contrast material.

(A) CT of the chest, coronal view, performed after administration of intravenous contrast material, shows mediastinal lymphadenopathy. (B) CT of the abdomen, axial view, shows retroperitoneal lymphadenopathy. (C) MRI of the head, axial T1-weighted fat-suppressed image of the orbits, performed after administration of intravenous contrast material, shows enhancement of the irises with greater enhancement in the right globe than in the left globe, consistent with uveitis.

(A) Fundus photograph of the right eye. (B) Fundus photograph of the left eye.

Fundus photographs of the right eye (A) and left eye (B) show perivascular exudates and hemorrhages.

Laboratory results.

Laboratory data showing hemoglobin 10.2 g/dl (low), hematocrit 31.3% (low), platelet count 175,000-233,000 per μl, white-cell count 4690-5600 per μl, creatinine 0.75 mg/dl, alanine aminotransferase 17-28 U/liter, aspartate aminotransferase 31-34 U/liter, alkaline phosphatase 129 U/liter, albumin 4.2 g/dl, total protein 8.8 g/dl (elevated), C-reactive protein 2.8-3.6 mg/liter, erythrocyte sedimentation rate 90 mm/hr (elevated), angiotensin-converting enzyme 74 U/liter (normal), lysozyme 2.60-3.83 μg/ml (elevated), negative antinuclear antibody, and negative antineutrophil cytoplasmic antibody.

Sarcoidosis


A 14-year-old female patient presented with generalized pruritus accompanied by scleral icterus and petechiae/ecchymoses on the extremities for over 2 months. She had no fever, abdominal pain, or distension. Past medical history included amenorrhea, menstrual irregularities, and acne. She had been taking Chinese herbal medicines (specific components unknown) for approximately 9 months. Physical examination revealed clear consciousness, facial acne and pigmentation, mild scleral and mucocutaneous jaundice, soft abdomen without tenderness or rebound tenderness, and no lower extremity edema.

(A) MRI, T1-weighted sequence, basal ganglia. (B) MRI, T2-weighted sequence, basal ganglia. (C) MRI, diffusion-weighted imaging, basal ganglia. (D) MRI, T2 FLAIR sequence, basal ganglia.

(A) T1-weighted MRI showing hyperintense signal in deep basal ganglia (red arrow), indicating heavy metal deposition. (B) T2-weighted MRI showing slightly increased signal in basal ganglia (red arrow), indicating degeneration. (C) Diffusion-weighted imaging showing slightly high signal in basal ganglia (red arrow), indicating degeneration. (D) T2 FLAIR showing slightly high signal in deep basal ganglia (red arrow), indicating degeneration.

(A) Fundus diffuse light examination. (B) Slit lamp examination. Both show greenish-brown rings formed by the posterior elastic layer of the cornea (K-F rings).

Genetic analysis of the ATP7B gene, c.2333G>T (p.R778L) variant in exon 8.

ATP7B gene mutation analysis showing a clinically relevant variant c.2333G>T(p.R778L) located in exon 8 of the ATP7B gene, representing a homozygous missense mutation.

Pathological examination of liver tissue.(A) H&E staining, 100× magnification. (B) H&E staining, 100× magnification. (C) Masson staining, 100× magnification. (D) Rhodanine staining, 100× magnification.

(A) Moderate interface hepatitis with lymphocyte infiltration (red arrow), H&E staining, 100×. (B) Hepatocytes showing 'rosette' formation, H&E staining, 100×. (C) Masson staining showing pseudolobule formation, Masson staining, 100×. (D) Copper staining (rhodanine method) showing abundant reddish-brown coarse granular pigment deposition in hepatocytes, rhodanine staining, 100×.

Wilson disease

Endocrine, nutritional or metabolic diseases


A 16-year-old girl presented with intermittent abdominal pain that had developed 4 weeks before admission. The episodes of pain became more frequent over 2 weeks, increasing from every few days to twice daily and lasting approximately 2 minutes. The pain was sharp, rated 8/10, and worst in the epigastrium and upper quadrants. Two weeks before admission, she developed new nausea and vomited three times. She was unable to attend school. At initial evaluation at another hospital, she had a temperature of 36.6°C, heart rate 105 beats per minute, blood pressure 125/66 mm Hg, respiratory rate 18 breaths per minute, and oxygen saturation 99% on room air. She had dry mucous membranes and diffuse abdominal tenderness with guarding on palpation of the epigastrium and upper quadrants. Laboratory tests showed white-cell count 14,900 per microliter, hemoglobin 11.3 g per deciliter, and normal urinalysis. Abdominal and pelvic ultrasonography showed no abnormalities, although the appendix was not visualized. The patient continued to have intermittent episodes of abdominal pain and nausea over the following week, with pain worsening after taking ibuprofen. One week before admission, pain woke her from sleep. On the day of admission, episodes lasted 15 minutes and she vomited five times. She described severe pain occurring abruptly, followed by nausea; vomiting decreased pain severity. The pain was unrelated to menstruation, body position, time of day, or eating/drinking. She had decreased appetite, fatigue, dizziness, generalized weakness, and worsening constipation with last bowel movement 3 days before admission. Medical history included iron-deficiency anemia and anxiety disorder; she had pica as a toddler. She had normal growth and development. Medications included iron supplementation, oral contraception, and famotidine. She lived with her parents and sister, was sexually active with consistent condom use, and had last smoked marijuana 4 weeks before admission. Family history included peptic ulcer disease, heart disease, depression, and anxiety.

Laboratory results.

Laboratory data showed hemoglobin 10.8 g/dl (reference range 12.0-16.0), hematocrit 34.9% (36.0-46.0), white-cell count 15,720 per μl (4500-13,000), neutrophils 12,940 per μl (1800-8100), lymphocytes 1780 per μl (1200-5200), monocytes 500 per μl (200-1400), eosinophils 350 per μl (0-1000), basophils 80 per μl (0-400), platelet count 620,000 per μl (150,000-450,000), mean corpuscular volume 69.5 fl (78.0-98.0), erythrocyte sedimentation rate 32 mm/hr (0-19), and C-reactive protein 4.6 mg/liter (0.0-8.0).

(A) Endoscopic image of the esophagus. (B,C) Endoscopic images of the stomach. (D) Surgically removed gastric and duodenal specimen.

(A) Endoscopic image of the esophagus shows normal esophageal mucosa. (B) Endoscopic image of the stomach shows normal mucosa and a trichobezoar with visible hair located in the gastric body. (C) Endoscopic image of the stomach shows normal mucosa and a trichobezoar with visible hair located in the gastric body. (D) The surgically removed gastric and duodenal trichobezoar with the tail that extended into the duodenum visible to the right.

(A) CT of the abdomen and pelvis with intravenous contrast, axial view. (B) CT of the abdomen and pelvis, coronal reconstruction.

(A) CT of the abdomen and pelvis performed after administration of intravenous contrast material, axial view, shows no abnormalities in the liver and spleen; heterogeneous and predominantly hypodense mottled materials are present within the gastric lumen (arrows). (B) CT of the abdomen and pelvis, coronal reconstruction image, shows no abnormalities in the appendix (black arrow) and no evidence of bowel obstruction; the heterogeneous intraluminal gastric contents are again visible (white arrow).

Trichobezoar

Injury, poisoning or certain other consequences of external causes


A 73-year-old woman presented with a 10-year history of severe paraspinal muscle atrophy and cerebellar ataxia. Her symptoms began at age 63 with a slight stooping posture and progressing to gait instability requiring a walking stick by age 68, and difficulty climbing stairs by age 70. She had moderate weakness of neck flexion, mild weakness of proximal limb muscles, poor balance with tandem gait without limb ataxia, and scored 25 points on the Mini-Mental State Examination. Laboratory findings showed elevated serum creatine kinase at 290 IU/l (normal 45-163), normal resting blood and CSF lactate levels, slightly low thyroid-stimulating hormone at 0.47 μIU/ml (normal 0.5-5.0), elevated antithyroglobulin antibody at 7.0 U/ml (normal <0.3), elevated antithyroid peroxidase antibody at 46.5 U/ml (normal <0.3), elevated rheumatoid factor at 152.3 IU/ml (normal <15.0), and mildly elevated antinuclear antibody (titer 1:80). Needle electromyography of biceps brachii and rectus femoris muscles showed mild myopathic features. Pure-tone audiometry indicated sensorineural and high-frequency hearing loss, and Holter monitoring revealed high-frequency premature contractions.

pedigree diagram, current patient marked as Patient 1, solid black symbols indicating affected individuals, open symbols representing healthy individuals, and gray symbols denoting those with elevated creatine kinase (CK) levels

Figure 1 presents the pedigree of the family affected by late-onset predominant axial myopathy and encephalopathy; it is a diagrammatic chart outlining familial relationships, with solid black symbols indicating affected individuals, open symbols representing healthy individuals, and gray symbols denoting those with elevated creatine kinase (CK) levels. The arrow points to the proband. This figure serves as a genetic and clinical overview and does not include clinical images or technical modalities such as imaging, pathology slides, or laboratory charts.

(A) Clinical photograph of patient posture. (B) Clinical photograph, dorsal view, paraspinal region.

a: The full-length figure indicates the posture of the patient showing her pushed-out waist. b: The dorsal view shows the marked atrophy of the paraspinal muscles of the patient.

CT of the T10 vertebral level.

CT of T10 reveals severe atrophy and fatty degeneration of the paraspinal muscles.

Brain MRI, FLAIR sequence.

Brain MRI FLAIR images of Patient 1 show moderate cerebellar atrophy and some cerebral cortical atrophy.

(A) Gomori trichrome staining of the right biceps brachii muscle. (B) SDH staining of the right biceps brachii muscle. (C) COX staining of the right biceps brachii muscle.

Histochemical analysis of the right biceps brachii muscle. a Gomori trichrome staining reveals typical ragged-red fibers. Histochemical analysis of serial sections of samples stained with b SDH or c COX shows a number of ragged-blue fibers with COX deficiency. a2c Bar 100 lm

Electron micrograph of the right biceps brachii muscle. (a) Scale bar 1 µm. (b) Scale bar 500 nm.

Electron micrograph of abnormal mitochondria in the right biceps brachii muscle. Abnormal mitochondria with paracrystalline inclusions that are suggestive of mitochondrial myopathy are shown. a bar 1 lm, b bar 500 nm

Respiratory chain enzyme activity assay normalized to citrate synthase. Current case marked as Patient 1.

Respiratory chain enzyme activities show complex I activity at 43.4% of normal, complex II at 73.4%, complex III at 70.5%, and complex IV at 54.7% of normal when normalized to citrate synthase.

Genetic analysis of muscle homogenate, DNA sequencing chromatogram, mutant load=64.7%. Genetic analysis of blood lymphocytes, DNA sequencing chromatogram. Current case marked as Patient 1

DNA sequencing chromatogram shows heteroplasmic m.602C>T mutation in muscle homogenate mitochondrial tRNA gene, with 64.7% mutant load, but not detectable in blood lymphocytes.

A new phenotype of mitochondrial disease characterized by familial late-onset predominant axial myopathy and encephalopathy

mitochondrial disease NOS

Myopathy

encephalopathy NOS


A male infant, 22 hours old, was admitted due to "repeated right-sided limb clonic seizures for 16 hours." The infant was born at 40+6 weeks gestational age via cesarean section after fetal heart monitoring showed frequent variable decelerations 1 hour before delivery. The amniotic fluid was reduced and grade I turbid, with no premature rupture of membranes. Apgar scores were 10 at 1, 5, and 10 minutes, and birth weight was 3380g. Starting 6 hours after birth, the infant developed right-sided limb clonic seizures without consciousness disturbance or cyanosis, which resolved spontaneously, occurring 4 times total. On admission, physical examination revealed: T 36.7°C, P 125/min, R 46/min, BP 74/47(52) mmHg, weight 3290g, head circumference 36cm. The infant was alert with good response, normal skin color, flat anterior fontanelle with normal tension, bilateral pupils equal and round with diameter 2.5mm and sensitive light reflexes, coarse breath sounds without rales, normal heart sounds and rhythm without murmurs, soft abdomen without palpable masses, normal bowel sounds at 2/min, normal limb activity and muscle tone, and normal primitive reflexes.

(A) Head MRI, DWI sequence. (B) Head MRI, ADC sequence.

(A) Head MRI DWI showing high signal; (B) ADC showing low signal

Head MRA.

Head MRA showing left middle cerebral artery main trunk and branches thicker than contralateral side, with M2 segment locally narrowed

(A) Head MRI, performed at 1 month follow-up, diffusion-weighted imaging (DWI). (B) Head MRI, performed at 1 month follow-up, apparent diffusion coefficient (ADC).

(A) Head MRI DWI at 1 month follow-up showing low signal; (B) ADC showing high signal

Neonatal left temporoparietal cerebral infarction

cerebral infarct


An 18-year-old boy was referred for evaluation of suspected adrenal insufficiency. He was born full term to a native Kashmiri couple. His younger brother had died at age 1 year with possible adrenal insufficiency, and his two other younger siblings were healthy. The patient presented with 6 months of generalized weakness, asthenia, fatigue, anorexia, and progressive hyperpigmentation of skin. Physical examination revealed a lean build (BMI 12.64 kg/m²), hyperpigmentation of tongue, buccal mucosa and skin, and a nasal twang to voice. His blood pressure was 100/60 mm Hg with postural drop. Neurological examination showed hyperactive deep tendon reflexes, and unremarkable sensory examination. He had significant past history including alacrimia diagnosed at age 8 years (confirmed by Schirmer test), dysphagia to liquids at age 12 years leading to diagnosis of achalasia cardia, and severe muscle wasting of small muscles of feet at age 15 years.

pedigree chart, current patient marked as proband

Figure 1 presents a family pedigree chart depicting the proband and the inheritance pattern of Allgrove (Triple A) syndrome within the described family, illustrating affected and unaffected family members without including any imaging, histopathology, or clinical photographic content.

Clinical photograph of the hands taken at the time of neurological examination.

Figure 2 is a clinical photograph depicting the patient's hands, demonstrating wasting of the thenar and hypothenar muscles as well as pigmentation of the palmar creases, which are clinical features observed at the time of neurological examination and consistent with distal motor neuropathy and skin hyperpigmentation in the context of Allgrove syndrome.

Allgrove syndrome (Triple A syndrome) based on primary adrenal insufficiency with normal mineralocorticoid balance, alacrimia, achalasia cardia, and peripheral neuropathy

Allgrove syndrome

primary adrenal insufficiency

Congenital alacrimia

achalasia of cardia

peripheral neuropathy NOS


A man in his early 40s with no significant medical history presented to the emergency department with chest pain and shortness of breath of insidious but progressive onset over several weeks. Physical examination and routine laboratory workup were unremarkable. Chest X-ray revealed a right pneumothorax and a right upper lobe lung mass. CT of the chest with intravenous contrast revealed a large right-sided pneumothorax with minimal leftward displacement of the mediastinal structures and a 3.4 cm dense mass abutting the posterior right upper lobe pleura with cystic necrosis highly suspicious for malignancy. CT-guided biopsy of the mass showed a poorly differentiated non-small cell carcinoma with large pleomorphic tumor cells, moderate-to-large amounts of eosinophilic cytoplasm, focal rhabdoid features, scattered tumor giant cells, and identifiable mitotic figures. The tumor cells expressed CK7 and CK AE1/3 but were negative for TTF1, Napsin A, P40, SOX10 and CD45. PD-L1 staining using the 22C3 antibody was positive for high PD-L1 expression with a tumor proportion score of 90%. Endobronchial ultrasound with biopsy to stage the mediastinum was negative for carcinoma in the left level 4 paratracheal, right level 4, level 7 and right level 10. MRI of the head with and without contrast preoperatively revealed no intracranial metastasis.

H&E staining of resected pulmonary pleomorphic carcinoma.(A)40× magnification. (B)20× magnification.

(A) H&E staining, 40× magnification, showing carcinoma with large pleomorphic tumor cells and a rhabdoid appearance. (B) H&E staining, 20× magnification, showing focal epithelioid appearance.

(A) PET scan performed prior to mediastinal staging and surgical resection.

(A) PET scan performed prior to mediastinal staging and surgical resection showing a solitary peripheral intensely hypermetabolic pleural-based, lobulated right upper lobe mass.

Pleomorphic carcinoma of lung


A 29-year-old woman presented with a 7-week history of progressive pruritus throughout the body, nausea, bloating, and watery mustard-colored diarrhea that began after eating sushi. She had recently moved from New England to the southeastern United States. Initial treatment with methylprednisolone injection, hydroxyzine, and diphenoxylate-atropine at an urgent care clinic did not resolve symptoms. Three weeks later, jaundice developed along with right upper quadrant discomfort, decreased appetite, and amber-colored urine. Four weeks before presentation, laboratory tests showed alanine aminotransferase 327 U/L (reference 1-33), aspartate aminotransferase 104 U/L (reference 1-32), total bilirubin 5.8 mg/dL (reference 0.1-1.2), and CA 19-9 73 U/mL (reference 0-35). She had a history of anxiety and depression, took no medications, and had no drug allergies. Family history included colon cancer in maternal grandmother, maternal grandfather, and paternal grandmother; breast cancer in maternal and paternal aunts; and thyroid cancer in father. On examination, temperature was 36.9°C, blood pressure 155/82 mm Hg, pulse 94 beats per minute, respiratory rate 20 breaths per minute, and oxygen saturation 100% while breathing ambient air. She was thin and appeared jaundiced with scleral icterus and diffuse excoriations from scratching.

(A) Coronal contrast-enhanced CT of the abdomen. (B) Axial contrast-enhanced CT of the abdomen. (C) Coronal magnetic resonance cholangiopancreatography of the abdomen, thick-section. (D) Axial gadolinium-enhanced T1-weighted MRI of the abdomen. (E) Endoscopic ultrasonography of the abdomen.

(A) Coronal contrast-enhanced CT image shows diffuse intrahepatic and extrahepatic biliary ductal dilatation and pancreatic ductal dilatation (double-duct sign). (B) Axial contrast-enhanced CT image shows a hypodense region in the pancreatic head and uncinate process at the site of duct obstruction. (C) Coronal thick-section magnetic resonance cholangiopancreatographic image shows dilatation of the biliary ducts and pancreatic ducts with an abrupt transition in the pancreatic head. (D) Axial gadolinium-enhanced T1-weighted magnetic resonance image shows a heterogeneously enhancing mass in the region of the pancreatic head. (E) Endoscopic ultrasonographic image shows a hypoechoic mass in the pancreatic head.

Laboratory results on admission to first hospital and on admission to second hospital.

Laboratory data on admission to first hospital showed hemoglobin 13.6 g/dL, white cell count 8290/μL with eosinophils 912/μL, platelet count 228,000/μL, glucose 162 mg/dL, lipase 72 U/L, alanine aminotransferase 327 U/L, aspartate aminotransferase 104 U/L, alkaline phosphatase 172 U/L, total bilirubin 5.8 mg/dL, albumin 4.10 g/dL, and carbohydrate antigen 19-9 73 U/mL. On admission to second hospital, alanine aminotransferase was 85 U/L, aspartate aminotransferase 267 U/L, alkaline phosphatase 150 U/L, total bilirubin 6.7 mg/dL, and CA 19-9 79 U/mL.

(A) Aspirate, Papanicolaou staining. (B) Core-biopsy specimen, hematoxylin and eosin staining. (C) Aspirate, Diff-Quik staining. (D) Cell block, hematoxylin and eosin staining.

(A) Papanicolaou staining of aspirate shows benign ductal epithelial cells with small, uniform, evenly spaced nuclei. (B) Hematoxylin and eosin staining of the corresponding core-biopsy specimen shows benign atrophic pancreatic acinar cells and an islet separated by fibrosis. (C) Diff-Quik staining of additional aspirate shows a cluster of atypical epithelial cells with nuclear crowding and irregularly shaped nuclear contours. (D) Hematoxylin and eosin staining of the corresponding cell block shows a group of highly atypical epithelial cells with nuclear pallor, irregular nuclear membranes, and abundant foamy cytoplasm next to a strip of benign ductal cells.

(A) Pancreaticoduodenectomy specimen, H&E staining. (B, C, D) Pancreaticoduodenectomy specimen, H&E staining, higher magnification.

(A) Hematoxylin and eosin staining of the pancreaticoduodenectomy specimen shows numerous malignant infiltrating glands. (B, C, D) At higher magnification, carcinoma glands can be identified in a dense cellular stroma. There is a focus of perineural invasion and evidence of metastasis to a lymph node.

(A) Contrast-enhanced CT, axial view, liver segment 4. (B) Contrast-enhanced CT, axial view, region posterior to the superior mesenteric vessels at the surgical resection bed. (C) MRI, axial view, gadolinium-enhanced T1-weighted sequence, liver segment 8. (D) MRI, axial view, gadolinium-enhanced T1-weighted sequence, liver segment 4. (E, F) 18F-fluorodeoxyglucose positron emission tomography, liver.

(A) Axial contrast-enhanced CT image shows an 8-mm hypodense lesion in liver segment 4 and (B) soft-tissue changes posterior to the superior mesenteric vessels at the surgical resection bed. (C) Axial gadolinium-enhanced T1-weighted MRI shows a peripherally enhancing lesion in liver segment 8 and (D) another in liver segment 4, findings suggestive of liver metastasis. (E, F) 18F-fluorodeoxyglucose (FDG)-positron-emission tomographic images show intense FDG avidity within the liver lesions.

Ductal adenocarcinoma of pancreas


A 27-year-old man from El Salvador presented to the emergency department with leg weakness. He had been in his usual state of health until 3 days before presentation, when myalgias developed in his upper legs. On the morning of presentation, he could not lift his legs to move in bed or stand up, and had weakness in his arms. He had moved to Boston from El Salvador 5 months before presentation and had been experiencing difficulty sleeping, loose stools, weight loss of approximately 5 kg, and hand tremors for several months, which he attributed to stress. Four days before presentation, he began taking an herbal supplement (Nervitran) intended to reduce stress. On examination, he had temporal temperature 36.2°C, blood pressure 144/79 mm Hg, pulse 96 beats per minute, respiratory rate 18 breaths per minute, oxygen saturation 99% on ambient air, and BMI 21.6. He had conjunctival injection in both eyes, muscle strength 4/5 in upper extremities and 3/5 in lower extremities, 3+ patellar reflexes, and fine tremor in hands. Laboratory results showed severe hypokalemia (potassium 1.8 mmol/liter), elevated liver enzymes (AST 56 U/liter, ALT 65 U/liter), alkaline phosphatase 137 U/liter, total bilirubin 1.3 mg/dl, creatine kinase 382 U/liter, and aldolase 9.9 U/liter. Venous blood gases showed pH 7.29.

Laboratory results on presentation.

Laboratory data on presentation showing sodium 141 mmol/liter, potassium 1.8 mmol/liter, chloride 106 mmol/liter, carbon dioxide 23 mmol/liter, urea nitrogen 17 mg/dl, creatinine 0.53 mg/dl, glucose 141 mg/dl, anion gap 12 mmol/liter, calcium 10.4 mg/dl, magnesium 1.8 mg/dl, alkaline phosphatase 156 U/liter, alanine aminotransferase 67 U/liter, aspartate aminotransferase 54 U/liter, total bilirubin 1.3 mg/dl, direct bilirubin 0.3 mg/dl, international normalized ratio 1.1, albumin 4.1 g/dl, creatine kinase 382 U/liter, aldolase 9.9 U/liter, and venous blood gases showing pH 7.29, partial pressure of carbon dioxide 56 mm Hg, partial pressure of oxygen 32 mm Hg.

(A) Transverse grayscale ultrasound of the thyroid gland. (B) Transverse color Doppler ultrasound of the thyroid gland.

(A) Grayscale transverse ultrasound image shows an enlarged thyroid gland with heterogeneous echotexture. (B) Color Doppler transverse image shows diffusely increased vascularity.

(A) Thyroid resection specimen, H&E staining, low magnification. (B) Thyroid resection specimen, H&E staining, high magnification. (C) Thyroid resection specimen, H&E staining. (D) Thyroid resection specimen, H&E staining. (E) Thyroid resection specimen, H&E staining. (F) Thyroid resection specimen, H&E staining.

(A) Hematoxylin and eosin staining of thyroid resection specimen at lower magnification showing lymphoid aggregates with germinal centers (arrows) that are the hallmark of chronic thyroiditis, with all follicles being macrofollicles typically seen in normal thyroid tissue. (B) Higher magnification showing lymphoid aggregates with germinal centers (arrows). (C) Graves' disease evidenced by hyperplasia in nodular pattern with papillary architectural projections into colloid-rich follicles (arrows). (D) Papillary projections (arrow) have fibrovascular cores and round, normochromatic nuclei. (E) Empty follicles (asterisks) indicate excreted colloid after stimulation by thyroid-stimulating immunoglobulin. (F) Mixed pattern of compressed, empty follicles (center) and normal macrofollicles (periphery) indicative of effective medical treatment.

Thyrotoxic periodic paralysis associated with Graves' disease

Thyrotoxic periodic paralysis

Graves disease


A 39-year-old man presented to the emergency department during the summer with a 4-day history of fever with shaking chills, diffuse headache, and fatigue following his return from a 2-week trip to East Africa. During his trip to Tanzania, he had been on safari without animal contact but received mosquito bites, especially during the first days. He consumed cooked shrimp and lobster and a small amount of raw tuna. On the second-to-last day of the trip, he developed nausea, vomiting, and nonbloody diarrhea. Upon returning to Massachusetts, he experienced fever (38.3°C to 39.5°C), shaking chills, diffuse headache, and lower back pain. He reported weakness, anorexia, decreased urine output with dark urine, and blurry vision during fever episodes. His medical history included degenerative knee disease with previous glucocorticoid injections. On examination, he had a temperature of 38.9°C, blood pressure 113/62 mm Hg, facial flushing, mild scleral icterus, and dark brown urine.

Laboratory results on initial evaluation.

Laboratory data on initial evaluation showed hemoglobin 17.6 g/dl, hematocrit 51.2%, platelet count 24,000/μl (reference: 150,000-400,000), creatinine 1.64 mg/dl (reference: 0.60-1.50), alanine aminotransferase 119 U/liter (reference: 10-55), aspartate aminotransferase 137 U/liter (reference: 10-40), total bilirubin 3.3 mg/dl (reference: 0.0-1.0), direct bilirubin 1.5 mg/dl (reference: 0.0-0.4), haptoglobin <10 mg/dl (reference: 30-200), and venous blood pH 7.41.

(A) Chest radiograph, frontal view. (B) Abdominal ultrasound, liver.

(A) Single-view frontal chest radiograph shows no evidence of pneumonia or pulmonary edema. Electrocardiogram leads are visible. (B) Limited abdominal ultrasound image shows echogenic liver parenchyma indicative of mild hepatic steatosis but is otherwise unremarkable.

(A) Rapid antigen test for malaria. (B) Thin peripheral-blood smear, Giemsa staining, parasitemia level 36%. (C) Thin peripheral-blood smear, Giemsa staining. (D) Thin peripheral-blood smear, Giemsa staining.

(A) Rapid antigen test for malaria shows positive bands at test 1 (T1) and test 2 (T2) lines, indicating Plasmodium falciparum infection. (B) Giemsa staining of thin peripheral-blood smear shows abundant intraerythrocytic ring forms with estimated parasitemia level of 36%. (C) Ring form with characteristic 'headphone' appearance. (D) Maturing trophozoite producing golden-brown malaria pigment (arrow).

Malaria due to Plasmodium falciparum

Certain infectious or parasitic diseases


A 33-year-old male worker presented with a 20-day history of cough and sputum production. The symptoms began after catching cold, with yellow-white sticky sputum in small amounts, without hemoptysis, fever, chills, chest pain, or dyspnea. He had been treated at a local clinic with intravenous therapy (details unknown) without improvement. Seven days prior to admission, his cough worsened, particularly at night causing sleep difficulty, sometimes accompanied by right-sided chest pain. He was previously healthy with no significant medical history, smoked about 10 cigarettes daily for over ten years, and had no alcohol consumption history. Physical examination revealed: T 36.2℃, P 112/min, R 19/min, BP 126/85mmHg. Chest examination showed symmetric thorax without deformity, equal respiratory movements, symmetric vocal fremitus, clear percussion notes bilaterally, coarse breath sounds in both lungs with a small amount of wet rales audible in the right lung, no dry rales or pleural friction rubs.

Chest CT of the right lower lobe performed on 2021.4.1.

Chest CT performed on 2021.4.1 showing multiple abnormal densities in the right lower lobe, likely inflammatory changes.

(A) Lung tissue smear, H&E staining, low magnification. (B) Lung tissue, H&E staining, low magnification.

Lung tissue smear pathology results showing numerous acute and chronic inflammatory cells, a small amount of phagocytic cells and Cryptococcus (HE staining, low magnification); Lung tissue showing fibrous granulation tissue, necrotic tissue, and fibrous exudate containing numerous Cryptococcus (HE staining, low magnification).

cryptococcal pneumonia


A 21-year-old woman presented with a 4-month history of progressively worsening abdominal pain in the right lower quadrant, initially dull and aching but increasing in duration, frequency, and severity. She also reported fatigue, irritability, and weight gain of 4.5 kg despite increased exercise and decreased food intake. The patient had a history of hypothyroidism, anxiety, irritable bowel syndrome, and migraines. She had previously taken oral contraceptives but switched to a levonorgestrel-releasing IUD 6 months prior. Physical examination revealed blood pressure 119/73 mm Hg, heart rate 62 beats per minute, BMI 28.4, a firm thyroid with a small nodule on the right side, and a small hernia with a thrill at the right inguinal ring. Laboratory tests showed normal complete blood count, electrolytes, glucose, kidney, liver, and thyroid function. Screening tests for gonorrhea, chlamydia, HIV, and syphilis were negative.

(A) Sagittal ultrasound of the right liver region. (B) MRI, T2-weighted sequence, right adrenal gland. (C) Diffusion-weighted MRI. (D) CT scan before contrast administration, density=33 Hounsfield units. (E) CT scan during portal-venous phase, density=74 Hounsfield units. (F) CT scan during 15-minute delayed phase, density=45 Hounsfield units; absolute washout=71%.

(A) Sagittal ultrasound image shows a hypoechoic mass posterior to the right lobe of the liver. (B) MRI T2-weighted image shows a mass arising from the right adrenal gland that is isointense. (C) Diffusion-weighted image shows diffusion restriction. (D) CT image before contrast administration shows density of 33 Hounsfield units. (E) CT during portal-venous phase shows density of 74 Hounsfield units. (F) CT during 15-minute delayed phase shows density of 45 Hounsfield units; the absolute washout is 71%.

(A) Hematoxylin and eosin staining of adrenal gland. (B) Hematoxylin and eosin staining of adrenal gland. (C) Hematoxylin and eosin staining of adrenal gland.

(A) Hematoxylin and eosin staining shows a sharply circumscribed mass, abutting normal adrenal gland, that has nodular architecture. (B) The mass is composed of oncocytic tumor cells that are growing diffusely in the nodules and have conspicuous mitotic activity (circled). (C) The tumor cells have rare, atypical mitoses (arrow).

Oncocytic adrenocortical carcinoma, low grade

Adrenocortical carcinoma


A 60-year-old man was transferred to this hospital for evaluation of new dyspnea, cough, neck swelling, and a lung mass. Three days before the current admission, the patient was transported to another hospital by ambulance. He had a 5-day history of sore throat, swelling of his neck and both arms, and orthopnea. He reported that he had had progressive dyspnea with walking or lifting items at his job for the past year; the dyspnea had been most prominent during the 4 months before this evaluation and had been accompanied by persistent nonproductive cough. His daughter, a health care worker, called emergency medical services when she noticed that he had facial redness and flushing and learned of the swelling of his neck and arms. On evaluation at the other hospital, the temperature was 35.6°C, the heart rate 78 beats per minute, the blood pressure 121/57 mm Hg, the respiratory rate 19 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The face was flushed, and the neck was swollen. Breath sounds were absent in the right lung fields. The patient had smoked two packs of cigarettes per day for 40 years and smoked marijuana occasionally. He drank five beers per day two times per week. His family history was notable for pancreatic cancer in his mother.

Laboratory test results on admission to another hospital and this hospital.

Laboratory data on admission to other hospital and this hospital showing hemoglobin 11.8 g/dl (other hospital) and 12.3 g/dl (this hospital), hematocrit 35.5% (other hospital) and 36.6% (this hospital), white-cell count 10,500 per μl (other hospital) and 11,560 per μl (this hospital), platelet count 342,000 per μl (other hospital) and 353,000 per μl (this hospital), sodium 129 mmol/liter (other hospital) and 132 mmol/liter (this hospital), potassium 4.5 mmol/liter (other hospital) and 3.9 mmol/liter (this hospital), chloride 94 mmol/liter (other hospital) and 98 mmol/liter (this hospital), carbon dioxide 29 mmol/liter (other hospital) and 24 mmol/liter (this hospital), urea nitrogen 12 mg/dl (other hospital) and 4 mg/dl (this hospital), creatinine 0.51 mg/dl (other hospital) and 0.61 mg/dl (this hospital), calcium 9.3 mg/dl (other hospital) and 8.3 mg/dl (this hospital), albumin 2.5 g/dl (other hospital), C-reactive protein 18.10 mg/dl (other hospital).

(A) Chest CT, transverse view, post-contrast. (B) Chest CT, transverse view, post-contrast. (C) Chest CT, coronal view, post-contrast. (D, E) Chest CT, coronal view, post-contrast.

(A) CT of the chest, transverse image, performed after the administration of intravenous contrast material, shows a central mass in the right upper lobe with enlarged right hilar and right mediastinal lymph nodes. (B) Transverse image shows that the brachiocephalic veins are distended, with no opacification. (C) Coronal image shows that the superior vena cava (SVC) is distended with no opacification, and extensive collateral veins in the right chest wall are present. (D) Coronal image shows stents in the internal jugular veins, the brachiocephalic veins, and the SVC. (E) Coronal image shows stents in the internal jugular veins, the brachiocephalic veins, and the SVC.

Bronchoscopy photograph of the right main-stem bronchus.

Photograph obtained during bronchoscopy shows the right main-stem bronchus completely obstructed as a result of extrinsic compression and mucosal edema.

(A) Aspirate sample, H&E staining. (B) Cell-block preparation.

(A) Hematoxylin and eosin staining of aspirate shows tumor cells with cytomorphologic features of adenocarcinoma, including large irregularly contoured nuclei with fine chromatin and prominent nucleoli as well as thin, translucent cytoplasm. (B) Cell-block preparation shows similar features.

PET-CT, after intravenous 18F-fluorodeoxyglucose administration.

Staging PET-CT image, obtained after the administration of intravenous 18F-fluorodeoxyglucose (FDG) tracer, shows intense FDG uptake in the central right upper lobe and right mediastinal nodes and in the right adrenal gland.

Poorly differentiated adenocarcinoma of the lung complicated by superior vena cava syndrome

lung adenocarcinoma

Acquired superior vena cava syndrome


A 27-year-old man presented with convulsions that had been occurring for 2 years. The patient had been in his usual state of health until 2 years before admission, when shaking of the trunk, arms, and legs occurred, lasting approximately 4-5 minutes and preceded by sharp pain in the back of the head radiating to the neck, blurred vision, palpitations, nausea, and difficulty concentrating. Four months before admission, while drinking alcohol at a party, his body suddenly became stiff and he fell backward, with shaking of the trunk, arms, and legs for 5-8 minutes with urinary incontinence. Three months before admission, he reported convulsions occurring approximately once per week despite treatment with levetiracetam. One month before admission, colleagues found him on the floor with shaking and clenching movements lasting approximately 2 minutes. On examination, he was awake and alert but did not speak, with stiff body appearance and intermittent nonrhythmic tremulous movements of the trunk, arms, and legs. He had extensive scarring from burns on the face, trunk, back, arms, and legs. The patient had a history of febrile seizure in childhood, several concussions, asthma, major depressive disorder, chronic PTSD, and panic disorder with agoraphobia. His father died of heart disease and his mother had schizoaffective disorder and post-traumatic epilepsy. Blood levels of glucose, electrolytes, liver function, and kidney function were normal. Blood lactate level was 2.4 mmol/L (reference range 0.5-2.2) and creatine kinase level was 489 U/L (reference range 60-400).

EEG obtained over 10 seconds during a convulsive episode.

EEG obtained over a period of 10 seconds during a convulsive episode. Multiple eye movements occurred. There was a brief period of eye closure correlating with a normal 11-Hz posterior-dominant rhythm, followed by multiple eye blinks correlating with attenuation of the posterior-dominant rhythm. No epileptiform features were noted at any time during the episode.

Seizure NOS


A 57-year-old woman with resected stage IIIC cutaneous melanoma presented with fever. She had been in her usual state of health until 4 months before admission, when bleeding developed from a lesion on the right side of the scalp. Evaluation revealed ulcerated melanoma with positive margins. Three months before admission, wide local excision of the scalp lesion and neck lymph-node dissection were performed, revealing metastatic melanoma in 2 of 26 lymph nodes. Molecular profiling identified the BRAF V600E mutation. One month before admission, she began adjuvant therapy with dabrafenib and trametinib. One day after starting treatment, fever and nausea developed. Symptoms resolved after temporary discontinuation of therapy and antipyretics. Two weeks before admission, fever recurred. On presentation, she had a temperature of 40.2°C, blood pressure 85/53 mm Hg, pulse 108 beats per minute, and oxygen saturation 94% on ambient air. She was diaphoretic and appeared ill. Physical examination revealed mild tenderness in the right upper quadrant. No rash was present.

Laboratory test results and urinalysis.

Laboratory data showed white-cell count 5190 per microliter with 20% bands and 10% metamyelocytes, platelet count 87,000 per microliter, creatinine 2.73 mg/dl, AST 190 U/liter, ALT 62 U/liter, alkaline phosphatase 173 U/liter, total bilirubin 1.9 mg/dl, d-dimer >10,000 ng/ml, fibrinogen 135 mg/dl, and creatine kinase 1679 U/liter. Urinalysis showed turbid yellow urine with 2+ blood and 1+ protein.

(A) Ultrasound of right upper quadrant. (B) Ultrasound of common bile duct, diameter 3 mm. (C) CT of abdomen and pelvis without intravenous contrast, mean liver attenuation 36 HU, mean spleen attenuation 46 HU. (D-F) CT of chest without intravenous contrast.

(A) Ultrasound of right upper quadrant showing mobile echogenic focus indicating cholelithiasis without gallbladder-wall thickening or pericholecystic fluid. (B) Ultrasound showing normal common bile duct measuring 3 mm. (C) CT of abdomen and pelvis without intravenous contrast showing diffuse hypoattenuation of liver (mean 36 HU vs spleen 46 HU) suggesting hepatic steatosis. (D-F) CT of chest without intravenous contrast showing smooth interlobular septal thickening at apex and lung bases, small bilateral pleural effusions, and bronchial wall thickening, findings suggesting pulmonary edema.

(A) Core liver biopsy specimen, H&E staining. (B) H&E staining. (C) H&E staining. (D) Acid-fast staining. (E) Grocott-Gomori methenamine silver staining. (F) In situ hybridization for Epstein-Barr virus-encoded RNA.

(A) Core liver biopsy specimen, H&E staining, showing well-formed nonnecrotizing epithelioid granulomas involving lobular parenchyma. (B) H&E staining showing granulomas and numerous apoptotic hepatocytes. (C) H&E staining showing granulomas involving portal tracts without histologically significant biliary injury. (D) Acid-fast staining negative for organisms. (E) Grocott-Gomori methenamine silver staining negative for fungal organisms. (F) In situ hybridization for Epstein-Barr virus-encoded RNA negative.

BRAF–MEK inhibitor–related toxic effects

toxic effects of drugs NOS

toxic effects of drugs NOS


A 69-year-old male patient presented with lower abdominal pain. Physical examination revealed a flat abdomen without varicose veins, soft abdomen, with a palpable 3 cm×4 cm hard mass in the left lower abdomen, positive lower abdominal tenderness without rebound tenderness. Bowel sounds were normal at 4 times per minute. The patient had a history of cataracts for over one year, denied history of coronary heart disease, diabetes, hypertension, hepatitis, tuberculosis, or other acute or chronic infectious diseases. He denied food or drug allergies, trauma, blood transfusion history, or other surgical history.

(A) Lower abdominal CT, coronal view. (B) Lower abdominal CT, sagittal view. CT measurement: sigmoid colon wall thickness approximately 2 cm, lesion length 6.4 cm, soft tissue protruding into the bladder cavity measuring approximately 2 cm, with multiple enlarged lymph nodes.

(A) Lower abdominal CT, coronal view showing soft tissue protruding into the bladder (yellow arrow). (B) Lower abdominal CT, sagittal view showing soft tissue protruding into the bladder (yellow arrow). CT findings: sigmoid colon is tortuous and elongated, with thickened bowel wall measuring approximately 2 cm at the thickest point, length 6.4 cm, blurred surrounding fat spaces, unclear demarcation with adjacent bladder wall, with soft tissue shadow protruding into the bladder cavity measuring approximately 2 cm, surrounded by flocculent slightly hyperdense shadows and multiple enlarged lymph nodes. CT results suggest sigmoid colon cancer invading the bladder with surrounding lymph node metastasis.

(A) Urine liquid-based cytology, H&E staining, 200× magnification. (B–D) Urine liquid-based cytology, H&E staining, 400× magnification.

(A) Urine liquid-based cytology showing individual scattered tumor cells, H&E ×200. (B) Urine liquid-based cytology showing small clusters of tumor cells, H&E ×400. (C) Urine liquid-based cytology showing tumor cells with moderate cytoplasm, hyperchromatic nuclei, extremely irregular nuclear membranes, and marked nuclear atypia, H&E ×400. (D) Urine liquid-based cytology showing rare columnar tumor cells with palisading arrangement and oval nuclei, H&E ×400.

(A) Immunocytochemical staining, 400× magnification, CDX-2 positive. (B) Immunocytochemical staining, 400× magnification, GATA3 negative.

(A) CDX-2 positive, immunocytochemical staining ×400. (B) GATA3 negative, immunocytochemical staining ×400. Immunocytochemical staining results: positive for CDX-2 and Villin; negative for GATA3 and Uroplakin III.

(A) Sigmoid colon histopathology, H&E staining, 200× magnification. (B) Immunohistochemistry, 200× magnification; CDX-2 positive; CDX-2, CK20, CK8/18 positive; GATA3, Uroplakin III, CK7 negative; MLH1(+), MSH2(+), MSH6(+), PMS2(+); S100 (no nerve invasion), CD34 (vascular invasion), D2-40 (no lymphatic invasion); Ki-67 proliferation index ≈60%.

(A) Sigmoid colon histopathology showing atypical glands infiltrating in fibrous stroma, H&E ×200. (B) CDX-2 positive, immunohistochemistry ×200. Immunohistochemical results: CDX-2, CK20, CK8/18 positive; GATA3, Uroplakin III, CK7 negative; MLH1(+), MSH2(+), MSH6(+), PMS2(+), S100 (no nerve invasion detected), CD34 (vascular invasion detected), D2-40 (no lymphatic invasion detected), Ki-67 proliferation index approximately 60%.

Sigmoid colon adenocarcinoma invading the bladder

Adenocarcinoma of sigmoid colon

Mucinous cystic neoplasm with associated invasive carcinoma of other or unspecified parts of biliary tract[Gallbladder]


A 6-year-old Japanese boy. He was born at term after an uncomplicated pregnancy. At 19 months, he was referred due to inability to walk unaided, and brain MRI was normal at that time. His linear growth started to slow from 5 months of age. At 38 months, his height was 84.5 cm with normal thyroid function and low baseline IGF-I. Growth hormone stimulation tests showed peak GH response to arginine of 4.60 ng/mL and to clonidine of 2.41 ng/mL, leading to diagnosis of partial growth hormone deficiency. At 6 years of age, he presented with painful knee joints, height 109.5 cm, arm span 111 cm, with some clumsiness in motion. Development was appropriate for age except for motor clumsiness. Laboratory data showed normal serum calcium, phosphate, alkaline phosphatase, intact PTH, IGF-I, and thyroid function, with undetectable TRAP activity. No immunological abnormalities were found. Bone mineral density was normal.

pedigree chart, current patient marked in black

A: Figure 1 (A) presents a pedigree chart depicting the proband’s family structure, indicating the unaffected parents and sibling, with ages and final heights noted, and the affected 6-year-old male patient highlighted, but does not display laboratory, imaging, or clinical photographic data; its content is limited to family relationships and auxological parameters, rather than any imaging or sample analysis modality.

Growth curve illustrating height measurements from birth to 38 months.

Growth curve shows height declining from normal at birth to -2.89 SD at 38 months when GH therapy was commenced, with subsequent improvement in growth velocity

Clinical photographs at 6 years of age, frontal and lateral views.

A: Clinical photographs depicting the patient at 6 years of age demonstrate normal facial features and body proportions, with images taken in both frontal and lateral views to document overall physical appearance at the time of musculoskeletal symptom onset.

Spinal radiograph.

Spinal radiograph showing generalized platyspondyly with irregular endplates and irregular ossifications in the posterior vertebral bodies

Knee radiograph.

Knee radiograph showing mild metaphyseal dysplasia with shaved contour and marginal spur in distal femoral metaphyses, lesser changes in proximal tibial metaphyses, and mild cupping proximal fibular metaphyses

Hip and wrist radiographs.

Hip and wrist radiographs showing similar metaphyseal changes as seen in the knee

CT of the brain.

Brain CT showing bilateral calcifications of the basal ganglia

Genetic analysis.

Chromatograms showing novel heterozygous ACP5 mutations: splice-site mutation (c.736-2 A>C) and nonsense mutation (c.526 C>T; p.R176X)

Quantitative RT-PCR analysis of IFI27, IFIT1, IFI44L, ISG15, RSAD2, and SIGLEC1.

Quantitative RT-PCR showing marked upregulation of interferon-stimulated genes (IFI27, IFIT1, IFI44L, ISG15, RSAD2, SIGLEC1) in patient compared to healthy controls

Spondyloenchondrodysplasia (SPENCD) with partial growth hormone deficiency

Spondyloenchondrodysplasia

Growth hormone deficiency


A newborn girl was admitted to the neonatal intensive care unit (NICU) because of cardiorespiratory arrest at delivery. The mother was a 19-year-old woman (gravida 1, para 1) with a history of hepatitis C virus infection. Pregnancy was complicated by urogenital Chlamydia trachomatis infection treated in the second trimester and gestational hypertension. Serial ultrasound surveys between 20 weeks 1 day and 39 weeks 6 days of gestation revealed dilatation of the urinary tract on the right side. At 40 weeks 0 days of gestation, spontaneous rupture of membranes occurred, and after 22 hours 39 minutes of labor, a cesarean section was performed due to nonreassuring fetal status. The amniotic fluid was stained with meconium. The newborn was delivered in breech position with birth weight 3575 g (62nd percentile), length 50 cm (42nd percentile), and head circumference 35.5 cm (72nd percentile). She had limp tone and no respiratory effort. After 16 minutes of resuscitation including intubation, cardiopulmonary resuscitation, epinephrine administration, and normal saline boluses, spontaneous circulation was restored. Apgar scores at 1, 5, 10, 15, and 20 minutes were 1, 0, 0, 1, and 3, respectively. On arrival in the NICU, the axillary temperature was 34.9°C, heart rate 141 beats per minute, and blood pressure 84/59 mm Hg. Oxygen saturation was 97% while receiving oxygen through mechanical ventilation. Therapeutic hypothermia was initiated.

(A) Chest radiography on the day of birth. (B) Chest radiography on day 2. (C) Chest radiography after left needle thoracentesis. (D) Chest radiography on day 21.

(A) Chest radiography on the day of birth revealed a small-to-moderate pneumothorax in the medial aspect of the pleural cavity on the right side. (B) On day 2, after needle thoracentesis on the right side, the right pneumothorax has resolved and a large left pneumothorax has developed with extensive collapse of the left lung. (C) After needle thoracentesis on the left side, the left pneumothorax has decreased in size and inflation of the left lung has increased. (D) On day 21, the pneumothorax findings have resolved, but an opacity is present in the left lower lobe that has persisted since day 16.

(A) Chest ultrasonography with color Doppler, performed on day 21. (B) Chest CT angiography, performed on day 23. (C) Chest CT angiography, performed on day 149.

(A) Ultrasonography of the chest with color Doppler on day 21 revealed a predominantly echogenic mass in the left lower lobe with a suspected arterial supply from the abdominal aorta. (B) CT angiography of the chest on day 23 confirmed a heterogeneous masslike area of consolidation in the lingula and left lower lobe with a feeding artery arising from the abdominal aorta. (C) Follow-up CT angiography on day 149 showed that the previous area of consolidation has been replaced by hyperlucency suggestive of cystic changes and air trapping.

Intralobar sequestration of lung


A 79-year-old man was admitted to this hospital because of involuntary movements on the left side and transient unresponsiveness. The patient had been in his usual state of health until 9 months before admission, when involuntary movements of the left shoulder and left side of the face developed. The movements were described by the patient as twitching, were not associated with a change in the level of consciousness, and resolved after 1 to 2 minutes. During the next 6 months, the patient had similar episodes approximately once per month, but the episodes increased in duration, lasting 5 to 6 minutes. Three months before admission, the episodes of involuntary movements increased in frequency. The physical examination was normal. Results of kidney-function tests were normal, as were blood levels of glucose and electrolytes, except for the sodium level, which was 129 mmol per liter (reference range, 135 to 145). There was a history of inappropriate antidiuretic hormone secretion, and the sodium level was similar to levels obtained during the past 4 years. Two months before admission, the patient reported that the episodes of involuntary movements had increased in both frequency and duration, occurring once or twice per day and lasting approximately 10 minutes. Episodes began with tingling and numbness in the left leg that prompted the patient to voluntarily stomp the left foot to relieve the uncomfortable sensation. Then, the patient had involuntary movements that he described as an uncontrollable invisible force moving the left leg and arm, with hyperextension of the arm backward and pronation of the wrist. There was associated numbness in the distal portions of the left third, fourth, and fifth fingers and involuntary movement of the left cheek. No prodromal symptoms occurred. The patient had awareness during the episodes, and after the episodes, he felt fatigued but had a normal level of consciousness, without confusion. Three weeks before admission, the patient reported that the episodes of involuntary movements still occurred on a daily basis but had decreased in duration and involved only the left leg, without abnormal movements of the arm or face. Dizziness, headache, and weakness had developed and were attributed to the use of levetiracetam. On the morning of admission, an episode of involuntary movements of the left leg and left shoulder occurred and persisted for 1 hour. Several hours after the symptoms abated, the patient's wife found the patient to be unresponsive; he was sitting in a chair. Emergency medical services were called, and when they arrived, the patient was responsive. The fingerstick blood glucose level was 180 mg per deciliter (10.0 mmol per liter) and the blood pressure 110/80 mm Hg. The patient was transported to the emergency department of this hospital for further evaluation. In the emergency department, the patient reported dysuria and increased urinary frequency. The patient's daughter noted that he had been more anxious during the past 3 years and occasionally had trouble with memory. Other medical history included Barrett's esophagus, benign prostatic hypertrophy, chronic hepatitis B virus infection, eczema, gastroesophageal reflux disease, hypertension, nonischemic cardiomyopathy, and osteoporosis. There was no history of head trauma or extended loss of consciousness. Medications included aspirin, atorvastatin, doxazosin, finasteride, omeprazole, metoprolol, sacubitril, and valsartan. There were no known drug allergies. The patient was a lifelong nonsmoker and drank alcohol rarely; he did not use illicit drugs. His mother had had gastric cancer, and his sister had had esophageal cancer; there was no family history of seizures. On examination, the temporal temperature was 36.8°C, the blood pressure 152/97 mm Hg, the pulse 65 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96% while the patient was breathing ambient air. The body-mass index was 21.7. The blood pressure decreased to 130/63 mm Hg with standing. The patient was alert and interactive. The lower jaw was held to the left, but the nasolabial folds and smile were symmetric with activation. There were nonrhythmic, nonstereotyped, writhing movements of the left arm. Tone was normal, and strength was assessed as 5 out of 5 in the arms and legs. Results of liver-function and kidney-function tests were normal, as were blood levels of glucose and electrolytes, except for the sodium level, which was 125 mmol per liter. The lactate level was 2.1 mmol per liter (19 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter [5 to 18 mg per deciliter]). The urinalysis was normal.

(A) MRI of the head performed three months before admission, T1-weighted post-contrast image. (B) CT angiogram of the head and neck, coronal maximum-intensity-projection image at the level of the carotid bifurcations.

(A) MRI of the head performed three months before admission, T1-weighted image obtained after the administration of intravenous contrast material, shows a focus of cortical enhancement in the right middle frontal gyrus that was thought to be a small vascular anomaly. (B) CT angiogram of the head and neck, coronal maximum-intensity-projection image derived at the level of the carotid bifurcations, shows heavily calcified atherosclerotic plaque with severe stenosis of the distal right common carotid artery, extending into the proximal right internal carotid artery.

Doppler ultrasound of the carotid arteries.

Doppler ultrasound image of the carotid arteries shows elevated Doppler flow velocities within the proximal right internal carotid artery. The Doppler waveform contours have poststenotic turbulence.

Transient ischaemic attack


A 71-year-old woman with recurrent breast cancer and diffuse cutaneous systemic sclerosis presented with 7 months of progressive fatigue and dyspnea on exertion. Two months before admission, she developed worsening dyspnea, palpitations, and dizziness. Laboratory studies revealed hemolytic anemia with low haptoglobin (<15 mg/dl), elevated lactate dehydrogenase (675 U/liter), and schistocytes on peripheral blood smear. Direct antiglobulin test was negative, complement levels were low, and a low titer of cold agglutinins was present. Testing for antibodies against β2-glycoprotein I and cardiolipin was negative, as was lupus anticoagulant screening. Flow cytometry showed no aberrant clonal population or evidence of paroxysmal nocturnal hemoglobinuria. CT of the chest, abdomen, and pelvis showed bilateral mediastinal and hilar lymphadenopathy unchanged from 2 years earlier. On examination, she had jaundice, scleral icterus, a well-healed lumpectomy scar on the left breast, mild skin thickening on hands and feet, and a BMI of 17. Laboratory findings on admission included hematocrit 14.8%, hemoglobin 5.3 g/dl, platelet count 43,000/μl, reticulocyte count 15.8%, elevated ferritin (18,050 μg/liter), total bilirubin 4.1 mg/dl, creatinine 2.87 mg/dl, and proteinuria with protein:creatinine ratio 6.41.

(A–C) Peripheral-blood smear, Wright-Giemsa staining.

Peripheral-blood smear with Wright-Giemsa staining showing (A) anisopoikilocytosis and schistocytes (arrows), (B) teardrop cells (arrows), and (C) immature myeloid precursors (arrow) and nucleated red cells (arrowheads).

(A) 18F-FDG PET-CT, anteroposterior maximum intensity projection. (B) 18F-FDG PET-CT, sagittal view, spine. (C) CT, sagittal view, spine. (D) 18F-FDG PET-CT, axial view, pelvis. (E) CT, axial view, pelvis.

18F-fluorodeoxyglucose (FDG) positron-emission tomography-CT showing (A) anteroposterior maximum intensity projection with diffuse, heterogeneous, abnormally increased FDG uptake in the axial and appendicular skeleton (arrows). (B) Sagittal images showing multiple focal sites of abnormal uptake in the spine (arrows), with no correlative lytic or blastic bone lesions on (C) CT. (D) Axial images of the pelvis showing multiple focal sites of abnormal uptake in the iliac bones and sacrum (arrows), with no correlative lytic or blastic bone lesions on (E) CT.

(A) Bone marrow core biopsy, H&E staining. (B) Bone marrow core biopsy, immunohistochemical staining for MNF116 (cytokeratin). (C) Bone marrow core biopsy, immunohistochemical staining for estrogen receptor.

Core-biopsy specimens of bone marrow showing (A) infiltration of atypical nonhematopoietic cells (outlined by dashed lines) on hematoxylin and eosin staining. (B) Immunohistochemical staining showing membranous staining for MNF116 (cytokeratin) in brown. (C) Nuclear staining for estrogen receptor in brown in the atypical cells.

Laboratory results on admission.

Laboratory data showing on admission: hematocrit 14.8%, hemoglobin 5.3 g/dl, white-cell count 13,340/μl with 82.1% neutrophils, platelet count 43,000/μl, mean corpuscular volume 101.4 fl, reticulocyte count 15.8%, prothrombin time 16.8 sec (INR 1.4), d-dimer 9321 ng/ml, haptoglobin <10 mg/dl, lactate dehydrogenase 5896 U/liter, ferritin 18,050 μg/liter, total bilirubin 4.1 mg/dl, direct bilirubin 0.4 mg/dl, albumin 3.8 g/dl, alanine aminotransferase 58 U/liter, aspartate aminotransferase 135 U/liter, alkaline phosphatase 77 U/liter.

Metastatic breast carcinoma with extensive bone marrow involvement

Breast carcinoma NOS

Metastatic breast carcinoma [primary breast carcinoma spreading elsewhere]

bone marrow metastasis


A 12-year-old boy with autism was admitted to this hospital because of decreased vision in both eyes. The patient had been in his usual state of health until 6 weeks before this admission, when he began to have difficulty seeing in both eyes. His vision was decreased when he woke up in the morning, improved throughout the day, and worsened again at night. Three weeks before the current admission, the patient told his parents about the vision changes. They took him to an optometry clinic for evaluation. Eyeglasses were not prescribed; a routine annual follow-up evaluation was scheduled. During the next 3 weeks, the patient noticed that the decrease in vision worsened. He typically walked on his toes and held onto his parents as he walked; however, 4 days before this admission, his parents noticed that he leaned on them heavily while walking. Two days before the current admission, they observed him walking into doors and walls and bumping into objects. On the day of this admission, the patient woke up screaming and panicked because he could not see. His parents brought him to the emergency department of this hospital. On evaluation, the patient reported that his vision had improved slightly throughout the day. He described darkening of his vision that was worse in the left eye than in the right eye. He was having difficulty identifying movement and details of objects, although he was able to see shapes and colors. The parents reported that the patient had been having puffiness and crusting of the eyes for 2 days, with no eye redness or pain. Review of systems was notable for 3 days of diarrhea and nausea. He had no fever, headache, rashes, mouth sores, joint pain, or weakness. The patient was born prematurely, at 7 months' gestation. Labor and delivery had taken place outside the hospital setting, and perinatal hypoxia had occurred. The patient had been taken urgently to another hospital, where he was resuscitated and then hospitalized in the neonatal intensive care unit for 2 months. The patient had autism and attention deficit–hyperactivity disorder (ADHD). He had developmental delays in speech, language, cognition, and fine motor skills. He had received all routine childhood vaccinations and was taking risperidone; there were no known drug allergies. The patient lived with his parents and older sister, all of whom were healthy. Ten months before this admission, they had moved from an urban area to a rural area in New England. The patient was in sixth grade and was enrolled in special education classes at school. He had been an avid player of video and virtual reality games, but his parents had removed the gaming systems from their home 2 months before the patient's vision changes had begun. He continued to watch videos on the computer and television; his parents noted that he did not sit close to the devices and sometimes looked at the wall instead of the screen. The patient's parents described him as a 'picky eater.' His diet consisted almost exclusively of hamburgers, french fries, ranch dressing, glazed doughnuts, and juice boxes. The patient avoided trying new foods and did not take vitamin pills or gummies because he disliked the taste or texture. On examination, the temporal temperature was 36.2°C, the blood pressure 104/71 mm Hg, the heart rate 94 beats per minute, and the oxygen saturation 98% while the patient was breathing ambient air. The height was 156 cm (70th percentile), the weight 40.3 kg (38th percentile), and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) 16.6. The patient was pale, alert, interactive, and wary of the physical examination. Mild periorbital swelling was present. The visual acuity in both eyes was limited to hand motion. The pupils were symmetric and reactive to light, and the extraocular movements were full. Color-vision testing, automated perimetry, fundus photography, and optical coherence tomography could not be performed because the patient had poor vision and was unable to cooperate. A slit-lamp examination was notable only for keratinization of the conjunctiva in both eyes. A funduscopic examination revealed pallor of the optic disk in both eyes. Examination of the peripheral retina was limited because the patient was unable to cooperate. Strength, sensation, reflexes, and coordination were normal. A gait examination revealed toe walking; the patient asked for assistance when walking. The abdomen was nontender. Horizontal ridges were present on the toenails, and there were scattered bruises on the arms and legs. No ulcers or rashes were seen.

Clinical photograph of the toenails obtained on the day of admission.

Clinical photograph of the toenails obtained on the day of the current admission shows horizontal ridges on the toenails.

(A) Head MRI, coronal T2-weighted sequence, including optic chiasm. (B) MRI of the optic radiations, axial T2-weighted sequence. (C) Orbit MRI, high-resolution coronal fluid-sensitive short-tau inversion recovery (STIR) sequence. (D) Orbit MRI, high-resolution coronal T2-weighted fat-suppressed sequence. (E) Sagittal three-dimensional fluid-attenuated inversion recovery (FLAIR) MRI of the calvarium and intracranial contents.

(A) Coronal T2-weighted image of the head and optic chiasm shows no abnormalities. (B) Axial T2-weighted image of the optic radiations shows no abnormalities. (C) High-resolution coronal image from a fluid-sensitive short-tau inversion recovery sequence of the orbits shows a very subtle hyperintense signal in the central portion of the optic nerves (arrow), which is more conspicuous in the left eye than in the right eye. (D) High-resolution coronal T2-weighted fat-suppressed image of the orbits shows no abnormal enhancement in the optic nerves or elsewhere in the orbit. (E) Sagittal three-dimensional image from a fluid-attenuated inversion recovery sequence shows marked thickening of the calvarium (arrow), without focal lesions; the intracranial contents appear normal.

Laboratory results on admission.

Laboratory data on admission shows white-cell count 5700 per μl, hemoglobin 12.3 g/dl, hematocrit 37.0%, mean corpuscular volume 89.4 g/dl, platelet count 216,000 per μl, sodium 137 mmol/liter, potassium 4.1 mmol/liter, chloride 104 mmol/liter, carbon dioxide 20 mmol/liter, urea nitrogen 6 mg/dl, creatinine 0.38 mg/dl, glucose 77 mg/dl, aspartate aminotransferase 17 U/liter, alanine aminotransferase 20 U/liter, alkaline phosphatase 422 U/liter, total bilirubin 0.4 mg/dl, albumin 3.6 g/dl, total protein 5.9 g/dl, prothrombin time 17.1 sec, prothrombin-time international normalized ratio 1.4.

Nutritional optic neuropathy due to multiple nutritional deficits, including vitamin A, copper, and zinc deficiencies

Nutritional optic neuropathy

Vitamin A deficiency

Copper deficiency

Zinc deficiency


A 36-year-old man presented with 18 days of fevers up to 39.5°C, preceded by a sensation of throat swelling. He had been in his usual state of health until 18 days before presentation, when he began to have a sensation of swelling in his throat. Three days later, his temperature was 38.4°C. He was initially treated with amoxicillin-clavulanic acid for presumptive streptococcal pharyngitis after white spots were noted on his tonsils at an urgent care clinic. Fevers persisted despite treatment, along with headaches and fatigue. The patient reported that the lower part of his neck felt swollen and that moving his neck caused discomfort, but he had no dysphagia, odynophagia, rhinorrhea, or rash. His medical history included seasonal allergies. He had traveled to the southwestern United States with his wife 2 weeks before symptom onset. His wife had experienced fever and sore throat during the trip that resolved spontaneously. He lived in Massachusetts, worked in an office setting, and had moved to the United States from Asia 7 years prior. On examination at the infectious diseases clinic, he was afebrile with blood pressure 144/98 mm Hg, pulse 130 beats per minute, and oxygen saturation 99% on room air. The oropharynx appeared normal without tonsillar exudates. There was no lymphadenopathy. Firm, nontender thyroid tissue was palpable in the anterior portion of the neck.

Laboratory results obtained 11 days before presentation.

Laboratory data obtained 11 days before the current presentation showed: hematocrit 43.8% (reference range 41.0-53.0), hemoglobin 14.6 g/dl (13.5-17.5), white-cell count 7320 per μl (4500-11,000), with differential count showing neutrophils 5100 per μl (1800-7700), lymphocytes 1430 per μl (1000-4800), monocytes 610 per μl (200-1200), eosinophils 130 per μl (0-900), basophils 30 per μl (0-300), immature granulocytes 20 per μl (0-100), and platelet count 375,000 per μl (150,000-400,000).

(A) Axial CT of the neck with intravenous contrast. (B) Coronal CT of the neck with intravenous contrast.

(A) Axial CT image of the neck obtained after administration of intravenous contrast material showing heterogeneous appearance of the thyroid gland with a possible nodule in the right lobe. (B) Coronal CT image of the neck obtained after administration of intravenous contrast material showing heterogeneous appearance of the thyroid gland with a possible nodule in the right lobe.

Subacute thyroiditis


A 32-year-old man presented with 2 weeks of confusion and headache and 2 days of fever. His wife noted anxiety-like behavior beginning 1 month before admission, followed by confusion (unable to recall children's ages or identify the date) starting 2 weeks before admission, accompanied by headache and neck stiffness. Two days before admission, fever developed. On the day of admission, he had worsening confusion and somnolence. The patient had a 10-year history of Behçet's disease with multiple complications including pulmonary embolism, iliac artery aneurysm and dissection, bilateral renal vein thrombosis, erythema nodosum, deep venous thrombosis, uveitis, inferior vena cava clot with superior vena cava syndrome requiring thrombectomy, and renal infarction. Flares typically included oral ulcers, genital ulcers, uveitis, or fever. He also had a history of lymphocyte-predominant meningitis 17 months prior and COVID-19 16 months prior. On examination, he was somnolent but arousable, fluctuating alertness, intermittently able to answer simple questions, temperature 39.5°C, oriented to person and place but not time, no neck stiffness, mild left eye injection, no oral or skin lesions, able to move arms and legs with no focal neurologic findings noted.

Laboratory results on admission.

Laboratory data on admission showed hemoglobin 14.5 g/dl, hematocrit 44.2%, white cell count 11,760/μl with neutrophils 9430/μl, lymphocytes 1100/μl, monocytes 1080/μl, eosinophils 800/μl, basophils 300/μl, platelet count 208,000/μl. HIV and treponemal antibodies were nonreactive, cryptococcal antigen negative, tuberculosis interferon-γ release assay negative, C-reactive protein 39.1 mg/L (reference <8.0), erythrocyte sedimentation rate 24 mm/hr (reference 0-13).

(A–F) MRI of the head performed on hospital day 5, FLAIR sequence.

MRI of the head performed on hospital day 5 showed fluid-attenuated inversion recovery (FLAIR) images with patchy hyperintense signal abnormalities in the pons (A), midbrain (B), inferior thalami (C), right lentiform nucleus (C,D), right posterior limb of internal capsule (E), left anterior thalamus (E), and right caudate head with upper anterior limb of internal capsule (F). No associated restricted diffusion, abnormal enhancement, hemorrhage, or mass effect. No evidence of acute arterial infarction or venous sinus thrombosis.

Behçet disease

encephalitis NOS


A 43-year-old female patient presented with a left-sided neck mass discovered one month prior. The mass was occasionally accompanied by spontaneous pain and showed progressive growth, measuring approximately 2.0cm×2.0cm at presentation. The patient had no fever, cough, or sputum production. She experienced occasional radiating headaches and intermittent left-sided back pain lasting several seconds that began 20 days prior, sometimes accompanied by chest tightness. She denied nausea, vomiting, sore throat, dysphagia, dyspnea, palpitations, or numbness of the limbs, joints, teeth, or face. The patient had previously received anti-inflammatory treatment with cephalosporins at an outside hospital with slight symptom relief, but symptoms recurred after discontinuation. A prior neck lymph node aspiration biopsy at a local hospital showed lymphocytic proliferative changes. Past medical history included a lymph node aspiration biopsy performed on May 28, 2021, at Xi'an Jiaotong University First Affiliated Hospital, with pathology results on May 31 showing cord-like lymphocytic proliferative changes, suggestive of Castleman disease based on immunohistochemistry. Physical examination revealed a hard mass measuring approximately 2.0cm×2.0cm at the anterior border of the left sternocleidomastoid muscle, with tenderness on pressure, poor mobility, no surface redness, ulceration, or elevated skin temperature, and no enlargement of ipsilateral subclavicular or axillary lymph nodes.

(A) Electronic nasopharyngolaryngoscopy of nasopharyngeal region. (B) Electronic nasopharyngolaryngoscopy of left epiglottis. (C) Electronic nasopharyngolaryngoscopy of bilateral vocal cords in open position. (D) Electronic nasopharyngolaryngoscopy of bilateral vocal cords during movement. (E) Electronic nasopharyngolaryngoscopy of bilateral vocal cords in closed position. (F) Electronic nasopharyngolaryngoscopy of lingual tonsil.

(A) Nasopharyngeal lymphoid tissue hyperplasia, electronic nasopharyngolaryngoscopy. (B) Left epiglottic cyst. (C) Bilateral vocal cords in open position. (D) Bilateral vocal cords during movement. (E) Bilateral vocal cords in closed position. (F) Lingual tonsil lymphoid follicular hyperplasia. The examination showed nasal septum deviation, epiglottic cyst, bilateral vocal cord nodules, and reflux laryngitis.

Neck color Doppler ultrasound, left cervical region II.

Neck color Doppler ultrasound showing hypoechoic mass in left cervical region II (enlarged lymph node?).

Left cervical lymph node pathology, H&E staining. Immunohistochemistry: CD30 (scattered cells positive). In situ hybridization: EBER negative. PAS stain negative. Silver stain negative. Acid-fast stain negative.

Pathology results showing lymph nodes from left cervical regions II and III with reactive lymphoid follicular hyperplasia, granulomatous inflammation with central abscess formation, suggestive of infectious disease with high possibility of cat scratch disease. Immunohistochemistry: CD30 (scattered cells positive). In situ hybridization: EBER negative. Special stains: PAS stain negative, silver stain negative, acid-fast stain negative.

Cat-scratch disease


A 42-year-old male patient presented with polyuria, polydipsia, nausea, vomiting, and fatigue for 3 months. He had nocturia 3-4 times per night with daily urine output of 3500-7000 ml, accompanied by thirst, polydipsia, nausea, vomiting, poor appetite, and limb weakness. His past medical history was significant for IgG4-related disease diagnosed in 2023 based on left submandibular lymph node biopsy. He had previously experienced left submandibular swelling in 2020, right eyelid swelling in 2021, and recurrent orbital swelling with pigmentation in 2023. Physical examination revealed right eyelid swelling, clear consciousness, normal visual fields and visual acuity, with no other significant findings on cardiopulmonary and abdominal examination.

(A) Clinical photograph, right eyelid, before glucocorticoid pulse therapy. (B) Clinical photograph, right eyelid, 10 days after glucocorticoid pulse therapy. (C) Clinical photograph, right eyelid, 1 week after continued glucocorticoid combined with immunosuppressant therapy.

(A) Physical examination before glucocorticoid pulse therapy showing right eyelid swelling. (B) 10 days after glucocorticoid pulse therapy, right eyelid swelling significantly improved. (C) After 1 week of continued glucocorticoid combined with immunosuppressant therapy, right eyelid swelling further improved.

Laboratory results before treatment.

Laboratory results before treatment showed: GH 0.42 ng/ml, PRL 24.56 ng/ml, LH 1.90 mIU/ml, FSH 3.20 mIU/ml, T 1.04 ng/ml, E2 20.20 pg/ml, P 0.30 ng/ml, ACTH 23.9 pg/ml, ROC 10.9 μg/dl, FT3 2.31 pg/ml, FT4 1.30 ng/dl, TSH 1.93 μIU/ml, IgG4 4362.0 mg/dl. Other findings included urine specific gravity 1.004, ESR 18 mm/h, uric acid 498.9 μmol/L, fasting blood glucose 2.73 mmol/L, serum sodium 149.30 mmol/L, serum potassium 3.47 mmol/L.

(A) Pre-treatment sagittal MRI of the pituitary gland. (B) Pre-treatment coronal MRI of the optic chiasm and bilateral optic tracts. (C) Pre-treatment sagittal contrast-enhanced MRI of the pituitary stalk, diameter 5.79 mm. (D) Pre-treatment coronal contrast-enhanced MRI of the pituitary gland.

(A) Pre-treatment sagittal MRI showing mild superior pituitary bulging (height ~8.4 mm) with homogeneous signal. (B) Pre-treatment coronal view showing optic chiasm and bilateral optic tract swelling. (C) Pre-treatment sagittal enhanced view showing markedly thickened pituitary stalk (diameter 5.79 mm) with strong enhancement. (D) Pre-treatment coronal enhanced view showing enlarged pituitary with homogeneous signal. Loss of posterior pituitary T1 hyperintensity was noted.

(A-C) PET of the pituitary region, coronal, sagittal, and axial views, SUVmax ~4.4. (D-F) CT of the pituitary region, coronal, sagittal, and axial views.

(A-C) PET images (coronal, sagittal, and axial views) showing band-like hypermetabolic signal in the pituitary region with radiotracer uptake in the thickened pituitary stalk area (SUVmax ~4.4). (D-F) CT images (coronal, sagittal, and axial views) showing slightly hyperdense area in the pituitary region with thickened pituitary stalk and blurred margins.

IgG4-related hypophysitis


A 71-year-old woman presented with a 3-day history of headache and fatigue, followed by sudden onset of confusion and language production difficulties while typing at work. The confusion resolved briefly but recurred later that evening. She had a history of myasthenia gravis (diagnosed 18 years prior, treated with mycophenolate mofetil for 7 years), vitamin B12 deficiency, and hypertension. Past surgical history included supracervical hysterectomy with bilateral salpingo-oophorectomy (31 years prior), transsternal thymectomy and wedge resection of right upper lobe for cortical thymoma (22 years prior), and sigmoid colectomy for recurrent diverticulitis (7 years prior). On examination at the current hospital, she had severe expressive aphasia, followed commands intermittently, disconjugate gaze at rest, motor strength 5/5 in left extremities and 4/5 in right extremities. Blood phosphorus was 2.2 mg/dL (reference range 2.6-4.5); other routine labs were normal.

(A,B) Brain MRI performed on hospital day 2, T1-weighted sequence with contrast, axial (A) and coronal (B) views. (C) Brain MRI, T2-weighted FLAIR sequence, axial view. (D) Brain MRI, T2-weighted FLAIR sequence, coronal view.

(A) Axial T1-weighted image obtained on hospital day 2 after contrast administration shows masslike heterogeneous enhancement centered in the left centrum semiovale extending to cortex. (B) Coronal T1-weighted image obtained on hospital day 2 after contrast shows same heterogeneous enhancement. (C) Axial T2-weighted FLAIR image shows surrounding signal hyperintensity and mass effect suggestive of vasogenic edema. (D) Coronal T2-weighted FLAIR image shows surrounding signal hyperintensity and mass effect.

Frozen section of brain tissue, H&E staining.

Frozen section of brain tissue examined intraoperatively shows brain parenchyma with atypical cells suggestive of cancer, with no acute inflammation present (H&E staining).

(A) Susceptibility-weighted imaging on postoperative day 1. (B) T2-weighted FLAIR imaging. (C) Three-dimensional T1-weighted imaging after contrast. (D) Diffusion-weighted imaging. (E) Coronal three-dimensional T1-weighted imaging after contrast.

(A) Susceptibility-weighted imaging on postoperative day 1 shows expected blooming indicating blood products at biopsy site. (B) T2-weighted FLAIR imaging shows worsening and expansion of signal hyperintensity compared to preoperative MRI. (C) Three-dimensional T1-weighted imaging after contrast shows worsening heterogeneous enhancement. (D) Diffusion-weighted imaging shows nonspecific punctate foci of restricted diffusion near biopsy site. (E) Coronal three-dimensional T1-weighted image after contrast shows enhancement surrounding biopsy site.

Brain tissue, H&E staining.

Permanent section of brain tissue shows dense collections of neutrophils in microabscesses (H&E staining).

(A) Gram staining of brain aspirate specimen, initial sample. (B) Gram staining of brain aspirate specimen, repeat sample. (C) MALDI-TOF mass spectrometry of brain aspirate specimen.

(A) Initial Gram's staining of brain aspirate specimen shows few gram-negative rods. (B) Repeat Gram's staining shows gram-positive organisms. (C) MALDI-TOF mass spectrometry results establish definitive diagnosis of Listeria monocytogenes infection.

Brain abscess due to infection with Listeria monocytogenes

abscess of brain

Listeriosis