Case of the Week
- Details
Case History
28 year-old male with inguinal lymphadenopathy. IHC shows many CD15-, CD30+ large cells. CD20+ and CD3+ large cells seen. Background lymphocytes mostly T-cells with inverted CD4/CD8 ratio. Ki-67 elevated throughout infiltrate. EBER shows scattered + cells.
- EBV+ classic Hodgkin lymphoma
- Acute EBV infection (infectious mononucleosis)
- EBV+ PTCL
- EBV+ DLBCL, NOS
- Details
Case History
A 30 year-old man presents with progressive left side weakness. Imaging shows a right parietal lobe cystic lesion. Testing of the surgical resection specimen demonstrates negative IHC staining for IDH1 (R132H). FISH test is positive for 1p/19q codeletion. What is the next step?
- Sign out as diffuse astrocytoma, WHO grade II.
- Sign out as anaplastic oligodendroglioma, WHO grade III.
- Submit for sequencing (NGS) to confirm IDH status.
- Submit for fusion gene panel.
- Details
Case History
22-year-old man with visual field deficit. Suprasellar mass resected which showed nuclear expression of beta-catenin.
- Anaplastic meningioma, WHO grade III
- Adamantinomatous craniopharyngioma
- Erosive basosquamous carcinoma
- Pilomatrix carcinoma
- Details
Case History
A 25-year-old man presented with right lower extremity erythema and right ankle pain. Basic laboratory investigations showed serum creatinine of 3.5 mg/dL, uric acid of 10 mg/dL and 3+ proteinuria. All serological workup was negative. Renal biopsy performed showed globally sclerotic glomeruli (PASH, Fig A), segmentally sclerotic glomeruli (Jones silver, Fig B) and multiple foci of amorphous, faintly crystalline material surrounded by narrow zone of inflammatory cells and fibrosis in the tubulointerstitium (H&E, Fig C), consistent with microtophi. IF and EM were unremarkable.
Based on LM findings, which of the following gene may be mutated?
- APOL-1
- VHL
- UMOD
- ACTN4
Answer: “C” UMOD (Uromodulin)
Brief explanation of the answer:
The constellation of findings by LM, i.e., global and segmental glomerulosclerosis and microtophi, in the setting of hyperuricemia at young age that is out of proportion to renal dysfunction is suggestive of familial juvenile hyperuricemic nephropathy (FJHN).
FJHN is a rare autosomal dominant disease, caused by mutation in uromodulin gene (UMOD) that encodes for uromodulin protein (Tamm-Horsfall protein), secreted by the thick ascending limb of the Henle loop. The pathogenesis of the condition is not clear. Postulated mechanism includes the extratubular deposition of mutant uromodulin, which has proinflammatory capabilities, with ensuing tubulointerstitial nephritis accompanied by defect in tubular excretion of urate. Abnormal uromodulin may also trigger apoptosis of kidney cells and cause progressive kidney disease.
Clinically, FJHN is characterized by hyperuricemia, gout and chronic renal disease. Renal impairment usually appears during the teenage years and slowly progress to 30s and leads to end stage renal failure within 10 to 20 years. Xanthine oxidase inhibitor early in the course of the disease have reported some benefit.
Case contributed by: Huma Fatima, M.D., Assistant Professor, Anatomic Pathology