Hemangioblastoma

Clinical History:

The patient is an elderly woman with a cerebellar cystic lesion with an enhancing mural nodule that has been monitored since 2003, now with recent progression of clinical symptoms.

Which immunohistochemical profile is most consistent with this tumor?

A. Inhibin +, PAX8 +, EMA +, CD10 +

B. Inhibin +, aquaporin-1 +, PAX8 −, EMA −

C. Inhibin +, PAX8 −, EMA +, PR -, SSTR2A –

D. Inhibin −, GFAP +, OLIG2 +, IDH1 R132H +

Answer:

B (Hemangioblastoma)

• The slides show a well-circumscribed, highly vascular tumor made of a rich capillary network with intervening large polygonal stromal cells that have vacuolated (lipidized) clear cytoplasm and hyperchromatic, mildly pleomorphic nuclei. Mitoses are scarce. The stromal cells are the neoplastic component and are classically inhibin (alpha) positive, other typically positive stains include aquaporin-1, S100 and NSE. PAX8, cytokeratin and EMA are typically negative.
• The key mimic is metastatic clear cell renal cell carcinoma, which shares clear cells, a rich vasculature, and CA IX and CD10 expression, so those stains do not separate the two. RCC is PAX8, EMA and keratin positive and inhibin negative (option A).
• Option C (clear cell/lipidized meningioma) would be EMA, PR and SSTR2A positive and inhibin negative. Option D (clear cell/oligodendroglioma-like diffuse glioma) would be GFAP/OLIG2 positive, often IDH-mutant, and inhibin negative.
• Hemangioblastoma is a CNS WHO grade 1 tumor that favors the cerebellum, and most commonly occurs sporadically, though it is the hallmark lesion of von Hippel-Lindau disease. Both settings involve biallelic VHL inactivation with HIF pathway activation. The slow growth fits a lesion followed for more than two decades.

Reference(s) / Additional Reading: 

• WHO Classification of Tumours Editorial Board. Central Nervous System Tumours. WHO Classification of Tumours, 5th ed., Vol. 6. Lyon: IARC; 2021.
• Louis DN, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251.
• Hoang MP, Amirkhan RH. Inhibin alpha distinguishes hemangioblastoma from clear cell renal cell carcinoma. Am J Surg Pathol. 2003;27(8):1152-1156.