Histology: A portion of the tissue contains cerebellar parenchyma, suggesting that this lesion is located in the posterior fossa. Half of the lesion consists of packets of small cells with clear to eosinophilic and granular cytoplasm, separated by delicate capillary vasculature. The other half of the lesion shows larger nests of cells with fibrillary to granular cytoplasm. There is minimal atypia, no appreciable mitotic activity, and no necrosis. Immunostains show the entirety of this lesion to be positive for inhibin.

Discussion: This is a hemangioblastoma in the brain, which can be sporadic but is also part of the von Hippel-Lindau disease spectrum caused by an autosomal dominant mutation in the VHL gene on chromosome 3. The lesions seen in this syndrome include hemangioblastomas, retinal angiomas, pancreatic and hepatic cysts, pheochromocytomas, and clear cell renal cell carcinomas. This particular hemangioblastoma is unique because in addition to the common “reticular” pattern of growth, it also demonstrates a partial cellular pattern, which is the area of larger expanded cellular nests. If this cellular region is sampled on frozen section, the lesion may be mistakenly classified as a low grade glioma. In one published series of hemangioblastomas, the cellular variant of hemangioblastoma accounted for ~10% of cases and had a higher proliferative rate and greater rate of recurrence. The differential diagnosis of hemangioblastoma includes other clear cell tumors, notably metastatic clear cell renal cell carcinoma, primary brain clear cell meningiomas, and metastatic neuroendocrine tumors with clear cytoplasm (malignant paragangliomas, clear cell neuroendocrine tumors of the pancreas, parathyroid carcinomas, etc). The immunophenotype of hemangioblastomas is unique; in contrast to the other lesions in the differential diagnosis, the neoplastic cells of hemangioblastoma label positivity for inhibin.