Neuropathologic features of central nervous system hemangioblastoma

Abstract

Hemangioblastoma is a benign, highly vascularized neoplasm of the central nervous system (CNS). This tumor is associated with loss of function of the VHL gene and demonstrates frequent occurrence in von Hippel-Lindau (VHL) disease. While this entity is designated CNS World Health Organization grade 1, due to its predilection for the cerebellum, brainstem, and spinal cord, it is still an important cause of morbidity and mortality in affected patients. Recognition and accurate diagnosis of hemangioblastoma is essential for the practice of surgical neuropathology. Other CNS neoplasms, including several tumors associated with VHL disease, may present as histologic mimics, making diagnosis challenging. We outline key clinical and radiologic features, pathophysiology, treatment modalities, and prognostic information for hemangioblastoma, and provide a thorough review of the gross, microscopic, immunophenotypic, and molecular features used to guide diagnosis.

Keywords: Brain; Cerebellar neoplasms; Hemangioblastoma; Neuropathology; von Hippel-Lindau disease.

Fig. 1.

Representative brain magnetic resonance imaging for hemangioblastoma. (A) T2/FLAIR and (B) T1-weighted post-contrast sequences showing a posterior fossa cystic mass with a mural enhancing nodule.

Fig. 2.

Intraoperative direct smear and frozen section findings of central nervous system hemangioblastoma. Representative intraoperative analysis of hemangioblastoma demonstrating (A) resistance to smear cytological preparation and (B) the presence of cells with vacuolated cytoplasm on frozen section.

Fig. 3.

Histopathological features of central nervous system hemangioblastoma. Representative permanent sections highlighting how hemangioblastomas are highly vascular neoplasms and may contain (A) abundant capillaries, (B) large branching vessels, and/or (C) areas of hemorrhage. (D) Stromal cells contain abundant foamy vacuolated cytoplasm. (E) Nuclear atypia may be seen in some stromal cells. (F) Hemangioblastomas often from well-demarcated border with adjacent brain parenchyma.

Fig. 4.

Immunohistochemical features of central nervous system hemangioblastoma. Immunohistochemical profiling for hemangioblastoma usually includes positivity for (A) inhibin alpha, (B) CAIX, and (C) CD31, with negativity for renal markers such as (D) PAX8.