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Hemangioblastoma

The Key Features

CLINICAL FEATURES

A benign or grade I tumor in the WHO Classification. Accounts for approximately 1-2% of intracranial tumors.
Locations: mostly in the cerebellum, especially the posterior cranial fossa, and is the most common primary adult intraaxial posterior fossa tumor. Cerebellar hemangioblastomas are frequently referred to as Lindau tumors. The second most common location is the spinal cord, but only accounts for 1-2% of hemangioblastomas, and they are almost exclusively intramedullary.
Male-to-female ratio approximately 2:1
Age: usually between the third and fifth decades. Rarely affect children.
Most cases occur sporadically, but 25% associate with the von Hippel-Lindau syndrome

Features for VHL association: younger age (3rd-4th decade vs 5th-6th decade); multiple tumors; and extra cranial.
In up to 20% of cases, the cells have endocrine function and produce erythropoetin that causes polycythemia.

GROSS FINDINGS

The cerebellar tumor often occurs as a cystic lesion with a mural mass usually abut the leptomeninges . The mural mass represents the real tumor. The spinal tumor typically intramedullary, discrete and usually in contact with the leptomeninges posterior.
The cut surface of the tumor are usually vascular/spongy and red-brown to yellow, due to their dense vasculature and high lipid content. They may include a cyst that contains a clear fluid, but solid tumors are as common as cystic ones. The tumor usually grows inside the parenchyma of the cerebellum, brain stem, or spinal cord; it is attached to the pia mater.

MICROSCOPIC FINDINGS

Architecture: The tumor is normally well-demarcated. Variable cellularity of highly cellular areas alternating with paucicellular regions composed of predominantly dilated vessels and cysts.
Cytology; consists of two distinct cellular components. 1). vasculature, consists of large feeding and draining vessels and innumerable intervening capillaries. The capillaries are composed of small, perivascular, endothelial cells that have dark compact nuclei and sparse cytoplasm; 2). Stromal cells (the actual neoplastic cells), contain multiple vacuoles and granular foamy cytoplasm rich in lipids. These stromal cells may show some nuclear pleomorphism, but mitotic figures rarely are seen. The nuclei of stromal cells are mainly medium in size, round, or reniform with scattered large hyperchromasia. The exact histogenetic origin of stromal cells is unknown.
Mast cells are commonly seen in the tumor that can be highlight with roluidine blue or Giemsa stain.

SUBTYPES

Cellular variant: aggregation of stromal cells in large cohesive nests and lobules with an epithelioid presentation. Higher recurrence.
Reticular variant: more common. composed of predominantly of small nests and individual cells, especially rich in reticulin.

DIFFERENTIAL DIAGNOSES

Metastatic renal cell carcinoma: similar histologic appearance and similar incidence in patients with von Hippel-Lindau syndrome. On HE stained sections, renal cell carcinoma can have necrosis, mitosis and large nucleoli, features almost always absent on hemangioblastoma. Renal cell carcinoma is also immunoreactive for cytokeratin, CD10, and EMA, while hemangioblastoma is positive for inhibin^,but negative for cytokeratin, CD10, and EMA.
Other neoplasms with clear cell features include clear cell epdneymomas, clear cell meningioma with prominent vascularity, central liponeurocytoma of the cerebellum, and other metastatic clear cell neoplasms. Ependymomas are strongly are strongly immunoreactive for GFAP. Clear cell meningioma usually contains areas with features of classic meningothelial pattern and they are also immunoreactive for EMA. Central liponeurocytoma contains adipocytes and the neurocytoma cells are immunoreactive for synaptophysin. Metastatic carcinoma are immunoreactive for cytokeratin and, often, EMA.
Capillary hemangioma: no vacuolated interstitial cells.

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

The stromal cells stain strongly for S100, NSE, vimentin, EGFR and PDGF-alpha and inhibin, and they are typically negative for EMA, cytokeratin, neurofilament, and synaptophysin. In a small number of cases, the stromal cells express glial fibrillary acidic protein (GFAP).
The admixed capillaries stain for with typical endothelial markers, CD31, CD34 and Factor-VIII.

ELECTRON MICROSCOPIC FINDINGS

CYTOGENETIC STUDIES

TREATMENT AND PROGNOSIS

REFERENCES