Hemangioblastoma

Epidemiology and Etiology:

• Sporadic:
• 30-65y generally
• M > F somewhat

Common sites:

•  Sporadic:
• cerebellum (most)
• medulla
• spinal cord
• VHL:
• subtentorial – cerebellum (most)
• retina
• intraspinal
• cranial nerves
• supratentorial meninges

Gross features:

•  cystic component
• highly vascular
• abutting the leptomeninges
• yellow in parts maybe (lipid in stromal cells)

Histologic features:

•  variable cellularity
• highly cellular areas alternating with paucicellular regions
• paucicellular regions composed of dilated vessels and cyst-like spaces
• variable number of stromal cells versus vascular elements
• Very vascular
• Large feeding and draining vessels
• Innumerable intervening capillaries
• Endothelial cells and pericytes
• Stromal cells are the neoplastic cells
• Lipid vacuoles – amount of lipid varies
• Cytoplasmic hyaline droplets (minority)
• Mast cells common
• Uniformly distributed
• Extramedullary erythropoiesis maybe
• cyst wall:
• dense layer of non-neoplastic piloid gliosis
• Rosenthal fibres abundant
• Mitoses uncommon
• No prognostic significance
• No histologic difference between sporadic and VHL-associated
• Reticular variant
• Small nests and individual cells
• Rich in reticulin
• Cellular variant:
• Larger lobules of cells predominating with vascular elements surrounding lobules
• Angioglioma:
• Hemangioblastoma mixed with glial element
• Astrocytoma, ependymoma, or oligodendroglioma

Immunophenotype:

Marker:	Sensitivity:	Specificity:
Inhibin		May be positive in renal cell carcinoma?
GFAP (neg)	Some have focal +
Reticulin (highlights vasculature)
CD31 (only non-neoplastic endothelial cells)
NSE
Neurofilament protein (neg)
Synaptophysin (neg)
S-100	Variable
CK (neg)
EMA (neg)	Occ. Focal +
EPO

Molecular features:

• sporadic (most):
• some have VHL mutations
• Familial:
• von Hippel-Lindau (VHL) disease

• without the inhibiting effect of normal VHL, stromal cells overexpress VEGF, with resultant angiogenesis

Other features:

• polycythemia (10%)
• tumoural production of erythropoietin
• Treatment:
• Surgical excision

References:

•  AFIP Tumours of the Central Nervous System (2007)