von Hippel-Lindau Disease: Review of Genetics and Imaging

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Key points

  • von Hippel-Lindau (VHL) disease is an autosomal-dominant, familial cancer syndrome that genetically predisposes affected individuals to characteristic tumors in multiple organs.

  • The natural history of VHL disease, including the development of tumors and disease severity, is highly variable.

  • Given the highly variable penetrance of disease, imaging study might be the first to raise suspicion of VHL disease when characteristic lesions are seen, such as multifocal renal cell carcinomas, bilateral

Genetics and pathology

The inheritance of VHL disease is autosomal-dominant; therefore, there is a 50% chance of inheriting the VHL gene from a carrier. Because there is variable gene expression, a wide spectrum of manifestations results with most patients with VHL gene mutation presenting with disease-related symptoms by the age of 65 years.1 The VHL gene, located on the short arm of chromosome 3 (3p25.5), is a tumor suppressor gene. Inactivation of its gene product, VHL protein, results in unregulated cell growth.7

Retinal hemangioblastomas

Retinal HBs generally are the first CNS lesions in VHL to come to clinical attention with lesions occurring at 25 years of age.9 They also occur frequently with 45% to 60% of VHL cases having a retinal lesion, and 50% are bilateral.9, 33 They have historically been called retinal angiomas or hemangiomas, but should be characterized as HBs because they are pathologically identical to other CNS HBs. They are histologically composed of significant vascular channels lined by cuboidal endothelial

Central nervous system hemangioblastomas

HBs of the CNS are classified as World Health Organization grade I tumors. Sixty percent to 80% of VHL patients will have a CNS HB. The cerebellum is the most common site (44%–72%), followed by spinal cord (13%–50%), brainstem, dorsal medulla and pons (10%–25%), and rarely, supratentorial structures, such as the optic pathways, choroid plexus, anterior pituitary, and infundibulum (1%).32, 39, 40 HBs tend to occur around the age of 30 years in VHL disease but can be seen earlier.9 The National

Endolymphatic sac tumor

The ELS is located at the end of the endolymphatic duct, at the aperture of the vestibular aqueduct, and lies within the dura of the posterior fossa. The ELS plays a role in the production and resorption of endolymph, which is found within the cochlea and semicircular canals. The ELSTs can grow outward into the cerebellopontine angle and mimic other tumors more commonly found at this site. They generally occur around 31 years of age.9 They are pathologically distinct from HBs and resemble

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    Disclosure Statement: The authors have nothing to disclose.

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