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von Hippel-Lindau (VHL) disease is an autosomal-dominant, familial cancer syndrome that genetically predisposes affected individuals to characteristic tumors in multiple organs.
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The natural history of VHL disease, including the development of tumors and disease severity, is highly variable.
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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
von Hippel-Lindau Disease: Review of Genetics and Imaging
Section snippets
Key points
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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Cited by (30)
Nervous system
2023, Multi-system Imaging Spectrum associated with Neurologic DiseasesVon Hippel-Lindau disease with extramedullary and pancreatic involvement
2022, Medical Journal Armed Forces IndiaCitation Excerpt :The sequencing of VHL gene is done including the coding exons and the intron-exon limits. The variations found are then compared with the 377 known intragenic mutations associated with VHL disease.5 The variant found in this patient was c.227_227 of the TCT region located in the exon 1 of the VHL gene, which indicates a heterozygous deletion in 227–229 nucleotides, which results in the elimination of phenylalanine at codon 76, a variant also found in patients with de novo mutations.11
Biological Treatments of Neurofibromatosis Type 2 and Other Skull Base Disorders
2021, Otolaryngologic Clinics of North AmericaCitation Excerpt :ELSTs develop from endolymphatic epithelium within the vestibular aqueduct.26 These tumors invade into the temporal bone and can cause hearing loss, tinnitus, vertigo, aural fullness, and facial-nerve dysfunction.26,27 ELSTs are found in 6% to 15% of VHL patients and are rare in the general population.27
Imaging of Tumor Syndromes
2021, Radiologic Clinics of North AmericaGenetic predisposition to cancer: Surveillance and intervention
2019, Seminars in Pediatric SurgeryImaging and Screening of Hereditary Cancer Syndromes
2017, Radiologic Clinics of North AmericaCitation Excerpt :The pancreas (35%–77%), central nervous system (CNS) (44%–72%), and kidneys (25%–60%) are the most commonly involved organs in VHL syndrome.45 Because most VHL-associated tumors show characteristic findings on imaging studies, radiologists play a major role in the initial diagnosis, surveillance of asymptomatic carriers, and posttreatment follow-up.46 VHL should be suspected in individuals with more than 1 CNS hemangioblastoma, or 1 hemangioblastoma with 1 visceral disorder, or any manifestation with a known family history.47
Disclosure Statement: The authors have nothing to disclose.