Investigation and Management of Apparently Sporadic Central Nervous System Haemangioblastoma for Evidence of Von Hippel-Lindau Disease

Genes (Basel). 2021 Sep 15;12(9):1414. doi: 10.3390/genes12091414.


Haemangioblastomas are rare, highly vascularised tumours that typically occur in the cerebellum, brain stem and spinal cord. Up to a third of individuals with a haemangioblastoma will have von Hippel-Lindau (VHL) disease. Individuals with haemangioblastoma and underlying VHL disease present, on average, at a younger age and frequently have a personal or family history of VHL disease-related tumours (e.g., retinal or central nervous system (CNS) haemangioblastomas, renal cell carcinoma, phaeochromocytoma). However, a subset present an apparently sporadic haemangioblastoma without other features of VHL disease. To detect such individuals, it has been recommended that genetic testing and clinical/radiological assessment for VHL disease should be offered to patients with a haemangioblastoma. To assess "real-world" clinical practice, we undertook a national survey of clinical genetics centres. All participating centres responded that they would offer genetic testing and a comprehensive assessment (ophthalmological examination and CNS and abdominal imaging) to a patient presenting with a CNS haemangioblastoma. However, for individuals who tested negative, there was variability in practice with regard to the need for continued follow-up. We then reviewed the results of follow-up surveillance in 91 such individuals seen at four centres. The risk of developing a potential VHL-related tumour (haemangioblastoma or RCC) was estimated at 10.8% at 10 years follow-up. The risks of developing a recurrent haemangioblastoma were higher in those who presented <40 years of age. In the light of these and previous findings, we propose an age-stratified protocol for surveillance of VHL-related tumours in individuals with apparently isolated haemangioblastoma.

Keywords: VHL; genetics; haemangioblastoma; renal cell carcinoma.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Central Nervous System Neoplasms / diagnosis
  • Central Nervous System Neoplasms / epidemiology
  • Central Nervous System Neoplasms / genetics
  • Cerebellar Neoplasms / diagnosis
  • Cerebellar Neoplasms / epidemiology*
  • Cerebellar Neoplasms / genetics
  • Clinical Audit
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Genetic Testing
  • Germ-Line Mutation
  • Hemangioblastoma / diagnosis
  • Hemangioblastoma / epidemiology*
  • Hemangioblastoma / genetics
  • History, 21st Century
  • Humans
  • Male
  • Middle Aged
  • Population Surveillance
  • Retrospective Studies
  • Risk Factors
  • United Kingdom / epidemiology
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics
  • Young Adult
  • von Hippel-Lindau Disease / diagnosis*
  • von Hippel-Lindau Disease / epidemiology*
  • von Hippel-Lindau Disease / genetics


  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human