title: Prospective natural history study of central nervous system hemangioblastomas in von Hippel-Lindau disease.
abstract: OBJECTIVE
  The tumors most frequently associated with von Hippel-Lindau (VHL) disease are hemangioblastomas. While they are associated with significant neurological impairment and mortality, their natural history and optimal management have not been fully defined.
  
  
  METHODS
  Patients with VHL were enrolled in a prospective study designed to define the natural history of CNS hemangioblastomas. In the present analysis, serial imaging, laboratory, genetic, and clinical data were evaluated in those with at least 2 years of follow-up data.
  
  
  RESULTS
  At study entrance 225 patients (111 males, 114 females) harbored 1921 CNS hemangioblastomas in the supratentorial compartment (21 tumors [1%]), cerebellum (865 [45%]), brainstem (129 [7%]), spinal cord (689 [36%]), cauda equina (212 [11%]), and nerve roots (5 [0.3%]; follow-up 15,819 hemangioblastoma-years). Increased tumor burden was associated with partial deletions in the VHL gene (p = 0.005) and male sex (p = 0.002). Hemangioblastoma development (median 0.3 new tumors/year) was associated with younger age (p < 0.0001) and more tumors at study entrance (p < 0.0001). While 1278 hemangioblastomas (51%) did not grow, 1227 hemangioblastomas (49%) grew in a saltatory (886 [72%]), linear (76 [6%]), or exponential (264 [22%]) pattern. Faster tumor growth was associated with male sex (p = 0.001), symptomatic tumors (p < 0.0001), and tumors associated with cysts (p < 0.0001). Location-dependent tumor size was the primary predictor of eventual symptom formation (159 symptomatic tumors [6.3%]; area under the curve > 0.9).
  
  
  CONCLUSIONS
  Central nervous system hemangioblastoma burden in VHL is associated with partial germline deletions and male sex. Unpredictable growth of hemangioblastomas compromises assessment of nonsurgical therapies. The judicious treatment of symptom-producing hemangioblastomas, while avoiding unnecessary treatment of asymptomatic tumors that may not progress, can provide clinical stability.
authors.affiliation: Surgical Neurology Branch and.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Lonser
authors.forename: John A
authors.initials: JA
authors.lastname: Butman
authors.forename: Kristin
authors.initials: K
authors.lastname: Huntoon
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Asthagiri
authors.forename: Tianxia
authors.initials: T
authors.lastname: Wu
authors.forename: Kamran D
authors.initials: KD
authors.lastname: Bakhtian
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Edward H
authors.initials: EH
authors.lastname: Oldfield
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology* / Q000601:surgery; D016543:Central Nervous System Neoplasms / Q000150:complications* / Q000473:pathology / Q000601:surgery; D002648:Child; D005260:Female; D018325:Hemangioblastoma / Q000150:complications* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013116:Spinal Cord / Q000473:pathology* / Q000601:surgery; D016896:Treatment Outcome; D006623:von Hippel-Lindau Disease / Q000150:complications* / Q000473:pathology / Q000601:surgery