title: Biological and clinical impact of hemangioblastoma-associated peritumoral cysts in von Hippel-Lindau disease.
abstract: OBJECTIVE
  Peritumoral cysts are frequently associated with CNS hemangioblastomas and often underlie neurological morbidity and mortality. To determine their natural history and clinical impact, the authors prospectively analyzed hemangioblastoma-associated peritumoral cysts in patients with von Hippel-Lindau (VHL) disease.
  
  
  METHODS
  Patients with VHL disease who had 2 or more years of follow-up and who were enrolled in a prospective study at the National Institutes of Health were included. Serial prospectively acquired laboratory, genetic, imaging, and clinical data were analyzed.
  
  
  RESULTS
  One hundred thirty-two patients (of 225 in the VHL study with at least 2 years of follow-up) had peritumoral cysts that were followed for more than 2 years (total of 292 CNS peritumoral cysts). The mean age at study entrance was 37.4 ± 13.1 years ([mean ± SD], median 37.9, range 12.3-65.1 years). The mean follow-up was 7.0 ± 1.7 years (median 7.3, range 2.1-9.0 years). Over the study period, 121 of the 292 peritumoral cysts (41.4%) became symptomatic. Development of new cysts was associated with a larger number cysts at study enrollment (p = 0.002) and younger age (p < 0.0001). Cyst growth rate was associated with anatomical location (cerebellum cysts grew faster than spine and brainstem cysts; p = 0.0002 and p = 0.0008), younger age (< 35 years of age; p = 0.0006), and development of new neurological symptoms (p < 0.0001). Cyst size at symptom production depended on anatomical location (p < 0.0001; largest to smallest were found, successively, in the cerebellum, spinal cord, and brainstem). The most common location for peritumoral cysts was the cerebellum (184 cysts [63%]; p < 0.0001).
  
  
  CONCLUSIONS
  Peritumoral cysts frequently underlie symptom formation that requires surgical intervention in patients with VHL disease. Development of new cysts was associated with a larger number of cysts at study enrollment and younger age. Total peritumoral cyst burden was associated with germline partial deletion of the VHL gene.
authors.affiliation: Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio;|Surgical Neurology Branch and.
authors.forename: Kristin
authors.initials: K
authors.lastname: Huntoon
authors.affiliation: Office of the Clinical Director, National Institute of Neurological Disorders and Stroke;
authors.forename: Tianxia
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio;
authors.forename: J Bradley
authors.initials: JB
authors.lastname: Elder
authors.affiliation: Neuroradiology Section, Diagnostic Radiology, Clinical Center at the National Institutes of Health;
authors.forename: John A
authors.initials: JA
authors.lastname: Butman
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute;
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland; and.
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.affiliation: Surgical Neurology Branch and.|Department of Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Oldfield
authors.affiliation: Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio;|Surgical Neurology Branch and.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Lonser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D001933:Brain Stem / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D002648:Child; D017281:Cost of Illness; D003560:Cysts / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D018325:Hemangioblastoma / Q000150:complications* / Q000601:surgery*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D019635:Neurosurgical Procedures / Q000379:methods; D011446:Prospective Studies; D013131:Spine / Q000473:pathology; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000235:genetics / Q000473:pathology*
keywords: IQR = interquartile range; ROC = receiver operating characteristic; VHL = von Hippel-Lindau; central nervous system; cyst; hemangioblastoma; natural history; oncology; treatment; von Hippel-Lindau disease