Introduction: The most frequent von Hippel-Lindau disease (VHL)-associated tumors are hemangioblastomas. While hemangioblastomas are associated with significant neurologic impairment and mortality, their natural history and optimal management are not fully defined.
Methods: VHL patients were enrolled in a prospective study designed to define the natural history of central nervous system (CNS) hemangioblastomas. Prospective serial imaging, laboratory, genetic and clinical data were analyzed.
Results: Two hundred twenty-five (111 males; 114 females) patients 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%) at study entrance (follow-up, 15,819 hemangioblastoma-years). Increased tumor burden was associated with partial deletions in 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 1,278 hemangioblastomas (51%) did not grow, 1,226 hemangioblastomas (49%) grew in a saltatory (886 tumors; 72% of growing tumors), linear (76; 6%), or exponential (264; 22%) pattern. Faster tumor growth was associated with male sex (P=0.002), 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 [6.4%]; area under the curve greater than 0.9).
Conclusions: CNS hemangioblastoma burden in VHL is associated with partial germline deletions and male sex. Unpredictable growth of hemangioblastomas compromises assessment of non-surgical therapies. Judicious treatment of symptom-producing hemangioblastomas, while avoiding unnecessary treatment of asymptomatic tumors that may not progress, can provide clinical stability.
Patient Care: This research has direct impact on the clinical and surgical management of central nervous system hemangioblastomas. Specifically, features that predict symptom formation and need for treatment are now identified by this study, as well as features that impact tumor development and progression.
Learning Objectives: By the conclusion of this presentation, participants should be able to: 1) describe the natural history of central nervous system hemangioblastomas, 2) describe the factors that impact tumor development, growth and symptom formation and 3) identify most effective treatment strategies for these neoplasms.