Prospective natural history study of central nervous system hemangioblastomas in von Hippel-Lindau disease

Abstract

Object 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. Clinical trial registration no.: NCT00005902 (ClinicalTrials.gov).

Risk of new tumors in von Hippel–Lindau patients depends on age and genotype

“…Consistent with our results, Lonser et al 14 recently found that established CNS hemangioblastomas grew at significantly different rates depending on their anatomical location in the CNS. The contrasting manifestation rate profiles found in this study point toward two distinct development patterns at the two anatomical locations, although tumors in both locations are identical in their histopathology and origin.…”

“…Previous studies of vHL manifestation development have predominantly focused on either total or cumulative manifestation frequencies or on growth patterns of individual tumors. 6,7,[11][12][13][14][15] The few studies that have assessed growth patterns of vHL tumors have mostly assessed growth rates of individual tumors in relation to observation time regardless of the patients' ages. 12,13 Furthermore, many of these studies have solely included patients with clinical vHL or a specific manifestation type and have not taken asymptomatic VHL mutations carriers into account, 6,[12][13][14] which may bias the frequency estimates.…”

Netipinės Eigos Smegenėlių Hemangioblastoma. Klinikinis Atvejis

“…Hemangioblastoma yra nepiktybinis, lėtai augantis kraujagyslinės kilmės centrinės nervų sistemos navikas, dažniausiai nustatomas smegenėlėse, smegenų kamiene ir nugaros smegenyse [1][2][3][4][5][6][7]. Hemangioblastoma vystosi iš hemangioblastų, todėl gali plisti su krauju ar transformuotis į pirmines endotelines ląsteles [2].…”

“…Tai stipriai vaskuliarizuotas navikas, histologiškai gėry-binis, bet sukeliantis neurologinius deficitus ir susijęs su ženkliu mirštamumu [6,17]. Klinikinis pasireiškimas priklauso nuo naviko dydžio, lokalizacijos ir išplitimo į galvos ir nugaros smegenis [1][2][5][6]9]. Dažniausi simptomai yra galvos skausmai, ūžesys ausyse, galvos svaigimas, rankų ir kojų skausmai ir silpnumas, sensoriniai deficitai, eisenos sutrikimai ir spinalinė ataksija, dismetrija, nistagmas, hidrocefalija ir inkontinencija [1][2][5][6]9].…”

“…Klinikinis pasireiškimas priklauso nuo naviko dydžio, lokalizacijos ir išplitimo į galvos ir nugaros smegenis [1][2][5][6]9]. Dažniausi simptomai yra galvos skausmai, ūžesys ausyse, galvos svaigimas, rankų ir kojų skausmai ir silpnumas, sensoriniai deficitai, eisenos sutrikimai ir spinalinė ataksija, dismetrija, nistagmas, hidrocefalija ir inkontinencija [1][2][5][6]9]. Smegenų kamieno hemangioblastomos gali pasireikšti hipestezija, ataksija, NETIPINĖS EIGOS SMEGENĖLIŲ HEMANGIOBLASTOMA.…”