Effect of pregnancy on hemangioblastoma development and progression in von Hippel-Lindau disease Clinical article

Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
Journal of Neurosurgery (Impact Factor: 3.15). 08/2012; 117(5). DOI: 10.3171/2012.7.JNS12367
Source: PubMed

ABSTRACT Object Prior cases suggest that pregnancy increases the development and progression of CNS hemangioblastomas and/or peritumoral cysts. To determine the effect of pregnancy on CNS hemangioblastomas and peritumoral cysts, the authors prospectively evaluated serial clinical and imaging findings in patients with von Hippel-Lindau (VHL) disease who became pregnant and compared findings during pregnancy to findings in the same patients when they were not pregnant as well as to findings from a cohort of VHL patients who did not become pregnant. Methods Female VHL disease patients enrolled in a prospective natural history study who were of reproductive age (16-35 years at study entrance) were included. Analysis of serial clinical and imaging findings was performed. Results Thirty-six consecutive female VHL disease patients harboring 177 hemangioblastomas were included (mean follow-up [± SD] 7.5 ± 2.3 years). Nine patients (25%) became pregnant (pregnancy cohort). The mean rates of development of new hemangioblastomas and peritumoral cysts in these women during pregnancy (0.4 ± 0.4 tumors/year; 0.1 ± 0.2 cysts/year) did not differ significantly (p > 0.05) from the mean rates in the same group during nonpregnant periods (0.3 ± 0.4 tumors/year; 0.1 ± -0.1 cysts/year) or from the rate in the 27 patients who did not become pregnant (the no-pregnancy cohort: 0.3 ± 0.5 tumors/year; 0.1 ± 0.2 cysts/year). Hemangioblastoma growth rates were similar (p > 0.05) during pregnancy (mean 29.8% ± 42.7% increase in volume per year) compared with during nonpregnant periods (41.4% ± 51.4%) in the pregnancy cohort and the no-pregnancy cohort (34.3% ± 55.3%). Peritumoral cyst growth rates during pregnancy (571.0% ± 887.4%) were similar (p > 0.05) to those of the no-pregnancy cohort (483.9% ± 493.9%), but the rates were significantly higher for women in the pregnancy cohort during nonpregnant periods (2373.6% ± 3392.9%; p < 0.05 for comparison with no-pregnancy cohort). There was no significant difference (p > 0.05) in the need for resection or the mean age at resection between the pregnancy (28% of hemangioblastomas in cohort; mean patient age at resection 30.2 ± 2.6 years) and no-pregnancy cohorts (19%; 32.3 ± 5.6 years). Conclusions Pregnancy is not associated with increased hemangioblastoma or peritumoral cyst development or progression in patients with VHL disease.

  • [Show abstract] [Hide abstract]
    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 ( ).
    Journal of Neurosurgery 02/2014; DOI:10.3171/2014.1.JNS131431 · 3.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Von Hippel-Lindau disease is a rare genetic disorder which gives rise to a range of tumours including central nervous system haemangioblastomas. We report a case of caesarean section in a patient with symptomatic cerebellar haemangioblastomas associated with von Hippel-Lindau disease. An intracranial pressure monitor was inserted before surgery, which enabled intracranial pressure to be monitored throughout. The anaesthetic implications of von Hippel-Lindau disease are discussed and clinical options explored.
    International Journal of Obstetric Anesthesia 08/2014; 24(1). DOI:10.1016/j.ijoa.2014.08.008 · 1.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Hemangioblastomas (HBLs) of the central nervous system are benign vascular tumors that may occur sporadically or in von Hippel–Lindau disease (VHLD). We analyzed the clinical and radiological findings of HBLs focusing on recurrence. Material and Methods From 1998 to 2012, 36 patients with HBLs were treated. Twenty nine patients (80.6%, mean age 46.7 years) had sporadic HBLs and seven (19.4%, mean age 39 years) had HBLs associated with VHLD. Initially, the mass was totally removed in 32 patients, subtotally in one and partially in one, and gamma knife radiosurgery was done in two patients. The mean duration of follow-up was 48.4 months. We retrospectively analyzed the clinical and radiologic findings. Results The location of cerebellum and brainstem was common. The HBLs of spinal cord and cerebral hemisphere were related with VHLD. The common radiologic findings of sporadic HBLs showed a cyst with a mural nodule in 15 patients (51.7%) and pure solid lesion in eight (27.6%). In HBLs related with VHLD, five of seven patients had multiple lesions and pure solid mass was common. Three (10.3%) and two (28.6%) patients showed recurrence in sporadic and VHLD-related HBLs, respectively. Two totally resected mural nodules on the cyst showed recurrence with similar radiologic findings 3 years later in sporadic HBLs. In recurred HBLs related with VHLD, one pure solid mass and one mural nodule on cyst showed the local recurrences after the total resection 8 years later and associated with distant recurrence. Conclusions All patients should be more specifically followed to detect local and distant recurrence, even if the clinical course was benign and mass was totally removed.
    Clinical Neurology and Neurosurgery 08/2014; 123:90–95. DOI:10.1016/j.clineuro.2014.05.015 · 1.25 Impact Factor