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

Clinical article

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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.

Abbreviation used in this paper:VHL = von Hippel-Lindau.

Article Information

Address correspondence to: Russell R. Lonser, M.D., Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10, Room 3D20, Bethesda, Maryland 20892-1414. email: lonserr@ninds.nih.gov.

Please include this information when citing this paper: published online August 31, 2012; DOI: 10.3171/2012.7.JNS12367.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    A: Annualized rates of new tumor development of hemangioblastomas in patients who became pregnant (pregnancy cohort) during their pregnant and nonpregnant periods, as well as in patients who did not become pregnant (no-pregnancy cohort). The rate of tumor development over time did not differ significantly between pregnancy and nonpregnant periods in the patients who became pregnant or between patients who became pregnant compared with those who did not. B: Annualized relative growth rates of hemangioblastomas in pregnant patients during their pregnant and nonpregnant periods, as well as in patients who did not become pregnant. The tumor growth rate did not differ significantly between pregnant and nonpregnant periods in the patients who became pregnant or between patients who became pregnant compared with those who did not. C: Annualized rates of new hemangioblastoma-associated peritumoral cyst development in pregnant patients during their pregnant and nonpregnant periods, as well as in patients who did not become pregnant. The rate of cyst development over time was not significantly different between pregnant and nonpregnant periods in the patients who became pregnant or between patients who became pregnant and those who did not. D: Annualized relative growth rates of hemangioblastoma-associated peritumoral cysts in pregnant patients during their pregnant and nonpregnant periods, as well as in patients who did not become pregnant. There was no significant difference in cyst growth rate over time during pregnancy and nonpregnant periods in the patients who became pregnant or between the patients who became pregnant and those who did not. There was a statistically significant difference between the growth rate during nonpregnant periods in the patients who became pregnant and the growth rate in patients who did not become pregnant. Error bars represent standard error. N.S. = not significant.

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    Growth curves of 5 peritumoral cysts associated with hemangioblastomas in the pregnancy cohort. Cyst volumes are plotted in proportion to the volume at initial observation. Two cysts showed growth prior to pregnancy and continued through pregnancy. One cyst developed during pregnancy. Two of the cysts were associated with tumors that were present during 2 pregnancies. One cyst showed no growth during the first pregnancy, but grew during the second pregnancy. One cyst had no observable growth during 2 pregnancies, but was present at last follow-up. The gray bar represents pregnancy, with time 0 representing childbirth.

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