DOES THE HEMANGIOBLASTOMA EXIST OUTSIDE V ONHIPPEL-LINDAU DISEASE

Hemangioblastoma may arise in isolation (''sporadic'' cases) or as a m ajor manifestation of von Hippel-Lindau (VHL) disease, an autosomal do minant disorder with a prevalence of at least 1/36.000. In addition of central nervous system hemangioblastomas (cerebellum, spinal cord and retina), affected patients may develop renal cysts or carcinomas, phe ochromocytomas and pancreatic cysts. A multidisciplinary group includi ng neurosurgeons, geneticists, pathologists and clinicians from all in volved specialities has been organized to develop a national registrat ion of all hemangioblastoma and VHL patients. The findings of a prelim inary 10-year study (1983-1993) conducted in France are presented. Two hundred thirteen cases of hemangioblastoma were reviewed for their lo cation and genetic features. The majority (77 %) of the tumors were lo cated in the cerebellum whereas 23 % were located inside the spinal ca nal. By thorough clinical examination of the patients and systematic g enetic inquiry of their family background, it was found that 34,3 % of the total (58,7 % before age 30) were afflicted with VHL disease. Spi nal hemangioblastomas were more often related to VHL disease than infr a-tentorial locations (50 % versus 36,6 %). In addition, mean age at d iagnosis in VHL disease was significantly younger than in sporadic cas es (33,5 +/- 10 versus 43,6 +/- 15 years). Recent progress in VHL mole cular genetics led to the identification of the mutated gene to the di stal part of the short arm of chromosome 3 (3p25-3p26), paving the way to presymptomatic diagnosis and, hopefully, to elucidation of pathoge nesis, which may offer a further glimpse into tumorigenesis in general . Because of the usually early adulthood onset, accurate presymptomati c diagnosis of affected members would be of great benefit to VHL famil ies. However, the fact that very few mutations in the VHL gene are ide ntified precludes molecular diagnosis of ''sporadic'' hemangioblastoma s. In summary, this study reveals that VHL-related hemangioblastoma is a more common clinical problem that it was previously reported. Thus, all patients with an apparently isolated central nervous system heman gioblastoma should be investigated for evidence of VHL disease.