Central nervous system hemangioblastomas, endolymphatic sac tumors, and von Hippel-Lindau disease

Von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome caused by g ermline mutations of the VHL tumor suppressor gene. Major progress has been made in the last decade in both clinical and fundamental aspects of VHL. T he VHL gene product, pVHL, has major and multiple functions: pVHL regulates not only first angiogenesis but also extracellular matrix formation and th e cell cycle. A molecular diagnosis of VHL is now available, leading to a t ransformation in clinical management of patients and their families. Diagno sis of VHL has to be suspected in patients with a VHL-related tumor without familial history and especially in case of hemangioblastoma or endolymphat ic sac tumors. Such patients should be systematically investigated for clin ical and molecular evidence of VHL disease. Treatment of symptomatic hemang ioblastomas remains mainly neurosurgical, often in emergency, but stereotac tic radiosurgery is emerging as an alternative therapeutic procedure. In th e future, antiangiogenic drugs could represent a potential medical treatmen t of CNS hemangioblastomas in view of their highly vascular structure. Last ly, visceral manifestations of VHL disease are also of critical importance and require early detection for effective treatment.