Integra Foundation Award: Long-term natural history of hemangioblastomas in Von Hippel-Lindau disease: implications for treatment.

INTRODUCTION Von Hippel-Lindau disease (VHL) (OMIM193300) is an inherited multisystem cancer syndrome with visceral and central nervous system (CNS) manifestations.9 It is transmitted in an autosomal dominant fashion (chromosome 3p25) with greater than 90% penetrance by age 60 years.12 Visceral lesions consist of renal cell carcinomas and cysts, pancreatic islet cell tumors and cysts, pheochromocytomas, and papillary cystadenomas of the epididymis and broad ligament.9 The CNS manifestations of VHL include hemangioblastomas of the retina, brainstem, cerebellum, spinal cord, and nerve roots, as well as endolymphatic sac tumors (ELST).9 During the course of their lives, most patients with VHL require treatment of several symptom-producing hemangioblastomas of the cerebellum, brainstem, or spinal cord. However, many tumors never produce symptoms and do not require treatment. Detection at an early stage of the lesions that will produce symptoms and, ultimately, require treatment, would permit earlier excision of hemangioblastomas of the spinal cord, brainstem, or cerebellum, and may identify cerebellar hemangioblastomas for which treatment with radiosurgery can be justified at a stage before treatment is contraindicated because of tumor size or the presence of an associated cyst. Identification of variables predicting tumor behavior over several years requires an extended interval of observation. To define the long-term natural history of VHL and identify predictive tumor features for surgical intervention for CNS hemangioblastomas, we reviewed the serial clinical and magnetic resonance imaging (MRI) findings in all VHL patients followed at the National Institutes of Health (NIH) for longer than 10 years. PATIENTS AND METHODS