Renal Tumors in Patients with von Hippel-Lindau Disease: “State of Art Review”

The disease that has perpetuated the names of two prestigious European physicians, Eugen von Hippel and Arvid Lindau, is a familial syndrome characterised by the occurrence of highly vascular tumours in different organs1. Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant genetic disease (Online Mendelian Inheritance in Man 193300) that is estimated to occur in 1/36,000 live births and with clinical manifestations usually becoming apparent between 18 and 30 years. VHL germline mutation predisposes patients to renal cysts and carcinoma, central nervous system and retina hemangioblastoma, pancreatic cysts and neuroendocrine tumors, pheochromocytoma, endolymphatic sac tumors and epididymal or adnexal cystadenoma2. Clinical diagnosis requires one major manifestation of von HippelLindau disease in patients with a familial history, and at least two major manifestations including one haemangioblastoma in isolated cases. Patients are at high risk for early multiple and recurrent clear cell Renal Cell Carcinoma (RCC) 3. Total nephrectomy was systematically done in the past to prevent the risk of metastatic progression, which led to end stage renal disease requiring dialysis. Preserving normal renal parenchyma emerged as a major therapeutic goal in VHL cases. Since several groups reported that most RCC in VHL cases has low pathological grade, grows slowly and never becomes metastatic at less than 3 cm, in the early 1990s Nephron Sparing Surgery (NSS) was developed. The standard therapeutic procedure for RCC in VHL cases was to monitor small lesions by imaging and perform partial nephrectomy for any RCC that became 2.5 to 3 cm. During the last decade percutaneous ablative therapies, such as RFA and cryotherapy that were developed to treat localized RCC in select patients emerged as a novel nephron sparing therapy applicable to patients with VHL. The worldwide von Hippel-Lindau Family Alliance greatly contributes to such dissemination by organising International Symposia once every 2 years which are an excellent opportunity for doctors, scientists, and affected individuals to meet and exchange information on fundamental and clinical issues (http:// www.vhl.org)2.