Advanced renal cell carcinoma associated with von Hippel-Lindau disease: A case report and review of the literature

摘要

The autosomal dominant hereditary disorder von Hippel-Lindau (VHL) disease is caused by a germline mutation in the VHL gene. The symptoms of VHL include hemangioblastoma of the central nervous system, retinal angiomas, visceral tumors and multiple visceral cysts. However, advanced renal cell carcinoma (RCC) occurs in few VHL patients at initial diagnosis; in addition, sporadic VHL disease with de novo germline mutation is rare. The current study reports the clinical case of a 33-year-old Asian male patient diagnosed with advanced bilateral multicentric renal carcinomas. The patient underwent radical nephrectomy with embolectomy of the right kidney for treatment of T3b-stage RCC and laparoscopic nephron-sparing surgery of the left kidney. Sunitinib was administered following histological diagnosis and during follow-up. Genetic analysis revealed a missense mutation, c.194C>G (p.Ser65Trp). In addition, genetic analysis of the patient's parents and brothers, who were unaffected, confirmed a diagnosis of de novo VHL disease. To the best of our knowledge, the present study reports the first known case of a sporadic de novo germline mutation of VHL at c.194C>G. Current understanding of the molecular genetics and pathophysiology of VHL disease, as well as developments in surgical and target therapies for RCC have advanced in recent years; however, early detection through genetic screening and regular clinical surveillance of VHL disease patients and their families continues to be the primary basis for managing the disease.