Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

Abstract

Von Hippel-Lindau syndrome (VHLS) is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves. This review will discuss the key aspects of the current management of VHLS.

A Review of Von Hippel-Lindau Syndrome

“…Renal cysts are asymptomatic, and unlike autosomal dominant polycystic kidney disease, the incidence of chronic renal failure is low. Bilateral RCCs and renal cysts present in the third or fourth decade of life in these patients ( 22 ). Up to 70% of VHL patients develop RCC by 60 years of age; RCC is the leading cause of mortality in this group of patients ( 14 ).…”

von Hippel-Lindau Syndrome: Genetic Study of Case With a Rare Pathogenic Variant With Optic Nerve Hemangioblastoma, a Rare Phenotypic Expression

“…In general, renal cysts are asymptomatic and rarely result in renal failure, even when multiple and bilateral (7). Multiple and bilateral RCCs occur, respectively, in 30-45% and 30-50% of symptomatic patients who already have metastases, and lymph node metastases are described in 15% of CCR cases (7,34). Hematogenous metastases are relatively frequent in RCCs and involve mainly lung, liver, and bone, and pathogenic variants in the VHL gene are considered the most frequent causes of hereditary and sporadic RCCs (34).…”

“…Adrenal PCCs occur in 16-20% of patients with VHLS, are usually benign, uni or bilateral, and occasionally may be multifocal, although they are malignant in 5% of cases (34). In VHLS, PCCs manifest in younger patients when compared to sporadic PCCs, and of all the PCCs diagnosed in the population, 20% of them occur in patients with VHLS (1,7).…”

“…Clinical diagnosis of the disease is made by the family history of VHLS and the presence of at least one of the disease-associated tumors (CNS and/or retinal HBs, CCRs, pancreatic neuroendocrine tumors, or papillary cystadenoma of the epididymis) (5,6,34). In patients without a family history, the presence of two or more HBs in the CNS or the retina or the presence of an HB in the CNS or retina and a renal or pancreatic tumor, with the exception of the cysts of the epididymis and renal cysts, both common in the general population, are indicative of VHLS (1,5,7).…”

A Painful Finger: An Unusual Presentation of Von Hippel-Lindau-Associated Advanced Renal Cell Carcinoma

“…The incidence is estimated to be at 1 in 36,000 live births, with a penetrance of over 90% by the age of 65. Renal cell carcinoma occurs in 24-45% of VHL patients with a mean age at presentation of 39 years [10]. VHL syndrome is also associated with renal cysts that are typically multiple, bilateral and occur in up to 63% of patients.…”