Precancerous lesions in the kidney

Renal cell carcinoma (RCC), although occurring less frequently than prostat e and bladder cancer, is actually the most malignant urologic disease, kill ing >35% of affected patients. Therefore, investigation of the nature of pr emalignant lesions of the kidney is a relevant issue. Following the most re cent histological classification RCC can be subdivided into four categories : conventional RCC: papillary RCC; chromophobe RCC; and collecting duct car cinoma. In contrast to many genitourinary malignancies, premalignant alterations in the kidney an scarcely described. Intratubular epithelial dysplasia has be en recognized as the most common precursor of RCC. In analogy to prostatic intraepithelial neoplasia (PIN), the premalignant lesions of the kidney are described as high or low-grade renal intratubular neoplasia. In contrast, precancerous lesions have been described as part of the von Hippel-Lindau s yndrome (VHL) where the evolution from a simple cyst to an atypical cyst wi th epithelial hyperplasia to cystic or solid conventional-type RCC is well documented. Finally, in the genesis of papillary RCC an adenoma-carcinoma s equence has been recognized with specific genetic changes. There are no dat a on the epidemiology of premalignant lesions of the kidney, but research i nto the etiology of RCC has been extended substantially. Familial and genet ic factors are well documented in VHL disease, in hereditary papillary RCC, in the tuberous sclerosis complex and in familial RCC. Cigarette smoking a nd obesity are established risk factors for RCC. Hypertension or its medica tion has also been associated with an increased risk. Among dietary factors an inverse relation between risk and consumption of vegetables and fruit h as been found. Occupational exposure to substances such as asbestos and sol vents has been linked to an increased risk of RCC. Specific RCC variants have distinctive chromosome alterations and several g enes have been implicated in the development of RCC. Loss of material from the 3p chromosome characterizes conventional RCC and the deletion of the VH L suppressor gene plays an important role in the genesis of this RCC varian t, in contrast, numerical changes with trisomy of chromosomes 7 and 17 and loss of the sex chromosome are typical changes in papillary tumors, whereas papillary RCC have additional trisomies. Chromophobe RCC is characterized by loss of chromosomes with a combination of monosomies. Less consistent ge netic alterations are associated with collecting duct carcinoma. The traditional treatment of RCC is surgery by radical or partial nephrecto my. The latter approach carries a risk of tumor recurrence as a result of u nrecognized satellite lesions or premalignant lesions that might have been present at the time of surgery. However, the reported recurrence rates afte r partial nephrectomy are <1% and therefore the possible presence of premal ignant disease does not after the actual treatment strategy advocated. Alth ough multifocality and bilateral occurrence of RCC are much more Likely in cases of papillary RCC, biopsy of the renal remnant or contralateral kidney is not justified even in patients with this tumor type. Conversely, patien ts with RIN in a partial or radical nephrectomy specimen or in a renal biop sy taken for whatever reason should be subjected to closer follow-up with r egularly repeated ultrasound. When an effective chemopreventive regimen becomes available it might be use ful for patients with an inherited risk of RCC as well as in those who are at risk of tumor recurrence after intervention. Mass screening with the pur pose of detecting RCC at its earliest stage is not recommended at the prese nt time, but screening focused on certain risk groups can be advocated. Fur ther research is needed to identify avoidable risks, develop effective chem oprevention and recognize patients at risk.