Abstract:The recognition of chromophobe renal cell carcinoma (RCC) among other distinct types of renal cell tumors (RCT) based on light-microscopic features, such as cytoplasmic and nuclear characteristics, might pose a dilemma in some cases because of morphological pattern overlapping with renal oncocytoma or conventional RCC. The present article reviews chromophobe RCC with focus on aspects of its molecular pathology, which was shown using ancillary modern microarray-based technology that can distinguish it from its mimics and therefore be helpful for its correct diagnosis. Although the high resolution DNA-microarray analyses excluded with all certainty the occurrence of small specific alterations, the loss of entire chromosomes 2, 10, 13, 17 and 21 occurs exclusively in chromophobe RCC and therefore probes localized at these chromosomes might be used to establish the diagnosis of chromophobe RCC in cases with uncertain histology. The usefulness of proposed candidate genes selected by the global gene expression analyses in the diagnostic pathology is far below expectations. The conflicting staining patterns, together with the poor specificity of used antibodies, leads us to believe that these candidate immunomarkers might not help in the separation of chromophobe RCC, with the exception of CD82, which has recently been suggested to be used for routine histological diagnosis.Key words: chromophobe renal cell carcinoma, diagnosis, electron microscopy, histology, molecular markers.
Prehistory and epidemiologyBased on its morphological and electron-microscopic characteristics, chromophobe renal cell carcinoma (RCC) was delineated among experimental kidney tumors nitrosomorpholine-induced in rats.1 In 1985, Thoenes et al. described the first human renal carcinomas as an analogy to the cases in rodents showing similar morphology.2 They noticed a 4.6% incidence of the chromophobe variant in a series of 697 renal cell carcinoma cases. Initially, diagnosis of chromophobe RCC appeared to be straightforward as a result of its characteristic light microscopic features. The same authors 3 years later described an eosinophilic variant of chromophobe RCC, which can easily be confused with renal oncocytoma or "eosinophilic" clear cell carcinoma based on morphological characteristics.3 The latter discovery is also related to its close phenotypic similarity to "eosinophilic" clear cell carcinoma on the one hand and to oncocytoma on the other hand. Presently, chromophobe RCC is considered to account for approximately 5% of all cases of renal cell carcinoma. The mean age of incidence with chromophobe RCC in a series of 104 patients reported by Cindolo et al. 4 was in the sixth decade (58 years), with a range in age of 27-86 years, and the number of men and women was roughly equal. Mortality was less than 10%.