Strength of molecular cytogenetic analyses for adjusting the diagnosis of renal cell carcinomas with both clear cells and papillary features: a study of three cases

Histological features are usually sufficient for providing an accurate diagnosis of renal cell carcinomas (RCC). However, the morphological appearance might sometimes be misleading. For instance, RCC with papillary areas and extensive clear cell changes may be difficult to classify either as clear cell renal carcinoma or as papillary renal cell carcinoma (pRCC). We used the combination of immunohistochemistry, conventional cytogenetics, fluorescence in situ hybridization (FISH), bacterial artificial chromosomes comparative genomic hybridization arrays and high-density single nucleotides polymorphism arrays (SNP arrays) to characterize three cases of RCC showing a predominant cytology of cells with clear cytoplasm and variable amounts of papillary areas. In accordance with the 2004 World Health Organization (WHO) classification, we initially assessed the diagnosis of clear cell RCC for one of the cases and unclassified RCC for the two remaining cases. However, because of a strong immunohistochemical labeling for α-methylacyl-CoA racemase, as well as the presence of a gain of chromosomes 7 and 17, we concluded that two of these tumors were actually pRCC. As for the third case, because of the presence of both pCCR and ccCCR molecular cytogenetic aberrations, including gains of chromosomes 7 and 17, loss of chromosome Y and whole chromosome 3 loss of heterozyosity (isodisomy), the final diagnosis was hybrid tumor cc-pRCC, so-called “unclassified RCC” according to the WHO classification. Our observations demonstrate the necessity to use immunohistochemical and cytogenetic tools in all cases of RCC showing unusual features. The combination of FISH and SNP arrays is prevailing for characterizing cases with hybrid features.