Papillary renal cell carcinoma, formerly known as Type 2: a single institutional study addressing histologic and molecular features.

aimsPapillary renal cell carcinoma (pRCC) accounts for 15%-20% of RCC cases and is the second most common histologic subtype of RCC. In contrast to other common RCC subtypes, there continues to be ongoing debate about how to classify RCCs with papillary architecture and eosinophilic cytoplasm given the heterogeneity of histologic, IHC and molecular findings. Our study set out to characterize the histologic features and molecular alterations in cases that were originally diagnosed as pRCC, Type 2 or high-grade pRCC in a single institutional study (n = 63). METHODS AND

resultsHistologically, the vast majority of the cases had a papillary pattern (n = 59). There were three cases that had a mixed solid and papillary pattern and one case that had a sarcomatoid architectural pattern. The cases were composed of large cells with eosinophilic cytoplasm, pseudostratified or apically oriented nuclei and prominent nucleoli. Molecular analysis of these cases revealed a wide range of genes that were mutated, with the most common ones being SETD2 (n = 9), PBRM1 (n = 5), KDM6A (n = 7), PMS2 (n = 4), NF2 (n = 7) and TERT (n = 7). Our study further identified cases that had molecular mutations in the RTK/RAS pathway (KRAS and NRAS), PI3K pathway (TSC2), TP53 pathway (TP53 and CHEK2) and copy number alterations in the cell cycle pathway (CDKN2A and CCND3).

conclusionsThese findings highlight the need to molecularly characterize these lesions as there is no specific histologic finding to identify cases that harbour different pathogenic alterations in specific genes.