Cytohistopathologic hybrid renal cell carcinoma with papillary and clear cell features

Clear cell (CRCC) and papillary (PRCC) renal cell carcinomas (RCC) are the two most frequent subtypes of RCC. In this study, we studied RCC which displayed a hybrid morphology with areas of PRCC and CRCC or which contained papillary structures with clear cell changes (CCC). Consecutive cases of RCC collected over a 12-year period were reviewed to identify RCC with papillary structures and a possible admixture between CRCC and non-oncocytic PRCC. Special stains for glycogen and immunostaining for cytokeratin 7 were applied to sections containing both areas of classical PRCC and PRCC with CCC. Of the total of 541 RCC retrieved, there were 68 non-oncocytic RCC having papillary structures that could be grouped into: (a) group 1 (15 cases), CRCC with areas of papillary formation; (b) group 2a (9 cases), PRCC with extensive CCC with areas of foamy epithelial cells or macrophages; (c) group 2b (18 cases), RCC with areas of classical PRCC with focal CCC; and (d) group 3 (26 cases), RCC with features of groups 2a and 2b and containing areas of classical CRCC. There was a high rate (12/68) of sarcomatous transformation in the study cases. Groups 2 and 3 were associated with a higher rate of vascular invasion, distant metastasis, and mortality than classical PRCC and a higher rate of lymph node metastasis than CRCC. Our study identifies two groups of RCC (referred to as groups 2 and 3) that exhibit characteristic cytohistopathologic hybrid features that set them apart from classical RCC. This type of hybrid tumor seems to be associated with a more aggressive biologic behavior, and its recognition may facilitate the classification of RCC with ambiguous morphology.