Renal cell carcinoma with clear cell and papillary features

Context.-The diagnosis of primary renal cell carcinomas (RCCs) with both papillary architecture and cells with clear cytoplasm can be diagnostically challenging for practicing pathologists. The 4 main neoplasms in the differential diagnosis are clear cell RCC, papillary RCC, clear cell papillary RCC, and Xp11 translocation RCC. Accurate diagnosis has both prognostic and therapeutic implications. Objective.-To highlight the helpful cytomorphologic, immunohistochemical, and cytogenetic features of each of these entities to enable reproducible classification. Data Sources.-Published peer-reviewed literature was reviewed, accompanied by the authors' personal experiences. Conclusions.-Key morphologic clues and a focused immunohistochemical panel, including CK7, α-methylacyl coenzyme A racemase (AMACR), TFE3, cathepsin K, and carbonic anhydrase IX (CAIX), now allow most resected RCCs with papillary architecture and clear cells to be accurately classified. In other cases, cytogenetic and molecular findings can establish the diagnosis. Despite these tools, some RCCs with papillary architecture and clear cells do not fit into any of the described entities and currently remain unclassified.