Tumors masquerading as type 2 papillary renal cell carcinoma: pathologists’ ever-expanding differential diagnosis for a heterogeneous group of entities

•“Type 2 papillary RCC” likely represents a heterogeneous group of entities•RCC diagnosis increasingly requires exclusion of molecularly-defined tumors•New pathology guidelines suggest against subtyping papillary RCC•Additional changes to classification schemata are expected Although papillary renal cell carcinoma has historically been classified as either type 1 or type 2, data from The Cancer Genome Atlas (TCGA) has demonstrated significant genomic heterogeneity in tumors classified as “type 2 papillary renal cell carcinoma” (T2PRCC). Papillary renal cell carcinoma is expected to have a favorable clinical course compared to clear cell renal cell carcinoma (CCRCC). However, tumors with poor outcome more similar to CCRCC were included in the T2PRCC cohort studied by the TCGA. The differential diagnosis for T2PRCC includes a variety of other renal tumors, including aggressive entities such as TFE3 translocation-associated renal cell carcinoma, TFEB-amplified renal cell carcinoma, fumarate hydratase-deficient renal cell carcinoma, high-grade CCRCC, and collecting duct carcinoma. Accurate classification of these tumors is important for prognostication and selection of therapy.