Synchronous Clear Cell and Papillary Renal Cell Carcinoma Collision Tumor Confirmed by Component-Specific Next-Generation Sequencing: A Case Report.

Synchronous clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) within the same kidney are uncommon, and distinguishing a true collision tumor from a composite neoplasm with shared clonal origin requires molecular confirmation. We report an 83-year-old woman who underwent radical nephrectomy for an incidentally detected left renal mass. Pathologic examination revealed two well-demarcated adjacent tumors (3.3 cm and 3.2 cm) with characteristic morphologic and immunophenotypic features of ccRCC and pRCC, both staged pT1a. Separate next-generation sequencing analyses demonstrated completely distinct molecular profiles: the pRCC harbored RHEB p.Y35C and TERT promoter mutations with TMB-High status, whereas the ccRCC contained truncating alterations in PBRM1, ARID1A, and TGFBR1. No shared somatic mutations were identified, confirming independent clonal origins and establishing this as a true collision tumor. This case illustrates the value of per-component molecular profiling for histologically discordant renal tumors.