Utility of Next-Generation Sequencing in Renal Neoplasia, Including Tumors With Clear Cytoplasm and Rare Phenotypes (ELOC/MITF Alterations and Mismatch Repair Deficiency)

OBJECTIVE: To define the clinical utility of next-generation sequencing (NGS) of renal tumors, including carbonic anhydrase 9-positive renal neoplasia with clear cell features (ccRCN) that include ELOC (for expansion of gene symbols, use search tool at www.genenames.org) and MTOR/TSC1/TSC2-mutated renal cell carcinoma (RCC) with fibromyomatous stroma (ELOC-RCCfms and M/TSC-RCCfms, respectively), as these tumors often have overlapping features. PATIENTS AND METHODS: Renal tumors (n=234) diagnosed between August 1, 2021, and June 15, 2025, were submitted for genomic profiling using Clinical Laboratory Improvement Amendments-validated 515-gene (n=30), 30-gene (n=175), and smaller (