Molecularly defined renal carcinomas (MDRC) represent a heterogeneous group of tumours characterized by disease-defining genetic alterations, and the documentation of these mutations is necessary for their diagnosis. This group includes TFE3-rearranged renal cell carcinoma (RCC), TFEB-rearranged RCC, TFEB-amplified RCC, fumarate hydratase (FH)-deficient RCC, succinate dehydrogenase (SDH)-deficient RCC, SMARCB1-deficient renal medullary carcinoma (RMC), ALK-rearranged RCC, and ELOC-mutated RCC. Although they account for only about 5% of RCC, they are clinically significant due to distinctive biology, frequent diagnostic pitfalls, and therapeutic implications. Many pathology laboratories lack immediate access to fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) to confirm MDRC; this review emphasizes morphologic recognition and immunohistochemical surrogates, followed by rational triage for ancillary testing when available.
Histopathology. 2026 Jan [Epub]
Mahmut Akgul, Rose S George, Stephanie E Siegmund, Murat Oktay, Ankur R Sangoi, Sean R Williamson, Liang Cheng
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Department of Pathology, Memorial Hospital, Istanbul, Turkey., Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA., Department of Pathology and Laboratory Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA., Department of Pathology and Laboratory Medicine, Department of Surgery (Urology), Brown University Warren Alpert Medical School, the Legorreta Cancer Center at Brown University, and Brown University Health, Providence, RI, USA.