Renal cell carcinoma (RCC) subtypes are increasingly being discerned via their molecular underpinnings. Frequently this can be correlated to histologic and immunohistochemical surrogates, such that only simple targeted molecular assays, or none at all, are needed for diagnostic confirmation. In clear cell RCC, VHL mutation and 3p loss are well known; however, other genes with emerging important roles include SETD2, BAP1, and PBRM1, among others. Papillary RCC type 2 is now known to include likely several different molecular entities, such as fumarate hydratase (FH) deficient RCC. In MIT family translocation RCC, an increasing number of gene fusions are now described. Some TFE3 fusion partners, such as NONO, GRIPAP1, RBMX, and RBM10 may show a deceptive fluorescence in situ hybridization result due to the proximity of the genes on the same chromosome. FH and succinate dehydrogenase deficient RCC have implications for patient counseling due to heritable syndromes and the aggressiveness of FH-deficient RCC. Immunohistochemistry is increasingly available and helpful for recognizing both. Emerging tumor types with strong evidence for distinct diagnostic entities include eosinophilic solid and cystic RCC and TFEB/VEGFA/6p21 amplified RCC. Other emerging entities that are less clearly understood include TCEB1 mutated RCC, RCC with ALK rearrangement, renal neoplasms with mutations of TSC2 or MTOR, and RCC with fibromuscular stroma. In metastatic RCC, the role of molecular studies is not entirely defined at present, although there may be an increasing role for genomic analysis related to specific therapy pathways, such as for tyrosine kinase or MTOR inhibitors.
The American journal of surgical pathology. 2020 Apr 03 [Epub ahead of print]
Sean R Williamson, Anthony J Gill, Pedram Argani, Ying-Bei Chen, Lars Egevad, Glen Kristiansen, David J Grignon, Ondrej Hes
Department of Pathology and Laboratory Medicine and Henry Ford Cancer Institute, Henry Ford Health System., NSW Health Pathology, Department of Anatomical Pathology., Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY., Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden., Institute of Pathology, University Hospital Bonn, Bonn, Germany., Department of Pathology, Indiana University School of Medicine, Indianapolis, IN., Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Pilsen, Czechia.