b'Increased Molecular Identification Updates Renal Cell Carcinoma ClassificationsRenal cell carcinoma (RCC) makes up more than 90% of malignancies of the kidneys, and the World Health Organization recently delineated 21 subtypes. Among those are molecularly defined renal carcinomas. The researchers said the more-specific understanding of cancer types is expected to aid treatment. By Annette M. BoyleRICHMOND, VAForty years ago, the only rec- as those treated by the VA. For early-stage disease, the ognized form of kidney cancer was renal cell car- authorsrecommendradicalsurgicalexcisionalong cinoma (RCC). Today, RCC still accounts for morewith lymphadenectomy in children. For advanced dis-than 90% of malignancies in the kidney, but now theease, no standard of care has been developed, but the WorldHealthOrganization(WHO)delineates21NationalComprehensiveCancerNetwork(NCCN) subtypes, with significant differences in aggressive- guidelines note that this type has shown some response ness and treatment options. to combined tyrosine kinase inhibitor/immunotherapy Further,thelatestWHOclassificationsystemofapproaches. A phase II clinical trial evaluating the use urinaryandmalegenitaltumorsexpandsbeyondof axitinib plus nivolumab in unresectable or meta-thelocation,morphologicandimmunohistochemi- static TFE3-rearranged RCC is in progress.calcharacterizationsofpreviouscategorizationstoTFEB-altered RCC: TFEB-rearranged mutation is include an entirely new group, molecularly definedmost often seen in younger patients, often in their 30s, renal carcinomas. and is typically more indolent than TFE3-rearranged Three new types of tumors are delineated in the clas- RCC or ccRCC, whereas the more aggressive TFEB-sification system: elongin C (ELOC)-mutated renalamplified RCCs are found in patients of about 60 years cell tumors, eosinophilic solid cystic renal cell tumorsof age. Both are included in this new category. In the and anaplastic lymphoma kinase (ALK)-rearrangedabsence of a recommended systemic treatment, the renal cell tumors. In addition, the first molecularlyresearchers emphasized the need for interdisciplinary defined type, previously known as Xp11.2 transloca- consultation for treatment planning. They also noted tionRCC,receivedanewname, TFE3-rearrangedthat the vascular endothelial growth factor receptor RCC. Others in the category include TFEB-altered,pathway is a possible therapeutic target and that some fumaratehydratase-deficient,succinatedehydroge- reports indicate durable complete response to PD-L1 nase-deficient and SMARCB1-deficient renal medul- inhibitor therapy. lary carcinoma. ELOC-mutated RCC: Formerly known as TCEB1-ResearchersattheMcGuireHunterVAMCinmutated RCC, ELOC-mutated RCC typically affects Richmond,VA,andVirginiaCommonwealthmen age 40 and older. Studies are mixed on the degree University (VCU) School of Medicine recently doveof aggressiveness of this subtype, and recommenda-into the implications for treatment and developmenttions for treatment are lacking.of RCC therapies arising from the new category in anFumaratehydratase(FH)-deficientRCC: article in Urologic Oncology. 1 ImmunohistochemicalanalysisofFH-deficient TFE3-rearrangedRCC:WhileseveraloftheRCCsoftenfindcompletelossofFHexpression. molecularly defined malignancies are more indolentIt is notable for its rapid progression, with Steven than clear cell RCC (ccRCC), the most common typeSmith, MD, PhD, and Lance Hampton, MD, both of of kidney cancer, TFE3-rearranged RCC is at leastthe Richmond VAMC and VCU and their colleagues equally aggressive, particularly in older patients, suchnotingthatthisrareandremarkablyaggressive 62'