The New WHO Category of "Molecularly Defined Renal Carcinomas": Clinical and Diagnostic Features and Management Implications

Jonathan Kanakaraj; Justin Chang; Lance J Hampton; Steven Christopher Smith

doi:10.1016/j.urolonc.2024.02.003

The New WHO Category of "Molecularly Defined Renal Carcinomas": Clinical and Diagnostic Features and Management Implications

Urol Oncol. 2024 Mar 21:S1078-1439(24)00333-8. doi: 10.1016/j.urolonc.2024.02.003. Online ahead of print.

Authors

Jonathan Kanakaraj¹, Justin Chang¹, Lance J Hampton², Steven Christopher Smith³

Affiliations

¹ Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA.
² Division of Urology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA; Department of Pathology, Richmond Veterans Affairs Medical Center, Richmond, VA; VCU Massey Comprehensive Cancer Center, Richmond, VA.
³ Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA; Division of Urology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA; Department of Pathology, Richmond Veterans Affairs Medical Center, Richmond, VA; VCU Massey Comprehensive Cancer Center, Richmond, VA. Electronic address: steven.c.smith@vcuhealth.org.

PMID: 38519377
DOI: 10.1016/j.urolonc.2024.02.003

Abstract

The evolution of classification of renal tumors has been impacted since the turn of the millennium by rapid progress in histopathology, immunohistochemistry, and molecular genetics. Together, these features have enabled firm recognition of specific, classic types of renal cell carcinomas, such as clear cell renal cell carcinoma, that in current practice trigger histologic-type specific management and treatment protocols. Now, the fifth Edition World Health Classification's new category of "Molecularly defined renal carcinomas" changes the paradigm, defining a total of seven entities based specifically on their fundamental molecular underpinnings. These tumors, which include TFE3-rearranged, TFEB-altered, ELOC-mutated, fumarate hydratase-deficient, succinate dehydrogenase-deficient, ALK-rearranged, and SMARCB1-deficient renal medullary carcinoma, encompass a wide clinical and histopathologic phenotypic spectrum of tumors. Already, important management aspects are apparent for several of these entities, while emerging therapeutic angles are coming into view. A brief, clinically-oriented introduction of the entities in this new category, focusing on relevant diagnostic, molecular, and management aspects, is the subject of this review.

Keywords: SMARCB1-deficient renal medullary carcinoma; TFE3-rearranged renal cell carcinoma, TFEB-altered renal cell carcinoma, ELOC-mutated renal cell carcinoma, fumarate hydratase-deficient renal cell carcinoma, succinate dehydrogenase-deficient renal cell carcinoma, ALK-rearranged renal cell carcinoma.

Publication types

Review