At Global Voices in Renal Oncology (VIRO) 2025, organized by OncoDaily, Dr. Payal Kapur, Professor of Pathology at UT Southwestern Medical Center, delivered a talk on “Pathologic Evaluation of Variant Histologies in RCC.”
She emphasized that while clear cell RCC dominates the field, more than a quarter of renal tumors fall into non–clear cell categories, including papillary, chromophobe, oncocytic, and other subtypes. Recognizing these distinctions is crucial, as management strategies and prognosis vary significantly.
Dr. Kapur explained that historically, “variant” histologies were grouped together in a broad and sometimes confusing manner. The 2022 WHO classification clarified this by using the term subtype for morphologic entities, reserving variant for genetic alterations. This shift reflects the growing understanding of RCC’s molecular and morphologic diversity.
She highlighted newly recognized entities such as low-grade oncocytic tumors (LOTs), eosinophilic vacuolated tumors (EVTs), and TSC/MTOR pathway–associated RCC, each with distinct histopathologic and molecular features. For example, LOTs often sporadic or associated with syndromes like tuberous sclerosis show unique morphology, strong CK7 positivity, and clustering patterns distinct from oncocytomas and chromophobe RCC. Importantly, no metastatic potential has been documented in LOTs to date.
Dr. Kapur also discussed aggressive subsets, such as dedifferentiated chromophobe RCC, which can exhibit sarcomatoid or anaplastic transformation and are linked with poor outcomes. Molecular analyses suggest that chromosomal duplication and TP53 mutations may drive progression toward dedifferentiation and metastasis.
She reviewed other rare but clinically relevant entities, including TFEB- and TFE3-rearranged RCC, ELOC-mutated RCC, ALK-rearranged RCC, FH-deficient RCC, and SMARCB1-deficient RCC, underscoring how precision classification not only informs diagnosis but also carries therapeutic implications for example, the potential responsiveness of ALK-rearranged RCC to targeted ALK inhibitors.
Dr. Kapur closed by stressing that integrating clinical context, morphology, immunohistochemistry, and molecular testing is essential for accurate diagnosis and optimal patient management. This refined classification framework ensures that variant histologies are no longer overlooked but are instead recognized as distinct entities with implications for prognosis and treatment.
Join us in this conversation.