Renal Cell Carcinoma: Histopathology, Molecular Features, and the Emerging Role of Organoid Models

Renal cell carcinoma (RCC) accounts for approximately 90% of kidney malignancies and comprises a heterogeneous group of tumors with distinct histological and molecular features. More than 20 histological subtypes have been defined within an integrated classification framework that incorporates histomorphology and is increasingly informed by recurrent molecular differences. Given the intrinsic resistance to conventional chemotherapies, treatment of advanced RCC primarily relies on tyrosine kinase inhibitors and immune checkpoint blockade; however, responses are often transient, and only a subset of patients derive durable benefits. Accordingly, personalized medicine strategies that guide treatment selection based on tumor biology have a high potential to improve patient care in RCC. Patient-derived organoids have emerged as promising preclinical models to study individual tumors and to evaluate drug responses in a timely, non-invasive, and personalized manner. However, their clinical applicability remains limited by variability in culture conditions and incomplete recapitulation of the tumor microenvironment. This review summarizes the key histological and molecular features of major RCC subtypes, outlines the application of patient-derived organoids in RCC research, and discusses current gaps that, if addressed, could strengthen organoid-based approaches for precision medicine in RCC.