Abstract:TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare subtype of kidney cancer driven by Xp11.2 translocations, characterized by molecular heterogeneity due to TFE3 gene fusions with various partner genes. This article provides a systematical review of the molecular mechanisms, diagnostic approaches, and therapeutic advances, with a particular focus on the impact of different fusion partners on clinicopathological behavior, invasive potential, and patient prognosis. We emphasize that subtyping based on the fusion partner is pivotal for advancing the management of this disease from a traditional histopathological classification towards a molecularly-driven framework. This paradigm shift is critically important for guiding individualized surgery, combination therapies of targeted agents with immunotherapy, and prognostic assessment. The implementation of a stratified diagnostic pathway that integrates morphology, immunohistochemistry, and molecular testing, holds the promise of achieving precise identification and subtyping, thereby guiding the development of future personalized treatment strategies.
