Renal cell carcinoma unclassified with medullary phenotype: a case report and review of the literature

Renal medullary carcinoma (RMC) is a highly aggressive tumor characterized by SMARCB1/INI1 deficiency, predominantly affecting young blacks with sickle cell disease. Recently, the provisional diagnostic entity "renal cell carcinoma unclassified with medullary phenotype" (RCCU-MP) has been proposed to describe tumors exhibiting RMC-like histopathological features and loss of SMARCB1/INI1 expression, but occurring in patients without sickle cell disease. Here, we report a 55-year-old Chinese male patient without sickle cell disease who presented with an 8-cm left renal mass. Histopathological examination revealed a high-grade renal cell carcinoma with complete loss of SMARCB1/INI1 expression by immunohistochemistry. Based on these findings, a diagnosis of RCCU-MP was made. To the best of our knowledge, this represents the first internationally reported RCCU-MP case of Chinese origin, with only one prior case documented in domestic Chinese literature. Given the exceptional rarity of RCCU-MP and its overlapping characteristics with RMC, we systematically analyze the clinical features, pathological morphology, and immunohistochemistry of RCCU-MP separately. Additionally, we explore potential molecular pathogenesis and emerging therapeutic strategies based on recent evidence.