Clinicopathological features of SMARCB1/INI1-deficient medullary-like renal cell carcinoma: Report of 3 cases and literature review

Abstract

SMARCB1/INI1-deficient medullary-like renal cell carcinoma (MLRCC), also used to be known as unclassified renal cell carcinoma with medullary phenotype (RCCU-MP), is an extremely rare and highly aggressive kidney tumor. The 2022 World Health Organization (WHO) classification proposes that high-grade renal cell carcinomas exhibiting morphological and immunophenotypic features identical to renal medullary carcinoma, but without evidence of sickle cell trait or disease, should be diagnosed as SMARCB1/INI1-deficient medullary-like renal cell carcinoma(MLRCC) and classified as a subtype of SMARCB1-deficient renal medullary carcinoma (RMC). To date, only 15 cases of MLRCC have been reported in the literature, primarily as case reports. This study presents three additional cases of MLRCC, all without a history of hemoglobinopathy or relevant family history. Histopathologically, all tumors exhibited nested, cord-like, and reticular/microcystic growth patterns that closely resemble those of classical renal medullary carcinoma, yet differ in epidemiological characteristics such as age and ethnic distribution. The tumor cells showed significant atypia with high-grade nuclear features and one case displayed focal rhabdoid morphology. Associated findings included necrosis, extensive stromal fibrosis, myxoid change, and a prominent inflammatory infiltrate with aggregates. Immunohistochemically, all three cases were positive for CK and Vimentin, and showed a complete loss of SMARCB1/INI1 protein expression. Currently, no standard treatment regimen has been established for this disease. Given its highly aggressive nature, early and accurate diagnosis is crucial. Pathologists must integrate clinical history, morphological characteristics, immunophenotype for a comprehensive diagnosis.