SMARCB1-deficient Medullary-Like Renal Cell Carcinoma Without SMARCB1/INI1 Gene Deletion.

Abstract

High-grade renal cell carcinoma with morphology and immunophenotypic features identical to renal medullary carcinoma, occurring in a patient without evidence of sickle cell trait or disease, is proposed to be diagnosed as renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) and classified as a subtype of SMARCB1-deficient renal medullary carcinoma in the World Health Organization (WHO) 2022 edition. So far, about twelve tumors of RCCU-MP have been reported in the literature. Herein, we extend this observation to a tumor of RCCU-MP in a 39-year-old patient, morphologically similar to renal medullary carcinoma. SMARCB1 expression was absent by immunohistochemistry, but there was no evidence of hemoglobinopathy. The tumor cells were positive for keratin19, PAX8 and PAX2. GATA3, OCT3/4, and ALK were negative. Fluorescence in situ hybridization was conducted to detect the SMARCB1 gene locus on chromosome 22 (22q11.23 region). The results showed no evidence of deletion or translocation involving the gene. Perirenal lymph node metastases were detected. The patient did not receive any treatment. Six months after surgery, she developed a local recurrence. In addition to SMARCB1 gene deletion or translocation, other factors may be associated with the loss of INI1 (SMARCB1) protein. The presence of perirenal lymph node metastases and recurrence despite nephrectomy is indicative of the poor prognosis of this tumor. Further investigation of the relationship between the loss of SMARCB1 protein and the development of RCCU-MP might improve our understanding of the pathogenesis of this malignant tumor.