SMARCA2::CREM fusions have been reported in a small number of rare and heterogeneous neoplasms across various anatomic sites. Although several morphologic features overlap among the reported cases, they can pose significant diagnostic challenges due to their variable morphology and nonspecific immunophenotype. They may also be underrecognized in clinical practice because SMARCA2 and CREM are not routinely included in many clinical fusion gene panels. SMARCA2::CREM fusion genes have been most frequently found in intracranial mesenchymal tumors and hyalinizing clear cell carcinomas, and previous studies of SMARCA2::CREM fusion-positive tumors have consistently shown the retained expression of SWItch/Sucrose Nonfermentable (SWI/SNF) complex proteins, including BRG1, BRM, and INI1. In this case report, we describe the first gynecologic tumor harboring the SMARCA2::CREM fusion gene, diagnosed in a 39-year-old woman. Histologically, the tumor exhibited spindle cell and epithelioid components, with rhabdoid features in some areas. Immunohistochemistry demonstrated epithelial marker positivity in the epithelial component, along with retained expression of BRG1 and INI1. Whole-transcriptome sequencing revealed SMARCA2::CREM fusion that was not detected by the in-house fusion gene panel. This case contributes additional data to the limited literature on tumors with SMARCA2::CREM fusions. It highlights the potential utility of comprehensive molecular testing, including broader fusion panels or whole-transcriptome sequencing, in the evaluation of diagnostically challenging uterine neoplasms.
Okamoto et al. (2026) studied this question.