Uterine Leiomyosarcoma with a Novel RAB2A-PLAG1 Gene Fusion

Abstract

Abstract Uterine leiomyosarcoma (ULMS) is the most common subtype of uterine sarcoma and constitutes 1% of all uterine malignancies. In some cases, distinguishing ULMS from endometrial stromal sarcoma (ESS) can be challenging because they may display histological and immunohistochemical overlaps. In such cases, molecular studies such as RNA sequencing to detect gene rearrangements can help arrive at a definitive diagnosis. We report a unique case of ULMS with a novel RAB2A-PLAG1 gene fusion. To our knowledge, this is the first reported case in English literature. Case Presentation: An 80-year-old woman presented to our hospital with a one-month history of pelvic pain and abnormal uterine bleeding. Imaging was notable for a large necrotic uterine mass, thickened endometrium, and uterine fibroids. Subsequent endometrial biopsy (EMB) revealed an unremarkable transformation zone of the epithelium. After four months, the patient presented with persistent symptoms. A solid mass within the endometrium was observed on the imaging. Endometrial curettage (EMC) revealed a malignant uterine mesenchymal neoplasm, with histological findings suggestive of ULMS and ESS. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy. Immunohistochemical analysis of the resected specimen was inconclusive. RNA sequencing revealed a novel RAB2A-PLAG1fusion, and ULMS was diagnosed. Conclusion: This is the first case of ULMS with a RAB2A-PLAG1 gene fusion. Pathologists should be aware of the extensive morphological and immunophenotypic overlap between the various uterine mesenchymal neoplasms. In challenging cases, molecular studies are crucial for pathologists to arrive at a final diagnosis.