Uterine Leiomyosarcoma with a Novel RAB2A-PLAG1 Gene Fusion

Abstract

Abstract Uterine leiomyosarcoma (ULMS) constitutes 1% of all uterine malignancies and is the most common subtype of uterine sarcoma. In some cases, distinguishing ULMS from endometrial stromal sarcoma (ESS) can be challenging as they may display histological and immunohistochemical overlap. In such cases, molecular studies such as RNA sequencing to detect gene rearrangements can help arrive at the definitive diagnosis. We report a unique case on ULMS with a novel RAB2A-PLAG1 gene fusion, which to our knowledge, is the first case reported in the 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, a thickened endometrium, and uterine fibroids. A subsequent endometrial biopsy (EMB) revealed an unremarkable transformation zone epithelium. After 4 months, the patient presented with persistent symptoms. One solid mass within the endometrium was found on imaging. Endometrial curettage (EMC) revealed a malignant uterine mesenchymal neoplasm with histologic findings suggestive of ULMS and ESS. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy. Immunohistochemical study performed on the resection specimen was inconclusive. RNA sequencing identified a novel RAB2A-PLAG1 gene fusion, and a diagnosis of ULMS was rendered. Conclusion: This is the first case of a ULMS with RAB2A-PLAG1 gene fusion. Pathologists should be cognizant of the extensive morphologic and immunophenotypic overlap between various uterine mesenchymal neoplasms. In challenging cases, molecular studies are crucial in allowing the pathologist to arrive at the final diagnosis.