RNF19A::PLAG1-rearranged uterine mesenchymal tumor with myofibroblastic features and focal adipocytic differentiation: broadening the histologic and molecular genetic spectrum of PLAG1-rearranged uterine mesenchymal neoplasms.

In the uterus, PLAG1-rearranged mesenchymal tumors are increasingly recognized, most being myxoid leiomyosarcomas. Here we report a unique PLAG1-rearranged uterine mesenchymal tumor with myofibroblastic features and focal adipocytic differentiation in a 50‑year‑old woman. The 2.7‑cm tumor, preoperatively suspected as leiomyoma, showed bland spindle to epithelioid cells arranged in solid sheets or fascicles within a predominantly fibrous stroma with focal myxoid change, admixed with scattered mature adipocytes. Mitotic activity was low and necrosis was absent. The tumor cells co‑expressed CD34, desmin, estrogen receptor, and progesterone receptor, retained RB1 expression, and were negative for smooth muscle actin, h‑caldesmon, and cytokeratin. Targeted RNA sequencing identified an in‑frame RNF19A(ex1)::PLAG1(ex3) fusion, which was confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. Fluorescence in situ hybridization demonstrated PLAG1 gene rearrangement and also revealed PLAG1 copy number gain. Diffuse nuclear PLAG1 expression by immunohistochemistry further confirmed the molecular findings. The patient is recurrence‑free at 4 months of follow‑up. This distinctive combination of myofibroblastic features, focal adipocytic differentiation, and PLAG1 rearrangement has not been previously reported in a uterine mesenchymal tumor. This case broadens the histologic and molecular genetic spectrum of PLAG1-rearranged uterine mesenchymal tumors and highlights the diagnostic value of molecular testing in unusual uterine spindle cell lesions.