Abstract
We report a uterine myxoid mesenchymal tumor with a novel SS18::VEZF1 gene fusion. The current lesion was identified in a 53-year-old woman who presented with symptomatic "fibroids" showing accelerated growth and heterogeneous morphology on radiologic assessment. Microscopic examination revealed a well-demarcated neoplasm, and the tumor exhibited alternating hypocellular/hyalinized and hypercellular areas, composed of a monomorphic proliferation of spindle, ovoid, and epithelioid cells arranged in sheets. These cells were embedded within either a hyalinized collagenous stroma or abundant myxoid stroma. Tumor cells were frequently located around blood vessels and exhibited amphophilic or eosinophilic cytoplasm and elongated or ovoid-shaped nuclei with coarsely clumped chromatin. No mitoses, pleomorphism, or necrosis was identified. Immunohistochemically, the tumor was positive for CD10, CD34, TLE1, estrogen, and progesterone receptors. It was negative for h-caldesmon, desmin, smooth muscle actin, smoothelin, myosin, cyclin D1, S100, ALK, EMA, panTRK, and SS18-SSX. Targeted RNA sequencing revealed an SS18::VEZF1 gene fusion (breakpoint: exon 9-exon 2), which was confirmed by FISH (SS18). In conclusion, RNA sequencing was useful in identifying the fusion event, thereby excluding potential mimics with uncommon morphology or ambiguous immunophenotype.