Uterine Myxoid Mesenchymal Tumor With a Novel SS18::VEZF1 Gene Fusion, Lacking Worrisome Histological Features

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.