Uterine Tumor Resembling Ovarian Sex Cord Tumor With Aggressive Histologic Features Harboring a GREB1-NCOA2 Fusion: Case Report With a Brief Review

Abstract

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain lineage, that shows predominantly sex cord-like differentiation with a broad range of histologic appearances and polyphenotypic immunohistochemical features. Although generally having a favorable prognosis, a subset can recur/metastasize. Most recently, several studies of UTROSCT have described novel fusion genes involving ESR1 and GREB1 as the 5 partner, and NCOA1-3 as the 3 partner. Genotype and phenotype correlation has suggested that GREB1-rearranged tumors may have a higher tendency to behave aggressively. Herein, we report a UTROSCT with aggressive histologic features harboring a GREB1-NCOA2 fusion. A 51-yr-old woman presented with menometrorrhagia and progressive dysmenorrhea and was found to have a submucous uterine lesion by ultrasonography. Gross examination of the hysterectomy specimen showed an 8.5-cm, polypoid, soft, intracavitary mass. Histologic examination revealed a deeply invasive neoplasm composed of uniform round to plump spindle cells, arranged predominantly in diffuse sheets and fascicles and focally in anastomosing cords patterns. Groups of rhabdoid tumor cells were occasionally noted. Worrisome features, including increased mitotic figures (up to 3/10 high power fields), geographic necrosis, and lymphovascular invasion, were evident. Immunohistochemical analysis showed variable positivity for epithelial, smooth muscle, neuroendocrine, and sex cord markers, as well as hormone receptors. RNA sequencing revealed an in-frame fusion between exon 3 of GREB1 and exon 14 of NCOA2. Fluorescence in situ hybridization analyses confirmed rearrangements of both the GREB1 and NCOA2 loci. Our case lends further supports that GREB1-rearranged UTROSCTs frequently exhibit aggressive histological features with inconspicuous sex cord-like differentiation.