ZC3H7B-BCOR-Rearranged Endometrial Stromal Sarcomas: A Distinct Subset Merits its Own Classification?

A 41-yr-old lady with abnormal uterine bleeding underwent total abdominal hysterectomy. Histologic assessment revealed an endometrial stromal sarcoma (ESS) with minimal cytologic atypia and low mitotic count (up to 7/10 high-power fields) with only focal myxoid areas, morphologically corresponding to a low-grade ESS. Immunohistochemical stains showed cyclin D1 and CD10 positivity, and negative staining for CD117 and progesterone receptor. This tumor was clinically aggressive and recurred 6 mo later. The patient died 19 mo following initial diagnosis. Molecular analysis revealed a ZC3H7B (exon 10)-BCOR (exon 7) gene fusion. Subsequent BCOR immunohistochemistry was weakly positive. ESS with ZC3H7B-BCOR gene fusion is classified as a low-grade ESS in some classification schemes, and is also characterized as being typically myxoid. This report supports emerging evidence that ESS with ZC3H7B-BCOR gene fusion may have an aggressive clinical course in spite of its low-grade histology. This report further expands the morphologic spectrum of ZC3H7B-BCOR fusion ESS to include nonmyxoid histology. Finally, this report underlines the value of molecular analysis in the proper classification of this aggressive tumor with deceptive low-grade histology.