High-grade
endometrial stromal sarcoma likely encompasses underrecognized
tumors harboring genetic abnormalities besides YWHAE-NUTM2 fusion. Triggered by three initial
endometrial stromal sarcomas with ZC3H7B-BCOR fusion characterized by high-grade morphology and aggressive clinical behavior, we herein investigate the clinicopathologic features of this genetic subset by expanding the analysis to 17 such
tumors. All of them occurred in adult women with a median age of 54 (range, 28-71) years. They were predominantly based in the endomyometrium and demonstrated tongue-like and/or pushing myometrial invasion. Most were uniformly cellular and displayed haphazard fascicles of spindle cells with mild to moderate nuclear atypia. Myxoid matrix was seen in 14 of 17 (82%)
tumors, and
collagen plaques were seen in 8 (47%). The mitotic index was ≥10 mitotic figures/10 high-power fields (HPFs) in 14 of 17 (82%)
tumors with a median of 14.5 mitotic figures/10 HPFs. No foci of conventional or variant low-grade
endometrial stromal sarcoma were seen. All
tumors expressed CD10 with only limited or absent
desmin, SMA and/or h-
caldesmon staining. ER and PR expression in >5% of cells was seen in 4 of 12 (33%)
tumors. Diffuse
cyclin D1 and BCOR immunoreactivity was present in 7 of 8 (88%) and 7 of 14 (50%)
tumors, respectively. Fluorescence in situ hybridization or targeted
RNA sequencing confirmed ZC3H7B-BCOR fusion in all
tumors, including four and two previously diagnosed as
myxoid leiomyosarcoma and undifferentiated uterine
sarcoma, respectively. Limited clinical data suggest that patients present at higher stage and have worse prognosis compared with published outcomes in low-grade
endometrial stromal sarcoma.
Tumors with ZC3H7B-BCOR fusion constitute a distinct group of
endometrial stromal sarcomas with high-grade morphology that should be distinguished from other uterine mesenchymal
neoplasms that may demonstrate myxoid morphology.