Endometrial stromal sarcoma – the new genetic paradigm

Endometrial stromal sarcoma (ESS) is a gynaecological sarcoma that is composed of cells that resemble those of proliferative‐phase endometrial stroma. The 2014 World Health Organization tumour classification system separates ESS into low‐grade and high‐grade types, which are histologically, genetically and clinically distinct from undifferentiated uterine sarcoma (UUS). Low‐grade ESSs frequently contain chromosomal rearrangements that result in JAZF1–SUZ12 fusion or equivalent genetic fusions. Although most low‐grade ESSs show classic histological features that closely resemble those of proliferative‐phase endometrial stroma, there are several histological variants that are associated with the same genetic fusions as seen in the classic type. High‐grade ESS is defined by the presence of YWHAE–NUTM2A/B (YWHAE–FAM22A/B) fusions. High‐grade ESSs are clinically more aggressive than low‐grade ESSs, but are associated with a lower mortality rate than UUSs. The histological and immunophenotypic features of these different types of ESS, and their diagnostic considerations, are the subjects of this review.