Endometrial stromal tumors of the uterus: Epidemiology, pathological and biological features, treatment options and clinical outcomes

Highlights•ESTs are rare malignancies, mainly affecting peri- or postmenopausal women.•Most common genetic alteration identified in LG-ESS is the JAZF1-SUZ12 rearrangement.•YWHAE-NUTM2A/B and BCOR rearrangements characterize two subtypes of HG-ESS.•The absence of specific genetic abnormalities is the actual hallmark of UUS.•LG-ESSs usually express estrogen and progesterone receptors.AbstractEndometrial stromal tumors (EST) are uterine mesenchymal tumors, which histologically resemble endometrial stroma of the functioning endometrium. The majority of EST are malignant tumors classified as low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS).Overall, ESTs are rare malignancies, with an annual incidence of approximately 0.30 per 100′000 women, mainly affecting peri- or postmenopausal women.The most common genetic alteration identified in LG-ESS is the JAZF1-SUZ12 rearrangement, while t(10;17)(q23,p13) translocation and BCOR gene abnormalities characterize two major subtypes of HG-ESS. The absence of specific genetic abnormalities is the actual hallmark of UUS. Unlike HG-ESSs, LG-ESSs usually express estrogen and progesterone receptors.Total hysterectomy without morcellation and bilateral salpingo-oophorectomy (BSO) is the first-line treatment of early-stage LG-ESS. Ovarian preservation, fertility-sparing treatment, and adjuvant hormonal therapy ± radiotherapy may be an option in selected cases. In advanced or recurrent LG-ESS, surgical cytoreduction followed by hormonal treatment, or vice versa, are acceptable treatments. The standard treatment for apparently early-stage HG-ESS and UUS is total hysterectomy without morcellation with BSO. Ovarian preservation and adjuvant chemotherapy ± radiotherapy may be an option. In advanced or recurrent HG-ESS, surgical cytoreduction and neoadjuvant or adjuvant chemotherapy can be considered. Alternative treatments, including biological agents and immunotherapy, are under investigation.LG-ESSs are indolent tumor with a 5-year overall survival (OS) of 80–100% and present as stage I-II at diagnosis in two third of patients. HG-ESSs carry a poor prognosis, with a median OS ranging from 11 to 24 months, and 70% of patients are in stage III-IV at presentation. UUS median OS ranges from 12 to 23 months and, at diagnosis, 70% of patients are in stage III-IV.The aim of this review is to assess the clinical, pathological, and biological features and the therapeutic options for malignant ESTs.