Endometrial and other rare uterine sarcomas : Diagnostic aspects in the context of the 2020 WHO classification

Abstract

Uterine sarcomas are aheterogeneous group of rare malignancies. Mostly (40-50%), they are leiomyosarcomas, followed by endometrial stromal sarcomas (ESS), low-grade (LG) and high-grade (HG), as well as undifferentiated sarcoma of the uterus (UUS) and adenosarcomas (AS). Other, non-organ-specific tumours such as NTRK-rearranged spindle cell neoplasia, perivascular epithelioid cell tumour (PEComa) and inflammatory myofibroblastic tumour (IMT) are extremely difficult to differentiate.In the most recent WHO classification, endometrial stromal tumours are subdivided as follows: benign, expansively growing endometrial stromal nodule (ESN) with sharp demarcation, the histologically similar-looking LG-ESS with infiltrative growth, the highly malignant HG-ESS and, as adiagnosis of exclusion, the highly aggressive UUS lacking specific lines of differentiation. LG-ESS can be differentiated from HG-ESS in most cases histomorphologically and immunohistochemically, but molecular investigations are necessary in individual cases. HG-ESS can be divided into 4subtypes (YWHAE/NUTM2 fusion low-grade component, YWHAE/NUTM2 fusion high-grade component, ZC3H7B-BCOR fusion or BCOR-ITD) on the basis of molecular findings. Prognostically unfavourable factors in AS are severe sarcomatous overgrowth, deep myometrial invasion, high-grade histology and lymphatic vessel invasion. Tumours with NTRK fusion are immunohistochemically positive for S100 and TRK. PEComas express cathepsin K and HMB45, as well as TFE3 when translocation is present. Almost every IMT shows an alteration in the ALK gene In the case of overlapping morphology and simultaneous therapeutic and prognostic relevance, it is becoming increasingly important to verify or confirm the suspected histomorphological diagnosis by immunohistochemical and possibly molecular investigations.