Uterine sarcomas and rare uterine mesenchymal tumors with malignant potential. Diagnostic guidelines of the French Sarcoma Group and the Rare Gynecological Tumors Group

The landscape of uterine sarcomas is becoming increasingly complex with the description of new entities associated with recurrent molecular alterations. Uterine sarcomas, as well as soft tissue sarcomas, can be distinguished into complex genomic sarcomas and simple genomic sarcomas. Leiomyosarcoma and pleomorphic type undifferentiated uterine sarcoma belong to the first group. Low-grade and high-grade endometrial stromal sarcomas, NTRK, COL1A1::PDGFB, ALK, RET, ROS1 associated sarcomas, and SMARCA4 deficient uterine sarcoma belong to the second group. Leiomyosarcoma is the most common uterine sarcoma followed by endometrial stromal sarcomas. Three different histologic subtypes of leiomyosarcomas are recognized with distinct diagnostic criteria and different clinical outcomes, the myxoid and epithelioid leiomyosarcomas being even more aggressive than the fusiform type. The distinction between low-grade and high-grade endometrial stromal sarcoma is based first on morphology and immunohistochemistry. The detection of fusion transcripts helps in the diagnosis. Definitely recognized as a separate entity, uterine PEComa is a rare tumor whose diagnostic criteria are being recently defined. Uterine PEComa has a specific algorithm stratifying the tumors into uncertain malignant potential and malignant tumors. Embryonal rhabdomyosarcomas of the uterine cervix are not restricted to children but can also be observed in adult women and are almost always DICER1 mutated, unlike embryonal rhabdomyosarcoma of the vagina which are DICER1wild-type, and adenosarcoma which can be DICER1 mutated but with less frequency. As sarcomas associated with fusion transcripts involving the NTRK, ALK, COL1A1::PDGFB genes can benefit from targeted therapy, systematic detection are now relevant especially for patients with high risk of relapse or in recurrent setting. The integration of molecular data with dedicated expert pathology review for histology and clinical data allows better identification of uterine sarcomas in order to better treat them.