Uterine sarcomas with KAT6B/A::KANSL1 fusion represent a new entity characterized by bland morphology, commonly with hybrid features of low-grade endometrial stromal sarcoma (LG-ESS) and tumors with smooth muscle differentiation. In our study, we performed a detailed morphological, immunohistochemical, and molecular analysis of 9 cases of these tumors. Six of those had been originally diagnosed as LG-ESS, one as leiomyoma, one as leiomyosarcoma, and the remaining case as sarcoma with the KAT6B/A::KANSL1 fusion. Seven cases showed overlapping features between endometrial stromal and smooth muscle tumors, one case resembled cellular leiomyoma, and one case resembled high-grade endometrial stromal sarcoma. Immunohistochemically, the tumors showed a common expression of smooth muscle markers and endometrial stromal markers. Molecular findings showed the KAT6B/A::KANSL1 fusion in all cases (by NGS and FISH). In addition, mutations affecting genes such as TP53, PDGFRB, NF1, RB1, PTEN, ATM, RB1, FANCD2, and TSC1 were present in all 5 cases with aggressive behavior. One patient with no evidence of disease showed no additional mutations, while another harbored a mutation of a single gene (ERCC3). Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.

Danylo Halytsky Lviv National Medical University Lviv Ukraine

Department of Pathology 1st Faculty of Medicine Charles University and General University Hospital Prague Studničkova 2 Prague 2 12800 Czech Republic

Department of Pathology and Molecular Medicine 3rd Faculty of Medicine Charles University Thomayer University Hospital Prague Czech Republic

Department of Pathology Charles University 3rd Faculty of Medicine University Hospital Kralovske Vinohrady 10034 Prague Czech Republic

Department of Pathology Charles University Faculty of Medicine in Plzeň Bioptical Laboratory Ltd Plzeň Czech Republic

Department of Tumor Pathology Maria Sklodowska Curie National Research Institute of Oncology Krakow Branch Krakow Poland

Gynecologic Oncology Centre Department of Gynaecology Obstetrics and Neonatology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Gynecologic Oncology Unit La Paz University Hospital Madrid Spain

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Oncological Gynecology Department Lower Silesian Oncology Pulmonology and Hematology Center Wroclaw Poland

Oncology Department Wroclaw Medical University Wroclaw Poland

Pathology Department La Paz University Hospital Madrid Spain

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