Dundr Pavel, Dvořák Jiří, Krausová Michaela, Hojný Jan, Hájková Nikola, Stružinská Ivana, Němejcová Kristýna, Ondič Ondřej, Michal Michael, Michalová Květoslava, Berjón Alberto, Jedryka Marcin, Książek Mariusz, Poprawski Tymoteusz, Ryś Janusz, Volodko Nataliya, Zapardiel Ignacio, Zima Tomáš, Cibula David, Poncová Renata, Matěj Radoslav, Kendall Bártů Michaela
Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 2, Prague 2, 12800, Czech Republic.
Department of Pathology, Charles University, Faculty of Medicine in Plzeň, Bioptical Laboratory, Ltd, Plzeň, Czech Republic.
Virchows Arch. 2025 Mar;486(3):551-562. doi: 10.1007/s00428-024-03994-3. Epub 2024 Dec 4.
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.
具有KAT6B/A::KANSL1融合的子宫肉瘤代表一种新的实体，其形态学表现平淡，通常具有低级别子宫内膜间质肉瘤（LG-ESS）和平滑肌分化肿瘤的混合特征。在我们的研究中，我们对9例此类肿瘤进行了详细的形态学、免疫组织化学和分子分析。其中6例最初被诊断为LG-ESS，1例为平滑肌瘤，1例为平滑肌肉瘤，其余1例为具有KAT6B/A::KANSL1融合的肉瘤。7例显示子宫内膜间质和平滑肌肿瘤之间的重叠特征，1例类似细胞性平滑肌瘤，1例类似高级别子宫内膜间质肉瘤。免疫组织化学显示，这些肿瘤共同表达平滑肌标志物和子宫内膜间质标志物。分子检测结果显示所有病例均存在KAT6B/A::KANSL1融合（通过二代测序和荧光原位杂交）。此外，在所有5例具有侵袭性行为的病例中均存在影响TP53、PDGFRB、NF1、RB1、PTEN、ATM、RB1、FANCD2和TSC1等基因的突变。1例无疾病证据的患者未显示其他突变，而另1例携带单个基因（ERCC3）的突变。在8例有随访信息的患者中，2例死于疾病，3例目前仍患有疾病，3例无疾病证据。正确识别具有KAT6B/A::KANSL1融合的肿瘤至关重要，因为尽管大多数病例形态学表现平淡，但这些肿瘤有侵袭性行为的倾向。
