Flídrová M, Dundr P, Vránková R, Němejcová K, Cibula D, Poncová R, Michalová K, Bouda J, Laco J, Ndukwe M, Ryś J, Książek M, Berjon A, Zapardiel I, Franin I, Njavro A, Hausnerová J, Bretová P, Židlík V, Klát J, Krasznai ZT, Poka R, Volodko N, Yezhova I, Pilka R, Marek R, Kolnikova G, Krkoška M, Halaška M, Drozenová J, Dolinská D, Kalist V, Bobiński M, Ostrowska-Leśko M, Bizoń M, Sawicki W, Stukan M, Grabowska K, Jędryka M, Poprawski T, Stolnicu S, Căpîlna ME, Špůrková Z, Zikán M, Ciccarone F, Scambia G, Sharashenidze A, Gudadze M, Piatnytska T, Varchak I, and Kendall Bártů M
Low-grade endometrial stromal sarcoma (LG-ESS) can present diagnostic challenges, due to its overlapping morphological features with other uterine mesenchymal tumors. Misdiagnosis rates remain significant, and immunohistochemical data for LG-ESS are limited to small series and inconsistent antibody panels. This study aimed to refine the IHC profile of LG-ESS by analyzing a large, molecularly confirmed series of 147 cases using a panel of 24 antibodies, including newer markers like transgelin and smoothelin. CD10 and IFITM1, key endometrial stromal markers, were expressed in 86% (92% of those extensively) and 69% (60% of those extensively) of cases, with fusion-positive tumors showing significantly higher expression. Smooth muscle markers (α-SMA, desmin, h-caldesmon, calponin, transgelin) were variably expressed, predominantly in focal or low-intensity patterns, with α-SMA reaching the highest frequency of expression (44%). However, the intensity of smooth muscle marker expression was usually very low. Smoothelin was rarely expressed. Hormone receptors were frequently positive, with PR showing a higher frequency (92% vs. 83%) and intensity than ER. Markers like S-100, HMB45, and CD117 were largely negative; all tumors were p53 wild-type, with preserved SMARCB1/SMARCA4 expression and ALK and ROS1 negativity. This work represents the largest molecularly validated IHC study on LG-ESS, providing a robust diagnostic profile for routine pathology. By addressing key diagnostic limitations and examining newer markers, our study supports a more standardized approach to diagnosing LG-ESS and underscores the value of immunohistochemical panels, particularly in fusion-negative tumors where diagnosis relies on morphological and immunohistochemical interpretation. These findings contribute critical data for improving diagnostic accuracy., Competing Interests: Declarations. Ethics approval: The study has been approved by the Ethics Committee of General University Hospital in Prague in compliance with the Helsinki Declaration (No. 2140/19 S-IV). The Ethics Committee waived the requirement for informed consent, as according to the Czech Law (Act. no. 373/11, and its amendment Act no. 202/17) it is not necessary to obtain informed consent in fully anonymized studies. Competing interests: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (© 2025. The Author(s).)