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The Rare Gynecologic Sarcoma study involved 23 institutions from 10 countries focusing on myxoid leiomyosarcoma and non-smooth muscle uterine sarcomas. Here, we present the main results of the study, including the comparison between the original and final diagnosis, the frequency and type of molecular aberrations, and the clinicopathologic outcomes. A total of 379 cases were included, with available results for next-generation sequencing (NGS) RNA in 338 of 379 cases and NGS DNA in 335 of 379 cases. According to the original diagnoses, the study included 204 cases of low-grade endometrial stromal sarcoma (LG-ESS), 75 cases of high-grade endometrial stromal sarcoma (HG-ESS), 74 cases of undifferentiated uterine sarcoma (UUS), 17 cases of myxoid leiomyosarcoma, and 9 cases of unclassifiable sarcoma. The results of our second reading showed that 29% (110/379) of all the tumors had been originally misdiagnosed. After the reclassification, the final diagnoses were 147 cases of LG-ESS, 69 cases of HG-ESS, 58 cases of UUS, 3 cases of LG-ESS with high-grade transformation, 7 cases of perivascular epithelioid cell tumor, 9 cases of uterine tumor resembling ovarian sex cord tumor, 8 cases of tumors with a KAT6B/A::KANSL1 fusion, 2 cases of tumors with an NTRK fusion, 29 cases of undifferentiated carcinoma, and 47 tumors with smooth muscle differentiation. The molecular testing showed that LG-ESS harbor a recurrent fusion in 75.9% and HG-ESS in 43.7% of cases. The results of our study emphasize the diagnostic, prognostic, and predictive significance of molecular testing in mesenchymal uterine tumors., (Copyright © 2025 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

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).)

Background : Ovarian, fallopian tube, and primary peritoneal cancers often share clinical characteristics and are typically diagnosed at advanced stages due to nonspecific symptoms. The utility of tumor markers, particularly CA125 and HE4, in the diagnosis and follow-up of these cancers remains an area of active investigation. Objectives : The CEEGOG (Central and Eastern European Gynecologic Oncology Group) OX-01 study aimed to evaluate HE4's role alongside CA125 in follow-up for advanced-stage ovarian, fallopian tube, and primary peritoneal cancers. It assessed the potential for detecting recurrence using marker elevation and imaging methods, examining the necessity of dynamic monitoring and current cut-off values' accuracy for early relapse detection. Methods : In this multicenter prospective cohort study, 117 eligible patients with Stage III-IV cancers were included. Patients had elevated CA125 or HE4 at diagnosis and achieved complete remission after first-line treatment. HE4 and CA125 levels were monitored every 3-4 months in the first two years and every six months thereafter. CT scans were performed if markers exceeded set thresholds or increased by over 20%. Results : During a median follow-up of 13.7 months, 73% of patients relapsed. Median HE4 levels were significantly higher in relapsed patients. A 10 IU/mL increase from baseline in CA125 had a sensitivity of 83% and specificity of 93%, while a 15 pmol/L increase in HE4 had a sensitivity of 74% and specificity of 92% for predicting relapse up to three months before CT scan detection. Conclusions : The study found that dynamic changes in HE4 and CA125 levels, rather than predefined cut-off values, are crucial for early relapse detection. These markers may offer a significant lead time over imaging, potentially enabling earlier intervention. Further research is needed to validate these findings.

Background: Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. However, the lack of standardisation of volumetric LLL assessment hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective trial that have implications for LLL assessment standardisation., Methods: In the prospective international multicentre trial SENTIX, a group of 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral sentinel lymph node biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery., Results: Patient LVC substantially fluctuated in both positive and negative directions, which were comparable in frequency up to ±14% change. Thirty-eight patients experienced persistent LVC increase >10% classified as LLL, with nine months median time to onset. Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits. No significant correlation between LVC >10% and a patient-reported swelling was observed., Conclusions: Given that we observed comparable fluctuations of the the lower-limb volumes after surgical treatment of cervical cancer in both positive and negative direction up to ±14%, the diagnostic threshold for LLL diagnosis based on LVC should be increased to >15% LVC. The distinction of transient oedema from persistent LLL requires repeated measurements. Also, as one-third of LLL cases are diagnosed >1-year post-surgery, a sufficient follow-up duration needs to be ensured. Patient-reported swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment., Trial Registration: ClinicalTrials.gov: NCT02494063., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We are reporting a case of endometrial lymphoepithelioma-like carcinoma (LELC) in a 63-year-old female. Microscopically, the tumor consisted of groups of tumor cells surrounded by dense lymphoplasmacytic infiltrate. Immunohistochemically, the tumour cells were positive for cytokeratins AE1/AE3, EMA, PAX8, p16, and estrogen receptors. Protein p53 showed an aberrant type of expression. Molecular genetic analysis revealed mutations in the TP53 and PIKP53CA genes. Based on our results, we believe that the tumor represents an unusual morphological variant of endometrial serous carcinoma.To the best of our knowledge, only six cases of LELC arising in endometrium have been reported in literature to date.