Objective: To report a case of polypoid ovarian endometrioma mimicking malignant transformation, review the literature on this rare entity, and highlight its implications for surgical management and fertility preservation. Design: Case report and literature review. Subject: One reproductive-age woman with suspected malignant transformation of an ovarian endometrioma. Exposure: Laparoscopic adnexectomy. Main Outcome Measure: Histopathologic confirmation of nonmalignant disease and review of surgical management in previously reported cases. Results: A 38-year-old woman desiring fertility preservation presented with a complex ovarian mass classified as O-RADS 4 on magnetic resonance imaging. Laparoscopic adnexectomy was performed for suspected malignancy. Final histopathologic examination confirmed a benign polypoid endometrioma. Review of the literature identified 22 reported cases, all managed surgically for presumed malignancy, with hysterectomy performed upfront in ten cases despite benign histology. Conclusion: Polypoid ovarian endometrioma is a rare mimic of ovarian malignancy that may lead to extensive surgery before histologic confirmation. Awareness of this entity is essential to reduce overtreatment and to support fertility-preserving management when appropriate.

•Placental site trophoblastic tumors (PSTT) express PD-L1, making them ideal targets for PD-1 and PD-L1 inhibitors.•For this PSTT patient seeking fertility-sparing treatment, PD-1 inhibition demonstrated complete and sustained response.•Despite anti PD-1 toxicity, there is potential for significant benefit when no alternative fertility-sparing options exists.

BACKGROUND:An average time to diagnosis of 7 years is commonly described for endometriosis; diagnostic delay for adenomyosis is unknown. This cross-sectional study aimed to describe diagnostic delay for endometriosis and adenomyosis and to investigate the factors associated with this delay. METHODS:Community of Patients for Research (ComPaRe)-Endometriosis is a prospective e-cohort of women with endometriosis and/or adenomyosis in France. About 6,949 participants were included. We used linear regression modeling to assess factors associated with diagnostic delay, after adjustment for age, education level, body mass index, number of comorbidities, and family history of the disease or of chronic pelvic pain (CPP). RESULTS:The average diagnostic delay was 10 years for endometriosis and 11 years for adenomyosis. Factors associated with a significantly longer diagnostic delay were year of diagnosis (+0.34 years, p < 0.0001), unemployment (+0.7 years, p = 0.01), number of comorbidities (+0.3 years, p < 0.0001), family history of the disease or of CPP (+1.1 years, p < 0.0001), severe dysmenorrhea before diagnosis (numeric-rating scale: +0.8 years, p < 0.0001), number of health professionals consulted before diagnosis (+0.3 years, p < 0.0001), and presence of multiple symptoms leading to first consultation (+1.6 years, p < 0.0001). In contrast, factors associated with a shorter delay were a financial position perceived as comfortable (-1.4 years, p < 0.0001), age at menarche (-0.6 years, p < 0.0001), and age at first symptoms (-0.8 years, p < 0.0001). CONCLUSIONS:This study highlights several factors associated with diagnostic delay among women with self-reported endometriosis and/or adenomyosis and provides new insights to improve care by informing both clinicians and patients. Attention to these profiles may improve disease management.

Abstract Introduction: Gynecologic carcinosarcomas (GynCS) are rare, aggressive uterine and ovarian cancers with a median survival under two years. Their biology is marked by epithelial-mesenchymal transition (EMT), driving dissemination and a biphasic carcinoma-sarcoma morphology. However, the molecular drivers of intratumoral heterogeneity beyond EMT remain poorly understood. This study seeks to clarify these mechanisms by characterizing the transcriptomic landscape of GynCS. Methods: Hematoxylin-eosin-saffron (HES) slides from 35 uterine and ovarian carcinosarcomas were reviewed by a gynecologic pathologist. A total of 251 tumoral tissue sectors, including carcinoma, sarcoma and mixed components, were selected for morphological assessment and bulk RNA sequencing (RNA-seq) using the SMARTer library preparation kit. Results: Among 35 tumors included in cohort, 33 (94%) were TP53-mutated, 2 (4%) had no specific molecular profile, 1 (2%) was mismatch repair-deficient and none was POLE-mutated. EMT expression signature correlated with histological features despite 26% of histologicaly sarcomatous sectors being reclassified as epithelial based on RNAseq (WISP classifier). Gene set enrichment analysis (GSEA) in all carcinoma sectors compared to all sarcoma sectors revealed a depletion in the response to inflammation and immunity as the main mechanism alongside EMT. Both cell-type deconvolution on RNA-seq data and immunohistochemical CD3 staining on FFPE slides suggest an enrichment in T cells, particularly cytotoxic T cells, in the tumor microenvironment of carcinoma sectors compared to sarcoma sectors. Within-tumor immune gene set analysis in a subset of tumors (n=15) revealed heterogeneous microenvironmental switch across patients, with 53% of tumors (n=8) shifting from a hot-to-cold microenvironment while most others (47%; n=7) remained immune-deprived. Gene expression profiles revealed the sustained activation of non-canonical NFκB pathway by cGAS-STING as a potentially leading cause of immune exhaustion and associated with EMT. Spatial RNAseq (Visium2) of 4 representative cases confirmed inflammation response as among most spatially variable features. Conclusion: This study suggests that chromosomal instability, acting through the cGAS-STING pathway, plays a dual role in driving immune exhaustion and promoting EMT as key biological features, despite notable inter-tumor variability in this process. These findings are consistent with existing literature on the non-canonical NFκB pathway. This work highlights potential therapeutic opportunities, including the emerging STING-targeted treatments and personalized immunotherapeutic strategies tailored to the unique immune landscape of each tumor. Citation Format: Amel Kime, Julie Berthet, Juliette Renard, Antoine Gaudet Chardonnet, Pierre Laurent-Puig, Jerome Alexandre, Bruno Borghese, Guillaume Beinse. Gynecologic carcinosarcomas beyond epithelial-mesenchymal transition: Morpho-transcriptomic evidence of an immune gradient in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6209.

Despite the widespread use of robot-assisted total laparoscopic hysterectomy (rTLH), there is still significant variability in how the procedure is performed, leading to inconsistencies in surgical outcomes and challenges in training. While existing curricula focus on technical skills, they lack formal models that capture procedural logic and variability. An expert-validated, standardized SPM is essential for improving reproducibility, enhancing surgical education, and enabling integration with artificial intelligence (AI)-driven systems. We sought to develop the first consensus-based surgical process model (SPM) for standard rTLH SPM (e.g., normal BMI, non-enlarged uterus) using a Delphi methodology involving international experts. A five-round Delphi study was conducted from November 2023 to October 2024 with 35 expert robotic gynecologic surgeons from 10 countries. Panelists iteratively reviewed, refined, and reached consensus on the phases, steps, and SPM paths of rTLH. Consensus was defined as ≥ 75

Epithelial ovarian cancer (EOC) is a leading cause of cancer mortality in women, often diagnosed at advanced stages. While first-line treatments improve survival, relapses remain common, with 5-year survival rates below 40

OBJECTIVE:Uterine and ovarian carcinosarcomas (OCSs) are rare and aggressive neoplasms. We assessed whether progression free survival after initial treatment (PFS1) was associated with the clinical benefit of chemotherapy after progression, estimated as overall survival (OS) after progression/relapse. METHODS:All consecutive patients treated with chemotherapy for stage I-IV uterine/OCS in Cochin University Hospital between 2010 and 2022 were included in this retrospective cohort. Association between PFS1 and OS after progressive disease (PD) was determined by Cox regression. Optimal PFS1 threshold for OS after PD prediction was determined by a time-dependent receiver operating characteristic-curve analysis. RESULTS:Forty patients treated for endometrial (n=32) or OCS (n=8) were included. Median PFS1 and OS after PD were 16 months 95% confidence interval (95% CI=11-not available [NA]) and 6 months (95% CI=2-15). In patients who relapsed/progressed (n=20), OS after PD was anticipated by PFS1 (Pearson r=0.61; area under the curve=0.79; 95% CI=0.6-1). At the threshold of PFS1 ≤/>9 months (n=6/n=7), median OS post PD were 2 months (0.1-NA) and 15 months (6-NA), for patients treated with platinum/anthracycline based chemotherapy in second line. Patients receiving best supportive care alone (n=7) had a median OS post PD of 8 months (1.3-NA). CONCLUSION:Our results highlight that a subgroup of carcinosarcomas patients exhibits a durable benefit from chemotherapy in the relapse settings, and suggest the use of PFS1, as a proxy of platinum-sensitivity, to select patients who might derive higher clinical benefit of a 2nd line of chemotherapy.

OBJECTIVE:We aimed to study whether the detection of circulating tumor DNA (ctDNA) may predict the risk of early relapse for patients with localized endometrial carcinoma. METHODS:Patients who underwent surgical resection at Cochin University Hospital (2021-2023) for International Federation of Gynecology and Obstetrics 2018 stage I to III endometrial carcinoma were prospectively included in a prospective biocollection cohort study. All patients had a plasma sample before surgery (EDTA collection tubes, 4-5 mL). After extraction and bisulfite-conversion of cell-free DNA, ctDNA was evaluated using a droplet-digital polymerase chain reaction assay targeting universally-hypermethylated positions in endometrial carcinoma (OXT, ZSCAN12 genes), and defined as significantly detected above the limit of detection. Patients were classified as high-risk based on 2022 European Society for Medical Oncology/European Society of Gynaecological Oncology/European Society of Pathology guidelines, or preoperative features (non-endometrioid histology, p53-abnormal tumors, or stage III). Events of interest were tumor progression or relapse (event-free survival). Adjusted-HR (aHR) was estimated using Cox regression. RESULTS:Among 128 patients included with median follow-up of 26 months (interquartile range; 15-35), ctDNA was detected in 18 patients (14%). Patients with ctDNA had a 1-year event-free rate of 67% (95% CI [48% to 92%]), vs 91% [82% to 100%] among patients without ctDNA. The ctDNA was detected in 10 (29%) patients among those with preoperative high-risk features (N = 34, 1-year event-free rate = 60% [36%-100%]). ctDNA was associated with event-free survival independently of stage (aHR = 4.26 [1.68-10.8]), 2022 guidelines high-risk (aHR = 3.72 [1.57-8.87]), or preoperative high-risk features (aHR = 3.98 [1.65-9.60]). CONCLUSIONS:Elevated ctDNA before surgery identifies a very high-risk subgroup of newly diagnosed endometrial carcinoma, suggestive of occult metastasis. Further studies are warranted to validate this finding and investigate the window of opportunity for neoadjuvant approaches.

Low-grade serous ovarian carcinoma is a rare subtype of epithelial ovarian cancer, accounting for less than 10% of serous malignancies. Compared to high-grade serous ovarian carcinoma, it follows an indolent course, often affects younger women, and demonstrates resistance to conventional cytotoxic chemotherapy. Low-grade serous ovarian is characterized by recurrent MAPK pathway alterations (KRAS, BRAF, NRAS) and frequent expression of functional hormone receptors, supporting the rationale for targeted and endocrine strategies. Optimal management relies on complete surgical cytoreduction. Endocrine therapy has shown promise, particularly in maintenance settings, and is being investigated in frontline strategies. MEK inhibitors, especially trametinib and avutometinib in combination with defactinib, have recently demonstrated improved outcomes in recurrent disease, while new combination strategies are under active evaluation to overcome resistance mechanisms. Immunotherapy remains of limited efficacy, though biomarker-driven combinations are explored. Ongoing biomarker-guided trials are expected to refine treatment paradigms.

The number of available hospital beds is decreasing in many countries. Reducing the length of hospital stay (LOS) and increasing bed turnover could improve patient flow. We evaluated whether robot-assisted surgery (RAS) had a beneficial impact on the LOS in a French hospital trust with a long-established robotic program (Assistance Publique–Hôpitaux de Paris, AP-HP). We extracted data from “Programme de Médicalisation des Systèmes d’Information” to determine the median LOS for adults in our trust after RAS versus laparoscopy and open surgery in 2021–2022 for eight target procedures, and compared data nationally and at similar academic centres (same database). We also calculated the number of hospitalisation days ‘saved’ using RAS. Overall, 9326 target procedures were performed at AP-HP: 3864 (41.4

Background: Radiation proctitis is a misunderstanding complication of chemoradiation in locally advanced cervical cancer. The objective of our study is to provide a detailed description and analysis of predictive factors associated with radiation proctitis in a retrospective cohort of patients treated by chemoradiation for locally advanced cervical cancer. Methods: All patients treated by exclusive chemoradiation or chemoradiation followed by brachytherapy for locally advanced cervical cancer from 2011 to 2017 were included in the study. A bivariate analysis was conducted to establish correlations between the occurrence of radiation proctitis and various clinical and technical variables. Results: A total of 128 patients were included in the study. The mean dose (SD) to the planning target volume was 47.1 Gy (6.2). Fifty-nine (46.1%) patients underwent brachytherapy. Sixteen patients (12.5%) developed radiation proctitis, grade 2 or higher in 12 patients (9.3%). In univariate analysis, anticoagulant or antiplatelet treatments (P=0.039), older age (P=0.049), rectal volume irradiated at 40 Gy (P=0.01) and 30 Gy (P=0.037) were significantly associated with the occurrence of a grade ≥2 radiation proctitis. The delivered dose to 2 cm3 of rectum (D2cm3) showed a potential association with the occurrence of radiation proctitis of all grades (P=0.064). Conclusion: This study highlights clinical and technical factors that should be considered in assessing the risk of radiation proctitis. These results contribute to a better understanding of this complication.

Adenoid cystic carcinoma of the Bartholin's gland (ACCBG) is a rare, slowly but aggressive malignancy. We reported the case of a 31-year-old woman who was treated by local excision and then hemi-vulvectomy, with positive margins and perineural invasion. Radiation therapy (RT) was then performed delivering 45Gy in 25 fractions in bilateral inguinal lymph nodes and 64.8Gy in 36 fractions on the vulvar area. After 30 months, there was no local relapse (LR) but the patient presented a histologically documented lung recurrence. Genomic profiling of the tumor showed a MYB-NFIB fusion transcript and a somatic mutation of PLCG1. A treatment by Lenvatinib was started. We conducted a literature review of 100 published cases. Patients were mainly treated by radical vulvectomy (30%), hemi-vulvectomy (17%), wide or local excision (21% and 24%, respectively) or other. Forty-four percent of patients received postoperative RT, more frequently in case of positive margin (71.9% versus 29.5%). RT may reduce the risk of LR regardless of margin status, with 15.4% vs. 41.9% of LR with or without RT, respectively, in patients with negative margins, and 13% vs. 33.3% of LR with or without RT, respectively, in patients with positive margins. The risk of relapse of any type was 40.9% in patients who received adjuvant RT vs. 48.2% in patients who did not. Median time to relapse was 24 months (range 6-156 months). The most frequent metastatic sites were lung (76.7%) and bone (26.7%). Optimal treatment for ACCBG is still not clearly defined but pooling the data from published case report help us better understand this rare disease and help in the therapeutic decision.

Clinical and histological characteristics of the patients included in our article.

Experimental protocol for establishment of inflammation-related mouse colon carcinogenesis along with representative IHC images of NRF2 expression in mice tumor.

Figure S1 shows the NTSR1 expression in A2780 cells and the carboplatin response in A2780 wild type and A2780-R1 cells.

Research question: Is there a change in magnetic resonance imaging (MRI) criteria of diffuse and focal phenotypes of adenomyosis before and after pregnancy? Design: A retrospective, monocentric, observational study in a single academic tertiary referral centre for endometriosis diagnosis and management. Women were followed for symptomatic adenomyosis, and without a prior history of surgery who give birth after 24+0 weeks. For each patient, pelvic MRI pre- and post-pregnancy was performed by two experienced radiologists with the same image acquisition protocol. Diffuse and focal adenomyosis MRI presentation were analysed before and after pregnancy. Results: Between January 2010 and September 2020, of the 139 patients analysed, 96 (69.1%) had adenomyosis at MRI distributed as follow: 22 (15.8%) presented diffuse adenomyosis, 55 (39.6%) focal adenomyosis and 19 (13.7%) both phenotypes. The frequency of isolated diffuse adenomyosis on MRI was significantly lower before versus after pregnancy (n = 22 [15.8%] versus n = 41 [29.5%], P = 0.01). The frequency of isolated focal adenomyosis was significantly higher before pregnancy than after pregnancy (n = 55 [39.6%] versus n = 34 [24.5%], P = 0.01). The mean volume of all focal adenomyosis lesions on MRI decreased significantly after pregnancy, from 6.7 2.5 mm(3) to 6.4 2.3 mm(3), P = 0.01. Conclusion: The current data indicate that, based on MRI, there is an increase in diffuse adenomyosis and a decrease in focal adenomyosis after pregnancy.

Supplementary figure showing that high concentrations of DMF display cytotoxicity in several cancer cell lines

•Recurrent endometrioma is linked to deep infiltrating endometriosis severity.•Patients with recurrent endometrioma exhibit more multiple deep infiltrating lesions.•Patients with recurrent endometrioma exhibit more digestive lesions.•Recurrent endometrioma tied to worsened pelvic pain.

Supplemental information about the method and materials used in our experiments.