Endometriosis, affecting 10% of women, is defined as implantation, survival, and growth of endometrium-like/endometriotic tissue outside the uterine cavity, causing inflammation, infertility, pain, and susceptibility to ovarian cancer. Despite extensive studies, its etiology and pathogenesis are poorly understood and largely unknown. The prevailing view is that the immune system of endometriosis patients fails to clear ectopically disseminated endometrium from retrograde menstruation. Exosomes are small extracellular vesicles that exhibit immunomodulatory properties. We studied the role of endometriotic tissue–secreted exosomes in the pathophysiology of endometriosis. Two exosome-mediated mechanisms known to impair the immune response were investigated: 1) downregulation of NKG2D-mediated cytotoxicity and 2) FasL- and TRAIL-induced apoptosis of activated immune cells. We showed that secreted endometriotic exosomes isolated from supernatants of short-term explant cultures carry the NKG2D ligands MICA/B and ULBP1-3 and the proapoptotic molecules FasL and TRAIL on their surface, i.e., signature molecules of exosome-mediated immune suppression. Acting as decoys, these exosomes downregulate the NKG2D receptor, impair NKG2D-mediated cytotoxicity, and induce apoptosis of activated PBMCs and Jurkat cells through the FasL- and TRAIL pathway. The secreted endometriotic exosomes create an immunosuppressive gradient at the ectopic site, forming a “protective shield” around the endometriotic lesions. This gradient guards the endometriotic lesions against clearance by a cytotoxic attack and creates immunologic privilege by induction of apoptosis in activated immune cells. Taken together, our results provide a plausible, exosome-based mechanistic explanation for the immune dysfunction and the compromised immune surveillance in endometriosis and contribute novel insights into the pathogenesis of this enigmatic disease.

Introduction: The primary aim was to determine the occurrence of lymph ascites 4–6 weeks after surgery for endometrial cancer. Secondary aims were to assess risk factors for lymph ascites and the association with lymphedema of the legs.Material and Methods: This was a post hoc analysis of an observational prospective multicenter study, performed in 14 Swedish hospitals that included 235 women undergoing surgery for early‐stage endometrial cancer between June 2014 and January 2018; 116 underwent surgery including pelvic and para‐aortic lymphadenectomy and 119 had surgery without lymphadenectomy. Lymph ascites (free intraabdominal fluid or encapsulated pelvic or para‐aortic fluid) was assessed by vaginal ultrasound 4–6 weeks postoperatively. Lymphedema was assessed using circumferential measurements of the legs preoperatively and 1 year postoperatively, enabling estimation of leg volume. A BMI‐standardized leg volume increase ≥10% was classified as lymphedema. Evaluation of risk factors was performed using multiple logistic regression.Results: Lymph ascites 4‐6‐weeks postoperatively occurred in 28.5% (67/235) of the women. The estimated volume of the lymph ascites in these women was mean 28 mL (standard deviation 48 mL) and median 14 mL (interquartile range 2–36 mL). Lymphadenectomy was a risk factor for lymph ascites (aOR 9.97; 95% CI 4.53–21.97) whereas the use of minimally invasive surgery (aOR 0.50; 95% CI 0.25–0.99) reduced the risk. Twenty‐two of 231 women (9.5%) developed lymphedema of the legs 1 year after surgery. The presence of lymph ascites was predictive of lymphedema (aOR 3.90; 95% CI 1.52–9.96).Conclusions: Lymph ascites was common 4–6 weeks after surgery but in a low and clinically insignificant volume. Lymphadenectomy was a strong risk factor for lymph ascites and the use of minimally invasive surgery seemed to reduce the risk. Detection of lymph ascites at early postoperative follow‐up may be a means of selecting patients at high risk of developing lymphedema after treatment with endometrial cancer for preventive measures against lymphedema progression.

Introduction: Endometriosis is a chronic, estrogen-dependent inflammatory disorder affecting approximately 10% of women of reproductive age. Retrograde menstruation is widely accepted as a primary mechanism for ectopic endometrial seeding; however, only a subset of individuals develop the disease. This suggests additional pathogenic processes. Increasing evidence suggests impaired immune surveillance as a central factor enabling ectopic endometrial tissue to persist and expand. This review aims to explore immune-associated pathogenic mechanisms in endometriosis, focusing on the interplay between natural killer (NK) cells, cytokines, and extracellular vesicles (EVs). Methods: This study was conducted as a narrative review. Relevant PubMed studies addressing immune dysfunction in endometriosis were identified, with emphasis on the role of NK cells, cytokines, EVs, and EV-mediated signaling. All material chosen for referral in the review consists of published reports that were critically evaluated and discussed. Results: Endometriosis is associated with impaired immune surveillance, characterized by reduced NK-cell cytotoxicity, driven by altered receptor expression and a shift toward regulatory NK-cell subsets. A dysregulated cytokine milieu combines pro-inflammatory signals that promote lesion growth with immunosuppressive factors that inhibit immune clearance of ectopic tissue. Lesion-derived EVs further contribute the lesions’ survival by suppressing cytotoxic immune function, inducing apoptosis of activated immune cells and promoting inflammation and angiogenesis. The referred results highlight key immunological mechanisms underlying endometriosis. Discussion: This review presents an immune-based model in which NK-cell dysfunction, cytokine imbalance, and EV-mediated signaling cooperate to establish an immune-privileged microenvironment that promotes the survival and growth of ectopic endometrial tissue. The immune escape mechanism, described here, highlights potential targets as candidates to be tested for immunomodulatory therapies. We conclude that endometriosis should be considered a disorder fundamentally linked to mechanisms of immune dysregulation.

Problem: NK‐cell dysfunction in endometriosis is suggested to contribute to the survival of ectopic endometrial tissue. However, the underlying causes of this impairment remain unclear. NK cells are divided into: CD56 ^+bright , which produce high amounts of cytokines but have low or no cytotoxic ability, and CD56 ^+dim , which are mainly cytotoxic. CD56 ^+bright NK cells, constitutively present in human endometrium (eNK cells), represent only 0–2% of NK cells in PBMC, where CD56 ^+dim cells dominate. Method of Study: NK‐cell subpopulations and NKG2D receptor expression in PBMC were analyzed by flow cytometry in two cohorts of untreated and treated endometriosis patients and healthy age‐matched controls. Results: Elevated numbers of CD56 ^+bright cells were observed in 8 of 21 untreated endometriosis patients compared to controls. These numbers were normalized following surgery and hormonal treatment. The NKG2D receptor expression was reduced in untreated patients compared to controls and treated patients. Conclusions: The significantly increased proportion of peripheral CD56 ^+bright  NK/eNK cells may result from migration of these cells from ectopic endometrial tissue. The downregulation of NKG2D receptor expression in PBMCs may be mediated by immunosuppressive endometriotic exosomes, as previously reported by us. Taken together, our results suggest that: (1) the impaired NK cell cytotoxicity in untreated endometriosis patients may be due both to an influx of CD56 ^+bright /eNK cells and exosome‐induced NKG2D receptor downregulation; and (2) elevated numbers of peripheral CD56 ^+bright NK cells could be considered as a potential diagnostic marker for endometriosis.

Objectives: This study aimed to investigate the diagnostic performance of imaging-based biomarkers from computed tomography (CT) and magnetic resonance imaging (MRI) for prediction of malignant and borderline malignant ovarian tumours. Methods: 195 consecutive patients with suspected primary epithelial ovarian cancer were included from the retrospective “Prognostic and Diagnostic Added Value of Medical Imaging in Staging and Treatment Planning of Gynaecological Cancer” (PRODIGYN) study. The radiological stage, according to the International Federation of Gynaecology and Obstetrics system (rFIGO), magnetic resonance imaging (MRI)-based Ovarian-Adnexal Reporting and Data System (O-RADS-MRI) score, and the mean apparent diffusion coefficient (ADC_mean) were investigated for prediction of ovarian malignancy, with histopathology as reference. The same imaging biomarkers were applied to the borderline tumour cohort (n = 33) to predict malignant/adverse features, such as micro-invasion. Results: The rFIGO stage demonstrated high accuracy for ovarian malignancy, with an area under the curve (AUC) of 0.98 (95% confidence interval (CI) = 0.97–0.99). On lesion level, the sensitivity and specificity of the O-RADS-MRI score to predict ovarian malignancy, after adjusting for correlated data structure, was 1 (CI: 0.96–1) and 0.82 (CI: 0.70–0.90), respectively. The performance of ADC_mean to predict ovarian malignancy on lesion level was moderately high, with AUC = 0.78 (95% CI 0.68, 0.88). Discrimination of adverse features in borderline tumours was not improved. Conclusions: rFIGO and O-RADS-MRI showed excellent performance and outperformed ADC_mean as predictive tools for ovarian malignancy but could not predict adverse features in borderline tumours.

Psammocarcinoma (PsC) represents a rare form of low-grade serous tumor of the ovary or peritoneum. Although ovarian cancer generally has a poor prognosis in its late stages, PsC seems to have a more indolent course. We present a patient with a history of unspecific abdominal pain for more than a year, with sudden acute onset of severe inguinal pain. On admission to the hospital, a computed tomography (CT) revealed a pelvic mass of suspected ovarian origin. Radical surgery was attempted but not achieved due to widespread tumor growth. Histopathological evaluation revealed estrogen receptor-positive stage III PsC. Tamoxifen treatment was thus initiated, still maintaining stable disease 10 years later. The patient has undergone extensive radiological work-up, including CT, chest X-ray, 18F-fluoro-deoxy-glucose positron emission tomography (PET)/CT, 99mTc- hydroxymethylene diphosphonate (HDP) bone scintigraphy, 18F-fluoro-thymidine (FLT) PET/CT, Tc-99m depreotide scintigraphy and magnetic resonance imaging. In conclusion, we demonstrate that PsC has characteristic radiological features and different imaging modalities can be suitable in different clinical situations. In contrast to most other ovarian cancers, PsC does not always warrant adjuvant chemotherapy, even in advanced stages. This emphasizes the need for a deeper knowledge of the biological behavior of this rare tumor, to select the optimal treatment strategy.