Search Results (280)

Endometrial cancer is increasingly diagnosed in patients who have not yet completed childbearing. For carefully selected patients with grade 1 endometrioid endometrial carcinoma confined to the endometrium, fertility-sparing treatment (FST) can preserve reproductive potential but requires rigorous histologic surveillance. In eligible patients, oral progestins and/or the levonorgestrel-releasing intrauterine system (LNG-IUS) remain the mainstay of fertility-sparing treatment, with hysteroscopic lesion resection incorporated in selected cases. Obesity, polycystic ovary syndrome, abnormalities in glucose metabolism, molecular subtype, and primary or acquired progestin resistance collectively contribute to heterogeneity in treatment response and the risk of recurrence. This narrative review critically integrates current guidelines, randomized controlled trials, prospective studies, retrospective cohorts, and early exploratory evidence to evaluate the biological rationale, clinical positioning, efficacy, safety, and maturity of evidence for progestin-based therapy, metabolic interventions, combined endocrine approaches, molecularly guided strategies, and exploratory immunotherapeutic approaches. We further propose an integrated clinical pathway encompassing candidate selection, molecular assessment, response evaluation, transition to pregnancy, retreatment after recurrence, and timely conversion to definitive surgery. Importantly, this review distinguishes guideline-supported approaches from adjunctive, investigational, and exploratory strategies. Major evidence gaps include inconsistent definitions of treatment response, limited prospective molecularly stratified data, uncertain reproductive safety of emerging systemic therapies, and insufficient long-term data on pregnancy outcomes and offspring. Full article

Endometriosis is a chronic, oestrogen-responsive inflammatory disease characterised by endometrial-like tissue outside the uterine cavity. Because retrograde menstruation is common, lesion establishment probably requires cellular competence and a permissive ectopic microenvironment. This hypothesis-driven narrative review evaluates fascin (FSCN1) as a candidate cytoskeletal effector and considers antecedent eutopic priming versus induction after ectopic adhesion. Functional evidence was integrated with a targeted public-data screen. Donor-level reanalysis of GSE179640 found no conclusive overall eutopic case–control difference and predominantly non-epithelial expression. Exploratory analysis of GSE203191 suggested higher FSCN1 expression within a HSPA6+ stromal subcluster in diagnosed cases, without a comparable epithelial signal or detectable increase in subcluster abundance. This small post hoc analysis remains hypothesis-generating. FSCN1 was absent from the published HECA stromal/macrophage differential-expression lists and was not prioritised by the 2023 endometriosis GWAS. The current evidence therefore argues against uniform epithelial or whole-eutopic overexpression but permits a lineage-restricted stromal state. Fascin participates in autophagy- and miR-145-sensitive invasion networks, although these pathways are pleiotropic. Validation requires cycle- and lineage-resolved tissue mapping, compositional controls, matched lesions, and direct FSCN1 perturbation. Fascin should currently be regarded as a candidate multi-marker component and preclinical target, not a validated biomarker or systemic therapeutic target. Full article

Background: Endometriosis is a chronic estrogen-dependent disease characterized by the presence of endometrial-like tissue outside the uterine cavity. Its pathogenesis involves interactions between inflammatory, angiogenic, hormonal, oxidative stress-related, and cell survival-associated pathways, contributing to lesion development and persistence. Current treatment options are often limited by adverse effects, incomplete symptom control, and high recurrence rates. Methods: This integrative review summarizes the molecular mechanisms involved in endometriosis and the potential role of natural bioactive compounds in their modulation. A literature search was conducted using PubMed, Scopus, and Web of Science, and evidence from experimental, animal, and clinical studies was reviewed. Results: Natural compounds such as curcumin, resveratrol, quercetin, EGCG (epigallocatechin-3 gallate) and genistein have been reported to modulate multiple pathways involved in endometriosis. Their biological activity includes modulation of inflammatory signaling, angiogenesis, estrogen-dependent processes, epithelial–mesenchymal transition, oxidative stress, and apoptosis. While some compounds influence several interconnected pathways, others appear to exert more selective effects. Conclusions: The findings summarized in this review suggest that natural bioactive compounds may influence several interconnected mechanisms involved in endometriosis. Although clinical evidence remains limited, these compounds warrant further investigation as potential adjuncts to current therapeutic approaches. Full article

Background/Objectives: Primary renal endometriosis with extrapelvic locations of endometriosis lesions is deemed extremely rare. Therefore, the aim of this review was to assess the current literature on renal endometriosis, encompassing a summary of recorded living-patient cases, imaging and pathological features, chosen therapeutic approaches, and patient outcomes. Methods: We performed a narrative review with a systematic identification and presentation of published cases of histopathologically proven kidney endometriosis. A literature search was carried out across PubMed, Scopus, and Web of Science for relevant studies, i.e., case reports and series that met predefined inclusion and exclusion criteria specified by the modified PECOS framework. Results: A total of 19 publications reporting a total of 20 reported cases were included in the in-depth analysis. The noted condition affected women of reproductive age, with a mean age of 37.4, with the most common presenting symptoms being lumbar or flank pain, gross hematuria, abdominal pain, and tenderness. Most were single-mass lesions detected on the right kidney, with a mean largest diameter of 6.7 cm. Most were CT-characterized as either hyperattenuating lesions, septate lesions with foci of calcifications and soft tissue components, or areas of necrosis or cystic change. As CT presented features that would not allow the exclusion of malignant kidney tumors, most patients were treated surgically with nephrectomy. Diagnosis was confirmed by histopathology of recorded endometrial glands and stroma. Conclusions: The diagnosis of these lesions is exceptionally challenging because of their nonspecific symptoms, the rare association with the menstrual cycle, the rarity of dysmenorrhea, and the occasional coexistence of ovarian endometriosis, with no distinct endometriosis-specific clinical and imaging pattern emerging. Full article

Endometriosis is a chronic inflammatory disorder characterized by the ectopic growth of endometrial-like tissue, leading to pelvic pain and infertility. Although cepharanthine has well-established anti-inflammatory properties, its therapeutic potential and underlying mechanisms in endometriosis remain largely unexplored. In this study, the effects of cepharanthine were evaluated using a surgically induced mouse model and immortalized human endometrial stromal cell models. Cepharanthine treatment significantly reduced the calculated lesion volume, whereas wet lesion weight did not differ significantly between the groups. Cepharanthine was also accompanied by reduced spleen weight and alterations in the CD4+ helper T-cell population in vivo. In immortalized human ovarian endometriotic stromal cells (ihOESCs), cepharanthine significantly decreased cell viability, induced apoptosis, and disrupted cell-cycle progression. Cepharanthine altered autophagy-related signaling, accompanied by increased acidic vesicle-associated signals and accumulation of LC3B-II and p62/SQSTM1; however, the direction of autophagic flux remains unclear. These changes were associated with elevated reactive oxygen species production, intracellular Ca²⁺ redistribution, and mitochondrial dysfunction. Collectively, these findings indicate that cepharanthine reduces calculated lesion volume in vivo and alters mitochondrial function, autophagy-related signaling, apoptosis and cell-cycle progression in ihOESCs, supporting its potential as a therapeutic candidate. Full article

Endometriosis is a chronic, inflammatory, estrogen-dependent disease that affects approximately 6–10% of women of reproductive age. The present study aimed to investigate the expression of 48 immune-related genes in different types of biological samples from patients with histologically confirmed endometriosis compared to a control group. We analyzed (1) patients’ endometrial tissue, ectopic lesions, and menstrual and venous blood, as well as (2) the control group’s endometrial tissue and menstrual and venous blood. After RNA isolation, expression analysis of 48 immune-related genes was performed using NanoString nCounter^® Elements XT technology. All samples were normalized using nSolver Analysis Software, including control normalization and the use of a reference gene, as well as additional approaches for the detection of reliable differential expression. Expressions of the analyzed genes were similar in venous blood between patients and the controls; no significant dysregulation was found in menstrual blood. Most of the analyzed genes were upregulated in patients’ endometria. Three genes attracted our attention due to their overexpression in ectopic lesions. We were able to demonstrate the differential expression of three genes in ectopic lesions, suggesting their association with the development of endometriosis—THBS1, CHGB, and CYR61. The evidently higher expression of THBS1 in the ectopic lesions nominates this molecule as a potential therapeutic target in endometriosis as well. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disorder characterized by the functional engraftment of endometrial-like stroma and glands outside the uterine cavity, encompassing a heterogeneous phenotypic spectrum that ranges from deep infiltrating lesions to subtle, atypical or non-pigmented peritoneal implants. Emerging evidence suggests an association between endometriosis and cutaneous melanoma. The aim of this study was to evaluate whether women with endometriosis have an increased risk of developing melanoma and to explore potential biological mechanisms underlying this association. This review was conducted in accordance with PRISMA guidelines. A comprehensive search of PubMed/MEDLINE, Scopus, and the Cochrane Library was performed for studies published in English up to 1 February 2025. Eligible studies were restricted to cohort and casecontrol designs evaluating the association between histopathologically radiologically verified endometriosis comprising distinct phenotypes and subtle atypical lesions and histologically confirmed cutaneous melanoma. Two independent reviewers executed study selection based on these strict eligibility criteria, and due to marked clinical heterogeneity, data were synthesized qualitatively. A total of 326 records were identified, of which 17 studies met the inclusion criteria. Genetic and biomolecular evidence revealed shared susceptibility loci and common molecular pathways, including TP53, PTEN, CDKN2A, and estrogen receptor mediated signaling, suggesting a biological link between the two conditions. Epidemiological studies consistently reported a modestly increased risk of melanoma in women with endometriosis, with hazard ratios ranging from 1.50 to 1.82 (95% Confidence Interval [CI]: 1.21–2.41). This association appeared more pronounced in younger women and in those with a personal or family history of dysplastic nevi or melanoma. Limited data also suggest a reverse association, with increased occurrence of endometriosis among women with melanoma. Endometriosis and melanoma share distinct genetic architectures, characterized by shared susceptibility loci at the chromosome 9p21 region (encompassing CDKN2A/B), alongside convergent hyperestrogenemic signaling via estrogen receptor-beta (ERβ) and systemic natural killer (NK) cell immunotolerance axes. These shared molecular pathways support a biologically plausible correlation, although causal links remain unproven due to pervasive study heterogeneity and surveillance biases. Current evidence suggests a modest epidemiological link; however, heterogeneity among studies limits definitive conclusions. Full article

Transvaginal ultrasound (TVS) remains the most frequently performed examination in gynecological patients to evaluate the uterine cavity. Visualization of the endometrium may be limited due to certain uterine positions, particularly axial and retroverted orientations. Alternative diagnostic methods, such as transabdominal ultrasound (TAS) and transrectal ultrasound (TRS), may be useful in patients in whom visualization is suboptimal using the TVS. The aim of the study was to analyze the literature regarding the diagnostic performance of TVS, TAS, and TRS in detecting uterine cavity abnormalities in women with various uterine positions. Studies evaluating ultrasound assessment of uterine cavity pathologies with reference to uterine position were included in this review. The available research suggests that uterine position may influence ultrasound visualization. TAS has been shown to demonstrate lower diagnostic reliability in retroverted or axial uteri, particularly in patients with obesity or when focal lesions are present. TRS may provide improved assessment of endometrial thickness in patients with axial uteri compared with TVS. Uterine position may be a factor affecting the accuracy of evaluation of the uterine cavity in ultrasound. Awareness of these limitations and the use of additional imaging modalities may improve diagnostic accuracy in selected patients. Further studies are needed. Full article

Gynecological malignancies and breast cancer impose substantial health and economic burdens. This review examines how local and systemic microbiota may affect epithelial integrity, inflammation, estrogen metabolism, and immunity. The vaginal ecosystem is the most extensively studied female microbial niche. Cervical cancer serves as the most illustrative clinical example: loss of stable Lactobacillus crispatus dominance and increased prevalence of anaerobic bacteria (anaerobic dysbiosis) are associated with persistent HPV infection, which directly elevates the risk of cervical precancerous lesions. The estrobolome is particularly relevant in endometrial cancer, where intestinal bacterial beta-glucuronidase activity may increase estrogen reabsorption, particularly in obesity and metabolic disease. In ovarian cancer, microbiota is being studied as a possible risk modifier in BRCA1 carriers, but the evidence remains exploratory. In breast cancer, intratumoral bacteria may shape the immune microenvironment, particularly in triple-negative disease. The primary limitation of current research is methodological heterogeneity. Low-biomass samples, such as those from the ovary or endometrium, are highly susceptible to technical contamination. Most studies are cross-sectional and cannot establish causality. Current evidence supports microbiota as a modifier, not a standalone marker or a substitute for standard diagnosis and treatment. Its most plausible near-term role is in multiparameter risk or response models, pending standardized prospective validation. Full article

Objective. Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion associated with a substantial risk of concurrent endometrial carcinoma. This study aimed to evaluate whether preoperative endometrial thickness measured by transvaginal ultrasonography could predict concurrent endometrial carcinoma in patients diagnosed with EIN. Methods. This retrospective study included 102 patients diagnosed with EIN on endometrial sampling who subsequently underwent hysterectomy. Demographic and clinical data and preoperative endometrial thickness were collected, and final histopathology after hysterectomy was recorded. Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression were performed. Results. The median endometrial thickness was 13 mm (range 4–45), and most patients were postmenopausal (68.6%). Final pathology revealed endometrial carcinoma in 50 patients (49.0%) and persistent EIN in 52 (51.0%). Endometrial thickness significantly predicted concurrent carcinoma (AUC 0.679, 95% CI 0.575–0.784; p = 0.002), with an optimal cut-off of 14.5 mm (sensitivity 58.0%, specificity 75.0%). Carcinoma was found in 69.0% of patients with thickness ≥ 14.5 mm versus 35.0% below this value (p < 0.001). On multivariable analysis, endometrial thickness (OR 1.15 per mm; 95% CI 1.05–1.24; p = 0.001) and age (OR 1.11; 95% CI 1.02–1.19; p = 0.007) were independently associated with concurrent carcinoma. Conclusions. Preoperative endometrial thickness is independently associated with concurrent endometrial carcinoma in patients diagnosed with EIN. A thickness of 14.5 mm or greater may indicate a higher risk of malignancy; however, given its moderate diagnostic accuracy, it should complement rather than replace a comprehensive preoperative assessment. Full article

Background/Objectives: Endometriosis manifests as ectopic endometrial tissue outside the uterine cavity. This lesion can sometimes appear at unusual anatomical sites or within the intestinal tract, growing and mimicking cancer. Such tumor-like endometriosis lesions are relatively uncommon and biologically intriguing. Methods: This study is a retrospective case series of 14 patients presenting with tumor-like endometriosis at a single institution between 2007 and 2023. Laser capture microdissection was used to isolate epithelial cells from endometriotic glands in tissue sections from formalin-fixed, paraffin-embedded blocks, and the microdissected epithelium was analyzed for cancer driver mutations. Results: Unlike conventional endometriosis, these tumor-like lesions were generally sizable and clinically presented in the groin area, aortic wall, omentum, bowel wall, or lymph nodes, all of which raised suspicion for malignancy, despite 11 (78.6%) of the 14 cases having a history of or clinical signs of endometriosis. A total of 11 cancer-driver mutations were identified in 6 of the 14 patients, with four patients harboring multiple mutations. Recurrent mutations included KRAS-activating mutations in four cases and ARID1A-inactivating mutations in two cases. Additional mutations involved PIK3CA, CTNNB1, CHD4, MYD88, and STAG2. Conclusions: This study detected mutations in KRAS, ARID1A, PIK3CA, CTNNB1, and MYD88 in endometriotic lesions, consistent with previous literature, and identified newly reported mutations in CHD4 and STAG2. Not every tumor-like lesion harbored cancer driver mutations. Full article

Background and Clinical Significance: The primary occurrence of low-grade endometrial stromal sarcoma (LG-ESS) at extrauterine sites, termed extrauterine ESS (EESS), is exceedingly rare. Case Presentation: A 49-year-old female, gravida 2 para 2 (all deliveries by cesarean section), presented with a 1-month history of epigastric and left upper quadrant abdominal pain. Abdominal computed tomography revealed a lobulated mass, measuring 4.6 cm, in the left upper quadrant with focal attachment to the splenic flexure of the colon. She underwent a laparoscopic partial gastrectomy and colectomy at a referral institution. Surgical pathology identified a 6.0 × 5.0 × 4.0 cm lobulated tumor involving the stomach with colonic invasion, diagnosed as LG-ESS (pT3N0). Immunohistochemistry showed a CD10-reactive lesion. The patient was referred to our institution for definitive gynecological surgery. After prophylactic ureteral double-J catheter insertion, she underwent laparoendoscopic single-site (LESS) total hysterectomy with bilateral salpingo-oophorectomy. The final histopathological examination of the hysterectomy specimen revealed intramural leiomyomas and benign ovarian cysts, with no evidence of ESS within the uterine corpus or adnexa. These findings confirmed a true primary EESS of nonuterine origin, consistent with AJCC stage 3 disease. The patient recovered uneventfully and was discharged during outpatient follow-up. Conclusions: This case represents one of the very few reported instances of primary LG-EESS involving the stomach and colon, simultaneously managed with a staged multidisciplinary surgical approach, including gastrointestinal resection followed by LESS hysterectomy and bilateral salpingo-oophorectomy. Full article

Background and Clinical Significance: Abdominal wall endometriosis (AWE) is an ectopic endometrial tissue embedded into the anterior abdominal wall, mainly infiltrating the rectus abdominis or oblique muscles and subcutaneous tissue. In most cases, AWE is associated with surgical scars after obstetrical and gynecological, as well as non-gynecological surgeries. Case Presentation: A 51-year-old female patient presented to the ultrasound outpatient clinic with a non-cyclic painful, palpable nodular mass located in the postoperative scar in the right lower abdominal quadrant. She underwent an appendectomy at the age of 9 (premenarchal period). The patient had regular menstrual cycles, one cesarean section and two vaginal deliveries, denied any trauma to that abdominal region, and had no history of pelvic endometriosis. Her past medical history was also remarkable for left-sided breast cancer, and she was worried it could be metastasis. Following imaging evaluation, a preliminary diagnosis was a benign lesion in the post-appendectomy scar, most likely a suture granuloma, also known as Schloffer’s tumor. Fine-needle aspiration was performed, and findings were primarily suspicious for AWE. The patient was then referred to an abdominal surgeon for excision of the affected area, and subsequent histopathological analysis confirmed that the mass was AWE. Conclusions: Imaging findings of a mass in the abdominal wall are not pathognomonic for AWE; only histopathological examination can confirm the diagnosis. If a painful nodular mass is located adjacent to a surgical scar in a female patient, AWE should be a leading consideration in the differential diagnosis, along with suture granuloma in cases of old surgical scars. Full article

Endometriosis is a disease associated with pain symptoms and reduced fertility, characterized by the presence of endometrial tissue outside the uterus. SETD3 is an actin-specific histidine N-methyltransferase that regulates actin stability and flexibility. Here, we investigate the effects of altered SETD3 expression on cytoskeletal function and endometriotic cell motility. SETD3 expression in endometriotic lesions was analyzed using EndometDB, and in uteri of the superfertile Dummerstorf mouse line FL1 by RT-qPCR. The functional impact of siRNA-mediated SETD3 depletion on endometriotic 12Z cells and primary endometriotic stroma cells was studied in vitro. Cell motility, contractility, invasiveness, morphology and gene expression were analyzed by RT-qPCR, Western blotting, immunofluorescence, scratch wound, collagen contraction and Matrigel invasion assays. In patient tissue, SETD3 expression was slightly increased in deep endometriotic lesions, whereas SETD3 was downregulated 1.6-fold in the uteri of superfertile mice. SETD3 depletion delayed cell motility, reduced invasiveness of 12Z cells, and reduced the capability to contract collagen gels. Cytoskeletal gene expression was moderately changed. Our data suggest that the histidine N-methyltransferase SETD3 contributes to cytoskeletal remodeling that plays a key role in cell migration and invasion. A dysregulation of SETD3 could therefore be related to the pathogenesis of endometriosis, particularly in deep endometriosis. Full article

Endometriosis is a long-term gynecological condition marked by the growth of endometrial-like tissue outside the uterus, which undergoes proliferation, bleeding, and regeneration. This disease is associated with disrupted steroid hormone signaling, notably progesterone (P4) resistance and estradiol (E2) dominance. P4 resistance has been associated with impaired activation of the progesterone receptor (PR) and reduced transcription of P4 target genes, while elevated E2 levels induce estrogen receptor (ER)-mediated signaling, enhancing estrogen-dependent lesion growth. This hormonal imbalance contributes to a pro-inflammatory microenvironment, chronic pelvic pain, infertility, and enhanced neuroangiogenesis. Emerging evidence indicates that the coordinated regulation of neurotrophins and sex hormones promotes nerve fibers and blood vessel growth and invasion within endometriotic lesions. P4 and E2 have been shown to modulate the expression of key neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). This review presents current evidence on the interplay between neurotrophins and ovarian steroids in endometriosis, with a specific focus on their contribution to neuroangiogenesis and pain pathophysiology. The review includes articles in English containing the Medical Subject Headings (MeSH) terms: “endometriosis”, “neurotrophins”, “nerve growth factor”, “brain-derived neurotrophic factor”, “neuroangiogenesis”, “progesterone”, and “estradiol”, found in the PubMed database published between 2000 and 24 May 2026. This review included a range of original research articles, systematic reviews, meta-analyses, prospective observational studies, case–control studies, and review papers, for a total of 122 articles. Full article