Valeria Masciullo

Background/Objectives: Fertility-sparing treatment (FST) is an accepted option for selected women with atypical endometrial hyperplasia (AEH) and early-stage endometrioid endometrial cancer (EC). While combined progestin therapy and hysteroscopic approaches yield the best outcomes, the surgical component has long lacked standardization. This study aimed to evaluate oncological and reproductive outcomes following a standardized hysteroscopic fertility-sparing approach. Methods: This retrospective single-center study included women of reproductive age diagnosed with AEH or grade 1–2 endometrioid EC between 2021 and 2024 at the Digital Hysteroscopic Clinic CLASS Hysteroscopy, Fondazione Policlinico A. Gemelli IRCCS, Rome. All patients were treated using a standardized hysteroscopic approach based on lesion type and disease extension, combined with progestin therapy. Oncological outcomes included complete response (CR), time to CR and recurrence. Reproductive outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR). Multivariate analysis was performed to identify factors associated with CR and relapse. Results: A total of 138 patients were included (79 AEH, 59 EC). CR rates were high and comparable between AEH (94.9%) and EC (98.2%), with a median time to response of 6 months. Recurrence rates did not differ significantly between groups (16.7% AEH vs. 26.8% EC). CPR was similar (47.5% AEH vs. 54.8% EC), with LBR exceeding 50% among women who conceived. Multivariate analysis identified age ≥ 35 years as the only factor associated with reduced response and increased relapse risk. Conclusions: A standardized hysteroscopic fertility-sparing approach combined with progestin therapy provides excellent oncologic control and favorable reproductive outcomes. Lesion severity did not affect outcomes when hysteroscopic removal was adequately performed, while patient age remains a key determinant of outcomes.

Background and Objective: Adenomyosis is a benign gynaecological condition marked by the presence of endometrial tissue within the myometrium, frequently associated with dysmenorrhoea, menorrhagia, chronic pelvic pain, and infertility. While histological examination remains the diagnostic gold standard, its invasive nature underscores the importance of identifying accurate non-invasive alternatives. Timely and reliable preoperative diagnostics are essential to avoid unnecessary hysterectomies and to consider conservative treatments. Imaging modalities such as transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) have shown potential in diagnosing adenomyosis, assessing myometrial involvement, and monitoring patients under conservative management. This narrative review aims to evaluate the diagnostic accuracy and feasibility of TVUS and MRI as non-invasive diagnostic tools for adenomyosis. Methods: A literature search was conducted on PubMed for studies published between January 2014 and September 2024. Only clinical trials comparing imaging techniques—specifically TVUS and MRI—with histological diagnosis were included. All studies were in English to ensure consistency in terminology. The focus on English-language sources may have limited the inclusion of potentially relevant research in other languages, introducing a minor risk of language bias. Given the heterogeneity of the selected studies, a formal risk of bias assessment was not performed. Key Content and Findings: Twelve eligible studies were identified. TVUS demonstrated an average sensitivity of 78.5% and specificity of 70.7%, while MRI showed a sensitivity of 64.8% and specificity of 87.5%. Specific ultrasound markers such as junctional zone (JZ) thickness (JZmax ≥8 mm), fan-shaped striations, and the “question mark” sign were associated with high specificity. In contrast, myometrial heterogeneity showed high sensitivity. Conclusions: The findings confirm TVUS as a reliable first-line diagnostic tool, particularly where histology or MRI is not readily accessible. A standardized classification system would improve diagnostic consistency, especially as emerging studies suggest correlations between imaging features and symptom severity. Younger women often present with milder, focal disease, while older patients typically exhibit diffuse forms. The integration of advanced imaging technologies with biomarkers may further enhance diagnostic precision, reduce the reliance on invasive procedures, and support fertility-preserving, patient-centred therapeutic strategies.

Chronic endometritis (CE) is the persistent inflammation of the endometrial lining associated with infertility and various forms of reproductive failures. The diagnosis of CE is based on the histological evidence of stromal plasma cells; however, standardized methods to assess plasma cells are still lacking. In the present paper, we aimed to determine the most appropriate plasma cell threshold to diagnose CE based on pregnancy outcomes. Three electronic databases were searched from their inception to February 2022 for all studies comparing pregnancy outcomes between patients with CE and patients without CE. The relative risk (RR) of pregnancy, miscarriage, and/or live birth rates were calculated and pooled based on the plasma cell threshold adopted. A p-value < 0.05 was considered significant. Nine studies adopting different thresholds (1 to 50 plasma cells/10 HPF) were included. In the meta-analysis, we only found a significant association between miscarriage rate and a plasma cell count ≥ 5/10 HPF (RR = 2.4; p = 0.007). Among studies not suitable for meta-analysis, CE showed an association with worsened pregnancy only when high thresholds (10 and 50/10 HPF) were adopted. In conclusion, our study suggests that the presence of plasma cells at low levels (<5/10 HPF) may not predict worsened pregnancy outcomes. Based on these findings, a threshold of ≥5 plasma cells/10 HPF may be more appropriate to diagnose CE.

Primary mucinous cystadenocarcinoma (MCA) is a rare breast carcinoma subtype showing overlapping histopathological features with mucinous cystadenocarcinoma of the ovary and pancreas. Current literature data suggest a favorable prognosis of breast MCAs despite its immunoprofile usually revealing lack of expression of estrogen receptor, progesterone receptor and HER-2 and high Ki67. As far as we know, only 36 cases have been reported in the literature to date. Its ambiguous morpho-phenotypic profile makes histological diagnosis very challenging. It must be distinguished from typical mucin-producing breast carcinomas and, above all, metastases from the same histotype in other sites (ovary, pancreas, appendix). Herein, we report the case of a primary breast MCA occurring in a 41-year-old female with peculiar histological features.

Beta-catenin is involved in intercellular adhesion and participates in the Wnt signaling pathway. This study evaluated the expression pattern and prognostic value of β-catenin in a series of endometrial carcinoma patients. Immunohistochemical analyses were used to assess the expression and subcellular localization of β-catenin from tissue sections of 74 patients with endometrial carcinoma. No correlation was found between beta-catenin expression and clinicopathological parameters. Patients expressing nuclear β-catenin (n = 13; 16%) showed a more favorable prognosis than patients expressing membranous β-catenin; the 5-year disease-related survival rate was 100% for cases expressing nuclear β-catenin, compared with 73.8% (SE 0.08) of cases expressing membranous β-catenin (p = 0.04). Although statistical significance was not reached (p = 0.15), cases expressing nuclear β-catenin showed a 5-year disease-free survival rate of 90.9% (SE 0.08) compared with 67.4% (SE 0.08) of cases expressing membranous β-catenin. Univariate Cox analysis revealed that membranous β-catenin expression was found to be associated with a relative risk of death of 33.9 (p = 0.04). The stage of disease (p = 0.0006), histology (p = 0.003), and grading (p = 0.008) were also significantly correlated with disease-free survival according to univariate Cox analyses. Determining β-catenin expression and localization patterns may predict survival in patients with endometrial cancer and, therefore, should be considered a potential prognostic marker of disease.

Introduction: Lynch Syndrome (LS) represents the hereditary condition that is most frequently associated with endometrial cancer (EC). The aim of this study is to assess the presence of Lynch Syndrome (LS) in young women with mismatch repair (MMR)-deficient atypical endometrial hyperplasia (AEH) and non-myoinvasive FIGO G1 endometrioid EC and its possible impact on the outcome of conservative treatment.Methods: Six MMR-deficient cases identified from a previous cohort of 69 conservatively treated patients were selected to be screened for germline mutations in MMR genes. In each patient, the outcomes of conservative treatment for AEH and EEC, including response, relapse, progression, and pregnancy, were assessed.Results: Five out of 6 patients underwent genetic test for LS. Three out of these 5 patients showed a positive genetic test. Patient 1 showed the c.942 + 2 T>A heterozygous variant of MSH2 mutation; after 12 months of complete response, she had relapse and progression of disease. Patient 4 showed the c.2459-1G>C variant of MSH2 mutation; after complete response, she failed to achieve pregnancy; she had relapse after 24 months and underwent hysterectomy. Patient 6 showed the c.803 + 1 heterozygous variant of PMS2 mutation; she had relapse of disease after 18 months from the first complete response and then underwent hysterectomy.Conclusions: In this series, 3 out of 6 women with MMR-deficiency had LS. None of the patients achieved pregnancy, and those who responded to treatment had subsequent relapse of disease. Patients undergoing fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer should perform MMR immunohistochemical analysis in order to screen LS.

Despite the worldwide accomplishment of manual counting procedures of surgical textiles and instruments, cases of retained (forgotten) surgical items (RSIs) still occur. Gauzes are the most frequen...

Background: Pinopode expression has been suggested as a marker of endometrial receptivity. Methods: We set up an experimental study comparing endometrial tissue from recurrent pregnancy loss (RPL, n = 30) and fertile control (CTR, n = 20) women in terms of pinopode expression/morphology; expression of thrombomodulin (TM) and ezrin; cytoskeletal organization. Endometrial samples were collected during implantation window and evaluated by scanning electron microscopy, western blot, and immunofluorescence. Results: We found that RPL endometrial tissue showed: (i) increased pinopodes density (* p < 0.05); (ii) a reduced diameter of pinopodes (* p < 0.05); (iii) a decreased TM and ezrin expression (p < 0.05). Additionally, confocal images showed a significantly reduced expression of phosphorylated (p)-ezrin, confirming the results obtained through immunoblot analysis. Immunofluorescence staining showed that in CTR samples, junctions between cells are intact and clearly visible, whereas actin filaments appear completely lost in RPL endometrial samples; this suggests that, due to the impaired expression and activity of TM and ezrin, actin does not bind to plasma membrane in order to orchestrate the cytoskeletal actin filaments. Conclusions: Our findings suggest that an impaired expression of TM and expression/activation of ezrin may affect the connection between the TM and actin cytoskeleton, impairing the organization of cytoskeleton and, eventually, the adequate pinopode development.