Surgical nodal assessment for endometrial hyperplasia - A meta-analysis and systematic review.

OBJECTIVE: Endometrial intraepithelial neoplasia (EIN) and atypical hyperplasia (AH) are recognized precursors for endometrial cancer (EC). Most current guidelines do not recommend the routine surgical evaluation of lymph nodes (LN), although recent studies indicate increased use of sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of EIN/AH. We aimed to evaluate the rates of positive LN and its effect on the incidence of upstaging of EIN/AH patients, complications, and adjuvant treatment administration. METHODS: A systematic review and meta-analysis was conducted in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science, Clinicaltrials.gov and Cochrane Library. Included were studies investigating lymph node evaluation in patients diagnosed with EIN/AH, presenting results of LN assessment and/or comparisons of hysterectomy results with and without lymph node assessment. This analysis was registered at PROSPERO International prospective register of systematic reviews (CRD42023443598). RESULTS: A total of 447 studies were initially identified through database searching. The current analysis includes 7 studies comprising 1791 atypical endometrial hyperplasia patients who underwent hysterectomy with lymph node assessment. The incidence of positive lymph nodes among those who had undergone any LN evaluation was found to be 1.1% (95% CI 0.3%-2%). The rate of positive LNs was 1.4% (95% CI 0.2%-1.9%) among those who had undergone specifically SLN. 319 (44.3%, 95% CI 34%-54.7%) patients of the patients initially diagnosed with EIN/AH (n = 699), were finally upgraded to EC diagnosis. Fifteen percent of the final EC diagnosed patients were treated with adjuvant treatment. No significant difference regarding complication rates was noticed. CONCLUSIONS: Our review indicates that the rate of metastatic LNs is <2% in patients undergoing surgical nodal evaluation for EIN/AH. However, the rate of complication for SLN mapping is low and may have an impact on postoperative therapy decisions in those diagnosed with malignancy.

Racial disparities in the treatment of endometrial intraepithelial neoplasia in postmenopausal women.

Disparities in endometrial cancer has increased during the past decade with Black women more likely to be diagnosed at a later stage and have higher mortality. The majority of research has been focused on cultural barriers, socioeconomic status, lack of access to care, comorbidities, and tumor histology to explain these disparities. Limited studies have been conducted on the disparity in the treatment of endometrial intraepithelial neoplasia(EIN). We sought to analyze the differences in treatment used in the management of postmenopausal women with EIN to evaluate whether race/ethnicity is a contributing factor. An IRB approved retrospective study was conducted amongst women at a single institution diagnosed with EIN. Ethnicity/race was defined as non-Hispanic White, non-Hispanic Black, Hispanic, and Asian. Demographic and clinical data was extracted. Multivariable logistic regression was used to examine the association between ethnicity/race and treatment, adjusted for age, BMI, and underlying medical conditions such as cardiovascular disease and diabetes. In total, 254 patients were analyzed. A significant association between ethnicity/race and treatment with non-Hispanic Black women less likely to be treated with surgical management compared to non-Hispanic White women (OR = 0.326, 95 %CI 0.129-0.827, p = 0.026). Importantly, after adjusting for clinical risk factors(age, BMI, CVD, diabetes), non-Hispanic Black women remained at an increased risk of not undergoing surgical intervention (OR = 0.333, 95 % CI 0.125-0.882, p = 0.027). Future research is imperative to evaluate the root cause of this disparity in the healthcare system.

Treatment outcomes according to various progestin treatment strategies in patients with atypical hyperplasia/endometrial intraepithelial neoplasia - Multicenter retrospective study (KGOG2033).

OBJECTIVE: To investigate pathologic complete response (pCR) and recurrence outcomes using various progestin treatment strategies in patients with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN). METHODS: Medical records of patients diagnosed with AH/EIN and undergoing follow-up endometrial biopsy after progestin treatment between 2011 and 2020 were retrospectively reviewed. Clinical factors and treatment outcomes were analyzed according to initial progestin treatment (oral progestin [OP], levonorgestrel-releasing intrauterine device [LNG-IUD], and combination), OP dose, and maintenance treatment using Pearson's χ2, Fisher's exact test, and Kaplan-Meier analysis. RESULTS: Of 124 patients included, 74, 37, and 13 were in the OP, LNG-IUD, and combination groups, respectively. The pCR rate was 79.8% and recurrence rate was 21.2%. The pCR rates within 3 and 6 months were significantly higher in the OP group than in the LNG-IUD group, but were not significantly different within 12 and 24 months. Recurrence rate was significantly higher in the OP group than in the LNG-IUD group. The pCR rate and recurrence rate had no significant differences between the combination group and the other groups. Excluding the LNG-IUD group, 53 and 34 patients received low- and high-dose OP, respectively. The pCR and recurrence rates were comparable between the low- and high-dose OP groups. Maintenance therapy was significantly associated with lower recurrence rate. CONCLUSIONS: Although OP alone achieved more short-term pCR than the other groups, more recurrences occurred after pCR than LNG-IUD alone. High-dose OP as well as combination of OP and LNG-IUD did not increase pCR or reduce recurrence. Maintenance therapy may reduce the recurrence rate after pCR.

Role of sentinel lymph node evaluation during hysterectomy for preoperative pathology diagnosis of endometrial intraepithelial neoplasia in a community hospital setting.

OBJECTIVE: To determine the utility of sentinel lymph node (SLN) evaluation during hysterectomy for endometrial intraepithelial neoplasia (EIN) in a community hospital setting and identify descriptive trends among pathology reports from those diagnosed with endometrial cancer (EC). METHODS: We reviewed patients who underwent hysterectomy from January 2015 to July 2022 for a pathologically confirmed diagnosis of EIN obtained by endometrial biopsy (EMB) or dilation and curettage. Data was obtained via detailed chart review. Statistical testing was utilized for between-group comparisons and multivariate logistic regression modeling. RESULTS: Of the 177 patients with EIN who underwent hysterectomy during the study period, 105 (59.3%) had a final diagnosis of EC. At least stage IB disease was found in 29 of these patients who then underwent adjuvant therapy. Pathology report descriptors suspicious for cancer and initial specimen type obtained by EMB were independently and significantly associated with increased odds of EC diagnosis (aOR 8.192, p < 0.001;3.746, p < 0.001, respectively). Operative times were not increased by performance of SLN sampling while frozen specimen evaluation added an average of 28 min to procedure length. Short-term surgical outcomes were also similar between groups. CONCLUSION: Patients treated for EIN at community-based institutions might be more likely to upstage preoperative EIN diagnoses and have an increased risk of later stage disease than previous research suggests. Given no surgical time or short-term outcome differences, SLN evaluation should be more strongly considered in this practice setting, especially for patients diagnosed by EMB or with pathology reports indicating suspicion for EC.

Machine learning for prediction of concurrent endometrial carcinoma in patients diagnosed with endometrial intraepithelial neoplasia.

OBJECTIVE: To identify predictive clinico-pathologic factors for concurrent endometrial carcinoma (EC) among patients with endometrial intraepithelial neoplasia (EIN) using machine learning. METHODS: a retrospective analysis of 160 patients with a biopsy proven EIN. We analyzed the performance of multiple machine learning models (n = 48) with different parameters to predict the diagnosis of postoperative EC. The prediction variables included: parity, gestations, sampling method, endometrial thickness, age, body mass index, diabetes, hypertension, serum CA-125, preoperative histology and preoperative hormonal therapy. Python 'sklearn' library was used to train and test the models. The model performance was evaluated by sensitivity, specificity, PPV, NPV and AUC. Five iterations of internal cross-validation were performed, and the mean values were used to compare between the models. RESULTS: Of the 160 women with a preoperative diagnosis of EIN, 37.5% (60) had a post-op diagnosis of EC. In univariable analysis, there were no significant predictors of EIN. For the five best machine learning models, all the models had a high specificity (71%-88%) and a low sensitivity (23%-51%). Logistic regression model had the highest specificity 88%, XG Boost had the highest sensitivity 51%, and the highest positive predictive value 62% and negative predictive value 73%. The highest area under the curve was achieved by the random forest model 0.646. CONCLUSIONS: Even using the most elaborate AI algorithms, it is not possible currently to predict concurrent EC in women with a preoperative diagnosis of EIN. As women with EIN have a high risk of concurrent EC, there may be a value of surgical staging including sentinel lymph node evaluation, to more precisely direct adjuvant treatment in the event EC is identified on final pathology.

Fertility After Endometrial Intraepithelial Neoplasia and Early Endometrial Cancer: Ovulation Induction May Shorten Time to Conception.

The purpose of this study was to determine whether utilization of assisted reproductive technology following clearance of endometrial intraepithelial neoplasia (EIN) or early endometrial cancer (EC) shortens time to conception (TTC) and reduces recurrence. Patients aged 18 to 45 with EIN or early EC who achieved pathologic response following progesterone treatment were identified via retrospective chart review. Study groups included patients who pursued ovulation induction (OI), in vitro fertilization (IVF), and spontaneous pregnancy. Primary outcomes were TTC and recurrence rate. Three hundred forty-six charts were reviewed, with 86 patients meeting inclusion criteria and 53 attempting pregnancy. Of those 53 patients, 11 became pregnant and seven had a live birth. Median times to pregnancy were 183 days for IVF, 54 days for OI, and 347 days for spontaneous conception (p < 0.05). No differences were seen in recurrence or progression based on attempted pregnancy method, nor with duration of fertility treatment. Forty-two of 86 patients (49%) were lost to follow-up. For patients with a history of treated EIN or EC, OI may decrease TTC. Larger prospective studies are needed to definitively answer this question. Although no differences in recurrence or progression were identified, the significant loss to follow-up rate in this study is concerning and warrants further investigation.

Glandular Crowdings in Endometrial Polyps: Clinical Follow-Up and Possible Worrisome Features.

INTRODUCTION: Interpretation of changes and premalignant lesions in endometrial polyps can be challenging. We evaluated the clinical course of patients with focal gland crowdings in endometrial polyps via repeat biopsies and searched for possible morphological findings in the initial biopsy that may foresee a premalignant course. METHODS: Specimens diagnosed as endometrial polyp and focal gland crowding in patients who had a repeat biopsy in a 1-year period were reexamined. Morphological findings in the initial biopsies were recorded. The group whose repeat biopsies were "premalignant or malignant" (Group 1), and the group with "benign" repeat biopsies (Group 2) were compared. RESULTS: "Endometrial polyp and gland crowdings" was diagnosed in 115 specimens of which 38 patients had repeat biopsies. Among these 8 (21%) were diagnosed as "endometrial intraepithelial neoplasia (EIN)" (Group 1) and 30 (79%) as "benign" (Group 2). Morphological features in the initial biopsies were evaluated; PAX2 loss was 6 of 8 (75%) for Group 1 and 7 of 30 (23%) for Group 2 (P = .020), and altered epithelial cytological features were present in 5 of 8 (62%) versus 4 of 30 (13%) (P = .015), both significantly higher in Group 1. Dark intraluminal secretion, intraluminal histiocytes, intraglandular epithelial proliferation, and mean diameter of crowded gland areas were not statistically different between the 2 groups. CONCLUSION: "Focal gland crowdings" in endometrial polyps do carry a risk of EIN in subsequent biopsies. We suggest that the loss/decrease of PAX2 and altered epithelial cytological features in these areas in the initial biopsy are indicative of a premalignant course.

Recent advances in the management of postmenopausal women with non-atypical endometrial hyperplasia.

Non-atypical endometrial hyperplasia is a benign disease without significant somatic genetic changes. Postmenopausal women with non-atypical endometrial hyperplasia have a significant risk of progression to endometrial cancer and persistent endometrial hyperplasia. Most cases of atypical endometrial hyperplasia in postmenopausal women are treated surgically, including hysterectomy. At present, the treatment of postmenopausal women with non-atypical endometrial hyperplasia is still controversial. Correct and timely diagnosis and treatment are of great significance to prevent progression of the lesion. This study mainly provides an updated synthesis of the literature that investigates the etiology, diagnosis and treatment of postmenopausal women with non-atypical endometrial hyperplasia. As of December 2022, a literature search related to postmenopausal non-atypical endometrial hyperplasia was conducted on the PubMed database. For most postmenopausal patients with non-atypical endometrial hyperplasia, regular re-examination should be performed during conservative treatment. For postmenopausal patients with endometrial cancer risk factors, persistent non-atypical endometrial hyperplasia or progesterone contraindications, hysterectomy and bilateral salpingo-oophorectomy should be the first choice.

Association of body mass index with early age at diagnosis of endometrial intraepithelial neoplasia.

OBJECTIVE: Elevated body mass index (BMI) is a risk factor for endometrioid endometrial cancer and its precursor, endometrial intraepithelial neoplasia (EIN). Our objective was to describe the association between BMI and age at EIN diagnosis. METHODS: We conducted a retrospective study of patients diagnosed with EIN from 2010 to 2020 at a large academic medical center. Patient characteristics were stratified by menopausal status and compared using a chi-square or t-test. We used linear regression to determine the parameter estimate (ß) and 95% confidence interval for the association between BMI and age at diagnosis. RESULTS: We identified 513 patients with EIN; 503 (98%) had complete medical records. Premenopausal patients were more likely to be nulliparous and to have polycystic ovary syndrome than postmenopausal patients (both p ≤ 0.001). Postmenopausal patients were more likely to have hypertension, type 2 diabetes, and hyperlipidemia (all p ≤ 0.02). There was a significant linear association between BMI and age at diagnosis in premenopausal patients (ß = -0.19 (95% CI: -0.27, -0.10). In premenopausal patients, for every 1-unit increase in BMI, age at diagnosis decreased by 0.19 years. No association was observed in postmenopausal patients. CONCLUSIONS: In a large cohort of patients with EIN, increasing BMI was associated with an earlier age at diagnosis in premenopausal patients. This data suggests consideration of endometrial sampling in younger patients with known risk factors for excess estrogen exposure.

Localized Endometrial Proliferations of Pregnancy are Clonal Glandular Outgrowths Characterized by PTEN Loss and PIK3CA Pathogenic Variants.

Gestational endometrium can demonstrate a spectrum of atypical but benign changes. One such lesion is localized endometrial proliferation of pregnancy (LEPP), first described in a series of 11 cases. To understand its biological and clinical importance, we explore the pathologic, immunophenotypic, and molecular features of this entity. Nine cases of LEPP identified in 15 years were retrieved from departmental archives and reviewed. Immunohistochemistry and next-generation sequencing using a comprehensive 446-gene panel were performed when the material was available. Eight cases were identified in curettage specimens performed after first-trimester pregnancy loss, and 1 in the basal plate of a mature placenta. The mean patient age was 35 (range 27-41) years. The mean lesion size was 6.3 (range 2-12) mm. Architectural patterns, often coexisting in the same case, included cribriform (n = 7), solid (n = 5), villoglandular (n = 2), papillary (n = 2), and micropapillary (n = 1). Cytologic atypia was mild in 7 cases and moderate in 2. Mitotic activity was low (up to 3 per 2.4 mm2). All lesions were associated with neutrophils. Background Arias-Stella phenomenon was present in 4 cases. Immunohistochemistry was performed in 7 LEPP, all of which demonstrated wildtype p53, retained MSH6 and PMS2, membranous beta-catenin, and positive estrogen receptor (mean 71%) and progesterone receptor (mean 74%). All were negative for p40 except 1 case (focal weak positivity). PTEN was markedly reduced in background secretory glands in all cases; in 5/7, LEPP foci showed a complete absence of PTEN expression. PIK3CA pathogenic variants were identified in 4/4 cases sequenced; 3/4 had inactivating PTEN mutations. Follow-up, available in 8 patients (mean length = 51 months, range 7-161), was conservative with observation only and showed no persistence or adverse outcomes. LEPP is characterized by intraglandular cribriform/solid architecture, positive estrogen receptor/progesterone receptor, PTEN loss, and PIK3CA and PTEN mutations. Although our findings indicate that LEPP is neoplastic, for now, we advise against diagnosing LEPP as endometrial carcinoma or hyperplasia because LEPP has a particular clinicopathologic context (concurrent gestation), distinct morphology (purely intraepithelial complex growth), and indolent outcome. Thus, it should be distinguished from endometrial intraepithelial neoplasia and carcinoma for which therapeutic interventions are indicated.

Fertility-Sparing Treatment and Assisted Reproductive Technology in Patients with Endometrial Carcinoma and Endometrial Hyperplasia: Pregnancy Outcomes after Embryo Transfer.

The goal of fertility-sparing treatment (FST) for patients desiring future fertility with EMCA, and its precursor EH, is to clear the affected tissue and revert to normal endometrial function. Approximately 15% of patients treated with FST will have a live birth without the need for assisted reproductive technology (ART). Despite this low number, little information exists on the pregnancy outcomes of patients who utilize ART. The purpose of this study was to evaluate pregnancy outcomes following embryo transfer in patients with EMCA or EH who elected for FST. This retrospective cohort study at a large urban university-affiliated fertility center included all patients who underwent embryo transfer after fertility-sparing treatment for EMCA or EH between January 2003 and December 2018. Primary outcomes included embryo transfer results and a live birth rate (defined as the number of live births per number of transfers). There were 14 patients, three with EMCA and 11 with EH, who met the criteria for inclusion with a combined total of 40 embryo transfers. An analysis of observed outcomes by sub-group, compared to the expected outcomes at our center (patients without EMCA/EH matched for age, embryo transfer type and number, and utilization of PGT-A) showed that patients with EMCA/EH after FST had a significantly lower live birth rate than expected (Z = -5.04, df = 39, p < 0.01). A sub-group analysis of the 14 euploid embryo transfers resulted in a live birth rate of 21.4% compared to an expected rate of 62.8% (Z = -3.32, df = 13, p < 0.001). Among patients with EMCA/EH who required assisted reproductive technology, live birth rates were lower than expected following embryo transfer when compared to patients without EMCA/EH at our center. Further evaluation of the impact of the diagnosis, treatment, and repeated cavity instrumentation for FST is necessary to create an individualized and optimized approach for this unique patient population.

Artificial intelligence for prediction of endometrial intraepithelial neoplasia and endometrial cancer risks in pre- and postmenopausal women.

BACKGROUND: The current approach to endometrial cancer screening requires that all patients be able to recognize symptoms, report them, and carry out appropriate interventions. The current approach to endometrial cancer screening could become a problem in the future, especially for Black women and women from minority groups, and could lead to disparities in receiving proper care. Moreover, there is a lack of literature on artificial intelligence in the prediction and diagnosis of endometrial intraepithelial neoplasia and endometrial cancer. OBJECTIVE: This study analyzed different artificial intelligence methods to help in clinical decision-making and the prediction of endometrial intraepithelial neoplasia and endometrial cancer risks in pre- and postmenopausal women. This study aimed to investigate whether artificial intelligence may help to overcome the challenges that statistical and diagnostic tests could not. STUDY DESIGN: This study included 564 patients. The features that were collected included age, menopause status, premenopausal abnormal bleeding and postmenopausal bleeding, obesity, hypertension, diabetes mellitus, smoking, endometrial thickness, and history of breast cancer. Endometrial sampling was performed on all women with postmenopausal bleeding and asymptomatic postmenopausal women with an endometrial thickness of at least 3 mm. Endometrial biopsy was performed on premenopausal women with abnormal uterine bleeding and asymptomatic premenopausal women with suspected endometrial lesions. Python was used to model machine learning algorithms. Random forest, logistic regression, multilayer perceptron, Catboost, Xgboost, and Naive Bayes methods were used for classification. The synthetic minority oversampling technique was used to correct the class imbalance in the training sets. In addition, tuning and boosting were used to increase the performance of the models with a 5-fold cross-validation approach using a training set. Accuracy, sensitivity, specificity, positive predictive value, and F1 score were calculated. RESULTS: The prevalence of endometrial or preuterine cancer was 7.9%. Data from 451 patients were randomly assigned to the training group, and data from another 113 patients were used for internal validation. Of note, 3 of 9 features were selected by the Boruta algorithm for use in the final modeling. Age, body mass index, and endometrial thickness were all associated with a high risk of developing precancerous and cancerous diseases, after fine-tuning for the multilayer computer to have the highest area below the receiver operating characteristic curve (area under the curve, 0.938) to predict a precancerous disease. The accuracy was 0.94 for predicting a precancerous disease. Precision, recall, and F1 scores for the test group were 0.71, 0.50, and 0.59, respectively. CONCLUSION: Our study found that artificial intelligence can be used to identify women at risk of endometrial intraepithelial neoplasia and endometrial cancer. The model is not contingent on menopausal status or symptoms. This may be an advantage over the traditional methodology because many women, especially Black women and women from minority groups, could not recognize them. We have proposed to include patients to provide age and body mass index, and measurement of endometrial thickness by either sonography or artificial intelligence may help improve healthcare for women in rural or minority communities.

Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

OBJECTIVE: To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. METHODS: Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. RESULTS: One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. CONCLUSIONS: Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

Impacts of ovarian reserve on conservative treatment for endometrial cancer and atypical hyperplasia.

Objectives: Real-world data indicated that some endometrial atypical hyperplasia (EAH) and early endometrial carcinoma (EEC) patients of fertility preservation had a normal ovarian reserve, while some had a decreased ovarian reserve (DOR). This study was designed to investigate the effect of baseline ovarian reserve on the treatment of EAH and EEC patients who ask for preservation of fertility. Methods: This was a prospective cohort study conducted at a single university-affiliated fertility center. A total of 102 EAH and EEC patients who received fertility-preserving treatment between March 2019 and August 2020 were included and divided into a DOR group (n=22) and a non-DOR group (n=80). Results: The 32-week CR rate of the non-DOR group was significantly higher than that of the DOR group (60.3% vs. 33.3%, P =0.028). The DOR group had a longer treatment duration to achieve CR than the non-DOR group (40.07 vs. 29.71 weeks, P=0.008, HR: 0.54, 95% CI: 0.36-0.86). Multivariate logistic regression analyses demonstrated that DOR (OR: 0.35, 95% CI: 0.13-0.99, P=0.049) and BMI ≥25 kg/m2 (OR: 0.40, 95% CI: 0.17-0.92, P=0.031) were negatively associated with 32-week CR. Conclusions: Decreased baseline ovarian reserve is negatively correlated with the efficacy of fertility-preserving treatment in EAH and EEC patients, as this group has a lower CR rate and a longer treatment duration to achieve CR than those without DOR.

Is hemoglobin A1c valuable for predicting concurrent endometrial cancer in diabetic women with endometrial intraepithelial neoplasia?

AIM: The purpose of this study was to determine the predictive value of preoperative hemoglobin A1c (HgA1c) level for endometrial cancer in diabetic women with endometrial intraepithelial neoplasia (EIN). MATERIALS AND METHODS: Six hundred patients with EIN were retrospectively studied in a tertiary referral center in Turkey between January 2014 and December 2021. One hundred and thirteen diabetic patients with EIN who met the inclusion criteria were enrolled in the study and divided into three groups according to the final pathological results: Group 1 with benign findings (n = 29), Group 2 with EIN (n = 34) and Group 3 with endometrial cancer (n = 50). Demographic, clinical and biochemical characteristics were compared among the three groups. Receiver operating characteristic analysis (ROC) was used to evaluate the predictive value of HgA1c for concurrent endometrial cancer in EIN. RESULTS: Mean preoperative HgA1c levels were different among three groups (5.41 ± 0.64, 6.01 ± 0.72, 6.65 ± 1.15, p < 0.001, respectively). The highest value of HgA1c level was found in cancer group and difference within pairs was statistically significant (p < 0.001). Age and duration of menopause were also different among groups (p < 0.005). After adjustment of HgA1c level for age and duration of menopause differences were maintained (p < 0.001), the cutoff value was detected as ≥6.05% for HgA1c and sensitivity, specificity was 60%, 70%, respectively (p < 0.001). CONCLUSIONS: HgA1c could be used in prediction of endometrial cancer. The optimal cutoff value determined in our study could be considered in predicting endometrial cancer in diabetic women with EIN.

A case of endometrial intraepithelial neoplasia in a transgender man on testosterone therapy.

Testosterone is commonly used as gender-affirming therapy to induce masculinization in transmasculine individuals. The effects of testosterone therapy on endometrial tissue are complex, and while some patients experience endometrial atrophy while taking testosterone, others do not. Reports of gynecologic malignancies, and endometrial cancer in particular, in transmasculine patients taking testosterone are extremely rare (Urban et al., May 2011, Jeevananthan and Iyengar, 2021, Agnieszka Bobola, 2021). Here we report a case of endometrial intraepithelial neoplasia in a transgender man taking testosterone.

Diagnosis of endometrium hyperplasia and screening of endometrial intraepithelial neoplasia in histopathological images using a global-to-local multi-scale convolutional neural network.

BACKGROUND AND OBJECTIVE: Endometrial hyperplasia (EH), a uterine pathology characterized by an increased gland-to-stroma ratio compared to normal endometrium (NE), may precede the development of endometrial cancer (EC). Particularly, atypical EH also known as endometrial intraepithelial neoplasia (EIN), has been proven to be a precursor of EC. Thus, diagnosing different EH (EIN, hyperplasia without atypia (HwA) and NE) and screening EIN from non-EIN are crucial for the health of female reproductive system. Computer-aided-diagnosis (CAD) was used to diagnose endometrial histological images based on machine learning and deep learning. However, these studies perform single-scale image analysis and thus can only characterize partial endometrial features. Empirically, both global (cytological changes relative to background) and local features (gland-to-stromal ratio and lesion dimension) are helpful in identifying endometrial lesions. METHODS: We proposed a global-to-local multi-scale convolutional neural network (G2LNet) to diagnose different EH and to screen EIN in endometrial histological images stained by hematoxylin and eosin (H&E). The G2LNet first used a supervised model in the global part to extract contextual features of endometrial lesions, and simultaneously deployed multi-instance learning in the local part to obtain textural features from multiple image patches. The contextual and textural features were used together to diagnose different endometrial lesions after fusion by a convolutional block attention module. In addition, we visualized the salient regions on both the global image and local images to investigate the interpretability of the model in endometrial diagnosis. RESULTS: In the five-fold cross validation on 7812 H&E images from 467 endometrial specimens, G2LNet achieved an accuracy of 97.01% for EH diagnosis and an area-under-the-curve (AUC) of 0.9902 for EIN screening, significantly higher than state-of-the-arts. In external validation on 1631 H&E images from 135 specimens, G2LNet achieved an accuracy of 95.34% for EH diagnosis, which was comparable to that of a mid-level pathologist (95.71%). Specifically, G2LNet had advantages in diagnosing EIN, while humans performed better in identifying NE and HwA. CONCLUSIONS: The developed G2LNet that integrated both the global (contextual) and local (textural) features may help pathologists diagnose endometrial lesions in clinical practices, especially to improve the accuracy and efficiency of screening for precancerous lesions.

Should body mass index replace age to drive the decision for endometrial sampling in premenopausal women with abnormal uterine bleeding?

OBJECTIVE: This study aimed to evaluate risk factors for endometrial intraepithelial neoplasia/malignancy in premenopausal women with abnormal uterine bleeding or oligomenorrhea. Specifically, we aimed to elucidate whether body mass index (BMI) or age confers a higher risk. STUDY DESIGN: A retrospective cohort study was performed at a large academic center examining risk factors for endometrial hyperplasia/malignancy in premenopausal women undergoing endometrial sampling. RESULTS: Of the 4170 women ages 18-51 who underwent endometrial sampling from 1987 to 2019, 77 (1.85%) were found to have endometrial intraepithelial neoplasia or malignancy. Clinical predictors of EIN/malignancy in this population included obesity (OR: 3.84, 95%, p < .001), Body mass index [(OR30 vs. 25:2.11, p < .001) and OR35 vs. 30: 1.65, p < .001], Diabetes (OR: 3.6, p-value <.001), hormonal therapy use (OR: 2.93, p < .001), personal history of colon cancer (OR: 9.90, p = .003), family history of breast cancer (OR: 2.65, p < .001), family history of colon cancer (OR: 3.81, p < .001), and family history of endometrial cancer (OR: 4.92, p = .033). Age was not significantly associated with an increased risk of disease. Adjusting for other factors, a model using BMI to predict the risk of EIN/malignancy was more discriminative than a model based on age. CONCLUSIONS: Increased BMI, may be more predictive of endometrial hyperplasia/malignancy than age in premenopausal women with abnormal uterine bleeding. Modification of evaluation guidelines in a contemporary demographic setting could be considered.

Expression of extracellular matrix proteins nidogen-1 and legumain in endometrial carcinomas.

PURPOSE: Our purpose was to comparatively investigate the expressions of nidogen-1 (NID1) and legumain (LGMN) in patients with endometrial cancer, endometrial intraepithelial neoplasia, and proliferative endometrium. METHODS: A cross-sectional, single-center study was performed by the obstetrics and gynecology and pathology departments of our institution. The relationships between descriptive data, clinicopathologic information, and immunohistochemical expressions of NID1 and LGMN were investigated. RESULTS: The histological grades of endometrial cancers (n = 124) as classified by FIGO included 1 (41, 21.1%), 2 (48, 24.7%), and 3 (35, 18.0%). The medians and ranges of deep and superficial NID1 expressions were 50.00 (0-285) and 5.00 (0-100), respectively. The intensity of legumain expression was noted as negative (30, 24.2%), mild (16, 12.9%), moderate (27, 21.8%), or strong (51, 41.1%). Median disease-free survival and overall survival were 75.00 (range: 1 to 170) months and 77.00 (range: 1 to 170) months, respectively. Patients with more intense expression of NID1 and LGMN displayed a higher histological grade. These patients were more likely to have a positive peritoneal cytology, larger tumor size, higher tendency for myometrial or lymphovascular invasion, involvement of ovaries, cervix, omentum, as well as lymph node metastasis, and recurrence. CONCLUSION: Our data indicated that the expressions of NID1 and LGMN may have important diagnostic implications in endometrial pathologies. Further studies should be performed to understand the significance of NID1 and LGMN in the pathogenesis of endometrial tumors.