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Objective: To assess the performance of simultaneous endometrial aspiration and sonohysterography to screen for endometrial cancer or hyperplasia in women aged 50 years or older., Methods: We conducted a prospective study from February 2014 to October 2020 at the ultrasound unit of a large urban academic medical center. The study included 1,635 women aged 50 years or older referred for endometrial evaluation, with follow-up through January 2021. Participants underwent saline infusion sonohysterography combined with ultrasound-guided endometrial aspiration. The primary outcome measured was a diagnosis of endometrial cancer or hyperplasia within 1 year from screening. The diagnostic accuracy of the combined evaluation method, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed., Results: Of 1,170 women who completed the study protocol, 82 (7.0%) had endometrial cancer and 42 (3.6%) had endometrial hyperplasia. Of all patients who developed cancer during the follow-up period, 85.5% were diagnosed within 1 year after evaluation. The application of simultaneous endometrial aspiration and sonohysterography together demonstrated a sensitivity of 99.1%, specificity of 24.9%, PPV of 11.8%, and NPV of 99.6%. Using a theoretical sequential approach, assuming an endometrial aspiration is performed only in patients determined to be high risk by sonohysterography, demonstrated a sensitivity of 93.4%, specificity of 99.9%, PPV of 99.0%, and NPV of 99.3%., Conclusion: Simultaneous endometrial aspiration and sonohysterography is an effective one-stop outpatient screening tool for detecting endometrial cancer and hyperplasia in women aged 50 years or older. With the integration of two screening modalities into a single procedure, simultaneous endometrial aspiration and sonohysterography may overcome the limitations inherent in each of the currently recommended methods individually, potentially improving patient prognosis and streamlining the diagnostic process., Competing Interests: Financial Disclosure Haotian Wu disclosed receiving payments from Montefiore. The other authors did not report any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To determine the cutoff value for endometrial thickness (ET) that prompts a biopsy in asymptomatic postmenopausal women with an incidental finding of thickened endometrium, and to develop a risk prediction model., Methods: This is a retrospective cohort analysis of the clinical records of the Hysteroscopic Center of Fu Xing Hospital, Capital Medical University, Beijing, China. We collected asymptomatic postmenopausal women who presented with an ET of ≥4 mm (double-layer) as an incidental finding. We stratified the participants into non-malignant and malignant groups based on pathology results and assessed differences between the two groups. A receiver operating characteristic curve (ROC) was used to identify the cutoff value of ET for predicting endometrial malignancy. Logistic regression models were also constructed to predict the risk of malignancy., Results: A total of 581 consecutive eligible cases were included. The optimal cutoff value for ET was 8 mm, with a maximum area under the curve (AUC) of 0.755 (95 % CI: 0.645-0.865). In addition to ET, the regression model incorporated diabetes, blood flow signal, BMI, and hypertension to predict the risk of malignancy. A ROC curve constructed for the model yielded an AUC of 0.834 (95 % CI: 0.744-0.924)., Conclusion: It is reasonable to offer hysteroscopy and visually-directed endometrial biopsy for asymptomatic postmenopausal women when ET is 8 mm or above. For those with an ET between 4 and 8 mm, further decision to perform biopsy should be determined on an individual basis, considering risk factors and blood flow signals of the endometrium., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Areas of gland crowding that do not fulfil diagnostic criteria of endometrioid intra-epithelial neoplasia (EIN) are often encountered in endometrial biopsies. In this study, we document the prevalence of neoplastic outcome in patients with these subdiagnostic lesions (SL) and assess the utility of morphological features and a three-marker immunohistochemistry panel (PAX2, PTEN, beta-catenin) to predict outcome., Methods and Results: Of 430 women with SL on endometrial sampling at Brigham and Women's Hospital between 2001 and 2021 with available follow-up biopsy, 72 (17%) had a neoplastic outcome (EIN or endometrioid carcinoma). Multilayered epithelium and mitoses in SL were statistically associated with a neoplastic outcome. Abnormal three-marker staining was observed in 93% (53 of 57) of SL with neoplastic outcome and 60% (37 of 62) of a control group with benign outcome. Among the 72 patients with neoplastic outcome, EIN/carcinoma tissue was available in 33; of these, 30 (91%) showed abnormal staining for one or more markers. Remarkably, in 84% of these cases the EIN/carcinoma had the aberrant expression seen in the preceding SL. Based on a prevalence of 17%, the positive and negative predictive values of abnormal staining in one or more markers were 24 and 97%, respectively., Conclusions: The presence of SL warrants clinical surveillance and repeat sampling because it is followed by endometrioid neoplasia in a significant subset of patients. Normal three-marker staining identifies women with a very low risk of neoplastic outcome. Conversely, abnormal staining is frequent in SL with benign outcome leading to poor specificity and positive predictive value., (© 2024 John Wiley & Sons Ltd.)

Objective: To develop predictive models for endometrial hyperplasia and endometrial cancer in patients with recurrent abnormal uterine bleeding (AUB)., Methods: This retrospective cohort study analyzed patients with recurrent AUB who had previous endometrial sampling that showed benign results between January 2013 and December 2021. A model was constructed from the significant factors associated with endometrial hyperplasia and endometrial cancer using multivariate logistic regression. Risk scores were calculated from the log odds of each significant predictive factor and were subsequently subcategorized into risk groups. The overall performance and internal validation of the model were assessed with the area under the receiver operating characteristic curve (AUC) and bootstrap methods., Results: Of the total 456 patients with recurrent AUB, endometrial hyperplasia and endometrial cancer were detected in 8.3% and 2.2% of cases, respectively. The average interval between the first and second endometrial samplings was 25.1 months. Factors significantly associated with endometrial hyperplasia and endometrial cancer included age older than 45 years (odds ratio [OR] 2.86, 95% CI, 1.31-7.03), nulliparity (OR 3.50, 95% CI, 1.76-6.85), a history of endometrial polyp (OR 3.69, 95% CI, 1.93-7.05), and an interval of less than 12 months between sampling (OR 2.36, 95% CI, 1.25-4.42). Predictive factors were scored and categorized into three groups: 0-3, 5-8, and 9-11 points. The corresponding risks for endometrial hyperplasia and endometrial cancer in these groups were 4.7%, 15.5%, and 57.1%, respectively. The AUC was 73.1%, with a mean absolute error of 0.01., Conclusion: Endometrial hyperplasia and endometrial cancer occur at low incidence among one-fifth of patients with AUB who experience recurrent bleeding. Older age, nulliparity, a history of endometrial polyps, and an interval of less than 12 months between samplings are predictive factors for endometrial hyperplasia and endometrial cancer in this cohort., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

• Endometrial hyperplasia can be classified as either hyperplasia without atypia or atypical hyperplasia. • Abnormal uterine bleeding is the most common symptom of endometrial hyperplasia. Transvaginal ultrasound is recommended for initial imaging to evaluate endometrial hyperplasia (evidence level 2+), while transrectal ultrasound is recommended for virgo patients (evidence level 3). • Endometrial biopsy should be used to confirm diagnosis in patients where endometrial lesions are suspected. Effective histological approaches to make definite diagnoses include diagnostic curettage (evidence level 2++), hysteroscopic-guided biopsy (evidence level 2+) and endometrial aspiration biopsy (evidence level 2-). • Progesterone is the preferred medication for the treatment of endometrial hyperplasia without atypia. Compared to oral progestins, placement of a levonorgestrel-releasing intrauterine system (LNG-IUS) has been associated with higher regression rates, lower recurrence rates and fewer adverse events which can be the initial treatment method. (Meta evidence level 1-, RCT evidence level 2+). Ultrasound and endometrial biopsies should be performed every 6 months during treatment to evaluate its effect and treatment should continue until no pathological changes are observed in two consecutive endometrial biopsies. Hysterectomy is not the preferred choice of treatment for patients with endometrial hyperplasia without atypia. • Minimally invasive hysterectomy is indicated for patients with endometrial atypical hyperplasia (evidence level 1+), bilateral fallopian tubes should also be removed (evidence level 2+). In cases where surgery cannot be tolerated, fertility is desired or the patient is younger than 45 years old, medical therapy is recommended (evidence level 3). LNG-IUS is the preferred medical therapy method (evidence level 2+). Endometrial pathologic evaluation should be performed every 3 months during conservative treatments, with adjustments made to dosages or approaches based on observed response to medication. Treatment should continue until no pathological changes are detected in two consecutive endometrial biopsies (evidence level 2++). There is no indication of sentinel lymph nodes biopsy and/or lymphadenectomy for hyperplasia with or without atypia. • Total hysterectomy is recommended to treat patients with recurrent endometrial atypical hyperplasia (evidence level 3); however, medical conservative therapy may be considered for patients hoping to become pregnant in the future. • Patients with fully regressed disease who would like to become pregnant should be advised to seek assistance through assisted reproductive technologies (evidence level 3). • Long-term follow-up is suggested for patients after endometrial hyperplasia treatment (evidence level 2+). Patient education is imperative for improving medication adherence, increasing regression rates and lowering recurrence rates (evidence level 3)., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest to disclose., (© 2024 Published by Elsevier Ltd.)

Background: Inflammation has an important role in the progression of endometrial carcinoma., Aims: The aim of this study is to find the association between neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and endometrial carcinoma. The study also focuses on the association of CA125, NLR, and PLR with histopathological parameters in endometrial carcinoma that are of prognostic importance., Materials and Methods: This is a prospective cross-sectional study on 57 biopsy-proven cases of endometrial hyperplasia and carcinoma conducted over a period of two years. The NLR, PLR, and CA125 were calculated and recorded in all the 57 cases., Results: The 57 cases were divided into three groups: endometrial hyperplasia without atypia group which included 36 cases, endometrial atypical hyperplasia group which included 10 cases, and the endometrial carcinoma group which included 11 cases. Comparison was done between the groups, and parity, NLR, PLR, and CA125 were found to be significant, but patient age and postmenopausal status were not significant. NLR, PLR, and CA125 were found to increase with higher grade, pT-stage, and nodal stage for the endometrial carcinoma cases., Conclusion: NLR, PLR, and CA125 were marginally increased or normal in the case of endometrial hyperplasia without atypia and endometrial atypical hyperplasia, while they were significantly increased in endometrial carcinoma, and also correlated with an increase in grade, pT-stage, and nodal stage. Hence, these can be considered for additional screening as diagnostic, prognostic, and predictive markers in case of abnormal uterine bleeding with endometrial pathology., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Objective: Reproducible diagnoses of endometrial hyperplasia (EH) remains challenging and has potential implications for patient management. This systematic review aimed to identify pathologist-specific factors associated with interobserver variation in the diagnosis and reporting of EH., Methods: Three electronic databases, namely MEDLINE, Embase and Web of Science, were searched from 1st January 2000 to 25th March 2023, using relevant key words and subject headings. Eligible studies reported on pathologist-specific factors or working practices influencing interobserver variation in the diagnosis of EH, using either the World Health Organisation (WHO) 2014 or 2020 classification or the endometrioid intraepithelial neoplasia (EIN) classification system. Quality assessment was undertaken using the QUADAS-2 tool, and findings were narratively synthesised., Results: Eight studies were identified. Interobserver variation was shown to be significant even amongst specialist gynaecological pathologists in most studies. Few studies investigated pathologist-specific characteristics, but pathologists were shown to have different diagnostic styles, with some more likely to under-diagnose and others likely to over-diagnose EH. Some novel working practices were identified, such as grading the "degree" of nuclear atypia and the incorporation of objective methods of diagnosis such as semi-automated quantitative image analysis/deep learning models., Conclusions: This review highlighted the impact of pathologist-specific factors and working practices in the accurate diagnosis of EH, although few studies have been conducted. Further research is warranted in the development of more objective criteria that could improve reproducibility in EH diagnostic reporting, as well as determining the applicability of novel methods such as grading the degree of nuclear atypia in clinical settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 McCoy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: The effectiveness of hysteroscopy in diagnosing endometrial lesions has been demonstrated, showing high diagnostic accuracy for malignant endometrial lesions. Although the characteristic appearances of atypical and malignant endometria have been reported, they are not definitive and sometimes complicated. This study aimed to identify a small number of characteristic features to detect endometrial abnormalities using a simple judgment system and analyze the diagnostic characteristics and their accuracy in endometrial malignancy diagnosis., Methods: We performed a retrospective analysis of hysteroscopy video data of 250 patients, of which we selected for analysis based on pathology examination 152 cases with benign changes, 16 with atypical endometrium, and 18 with carcinoma in situ or endometrial cancer. Endometrial characteristics assessed included protrusion, desquamation, extended vessel, atypical vessel, and white/yellow lesion., Results: Multivariable analysis revealed that desquamation (p = 0.001, odds ratio [OR] 5.28), atypical vessels (p < 0.001, OR 8.50), and white/yellow lesions (p = 0.011, OR 1.37) were significant predictors for endometrial malignancy. From their contribution status, scoring points of 4, 6, and 1 were settled according to the odds ratio proportions. When scores ≥5 (at least both desquamation and white/yellow lesions or only atypical vessels) were used to define endometrial malignancy, sensitivity and specificity were 100% and 92%, respectively. When detecting cancer, atypical, and benign cases, sensitivity and specificity were 88% and 90%, respectively., Conclusion: Our characteristics hysteroscopic findings showed a higher predictive ability in detecting endometrial malignancies. However, further examination with more cases would be needed to accurately diagnose endometrial malignancy by hysteroscopy., (© 2024 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

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., (© 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Endometrial hyperplasia (EH) is a precusor lesion for endometrial cancer (EC), the commonest gynaecological malignancy in high-income countries. EH is a proliferation of glandular tissue, classified as either non-atypical endometrial hyperplasia (NEH) or, if the cytological features are abnormal, atypical endometrial hyperplasia (AEH). The clinical significance of AEH is that patients face both a high risk of having occult EC and a high risk of progression to EC if untreated. Recommendations on the care of women with EH were introduced by United Kingdom-wide guidance (Green-top Guide No. 67, 2016). National adherence to guidance is unknown. We aimed to describe the care of patients with EH; to compare the patterns of care for those with EH with national guidance to identify opportunities for quality improvement; and to compare patterns of care prior to and following the introduction of national guidance to understand its impact., Methods and Findings: In this UK-wide patient-level clinical audit, we included 3,307 women who received a new histological diagnosis of EH through a gynaecology service between 1 January 2012 and 30 June 2020. We described first-line management, management at 2 years, and surgical characteristics prior to and following national guidance for EH using proportions and 95% confidence intervals (CIs) and compared process measures between time periods using multilevel Poisson regression. Of the 3,307 patients, 1,570 had NEH and 1,511 had AEH between 2012 and 2019. An additional 85 patients had NEH and 141 had AEH during 2020. Prior to national guidance, 9% (95% CI [6%, 15%]) received no initial treatment for NEH compared with 3% (95% CI [1%, 5%]) post-guidance; 31% (95% CI [26%, 36%]) and 48% (95% CI [43% 53%]) received an intrauterine progestogen, respectively, in the same periods. The predominant management of women with AEH did not differ, with 68% (95% CI [61%, 74%]) and 67% (95 CI [63%, 71%]) receiving first-line hysterectomy, respectively. By 2 years, follow-up to histological regression without hysterectomy increased from 38% (95% CI [33%, 43%]) to 52% (95% CI [47%, 58%]) for those with NEH (rate ratio (RR) 1.38, 95% CI [1.18, 1.63] p < 0.001). We observed an increase in the use of total laparoscopic hysterectomy among those with AEH (RR 1.26, 95% CI [1.04, 1.52]). In the later period, 37% (95% CI [29%, 44%]) of women initially diagnosed with AEH who underwent a first-line hysterectomy, received an upgraded diagnosis of EC. Study limitations included retrospective data collection from routine clinical documentation and the inability to comprehensively understand the shared decision-making process where care differed from guidance., Conclusions: The care of patients with EH has changed in accordance with national guidance. More women received first-line medical management of NEH and were followed up to histological regression. The follow-up of those with AEH who do not undergo hysterectomy must be improved, given their very high risk of coexistent cancer and high risk of developing cancer., Competing Interests: JG contributed to Green-top Guideline No.67 on behalf of the British Society for Gynaecological Endoscopy., (Copyright: © 2024 Henderson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients., Methods: We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients., Results: Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828-0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05)., Conclusion: We have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment., (© 2024. The Author(s).)

Competing Interests: Financial Disclosure The author did not report any potential conflicts of interest.

It is not standardised what is the endometrial thickness that discriminates between normal and potentially malignant. The objective of this study was to determine the endometrial thickness cut-off point from which the risk of endometrial cancer (EC) increases in asymptomatic postmenopausal women; and to evaluate the risk factors linked to malignant endometrial pathology as well as other associated ultrasound findings.This was a retrospective observational study that included hysteroscopies performed at the Hospital Materno-Infantil on 267 asymptomatic menopausal women with an increase in endometrial thickness (AET) >5 mm, from 2015 to 2019. The results shows that the prevalence of malignant pathology in asymptomatic postmenopausal women with a casual finding of endometrial thickening was 3.7%. This percentage was 16.3% when the cut-off point of AET was established at 10 mm. There was a significant association for the diagnosis of malignant pathology with this cut-off point.There is a significant association between the 10 mm endometrial thickness cut-off point from which the risk of EC increases in asymptomatic postmenopausal women.Impact statement What is already known on this subject? Several studies have established the cut-off point for asymptomatic endometrial thickening (AET) for atypical endometrial hyperplasia and endometrial cancer at 10 mm. Although no cut-off point has optimal accuracy for the diagnosis of malignant endometrial pathology, it has been found that with a cut-off value of AET >10 mm no cases are missed. Likewise, a cut-off point of AET > 11 mm may provide a balance between cancer detection and histopathological workup extension. What do the results of this study add? A significant association was found at the cut-off point of AET > 10 mm, which suggests that screening postmenopausal women at this thickness is acceptable and unlikely to miss cases of endometrial hyperplasia and endometrial cancer. What are the implications of these findings for clinical practice and/or further research? After analysing our results we can conclude, like other published studies, that by establishing a cut-off point of 10 mm we obtain a good discrimination between benign and malignant pathology, which would allow us to diagnose 100% of malignant pathology. Above this cut-off point, the risk of endometrial cancer increases, and it would therefore be advisable to extend the study. A multicentre study is needed to confirm the cut-off point at which the risk of endometrial cancer increases in postmenopausal women with asymptomatic endometrial thickening.

Background: Demographic features, suggestive gynaecological symptoms, and immunohistochemical expression of endometrial β-catenin have a prognostic capacity for endometrial hyperplasia and carcinoma. This study assessed the interaction of all variables and developed risk stratification for endometrial hyperplasia and carcinoma., Methods: This cross-sectional study was conducted from January 2023 to July 2023 at two teaching hospitals in Makassar Indonesia. Patients (< 70 years old) with suggestive symptoms of endometrial hyperplasia or carcinoma or being referred with disease code N.85 who underwent curettage and/or surgery for pathology assessment except those receiving radiotherapy, or chemotherapy, presence of another carcinoma, coagulation disorder, and history of anti-inflammatory drug use and unreadable samples. Demographic, and clinical symptoms were collected from medical records. Immunohistochemistry staining using mouse-monoclonal antibodies determined the β-catenin expression (percentage, intensity, and H-score) in endometrial tissues. Ordinal and Binary Logistic regression identified the potential predictors to be included in neural networks and decision tree models of histopathological grading according to the World Health Organization/WHO grading classification., Results: Abdominal enlargement was associated with worse pathological grading (adjusted odds ratio/aOR 6.7 95% CI 1.8-24.8). Increasing age (aOR 1.1 95% CI 1.03-1.2) and uterus bleeding (aOR 5.3 95% CI 1.3-21.6) were associated with carcinoma but not with %β-catenin and H-Score. However, adjusted by vaginal bleeding and body mass index, lower %β-catenin (aOR 1.03 95% 1.01-1.05) was associated with non-atypical hyperplasia, as well as H-Score (aOR 1.01 95% CI 1.01-1.02). Neural networks and Decision tree risk stratification showed a sensitivity of 80-94.8% and a specificity of 40.6-60% in differentiating non-atypical from atypical and carcinoma. A cutoff of 55% β-catenin area and H-Score of 110, along with other predictors could distinguish non-atypical samples from atypical and carcinoma., Conclusion: Risk stratification based on demographics, clinical symptoms, and β-catenin possesses a good performance in differentiating non-atypical hyperplasia with later stages., (© 2023. The Author(s).)

Summary: Endometrial intraepithelial neoplasia (EIN) or atypical endometrial hyperplasia (AEH) often is a precursor lesion to adenocarcinoma of the endometrium. Hysterectomy is the definitive treatment for EIN-AEH. When a conservative (fertility-sparing) approach to the management of EIN-AEH is under consideration, it is important to attempt to exclude the presence of endometrial cancer to avoid potential undertreatment of an unknown malignancy in those who have been already diagnosed with EIN-AEH. Given the high risk of progression to cancer, those who do not have surgery require progestin therapy (oral, intrauterine, or combined) and close surveillance. Although data are conflicting and limited, studies have demonstrated that treatment with the levonorgestrel-releasing intrauterine device results in a higher regression rate when compared with treatment with oral progestins alone. Limited data suggest that cyclic progestational agents have lower regression rates when compared with continuous oral therapy. After initial conservative treatment for EIN-AEH, early detection of disease persistence, progression, or recurrence requires careful follow-up. Gynecologists and other clinicians should counsel patients that lifestyle modification resulting in weight loss and glycemic control can improve overall health and may decrease the risk of EIN-AEH and endometrial cancer., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the rate of atypical hyperplasia (AH) underestimating endometrial cancer (EC) comparing endometrial biopsy (EB) accomplished by hysteroscopic biopsy with dilatation and curettage (D&C). Second, to compare the two techniques to foresee EC grading., Methods: This trial was based on the findings of two Gynecological Departments within the same Public Utility, sharing pathological service and database but routinely performing EB under hysteroscopic visualization (group A) or hysteroscopy followed by D&C (group B). We retrieved the clinical data of patients showing EC on hysterectomy throughout a 10-year period. The accuracy of hysteroscopic-view diagnosis and EB pathology were compared, having the pathologic findings of hysterectomy as reference., Results: A total of 161 patients met the inclusion criteria. Among these, 109 and 52 were included in groups A and B, respectively. In group A, 32.1% of patients underwent EB in an out-patient setting. To foresee EC, hysteroscopic view showed a sensitivity of 82.5% and 70.2% in groups A and B, respectively (P = 0.019). An underestimation of EC diagnosed as AH on EB was found in 20 patients (12.4%). Among these, 18 (16.5%) and 2 (3.8%) were included in groups A and B, respectively (P = 0.022). In group A, a fault diagnosis of AH resulted higher when EB was performed as out-patient setting (P = 0.006). EB allowed the grading of EC in 73.3% and 90.3% of patients in groups A and B, respectively. The agreement was 73.7% and 85.1%, leading to moderate (κ = 0.56) and good (κ = 0.77) "κ" coefficient of concordance for groups A and B, respectively., Conclusions: EB performed by D&C lowers the rate of AH underestimating concurrent EC and improves the grading agreement when compared with hysteroscopic sampling., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasm (AH/EIN) within endometrial polyps (EMPs) often poses a diagnostic conundrum. Our previous studies demonstrated that a panel of immunohistochemical (IHC) markers consisting of PAX2, PTEN, and β-catenin can be effectively utilized for the identification of AH/EIN. A total of 105 AH/EIN within EMP were analyzed using the 3-marker panel. We also evaluated these cases for the presence of morules. Benign EMP (n=90) and AH/EIN unassociated with polyp (n=111) served as controls. Aberrant expression of PAX2, PTEN, or β-catenin was observed in AH/EIN in EMP in 64.8%, 39.0%, and 61.9% of cases, respectively. At least 1 IHC marker was abnormal in 92.4% of cases. Overall, 60% of AH/EIN in EMP demonstrated abnormal results for≥2 IHC markers. The prevalence of PAX2 aberrancy was significantly lower in AH/EIN in EMP than in nonpolyp AH/EIN (64.8% vs. 81.1%, P =0.007), but higher than in benign EMP (64.8% vs. 14.4%, P <0.00001). The prevalence of β-catenin aberrancy was significantly higher in AH/EIN in EMP than in nonpolyp AH/EIN (61.9% vs. 47.7%, P =0.037). All control benign EMP demonstrated normal expression of PTEN and β-catenin. Morules were present in 38.1% of AH/EIN in EMP versus 24.3% in nonpolyp AH/EIN, and absent in benign EMP. A strong positive association was found between β-catenin and morules (Φ=0.64). Overall, 90% cases of atypical polypoid adenomyoma (n=6) and mucinous papillary proliferation (n=4) showed IHC marker aberrancy. In conclusion, the 3-marker IHC panel (PAX2, PTEN, and β-catenin) is (1) a useful tool in the diagnosis of AH/EIN in EMP; (2) PAX2 loss should be interpreted with caution and in combination with morphology and other markers., Competing Interests: Conflicts of Interest and Source of Funding: Supported by the Philip O’Bryan Montgomery endowment fund, UTSW to K.M., Mark and Jane Gibson Distinguished Professorship endowment fund to W.Z., and start-up fund and intramural research fund of the Department of Pathology, UTSW to H.C. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the contribution of PAX2, ARID1A, and FOXA1 biomarkers to diagnosis in cases with atypical endometrial hyperplasia (AEH)., Study Design: Descriptive Study. Place and Duration of the Study: Pathology Department of Umraniye Training and Research Hospital, from January 2018 to December 2020., Methodology: Curettage materials of 100 patients diagnosed with AEH which stained PAX2, ARID1A, and FOXA1, were evaluated. The staining patterns in the atypical endometrial glandular areas were grouped as slight-no loss, moderate loss, and complete loss / severe loss for all three biomarkers. Complete or/severe loss in AEH was considered helpful in the diagnosis., Results: Complete loss / severe loss rates in curettages were 84% for PAX2, 5% for ARID1A, and 15% for FOXA1, respectively. When used in combination, complete loss / severe loss rates were 85% in at least one of the three markers, 84% in PAX2 and/or ARID1A, 85% in PAX2 and/or FOXA1, and 17% in ARID1A and/or FOXA1., Conclusion: Although all 3 biomarkers showed marked staining loss, PAX2 is the most sensitive biomarker for the diagnosis of AEH in curettage materials., Key Words: Endometrium, Atypical hyperplasia, PAX2, ARID1A, FOXA1.

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 (β) 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 (β = -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., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Published by Elsevier Inc.)

Background: An increasing number of atypical endometrial hyperplasia (AEH) or endometrial cancer (EC) patients with fertility requirements choose conservative management, such as oral high-dose progesterone. Most of them use assisted reproductive technology (ART) to become pregnant after experiencing remission. However, the outcome of pregnancy is not ideal, probably because of long-term drug application in large doses or invasive uterine cavity treatment., Case Report: We presented a case of AEH who underwent direct pregnancy with good results without any treatment for her pathological endometrium. We described her endometrial histological results pre-and post-pregnancy in detail, hitherto absent from reports on this topic., Conclusions: Patients with a strong desire to bear children at the time of an AEH diagnosis could consider taking 1-2 years to try a pregnancy before treating their AEH.

Purpose: This study aimed to identify the risk factors and sonographic variables that could be integrated into a predictive model for endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) in women with abnormal uterine bleeding (AUB)., Materials and Methods: This retrospective study included 1837 patients who presented with AUB and underwent endometrial sampling. Multivariable logistic regression was developed based on clinical and sonographic covariates [endometrial thickness (ET), resistance index (RI) of the endometrial vasculature] assessed for their association with EC/AEH in the development group (n=1369), and a predictive nomogram was proposed. The model was validated in 468 patients., Results: Histological examination revealed 167 patients (12.2%) with EC or AEH in the development group. Using multivariable logistic regression, the following variables were incorporated in the prediction of endometrial malignancy: metabolic diseases [odds ratio (OR)=7.764, 95% confidence intervals (CI) 5.042-11.955], family history (OR=3.555, 95% CI 1.055-11.971), age ≥40 years (OR=3.195, 95% CI 1.878-5.435), RI ≤0.5 (OR=8.733, 95% CI 4.311-17.692), and ET ≥10 mm (OR=8.479, 95% CI 5.440-13.216). A nomogram was created using these five variables with an area under the curve of 0.837 (95% CI 0.800-0.874). The calibration curve showed good agreement between the observed and predicted occurrences. For the validation group, the model provided acceptable discrimination and calibration., Conclusion: The proposed nomogram model showed moderate prediction accuracy in the differentiation between benign and malignant endometrial lesions among women with AUB., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Background: Endometrial thickness (ET) measurement was an alternative method for predicting abnormal endometrial pathology in postmenopausal bleeding. Cut-off value of ET measurement could not be use in perimenopausal bleeding., Objective: Aim of this study was to investigate appropriate ET cut-off value for perimenopause women with abnormal uterine bleeding (PEMB) and abnormal endometrial histopathology., Material and Methods: This was a cross-sectional study. PEMB at Bhumibol Adulyadej Hospital between July 2018 and June 2022 were recruited. Subjects who met inclusion criteria underwent ET measurement and endometrial biopsy via endometrial aspirator. Participants who had histopathology report of endometrial hyperplasia and more were classified as the study group. The Control group were subjects with no endometrial hyperplasia or cancer. Demographic and clinical character data were included. Correlation of ET and endometrial histopathology were calculated for statistical significance., Results: A total of 304 cases were included. After exclusion, 254 subjects were recruited for this study. There were 22 and 232 cases in the study and control groups, respectively. The mean age and body mass index (BMI) of participants were 44.7 years old and 27.5 kg/m2, respectively. Prevalence of endometrial hyperplasia and cancer in perimenopausal uterine bleeding were 7.5 (19/254) and 1.2 (3/254) percent, respectively. Endometrial thickness equal to and more than 8 mm was associated with abnormal endometrial histopathology with statistical significance. Age, BMI, nulliparity, anovulatory bleeding history, hypothyroidism, diabetes mellitus and anovulation state of both groups were comparable., Conclusions: Endometrial thickness equal or more than 8 mm were significantly associated with endometrial hyperplasia or more among perimenopausal women with abnormal uterine bleeding.

Objectives: The aim of this study is to evaluate the place of serum soluble L1 cell adhesion molecule (sL1CAM) level in the diagnosis of endometrial cancer and its relationship with clinicopathological features., Material and Methods: This cross-sectional study was performed with 146 patients who underwent endometrial biopsy and whose pathology results were reported as benign endometrial changes (n = 30), endometrial hyperplasia (n = 32) or endometrial cancer (n = 84). The sL1CAM level between the groups was compared. The relationship between clinicopathological features and serum sL1CAM was evaluated in patients with endometrial cancer., Results: The mean serum sL1CAM level in patients with endometrial cancer was significantly higher than in patients without cancer. The sL1CAM value was statistically significantly higher in the group with endometrial cancer, than the group with endometrial hyperplasia (p < 0.001) and the group with benign endometrial changes (p < 0.001). There was no statistically significant difference in terms of sL1CAM between the group of patients with endometrial hyperplasia and the group of patients with benign endometrial changes (p = 0.954). sL1CAM value in type 2 endometrial cancer was statistically significantly higher than Type1 (p = 0.019). High sL1CAM level in patients with type 1 cancer was associated with poor clinicopathological features. However, no correlation was observed between clinicopathological features and serum sL1CAM level in type 2 endometrial cancers., Conclusions: Serum sL1CAM may be an important marker for evaluating the diagnosis and prognosis of endometrial cancer in the future. There may be a relationship between increased serum sL1CAM level in type 1 endometrial cancers and poor clinicopathological features.

The objectives of this Clinical Expert Series on endometrial hyperplasia are to review the etiology and risk factors, histologic classification and subtypes, malignant progression risks, prevention options, and to outline both surgical and nonsurgical treatment options. Abnormal uterine and postmenopausal bleeding remain the hallmark of endometrial pathology, and up to 10-20% of postmenopausal bleeding will be either hyperplasia or cancer; thus, immediate evaluation of any abnormal bleeding with either tissue procurement for pathology or imaging should be undertaken. Although anyone with a uterus may develop atypical hyperplasia, also known as endometrial intraepithelial neoplasia (EIN), genetic predispositions (eg, Lynch syndrome), obesity, chronic anovulation, and polycystic ovarian syndrome all markedly increase these risks, whereas use of oral contraceptive pills or progesterone-containing intrauterine devices will decrease the risk. An EIN diagnosis carries a high risk of concomitant endometrial cancer or eventual progression to cancer in the absence of treatment. The definitive and curative treatment for EIN remains hysterectomy; however, the obesity epidemic, the potential desire for fertility-sparing treatments, the recognition of varying rates of malignant transformation, medical comorbidities, and an aging population all may factor into decisions to employ nonsurgical treatment modalities., Competing Interests: Financial Disclosure Susan C. Modesitt reports receiving payment from Elsevier for an editor-in-chief position. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Due to the increasing popularity of minipigs as pets, the frequency of presentation to the veterinarian is increasing as well. In addition to routine measures such as claw trimming, vaccination and antiparasitic treatment, diagnostics, and therapy of diseased minipigs are also common activities in the veterinary practice. In recent years, we have noticed more and more pathological changes of the female genital tract of uncastrated minipigs. There are also some case reports available in the international literature in this regard. The following case report describes the diagnostic procedures and ovariohysterectomies of 2 13-year-old female minipigs in detail. In these cases, uterine adenocarcinoma, and uterine carcinoma, respectively, combined with cystic endometrial hyperplasia (CEH) of the endometrium were diagnosed., Competing Interests: The authors declare no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The risk of undertreating occult endometrial cancer is a problem faced by gynecologists when treating endometrial hyperplasia. The objective of this study is to highlight diagnostic adjuncts to endometrial sampling techniques to improve preoperative detection of co-existing cancer. A systematic search of databases till July 2021: PubMed, ISI-Clarivate Web of Science, Scopus, and CENTRAL. A search of the related literature was also carried out. Two authors screened potential studies. Studies were included if they examined the diagnostic performance of any predictors of concurrent cancer in patients diagnosed with endometrial hyperplasia. Authors charted variables related to literature characteristics (e.g., authors, year of publication), population characteristics (e.g., preoperative diagnoses), and variables related to our research questions (e.g., postoperative diagnoses, risk predictors). After screening 591 potential studies, 28 studies were included. Studies included the data of 7409 endometrial hyperplasia patients with 2377 concurrent endometrial cancer cases (32.1%). Forty potential predictors of concurrent cancer were investigated. We examined three categories of potential predictors: clinical (22 studies), histopathologic/imaging (16 studies), and molecular (six studies) predictors. The proposed predictors, age, menopausal status, diabetes, WHO and endometrial intraepithelial neoplasia histopathologic criteria, pelvic magnetic resonance imaging, and molecular profiling are promising diagnostic adjuncts., (© 2022 International Federation of Gynecology and Obstetrics.)

Background: Atypical endometrial hyperplasia (AEH) is the precursor lesion in endometrial carcinoma, the most common gynaecological malignancy in New Zealand, with inequities in disease burden and outcome for Māori and Pacific women., Aims: In women diagnosed with AEH at two hospitals, to audit five standards of care for surgical management and time-to-treatment, and identify variation in care by ethnicity and other factors., Materials and Methods: Demographic, referral, diagnostic and treatment characteristics were collected for women with a new AEH diagnosis between 1/1/2019 and 31/12/2020. Surgical management and time-to-treatment were audited against Royal College of Obstetricians and Gynaecologists and New Zealand Ministry of Health Faster Cancer Treatment recommendations., Results: Of 124 participants, 60% were Pacific, 86% premenopausal, and 80% had obesity. For 55 women managed surgically, surgical standards of care were met. There were delays between referral, diagnosis and treatment - only 18% and 56% of women met the 62-day (referral to treatment) and 31-day (decision-to-treat to treatment) targets, respectively. Wait times were prolonged for women who had dilation and curettage (vs pipelle), magnetic resonance imaging (MRI) (vs no MRI), and surgery (vs medical management). Ethnic disparities were not identified for any standard., Discussion: Delays to treatment were found throughout women's journeys. Hospital services can streamline their clinical pathways for women referred for abnormal uterine bleeding, flagging obesity as a high suspicion for cancer indicator, increasing access to endometrial sampling in primary care and establishing 'one-stop-shop' outpatient assessment with empiric initiation of intrauterine progestogen., (© 2022 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: Dual-specificity phosphatase 6 (Dusp6) was proposed as a predictive marker of response of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) to conservative treatment. However, its predictive accuracy has never been calculated. We aimed to define it in conservatively treated AEH and EEC., Methods: All patients <45 years with AEH or EEC and conservatively treated with hysteroscopic resection + LNG-IUD insertion from 2007 to 2018 were retrospectively assessed. Dusp6 immunohistochemical expression was assessed and dichotomized as "strong" vs "weak". Relative risk (RR) for "no regression" and "recurrence" or AEH/EEC was calculated. Predictive accuracy was calculated as sensitivity, specificity, positive and negative predictive values (PPV, NPV) and area under the curve (AUC) on receiver operating characteristic curve., Results: Thirty-six women were included. Weak Dusp6 immunohistochemical expression was significantly associated with increased risk of resistance to treatment, with a RR = 16 (P = 0.0074); predictive accuracy analysis showed sensitivity = 80%, specificity = 90%, PPV = 57.1%, NPV = 96.4%, AUC = 0.85. A weak Dusp6 expression was not significantly associated with the risk of recurrence after an initial regression (RR = 0.4; P = 0.53)., Conclusion: Weak Dusp6 expression appears as a significant predictor of resistance of AEH/EEC to fertility-sparing treatment, with moderate predictive accuracy. Weak Dusp6 expression is significantly associated with resistance of atypical endometrial hyperplasia or early endometrial cancer to fertility-sparing treatment, with moderate predictive accuracy., (© 2021 International Federation of Gynecology and Obstetrics.)

Background. The interpretation of histopathological changes of endometrial hyperplasia with or without atypia can be challenging. We aim to investigate the role of specific immunohistochemical markers in the endometrial stroma to classify endometrial hyperplasia in difficult cases. Methods and Results. We retrospectively reviewed and reclassified (WHO 2014): 47 specimens with endometrial hyperplasia without atypia, 33 with atypical hyperplasia (AH), and 13 endometrioid adenocarcinomas. We performed IHC for B-catenin, E-cadherin, p16, estrogen receptors and progesterone receptors, and B-cell lymphoma 2 (BCL2). Percentage of positive stromal cells was calculated. B-catenin was equally expressed in the stroma of both hyperplasia and AH (mean 60%, 50%; P  = .17) and was absent from adenocarcinoma (0%, hyperplasia vs adenocarcinoma; P  < .0001, AH vs adenocarcinoma; P  < .0001). E-cadherin was not expressed in the stroma of any lesion, while p16 expression levels were not statistically different (hyperplasia vs AH; P  = .46, hyperplasia vs adenocarcinoma; P  = .22, AH vs adenocarcinoma; P  = .48). Estrogen and progesterone were highly identified in stromal cells of hyperplasia (80%) and diminished in AH (respectively, at 30% and 60%, hyperplasia vs AH; P  < .0001), and in adenocarcinoma (0% and 40%, respectively). Finally, BCL2 was not differentially expressed (hyperplasia vs AH; P  = .33, hyperplasia vs adenocarcinoma; P  = .17, AH vs adenocarcinoma; P  = .36). Conclusion . Estrogen and progesterone were strongly expressed in stroma exclusively of hyperplasia, while B-catenin was particularly expressed in hyperplasia and AH. Use of these markers can be useful in the differential diagnosis of hyperplasia from AH, and AH from adenocarcinoma in challenging cases.

Background: Abnormal uterine bleeding is a common cause of hospital admission in perimenopausal women. It can be the first sign of many diseases such as endometrial cancer and endometrial hyperplasia. Endometrial sampling is valuable in early diagnosis and treatment. Although hysterectomy is the gold standard in the diagnosis of endometrial pathology, it is not considered an acceptable method for diagnosis. With the principle of "see and treat, hysteroscopy seems to be the most successful method., Methods: After obtaining the necessary ethics committee approval, we obtained liquid-based cytology samples of our perimenopausal patients who frequently applied to our outpatient clinic with abnormal uterine bleeding. To conduct endometrial sampling of our patients, we used pipelle aspiration method in our 75-disease group and direct hysteroscopic sampling method in our other 75 disease group. We then compared the pre- and postoperative pathology results., Results: There was no statistically significant difference between preoperative and postoperative pathological results in both pipelle and hysteroscopic sampling groups., Conclusions: Evaluation of endometrial pathologies by hysteroscopic method and pipelle method has high sensitivity and specificity. Gynecologists may determine the method preference according to the status of the health system together with their patients.

Numerous studies show that some biomarkers are aberrantly expressed in endometrial endometrioid adenocarcinoma (EMAC) and endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) compared to endometrial benign lesions. Because of low sensitivity and/or specificity, the utility of these markers to distinguish EMAC and EAH/EIN from benign endometrial lesions is limited. YTH domain family 2 (YTHDF2) is a functional N 6 -methyladenosine (m 6 A)-specific reader protein that mainly regulates mRNA stability. Aberrant YTHDF2 expression has been reported in many cancers and plays important functions in tumorigenesis and cancer progression. However, its expression in endometrial benign and malignant lesions has not been investigated. We evaluated YTHDF2 mRNA and protein expression in EMAC and normal endometrium using the UALCAN database and validated the bioinformatic results in EMAC cells using qRT-PCR, Western blot, and immunohistochemical (IHC) staining. We found that YTHDF2 was weakly expressed in normal endometrium, benign endometrial lesions, endometrial hyperplasia without atypia, and adenomyosis. In contrast, YTHDF2 was upregulated in EAH/EIN and EMAC. These results indicate that YTHDF2 immunostaining may be a useful tool to distinguish EAH/EIN from EHWA. Finally, YTHDF2 expression can accurately assess the depth of myometrial invasion (DMI) in EMAC when EMAC coexists with adenomyosis., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Aims: Distinction between well-differentiated endometrial carcinoma (EMCA) with microglandular/mucinous features and benign endocervical microglandular hyperplasia (MGH) can be a diagnostic challenge, especially when tissue is limited. The immunostains used to distinguish endocervical and endometrial carcinoma are less useful when the differential diagnosis is MGH. Here, we investigate the utility of p63 and phosphatase and tensin homologue (PTEN) to aid accurate classification., Methods and Results: Cases obtained from our pathology archives included 25 EMCA with mucinous/microglandular features, 26 MGH and nine atypical microglandular proliferations. Cases were assessed for glandular architecture, presence of mucinous and/or eosinophilic luminal secretions, subnuclear vacuoles, foamy histiocytes, inflammation, squamous metaplasia, cytological atypia and mitotic activity. The presence and pattern of immunohistochemical staining for p63 and PTEN was recorded. Microglandular proliferations with cytological atypia, mitotic activity, foamy histiocytes and complex glandular architecture were more commonly seen in EMCA, while small glands, bland nuclei and subnuclear vacuoles were enriched in MGH. All MGH cases displayed p63-positive subcolumnar reserve cells and retained PTEN expression. Four EMCA cases showed non-specific focal p63 staining either at the surface of the tumour or in areas of squamous differentiation. p63 and PTEN immunostains accurately predicted the final diagnosis for 3 atypical microglandular proliferation cases with follow-up., Conclusions: While there are morphological characteristics that differentiate EMCA and MGH, there is frequent overlap between these entities. Nonetheless, the pattern and extent of p63 and PTEN can aid accurate classification. Consistent p63-positive subcolumnar reserve cells were seen only in MGH., (© 2022 The Authors. Histopathology published by John Wiley & Sons Ltd.)

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.

Endometrial diseases, including endometrial polyps (EP), endometrial cancer (EC) and endometrial hyperplasia (EH), are common gynecological diseases that affect women of childbearing and perimenopausal age. Clinically, biopsy or imaging methods are usually used to screen and diagnose these diseases; however, due to the invasiveness and heterogeneity of these tests, a noninvasive, convenient, objective and accurate biomarker is needed for the differential diagnosis of EP, EC or EH. In the present study, serum samples from 326 patients with endometrial diseases and 225 healthy volunteers were analyzed using nontargeted lipidomics. A combination of multivariate and univariate analyses was used to identify and qualify six, eight and seven potential biomarkers in the sera from patients with EP, EC and EH, respectively. Using a logistic regression algorithm and receiver operating characteristic (ROC) curve analysis, a biomarker panel including four specific EP biomarkers, 6-keto-PGF1α, PA(37:4), LysoPC(20:1) and PS(36:0), showed good classification and diagnostic ability in distinguishing EP from EC or EH. The biomarker panel for distinguishing EP from EC yielded an area under the curve (AUC) of 0.915, sensitivity of 100% and specificity of 72.41%, while that for distinguishing EP from EH yielded an AUC of 1.000, sensitivity of 100% and specificity of 100%. The two diagnostic models also showed good diagnostic abilities in the validation set. Therefore, this biomarker panel can be used as a rapid diagnostic method to assist in imaging examinations and provide a reference for clinicians in the identification and diagnosis of endometrial diseases., (© 2022 UICC.)

Early detection of endometrial cancer, especially its precancers, remains a critical and evolving issue in patient management and the quest to decrease mortality due to endometrial cancer. Due to many factors such as specimen fragmentation, the confounding influence of endogenous or exogenous hormones, and variable or overlapping histologic features, identification of bona fide endometrial precancers and their reliable discrimination from benign mimics remains one of the most challenging areas in diagnostic pathology. At the same time, the diagnosis of endometrial precancer, or the presence of suspicious but subdiagnostic features in an endometrial biopsy, can lead to long clinical follow-up with multiple patient visits and serial endometrial sampling, emphasizing the need for accurate diagnosis. Our understanding of endometrial precancers and their diagnosis has improved due to systematic investigations into morphologic criteria, the molecular genetics of endometrial cancer and their precursors, the validation of novel biomarkers and their use in panels, and more recent methods such digital image analysis. Although precancers for both endometrioid and non-endometrioid carcinomas will be reviewed, emphasis will be placed on the former. We review these advances and their relevance to the histopathologic diagnosis of endometrial precancers, and the recently updated 2020 World Health Organization (WHO) Classification of Female Genital Tumors., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Clinical application of exogenous hormone as a method of contraception and/or treatment of various gynecologic disorders is exceedingly common. Unfortunately, the concurrent use of these agents also complicates the interpretation of pathology specimens. Various studies have shown that morphologic changes induced by hormonal therapies are present in both non-neoplastic and neoplastic tissues within the women's reproductive tract. It is important to understand the exogenous hormone induced morphologic changes, as it helps the pathologists make the accurate diagnosis, and in turn, guide clinicians to make optimal clinical decisions. In this review, we summarize the morphologic changes in both neoplastic and non-neoplastic endometrial, cervical, and myometrial surgical specimens after hormonal therapies, particularly after progestin treatment. In the endometrium, particularly in the scenario of progestin-treated atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN), there is notoriously poor interobserver agreement and difficulty in assessing for the residual disease. We summarize current literature and propose our recommended approach in assessing these challenging endometrial biopsies, including a diagnostic algorism, the use of PAX-2, PTEN, beta-catenin immunohistochemistry panel, as well as consistency in diagnostic wording of the report. In the cervix, progestin makes dysplastic lesions appear metaplastic, thus high-grade squamous dysplastic lesions may be easily missed. Within the myometrium, lesions such as adenomyosis may show various degree of decidualization, while smooth muscle neoplasms may show apoplectic changes, and stromal lesions including endometrial stromal sarcoma may show more eosinophilic cytoplasm. All such changes may pose more or less diagnostic challenges in our daily practice. However, most are readily recognizable when we understand particular hormone related scenarios., (Copyright © 2021. Published by Elsevier Inc.)

The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the World Health Organization 2020 Classification specifies that loss of Pten, Pax2, or mismatch repair proteins are desirable diagnostic criteria. Other markers, most notably β-catenin and Arid1a, are also aberrantly expressed in some AH/EIN. However, the performance of some markers individually-and more importantly as a group-has not been rigorously explored, raising questions as to which marker(s) or combination(s) is the most effective in practice. Formalin-fixed paraffin-embedded tissue sections from AH/EIN cases (n=111) were analyzed by immunohistochemistry for 6 markers: Pax2, Pten, Mlh1, β-catenin, Arid1a, and p53. Aberrant expression was tabulated for each case and marker. An additional set of normal endometria (n=79) was also analyzed to define optimal diagnostic criteria for marker aberrance. The performance characteristics of each marker, the entire panel, and subsets thereof were quantitatively and statistically analyzed. In order of number of cases detected, the most frequently aberrant markers in AH/EIN were Pax2 (81.1% of cases), Pten (50.5%), β-catenin (47.7%), Arid1a (7.2%), Mlh1 (4.5%), and p53 (2.7%). The majority of cases showed aberrant expression of ≥2 markers. All 6 markers together identified 92.8% of cases. Arid1a, Mlh1, and p53 were robust and readily scored markers, but all cases showing aberrant expression of these 3 markers were also detected by Pax2, Pten, or β-catenin. A focused panel of only 3 markers (Pax2, Pten, and β-catenin) showed optimal performance characteristics as a diagnostic adjunct in the histopathologic diagnosis of AH/EIN. Use of this panel is practicable and robust, with at least 1 of the 3 markers being aberrant in 92.8% of AH/EIN., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Histologic assessment of response to progestogen therapy is a cornerstone of nonsurgical management of atypical hyperplasia/low-grade endometrioid carcinoma. Pathologists are required to assess whether there is ongoing preneoplastic or neoplastic change in the biopsies (often multiple) taken during therapy. There have been few studies documenting the specific histologic changes induced by therapeutic progestogens and currently there are no guidelines on terminology used in this scenario. Given the need for uniformity in reporting and the lack of guidance in the current literature, we initiated an online survey (including questions, categories of reporting, and scanned slides for assessment) which was sent to all members of British Association of Gynaecological Pathologists (BAGP) and the International Society of Gynecological Pathologists (ISGyP) with the aim to assess the variability among pathologists in reporting these specimens and to come up with a consensus-based terminology for reporting of endometrial biopsies from women on progestogen therapy for endometrial atypical hyperplasia/endometrioid carcinoma. In total, 95 pathologists participated in this survey. This manuscript elaborates on the results of the survey with recommendations aimed at promoting uniform terminology in reporting these biopsies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

Endometrial hyperplasia is defined as a common clinical disorder caused by the increased levels of estrogens with low levels of progesterone; therefore, this hormonal imbalance leads to an increase in the proliferation rate of the endometrial cells. Endometrial carcinoma is one of the most important malignancies affecting women all over the world "accounting for 37.7% of all other disorders affecting the female reproductive system". The expression of the Ki-67 protein is related to the proliferative behavior of malignant tumor cell populations of their own, allowing it to be used as a marker of tumor aggressiveness. The present study was conducted to examine the expression of the proliferation marker, Ki-67 in various endometrial lesions. Ki-67 expression was evaluated in 60 endometrial samples that resulted as either endometrial curetting or hysterectomy specimens, diagnosed with simple hyperplasia (n=10), complex hyperplasia (n=20), atypical hyperplasia (n=6), and endometrial carcinoma (n=24). In patients with endometrial carcinoma, there was an increased expression of Ki-67, compared to proliferative endometrium and simple hyperplasia ( P -value=0.0001). There was no such discrepancy between atypical hyperplasia and endometrial carcinoma cases. The expression of Ki-67 showed a positive association with the degree of endometrial cancer ( P -value=0.0013), however, not with the age of the patients ( P -value&gt;0.05). There is a wide range of variations in the proliferation rate within the development of different endometrial lesions, including benign and malignant lesions. Our findings may be of value in differential diagnosis and prognosis of endometrial hyperplasia and endometrial carcinoma.

In the United Kingdom, endometrial biopsy reports traditionally consist of a morphologic description followed by a conclusion. Recently published consensus guidelines for reporting benign endometrial biopsies advocate the use of standardized terminology. In this project we aimed to assess the acceptability and benefits of this simplified "diagnosis only" format for reporting non-neoplastic endometrial biopsies. Two consultants reported consecutive endometrial biopsies using 1 of 3 possible formats: (i) diagnosis only, (ii) diagnosis plus an accompanying comment, and (iii) the traditional descriptive format. Service users were asked to provide feedback on this approach via an anonymized online survey. The reproducibility of this system was assessed on a set of 53 endometrial biopsies among consultants and senior histopathology trainees. Of 370 consecutive benign endometrial biopsies, 245 (66%) were reported as diagnosis only, 101 (27%) as diagnosis plus a brief comment, and 24 (7%) as diagnosis following a morphologic description. Of the 43 survey respondents (28 gynecologists, 11 pathologists, and 4 clinical nurse specialists), 40 (93%) preferred a diagnosis only, with 3 (7%) being against/uncertain about a diagnosis only report. Among 3 histopathology consultants and 4 senior trainees there was majority agreement on the reporting format in 53/53 (100%) and 52/53 (98%) biopsies. In summary, we found that reporting benign specimens within standardized, well-understood diagnostic categories is an acceptable alternative to traditional descriptive reporting, with the latter reserved for the minority of cases that do not fit into specific categories. This revised approach has the potential to improve reporting uniformity and reproducibility., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

Introduction: In Japan, endometrial cytology is widely performed to evaluate the status of the endometrium in women with suspected endometrial cancer. A new classification system for endometrial cytology has recently been used: the Yokohama system, based on a descriptive reporting format. This study aimed to clarify the triage for patients with atypical endometrial cells of undetermined significance (ATEC-US) when followed by negative endometrial cytology., Methods: We enrolled patients diagnosed with ATEC-US at the Cancer Institute Hospital between January 2016 and December 2017, based on the following inclusion criteria: (1) ATEC-US diagnosed by office endometrial cytology, with or without office endometrial biopsy; (2) follow-up endometrial cytology was performed 3-6 months after initial sampling, with a negative result for malignancy; and (3) no prior history of conservative treatment with progestin for endometrial cancer or atypical endometrial hyperplasia (ATEC-A). Among eligible patients, we analyzed those later diagnosed by endometrial biopsy with ATEC-A or carcinoma., Results: Among 187 patients, 65 met the inclusion criteria. Forty-two patients (64.6%) were observed for more than 24 months. Two patients (3.1%) developed ATEC-A during a median observation time of 26.5 months; the times to diagnosis were 32 months and 22 months., Discussion/conclusion: No patient developed ATEC-A or worse within 1 year. For patients with ATEC-US, if negative cytology is obtained at the next examination, a close follow-up is not necessary., (© 2022 S. Karger AG, Basel.)

This study aimed to investigate the differences in oxidative stress index (OSI) and kisspeptin levels in clinically asymptomatic dogs with cystic endometrial hyperplasia (CEH) compared to healthy and pregnant dogs, and to determine the usability of the obtained results in the diagnosis of asymptomatic CEH. The study comprised three groups; a healthy (n = 8), a pregnant (n = 10) and a CEH (n = 10). All dogs in the three groups were included in the study at the 30 ± 3th day after estrus, and blood samples were collected for analysis of kisspeptin, total antioxidant status (TAS), total oxidant status (TOS), progesterone (P4), estradiol (E2) and some biochemical parameters (TSH; thyroid stimulating hormone, ALT; alanine aminotransferase, AST; aspartate aminotransferase, ALP; alkaline phosphatase, LDH; lactate dehydrogenase, CRE; creatine and BUN; blood urea nitrogen). In addition, OSI value was calculated. P4 and ALT and BUN levels were significantly lower and higher in CEH group than the pregnant group, respectively (p < .05). While kisspeptin and TAS levels were significantly lower in CEH group compared to the healthy and pregnant groups (p < .01), OSI level increased dramatically. In conclusion, it was confirmed that CEH clearly affected kisspeptin and OSI levels, and it is thought that these parameters may be an alternative diagnostic tool for the detection of CEH after further studies., (© 2021 Wiley-VCH GmbH.)

Background: Endometrial thickness (ET) is closely related to many gynecological symptoms. The measurement of ET is also an important tool for evaluating adverse symptoms such as bleeding in postmenopausal women. However, the significance of ET in asymptomatic women is still unclear. The purpose of this study was to determine the correlation between ET and the incidence of endometrial lesions in asymptomatic women after menopause, and to statistically analyze the correlation with a 5 mm cutoff value., Methods: A systematic literature search was conducted in May 2021 to screen out articles that reported that ET measurement was used to diagnose endometrial carcinoma (EC), endometrial hyperplasia (EH), and endometrial polyps (EP) in asymptomatic postmenopausal women who did not use hormone replacement therapy (HRT). The endometrial membrane was set at 5 mm as the cut-off, and using 5 mm as the cut-off of the ET, the relationship between the thickness of the endometrium and the prevalence of EC, EH, and EP was evaluated. Relative risk (RR) and standardized mean difference (SMD) were extrapolated with 95% confidence interval (CI)., Results: After screening, 9 studies reported a total of 3,620 cases of asymptomatic postmenopausal women whose ET was measured. Among them, there were 1,758 cases of ET <5 mm, the probability of EC, EH, and EP were 0.284% (5/1,758), 0.398% (7/1,758), and 0.626% (11/1,758), respectively. In another 1,862 cases with ET ≥5 mm, the probabilities of EC, EH, and EP were 1.128% (21/1,862), 1.128% (21/1,862), and 1.557% (29/1,862), respectively. The results showed that ET can be used as a risk factor for predicting EC and other pathological changes., Discussion: The results of this meta-analysis show that when the ET is greater than 5 mm, the incidence of EC, EH, and EP increases significantly. It is reasonable to use ET as a screening test for EC and EH in asymptomatic postmenopausal women.

Objective: The weak estrogenic-like effect of selective estrogen receptor modulator (SERM) may lead to series of endometrial lesions, including proliferation, hyperplasia, polyp formation, and even endometrial cancer. This study aimed to explore the effectiveness of different endometrial thickness in diagnosis of endometrial hyperplasia during SERM therapy in premenopausal patients., Methods: The clinical data of 115 patients receiving hysteroscopic endometrial biopsy during SERM therapy in Peking Union Medical College Hospital, China from January 2010 to December 2018 were retrospectively analyzed., Results: Average age at the beginning of SERM therapy was 43.4 ± 5.7 years old. Mean duration time of SERM therapy was 31.0 ± 22.1 months. The mean endometrial thickness was 14.3 ± 6.1 mm. 4 cases of atypical endometrial hyperplasia (3.5 %), and 4 cases of endometrial hyperplasia without atypia (3.5 %) were detected. Endometrial thickness was higher in endometrial hyperplasia patients than in no endometrial hyperplasia patients (18.8 vs 13.9 mm, p = 0.029). Endometrial thickness in 8 out of 8 endometrial hyperplasia patients and 38 out of 107 no endometrial hyperplasia patients were ≥ 15 mm (p = 0.002). The negative predictive value in the diagnosis of endometrial hyperplasia during SERM therapy in premenopausal patients was 100 % when endometrial thickness < 15 mm chosen as cutoff value., Conclusion: Endometrial hyperplasia was less likely to occur in premenopausal patients during SERM therapy when endometrial thickness < 15 mm., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background and Objectives : Endometrial hyperplasia (EH) is a precursor lesion to endometrial cancer (EC), and when cellular atypia is present, in 40% of cases, they are diagnosed with EC on hysterectomy. Usually, EH is clinically manifested by uterine bleeding. In patients with oral anticoagulant therapy (OAT), the uterus is the second most common source of bleeding. The aim of the study was to show that uterine bleeding in postmenopausal patients undergoing OAT may reveal precancerous endometrial lesions with atypia, or neoplastic lesions in patients with an initial diagnosis of endometrial hyperplasia without atypia (non-atypical endometrial hyperplasia, NAEH) on dilation and curettage (D&C). We will be able to estimate the risk of a postmenopausal female patient with uterine bleeding during an OAT to have a precancerous endometrial lesion. Materials and Methods : The subjects of the study were 173 female patients with uterine bleeding, who have had total hysterectomy with bilateral salpingoovarectomy, of whom 99 underwent an OAT. There were 101 female patients initially diagnosed with NAEH, of which 60 did not have anticoagulant treatment (mean age 57.36 ± 6.51) and 41 had anticoagulant treatment (mean age 60.39 ± 7.35) ( p = 0.006). From the pathology diagnosis moment, the surgery was performed at 42.09 ± 14.54 days in patients without OAT and after 35.39 ± 11.29 days in those who received such treatment ( p = 0.724). Results : Initial diagnosis of NAEH established at D&C was changed at the final diagnosis after hysterectomy in EH with cellular atypia (atypical endometrial hyperplasia AEH) or EC in 18.18% of patients without OAT, and in 40.54% of patients who received this treatment. Conclusions : Based on a logistic regression model, it is estimated that female patients with an initial histopathological diagnosis of NAEH and who underwent OAT have, on average, 4.85 times greater odds (OR = 4.85, 95% CI 1.79-14.06) than the others of being identified postoperatively with more advanced lesions.

A subtle 'burrowing' pattern of cervical stromal involvement by low-grade endometrioid adenocarcinoma of the uterine corpus is described in the literature. We report a small case series in which this pattern of cervical stromal involvement, warranting a diagnosis of endometrioid adenocarcinoma in the cervix, occurred in association with sometimes subtle endometrioid proliferations within the endometrium which fall short of the criteria for endometrioid adenocarcinoma and are in keeping with atypical hyperplasia or hyperplasia without atypia. In reporting this phenomenon, which has not been described previously, we highlight the importance of immunohistochemistry in the differential diagnosis, particularly in the exclusion of primary cervical glandular lesions, including those of mesonephric type. We discuss the differential with primary endometrioid adenocarcinoma (including minimal deviation type) of the cervix and other lesions and stress the importance of sampling the endometrium and lower uterine segment in their entirety in order to exclude an atypical hyperplasia or an adenocarcinoma in these locations. Although the pathogenesis of the cervical lesion we report is controversial, we believe that it is most likely a result of spread from the endometrium and results in the unusual occurrence of the malignant nature of the lesion being only apparent in the secondary rather than the primary lesion. We provide recommendations for reporting such cases and recommend designating them as stage II endometrial carcinoma, although the prognostic and management implications of such cases will only be clear once further cases with follow-up are reported., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Objectives: to compare the accuracy of preoperative and postoperative endometrial sampling obtained by dilatation and curettage (D&C), Pipelle and hysteroscopy to diagnose endometrial malignancies and to evaluate the adequacy of surgical treatment for these patients., Study Design: This retrospective record-based study was conducted at Gynecology Oncology Unit, Ain Shams University Maternity Hospital, Cairo, Egypt. Records of patients with an initial preoperative or a final postoperative pathological diagnosis of endometrial hyperplasia or endometrial malignancies were retrieved over a six year period from January 2013 until March 2019. The preoperative biopsy methods, results, postoperative pathology diagnosis and treatment received were recorded and analyzed., Results: Records of 395 patients were retrieved. Rates of agreement between initial and postoperative pathology for endometrial hyperplasia (with and without atypia) were 10% by D&C, 7.8% by Pipelle and zero % by hysteroscopy; for endometrioid adenocarcinoma grade 1, they were 40.7% by D&C, 40.6% by Pipelle and 20% by hysteroscopy; for endometrioid adenocarcinoma grades 2 and 3, they were 83.7% and 84.6% by D&C, 97% and 60% by Pipelle, and 100% by hysteroscopy, respectively. For type II endometrial cancer and endometrial stromal sarcoma, agreement rates were 100% by all biopsy methods. Out of 13 cases diagnosed with atrophic endometrium preoperatively, 11 cases were diagnosed as endometrial stromal sarcoma. Comparing accuracy of the three biopsy methods, D&C had highest sensitivity of 61.9%; hysteroscopy showed 100% specificity, while Pipelle was the least accurate method. Finally, 61.4% of the patients received adequate surgical treatment., Conclusion: There were excellent concordance rates between initial biopsy and postoperative pathology in diagnosis of high grade endometrioid and other endometrial malignancies compared to endometrial hyperplasia and low grade endometrioid adenocarcinoma. Patients diagnosed initially with atrophic endometrium or hyperplasia warranted more surveillance before their surgical treatment. It is crucial to develop protocols for increasing accuracy of endometrial sampling such as performing molecular studies for preoperative pathology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)