Adenomyosis is associated with proliferative endometrial disorders.

The prevalence of endometrial polyps (EPs) in the general female population is about 24%. Abnormal uterine bleeding is frequently the presenting symptom of EPs. The aim of this study was to determine the prevalence and characteristics of EPs in patients with abnormal uterine bleeding. The prevalence and characteristics of EPs were investigated in 961 patients with abnormal uterine bleeding who underwent dilatation and curettage between January and December 2006. Regarding histopathological features of EPs (presence of atypical hyperplasia or endometrial carcinoma), patients were divided into two groups: group A--patients who had EPs and EPs with hyperplasia without atypia (n = 204) and group B--patients who had EPs with atypical hyperplasia and EPs with carcinoma (n = 7). In 211 (21.94%) patients EPs were found with abnormal uterine bleeding. Histopathologically, there were 175 (82.94%) EPs, 29 (13.74%) EPs with hyperplasia without atypia, 5 (2.37%) EPs with atypical hyperplasia, and 2 (0.95%) EPs with endometrial carcinoma. Contrary to the patients with EPs and EPs with hyperplasia without atypia (group A), patients who had EPs with atypical hyperplasia and EPs with carcinoma (group B) were older (p < 0.05), and more commonly postmenopausal (p < 0.05) and with hypertension (p < 0.05), all of statistical significance. The prevalence of endometrial polyps in patients with abnormal uterine bleeding according to our data was 21.95%. Atypical hyperplasia and endometrial carcinoma were rarely confined to a polyp. Older age, postmenopausal period and hypertension may increase the risk of premalignant and malignant changes in endometrial polyps.

The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim was to compare our findings with published data on women with AUB. This was a prospective observational study of women presenting at one of seven centers specialized in gynecological ultrasonography, from 2011 until 2018, for indications unrelated to AUB. All patients underwent transvaginal ultrasound using the IETA examination and measurement techniques. Ultrasonography was performed as part of routine gynecological examination or follow-up of non-endometrial pathology, or as part of the work-up before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using the IETA terminology. Endometrial sampling was performed after the ultrasound scan. The histological endpoints were endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma, endometrial intraepithelial neoplasia (EIN), endometrial cancer (EC) and insufficient tissue. The findings in our cohort of women without AUB were compared with those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology. In this study (IETA3), we included 1745 women without AUB who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). Of these, 858 (49.2%) women were premenopausal and 887 (50.8%) were postmenopausal. Histology showed the presence of EC and/or EIN in 29 (1.7%) women, endometrial polyps in 1028 (58.9%), intracavitary myomas in 66 (3.8%), proliferative or secretory changes or hyperplasia without atypia in 144 (8.3%), endometrial atrophy in 265 (15.2%) and insufficient tissue in five (0.3%). Most cases of EC or EIN (25/29 (86.2%)) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2 mm (95% CI, 8.9-13.6 mm), being on average 2.4 mm (95% CI, 0.3-4.6 mm) thicker than their benign counterparts. Women with malignant endometrial pathology manifested more frequently non-uniform echogenicity (22/29 (75.9%)) than did those with benign endometrial pathology (929/1716 (54.1%)) (difference, +21.8% (95% CI, +4.2% to +39.2%)). Moderate to abundant vascularization (color score 3-4) was seen in 31.0% (9/29) of cases with EC or EIN compared with 12.8% (220/1716) of those with a benign outcome (difference, +18.2% (95% CI, -0.5% to +36.9%)). Multiple multifocal vessels were recorded in 24.1% (7/29) women with EC or EIN vs 4.0% (68/1716) of those with a benign outcome (difference, +20.2% (95% CI, +4.6% to +35.7%)). A regular endometrial-myometrial junction was seen less frequently in women with EC or EIN (19/29 (65.5%)) vs those with a benign outcome (1412/1716 (82.3%)) (difference, -16.8% (95% CI, -34.2% to +0.6%)). In women with endometrial polyps without AUB, a single dominant vessel was the most frequent vascular pattern (666/1028 (64.8%)). In women with EC, both in those with and those without AUB, the endometrium usually manifested heterogeneous echogenicity, but the endometrium was on average 8.6 mm (95% CI, 5.2-12.0 mm) thinner and less intensely vascularized (color score 3-4: difference, -26.8% (95% CI, -52.2% to -1.3%)) in women without compared to those with AUB. In both pre- and postmenopausal women, asymptomatic endometrial polyps were associated with a thinner endometrium, and they manifested more frequently a bright edge, a regular endometrial-myometrial junction and a single dominant vessel than did polyps in symptomatic women, and they were less intensely vascularized. We describe the typical ultrasound features of EC, polyps and other intracavitary histologies using IETA terminology in women without AUB. Our findings suggest that the presence of asymptomatic polyps or endometrial malignancy may be accompanied by thinner and less intensely vascularized endometria than their symptomatic counterparts. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms

Visually Directed Hysteroscopic Biopsy in the Evaluation of Abnormal Uterine Bleeding and Postmenopausal Bleeding: A Joint Society Practice Guideline.

The goal of this study was to evaluate safety after same-day discharge following minimally invasive hysterectomy for endometrial cancer and endometrial intraepithelial neoplasia in patients with and without morbid obesity (body mass index 40 kg/m2). Our secondary objective was to identify barriers to same-day discharge. Retrospective cohort study of patients undergoing minimally invasive hysterectomy for endometrial cancer and endometrial intraepithelial neoplasia from January 2016 to May 2022. Complications within 60 days of surgery were reviewed. Of those undergoing same-day discharge, we compared the 60-day complication rates between patients with and without morbid obesity. We compared demographic and clinical characteristics associated with same-day discharge. 1449 patients underwent minimally invasive hysterectomy during the study period, and 1029 (71%) were discharged the same day. 55 patients (5.3%) experienced a complication after same-day discharge. There was no difference in the frequency of complications between patients with (5.1%) and without (5.4%) morbid obesity (p = .86). Factors associated with not being discharged the same day included older age, higher body mass index, and several co-morbidities (all p < .05). Patients with morbid obesity were twice as likely to stay overnight after controlling for age, comorbidities, and surgical indication (adjusted OR 2.1, 95% CI 1.58 to 2.80). Despite concerns about the safety of same-day discharge in patients with morbid obesity, 60-day complication rates are not significantly different for this group compared to patients with a body mass index <40 kg/m2. Patients with morbid obesity were less likely to be discharged the same day after controlling for confounders.

To assess the ability of the International Endometrial Tumor Analysis (IETA)-1 polynomial regression model to estimate the risk of endometrial cancer(EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding. This was a retrospective study, in which we validated the IETA-1 model on the IETA-3 study cohort (n = 1745). The IETA-3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow-up of non-endometrial pathology, in the work-up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow-up of at least 1 year if endometrial sampling was not performed. The IETA-1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3)proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non-uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver-operating-characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio). The median age of the women in the IETA-3 cohort was 51 (range, 20-85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA-1 model had an AUC of 0.81 (95% CI, 0.73-0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32-0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62-0.73) (n = 1532). The IETA-1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95-0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75-0.91), compared with 0.62 (95% CI, 0.52-0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08-0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA-1 model gave an AUC of 0.81 (95% CI, 0.71-0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60-0.81) (difference in AUC, 0.11; 95% CI, 0.01-0.20). The IETA-1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Endometrial Biopsy: American College of Nurse-Midwives.

Guideline No. 390-Classification and Management of Endometrial Hyperplasia.

Molecular pathogenesis of endometrial intraepithelial neoplasia: Precursor to endometrial carcinoma

Our study is to determine the presence of endometrial intraepithelial neoplasia (EIN) in endometrial biopsy specimens classified by the 1994 World Health Organization (WHO) criteria for endometrial hyperplasia. Endometrial biopsy specimens that were stained with hematoxylin and eosin (HE) were examined and categorized by the WHO 1994 criteria and for the presence of EIN as defined by the International Endometrial Collaborative Group. β-catenin expression was examined by immunohistochemistry. A total of 474 cases of HE stained endometrial biopsy tissues were reviewed. There were 379 cases of simple endometrial hyperplasia, 16 with simple atypical endometrial hyperplasia, 48 with complex endometrial hyperplasia, and 31 with complex atypical endometrial hyperplasia. Among the 474 endometrial hyperplasia cases, there were 46 (9.7%) that were classified as EIN. Of these 46 cases, 11(2.9%) were classified as simple endometrial hyperplasia, 1 (6.3%) as simple atypical endometrial hyperplasia, 6 (12.5%) as complex endometrial hyperplasia, and 28 (90.3%) as complex atypical endometrial hyperplasia. EIN was associated with a higher rate of β-catenin positivity than endometrium classified as benign hyperplasia (72% vs. 22.5%, respectively, P < 0.001), but a lower rate than endometrial adenocarcinoma (72% vs. 96.2%, respectively, P < 0.001). In benign endometrial hyperplasia, high β-catenin expression was noted in the cell membranes, whereas in EIN and endometrial adenocarcinoma high expression was noted in the cytoplasm. In conclusion, EIN is more accurate than the WHO classification for the diagnosis of precancerous lesions of the endometrium.

Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia

Detection of endometrial intraepithelial neoplasia (EIN) in postmenopausal endometrium

Can malignant potential of endometrial polyps be determined by incorporating the endometrial intraepithelial neoplasia (EIN) classification?

Endometrial intraepithelial neoplasia (EIN), also known as atypical endometrial hyperplasia (AEH), is a precursor lesion of endometrial carcinoma (EC). In endometrial cancer patients, lymph node assessment with biopsy during hysterectomy is part of surgical staging. However, routine lymph node assessment for EIN is inconsistently utilized. This study aims to investigate the surgical management of EIN in the military to inform best-practice guidelines tailored for the Military Health System to avoid delays in care, manage cost, ensure military readiness and optimize clinical outcome. We performed a retrospective chart review of patients with EIN treated at 2 military treatment facilities over a 10-year period between July 1, 2013 and July 1, 2023. Pathology reports were queried to identify patients with a preoperative diagnosis of EIN. Patients not surgically managed were excluded. Statistical analysis was performed using chi-squared test and Wilcoxon rank-sum test. Independent associations were investigated using logistic regression modeling. There were 95 evaluable patients with an EIN diagnosis, including 43 (45.3%) patients upstaged to EC based on final pathology (95% CI: 35.0-55.8). Older patients diagnosed with EIN ≥65 years old and those with endometrial thickness ≥15 mm exhibited the highest risk for upstaging EIN to an EC diagnosis. Of the 50 patients who underwent lymph node assessment, none had positive lymph nodes. Patients diagnosed with EIN via hysteroscopy vs. an endometrial biopsy had the lowest risk of being upstaged to EC. Upstaging from EIN to EC occurred in 45.3% of the 95 patients emphasizing the value of performing surgicopathologic staging in this setting. In contrast, none of the 50 EIN patients who underwent lymph node resection had positive lymph nodes indicating morbidity risk with low likelihood of clinical benefit. We identified risk factors for upstaging to EC, including age ≥65 years and endometrial thickness ≥15 mm, and confirmed the diagnostic superiority of hysteroscopy. These findings have informed clinical practice guideline recommendations for the surgical management of EIN in the Military Health System.

Histopathologic diagnosis of endometrial biopsies is used to estimate the risk of progression to carcinoma and guide clinical management. Problems with the widely used World Health Organization (WHO) system for classifying endometrial hyperplasia (EH) have prompted the development of an alternative system based on endometrial intraepithelial neoplasia (EIN). The authors estimated progression risk associated with EIN among endometrial biopsies in a nested case-control study of EH progression. Index biopsies with original community pathology diagnoses of disordered proliferative endometrium (DPEM) or EH that were independently confirmed by a panel of pathologists were independently reviewed and assigned EIN classifications (inadequate, benign, EIN, or cancer) by a second panel of pathologists. Cases (N = 138) progressed to carcinoma at least 1 year (median, 6 years) after their index biopsy. Controls (N = 241) also had EH, did not progress to carcinoma, and were individually matched to cases based on age at EH, date of EH, and length of follow-up. By using conditional logistic regression, the authors estimated relative risks (RRs) with 95% confidence intervals (95% CIs) for progression to carcinoma for EIN versus benign. In the EIN system, 71 (52.6%) cases and 159 (66.8%) controls were classified as benign and 42 (31.1%) cases and 65 (27.3%) controls were classified as EIN. The RR for EIN versus benign was 7.76 (95% CI, 3.36-17.91). In the WHO system, the RR for atypical hyperplasia (AH) versus DPEM, simple hyperplasia, or complex hyperplasia was 9.19 (95% CI, 3.87-21.83). Among women observed for at least 1 year after receiving a biopsy-based EH diagnosis, EIN and AH were both found to have similarly increased risks of progression to carcinoma.