Diagnosis Of Endometrial Intraepithelial Neoplasia Research Articles

Hysterectomy with sentinel lymph node dissection in the setting of preoperative endometrial intraepithelial neoplasia and an endometrial stripe ≥20 mm: a cost-effectiveness analysis

ObjectivesRoutine lymph node assessment in patients with endometrial intraepithelial neoplasia is institution and surgeon-dependent without clear guidelines. We sought to determine if routine sentinel lymph node (SLN) dissection at the...

Association of Body Mass Index With Early Age at Diagnosis of Endometrial Intraepithelial Neoplasia

(Abstracted from Gynecol Oncol 2023;175:15–19) The development of endometrial intraepithelial neoplasia (EIN), a precursor lesion to endometrioid endometrial cancer, is related to prolonged and unopposed excess estrogen stimulation in the endometrium. The 2 conditions are frequently diagnosed concurrently.

Age as a Predictor of Time to Response for Patients Undergoing Medical Management of Endometrial Cancer

Objective: To explore the pathologic response rate to primary progesterone treatment in patients with Endometrial Intraepithelial Neoplasia (EIN) and early-stage endometrioid-type Endometrial Adenocarcinoma (EAC). Methods: Retrospective chart data were collected for patients with either EIN or EAC receiving primary progesterone treatment between 2015 and 2022. The presence of complete or partial response, time to response, and other demographic and treatment factors were recorded to determine independent predictors of response to progestin treatment. Results: In total, 112 women who were diagnosed with EIN or EAC were treated with upfront progestin therapy, of whom 79 had sufficient follow-up to assess response. Fifty patients (63%) responded, of whom 10 (20%) ultimately relapsed. Response was more robust among patients with EIN (79%, n = 33) compared with patients who had cancer (46%, n = 17). The median time to respond was 5.8 months overall. Diagnosis of EIN, younger age at diagnosis, and any pathologic evidence of progesterone effect were all predictors of treatment response. Younger patients had a significantly shorter time to partial or complete response with a median time to response of 5.9 months in patients ≤ 45 and 13.8 months in patients > 45. Conclusion: Our study demonstrated a lower overall response rate (63%) than reported in previous studies, especially for patients with cancer (46%). Younger patients had a significantly shorter time to respond than older patients. Pathologic progesterone effect observed at any time during treatment was a significant predictor of treatment response regardless of diagnosis and could serve as an early predictor of response to therapy.

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

ObjectiveElevated 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. MethodsWe 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. ResultsWe 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. ConclusionsIn 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.

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

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

Incidence of endometrial carcinoma in patients with endometrial intraepithelial neoplasia versus atypical endometrial polyp

ObjectiveOur study’s primary aim was to compare the incidence of endometrial carcinoma in patients with a presurgical diagnosis of endometrial intraepithelial neoplasia confined to the endometrium (EIN-E) versus endometrial intraepithelial...

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

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

Endometrial Hyperplasia.

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.

7868 The Incidence of Endometrial Carcinoma in Patients with Atypical Endometrial Hyperplasia Versus Atypical Endometrial Polyp

<h3>Study Objective</h3> To compare the incidence of endometrial carcinoma following hysterectomy in patients with presurgical diagnosis of EIN (endometrial intraepithelial neoplasia) of the endometrium versus EIN confined to endometrial polyp. <h3>Design</h3> Retrospective cohort study. <h3>Setting</h3> Tertiary university-affiliated hospital. <h3>Patients or Participants</h3> Eighty-eight women included in the study, of those, 50 women were diagnosed with EIN confined to a polyp (endometrial polyp group) and 38 women had endometrial EIN following endometrial biopsy (non-polypoid group). <h3>Interventions</h3> Medical records of women who underwent staging surgery for endometrial EIN or EIN confined to a polyp between 2014 and 2020 were reviewed. <h3>Measurements and Main Results</h3> The mean age at diagnosis was 60.2 ± 9.9 years in the endometrial polyp group as compared to 61.7 ± 12 years in the non-polypoid group (p=0.5). Eighty-nine percent of the women in the non-polypoid group presented with abnormal uterine bleeding (post/perimenopausal) whereas 46% of the women in the endometrial polyp group were asymptomatic (p=0.001). Pathology results following hysterectomy revealed concurrent endometrial carcinoma in 26% of women in the endometrial polyp group compared to 47% of women in the non-polypoid group (p=0.001). Eighty-four percent of cancers were grade-1 in the endometrial polyp group compared to 50% in the non-polypoid group(p=0.048). Only one patient in the non-polypoid group (5.6%) had lymph node involvement. <h3>Conclusion</h3> Concurrent cancer is less frequent with atypical endometrial polyp as compared to atypical endometrial hyperplasia. Still, the high incidence of endometrial carcinoma in both groups supports the current advice to perform hysterectomy and bilateral salpingo-oophorectomy for peri and post-menopausal women. Our data does not support performing sentinel lymph node dissection for EIN.

Early age at diagnosis of endometrial intraepithelial neoplasia and association with body mass index and other clinical factors (389)

Early age at diagnosis of endometrial intraepithelial neoplasia and association with body mass index and other clinical factors (389)

Endometrial stripe thickness: a preoperative marker to identify patients with endometrial intraepithelial neoplasia who may benefit from sentinel lymph node mapping and biopsy

ObjectivesThe goal of our study was to identify preoperative factors in patients with endometrial intraepithelial neoplasia that are associated with concurrent endometrial cancer to select patients who may benefit from...

Аномальные маточные кровотечения. Анализ результатов ультрасонографии по системе IETA

Objective. To study the features of the uterine cavity echo and the prognostic value of ultrasound signs of endometrial pathology in patients with abnormal uterine bleeding based on the terminology and recommendations of IETA. Patients and methods. The study included 196 women with abnormal uterine bleeding in the late reproductive period and premenopause and 54 patients with postmenopausal bleeding and/or ultrasound signs of endometrial pathology. All ultrasonography results were interpreted according to the IETA classification and terminology and were subsequently verified by histological examination. Results. In patients with endometrial intraepithelial neoplasia (EIN), the thickness of the endometrium was in the range of 9–19 mm and, according to this criterion, did not differ from endometrial hyperplasia without atypia. Only in some patients with EIN, the endometrial-myometrial junction was characterized by unevenness (16.7% in the reproductive period/premenopause and 22.2% in postmenopause). Compared with endometrial hyperplasia, EIN was dominated by uneven, heterogeneous echogenicity without cystic inclusions with a color scale 2–3 points. In endometrial cancer, the endometrial-myometrial junction was interrupted in 77.8–100% of cases, and the color score reached 4 points. Conclusion. Modern possibilities of ultrasonography allow improving the principles of early diagnosis of EIN and preinvasive endometrial carcinoma. Key words: ultrasound, IETA, endometrial cancer, endometrial intraepithelial neoplasia

Patients with endometrial intraepithelial neoplasia do not need routine lymph node sampling

<h3>Objectives:</h3> The use of sentinel lymph node (SLN) protocols in endometrial cancer has emerged as a standard of care for staging invasive endometrial cancers, while in endometrial intraepithelial neoplasia (EIN), their role is not well defined. We sought to identify preoperative characteristics that may predict the presence of concurrent endometrial cancer at the time of hysterectomy in order to identify who may benefit from nodal assessment at the time of hysterectomy. <h3>Methods:</h3> Using billing codes for EIN or complex endometrial hyperplasia, we identified all patients with a pre-operative diagnosis of EIN from 2010 through 2020. Those who subsequently underwent surgical management (i.e. minimally invasive or open hysterectomy±adnexal surgery and±lymph node dissection) were included in this analysis. Patients were excluded if they opted for medical management or if subsequent pathology review indicated an alternative preoperative diagnosis. Data was abstracted from medical records. Data are presented as n (%) and median (interquartile range); we used modified Poisson regression to calculate risk ratios (RR) and 95% confidence intervals (CI). <h3>Results:</h3> Of the 492 patients with a diagnosis of EIN, 378 patients underwent hysterectomy. Surgical pathology revealed 275 (73%) had EIN or no residual disease, and 103 (27%) had endometrial cancer. Age (p=0.003), race (p=0.02), and concurrent diagnosis of hypertension (p=0.02) were significantly associated with the presence of endometrial cancer on final pathology. Notably, the median preoperative endometrial thickness was significantly greater in the endometrial cancer group [14mm (10-19)] than in the EIN group [11mm (8-16); p=0.002]. When dichotomizing endometrial thickness, patients with a preoperative endometrial stripe ≥15mm were 1.77 times more likely to have endometrial cancer than those with an endometrial stripe <15mm (95% CI: 1.24-2.54). The corresponding RR for those with a preoperative endometrial stripe ≥20mm was 1.97 (95% CI: 1.34-2.90). A total of 5 patients (1.3%) were diagnosed with stage IB (>50% myometrial invasion) disease, 30 (8%) patients had tumors > 2cm, 1 (0.3%) had grade 3 histology, and 3 (0.8%) had lymphovascular space invasion (LVSI). In this cohort, only 10 (3%) of patients underwent lymph node evaluation at time of surgery based on intra-operative factors, including frozen section. <h3>Conclusions:</h3> In a large cohort of patients with a preoperative diagnosis of EIN, 27% were found to have invasive carcinoma, but very few patients had pathologic features portending increased risk of nodal metastasis. Even fewer met intraoperative criteria for lymph node evaluation. Increasing endometrial thickness may be a useful pre-operative marker to identify who is at higher risk for concurrent endometrial cancer and could be considered a criterion for use of a sentinel lymph node algorithm in patients with EIN. Prospective studies are warranted.

Is universal sentinel lymph node sampling indicated in endometrial intraepithelial neoplasia (EIN)?

Objective: The aim of this study was to identify the frequency for which a preoperative diagnosis of endometrial intraepithelial neoplasia (EIN) is upstaged to cancer at hysterectomy and sentinel lymph node (SLN) sampling would be indicated.

Interobserver variability in endometrial intraepithelial neoplasia

Introduction: Endometrial hyperplasia is a common disease and precursor of endometrial carcinoma. WHO hyperplasia classification system which is unreliable has confusing and overlapping criteria which prompted the development of a system based on Endometrial Intraepithelial Neoplasia (EIN). Objectives: (1) To review Endometrial Intraepithelial Neoplasia. (2) To reclassify WHO classification of endometrial hyperplasia into EIN and non-EIN category and to study the interobserver variability. Materials and Methods: In 102 patients diagnosed as WHO hyperplasia reclassification was done by 2 separate pathologists using EIN criteria 1) Glandular crowding. 2) Cytologic demarcation. 3) Size of the lesion should exceed 1mm. 4) Exclude benign processes 5) Exclude carcinoma. Inter observer variability was studied. Results: Out of 102 cases, 53 (51.96%) cases were earlier diagnosed as simple typical hyperplasia, 12 (11.76%) cases as complex typical hyperplasia, 21 (20.58%) cases as simple atypical hyperplasia and 16 (15.68%) cases as complex atypical hyperplasia. 26% were re-classified as EIN and 64% as non-EIN lesions by first pathologist. Second pathologist reclassified 28% as EIN and 62% as non-EIN lesions. Interobserver variability existed in only 2 cases of complex hyperplasia with atypia reclassified by second pathologist. Conclusion: EIN criteria has less interobserver variability than WHO classified hyperplasia system and can be easily applied to routine haematoxylin and eosin sections. EIN diagnosis prevents the progression to endometrial adenocarcinoma and helps in clinical management which is less intensive than for adenocarcinoma.

Hysterectomy with sentinel lymph node biopsy in the setting of pre-operative diagnosis of endometrial intraepithelial neoplasia: A cost-effectiveness analysis

ObjectivesSentinel lymph node biopsy (SLNB) may be considered in the setting of a pre-operative diagnosis of endometrial intraepithelial neoplasia (EIN) due to high rates of concurrent invasive cancer. The aim of this study is to compare the cost-effectiveness of different surgical management strategies for a pre-operative diagnosis of EIN. MethodsA decision model was developed from a third party payer perspective to compare four surgical strategies for the management of EIN: (1) hysterectomy; (2) hysterectomy with frozen section (hysterectomy + frozen); (3) hysterectomy with SLNB (hysterectomy + SLNB); (4) hysterectomy with frozen section and SLNB (hysterectomy + frozen + SLNB). The probability that frozen section identifies high- or low-risk cancer, final pathology distribution, adjuvant treatments, and surgery/imaging costs were abstracted from the literature, Medicare reimbursement data, and the financial department of a private academic hospital. Adjuvant treatments were determined through NCCN guidelines and published studies. Effectiveness was quantified as percentage of patients who received the guideline-based treatment that aligned with their true stage. ResultsThe base case cost and effectiveness of each strategy was: hysterectomy-$4383/89%, hysterectomy + frozen-$5220/99.2%, hysterectomy + SLNB-$5354/94.7% and hysterectomy + frozen + SLNB-$5938/99.6%. Hysterectomy + frozen had an incremental cost effectiveness ratio of $8111 per patient who received adjuvant treatment that aligned with true stage compared to hysterectomy. Hysterectomy + frozen + SLNB had an ICER of $168,171 per additional patient who received adjuvant treatment that aligned with their true stage compared to hysterectomy + frozen. ConclusionHysterectomy + frozen + SLNB is a costly strategy for pre-operative EIN when compared to hysterectomy + frozen, with limited clinical benefit. Hysterectomy with frozen section and subsequent intraoperative staging decisions should continue to be standard of care.

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

ObjectiveThe reported frequency of malignant or premalignant changes confined to endometrial polyps (EP) is 0.5–6%. The management of atypical endometrial hyperplasia (AEH) confined to EP is not yet established. Recently, an alternative pathological nomenclature has emerged using the term endometrial intraepithelial neoplasia (EIN) instead of atypia. The objective of this study was to evaluate the safety of conservative hysteroscopic resection of endometrial polyps with AEH or EIN. MethodsRetrospective cohort study of all cases of hysteroscopic resections of EP was performed at a single center between the years 2000–2011. All patients with a pathologic diagnosis of AEH in EP were included. A post-hoc revision of the pathologic specimens was made according to the EIN classification. ResultsOf the 32 patients with AEH in EP, 25 had normal endometrial curetting. Even with AEH confined to EP, 12 cases (48%) showed AEH (11 cases) or carcinoma (1 case) in the hysterectomy specimens. EIN in EP (14 cases) was correlated with 57% of diagnosis of EIN or carcinoma in the uterus; whereas in the absence of EIN in EP only 1 of 9 cases showed EIN in the final pathologic specimen (p=0.002), and none with carcinoma, which yields a PPV of 14% and a NPV of 100%. ConclusionThe diagnosis of EIN in EP may be a better predictor than AEH for endometrial involvement with malignant or pre-malignant neoplasms. The safety of conservative hysteroscopic resection of EP with AEH/EIN is questioned.

Endometrial intraepithelial neoplasia with secretory differentiation: diagnostic features and underlying mechanisms

Endometrial intraepithelial neoplasia (EIN) with secretory differentiation and ordinary EIN occurring in a secretory context are rare but recognized findings. We determined how often secretory differentiation in EIN was associated with evidence of circulating progestins in the background endometrium, and studied clinical characteristics and clinical outcomes of affected patients. We selected 41 patients with secretory differentiation in either the EIN itself (n=31) and/or background endometrium (n=38). Most (90%, 28/31) secretory EINs were associated with circulating progestins. Rare exceptions were observed, suggesting that secretory EIN may occur as a hormone-independent phenomenon. Circulating progestins are not sufficient, however, to induce EIN secretory differentiation, as 26% (10/38) of EIN within a secretory background were of the ordinary (non-secretory) type. EIN patients with secretory endometrium in the background are younger (averaging 45 years) than the aggregate group of all patients with EIN (53 years in previously published studies) and are often premenopausal with a cyclical source of endogenous progestins. Involution of EIN during follow-up was more frequent (81%, 17/21) for those with a secretory background at the time of initial EIN diagnosis compared with historical averages (25%, 36/142). These results suggest a potential role for endogenous progesterone, as well as therapeutic progestins, in modulating EIN outcomes.

Utility of PAX2 as a Marker for Diagnosis of Endometrial Intraepithelial Neoplasia

Diagnosis of endometrial intraepithelial neoplasia (EIN) requires learning new criteria. Two trainees rendered diagnoses based on biopsy findings, and then measured the effect of reviewing PAX2 on their interpretation. Fifty-two endometrial biopsy specimens diagnosed as having EIN were evaluated using EIN criteria. Background endometrial pattern, altered differentiation, and any features complicating diagnosis were noted. PAX2 stains were scored as confusing, helpful, or noncontributory. Fifty-two cases generated 104 passes; 82% were rediagnosed as EIN. The diagnosis was complicated because of altered differentiation (14%), EIN and background separation (13%), large lesions lacking background (11%), and secretory background (8%). PAX2 was most helpful in cases with secretory backgrounds and when EIN lacked adjacent normal tissue, and most confusing when scoring was ambiguous (14%). The diagnosis of EIN can be difficult when: (1) the lesion cannot be easily compared with background; (2) there is a confounding process; and (3) gland differentiation is altered. PAX2 can be of assistance in delimiting EIN lesions.

Prediction of coexistent carcinomas risks by subjective EIN diagnosis and comparison with WHO classification in endometrial hyperplasias

Endometrial intraepithelial neoplasia (EIN) classification is proposed as a new diagnostic system to resolve the limitations of the World Health Organization (WHO) classification in routine practice. Our aim was to find out whether EIN classification excels the WHO classification regarding the accurate prediction of coexisting endometrial carcinomas (EC) in biopsy specimens.We retrospectively re-classified 139 WHO-classified endometrial hyperplasia (EH) cases by subjective EIN diagnosis and compared the incidence of coexisting carcinomas using two classification systems by re-evaluating biopsy and corresponding hysterectomy specimens.Of 139 WHO-classified hyperplasia cases, 36 and 103 were classified as benign and EIN cases, respectively. Forty of 93 cases with atypical EH had EC at hysterectomy as compared with 2/46 cases without atypical EH, while EC was detected in 42/103 cases with EIN, and in 0 of 36 cases without EIN. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for atypical EH vs. non-atypical EH in biopsy specimen was 95.2%, 45.4%, 43.0% and 95.7%, respectively. For EIN vs. benign, the sensitivity was 100% and the specificity was 37.1%.The incidence of coexisting carcinomas in EIN cases was similar to that in atypical EH cases. However, regarding the exclusion of coexisting carcinomas, EIN criteria of benign lesions excelled the WHO criteria of non-atypical EH/CH.