{"paper_id":"b452dd42-61b9-4b40-bb44-bc551cd98390","body_text":"RESEARCH Open Access\n© The Author(s) 2025. Open Access  This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 \nInternational License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you \ngive appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the \nlicensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or \nother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the \nmaterial. 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World Journal of Surgical Oncology           (2025) 23:24 \nhttps://doi.org/10.1186/s12957-025-03677-6\nWorld Journal of Surgical \nOncology\n*Correspondence:\nSompop Kuljarusnont\nsompop.kul@mahidol.edu\n1Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj \nHospital, Mahidol University, Bangkok 10700, Thailand\n2Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol \nUniversity, Bangkok, Thailand\nAbstract\nObjectives To determine the prevalence of occult endometrial carcinoma in patients with endometrial intraepithelial \nneoplasia (EIN) post-hysterectomy and identify pre-hysterectomy risk factors predictive of occult carcinoma.\nMethods This retrospective study included patients diagnosed with EIN between 2007 and 2021 who underwent \nhysterectomy as primary treatment. An expert gynecologic pathologist reviewed pathological slides. Data collected \nfrom medical records included demographic and gynecologic information, sonographic findings, and surgical \nand pathological outcomes. The prevalence of occult endometrial carcinoma was calculated. Descriptive statistics \nevaluated carcinoma incidence, and logistic regression analysis identified independent risk factors.\nResults A total of 113 patients were evaluated. The median time to hysterectomy was 9.1 weeks (range 5.8–12.8 \nweeks). Post-hysterectomy, 36 patients (31.8%) were diagnosed with endometrial carcinoma, all endometrioid type. \nOf these, 88.9% were stage I per the International Federation of Gynecology and Obstetrics classification system, and \n11.1% were at high risk for nodal metastasis. Predictive factors for occult carcinoma included the intraoperative gross \nlesion size (2 cm or larger and less than 2 cm) and endometrial aspiration. Adjusted odds ratios were 6.723 (95% CI \n2.338 to 19.333) for lesions 2 cm or larger, 3.381 (95% CI 1.128 to 10.132) for lesions less than 2 cm, and 2.752 (95% CI \n1.092 to 6.936) for endometrial aspiration.\nConclusions Occult endometrial carcinoma was identified in 31.8% of patients with a pre-hysterectomy EIN \ndiagnosis. The significant predictors were endometrial aspiration and the presence of a gross lesion during surgery.\nKeywords Cancer, EIN, Endometrial intraepithelial neoplasia, Endometrium, Occult endometrial carcinoma\nPrevalence of occult endometrial carcinoma \nin patients with endometrial intraepithelial \nneoplasia who underwent hysterectomy\nWaraphon Thongsang1 , Sompop Kuljarusnont1* , Suchanan Hanamornroongruang2  and \nIrene Ruengkhachorn1\n\nPage 2 of 7\nThongsang et al. World Journal of Surgical Oncology            (2025) 23:24 \nIntroduction\nEndometrial intraepithelial neoplasia (EIN) is recog -\nnized as a precancerous lesion of the endometrium. This \ncondition was previously designated “complex atypical \nhyperplasia” according to the 1994 World Health Orga -\nnization classification, which was adapted from Kurman’s \nclassification. The EIN classification was established by \nthe World Health Organization in 2003 and was upheld \nthrough the 2020 edition. It has been endorsed by both \nthe American College of Obstetricians and Gynecologists \nand the Royal College of Obstetricians and Gynecologists \n[1– 5]. Studies have demonstrated that the prevalence of \noccult endometrial carcinoma among patients with EIN \nwho undergo hysterectomy ranges from 27 to 53%. The \ncurrent standard treatment for EIN is total hysterectomy. \nSurgeons may also consider bilateral salpingo-oophorec -\ntomy, particularly for patients at greater risk of occult \ncarcinoma. However, these patients might face prolonged \nhormonal exposure due to surgical menopause [3– 5]. \nPreoperative identification of patients with EIN who \nare at increased risk for occult endometrial carcinoma \ncan substantially enhance counseling and inform sur -\ngical decisions. Such identification can influence the \nconsideration of additional procedures such as bilat -\neral salpingo-oophorectomy or the assessment of lymph \nnode metastasis. Conversely, recognizing patients at low \nrisk for occult carcinoma can facilitate the selection of \nuterus-preserving treatments, thereby optimizing repro -\nductive and oncological outcomes.\nSeveral studies have reported predictive factors for \noccult endometrial carcinoma. These factors include \nage (using a cutoff of 50 years), diabetes mellitus, body \nmass index, transvaginal ultrasonography assessments of \nendometrial thickness, endometrial tissue biopsy tech -\nniques, and specific pathological characteristics [ 6– 9]. \nThe current study aimed to determine the prevalence of \noccult endometrial carcinoma in hysterectomy speci -\nmens and to identify pre-hysterectomy risk factors pre -\ndictive of occult carcinoma.\nMaterials and methods\nFollowing approval from the Siriraj Institutional Review \nBoard (COA numbers Si 281/2020 and Si 581/2024), a \nretrospective chart review was conducted. Human Ethics \nand Consent to Participate declarations were not appli -\ncable and the study were accordance with the principles \noutlined in the Declaration of Helsinki. The medical \nrecords of women who were diagnosed with EIN between \n2007 and 2021 and subsequently underwent hysterec -\ntomy with or without bilateral salpingo-oophorectomy at \nSiriraj Hospital.\nAll pathological slides were reviewed by an experi -\nenced gynecologic pathologist (S.H.) to confirm the \ndiagnosis of EIN. The diagnoses of EIN were based on \nvarious methods of endometrial tissue collection, includ -\ning endometrial aspiration, sampling, fractional curet -\ntage, or hysteroscopy. Patients were excluded if their \npathology reviews did not confirm EIN, if they did not \nundergo hysterectomy, or if their medical information \nwas incomplete. Demographic data, imaging results, \npathology findings, operative records, and pathology \nreports were extracted and recorded.\nHigh-risk carcinoma, which indicates regional lymph \nnode dissection, was defined according to the following \nthree criteria:\n  • The International Federation of Gynecology and \nObstetrics (FIGO) defines high-risk carcinoma as \n(i) grade 1 endometrioid with > 50% myometrial \ninvasion, (ii) grade 2 or 3 endometrioid with \nmyometrial invasion, or (iii) non-endometrioid types \n[8]. \n  • The Gynecologic Oncology Group (GOG) 167 \ndefines high-risk carcinoma as (i) any grade with \nmyometrial invasion, or (ii) grade 2 or grade 3 \nendometrioid or non-endometrioid carcinoma [10]. \n  • The Mayo criteria classify high-risk carcinoma as (i) \ngrade 1 or grade 2 endometrioid > 2 cm, (ii) > 50% \nmyometrial invasion, or (iii) grade 3 endometrioid or \nnon-endometrioid [6, 11]. \nStatistical analyses were performed using PASW Statis -\ntics, version 18 (SPSS Inc., Chicago, IL, USA). Descrip -\ntive statistics were utilized for continuous demographic \ndata, which are presented as the means and standard \ndeviations or as medians and ranges. Categorical data are \nreported as numbers and percentages. Stepwise logistic \nregression analysis identified factors predicting occult \nendometrial carcinoma in hysterectomy specimens, with \nvariables with p < 0.05 included in the multivariable anal -\nysis. The results are reported using odds ratios (ORs) and \n95% confidence intervals (CIs). A p value < 0.05 was con -\nsidered to indicate statistical significance.\nResults\nOne hundred and thirty patients were eligible, but 15 \nwere excluded due to choosing medical treatment, and \n2 were re-diagnosed with benign endometrial hyperpla -\nsia. A total of 113 patients were enrolled in the study. The \ndemographic, clinical, and pathological characteristics of \nthe patients are detailed in Table  1. Patient ages ranged \nfrom 27 to 71 years, with a median age of 48.0 years \n(interquartile range [IQR] 39.0–54.0 years). The median \nbody mass index was 28.60 kg/m 2 (IQR 23.36–35.11 kg/\nm2). The median parity was 1 (IQR 0–2); 56 patients were \nnulliparous, 17 had one parity (P1), 28 had two parities \n(P2), and 12 had three parities (P3). Transvaginal sonog -\nraphy was performed before endometrial tissue biopsy in \n\nPage 3 of 7\nThongsang et al. World Journal of Surgical Oncology            (2025) 23:24 \n70 cases. The median time to hysterectomy was 9.1 weeks \n(range 5.8–12.8 weeks). Post-hysterectomy, 36 patients \n(31.8%) were diagnosed with endometrial carcinoma.\nThe tumor characteristics of the 36 patients diagnosed \nwith carcinoma are presented in Table  2. Histopatho -\nlogical examination revealed all carcinomas to be of the \nendometrioid type, with 32 tumors classified as grade 1, \nthree as grade 2, and one as grade 3. Of these patients, \n32 were classified as stage I according to the 2023 FIGO \nclassification. Four patients presented with stage III dis -\nease: one had metastasis to the fallopian tube, one to both \nthe tubal and ovarian regions, one to the tubal and pel -\nvic nodes, and one to the ovary. Among the 113 patients \nwith EIN, 3.5% (4 patients) were classified as high risk by \nthe FIGO criteria, 14.1% (16 patients) by the GOG crite -\nria, and 18.5% (21 patients) by the Mayo criteria. Specific \nTable 1 Patient demographics and clinical data for 113 patients \ndiagnosed with endometrioid intraepithelial neoplasia who \nunderwent hysterectomy\nVariables N (%)\nAge, y\n< 50 64 (56.6)\n≥ 50 49 (43.4)\nBMI, kg/m2\n< 30 63 (55.8)\n≥ 30 50 (44.2)\nParity\nNulliparous 56 (49.6)\nMultiparous 57 (50.4)\nMenopause status\nPremenopausal 83 (73.5)\nPostmenopausal 30 (26.5)\nBreast cancer 3 (2.7)\nDiabetes mellitus 17 (15.0)\nHypertension 26 (23.0)\nEndometrial thickness by transvaginal sonography\nNot evaluated 43 (38.1)\n< 1 cm 14 (12.4)\n1 to < 2 cm 22 (19.5)\n≥ 2 cm 34 (30.1)\nEndometrial biopsy methods\nEndometrial sampling 62 (54.9)\nFractional curettage 47 (41.6)\nHysteroscopy resection or biopsy 4 (3.5)\nIntraoperative tumor size\nNo lesion 56 (49.6)\n< 2 cm 27 (23.9)\n≥ 2 cm 33 (29.2)\nOperations\nHysterectomy 7 (6.0)\nHysterectomy plus BS 22 (19.0)\nHysterectomy plus BSO 61 (54.0)\nHysterectomy plus BS/BSO plus LNS 23 (19.8)\nPathology tumor size\nNo gross lesion 42 (37.2)\nGross lesion ≤ 2 cm 33 (29.2)\nGross lesion > 2 cm 38 (33.6)\nPathology from hysterectomy specimen\nNormal endometrium 19 (16.8)\nEndometrioid intraepithelial neoplasia 58 (51.3)\nEndometrioid endometrial carcinoma 36 (31.9)\nAbbreviations : BMI, body mass index; BS, bilateral salpingectomy; BSO, bilateral \nsalpingo-oophorectomy; LNS, pelvic with or without para-aortic lymph nodes \nsampling\nTable 2 Clinicopathological features of 36 patients with \nconcurrent endometrial carcinoma\nVariables N (%)\nIntraoperative tumor size\nNo lesion 8 (22.2)\n< 2 cm 11 (30.6)\n≥ 2 cm 17 (47.2)\nPathology tumor size\nNo gross lesion 6 (14.3)\nGross lesion < 2 cm 9 (27.3)\nGross lesion ≥ 2 cm 21 (55.3)\nGrading\nGrade 1 32 (88.9)\nGrade 2 3 (8.3)\nGrade 3 1 (2.8)\nMyometrial invasion\nNo 21 (86.7)\nInvasion ≤ 1/2 12 (10.6)\nInvasion > 1/2 3 (2.7)\nHigh-risk per FIGO criteria 4 (11.1)\nHigh-risk per GOG 167 criteria 16 (44.4)\nHigh-risk features per Mayo criteria 21 (58.3)\nLymph-vascular space invasion 1 (0.9)\nCervical stromal invasion 1 (0.9)\nTubal involvement, n = 36 3\nOvarian metastasis, n = 27 2\nPelvic lymphadenectomy, n = 23\nNegative 22\nPositive 1\nPara-aortic lymphadenectomy, n = 14\nNegative 14\nPositive 0\nFIGO stages\nIA 31 (86.1)\nNo myometrial invasion 10\nMyometrial invasion < 50% 21\nIB 1 (2.8)\nIIIA 3 (8.3)\nIIIC1 1 (2.8)\nAdjuvant treatment\nNone 31 (86.1)\nRadiation 1 (2.8)\nChemotherapy 4 (11.1)\nAbbreviations : FIGO, International Federation of Gynecology and Obstetrics; \nGOG, Gynecologic Oncology Group\n\nPage 4 of 7\nThongsang et al. World Journal of Surgical Oncology            (2025) 23:24 \nanalysis of the 36 patients with carcinoma revealed that \nthe proportions of high-risk classifications were notably \ngreater: 11.1% according to FIGO, 44.4% according to \nGOG, and 68.3% according to the Mayo criteria.\nThe univariable analysis revealed that the variables \nassociated with occult endometrial carcinoma were \nendometrial aspiration, intraoperative tumor size, nul -\nliparity, and a body mass index greater than 30  kg/m 2 \n(Table  3). The multivariable analysis determined that \nendometrial aspiration and intraoperative lesion size \nwere independent predictors of occult carcinoma.\nDiscussion\nThe significance of EIN lies not only in its role as a pre -\ncursor lesion but also in its association with occult \nendometrial carcinoma. The high prevalence of these car-\ncinomas underscores the risk of preoperatively undiag -\nnosed malignancy in patients diagnosed with EIN. Some \npatients undergo hysterectomy, with or without salpingo-\noophorectomy, which was deemed inappropriate in cer -\ntain cases. This situation may be especially concerning \nfor those desiring uterus-preserving treatments. The risk \nof occult carcinoma can influence the decision to opt for \nhysterectomy over medical management for EIN. This \nstudy uniquely contributes to the understanding of occult \nendometrial carcinoma by identifying independent pre -\ndictive factors such as endometrial sampling and intra -\noperative gross tumor volume, which can inform more \naccurate clinical decision-making.\nOur investigation identified a 31.8% prevalence of \noccult endometrial carcinoma among patients with pre -\nexisting EIN, a figure that aligns with previously reported \nrates ranging from 27–53%. 5–8,10  The variability in these \nrates may be attributed to differences in demographic \nand ethnic backgrounds among the populations sam -\npled. Physicians should consider these proportions when \nTable 3 Predictive factors for occult endometrial carcinoma in patients with endometrioid intraepithelial neoplasia who underwent \nhysterectomy\nVariables ECA\nN (%)\nOR (95% CI) P value aOR (95% CI) P value\nAge, y\n< 50, n = 64 23 (35.9) Reference 0.289\n≥ 50, n = 49 13 (26.9) 0.644 (0.285–1.453)\nBMI (kg/m2)\n≤ 30, n = 63 15 (23.8) Reference 0.041\n> 30, n = 50 21 (42.0) 2.317 (1.034–5.194)\n< 23, n = 25 7 (28.0) Reference 0.639\n≥ 23, n = 88 29 (33.0) 1.264 (0.475–3.367)\nParity\nMultiparous, n = 56 13 (22.8) Reference\nNulliparous, n = 57 23 (41.1) 1.801 (1.017–3.189) 0.037\nMenopausal status\nPremenopausal, n = 83 29 (34.9) Reference 0.242\nPostmenopausal, n = 33 7 (23.3) 0.567 (0.217–1.478)\nDiabetes mellitus\nNo, n = 96 30 (31.3) Reference 0.742\nYes, n = 17 6 (35.3) 1.200 (0.406–3.549)\nHypertension\nNo, n = 87 26 (29.9) Reference 0.412\nYes, n = 26 10 (38.5) 1.466 (0.588–3.657)\nEndometrium thickness\n< 2 cm, n = 36 9 (25.0) Reference 0.236\n≥ 2 cm, n = 34 13 (38.2) 1.857 (0.667–5.168)\nEndometrial biopsy methods\nFC/hysteroscopy, n = 51 11 (21.6) Reference 0.036 Reference 0.032\nES, n = 62 25 (40.3) 2.457 (1.063–5.682) 2.752 (1.092–6.936)\nIntraoperative gross lesion\nNo gross lesion, n = 56 10 (17.9) Reference Reference\nGross lesion < 2, n = 38 15 (39.5) 3.867 (1.320-11.327) 0.014 3.381 (1.128–10.132) 0.030\nGross lesion ≥ 2, n = 19 11 (57.9) 5.977 (2.264–16.503) 0.001 6.723 (2.338–19.333) < 0.001\nAbbreviations : aOR, adjusted odds ratio; BMI, body mass index; CI, confidence interval; ECA, endometrium carcinoma; ES, endometrial sampling; FC, fractional \ncurettage; OR, odds ratio; TVS, transvaginal sonography\n\nPage 5 of 7\nThongsang et al. World Journal of Surgical Oncology            (2025) 23:24 \nchoosing the treatment modality or surgical procedure. \nAdditionally, while our 31.8% prevalence is consistent \nwith reported rates, our study uniquely identifies inde -\npendent predictive factors, such as endometrial sampling \nand intraoperative gross tumor volume, in a population \nwith specific clinical features, thus filling a gap in the \nexisting literature.\nNotably, all occult carcinomas identified in our cohort \nwere of the endometrioid type, suggesting that EIN is a \nprecursor to endometrioid endometrial carcinoma. A \nsizeable majority (88.9%) of these carcinomas were classi-\nfied as stage I, consistent with prior findings [5, 9, 12– 14]. \nStandard surgical treatment for endometrial carcinoma \nincludes extrafascial hysterectomy and bilateral salpingo-\noophorectomy, with selective lymph node dissection rec -\nommended in patients with high-risk carcinoma to have \nnodal metastasis. The current study highlights consider -\nable variability in the delineation of high-risk carcinoma, \ndepending on the classification criteria employed. Unlike \nprior studies that may use differing criteria for high-risk \nclassification, our research utilizes consistent method -\nology, demonstrating the need for clearer standardiza -\ntion in defining high-risk carcinoma to guide surgical \ndecision-making.\nPrevious studies have identified pre-hysterectomy \nfactors that can predict occult carcinoma in patients \ndiagnosed with EIN, such as preoperative sonogra -\nphy assessing endometrial stripe thickness, endome -\ntrial biopsy techniques, and intraoperative tumor size. \nTransvaginal sonography is a valuable tool for evaluating \npatients with abnormal uterine bleeding, particularly in \nassessing endometrial carcinoma risk through endome -\ntrial thickness measurements. For example, Vetter et al. ’s \nstudy involving 169 women with EIN reported that an \nendometrial thickness cutoff of ≥ 2  cm was an indepen -\ndent predictor for occult carcinoma, with an adjusted OR \nof 4.0 (95% CI 1.6 to 10.1). Additionally, they reported \nthat 44% of EIN patients exhibited tumor characteristics \nindicative of lymph node metastasis based on the Mayo \ncriteria [ 6]. However, our findings suggest that sonog -\nraphy alone may overlook occult carcinomas in EIN \npatients. Thus, combining sonography with additional \ndiagnostic methods, such as endometrial biopsy or curet-\ntage, may improve diagnostic accuracy and guide appro -\npriate management decisions.\nSimilarly, Abt et al. ’s study of 378 women with EIN \nusing endometrial thickness cutoffs of ≥ 1.5  cm and \n≥ 2 cm yielded adjusted ORs of 1.6 (95% CI 1.1–2.3) and \n1.9 (95% CI 1.3–2.8), respectively. They revealed that 31% \nof women diagnosed with carcinoma were classified as \nhigh risk according to the Mayo criteria [ 14]. In contrast, \nthe present investigation found no significant association \nbetween endometrial thickness and occult carcinoma. \nThis lack of association may be due to the relatively small \nsample size (70 women undergoing sonography), which \nmight not have provided sufficient statistical power to \nvalidate the predictive value of sonographic measure -\nments. While transvaginal sonography remains a widely \nused predictive tool, our study highlights discrepancies \nin endometrial thickness measurements, underscoring \nthe need for tailored sonographic assessments, particu -\nlarly in populations with specific clinical features or risk \nfactors. A larger cohort may offer the statistical power \nrequired to validate the predictive value of sonographic \nmeasurements. Future studies with expanded popula -\ntions and multicenter designs are necessary to confirm \nour findings and ensure generalizability.\nEndometrial biopsy emerged as an independent pre -\ndictor of occult carcinoma in this study, corroborat -\ning findings from previous research. A study comparing \nendometrial biopsy to dilatation and curettage in women \nwith complex atypical hyperplasia revealed markedly \ndifferent rates of occult carcinoma: 45.9% for endome -\ntrial biopsy versus 26.8% for dilatation and curettage \n(p < 0.001).8 In another study, the risk of occult carci -\nnoma was twice as high in women who underwent endo -\nmetrial sampling than in those who had dilatation and \ncurettage-based biopsy techniques (OR 2.0, 95% CI 1.4 to \n2.9) [7]. These findings suggest that curettage-based tech-\nniques offer greater accuracy than endometrial aspira -\ntion in detecting carcinoma within the EIN cohort. This \nincreased accuracy is likely due to the more comprehen -\nsive tissue sample obtained through curettage.\nOur findings further affirm the importance of biopsy \ntechniques, particularly dilatation and curettage, in \ndetecting occult carcinoma. While endometrial biopsy \nis less invasive, its lower accuracy compared to curettage \nsuggests that a sequential approach may offer optimal \ndiagnostic precision. Performing curettage after an initial \nbiopsy can confirm pathology and improve preoperative \ndecision-making. Although endometrial biopsy emerged \nas a significant predictive factor in our study, our results \nuniquely highlight differences in aspiration accuracy and \nsample variability. These findings suggest that a com -\nbined approach, incorporating both biopsy and curettage, \ncould enhance diagnostic accuracy for occult carcinoma \nand guide more effective treatment planning.\nA larger intraoperative tumor size has been robustly \nidentified as an independent predictor of occult carci -\nnoma. Theoretically, larger tumor sizes in endometrial \ncarcinoma correlate with increased rates of lymph node \nmetastasis, as stated by the Mayo criteria [ 11]. Although \nthis factor often aligns with the sonographic assessment \nof endometrial thickness, it becomes critically important \nwhen preoperative sonography is not conducted. During \nhysterectomy, intraoperative examination of the uterine \ncavity is essential not only for detecting occult carcinoma \nbut also for assessing the risk of nodal involvement. Our \n\nPage 6 of 7\nThongsang et al. World Journal of Surgical Oncology            (2025) 23:24 \nidentification of tumor size as a predictive factor fur -\nther emphasizes the importance of intraoperative gross \nexamination, particularly when preoperative imaging is \nunavailable or inconclusive.\nA key strength of this study was its review of pathology \nspecimens from a substantial number of patients, which \nwas performed by a gynecologic pathologist using EIN \nterminology. However, the clinical outcomes of patients \ndiagnosed with endometrial carcinoma have yet to be \nreported. While our study benefits from a rigorous path -\nological review and the use of EIN terminology, the rela -\ntively small sample size is a limitation that may restrict \nthe generalizability of certain findings. This underscores \nthe importance of validating our results in larger, more \ndiverse cohorts to strengthen their clinical applicability.\nThere is currently no precise risk stratification system \nfor predicting occult carcinoma and nodal involvement. \nSome studies have evaluated molecular markers, such \nas the loss of phosphatase and tensin homologs, mis -\nmatch repair deficiency, or p53 expression, as potential \npredictors of increased risk for occult carcinoma [ 12]. \nTo better guide lymphadenectomy decisions, future \nresearch should prospectively evaluate various methods \nfor enhancing the prediction of occult carcinoma. These \nmethods include measuring endometrial thickness using \nvaginal sonography at different cutoff points, conducting \nDoppler flow studies, and repeating endometrial biopsies \nvia fractional curettage or hysteroscopy. Additionally, \nthe use of immunohistochemistry and the assessment of \nfrozen section accuracy are crucial for predicting occult \ncarcinoma and evaluating nodal metastasis risk. Further \nrefinements in diagnostic tools, such as combining sono -\ngraphic and biopsy findings with molecular markers like \np53 expression or mismatch repair deficiency, may pro -\nvide a more comprehensive risk stratification system for \noccult carcinoma. Future research should prioritize the \ndevelopment and validation of multimodal diagnostic \nframeworks to improve clinical decision-making.\nConclusions\nOccult endometrial carcinoma was identified in 31.8% of \npreoperatively diagnosed EIN patients who underwent \nhysterectomy, with endometrial sampling and intraop -\nerative gross tumor volume emerging as independent \npredictors. This study provides critical data on the preva-\nlence and risk factors associated with occult carcinoma \nin EIN patients, emphasizing the diagnostic challenges \nencountered in clinical practice. The findings highlight \nthe importance of adopting a multimodal diagnostic \napproach to enhance diagnostic accuracy and support \nmore informed clinical decision-making for patients with \nEIN.\nAcknowledgements\nThe authors gratefully acknowledge Doctor Saowalak Hunnangkul, PhD, for \nassistance with the statistical analysis and Miss Sarocha Boonkate for the data \ncollection. The authors are also indebted to Mr David Park for editing this \npaper in English.\nAuthor contributions\nAll the authors contributed to the study design. W.T., S.H., and I.R. collected \nthe data. W.T., S.K., and I.R. were responsible for the data analysis and \ninterpretation. W.T. drafted the manuscript, while S.K. and I.R. revised it for \nimportant intellectual content. All authors approved the final version of the \nmanuscript.\nFunding\nNothing to disclose.\nData availability\nNo datasets were generated or analysed during the current study.\nDeclarations\nEthics norm or standard\nThe research was conducted in accordance with the principles outlined in the \nDeclaration of Helsinki.\nHuman ethics and consent to participate declarations\nHuman Ethics and Consent to Participate declarations: not applicable.\nConsent to participate\nSince no individual participants were involved, there was no need for a \nconsent to participate.\nCompeting interests\nThe authors indicate no potential conflicts of interest.\nReceived: 6 October 2024 / Accepted: 19 January 2025\nReferences\n1. Mutter GL. Endometrial intraepithelial neoplasia (EIN): will it bring order to \nchaos? The endometrial collaborative group. Gynecol Oncol. 2000;76(3):287–\n90. https:/ /doi.or g/10.10 06/g yno.1999.5580.\n2. Sobczuk K, Sobczuk A. 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