Subclassification of atypical endometrial cells (Not Otherwise Specified vs favor neoplasia) on Pap tests: age-dependent risk of endometrial neoplasia

Sep 23, 2026

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Atypical endometrial cells (AEMc) detected in cervical cytology are rare but linked to higher risks of precancer and malignant lesions, while histopathological correlation data remain limited. A retrospective study of 163 women from 2019–2023 assessed immediate histologic outcomes after liquid-based cytology and high-risk HPV testing. Most cases were AEMc-NOS, with higher severity and more endometrial carcinoma in AEMc-FN. Age strongly related to disease severity, particularly in patients aged ≥45.

LanguageEnglish

CategoryHealthcare

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Pages12

Reading Time30 min

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Abstract

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Method

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Introduction

Zhou et al. Diagnostic Pathology (2026) 21:34 [https://doi.org/10.1186/s13000-026-01774-y](https://doi.org/10.1186/s13000-026-01774-y) Diagnostic Pathology RESEARCH Open Access Subclassification of atypical endometrial cells (Not Otherwise Specified vs favor neoplasia) on Pap tests: age-dependent risk of endometrial neoplasia Xin Zhou1,2†, Yi Zhou3†, Suming Huang1,2, Yanqiu Wang1,2, Qiuqin Zou1,2, Xuxi Yang1,2, Wanrun Lin4* and Feng Zhou1,2* Abstract Background Atypical endometrial cells (AEMc) detected in cervical cytology are uncommon yet significantly associated with an elevated risk of precancerous and malignant lesions. Nevertheless, limited data are available on the histopathological correlation of AEMc cases. This study aims to evaluate the immediate histological outcomes in women diagnosed with AEMc and to assess how HPV status and patient age influence oncogenic potential. Method A retrospective analysis was conducted on 163 women diagnosed with AEMc at the International Peace Maternity and Child Health Hospital between January 2019 and December 2023. Each patient underwent liquidbased cytology (LBC) and high-risk HPV (hrHPV) testing for 14 genotypes, followed by histological evaluation within six months after the cytological assessment. Result Among the 163 AEMc patients, 86 . 5%(141/163) were classified as AEMc-not otherwise specified (NOS) and 13. 5%(22/163) as AEMc-favor neoplasia (FN) . Histological analysis indicated that 2 . 5%(4/163) had precancerous lesions and 12. 9%(21/163) had cancer. Immediate pathological severity was significantly higher in AEMc-FN than in AEMc-NOS (p = 0 . 015), with endometrial carcinoma more prevalent in AEMc-FN (27 . 3% vs. 9. 9%, p = 0 . 037; odds ratio 3 . 30, 95% CI: 1.11–9. 79) . The diagnostic accuracy of AEMc-FN for endometrial carcinoma was 81 . 6%(95% CI: 74. 8%–87 . 3%) . hrHPV status did not reliably predict cancer risk stratification in AEMc, however, age was significantly associated with disease severity. Compared with younger patients, those aged > 65 years showed a markedly higher prevalence of high-grade endometrial glandular abnormalities (AEH +) and adenocarcinoma (AC) (p = 0.001 and p = 0 . 000401, respectively) . With an age cutoff of 45 years, older AEMc patients had an increased prevalence of AEH +and AC, a trend also evident in the AEMc-NOS subgroup. Conclusion Women aged ≥ 45 years, especially those classified as AEMc-NOS, exhibit a substantially higher risk of high-grade endometrial glandular lesions, underscoring the need for more vigilant follow-up. Given the significantly †Xin Zhou andYi Zhou contributed equally to this work. *Correspondence: Wanrun Lin [Wanrun.Lin@nih.gov](Wanrun.Lin@nih.gov)[ ](Wanrun.Lin@nih.gov)Feng Zhou [pathozf@163.com](pathozf@163.com) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/lice

FAQs

How were atypical endometrial cells (AEMc) classified in this study?

AEMc were categorized into AEMc-not otherwise specified (NOS) and AEMc-favor neoplasia (FN).

What did the histological analysis show about cancer and precancer risk?

Histology found precancerous lesions in a small fraction of patients and cancer in a larger fraction overall, with significantly greater immediate severity and more endometrial carcinoma in the AEMc-FN group than in AEMc-NOS.

Does high-risk HPV status predict cancer risk in AEMc patients?

High-risk HPV status did not reliably predict cancer risk stratification in AEMc, while age showed a significant association with disease severity.

What age-related findings influenced follow-up recommendations?

Women aged ≥45 years—especially those classified as AEMc-NOS—showed a substantially higher risk of high-grade endometrial glandular lesions, supporting more vigilant follow-up.

Sep 23, 2026

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