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

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. 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 liquid-based cytology (LBC) and high-risk HPV (hrHPV) testing for 14 genotypes, followed by histological evaluation within six months after the cytological assessment. 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. 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 higher prevalence of endometrial carcinoma in AEMc-FN patients compared to AEMc-NOS patients, it may be advisable for cytopathologists to annotate the presence or absence of “favor neoplasia” when diagnosing AEMc. Refining the diagnostic criteria for AEMc-FN may facilitate earlier detection of endometrial cancer.