Malignant transformation risk and management dilemmas of atypical lobular endocervical glandular hyperplasia: A retrospective cohort study comparing Peutz-Jeghers syndrome versus sporadic cases

OBJECTIVE: Atypical lobular endocervical glandular hyperplasia (ALEGH) is a high-risk precursor to gastric-type endocervical adenocarcinoma (G-EAC). However, its insidious nature and lack of standardized management pose significant clinical dilemmas, especially regarding the balance between preventing malignant progression and fertility preservation. We aimed to compare clinical characteristics and malignant potential between Peutz-Jeghers syndrome (PJS)-associated and sporadic ALEGH to provide evidence for clinical decision-making. METHODS: We conducted a retrospective comparative cohort study of the largest reported ALEGH cohort to date (n = 67; 31 PJS, 36 non-PJS) at the Obstetrics & Gynecology Hospital of Fudan University between January 2019 and December 2025. Clinical presentation, surgical pathology, and longitudinal outcomes were evaluated. RESULTS: The median age of the overall cohort was 40.0 years (interquartile range, 34.0-47.0). PJS-associated cases presented at a significantly younger age than sporadic cases (median 34.0 vs. 46.0 years; p < 0.001). Vaginal discharge was the predominant symptom (80.6%). Human papillomavirus testing (3.0% positive) and cytology (7.5% abnormal) demonstrated minimal diagnostic utility. Notably, 100% of hysterectomy specimens (65/65) showed residual gastric-type lesions despite prior local excision. Among the PJS patients who deferred hysterectomy beyond 6 months (n = 7), malignant progression to G-EAC occurred in 2 cases within 13 to 19 months. No progression was observed in the sporadic group (n = 5) during follow-up. CONCLUSIONS: PJS-associated ALEGH exhibits a potential for rapid progression toward G-EAC, with malignant transformation observed within 13 to 19 months in select cases. Given the inadequacy of local excision, prompt hysterectomy is recommended. For PJS patients electing to defer definitive surgery for fertility preservation, close and highly individualized monitoring (e.g., at 3- to 6-month intervals) is advisable; however, the optimal surveillance protocol remains to be established through future research.