Glandular Crowding of the Endometrium: Clinical Outcomes of a Diagnostic Gray Zone

Endometrioid intraepithelial neoplasia (EIN) is a well-defined premalignant lesion of the endometrium, characterized by crowded glands exceeding the amount of stroma, cytologic atypia distinct from background endometrium, and a sufficiently sized lesion (often designated as 1 mm). However, some endometrial samples contain foci of crowded glands that fall short of these criteria. These diagnostically indeterminate areas, often described as "atypical glandular crowding," present challenges in both interpretation and clinical management. To assess their significance, we conducted a retrospective review of endometrial specimens diagnosed with atypical glandular crowding over an 8-yr period (2016-2024) at Baystate Medical Center. Cases were identified through a free-text database search and included when at least one follow-up specimen was available within 1 yr of the index biopsy. Demographic, clinical, and histopathologic data were recorded, and outcomes were classified as benign, EIN, or carcinoma. Among 79,998 gynecologic specimens, 167 cases (0.2%) met the inclusion criteria, with 127 unique patients analyzed. Within 1 yr, 36 patients (28.3%) were diagnosed with EIN (n=31) or endometrioid carcinoma (n=5), most within 4 mo of the initial biopsy. Notably, roughly one-quarter of these cases arose within endometrial polyps, and their risk of EIN or carcinoma (~25%) was similar to that of nonpolypoid lesions. Thus, atypical glandular crowding carries a substantial short-term risk of a premalignant or malignant diagnosis on follow-up, with ~1 in 4 patients being diagnosed with EIN or carcinoma within a year. Recognition of this subdiagnostic but clinically significant pattern should prompt timely re-sampling, as early follow-up often reveals occult neoplastic lesions not captured in the initial biopsy.