Impact of Coexisting Adenomyosis on the Histopathological, Immunohistochemical, and Molecular Features of Endometrial Cancer and on Adjuvant Therapy Allocation: A Single-Center Retrospective Cohort Study

BACKGROUND AND AIMS: Adenomyosis is frequently found in hysterectomy specimens of women with endometrial cancer (EC), but its relationship with tumor characteristics remains debated. This study aimed to compare the histopathological, immunohistochemical (IHC) and molecular features of EC, and the allocation of adjuvant therapy, between patients with and without coexisting adenomyosis. METHODS: Single-center retrospective cohort study of consecutive women who underwent hysterectomy for EC at ARNAS Garibaldi Nesima, Catania, Italy, between January 2023 and September 2024, with complete IHC and molecular profiling. Adenomyosis was defined histopathologically. FIGO 2023 stage, histotype and grade, myometrial invasion, lymphovascular space invasion (LVSI), nodal status, p53 and p16 expression, POLE, mismatch repair (MMR), KRAS and PIK3CA status, and adjuvant therapy were compared using Fisher's exact and chi-square tests, with odds ratio (OR) and 95% confidence interval (CI). RESULTS: Of 87 patients, 27 (31.0%) had coexisting adenomyosis. Adenomyosis was associated with FIGO stage I (81.5% vs. 46.7%; OR 5.03, 95% CI 1.68-15.04; p = 0.003), myometrial invasion < 50% (66.7% vs. 35.0%; OR 3.71, 95% CI 1.42-9.70; p = 0.010), absent/focal LVSI (77.8% vs. 50.0%; OR 3.50, 95% CI 1.24-9.89; p = 0.019) and a lower proportion of grade 3 endometrioid tumors (3.7% vs. 26.7%; p = 0.017). No differences were observed in nodal status or in p53, p16, POLE, MMR, KRAS, or PIK3CA status. Fewer patients with adenomyosis received adjuvant therapy (29.6% vs. 58.3%; OR 0.30, 95% CI 0.11-0.80; p = 0.020). Multivariable adjustment was not feasible given the sample size. CONCLUSION: In this cohort, coexisting adenomyosis was associated with earlier-stage, less invasive EC and, consistently, with less frequent allocation to adjuvant therapy. These are univariate associations from a small, single-center retrospective series without survival data; they do not establish an independent or causal effect of adenomyosis and require confirmation in larger prospective multicenter studies.