Differential risk factors between uterine sarcomas and malignant mixed Müllerian tumors.
Authors: Hana Caroline , Costa Philippos Apolinario , D'Amato Gina Z. , Trent Jonathan C. 
Published: June 2021

e23551

Background: Uterine sarcomas are malignant tumors of the smooth muscle or connective tissue of the uterus. Its main histological types are leiomyosarcomas and endometrial stromal sarcomas, with recent classifications considering malignant mixed müllerian tumors (MMMT) as a dedifferentiated endometrial carcinoma rather than a primary uterine sarcoma. We hypothesize there are different risk factors which predispose to MMMT as compared to uterine sarcomas. This study investigates these risk factors to determine if they contribute to the development of either disease. Methods: Under an IRB-approved protocol, we identified patients with uterine sarcomas and MMMT treated at Sylvester Comprehensive Cancer Center and University of Miami Hospital between 2010 and 2020 by Patient Atlas (clinical database tool; Miami, FL). We compared the risk factors known to be associated with endometrial carcinomas between uterine sarcomas and MMMT using independent sample t-test, Chi Square, Spearman Rho and Pearson correlation. Results: A total of 59 patients with MMMT and 115 cases of uterine sarcoma were identified in our database. In the sarcoma group, the most common histology was leiomyosarcoma (n = 76, 66%). Upon analysis of the characteristics of the sarcoma and MMMT cohorts respectively, 38 (33%) vs 16 (27%) were Hispanics, 18 (15%) vs 13 (22%) had diabetes, 26 (22%) vs 20 (34%) used contraception or hormonal replacement therapy (HRT), 35 (30%) vs 17 (28%) were alcohol users, 26 (22%) vs 15 (25%) were smokers, and 54 (47%) vs 31 (52%) had a positive family history of cancer, with no statistically significant differences found (p > 0.05). The sarcoma group had a significantly lower age at diagnosis (AAD) (53 vs. 65, P < 0.001) and a larger tumor size (11.3 vs. 7.3 cm, p < 0.0005). Use of contraception or HRT was not significantly different among the 2 groups (χ(1) = 0.699, p = 0.4). Similarly, no significant difference was found in the mean age of menarche/menopause, patient’s weight, median gravidity and parity (p > 0.05). The patient’s weight and BMI negatively correlated with the AAD in the MMMT group (ρ = - 0.279, p = 0.043 and r = -0.274, p = 0.041 respectively). Older age at menopause was associated with older AAD in the sarcoma group (ρ = 0.571, p = 0.0001). Patients with higher gravidity and parity had an older AAD among the 2 groups (p ≤ 0.05). Conclusions: The uterine sarcoma patients had significantly younger AAD than the MMMT group, with the age at menopause being positively correlated with the AAD. The use of contraception or HRT were not significantly different among the 2 cohorts, suggesting that there could be an overlap of the risk factors of MMMT and uterine sarcomas. Interestingly, higher gravidity and parity were associated with an older AAD. In the MMMT group, patient’s weight and BMI were inversely associated with the AAD. Larger studies are needed to investigate whether similarities or discrepancies in the studied risk factors truly exist.