Objectives To estimate the incidence and to identify risk factors of leiomyosarcoma among women undergoing hysterectomy for presumed benign disease.

Methods This is a retrospective single-center study of consecutive patients who underwent total hysterectomy with benign indications at Del Ponte Hospital (Varese) between 01/01/2000 and 31/12/2019. Data were manually collected by operative records and institutional surgical reports, including demographic and histopathologic characteristics. Factors associated with the occurrence of unexpected uterine leiomyosarcoma (uLMS) were searched. Stratification by age, menopausal status and uterine weight was performed.

Results Overall, 4428 patients were included in the analysis and 24 (0,54%) had a final diagnosis of uLMS. Among 2936 patients with preoperative indication of uterine fibroids, the rate of uLMS was 0,99%. The increase of age at surgery resulted to be positively associated with the incidence of uLMS (from 0.09% in patients <45yo to 1.97% in patients >75yo; p=0.01). The absolute risk of LMS increased in post- vs. premenopausal patients (1.27% vs. 0.25%; p=0.001). Increase in uterine weight was also associated with higher risk of uLMS (p<0.001).

The pooled analysis included menopausal status (pre vs. post) and uterine weight (<1 kg vs. >1 kg); post-menopausal women with uterus weighting 1kg or more had an absolute risk of uLMS of 5.45%.

Conclusions The overall risk of uLMS in women undergoing hysterectomy for presumed benign indication is low. However, there is a significant increased risk in post-menopausal patients with enlarged uteri.