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. 2025 Sep;35(9):102010.
doi: 10.1016/j.ijgc.2025.102010. Epub 2025 Jul 11.

Comprehensive genomic profiling and clinico-pathologic characterization of primary ovarian leiomyosarcoma

Matteo Bruno  1 , Elisa De Paolis  2 , Angelo Minucci  3 , Alessia Piermattei  2 , Giulia Maneri  2 , Angela Santoro  4 , GianFranco Zannoni  4 , Giovanni Scambia  5 , Carolina Maria Sassu  5 , Francesca Ciccarone  5 , Camilla Nero  5 , Claudia Marchetti  5 , Anna Fagotti  5
Affiliations

Comprehensive genomic profiling and clinico-pathologic characterization of primary ovarian leiomyosarcoma

Matteo Bruno et al. Int J Gynecol Cancer. 2025 Sep.

Abstract

Objective: Primary ovarian leiomyosarcomas are exceptionally rare, accounting for less than 0.1% of ovarian malignancies. Their treatment strategies remain poorly defined, and data on comprehensive genomic profiling are lacking. This study aims to characterize the pathological features and genomic landscape of primary ovarian leiomyosarcoma, highlighting similarities with uterine leiomyosarcomas based on available literature.

Methods: We retrospectively analyzed 7 histologically confirmed cases of primary ovarian leiomyosarcoma diagnosed between 2013 and 2023 at a tertiary referral center. Clinical data, histopathological findings, and immunohistochemical profiles were reviewed. Genomic profiling was performed using the TruSight Oncology 500 assay, targeting 523 cancer-related genes. Only oncogenic or likely oncogenic alterations (Tier classification system I-II) were considered.

Results: All patients had International Federation of Gynecology and Obstetrics stage IA disease and underwent radical surgery. Two patients experienced pelvic recurrence; both showed increased Ki-67 and complete loss of estrogen and progesterone receptors in the relapsed tumors. Histologically, tumors exhibited spindle or epithelioid morphology with variable atypia and mitotic indices. Genomic profiling revealed a high prevalence of TP53 (71%) and PTEN (57%) alterations. Additional copy number alterations were identified in homologous recombination repair genes (BRCA2, CHEK1/2, and ATM), fibroblast growth factor (FGF) family members (FGF7/9/14), and platelet-derived growth factor receptor beta. Tumor mutational burden was low to medium in all cases, and microsatellite status was stable.

Conclusions: Primary ovarian leiomyosarcomas exhibit a complex genomic landscape marked by genomic instability, sharing key alterations with uterine leiomyosarcomas. TP53 and PTEN mutations may play a central role in their pathogenesis. This first genomic profiling analysis of ovarian leiomyosarcomas provides a basis for further research and potential targeted therapeutic approaches in this rare malignancy.

Keywords: Immunohistochemistry; Leiomyosarcoma; Molecular Features; Ovarian Cancer.

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Conflict of interest statement

Declaration of Interests CM is on the consultant/advisory board for Clovis, Pharmamar, GSK, AstraZeneca, and MSD, and received travel accommodation from Pharmamar and Roche. AF reports commercial interests with AstraZeneca, MSD, Johnson & Johnson, and Pharmamar. AF serves as an Associate Editor of the International Journal of Gynecological Cancer. Given her role as Editor, AF had no involvement in the peer review of this article and has no access to information regarding its peer review. CN is on the consultant/advisory board for GSK, AstraZeneca, and MSD.

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