Work

Rapid transformation of low-grade endometrial stromal sarcoma to BCOR-rearranged high-grade endometrial stromal sarcoma in a patient with Birt–Hogg–Dubé syndrome: A case report

Year: 2026

Type: article

Abstract: [Background] Low-grade endometrial stromal sarcoma (LG-ESS) generally follows an indolent clinical course, and high-grade transformation during disease progression is rare. [Case Presentation] We report a 44-year-old woman with Birt–Hogg–Dubé (BHD) syndrome who developed rapid transformation of LG-ESS to high-grade endometrial stromal sarcoma (HG-ESS). The patient underwent surgery for a presumed uterine leiomyoma and was diagnosed with FIGO stage IA LG-ESS. Six months after surgery, a vaginal cuff recurrence was detected and rapidly progressed despite letrozole treatment. Cytoreductive surgery was performed, and the recurrent tumor was diagnosed as HG-ESS. Re -review of the primary specimen revealed no high-grade component. Comprehensive genomic profiling of the recurrent tumor identified a ZC3H7B–BCOR fusion and MDM2 amplification, in addition to the germline pathogenic FLCN variant associated with BHD syndrome. Doxorubicin achieved a partial response, but the disease subsequently progressed during further treatment. This case demonstrates exceptionally rapid transformation from LG-ESS to BCOR -rearranged HG-ESS within 6 months. Although the temporal acquisition of the BCOR rearrangement could not be established because molecular testing was not performed on the primary tumor, the marked morphologic and clinical progression supports substantial tumor evolution. The identification of BCOR rearrangement and MDM2 amplification may provide insight into the aggressive clinical course. [Conclusions] This case highlights the potential value of comprehensive genomic profiling in recurrent ESS and suggests that MDM2 inhibitors may represent a future treatment strategy for selected patients.

Source: Gynecologic Oncology Reports

DOI: 10.1016/j.gore.2026.102238