A Distinct Subtype of Uterine Sarcoma: Case Report of a High-Grade Uterine Sarcoma With Myogenic Differentiation Harboring a PDGFRB Hotspot Mutation

Abstract

Background: High-grade sarcomas harboring PDGFRB hotspot mutations with myogenic differentiation represent a recently characterized and aggressive subset of uterine sarcomas. First described by Dermawan et al, these tumors exhibit distinct morphological, immunophenotypic, and molecular profiles that differentiate them from conventional leiomyosarcomas. To date, only 13 gynecological tumors with this genetic alteration have been reported in the literature. Patient Presentation: We report a 56-year-old female patient who presented with a large uterine tumor with pulmonary metastases. Histological evaluation demonstrated a high-grade spindle cell neoplasm with exclusively myofibroblastic morphology and absence of key leiomyosarcoma morphological features. Immunohistochemistry showed diffuse and strong positivity for H-caldesmon and complete negativity for desmin, smooth muscle actin, myogenin, MYOD1, ALK, estrogen receptor, and progesterone receptor. Next-generation sequencing identified a PDGFRB hotspot in-frame deletion (c.2547_2558del; p.D850_R853del) along with co-occurring mutations in TP53, MED12, NOTCH3, and others. The tumor was clinically staged as FIGO Stage IVB due to lung metastases. The patient passed away 4 months after surgery. Conclusion: This tumor highlighted the importance of recognizing high-grade uterine sarcomas with PDGFRB hotspot mutations as a distinct diagnostic entity. Their aggressive clinical behavior, combined with unique histopathological and genetic features, underscores the need for molecular testing to ensure accurate diagnosis. Tyrosine kinase inhibitors such as imatinib may hold therapeutic promise, but further research is needed to optimize treatment strategies.