Therapeutic Challenges in Metastatic Myxofibrosarcoma: A Case-Based Review.

Myxofibrosarcoma (MFS) is a histologically distinct and aggressive subtype of soft tissue sarcoma, most often affecting elderly individuals and commonly presenting in the extremities. Despite standard treatment modalities, including surgical resection, radiotherapy, and chemotherapy, MFS is notable for its high recurrence and metastatic potential. We present the case of a 64-year-old woman with stage IIIA MFS of the right thigh and progressive pulmonary metastases, despite undergoing radiotherapy, surgery, and systemic chemotherapy. Her disease course was complicated by genetic alterations, including NF1 and ATM mutations, suggesting potential responsiveness to targeted therapies such as MEK and PARP inhibitors. Histological and immunohistochemical findings confirmed a fibrohistiocytic origin, consistent with metastatic MFS. This case highlights the diagnostic and therapeutic challenges associated with MFS, emphasizing the need for improved molecular characterization and novel therapeutic strategies. While current treatments provide limited durable control, emerging insights into the tumor's genetic and immune landscape offer hope for more effective, personalized approaches.