Undifferentiated Pleomorphic Sarcoma

Excerpt

Undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma, is one of the most common high-grade soft tissue sarcomas in adults, comprising approximately 5% to 10% of all soft tissue sarcomas. It arises from primitive mesenchymal cells that lack a specific line of differentiation and typically occurs in the deep soft tissues of the extremities, particularly the thigh, followed by the trunk and retroperitoneum. UPS is characterized by marked cellular pleomorphism, atypical mitotic figures, and areas of necrosis on histology. The molecular pathogenesis remains poorly defined, involving highly complex and heterogeneous karyotypes without consistent or targetable genetic alterations, differentiating UPS from other sarcoma subtypes.

The clinical presentation of UPS usually involves a painless, progressively enlarging mass, though symptoms can vary depending on anatomic location and involvement of adjacent structures. Prognosis is determined by several factors, including tumor size, depth, anatomic site, and histologic grade, with high-grade, deep, and large tumors demonstrating an elevated risk of distant metastasis, most commonly to the lungs, followed by lymph nodes, bone, and liver.

Management requires an interprofessional approach and should be centralized at high-volume sarcoma centers to optimize outcomes. The cornerstone of treatment for localized disease is wide surgical resection with negative margins.[1]] Radiation therapy is frequently utilized preoperatively or postoperatively to improve local control, particularly for tumors in anatomically constrained sites. Systemic chemotherapy, most often with doxorubicin-based regimens, is considered in select patients with high-risk or metastatic disease, though overall response rates remain modest. Ongoing research into the tumor biology of UPS may pave the way for novel therapeutic approaches, including immunotherapy and molecularly targeted agents.