Undifferentiated pleomorphic sarcoma (UPS) arises from mesenchymal tissues and accounts for approximately 1% of adult malignancies. It is the most common type of malignant soft tissue sarcoma, primarily found in the extremities and retroperitoneum, but rarely presents in the gastrointestinal tract. Primary tumors of the mesentery are rare, though metastases to the mesentery from other anatomical sites are frequent. The standard of care of UPS involves surgical resection followed by adjuvant chemotherapy or radiation, though these treatments are often only partially effective. We report a case of high-grade UPS of the sigmoid colon with node positivity and local extension to the small bowel. The patient underwent an open en bloc resection of the sigmoid colon and small bowel, followed by adjuvant chemotherapy and radiation therapy, resulting in transient clinical improvement. However, the patient returned to the ER 12.5 weeks post-initial surgical resection with complaints of abdominal pain, nausea, vomiting, and diarrhea. An exploratory laparotomy revealed a new intra-abdominal mass, leading to a palliative resection. This case highlights the aggressive nature and poor prognosis of UPS, even with standard treatment. Ongoing clinical trials and emerging therapies are crucial for improving outcomes in UPS. Access to tumor profiling and precision therapies is essential for managing rare cancers like UPS. Further studies and clinical trials are imperative to develop more effective treatments and improve patient prognosis.
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