S6093 The Bleeding Giant: A Rare Case of Duodenal Undifferentiated Carcinoma with Osteoclast-Like Giant Cells Requiring Whipple Resection

Introduction: Sarcomatous malignancies are a broader term that refers to tumors resembling sarcomas (i.e., mesenchymal differentiation). Some sarcomatoid malignancies of the duodenum and pancreas exhibit features consistent with undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC), but are exceptionally rare and highly aggressive, often presenting with nonspecific symptoms during advanced disease. There is limited literature available to guide diagnosis and management. We present a rare case of a duodenal mass with sarcomatoid features, complicated by gastrointestinal bleeding, ultimately diagnosed as UC-OGC. Case Description/Methods: An 81-year-old woman with a remote history of bladder cancer, ileal conduit, and hysterectomy presented with melena, left lower quadrant pain, weakness, and nausea. Labs showed hemoglobin 9.8 g/dL with a BUN/Cr ratio of 45, concerning upper GI bleeding. Computed tomography abdomen revealed mucosal thickening in the proximal duodenum. Esophagogastroduodenoscopy demonstrated a large friable, malignant-appearing mass extending from the first to the second portion of the duodenum, occupying 50%–60% of the lumen. Biopsies revealed a high-grade sarcomatous malignancy composed of poorly differentiated atypical cells. Surgical oncology deemed the tumor resectable. The patient was discharged but returned with recurrent bleeding and underwent a pancreaticoduodenectomy (Whipple procedure) with Braun enteroenterostomy. Final pathology confirmed undifferentiated carcinoma with osteoclast-like giant cells and extensive lymphovascular invasion, with liver biopsy revealing metastatic disease. Discussion: This case highlights the diagnostic and therapeutic challenges of rare sarcomatoid and undifferentiated tumors of the duodenum, including undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC). UC-OGC shares key driver mutations with pancreatic ductal adenocarcinoma (KRAS, TP53, CDKN2A, SMAD4) yet displays distinct morphology and rapid clinical progression. These tumors often present late with bleeding or obstructive symptoms and carry a poor prognosis due to early metastasis and limited response to systemic therapies. Surgical resection remains the mainstay of treatment in select patients. UC-OGC should be considered in elderly patients with unexplained upper GI bleeding, and timely diagnosis requires close coordination between gastroenterology, surgery, pathology, and oncology teams.