S3615 Pancreatic PEComas: Diagnostic Challenges and Divergent Clinical Outcomes

Introduction: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors expressing both muscle and melanocytic markers. Primary PEComas involving the pancreas are even rarer, with fewer than 30 cases reported in the literature to date. This rarity complicates timely diagnosis and management. Here, we describe 2 distinct cases with a focus on highlighting diagnostic intricacies, clinical variability, and contrasting outcomes in pancreatic PEComas. Case Description/Methods: Case 1: A 38-year-old woman with past medical history of cholecystectomy, focal pancreatic necrosis debridement, presented with intermittent left upper quadrant abdominal pain, nausea, and vomiting, and was found to have a suspicious area of the pancreatic head concerning for neuroendocrine tumor on Computed tomography. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) revealed a PEComa (positive for HMB-45 and smooth muscle actin (SMA)). She underwent pancreatoduodenectomy with clear surgical margins and no lymph node involvement. Despite immediate postoperative complications including intra-abdominal abscess, she has remained disease-free at over 10 years of follow-up. Case 2: A 58-year-old man presented acutely with severe chest, abdominal, and back pain. Initial computed tomography revealed a complex pancreatic head and uncinate mass. Initial EUS-FNA showed poorly differentiated adenocarcinoma. However, repeat EUS-FNA, prompted by lack of treatment response and continued disease progression, subsequently confirmed malignant pancreatic PEComa, characterized by rapid progression and extensive vascular involvement. Despite aggressive multimodal therapy, including chemotherapy (Gemcitabine, Docetaxel) and targeted treatment (nab-sirolimus), disease progression continued with hepatic metastases and severe gastrointestinal bleeding, requiring interventional radiological embolization procedures. Persistent bleeding complications and rapid tumor advancement necessitated hospice care, and the patient died within 5 months of diagnosis. Discussion: These cases illustrate the clinical heterogeneity, diagnostic complexity, and diverse prognosis of pancreatic PEComas. Early surgical resection in Case 1 led to favorable long-term outcomes, whereas Case 2 demonstrates aggressive progression resistant to current therapies. These contrasting outcomes underscore the importance of early, accurate diagnosis, individualized therapeutic strategies, and further research into targeted therapies for aggressive PEComas.