S3453 Immune Checkpoint Inhibitor-Associated Eosinophilic Pancreatitis Presenting as a Pancreatic Mass

Introduction: Eosinophilic pancreatitis (EP) is a rare inflammatory condition characterized by diffuse pancreatic infiltration with eosinophils, elevated serum immunoglobulin E levels, and systemic eosinophilia. Herein, we report a case of EP presenting as an enlarging pancreatic mass in a patient receiving immune checkpoint inhibitor (ICI) therapy. Case Description/Methods: A 57-year-old man with a history of alcoholic chronic pancreatitis and metastatic squamous cell carcinoma of the lung on pembrolizumab presented with a 1-month history of generalized abdominal and back pain. Initial computed tomography of the abdomen & pelvis revealed a 3.5 cm hypo-enhancing mass in the pancreatic neck, with adjacent pancreatic ductal dilation and calcifications. An endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) was performed that showed atypical cells on Rapid Onsite Evaluation, though final cytology revealed eosinophil-rich inflammatory infiltrates without neoplasia. Due to inconclusive magnetic resonance imaging findings and concern for neoplasm in the setting of metastatic lung cancer, we repeated EUS-FNA, which confirmed persistent eosinophilic infiltration, reactive acinar tissue, and IgG4-positive plasma cells lacking features of autoimmune pancreatitis (AIP) or pancreatic neoplasm. Given his ongoing pembrolizumab therapy and associated systemic eosinophilia, we suspected ICI-related EP. We held the drug indefinitely and started him on pancreatic enzyme replacement therapy. Upon periodic follow-ups, his symptoms resolved, and serial computed tomography imaging showed a reduction in the size of the pancreatic mass. In light of these findings, immunotherapy may be cautiously reintroduced with steroids, pending oncological review and computed tomography in 3 months. Discussion: EP has an estimated incidence of less than 1%, with fewer than 20 reported cases, and lacks clear diagnostic criteria, making it a challenging entity to establish. It often presents with clinical and radiological findings resembling a pancreatic neoplasm. However, unlike malignancy, EP is a benign, steroid-responsive condition that may occur secondary to AIP, eosinophilic syndromes, or drug-induced adverse events. In our case, serial EUS-guided biopsies revealed dense eosinophilic infiltrates without features of malignancy or AIP. Given the history of ICI therapy and systemic eosinophilia, we suspected an ICI-related etiology, as these drugs are known to trigger eosinophilic infiltration. This case underscores the need to consider EP in ICI-treated patients with a pancreatic mass to avoid surgical interventions.