Diagnostic Uncertainty in Pancreatic Masses: the Critical Role of Excluding Malignancy in Suspected Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) is an uncommon inflammatory condition of the pancreas characterized by glandular enlargement and ductal narrowing arising from dysregulated immune activity. Its clinical and imaging overlap with pancreatic malignancy makes accurate distinction essential. We describe a case series of four patients who initially presented with a pancreatic mass suspicious for malignancy, but received a confirmed diagnosis of AIP following thorough diagnostic evaluation. The cohort comprised three male patients (aged 32, 55, and 68 years) and one female patient (aged 73 years). The predominant presenting features included abdominal pain (n=2), scleral icterus (n=3), and pruritus (n=1). Laboratory workup demonstrated elevated total and direct bilirubin in all patients, and serum IgG4 levels were above the normal range in every case. Cross-sectional abdominal imaging with contrast-enhanced CT or MRI identified a pancreatic mass in each patient. All four patients underwent endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) with rapid on-site evaluation (ROSE), none of which revealed evidence of malignancy. Histopathologic examination showed intact pancreatic acinar architecture in all cases; chronic inflammation and fibrosis were noted in three patients. IgG4 and CD138 immunohistochemical staining was non-reactive in three patients. All patients underwent endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent placement to address biliary obstruction. Interval ERCP confirmed resolution of the obstruction, enabling stent removal without subsequent recurrence. Following establishment of an AIP diagnosis, all patients were treated with a corticosteroid taper, resulting in symptomatic resolution and complete radiologic clearance of the pancreatic mass, with removal of biliary stents thereafter. Patients remained asymptomatic with no evidence of relapse at 3-, 6-, and 12-month follow-up intervals.