Clinicopathological features of type 1 autoimmune pancreatitis without elevated serum IgG4 level

Elevated serum IgG4 is a key diagnostic marker for type 1 autoimmune pancreatitis (AIP), but some patients lack IgG4 elevation, complicating diagnosis. This study investigated the clinicopathological features of AIP without elevated serum IgG4 levels. A total of 323 patients diagnosed with AIP at Hiroshima University Hospital and affiliated institutions were analyzed. Patients were categorized into IgG4-positive (≥ 135 mg/dL), IgG4-negative (< 135 mg/dL with "definite" or "probable" diagnosis), and possible (with "possible" diagnosis) groups. Comparative analysis was performed between the IgG4-positive (n = 281) and IgG4-negative (n = 20) groups. Segmental or focal narrowing of the main pancreatic duct (MPD) and retroperitoneal fibrosis were significantly more common in the IgG4-negative group (90.0% vs. 58.7%, P = 0.011; and 35.0% vs. 12.5%, P = 0.012, respectively). Although the number of pathological findings was comparable, the rate of surgical intervention was significantly higher in the IgG4-negative group (P < 0.001). No significant differences were observed in relapse rates or relapse sites between the two groups. These findings suggest that MPD narrowing and retroperitoneal fibrosis may be characteristic of AIP without elevated IgG4. Vigilant monitoring for relapse is warranted, regardless of serum IgG4 levels.