Autoimmune pancreatitis: Biopsy interpretation and differential diagnosis.

Autoimmune pancreatitis (AIP) is classified into type 1 (IgG4-related) and type 2 (IgG4-unrelated) and the interpretation of pancreatic biopsy findings plays a crucial role in their diagnosis. Needle biopsy of type 1 AIP in the acute or subacute phase shows a diffuse lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and the infiltration of many IgG4-positive plasma cells. In a later phase, changes become less inflammatory and more fibrotic, making interpretations more challenging. Confirmation of the lack of 'negative' findings that are unlikely to occur in type 1 AIP (e.g., neutrophilic infiltration, abscess) is important to avoid an overdiagnosis. The number of IgG4-positive plasma cells increases to >10 cells/high-power field (hpf), and the IgG4/IgG-positive plasma cell ratio exceeds 40 %. However, these are minimal criteria and typical cases show >30 positive cells/hpf and a ratio >70 % even in biopsy specimens. Therefore, cases with a borderline increase in this number or ratio need to be diagnosed with caution. In cases of ductal adenocarcinoma, the upstream pancreas rarely shows type 1 AIP-like changes; however, the ratio of IgG4/IgG-positive plasma cells is typically <40 %. Although the identification of a granulocytic epithelial lesion (GEL) is crucial for type 2 AIP, this finding needs to be interpreted in conjunction with a background dense lymphoplasmacytic infiltrate. An isolated neutrophilic duct injury can occur in peritumoral or obstructive pancreatitis. Drug-induced pancreatitis in patients with inflammatory bowel disease often mimics type 2 AIP clinically and pathologically. IL-8 and PD-L1 are potential ancillary immunohistochemical markers for type 2 AIP, requiring validation studies.