Available online 3 January 2024

Author links open overlay panelABSTRACT

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.

Section snippetsINTRODUCTION

With an increasing awareness of autoimmune pancreatitis (AIP), the number of cases diagnosed as AIP has increased in the last decade.1 A prompt and accurate diagnosis of AIP is beneficial for patients because corticosteroids rapidly ameliorate symptoms despite its malignant-looking appearance on imaging modalities.2,3 However, the number of cases miscategorized as AIP has also been increasing. These cases are treated with unnecessary steroids. Therefore, appropriate treatments are often

Type 1 AIP

Two types of AIP are widely recognized.2 Type 1 AIP is a more common, male-dominant disease that typically develops in adults older than 40 years. It is a pancreatic manifestation of IgG4-related disease (IgG4-RD), and approximately 60% of patients have extrapancreatic manifestations of IgG4-RD (e.g., sialadenitis, sclerosing cholangitis) at the time of the initial presentation.3,4 AIP is the leading manifestation of IgG4-RD; 60% of patients with IgG4-RD have type 1 AIP.4 Histologically, type

IMAGING FEATURES OF AIP

Three characteristic imaging findings are a diffuse or segmental enlargement of the pancreas (often ‘sausage-like’), a low-attenuating peripancreatic capsule-like rim, and irregular narrowing of the pancreatic duct.3 Although none of these are entirely specific for AIP, the presence of two or three of these findings is highly suggestive of the diagnosis of AIP. The ‘sausage-like’ enlargement tends to be overemphasized; similar findings are observed in acute interstitial pancreatitis or even the

Typical findings

If biopsy is performed in the acute or subacute phase, a full spectrum of the characteristic findings may be observed, including a diffuse lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis (Figure 1A and B). The number of IgG4-positive plasma cells increases to >10 cells/high-power field (hpf) and the IgG4/IgG-positive cell ratio exceeds 40%, which are the minimum criteria generally used for pancreatic biopsy specimens. Typical cases have >30 positive cells/hpf and a

Typical findings

Biopsy shows the features of pancreatitis with a significant lymphoplasmacytic infiltrate, in keeping with an immune-mediated process. Since the inflammatory process in type 2 AIP is duct-centered, the inflammatory infiltrate is more likely to be patchier than that in type 1 AIP, which shows lobule-centric diffuse inflammatory changes. Nevertheless, the degree of inflammation is higher than that typically observed in chronic alcoholic or idiopathic pancreatitis, which is an important finding to

Peritumoral pancreatitis

The background pancreatic tissue adjacent to pancreatic cancer shows variable degrees of fibrosis and inflammation, presumably due to duct obstruction, cancer-related immune reactions, and carcinoma invasion. Non-specific microscopic findings, such as fibrosis, an inflammatory infiltrate, and parenchymal atrophy, are typically observed. However, changes resembling type 1 AIP may also develop.29,30 The pancreatic parenchyma is enlarged with a dense lymphoplasmacytic infiltrate; storiform

CONCLUSIONS

To avoid an overdiagnosis of type 1 AIP, pathologists need to be aware that the proposed standards for IgG4-positive plasma cell counts and the IgG4/IgG-positive plasma cell ratio are minimal criteria, and borderline cases need to be diagnosed with caution. It is also important to assess not only positive, but also negative findings in cases of suspected type 1 AIP. The diagnosis of type 2 AIP is more challenging and requires a close clinicopathological correlation. Although GEL is a well-known

Financial support

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Author contributions

Review of the literature and drafting the manuscript.

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Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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