Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease characterized by prompt response to steroid therapy. AIP presents as two distinct subtypes which are highlighted in this synoptic review.
Type-1 autoimmune pancreatitis (AIP-1).
AIP-1 belongs to the group of IgG4-related diseases, and predominately affects white and Asian men 50 years or older with a male-to-female ratio of 3:1. Its diagnostic features can be summarized as three triads in radiology, histology, and clinical manifestation, respectively.
Radiographically, the triad consists of diffuse pancreatic enlargement, peripheral rim-like hypoenhancement, and absence of ductal dilation. The pancreas shows diffuse enlargement with loss of lobulated contours (so-called sausage pancreas). The peripheral rim-like hypoenhancement present in up to 40% of cases is a highly specific finding.
The histological triad includes periductal chronic inflammation, storiform cellular fibrosis, and obliterative phlebitis. The chronic inflammatory infiltrates are rich in IgG4-positive plasma cells, usually more than 300 per high power field, and a ratio of IgG4 to IgG cells greater than 40%. Obliterative phlebitis is defined by a cellular intraluminal infiltrate comprising lymphocytes and plasma cells. Dense lymphocytes and lymphoid follicles may be seen. However, there is no neutrophilic infiltrate or ductal dilation. Despite the inflammation, the lobular architecture of the pancreas is Preserved grossly and microscopically.
Clinical triad may include - elevated serum IgG4 level, extra-pancreatic organ involvement, and prompt resolution upon steroid therapy. Elevated serum IgG4 level is seen in up to 80% of cases. And serum levels of 2 times the upper limit of normal is very specific. Systemic manifestations of more than one extra-pancreatic organ are common. This finding aids the diagnosis and should be sought after.
Type-2 autoimmune pancreatitis (AIP-2)
AIP-2, also known as idiopathic duct-centric pancreatitis, constitutes less than 10% of total AIP cases. It affects males and females equally, often about 10 years younger than the AIP-1 group. Up to 44% of cases are associated with IBD (especially ulcerative colitis). However, it lacks extra-pancreatic and biliary involvement. No reliable serological markers can assist in diagnosis. Response to steroids may support the diagnosis.
Diagnosis of AIP2 is highly dependent on histological findings which may include the following.
Ductal inflammation with intraepithelial neutrophils (so-called, granulocytic epithelial lesion), and luminal neutrophilic abscesses.
Ductal epithelial erosion and granulation tissue formation.
Neutrophilic infiltration of the pancreatic acini.
Extensive fibrosis, but no apparent storiform or hypercellularity, and
Phlebitis without obliteration.
IgG4-positive plasma cells are seen in AIP-2, but the overall number, reactivity, and distribution do not mirror that in AIP1. Positive immunostain stain for PD-L1 on ductal cells in a membranous pattern is reportedly supportive of the diagnosis. Currently, no well-accepted diagnostic criteria are established. One proposed schema is periductal inflammation with one or more of the following: ductal/lobular abscesses, ductal ulceration with neutrophils, and PD-L1 on ductal cells in a membranous pattern.
Key References
Goyal, Surbhi, and Puja Sakhuja. “Autoimmune pancreatitis: Current perspectives.” Indian journal of pathology & microbiology vol. 64,Supplement (2021): S149-S159. doi:10.4103/ijpm.ijpm_59_21. https://pubmed.ncbi.nlm.nih.gov/34135159/
Yilmaz, Osman et al. “Navigating the Challenges Associated With a Diagnosis of Autoimmune Pancreatitis and IgG4-Related Sclerosing Cholangitis.” Archives of pathology & laboratory medicine, 10.5858/arpa.2021-0549-RA. 22 Sep. 2022, doi:10.5858/arpa.2021-0549-RA. https://pubmed.ncbi.nlm.nih.gov/36136300/
Detlefsen, Sönke, and Günter Klöppel. “IgG4-related disease: with emphasis on the biopsy diagnosis of autoimmune pancreatitis and sclerosing cholangitis.” Virchows Archiv : an international journal of pathology vol. 472,4 (2018): 545-556. doi:10.1007/s00428-017-2275-z. https://pubmed.ncbi.nlm.nih.gov/29196804/
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