Diagnostic features and differential diagnosis of autoimmune pancreatitis

A clinically and pathologically distinct form of chronic pancreatitis is now widely recognized and has been designated variably as lymphoplasmacytic sclerosing pancreatitis, duct-destructive (duct-centric) pancreatitis or autoimmune pancreatitis. This entity is currently defined by a constellation of clinical and pathologic findings, including the lack of both conventional risk factors for pancreatitis, such as alcohol use and gallstones, and their hallmark pattern of injury, including calcifications and pseudocysts. Histologically, it is characterized by lymphoplasmacytic inflammation with abundant IgG4-positive plasma cells that exhibit an affinity for ducts as well as venules ("peri-venulitis," with or without frank vasculitis). Inflammation is often associated with sclerosis and expansion of periductal tissue. In some cases, fibroblastic activity is prominent and resembles "inflammatory pseudotumor" or is even misdiagnosed as "inflammatory myofibroblastic tumor." In what appears to be a distinct subset of this entity, intraepithelial granulocytic infiltrates may be seen. Well-developed examples are readily recognized; however, lesser ones may be difficult to distinguish from other forms of pancreatitis based on morphology alone. This type of pancreatitis is considered an autoimmune process. In about 15% to 20% of patients, the clinical stigmata of autoimmune conditions are present at the time of diagnosis, and in many others, discovered subsequently. The usual "lymphoplasmacytic sclerotic" type tends to be associated with Sjogren, whereas the "granulocytic" subset, with inflammatory bowel disease. Most patients present with a pancreatic head mass, often with an accompanying stricture of the distal common bile duct, which thus radiologically resembles "pancreas cancer." In fact, this entity accounts for more than a third of the cases of pseudotumoral pancreatitis (mass-forming inflammatory lesions that resemble carcinoma). Elevated serum IgG4 levels are characteristic and may be very helpful in the differential diagnosis from tumors and tumor-like lesions of the pancreas which seldom result in levels above 135 mg/dL. The mean age of the patients with this condition is in the mid-50s; the subset with granulocytic intraepithelial lesions seem to be younger (mid 40s). Despite the autoimmune association, males are afflicted as commonly as (if not more than) females. Following resection, emergence of new fibro-inflammatory lesions in the remaining pancreaticobiliary tree has been noted in some cases; however, the process typically responds to steroids. It is important to recognize the distinctive clinicopathologic features of this entity, so that it can be diagnosed accurately and managed appropriately.