Diagnostic features and differential diagnosis of autoimmune pancreatitis

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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.

Section snippets

Clinical features

AIP is slightly more common in males (M/F = 2/1) despite the well known propensity of autoimmune conditions to occur in females. The patients seem to cluster into two clinico-pathologically distinct subsets.13 One type occurs predominantly in older men (mean age, mid-60s), is often associated with Sjögren syndrome, bile-duct stenosis, and morphologically exhibits the classical lymphoplasmacytic sclerotic pattern of “AIP.” The second is seen in younger patients (mean age, early 40s), show an

Pathologic characteristics

AIP is characterized by fibrosis and inflammation of pancreatic tissue, which typically manifests as enlargement of the pancreatic head, and constriction of the common bile duct. In a small percentage of cases, the lesion occurs in the tail, may involve the peripancreatic adipose tissue and cause adhesions to the surrounding organs including the colon or spleen. Diffuse involvement of pancreas may also occur but is uncommon.5, 9

Additional studies

Simple histochemical stains may help confirm the vascular involvement by the inflammatory process. Special stains that highlight the components of the vessels such as EVG or movat pentichrome,62 or in some cases, muscular or endothelial markers, may help confirm the presence of periphlebitis.

Immunohistochemical stain for IgG4 is becoming a very helpful adjunct for the diagnosis of AIP, not only in resection specimens, but also in biopsies.44, 63, 64, 65 Recent studies indicate that in many

Differential diagnosis

It is important to distinguish AIP from the other types of pancreatitis, in particular, alcoholic, because the management and prognosis are vastly different. This differential is challenging both at the clinical and pathologic levels, and the correlation of clinical and pathologic findings may be necessary. As discussed previously, lack of alcohol history has been advocated as one of the defining criteria for AIP. The morphologic findings are also helpful in this distinction.

Ductal dilation,

Fine needle aspiration biopsy

Patients with AIP often undergo fine-needle aspiration biopsy with the preoperative diagnosis of carcinoma. The presence of stromal fragments with lymphocytes greater than 30 per 60× has been found to be in favor of AIP,81 although it is by no means specific. Also, the stromal fragments are significantly more cellular in AIP cases.5, 81, 82, 83, 84 If these findings are evaluated in conjunction with the clinical and radiologic findings, they may help achieve the correct diagnosis, or at least

Management and outcome

Until recently, most AIPs have been resected due to the preoperative misdiagnosis of adenocarcinoma. This is still true for most patients. Following surgery, some patients experienced emergence of new foci of strictures or pseudotumors.16, 47, 48 There is overwhelming evidence in the literature that AIP is highly responsive to steroid therapy.25, 85, 86, 87, 88, 89, 90, 91 It is expected that as the clinical and pathologic criteria for the diagnosis of AIP are better defined it will become

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      The two types of chronic pancreatitis notorious for causing mass-like lesions, which are difficult to distinguish from carcinoma are autoimmune pancreatitis (AIP) and paraduodenal pancreatitis.2,5 AIP has been referred to as lymphoplasmacytic sclerosing pancreatitis, non-alcoholic duct-centric or duct-destructive chronic pancreatitis, sclerosing pancreatitis, and primary sclerosing cholangitis of the pancreas.2,5,6 AIP typically results in a mass or “pseudotumor” focused within the head of the pancreas.2,5,6

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