CT findings of type 2 autoimmune pancreatitis. (a) CT scan demonstrates diffuse pancreatic enlargement. (b) After steroid therapy, diffuse pancreatic enlargement is markedly improved on follow-up CT scan
Endoscopic retrograde pancreatography (ERP) findings in type 2 autoimmune pancreatitis. (a) ERP demonstrates skipped, multifocal irregular narrowing of the main pancreatic duct (arrow). (b) After steroid therapy, the narrowing of main pancreatic duct recovered to almost normal
Histopathology of Type 2 AIP
Type 1 AIP can be diagnosed on the basis of histological findings that fulfill three or more of the following conditions: periductal lymphoplasmacytic infiltrate without granulocytic infiltration, obliterative phlebitis, storiform fibrosis, and abundant IgG4-positive cells . In contrast, these features are very rarely seen in type 2 AIP in most instances . The definite diagnosis of type 2 AIP can be made based on the presence of granulocytic epithelial lesion (GEL) which is characterized by the infiltration of neutrophils into the lumen or epithelium of the pancreatic duct (Fig. 6.3). The finding of the so-called GEL is known to be specific to type 2 AIP . If GELs are identified in a pancreatic core biopsy (PCB) or resection specimen, it is pathognomonic for type 2 AIP . GEL often cause destruction and obliteration of the pancreatic duct lumen .
Granulocytic epithelial lesion is seen at interlobular ducts (arrows) and moderate mixed inflammatory cell infiltration is in the interlobular connective tissue (H&E, ×400)
GEL may not be present exclusively to type 2 AIP. A recent study reported that GEL could be found in up to 27 % of type 1 AIP although it consisted only of intraepithelial neutrophils . In addition, there is a report that typical LPSP coexisted with GEL . GEL seen in type 1 AIP may result from secondary changes developing on the background of LPSP due to a pancreatic ductal stricture. A previous study included GELs present in small intralobular ducts as well as those seen in medium- and large-sized interlobular ducts . However, some experts suggested that GEL in the intralobular duct should not be used as a diagnostic hallmark of type 2 AIP since this finding is not uncommon even in type 1 AIP . Given the some uncertainties surrounding GELs, a consensus definition of GELs based on more stringent criteria are necessary.
Clinical Manifestations of Type 2 AIP
When the clinical manifestations of patients with these two histological entities were compared, they were distinctly different (Table 6.1). Patients with type 2 are significantly younger than those with type 1, and type 2 AIP may be missed in young patients whom the pancreas is rarely biopsied . While the most frequent presenting symptom of type 1 AIP is obstructive jaundice, patients with type 2 are as likely to present with abdominal pain and pancreatitis [5, 17].
Differences between clinicopathologic profiles of type 1 and type 2 AIP
Type 1 AIP
Type 2 AIP
Lymphoplasmacytic sclerosingpancreatitis (LPSP)
Idiopathic duct-centric chronicpancreatitis (IDCP)
Asia > United States, Europe
Europe, United States > Asia
Obstructive jaundice (painless)
Obstructive jaundice/acute pancreatitis
Age at diagnosis
Serum IgG4 level
Periductal lymphoplasmacytic infiltrate,storiform fibrosis, obliterative phlebitis
Granulocytic epithelial lesion (GEL)
Tissue IgG4 stain
Many IgG4 (+) cells
None or very few IgG4 (+) cells
Other organ involvement
Bile duct, salivary gland, kidney, retroperitoneum
Patients with type 2 AIP have no collateral evidences such as elevated serum IgG4 and OOI which is of great help in nonsurgically diagnosing AIP . Inflammatory bowel disease (IBD), particularly ulcerative colitis, is more common in type 2 than type 1 AIP, although type 1 has a higher prevalence of it compared with the general population . Approximately 30 % of reported cases of type 2 AIP have associated IBD (Fig. 6.4).
Colonoscopic findings in type 2 autoimmune pancreatitis. Colonoscopy shows friable and erythematous colonic mucosa with loss of the normal vascular markings, which is compatible with ulcerative colitis
Compared with patients with type 2 AIP, patients with type 1 AIP are older, have increased serum IgG4 levels, and frequently show other organ involvement (OOI) such as proximal bile duct involvement, salivary gland involvement, kidney involvement, and retroperitoneal fibrosis . In contrast, patients with type 2 AIP are more than a decade younger, have normal serum IgG4 levels, and show an association with IBD. In seronegative AIP cases without OOI, determination of the AIP subtype may not be possible without the aid of histopathology because a proportion of histologically confirmed type 1 AIP can also show seronegativity and no OOI .