• computed tomography
• direct bilirubin
• duodenal papilla
• preoperative prediction
• scoring system

IgG4‐related sclerosing cholangitis (IgG4‐SC) is a distinct type of cholangitis frequently associated with autoimmune pancreatitis and currently recognized as a biliary manifestation of IgG4‐related disease. Although clinical diagnostic criteria of IgG4‐SC were established in 2012, differential diagnosis from primary sclerosing cholangitis and cholangiocarcinoma is sometimes difficult. Furthermore, no practical guidelines for IgG4‐SC are available. Because the evidence level of most articles retrieved through searching the PubMed, Cochrane Library, and Igaku Chuo Zasshi databases was below C based on the systematic review evaluation system of clinical practice guidelines MINDS 2014, we developed consensus guidelines using the modified Delphi approach. Three committees (a guideline creating committee, an expert panelist committee for rating statements according to the modified Delphi method, and an evaluating committee) were organized. Eighteen clinical questions (CQs) with clinical statements were developed regarding diagnosis (14 CQs) and treatment (4 CQs). Recommendation levels for clinical statements were set using the modified Delphi approach. The guidelines explain methods for accurate diagnosis, and safe and appropriate treatment of IgG4‐SC.

• Bile duct
• Guideline
• IgG4
• Sclerosing cholangitis
• Steroid

Autoimmune pancreatitis (AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4 (IgG4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreatic manifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.

• Immunoglobulin G
• Pancreatitis, chronic
• Pancreatitis
• Pancreatitis, sclerosing cholangitis, and sicca complex
• Sclerosing cholangitis
• Retroperitoneal fibrosis

Diffuse or segmental irregular narrowing of the main pancreatic duct (MPD), as observed by endoscopic retrograde cholangiopancreatography (ERCP), is a characteristic feature of autoimmune pancreatitis (AIP).

ERCP findings were retrospectively examined in 40 patients with AIP in whom irregular narrowing of the MPD was detected near the orifice. The MPD opening sign was defined as the MPD within 1.5 cm from the orifice being maintained. The distal common bile duct (CBD) sign was defined as the distal CBD within 1.5 cm from the orifice being maintained. Endoscopic findings of a swollen major papilla and histological findings of specimens obtained from the major papilla were examined in 26 and 21 patients, respectively.

The MPD opening sign was detected in 26 of the 40 patients (65%). The distal CBD sign was detected in 25 of the 32 patients (78%), which showed stenosis of the lower bile duct. The patients who showed the MPD opening sign frequently showed the distal CBD sign (p=0.018). Lymphoplasmacytic infiltration, but not dense fibrosis, was histologically detected in biopsy specimens obtained from the major papilla.

On ERCP, the MPD and CBD adjacent to the major papilla are frequently maintained in patients with AIP involving the pancreatic head. These signs are useful for diagnosing AIP on ERCP.

• Cholangitis, sclerosing
• Pancreatitis, chronic

In immunoglobulin G4 (IgG4)-related disease (RD), organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs. Although infiltration of many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and major duodenal papilla of patients with autoimmune pancreatitis, it cannot be diagnosed as a gastrointestinal lesion involved in IgG4-RD, because none of the following is observed in these lesions: a mass-like formation; dense fibrosis; or obliterative phlebitis. Based on our review of the literature, there appear to be two types of IgG4-related gastrointestinal disease. One is a gastrointestinal lesion showing marked thickening of the wall of the esophagus and stomach, consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma cells, which usually show submucosal spreading. The other is an IgG4-related pseudotumor occurring in gastrointestinal regions such as the stomach, colon, and major duodenal papilla, showing polypoid or mass-like lesions. Most solitary IgG4-related gastrointestinal lesions that are not associated with other IgG4-RD appear to be difficult to diagnose. It is of utmost importance to rule out malignancy. However, these lesions may respond to steroid therapy. To avoid unnecessary resection, IgG4-related gastrointestinal diseases should be considered in the differential diagnosis.

• Immunoglobulin G4
• Autoimmune pancreatitis
• Gastritis
• Colonic polyp
• Ulcerative colitis

• Animals
• Autoimmune Diseases/immunology
• Autoimmune Diseases/pathology
• Autoimmune Diseases/therapy
• Biomarkers/analysis
• Diagnosis, Differential
• Fibrosis
• Gastrointestinal Diseases/immunology
• Gastrointestinal Diseases/pathology
• Gastrointestinal Diseases/therapy
• Gastrointestinal Tract/immunology
• Gastrointestinal Tract/pathology
• Granuloma, Plasma Cell/immunology
• Granuloma, Plasma Cell/pathology
• Humans
• Immunoglobulin G/analysis
• Lymphocytes/immunology
• Plasma Cells/immunology
• Predictive Value of Tests

• FOXP3
• IgG4
• autoimmune pancreatitis
• duodenal papilla
• immunostaining
• relapse
• spontaneous remission

It is of utmost importance to differentiate autoimmune pancreatitis (AIP) from pancreatic cancer (PC). Segmental AIP cases are sometimes difficult to differentiate from PC. On endoscopic retrograde cholangiopancreatography, long or skipped irregular narrowing of the main pancreatic duct (MPD), less upstream dilatation of the distal MPD, side branches derived from the narrowed portion of the MPD, absence of obstruction of the MPD, and stenosis of the intrahepatic bile duct suggest AIP rather than PC. Abundant infiltration of IgG4-positive plasma cells is frequently and rather specifically detected in the major duodenal papilla of AIP patients. IgG4-immunostaining of biopsy specimens obtained from the major duodenal papilla is useful for supporting a diagnosis of AIP with pancreatic head involvement. On endoscopic ultrasonography (EUS), hyperechoic spots in the hypoechoic mass and the duct-penetrating sign suggest AIP rather than PC. EUS and intraductal ultrasonography sometimes show wall thickening of the common bile duct even in the segment in which abnormalities are not clearly observed with cholangiography in AIP patients. EUS-guided fine needle aspiration, especially EUS-guided Tru-Cut biopsy, is useful to diagnose AIP, as well as to exclude PC.

• Autoimmune pancreatitis
• Pancreatic cancer
• Endoscopic retrograde cholangiopancreatography
• Endoscopic ultrasonography-Fine needle aspiration
• IgG4

AIM: To examine the histological and immunohistochemical findings of biopsy specimens taken from the major duodenal papilla of autoimmune pancreatitis (AIP) patients.

METHODS: The major duodenal papilla in the resected pancreas of 3 patients with AIP and of 5 control patients [pancreatic carcinoma (n = 3) and chronic alcoholic pancreatitis (n = 2)] was immunostained using anti-CD4-T cell, CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major duodenal papilla of 2 patients with AIP and 5 control patients with suspected papillitis were prospectively taken during duodenoscopy and immunohistochemically examined.

RESULTS: Moderate or severe lymphoplasmacytic infiltration including many CD4-positive or CD8-positive T lymphocytes and IgG4-positive plasma cells (≥10/HPF), was observed in the major duodenal papilla of all 3 patients with AIP. The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with AIP, but in controls, there were only a few (≤3/HPF) IgG4-positive plasma cells infiltrating the major duodenal papilla.

CONCLUSIONS: An abundant infiltration of IgG4-positive plasma cells is specifically detected in the major duodenal papilla of patients with AIP. Although this is a preliminary study, IgG4-immunostaining of biopsy specimens taken from the major duodenal papilla may support the diagnosis of AIP.

• Autoimmune pancreatitis
• IgG4
• Major duodenal papilla

• Aged
• Ampulla of Vater/pathology
• Autoimmune Diseases/diagnosis
• Biopsy
• CD4-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/immunology
• Female
• Humans
• Immunoglobulin G/analysis
• Immunohistochemistry
• Male
• Middle Aged
• Pancreatitis/diagnosis
• Prospective Studies