Autoimmune pancreatitis type 2

Topic Completed: 24 January 2019

Revised: 6 December 2019

Revised: 28 January 2019

Copyright: (c) 2019,, Inc.

PubMed Search: Autoimmune pancreatitis type 2 [title]

David J. Escobar, M.D., Ph.D.
Maryam Kherad Pezhouh, M.D., M.Sc.
Page views in 2018: 10
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Cite this page: Escobar D, Pezhouh MK. Autoimmune pancreatitis type 2. website. Accessed December 13th, 2019.
Definition / general
  • 1 of 2 types of autoimmune pancreatitis, characterized by clinical evidence of jaundice, with or without formation of a pancreatic mass on radiographic imaging, with excellent clinical response to steroid treatment
  • Unlike type 1 autoimmune pancreatitis, type 2 is IgG4 negative and does not show extra pancreatic organ involvement and is not associated with increased IgG4 in serum or IgG4 positive plasma cells
  • Diagnosis requires histologic confirmation of granulocytic epithelial lesions (Pancreas 2011;40(3):352, Am J Surg Pathol 2003;27:1119)
Essential features
  • Characterized by clinically nonspecific signs and symptoms, radiographic evidence of pancreas enlargement, histologic evidence of destructive duct centric inflammation with granulocytic epithelial lesions, with an excellent response to treatment with steroids
  • Autoimmune pancreatitis type 2, idiopathic duct centric pancreatitis, autoimmune pancreatitis with granulocyte epithelial lesions, nonalcoholic duct destructive pancreatitis
  • Pancreas
  • No significant extra pancreatic involvement
  • Largely unknown
  • Largely unknown
Clinical features
  • Numerous, nonspecific signs and symptoms
  • Jaundice, weight loss, abdominal pain, diffuse enlargement or mass forming lesion on imaging
  • No biochemical evidence of pancreatitis, absent serum IgG4, no extra pancreatic organ involvement (Pancreas 2011;40:809)
  • An association with inflammatory bowel disease, especially ulcerative colitis, is observed in up to 15% of cases (Gastroenterology 2015;149:39)
Diagnostic criteria
  • Histologic examination of tissue is critical for diagnosis per International Consensus Diagnostic Criteria 2011 (Pancreas 2011;40(3):352)
  • Categorization as "definitive" or "probable" based on histologic criteria:
    • Level 1
      • Granulocytic infiltration of duct wall [aka granulocytic epithelial lesion(s)] with or without granulocytic acinar inflammation
      • Absent or scant IgG4 positive cells (0 - 10 cells/high powered fields)
    • Level 2
      • Granulocytic and lymphoplasmacytic acinar infiltrate
      • Absent or scant IgG4 positive cells (0 - 10 cells/high powered fields)
  • Definitive type 2 autoimmune pancreatitis:
    • Level 1 histologic findings with supportive findings on imaging or level 2 histologic findings, supportive findings on imaging, clinical inflammatory bowel disease and response to steroid treatment
  • Probable type 2 autoimmune pancreatitis:
    • Level 2 histologic findings, supportive findings on imaging, variable inflammatory bowel disease and response to steroid treatment
  • No serum biomarkers have been elucidated (Pancreas 2011;40:809)
  • No biochemical evidence of pancreatitis (normal serum amylase, lipase)
Radiology description
  • No specific radiologic features to distinguish type 2 from type 1
  • Contrast enhanced ultrasound (Endosc Ultrasound 2018;7:196):
    • Noninvasive imaging study; dynamic contrast enhancement improved discrimination between autoimmune pancreatitis and pancreatic ductal adenocarcinoma
    • Shows iso or hyperenhancement during the arterial and phases
  • CT (AJR Am J Roentgenol 2015;205:2):
    • Important imaging modality for differentiation from pancreatic cancer
    • Diffuse parenchymal involvement, sausage shaped
    • Delayed enhancement studies
    • Rim-like enhancement
  • Magnetic resonance (Pancreas 2018;47:1115, Radiology 2011;260:428)
    • T1 weighted: hypointense
    • T2: predominantly hyperintense
    • Dynamic study shows the effect of fibrosis widening the extracellular and extravascular spaces, resulting in hypointensity during pancreatic phase and contrast retention / hyperintensity during the delayed phase
  • Magnetic resonance cholangiopancreatography (Pancreas 2018;47:1115)
    • Stenosis of the main pancreatic duct, however with less upstream dilatation than seen in type 1 autoimmune pancreatitis
    • Rare / absent common bile duct stenosis and rare / absent stenosis of intrahepatic bile ducts, consistent with no extra pancreatic organ involvement in type 2 autoimmune pancreatitis compared to type 1 autoimmune pancreatitis
Radiology images

Images hosted on other servers:

Diffuse pancreas enlargement

Prognostic factors
  • Excellent prognosis (up to 99% remission) with steroid treatment
  • Low risk of recurrence (10 - 15%) (Gut 2013;62:1771)
Case reports
Microscopic (histologic) description
  • Confined to pancreas
  • Key histologic features:
    • Lymphoplasmacytic inflammation, predominantly periductal, although acini are also involved
    • Epithelium of medium and small sized duct walls infiltrated by neutrophils [(granulocytic epithelial lesion(s)] with or without granulocytic acinar inflammation
      • Often causes destruction of the pancreatic duct epithelium
  • Lobular fibrosis (but not storiform) and obliterative phlebitis, however less prominent than in type 1 autoimmune pancreatitis
  • Absent or scant IgG4 positive cells (plasma cells) (0 - 10 cells / high powered fields) (Gastroenterology 2015;149:39)
Molecular / cytogenetics images

Contributed by David J. Escobar, M.D., Ph.D.

Granulocyte epithelial lesion


Positive stains
  • IHC not necessary for diagnosis
  • One study has suggested a role for evaluating IL8 expression in ductal epithelium (85% versus 0% in type 1 autoimmune pancreatitis) and infiltrating neutrophils (100% versus 0% in type 1 autoimmune pancreatitis) (Am J Surg Pathol 2017;41:1129)
Negative stains
  • Scant or absent IgG4
Differential diagnosis
  • Pancreatic ductal adenocarcinoma
    • Most important entity to exclude when considering autoimmune pancreatitis
    • May present as jaundice, with infiltrative mass on radiographic imaging, variable serum IgG4 levels, variable elevated serum CA 19-9 levels
    • Radiographic findings may be similar with contrast enhancement
  • Autoimmune pancreatitis type 1
    • Associated with an older age group
    • Serum IgG4 levels may be elevated
    • Histology shows dense lymphoplasmacytic infiltrate, storiform fibrosis and obliterative phlebitis
    • IgG4 positive plasma cells may be present, considered IgG4 related if IgG4/IgG ratio > 40% (Virchows Arch 2018;472:545)
  • Alcoholic / gallstone pancreatitis
    • Acute pancreatitis that occurs in any age group
    • Elevated amylase and lipase
    • Histology is not needed for diagnosis, shows acute interstitial inflammation with spotty peripancreatic fat necrosis (mild cases) or large areas of saponification, hemorrhage and spotty widened viable acinar lumens (severe cases)
  • Chronic pancreatitis
    • Progressive inflammation and fibrosis of the pancreas, resulting in waxing and waning nausea, weight loss, fat malabsorption (steatorrhea) and diabetes
    • May have elevated serum CA 19-9
    • Histology reveals atrophy of acini and ducts with preservation of pancreatic lobular architecture, variable amount of fibrosis centered around ducts and between lobules and mild chronic inflammatory cell infiltrate (Mod Pathol 2007;20:S113)
Board review question #1
A 40 year old male presented with jaundice and abdominal imaging showed a pancreatic mass. Serum IgG4 levels were not elevated. Endoscopic ultrasound guided fine needle biopsy was performed and a representative photomicrograph is shown. Which of the following statements is true?

  1. Although serum IgG4 levels are not elevated, will have IgG4 positive cells
  2. Despite steroid therapy, the patient's symptoms will persist and this will support the most likely diagnosis
  3. Histopathologic findings in the photomicrograph are required for definitive diagnosis
  4. Most likely diagnosis is associated with systemic inflammation, with frequent involvement of extra pancreatic organs
Board review answer #1
C. According to the International Consensus Diagnostic Criteria established in 2011, the definitive diagnosis autoimmune pancreatitis type 2 requires tissue biopsy of the pancreas demonstrating granulocytic infiltration of the pancreatic duct wall [(granulocytic epithelial lesion(s)].
Answer choice A: IgG4 positive cells are absent in autoimmune pancreatitis type 2. This finding is more characteristic of autoimmune pancreatitis type 1.
Answer choice B: Both autoimmune pancreatitis types 1 and 2 respond to the steroid therapy.
Answer choice D: Autoimmune pancreatitis type 2 is not associated with extra pancreatic organ manifestations. This finding is more characteristic of autoimmune pancreatitis type 1.

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Board review question #2
A 45 year old woman presented with abdominal pain and jaundice. Abdominal imaging showed a diffusely enlarged sausage shaped pancreas and stenosis of the main pancreatic duct. Serum amylase, lipase and IgG4 levels were not elevated. During the workup, endoscopic ultrasound guided fine needle biopsy was performed and histologic sections showed pancreatic duct centric inflammation including ductal epithelium with intra-epithelial neutrophils. Upon further gathering of past medical history, the patient was most likely found to have which of the following?

  1. Ankylosing spondylitis
  2. Inflammatory bowel disease
  3. Salivary gland enlargement and thyroiditis
  4. Systemic lupus erythematosus
Board review answer #2
B. There is a known association between autoimmune pancreatitis type 2 and inflammatory bowel disease, especially ulcerative colitis, occurring in 15 - 20% of biopsy proven autoimmune pancreatitis type 2. The basis of this association is unclear.
Answer choice A: Ankylosing spondylitis is an inflammatory disease that is associated with HLA-B27 and is not known to be associated with autoimmune pancreatitis type 2.
Answer choice C: Autoimmune pancreatitis type 1 is an IgG4 related disease. Patients often present with extra pancreatic manifestations of systemic IgG4 related inflammation including enlarged salivary glands and Riedel thyroiditis or the sclerosing variant of Hashimoto thyroiditis.
Answer choice D: Systemic lupus erythematosus is not known to be associated with autoimmune pancreatitis type 2.

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