Pancreas
Pancreatitis
Autoimmune pancreatitis type 1

Editorial Board Member: Raul S. Gonzalez, M.D.
Deputy Editor: Debra Zynger, M.D.
Sabrina Sopha, M.D.

Topic Completed: 1 June 2018

Revised: 28 May 2019

Revised: 24 January 2019

Copyright: (c) 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: Autoimmune pancreatitis[TI] type 1[TI]

Sabrina Sopha, M.D.
Page views in 2018: 1,333
Page views in 2019 to date: 3,469
Cite this page: Sopha S. Autoimmune pancreatitis type 1. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/pancreasaiptype1.html. Accessed August 21st, 2019.
Definition / general
  • One of two types of autoimmune pancreatitis, frequently associated with IgG4 related disease and extrapancreatic manifestations of IgG4 disease
  • Autoimmune pancreatitis type 1 is a radiologic, clinical and serologic mimic of pancreatic adenocarcinoma but has an excellent long term outcome and 5 year survival rate, responding well to steroids and other immune modulators
Essential features
  • One of two types of autoimmune pancreatitis, frequently associated with IgG4 related disease and extrapancreatic manifestations of IgG4 disease
  • Autoimmune pancreatitis type 1 is a radiologic, clinical and serologic mimic of pancreatic adenocarcinoma but has an excellent outcome
Terminology
  • Autoimmune pancreatitis type 1 (AIP type 1), lymphoplasmacytic sclerosing pancreatitis (LPSP) and IgG4 related pancreatitis (IgG4-RP)
Epidemiology
Sites
  • Pancreas
  • Inflammation may also involve biliary tree (most common after pancreas), salivary gland, lacrimal gland, mesentery / retroperitoneum, pituitary gland (hypophysitis), thyroid (thyroiditis), prostate (prostatitis) and kidney (tubulointerstitial nephritis
)
Pathophysiology / etiology
  • Unclear; two hypotheses:
    • May involve a prior bacterial infection and molecular mimicry:
      • There is homology between human carbonic anhydrase II and H. pylori alpha carbonic anhydrase, as well as homology between ubiquitin protein ligase E3 component n-recognin 2 in acinar cells and the H. pylori plasminogen binding protein
      • H. pylori infection is hypothesized to create an immune response that may lead to autoimmune events due to these enzymatic homologies (Gastroenterology 2015;149:39)
    • Many patients (up to 88%) are "blue collar" workers, suggesting an environmental exposure factor, which may account for the male predominance (Gastroenterology 2015;149:39)
Clinical features
  • Complex and nonspecific
  • Painless jaundice, infiltrative mass on imaging, hypergammaglobulinemia, ± elevated serum IgG4, ± elevated serum CA 19-9, ± extrapancreatic organs involved, ± diabetes (Gastroenterol Res Pract 2017;2017:3246459)
Diagnosis
  • Per International Consensus Diagnostic Criteria (ICDC) 2011:
    1. Dense infiltration of plasma cells and lymphocytes
    2. Storiform / pinwheel fibrosis
    3. Obliterative phlebitis (late stages may only show remnant of vein on elastin stain), > 50 IgG4+ plasma cells per high powered field
  • Incompatible findings include neutrophilic microabscesses, granulomas, necrosis and multinucleated giant cells
  • ICDC criteria are most widely accepted but others exist (ICDC essentially overlaps with the Boston Criteria, Mod Pathol 2012;25:1181)
  • HISORt (histology, imaging, serology, other organ involvement and response to therapy) criteria include imaging, laboratory data, histology, response to steroids and extrapancreatic organ involvement (Virchows Arch 2018;472:545, Gastroenterology 2015;149:39, Gland Surg 2016;5:318)
Laboratory
  • Variable and nonspecific
  • Role of serum IgG4 is limited:
    • High serum IgG4 found in 4 - 10% of healthy controls and controls with other disease; 10.1% of patients with pancreatic cancer have elevated serum IgG4 (Gastroenterol Res Pract 2017;2017:3246459)
    • ~20% of autoimmune pancreatitis type 1 patients have normal serum IgG4 levels at presentation
    • In conjunction with kappa / lambda hybrid antibody, sensitivity increases from 79% to 90%
    • Sensitivity and specificity also increase to 76% and 93% when a cutoff of 140 mg/dL is used (Virchows Arch 2018;472:545)
  • May have autoantibodies against carbonic anhydrase II (55%), lactoferrin (75%) or pancreatic secretory trypsin inhibitor (33%) (Gastroenterology 2015;149:39, Gland Surg 2016;5:318)
  • CA 19-9, generally considered a tumor marker of pancreatic cancer, can be elevated
Radiology description
  • Ultrasound:
    • Use is attractive for noninvasiveness, low cost and ease of operation but does not show the irregular narrowing or stenosis of the pancreatic duct
    • Quantitative perfusion analysis in contrast enhanced ultrasound can highlight the vascular lesions, differentiating it from pancreatic cancer (Gastroenterol Res Pract 2017;2017:3246459)
  • Computed tomography (CT):
    • Most important imaging method for differentiating from pancreatic cancer
    • Shows diffuse morphological pancreatic enlargement ("sausage" pancreas), diminished contrast enhancement in the arterial phase and prolonged enhancement in the delayed / venous phase
    • May show a characteristic capsule-like density (Gastroenterol Res Pract 2017;2017:3246459)
  • Magnetic resonance imaging: hypointense T1 weighted signal and hyperintense T2 signal (Gastroenterol Res Pract 2017;2017:3246459, Gland Surg 2016;5:318)
  • Magnetic resonance cholangiopancreatography: narrow / segmental stenosis of main pancreatic duct and pancreatic segment of the common bile duct, proximal bile duct dilatation and gallbladder enlargement (Gastroenterol Res Pract 2017;2017:3246459)
  • Endoscopic ultrasound:
    • Limited role with 21% unsuccessful adequate tissue sampling
    • Endoscopic ultrasound fine needle aspiration (EUS-FNA) is not included in International Consensus Diagnostic Criteria (ICDC) as a method for histologic diagnosis (Gastroenterol Res Pract 2017;2017:3246459)
  • Positron emission computed tomography: useful in detecting extrapancreatic autoimmune disease when autoimmune pancreatitis type 1 is suspected (Gastroenterol Res Pract 2017;2017:3246459)
Radiology images

Images hosted on other servers:

CT

PET

Endoscopic ultrasound

Prognostic factors
Case reports
  • 50 year old Japanese man with hyperproteinemia and PET scan showing multiple uptakes in the pancreas, bilateral lacrimal glands, submandibular glands and many other sites (World J Gastroenterol 2015;21:9808)
  • 59 year old Japanese man with jaundice, hypergammaglobulinemia and multiple pancreatic masses (Case Rep Gastroenterol 2017;11:678)
  • 64 year old Japanese woman with new onset bleeding due to acquired hemophilia A (factor VIII inhibitor) with known longstanding disease (Int J Hematol 2018;108:335)
  • 70 year old Tunisian man with obstructive jaundice, abdominal pain and classic findings of autoimmune pancreatitis type 1 (Am J Case Rep 2017;18:822)
  • 76 year old Japanese woman with longstanding disease who presents with steroid refractory severe thrombocytopenia (Cureus 2017;9:e1724)
Treatment
Gross description
  • Disease is localized mainly in the pancreatic head, less frequently in the body / tail
  • Diffuse enlargement or "sausage" pancreas may be observed without a discrete mass
  • Segmental stenosis of the main duct may be seen
Gross images

Images hosted on other servers:

Nodular lesions

Microscopic (histologic) description
  • Three key histologic features:
  • Fourth feature, IgG4+ plasma cells, may or may not be present but should be considered IgG4 related disease if > 10 IgG4+ plasma cells/high powered field in biopsy specimens and > 50 IgG4+ plasma cells/high powered field in resection specimens, both with an IgG4/IgG ratio of > 40% (Gastroenterol Res Pract 2017;2017:3246459, Virchows Arch 2018;472:545)
  • Due to limited sample size, all three histologic features may not be present on core biopsy
Microscopic (histologic) images

Contributed by Anne Herdman Royal, M.D.

Lymphoplasmacytic infiltrate


Contributed by Raul Gonzalez, M.D.

Obliterative phlebitis



Contributed by Oyelele Adeyi, M.D.

Lymphoplasmacytic infiltrate and fibrosis

Lymphoplasmacytic infiltrate

Storiform fibrosis


Masson trichrome stain

IgG4 immunostain

Cytology images

Images hosted on other servers:

Type 1

Positive stains
  • Immunohistochemistry is largely unnecessary
  • IgG and IgG4: > 10 IgG4+ plasma cells/high powered field in biopsy specimens and > 50 IgG4+ plasma cells/high powered field in resection specimens, both with an IgG4/IgG ratio of > 40% (Gastroenterol Res Pract 2017;2017:3246459, Virchows Arch 2018;472:545)
  • Elastin highlights remnant veins in longstanding autoimmune pancreatitis; Masson trichrome highlights storiform fibrosis
  • DPC4 may be needed in difficult cases where the differential diagnosis includes pancreatic adenocarcinoma (DPC4 is lost in approximately 50% of pancreatic adenocarcinomas)
Differential diagnosis
  • Pancreatic ductal adenocarcinoma:
    • Main differential diagnosis
    • Both may show painless jaundice, an infiltrative pancreatic mass, ± elevated serum IgG4 and ± elevated serum CA 19-9
    • CT or MRI can show similar findings with contrast, including a fibrotic rim
    • Core needle biopsy may not show all three histologic features of autoimmune pancreatitis type 1
    • Should not cause inflammation in other glands as can be present in autoimmune pancreatitis type 1
  • Autoimmune pancreatitis type 2:
    • Younger age group associated with inflammatory bowel disease (not other IgG4 related sites of involvement), no male predominance (GE Port J Gastroenterol 2017;24:296)
    • Duct centric granulocytic abscesses and lobular (but not storiform) fibrosis
  • Follicular pancreatitis:
    • Inflammation with numerous lymphoid follicles, ± prominent germinal centers
    • Lacks storiform fibrosis, obliterative phlebitis and IgG4+ cells
  • Obstructive chronic pancreatitis: groups of acini and tubules scattered in fibrous tissue
Board review question #1
A patient presents with painless jaundice, a pancreatic mass on imaging, increased serum IgG4 and increased CA 19-9. Which of the following statements is false?

  1. Core biopsy diagnosis requires all three histologic features of autoimmune pancreatitis type 1
  2. Differential diagnosis includes autoimmune pancreatitis type 1 and pancreatic adenocarcinoma
  3. Normal serum IgG4 is possible in autoimmune pancreatitis type 1
  4. Presence of duct centric neutrophils would exclude the diagnosis of autoimmune pancreatitis type 1
Board review answer #1
A. Core biopsy does not require all three histologic features for diagnosis.

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Board review question #2
What statement about the photomicrograph from a pancreas resection specimen below is true?



  1. Absence of IgG4+ plasma cells excludes autoimmune pancreatitis type 1 from the differential diagnosis
  2. Inflammatory bowel disease is the most common extrapancreatic condition with this diagnosis
  3. Sclerosing cholangitis is the most common extrapancreatic condition with this diagnosis
  4. This is a duct centric inflammatory process and therefore autoimmune pancreatitis type 1 is excluded
Board review answer #2
C. Sclerosing cholangitis is the most common extrapancreatic condition with this diagnosis. This is a photomicrograph of autoimmune pancreatitis type 1. Although duct centric fibrosis is present, there are no neutrophils and the epithelium is intact and uninvolved. IgG4+ plasma cells may or may not be present and their absence does not exclude a diagnosis of autoimmune pancreatitis type 1. The most common extrapancreatic condition is sclerosing cholangitis (in contrast to autoimmune pancreatitis type 2, which is most frequently associated with inflammatory bowel disease).

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