Skip to main content

Advertisement

SpringerLink
Log in

Autoimmune pancreatitis: the clinicopathological characteristics of the subtype with granulocytic epithelial lesions

  • Review
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Autoimmune pancreatitis (AIP) has been established as a distinct form of chronic pancreatitis that is distinguishable from other types such as alcoholic, hereditary or obstructive chronic pancreatitis. AIP seems to be a global disease, since it has been reported in many different countries, especially from Japan, USA and Europe (Germany, Italy, United Kingdom). Typical histopathological findings in the pancreas in AIP include a periductal lymphoplasmacytic infiltration with fibrosis, causing narrowing of the involved ducts. The typical clinical features include presentation with obstructive jaundice/pancreatic mass and a dramatic response to steroids. However, while the reports from Japan describe uniform changes called lymphoplasmacytic sclerosing pancreatitis (LPSP) in the pancreas from AIP patients, the reports from Europe and USA distinguish two histopathologic patterns in AIP patients: one with the characteristics of LPSP and another with slightly different histological features, called idiopathic duct centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesions (GELs). This article reviews the evidence that GEL-positive AIP or IDCP is a second type of AIP, distinct from LPSP, in regard to pancreatic pathology, immunology and epidemiology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Detlefsen S, Sipos B, Feyerabend B, Klöppel G. Pancreatic fibrosis associated with age and ductal papillary hyperplasia. Virchows Arch. 2005;447:800–5.

    Article  PubMed  Google Scholar 

  2. Detlefsen S, Sipos B, Feyerabend B, Klöppel G. Fibrogenesis in alcoholic chronic pancreatitis: the role of tissue necrosis, macrophages, myofibroblasts and cytokines. Mod Pathol. 2006;19:1019–26.

    CAS  PubMed  Google Scholar 

  3. Weber SM, Cubukcu-Dimopulo O, Palesty JA, Suriawinata A, Klimstra D, Brennan MF, et al. Lymphoplasmacytic sclerosing pancreatitis: inflammatory mimic of pancreatic carcinoma. J Gastrointest Surg. 2003;7:129–37.

    Article  PubMed  Google Scholar 

  4. Zamboni G, Lüttges J, Capelli P, Frulloni L, Cavallini G, Pederzoli P, et al. Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens. Virchows Arch. 2004;445:552–63.

    Article  PubMed  Google Scholar 

  5. Zamboni G, Capelli P, Scarpa A, Bogina G, Pesci A, Brunello E, et al. Nonneoplastic mimickers of pancreatic neoplasms. Arch Pathol Lab Med. 2009;133:439–53.

    PubMed  Google Scholar 

  6. Finkelberg DL, Sahani D, Deshpande V, Brugge WR. Autoimmune pancreatitis. N Engl J Med. 2006;355:2670–6.

    Article  CAS  PubMed  Google Scholar 

  7. Pickartz T, Mayerle J, Lerch MM. Autoimmune pancreatitis. Nat Clin Pract Gastroenterol Hepatol. 2007;4:314–23.

    Article  CAS  PubMed  Google Scholar 

  8. Notohara K, Burgart LJ, Yadav D, Chari S, Smyrk TC. Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases. Am J Surg Pathol. 2003;27:1119–27.

    Article  PubMed  Google Scholar 

  9. Kawaguchi K, Koike M, Tsuruta K, Okamoto A, Tabata I, Fujita N. Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol. 1991;22:387–95.

    Article  CAS  PubMed  Google Scholar 

  10. Ectors N, Maillet B, Aerts R, Geboes K, Donner A, Borchard F, et al. Non-alcoholic duct destructive chronic pancreatitis. Gut. 1997;41:263–8.

    Article  CAS  PubMed  Google Scholar 

  11. Sugumar A, Klöppel G, Chari ST. Autoimmune pancreatitis: pathologic subtypes and their implications for its diagnosis. Am J Gastroenterol. 2009;104:2308–10.

    Article  PubMed  Google Scholar 

  12. Detlefsen S, Sipos B, Zhao J, Drewes AM, Klöppel G. Autoimmune pancreatitis: expression and cellular source of profibrotic cytokines and their receptors. Am J Surg Pathol. 2008;32:986–95.

    Article  PubMed  Google Scholar 

  13. Kojima M, Sipos B, Klapper W, Frahm O, Knuth HC, Yanagisawa A, et al. Autoimmune pancreatitis: frequency, IgG4 expression, and clonality of T and B cells. Am J Surg Pathol. 2007;31:521–8.

    Article  PubMed  Google Scholar 

  14. Zhang L, Notohara K, Levy MJ, Chari ST, Smyrk TC. IgG4-positive plasma cell infiltration in the diagnosis of autoimmune pancreatitis. Mod Pathol. 2007;20:23–8.

    Article  CAS  PubMed  Google Scholar 

  15. Detlefsen S, Drewes AM, Vyberg M, Klöppel G. Diagnosis of autoimmune pancreatitis by core needle biopsy: application of six microscopic criteria. Virchows Arch. 2009;454:531–9.

    Article  CAS  PubMed  Google Scholar 

  16. Kamisawa T, Imai M, Egawa N, Tsuruta K, Okamoto A. Serum IgG4 levels and extrapancreatic lesions in autoimmune pancreatitis. Eur J Gastroenterol Hepatol. 2008;20:1167–70.

    Article  CAS  PubMed  Google Scholar 

  17. Sahani DV, Kalva SP, Farrell J, Maher MM, Saini S, Mueller PR, et al. Autoimmune pancreatitis: imaging features. Radiology. 2004;233:345–52.

    Article  PubMed  Google Scholar 

  18. Uchida K, Yazumi S, Nishio A, Kusuda T, Koyabu M, Fukata M, et al. Long-term outcome of autoimmune pancreatitis. J Gastroenterol. 2009;44:726–32.

    Article  CAS  PubMed  Google Scholar 

  19. Uchiyama-Tanaka Y, Mori Y, Kimura T, Sonomura K, Umemura S, Kishimoto N, et al. Acute tubulointerstitial nephritis associated with autoimmune-related pancreatitis. Am J Kidney Dis. 2004;43:e18–25.

    Article  PubMed  Google Scholar 

  20. Sah RP, Chari ST, Pannala R, Sugumar A, Clain JE, Levy MJ, et al. Differences in clinical profile and relapse rate of type 1 vs type 2 autoimmune pancreatitis. Gastroenterology. 2010 (in press).

  21. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732–8.

    Article  CAS  PubMed  Google Scholar 

  22. Kamisawa T, Funata N, Hayashi Y, Tsuruta K, Okamoto A, Amemiya K, et al. Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut. 2003;52:683–7.

    Article  CAS  PubMed  Google Scholar 

  23. Kamisawa T, Nakajima H, Egawa N, Funata N, Tsuruta K, Okamoto A. IgG4-related sclerosing disease incorporating sclerosing pancreatitis, cholangitis, sialadenitis and retroperitoneal fibrosis with lymphadenopathy. Pancreatology. 2006;6:132–7.

    Article  CAS  PubMed  Google Scholar 

  24. Aparisi L, Farre A, Gomez-Cambronero L, Martinez J, De Las HG, Corts J, et al. Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis. Gut. 2005;54:703–9.

    Article  CAS  PubMed  Google Scholar 

  25. Choi EK, Kim MH, Lee TY, Kwon S, Oh HC, Hwang CY, et al. The sensitivity and specificity of serum immunoglobulin G and immunoglobulin G4 levels in the diagnosis of autoimmune chronic pancreatitis: Korean experience. Pancreas. 2007;35:156–61.

    Article  PubMed  Google Scholar 

  26. Hochwald SN, Hemming AW, Draganov P, Vogel SB, Dixon LR, Grobmyer SR. Elevation of serum IgG4 in Western patients with autoimmune sclerosing pancreatocholangitis: a word of caution. Ann Surg Oncol. 2008;15:1147–54.

    Article  PubMed  Google Scholar 

  27. Kleeff J, Welsch T, Esposito I, Löhr M, Singer R, Büchler MW, et al. Autoimmune pancreatitis—a surgical disease? Chirurg. 2006;77:154–65.

    Article  CAS  PubMed  Google Scholar 

  28. Löhr JM. What are the useful biological and functional markers of early-stage chronic pancreatitis? J Gastroenterol. 2007;42(Suppl 17):66–71.

    Article  PubMed  Google Scholar 

  29. Nahon UK, Levy P, O’Toole D, Belmatoug N, Vullierme MP, Couvelard A, et al. Is idiopathic chronic pancreatitis an autoimmune disease? Clin Gastroenterol Hepatol. 2005;3:903–9.

    Article  Google Scholar 

  30. Pearson RK, Longnecker DS, Chari ST, Smyrk TC, Okazaki K, Frulloni L, et al. Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist? Pancreas. 2003;27:1–13.

    Article  PubMed  Google Scholar 

  31. Fujimoto T, Kato J, Nasu J, Kuriyama M, Okada H, Yamamoto H, et al. Change of clinical characteristics of ulcerative colitis in Japan: analysis of 844 hospital-based patients from 1981 to 2000. Eur J Gastroenterol Hepatol. 2007;19:229–35.

    Article  PubMed  Google Scholar 

  32. Kim KP, Kim MH, Song MH, Lee SS, Seo DW, Lee SK. Autoimmune chronic pancreatitis. Am J Gastroenterol. 2004;99:1605–16.

    Article  PubMed  Google Scholar 

  33. Ito T, Nishimori I, Inoue N, Kawabe K, Gibo J, Arita Y, et al. Treatment for autoimmune pancreatitis: consensus on the treatment for patients with autoimmune pancreatitis in Japan. J Gastroenterol. 2007;42(Suppl 18):50–8.

    Article  PubMed  Google Scholar 

  34. Saito T, Tanaka S, Yoshida H, Imamura T, Ukegawa J, Seki T, et al. A case of autoimmune pancreatitis responding to steroid therapy. Evidence of histologic recovery. Pancreatology. 2002;2:550–6.

    Article  PubMed  Google Scholar 

  35. Asada M, Nishio A, Uchida K, Kido M, Ueno S, Uza N, et al. Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis. Pancreas. 2006;33:20–6.

    Article  CAS  PubMed  Google Scholar 

  36. Löhr JM, Faissner R, Koczan D, Bewerunge P, Bassi C, Brors B, et al. Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process. Am J Gastroenterol. 2010. doi:10.1038/ajg.2010.141.

  37. Okazaki K, Uchida K, Ohana M, Nakase H, Uose S, Inai M, et al. Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology. 2000;118:573–81.

    Article  CAS  PubMed  Google Scholar 

  38. Klöppel G, Detlefsen S, Feyerabend B. Fibrosis of the pancreas: the initial tissue damage and the resulting pattern. Virchows Arch. 2004;445:1–8.

    Article  PubMed  Google Scholar 

  39. Chari ST, Takahashi N, Levy MJ, Smyrk TC, Clain JE, Pearson RK, et al. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol. 2009;7:1097–103.

    Article  CAS  PubMed  Google Scholar 

  40. Kamisawa T, Okamoto A, Wakabayashi T, Watanabe H, Sawabu N. Appropriate steroid therapy for autoimmune pancreatitis based on long-term outcome. Scand J Gastroenterol. 2008;43:609–13.

    Article  CAS  PubMed  Google Scholar 

  41. Cornell LD, Chicano SL, Deshpande V, Collins AB, Selig MK, Lauwers GY, et al. Pseudotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease. Am J Surg Pathol. 2007;31:1586–97.

    Article  PubMed  Google Scholar 

  42. Deshpande V, Chicano S, Finkelberg D, Selig MK, Mino-Kenudson M, Brugge WR, et al. Autoimmune pancreatitis: a systemic immune complex mediated disease. Am J Surg Pathol. 2006;30:1537–45.

    Article  PubMed  Google Scholar 

  43. Detlefsen S, Bräsen JH, Zamboni G, Capelli P, Klöppel G. Deposition of complement C3c, IgG4 and IgG at the basement membrane of pancreatic ducts and acini in autoimmune pancreatitis. Histopathology. 2010 (in press).

  44. Taniguchi T, Okazaki K, Okamoto M, Seko S, Tanaka J, Uchida K, et al. High prevalence of autoantibodies against carbonic anhydrase II and lactoferrin in type 1 diabetes: concept of autoimmune exocrinopathy and endocrinopathy of the pancreas. Pancreas. 2003;27:26–30.

    Article  CAS  PubMed  Google Scholar 

  45. Uchida K, Okazaki K, Nishi T, Uose S, Nakase H, Ohana M, et al. Experimental immune-mediated pancreatitis in neonatally thymectomized mice immunized with carbonic anhydrase II and lactoferrin. Lab Invest. 2002;82:411–24.

    CAS  PubMed  Google Scholar 

  46. Yamamoto M, Naishiro Y, Suzuki C, Kokai Y, Suzuki R, Honda S, et al. Proteomics analysis in 28 patients with systemic IgG4-related plasmacytic syndrome. Rheumatol Int. 2010;30:565–8.

    Article  CAS  PubMed  Google Scholar 

  47. Frulloni L, Lunardi C, Simone R, Dolcino M, Scattolini C, Falconi M, et al. Identification of a novel antibody associated with autoimmune pancreatitis. N Engl J Med. 2009;361:2135–42.

    Article  CAS  PubMed  Google Scholar 

  48. Chari ST, Longnecker DS, Klöppel G. The diagnosis of autoimmune pancreatitis: a Western perspective. Pancreas. 2009;38:846–8.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Health Research Fund of Central Denmark Region.

Author information

Authors and Affiliations

  1. Department of Pathology, Technical University of Munich, Ismaninger-Str. 22, 81675, Munich, Germany

    Günter Klöppel

  2. Department of Pathology, University of Kiel, Kiel, Germany

    Günter Klöppel

  3. Department of Pathology, Odense University Hospital, Odense, Denmark

    Sönke Detlefsen

  4. Department of Gastroenterology, Mayo Clinic, Rochester, MN, USA

    Suresh T. Chari

  5. Department of Pathology, Dartmouth Medical School, Hanover, NH, USA

    Daniel S. Longnecker

  6. Department of Pathology, University of Verona, Verona, Italy

    Giuseppe Zamboni

Authors
  1. Günter Klöppel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sönke Detlefsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suresh T. Chari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel S. Longnecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giuseppe Zamboni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Günter Klöppel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klöppel, G., Detlefsen, S., Chari, S.T. et al. Autoimmune pancreatitis: the clinicopathological characteristics of the subtype with granulocytic epithelial lesions. J Gastroenterol 45, 787–793 (2010). https://doi.org/10.1007/s00535-010-0265-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-010-0265-x

Keywords

Search

Navigation