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Virchows Archiv

, Volume 445, Issue 6, pp 552–563 | Cite as

Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens

  • Giuseppe Zamboni
  • Jutta Lüttges
  • Paola Capelli
  • Luca Frulloni
  • Giorgio Cavallini
  • Paolo Pederzoli
  • Alexander Leins
  • Daniel Longnecker
  • Günter KlöppelEmail author
Original Article

Abstract

Background and Aims

Autoimmune pancreatitis seems to be a disease with a heterogeneous appearance. Our intention was to establish key diagnostic criteria, define grades of severity and activity, identify features of potential subtypes and evaluate the diagnostic relevance of biopsy specimens.

Methods

Histopathological criteria and clinical features were recorded in pancreatic resection specimens from 53 patients who were found to have chronic pancreatitis lacking pseudocysts, calculi, irregular duct dilatations, pancreas divisum and/or duodenal wall inflammation. The severity of the chronic inflammation was graded, and the activity of the acute inflammatory component and the granulocytic epithelial lesion (GEL) were determined. Additionally, pancreatic biopsy specimens from 9 patients with suspected AIP were assessed.

Results

Periductal lymphoplasmacytic infiltration was identified in all cases, followed in order of frequency by periductal fibrosis and venulitis. These changes were absent in 147 pancreatic specimens that showed chronic pancreatitis associated with pseudocysts, calculi, pancreas divisum and/or duodenal wall inflammation. In 90% of the cases, these chronic changes were graded as 3 or 4. In 81%, the inflammatory process resided in the head of the pancreas and involved the common bile duct. GELs were present in 42% of the patients, who had a mean age of 40.5 years, an almost equal male–female ratio and a high coincidence of ulcerative colitis or Crohn’s disease. Patients without GELs were older (mean age 64 years), showed a male preponderance, commonly had Sjögren’s syndrome and often developed recurrent bile-duct stenosis. Diagnostically relevant lesions were present in two of five wedge biopsy specimens and three of four fine-needle specimens.

Conclusions

Periductal lymphoplasmacytic infiltration and fibrosis, preferential occurrence in the pancreatic head and venulitis characterize autoimmune pancreatitis. GELs predominantly occur in a subset of patients who are younger, more commonly have ulcerative colitis and Crohn’s disease and seem to have fewer recurrences than patients without GELs. Pancreatic biopsy material proved to be a very helpful adjunct for establishing the diagnosis.

Keywords

Autoimmune pancreatitis Duct destructive chronic pancreatitis Histopathology Grading Biopsy 

Notes

Acknowledgements

Sincere thanks are due to the many pathologists who sent in cases for consultation. Specifically, we would like to thank Drs. Anita Goossens and Franz Borchert. We are grateful to M. Pacena and A. Paulus for their excellent technical assistance and K. Dege for editing the manuscript.

References

  1. 1.
    Abraham SC, Cruz-Correa M, Argani P, Furth EE, Hruban RH, Boitnott JK (2003) Lymphoplasmacytic chronic cholecystitis and biliary tract disease in patients with lymphoplasmacytic sclerosing pancreatitis. Am J Surg Pathol 27:441–451CrossRefPubMedGoogle Scholar
  2. 2.
    Abraham SC, Leach S, Yeo CJ, Cameron JL, Murakata LA, Boitnott JK, Albores-Saavedra J, Hruban RH (2003) Eosinophilic pancreatitis and increased eosinophils in the pancreas. Am J Surg Pathol 27:334–342CrossRefPubMedGoogle Scholar
  3. 3.
    Abraham SC, Wilentz RE, Yeo CJ, Sohn TA, Cameron JL, Boitnott JK, Hruban RH (2003) Pancreaticoduodenectomy (Whipple resections) in patients without malignancy. Are they all “chronic pancreatitis”? Am J Surg Pathol 27:110–120CrossRefPubMedGoogle Scholar
  4. 4.
    Axon ATR, Ashton MG, Lintott DJ (1979) Chronic pancreatitis and inflammatory bowel disease. Clin Radiol 30:179–182PubMedGoogle Scholar
  5. 5.
    Ball WP, Baggenstoss AH, Bargen JA (1950) Pancreatic lesions associated with chronic ulcerative colitis. Arch Pathol 50:347–358Google Scholar
  6. 6.
    Cavallini G, Frulloni L (2001) Autoimmunity and chronic pancreatitis: a concealed relationship. J O P 2:61–68Google Scholar
  7. 7.
    Chutaputti A, Burrell MI, Boyer JL (1995) Pseudotumor of the pancreas associated with retroperitoneal fibrosis: a dramatic response to corticosteroid therapy. Am J Gastroenterol 90:1155–1158PubMedGoogle Scholar
  8. 8.
    Clark A, Zeman RK, Choyke PL, White EM, Burrell MI, Grant EG, Jaffe MH (1988) Pancreatic pseudotumors associated with multifocal idiopathic fibrosclerosis. Gastrointest Radiol 13:30–32PubMedGoogle Scholar
  9. 9.
    Ectors N, Maillet B, Aerts R, Geboes K, Donner A, Borchard F, Lankisch P, Stolte M, Lüttges J, Kremer B, Klöppel G (1997) Non-alcoholic duct destructive chronic pancreatitis. Gut 41:263–268PubMedGoogle Scholar
  10. 10.
    Esposito I, Bergmann F, Penzel R, di Mola FF, Shrikhande S, Büchler MW, Friess H, Otto HF (2004) Oligoclonal T-cell populations in an inflammatory pseudotumor of the pancreas possibly related to autoimmune pancreatitis: an immunohistochemical and molecular analysis. Virchows Arch 444:119–126CrossRefPubMedGoogle Scholar
  11. 11.
    Fukushima N, Suzuki M, Abe T, Fukayama M (1997) A case of inflammatory pseudotumour of the common bile duct. Virchows Arch 431:219–224CrossRefPubMedGoogle Scholar
  12. 12.
    Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, Fukushima M, Nikaido T, Nakayama K, Usuda N, Kiyosawa K (2001) High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 344:732–738CrossRefPubMedGoogle Scholar
  13. 13.
    Hamano H, Kawa S, Ochi Y, Takayama M, Komatsu K, Muraki T, Kiyosawa K (2004) Recurrent attacks of autoimmune pancreatitis result in pancreatic stone formation. Pancreatology 4:297Google Scholar
  14. 14.
    Hardacre JM, Iacobuzio-Donahue CA, Sohn TA, Abraham SC, Yeo CJ, Lillemoe KD, Choti MA, Campbell KA, Schulick RD, Hruban RH, Cameron JL, Leach SD (2003) Results of pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis. Ann Surg 237:853–859CrossRefPubMedGoogle Scholar
  15. 15.
    Horiuchi A, Kawa S, Hamano H, Hayama M, Ota H, Kiyosawa K (2002) ERCP features in 27 patients with autoimmune pancreatitis. Gastrointest Endosc 55:494–499CrossRefPubMedGoogle Scholar
  16. 16.
    Kamisawa T, Egawa N, Nakajima H, Tsuruta K, Okamoto A, Kamata N (2003) Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma. Am J Gastroenterol 98:2694–2699PubMedGoogle Scholar
  17. 17.
    Kamisawa T, Funata N, Hayashi Y, Tsuruta K, Okamoto A, Amemiya K, Egawa N, Nakajima H (2003) Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut 52:683–687CrossRefPubMedGoogle Scholar
  18. 18.
    Kawaguchi K, Koike M, Tsuruta K, Okamoto A, Tabata I, Fujita N (1991) Lymphoplasmacytic sclerosing pancreatitis with cholangitis: variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol 22:387–395CrossRefPubMedGoogle Scholar
  19. 19.
    Klöppel G, Lüttges J, Löhr M, Zamboni G, Longnecker D (2003) Autoimmune pancreatitis: pathological, clinical, and immunological features. Pancreas 27:14–19CrossRefPubMedGoogle Scholar
  20. 20.
    Klöppel G, Detlefsen S, Feyerabend B (2004) Fibrosis of the pancreas: the initial tissue damage and the resulting pattern. Virchows Arch 445:1–8PubMedGoogle Scholar
  21. 21.
    Kojima E, Kimura K, Noda Y, Kobayashi G, Itoh K, Fujita N (2003) Autoimmune pancreatitis and multiple bile duct strictures treated effectively with steroid. J Gastroenterol 38:603–607CrossRefPubMedGoogle Scholar
  22. 22.
    Lindström E, Lindström F, Von Schenck H, Ihse I (1991) Pancreatic ductal morphology and function in primary Sjogren’s syndrome. Int J Pancreatol 8:141–149PubMedGoogle Scholar
  23. 23.
    Lysy J, Goldin E (1992) Pancreatitis in ulcerative colitis. J Clin Gastroenterol 15:336–339PubMedGoogle Scholar
  24. 24.
    Nonomura A, Minato H, Shimizu K, Kadoya M, Matsui O (1997) Hepatic hilar inflammatory pseudotumor mimicking cholangiocarcinoma with cholangitis and phlebitis—a variant of primary sclerosing cholangitis? Pathol Res Pract 193:519–525PubMedGoogle Scholar
  25. 25.
    Notohara K, Burgart LJ, Yadav D, Chari S, Smyrk TC (2003) Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases. Am J Surg Pathol 27:1119–1127CrossRefPubMedGoogle Scholar
  26. 26.
    Okazaki K, Chiba T (2002) Autoimmune related pancreatitis. Gut 51:1–4CrossRefPubMedGoogle Scholar
  27. 27.
    Palazzo JP, Chang CD (1993) Inflammatory pseudotumour of the pancreas. Histopathology 23:475–477PubMedGoogle Scholar
  28. 28.
    Pearson RK, Longnecker DS, Chari ST, Smyrk TC, Okazaki K, Frulloni L, Cavallini G (2003) Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist? Pancreas 27:1–13CrossRefPubMedGoogle Scholar
  29. 29.
    Potamianos S, Koutroubakis IE, Chatzicostas C, Rolles K, Burroughs AK, Kouroumalis EA (2000) Idiopathic fibrosing pancreatitis and Crohn’s disease: an interesting association. Eur J Gastroenterol Hepatol 12:1021–1024PubMedGoogle Scholar
  30. 30.
    Procacci C, Carbonin G, Biasiutti C, Frulloni L, Bicego E, Spoto E, El-Khaldi M, Bassi C, Pagnotta N, Talamini G (2001) Autoimmune pancreatitis: possibilities of CT characterization. Pancreatology 1:246–253CrossRefPubMedGoogle Scholar
  31. 31.
    Renner IG, Ponto GC, Savage WT3, Boswell WD (1980) Idiopathic retroperitoneal fibrosis producing common bile duct and pancreatic duct obstruction. Gastroenterology 79:348–351PubMedGoogle Scholar
  32. 32.
    Sarles H, Sarles JC, Muratore R, Guien C (1961) Chronic inflammatory sclerosis of the pancreas—an autoimmune pancreatic disease? Am J Dig Dis 6:688–698PubMedGoogle Scholar
  33. 33.
    Scully KA, Li SC, Hebert JC, Trainer TD (2000) The characteristic appearance of non-alcoholic duct destructive chronic pancreatitis. A report of 2 cases. Arch Pathol Lab Med 124:1535–1538PubMedGoogle Scholar
  34. 34.
    Scully RE, Mark EJ, McNeely BU (1982) Weekly clinicopathological exercises—case 6–1982. N Engl J Med 306:349–358PubMedGoogle Scholar
  35. 35.
    Seyrig JA, Jian R, Modigliani R, Golfain D, Florent C, Messing B, Bitoun A (1985) Idiopathic pancreatitis associated with inflammatory bowel disease. Dig Dis Sci 30:1121–1126PubMedGoogle Scholar
  36. 36.
    Sjögren I, Wengle B, Korsgren M (1979) Primary sclerosing cholangitis associated with fibrosis of the submandibular glands and the pancreas. Acta Med Scand 205:139–141PubMedGoogle Scholar
  37. 37.
    Sood S, Fossard DP, Shorrock K (1995) Chronic sclerosing pancreatitis in Sjögren’s syndrome: a case report. Pancreas 10:419–421PubMedGoogle Scholar
  38. 38.
    Uchida K, Okazaki K, Asada M, Yazumi S, Ohana M, Chiba T (2003) Case of chronic pancreatitis involving an autoimmune mechanism that extended to retroperitoneal fibrosis. Pancreas 26:92–94CrossRefPubMedGoogle Scholar
  39. 39.
    Waldram R, Kopelman H, Tsantoulas D, Williams R (1975) Chronic pancreatitis, sclerosing cholangitis, and sicca complex in two siblings. Lancet 550–552Google Scholar
  40. 40.
    Walsh SV, Evangelista F, Khettry U (1998) Inflammatory myofibroblastic tumor of the pancreaticobiliary region. Morphologic and immunocytochemical study of three cases. Am J Surg Pathol 22:412–418CrossRefPubMedGoogle Scholar
  41. 41.
    Weber SM, Cubukcu-Dimopulo O, Palesty JA, Suriawinata A, Klimstra D, Brennan MF, Conlon K (2003) Lymphoplasmacytic sclerosing pancreatitis: inflammatory mimic of pancreatic carcinoma. J Gastrointest Surg 7:129–139CrossRefPubMedGoogle Scholar
  42. 42.
    Wreesmann V, van Eijck CHJ, Naus DCWH, van Velthuysen MLF, Jeekel J, Mooi WJ (2001) Inflammatory pseudotumour (inflammatory myofibroblastic tumour) of the pancreas: a report of six cases associated with obliterative phlebitis. Histopathology 38:105–110CrossRefPubMedGoogle Scholar
  43. 43.
    Yoshida K, Toki F, Takeuchi T, Watanabe S, Shiratori K, Hayashi N (1995) Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci 40:1561–1568PubMedGoogle Scholar
  44. 44.
    Youssef N, Petitjean B, Bonte H, Terris B, de Saint Maur PP, Fléjou JF (2004) Non-alcoholic duct destructive chronic pancreatitis: a histological, immunohistochemical and in-situ apoptosis study of 18 cases. Histopathology 44:453–461PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Giuseppe Zamboni
    • 1
  • Jutta Lüttges
    • 2
  • Paola Capelli
    • 1
  • Luca Frulloni
    • 3
  • Giorgio Cavallini
    • 3
  • Paolo Pederzoli
    • 3
  • Alexander Leins
    • 4
  • Daniel Longnecker
    • 5
  • Günter Klöppel
    • 2
    Email author
  1. 1.Department of PathologyUniversity of VeronaVeronaItaly
  2. 2.Department of PathologyUniversity of KielKielGermany
  3. 3.Department of Surgical and Gastroenterological SciencesUniversity of VeronaVeronaItaly
  4. 4.Department of SurgeryUniversity of KielKielGermany
  5. 5.Department of PathologyDartmouth-Hitchcock Medical CenterLebanonUSA

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