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Pancreatic fibrosis associated with age and ductal papillary hyperplasia

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Abstract

Little is known about the frequency, type and pathogenesis of fibrotic changes that may occur in the pancreas of persons without any clinically apparent or macroscopically visible pancreatic disease. We screened pancreas specimens for the presence and pattern of fibrosis, determined the relationship between fibrosis, age, and duct lesions, and studied the fibrogenic mechanisms. In 89 postmortem specimens from persons without any known pancreatic disease (age range 20–86 years), fibrosis was recorded and graded and the patients were divided into two age classes (younger or older than 60 years). In addition, we analyzed the association between ductal papillary hyperplasia [i.e., pancreatic intraepithelial neoplasia type 1B (PanIN-1B)] and fibrotic foci in the pancreatic tissue to determine the potential impact of obliterating duct lesions on pancreatic fibrosis. Finally, we studied the occurrence in the pancreas of myofibroblasts, identified on the basis of their α-SMA and desmin positivity, and determined their relationship to the fibrotic foci. Thirty-eight (44%) of 89 pancreata showed scattered foci of lobular fibrosis affecting peripheral lobuli. Fibrotic changes were significantly more common in individuals older than 60 years. Fibrotic foci were commonly associated (p<0.05) with ductal papillary hyperplasia in ducts draining fibrotic lobuli. Myofibroblasts were detected in the fibrotic foci. The “normal” pancreas develops a specific type of focally accentuated fibrosis that is highly age related. This patchy lobular fibrosis in the elderly (PLFE) was closely associated with PanIN-1B lesions in the ducts, suggesting that the narrowing of a duct due to papillary hyperplasia of the epithelium may hamper secretion and cause fibrosis of the drained lobule. The presence of myofibroblasts in association with the fibrotic foci indicates an ongoing fibrogenic process.

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References

  1. Adsay NV, Merati K, Basturk O, Iacobuzio-Donahue C, Levi E, Cheng JD, Sarkar FH, Hruban RH, Klimstra DS (2004) Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms. Delineation of an “intestinal” pathway of carcinogenesis in the pancreas. Am J Surg Pathol 28:839–848

    Article  PubMed  Google Scholar 

  2. Allen-Mersh TG (1985) What is the significance of pancreatic ductal mucinous hyperplasia? Gut 26:825–833

    Article  PubMed  CAS  Google Scholar 

  3. Ammann RW, Heitz PU, Klöppel G (1996) Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study. Gastroenterology 111:224–231

    Article  PubMed  CAS  Google Scholar 

  4. Andea A, Sarkar F, Adsay NV (2003) Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma. Mod Path 16:996–1006

    Article  Google Scholar 

  5. Barth PJ, Ebrahimsade S, Hellinger A, Moll R, Ramaswamy A (2002) CD34+ fibrocytes in neoplastic and inflammatory pancreatic lesions. Virchows Arch 440:128–133

    Article  PubMed  CAS  Google Scholar 

  6. Cubilla AL, Fitzgerald PJ (1976) Morphological lesions associated with human primary invasive nonendocrine pancreas cancer. Cancer Res 36:2690–2698

    PubMed  CAS  Google Scholar 

  7. Haber PS, Keogh GW, Apte MV, Moran CS, Stewart NL, Crawford DHG, Pirola RC, McCaughan GW, Ramm GA, Wilson JS (1999) Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis. Am J Pathol 155:1087–1095

    PubMed  CAS  Google Scholar 

  8. Hruban RH, Adsay NV, Albores-Saavedra J, Compton C, Garrett ES, Goodman SN, Kern SE, Klimstra DS, Klöppel G, Longnecker DS, Lüttges J, Offerhaus GJA (2001) Pancreatic intraepithelial neoplasia. A new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 25:579–586

    Article  PubMed  CAS  Google Scholar 

  9. Hultquist GT, Jönsson LE (1965) Ligation of the pancreatic duct in rats. Acta Soc Med Ups 70:82–88

    PubMed  CAS  Google Scholar 

  10. Isaksson G, Ihse I, Lundquist I (1983) Influence of pancreatic duct ligation on endocrine and exocrine rat pancreas. Acta Physiol Scand 117:281–286

    Article  PubMed  CAS  Google Scholar 

  11. Junqueira LC, Carneiro J (1995) Pancreas. In: LC Junqueira, J Carneiro (eds) Basic histology, 8th edn. Lange Medical Publications, Los Altos

    Google Scholar 

  12. Kimura W, Nagai H, Kuroda A, Muto T, Esaki Y (1995) Analysis of small cystic lesions of the pancreas. Int J Pancreatol 18:197–206

    PubMed  CAS  Google Scholar 

  13. Klimstra DS (1997) Pancreas. In: SS Sternberg (ed) Histology for pathologists, 2nd edn. Lippincott-Raven, Philadelphia, pp 613–647

    Google Scholar 

  14. Klöppel G, Bommer G, Rückert K, Seifert G (1980) Intraductal proliferation in the pancreas and its relationship to human and experimental carcinogenesis. Virchows Arch, A Pathol Anat 387:221–233

    Article  Google Scholar 

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

    Article  PubMed  Google Scholar 

  16. Klöppel G, Maillet B (1993) Pathology of acute and chronic pancreatitis. Pancreas 8:659–670

    Article  PubMed  Google Scholar 

  17. Klöppel G, Maillet B (1998) Pathology of chronic pancreatitis. In: Beger H, Warshaw AL, Büchler M, Carr-Locke DL, Neoptolemos JP, Russell C, Sarr MG (eds) The pancreas, vol 1. Blackwell, Oxford, pp 720–723

    Google Scholar 

  18. Klöppel G, Solcia E, Longnecker DS, Capella C, Sobin LH (1996) Histological typing of tumours of the exocrine pancreas, 2nd edn. WHO International histological classification of tumours. Springer, Berlin Heidelberg New York

    Google Scholar 

  19. Kozuka S, Sassa R, Taki T, Masamoto K, Nagasawa S, Saga S, Hasegawa K, Takeuchi M (1979) Relation of pancreatic duct hyperplasia to carcinoma. Cancer 43:1418–1428

    Article  PubMed  CAS  Google Scholar 

  20. Lüttges J, Klöppel G (2000) Precancerous conditions of pancreatic carcinoma. J Hepatobiliary Pancreat Surg 7:568–574

    Article  PubMed  Google Scholar 

  21. Lüttges J, Reinecke-Lüthge A, Möllmann B, Menke MAOH, Clemens A, Klimpfinger M, Sipos B, Klöppel G (1999) Duct changes and K-ras mutations in the disease-free pancreas: analysis of type, age relation and spatial distribution. Virchows Arch 435:461–468

    Article  PubMed  Google Scholar 

  22. Pitchumoni CS, Glasser M, Saran RM, Panchacharam P, Thelmo W (1984) Pancreatic fibrosis in chronic alcoholics and nonalcoholics without clinical pancreatitis. Am J Gastroenterol 79:382–388

    PubMed  CAS  Google Scholar 

  23. Schmitz-Moormann P, Hein J (1976) Changes of the pancreatic duct system associated with aging: their relations to parenchyma (Article in German). Virchows Arch, A Pathol Anat 371:145–152

    Article  CAS  Google Scholar 

  24. Shek FWT, Benyon RC, Walker FM, McCrudden PR, Pender SLF, Williams EJ, Johnson PA, Johnson CD, Bateman AC, Fine DR, Iredale JP (2002) Expression of transforming growth factor-β1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis. Am J Pathol 160:1787–1798

    PubMed  CAS  Google Scholar 

  25. Shimizu M, Hayashi T, Saitoh Y, Itoh H (1989) Interstitial fibrosis in the pancreas. Am J Clin Pathol 91:531–534

    PubMed  CAS  Google Scholar 

  26. Sommers SC, Murphy SA, Warren S (1954) Pancreatic duct hyperplasia and cancer. Gastroenterology 27:629–640

    PubMed  CAS  Google Scholar 

  27. Stamm BH (1984) Incidence and diagnostic significance of minor pathologic changes in the adult pancreas at autopsy: a systematic study of 112 autopsies in patients without known pancreatic disease. Human Pathol 15:677–683

    Article  CAS  Google Scholar 

  28. Terris B, Ponsot T, Paye F, Hammel P, Sauvanet A, Molas G, Bernades P, Belghiti J, Ruszniewski P, Fléjou JF (2000) Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol 24:1372–1377

    Article  PubMed  CAS  Google Scholar 

  29. Valderrama R, Navarro S, Campo E, Camps J, Gimenez A, Pares A, Caballeria J (1991) Quantitative measurement of fibrosis in pancreatic tissue. Evaluation of a colorimetric method. Int J Pancreatol 10:23–29

    PubMed  CAS  Google Scholar 

  30. Wang RN, Klöppel G, Bouwens L (1995) Duct-to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia 38:1405–1411

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was part of the doctoral thesis of Sönke Detlefsen.

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Authors and Affiliations

  1. Department of Pathology, University of Kiel, Michaelisstrasse 11, 24105, Kiel, Germany

    Sönke Detlefsen, Bence Sipos, Bernd Feyerabend & Günter Klöppel

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  1. Sönke Detlefsen
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  2. Bence Sipos
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  3. Bernd Feyerabend
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  4. Günter Klöppel
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Correspondence to Günter Klöppel.

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Detlefsen, S., Sipos, B., Feyerabend, B. et al. Pancreatic fibrosis associated with age and ductal papillary hyperplasia. Virchows Arch 447, 800–805 (2005). https://doi.org/10.1007/s00428-005-0032-1

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  • DOI: https://doi.org/10.1007/s00428-005-0032-1

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