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Oligoclonal T-cell populations in an inflammatory pseudotumor of the pancreas possibly related to autoimmune pancreatitis: an immunohistochemical and molecular analysis

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Abstract

Inflammatory pseudotumors (IPT), also known as inflammatory myofibroblastic tumors (IMT), are benign inflammatory processes that may have an infectious etiology and are very rare in the pancreatico-biliary region. Recent studies suggest a biological distinction between IPT and IMT, the latter being a true neoplastic process. We describe a case of pancreatic IPT, originally diagnosed as malignancy, which presumably recurred 4 months after the operation. Histologically, the tumor consisted of a smooth muscle actin and CD68-positive spindle cell population and a more abundant mononuclear inflammatory cell population, primarily composed of macrophages and T-lymphocytes. Inflammatory cells were the source of connective tissue growth factor and transforming growth factor-β1 and tended to accumulate around nerves and blood vessels, as well as around residual pancreatic parenchymal elements, where an intense angiogenetic response was detected. Comparative genomic hybridization analysis of the tumor showed no chromosomal imbalances. Polymerase chain reaction-based analysis of T-cell receptor γ gene rearrangement revealed an oligoclonal pattern. These findings suggest that the pathogenesis of aggressive cases of IPT could be related to the development of an intense and self-maintaining immune response, with the emergence of clonal populations of T-lymphocytes. The relation of the pancreatic IPT to autoimmune pancreatitis is emphasized.

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References

  1. Abou-Shady M, Friess H, Zimmermann A, di Mola FF, Guo XZ, Baer HU, Buchler MW (2000) Connective tissue growth factor in human liver cirrhosis. Liver 20:296–304

    Article  CAS  PubMed  Google Scholar 

  2. Abrebanel P, Sarfaty S, Gal R, Chaimoff C, Kessler E (1984) Plasma cell granuloma of the pancreas. Arch Pathol Lab Med 108:531–532

    CAS  PubMed  Google Scholar 

  3. Arber DA, Kamel OW, van de Rijn M, Davis RE, Medeiros LJ, Jaffe ES, Weiss LM (1995) Frequent presence of the Epstein-Barr virus in inflammatory pseudotumor. Hum Pathol 26:1093–1098

    CAS  PubMed  Google Scholar 

  4. Biselli R, Boldrini R, Ferlini C, Boglino C, Inserra A, Bosman C (1999) Myofibroblastic tumours: neoplasias with divergent behaviour. Ultrastructural and flow cytometric analysis. Pathol Res Pract 195:619–632

    CAS  PubMed  Google Scholar 

  5. Bourguin A, Tung R, Galili N, Sklar J (1990) Rapid, nonradioactive detection of clonal T-cell receptor gene rearrangements in lymphoid neoplasms. Proc Natl Acad Sci U S A 87:8536–8540

    CAS  PubMed  Google Scholar 

  6. Broughan TA, Fischer WL, Tuthill RJ (1993) Vascular invasion by hepatic inflammatory pseudotumor. A clinicopathologic study. Cancer 71:2934–2940

    CAS  PubMed  Google Scholar 

  7. Brunn H (1939) Two interesting benign lung tumours of contradictory histopathology. Remarks in the necessity for maintaining the chest tumour registry. J Thorac Cardiovasc Surg 9:119–131

    Google Scholar 

  8. Chen Y, Blom IE, Sa S, Goldschmeding R, Abraham DJ, Leask A (2002) CTGF expression in mesangial cells: involvement of SMADs, MAP kinase, and PKC. Kidney Int 62:1149–1159

    Article  CAS  PubMed  Google Scholar 

  9. Cheuk W, Woo PC, Yuen KY, Yu PH, Chan JK (2000) Intestinal inflammatory pseudotumour with regional lymph node involvement: identification of a new bacterium as the aetiological agent. J Pathol 192:289–292

    Article  CAS  PubMed  Google Scholar 

  10. Coffin CM, Watterson J, Priest JR, Dehner LP (1995) Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 19:859–872

    CAS  PubMed  Google Scholar 

  11. Coffin CM, Dehner LP, Meis-Kindblom JM (1998) Inflammatory myofibroblastic tumor, inflammatory fibrosarcoma, and related lesions: an historical review with differential diagnostic considerations. Semin Diagn Pathol 15:102–110

    CAS  PubMed  Google Scholar 

  12. Dehner LP (2000) The enigmatic inflammatory pseudotumours: the current state of our understanding, or misunderstanding. J Pathol 192:277–279

    Article  CAS  PubMed  Google Scholar 

  13. Dehner LP, Coffin CM (1998) Idiopathic fibrosclerotic disorders and other inflammatory pseudotumors. Semin Diagn Pathol 15:161–173

    CAS  PubMed  Google Scholar 

  14. Dent GA, Baird DB, Ross DW (1991) Systemic idiopathic fibrosis with T-cell receptor gene rearrangement. Arch Pathol Lab Med 115:80–83

    CAS  PubMed  Google Scholar 

  15. di Mola FF, Friess H, Martignoni ME, Di Sebastiano P, Zimmermann A, Innocenti P, Graber H, Gold LI, Korc M, Buchler MW (1999) Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis. Ann Surg 230:63–71

    Article  PubMed  Google Scholar 

  16. Donner LR, Trompler RA, White RR 4th (1996) Progression of inflammatory myofibroblastic tumor (inflammatory pseudotumor) of soft tissue into sarcoma after several recurrences. Hum Pathol 27:1095–1098

    CAS  PubMed  Google Scholar 

  17. Esposito I, Friess H, Kappeler A, Shrikhande S, Kleeff J, Ramesh H, Zimmermann A, Buchler M (2001) Mast cell distribution and activation in chronic pancreatitis. Hum Pathol 32:1174–1183

    Article  CAS  PubMed  Google Scholar 

  18. Gomez-Roman JJ, Ocejo-Vinyals G, Sanchez-Velasco P, Nieto EH, Leyva-Cobian F, Val-Bernal JF (2000) Presence of human herpesvirus-8 DNA sequences and overexpression of human IL-6 and cyclin D1 in inflammatory myofibroblastic tumor (inflammatory pseudotumor). Lab Invest 80:1121–1126

    PubMed  Google Scholar 

  19. Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ (1999) Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors. Cancer Res 59:2776–2780

    CAS  PubMed  Google Scholar 

  20. Gupta S, Clarkson MR, Duggan J, Brady HR (2000) Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibrosis. Kidney Int 58:1389–1399

    Article  CAS  Google Scholar 

  21. 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 344:732–738

    Article  CAS  PubMed  Google Scholar 

  22. Isola J, DeVries S, Chu L, Ghazvini S, Waldman F (1994) Analysis of changes in DNA sequence copy number by comparative genomic hybridization in archival paraffin-embedded tumor samples. Am J Pathol 145:1301–1308

    CAS  PubMed  Google Scholar 

  23. Kasaragod AB, Lucia MS, Cabirac G, Grotendorst GR, Stenmark KR (2001) Connective tissue growth factor expression in pediatric myofibroblastic tumors. Pediatr Dev Pathol 4:37–45

    Article  CAS  PubMed  Google Scholar 

  24. Kloppel G, Luttges J, Lohr M, Zamboni G, Longnecker D (2003) Autoimmune pancreatitis: pathological, clinical, and immunological features. Pancreas 27:14–19

    Article  PubMed  Google Scholar 

  25. Koning GA, Schiffelers RM, Storm G (2002) Endothelial cells at inflammatory sites as target for therapeutic intervention. Endothelium 9:161–171

    Article  CAS  PubMed  Google Scholar 

  26. Kroft SH, Stryker SJ, Winter JN, Ergun G, Rao MS (1995) Inflammatory pseudotumor of the pancreas. Int J Pancreatol 18:277–283

    CAS  PubMed  Google Scholar 

  27. Kutok JL, Pinkus GS, Dorfman DM, Fletcher CD (2001) Inflammatory pseudotumor of lymph node and spleen: an entity biologically distinct from inflammatory myofibroblastic tumor. Hum Pathol 32:1382–1387

    Article  CAS  PubMed  Google Scholar 

  28. Menke DM, Griesser H, Araujo I, Foss HD, Herbst H, Banks PM, Stein H (1996) Inflammatory pseudotumors of lymph node origin show macrophage-derived spindle cells and lymphocyte-derived cytokine transcripts without evidence of T-cell receptor gene rearrangements. Implications for pathogenesis and classification as an idiopathic retroperitoneal fibrosis-like sclerosing immune reaction. Am J Clin Pathol 105:430–439

    CAS  PubMed  Google Scholar 

  29. Pettinato G, Manivel JC, De Rosa N, Dehner LP (1990) Inflammatory myofibroblastic tumor (plasma cell granuloma). Clinicopathologic study of 20 cases with immunohistochemical and ultrastructural observations. Am J Clin Pathol 94:538–546

    CAS  PubMed  Google Scholar 

  30. Sastre-Garau X, Couturier J, Derre J, Aurias A, Klijanienko J, Lagace R (2002) Inflammatory myofibroblastic tumour (inflammatory pseudotumour) of the breast. Clinicopathological and genetic analysis of a case with evidence for clonality. J Pathol 196:97–102

    Article  PubMed  Google Scholar 

  31. Simms RW, Korn JH (2002) Cytokine directed therapy in scleroderma: rationale, current status, and the future. Curr Opin Rheumatol 14:717–722

    Article  CAS  PubMed  Google Scholar 

  32. Stathopoulos G, Nourmand AD, Blackstone M, Andersen D, Baker AL (1995) Rapidly progressive sclerosing cholangitis following surgical treatment of pancreatic pseudotumor. J Clin Gastroenterol 21:143–148

    CAS  PubMed  Google Scholar 

  33. Umiker WO, Iverson L (1954) Postinflammatory “tumour” of the lung. Report of four cases simulating xanthoma, fibroma, or plasma cell granuloma. J Thorac Cardiovasc Surg 28:55–63

    Google Scholar 

  34. 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 22:412–418

    Article  CAS  PubMed  Google Scholar 

  35. 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 7:129–139

    Article  PubMed  Google Scholar 

  36. Wreesmann V, van Eijck CH, Naus DC, van Velthuysen ML, Jeekel J, Mooi WJ (2001) Inflammatory pseudotumour (inflammatory myofibroblastic tumour) of the pancreas: a report of six cases associated with obliterative phlebitis. Histopathology 38:105–110

    Article  CAS  PubMed  Google Scholar 

  37. Xing Z, Tremblay GM, Sime PJ, Gauldie J (1997) Overexpression of granulocyte-macrophage colony-stimulating factor induces pulmonary granulation tissue formation and fibrosis by induction of transforming growth factor-beta 1 and myofibroblast accumulation. Am J Pathol 150:59–66

    CAS  PubMed  Google Scholar 

  38. Zanger P, Kronsbein U, Merkle P, Bosse A (2002) Inflammatory myofibroblastic tumor of the pancreas with regional lymph node involvement. Pathologe 23:161–166

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 , Heidelberg, Germany

    Irene Esposito, Frank Bergmann, Roland Penzel & Herwart F. Otto

  2. Department of General Surgery, University of Heidelberg, Germany

    Fabio F. di Mola, Shailesh Shrikhande, Markus W. Büchler & Helmut Friess

  3. Department of Gastrointestinal Surgical Oncology, Tata Memorial Hospital, Mumbai, India

    Shailesh Shrikhande

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  1. Irene Esposito
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  2. Frank Bergmann
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  3. Roland Penzel
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  4. Fabio F. di Mola
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  5. Shailesh Shrikhande
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  7. Helmut Friess
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Correspondence to Irene Esposito.

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Esposito, I., Bergmann, F., Penzel, R. et al. Oligoclonal T-cell populations in an inflammatory pseudotumor of the pancreas possibly related to autoimmune pancreatitis: an immunohistochemical and molecular analysis. Virchows Arch 444, 119–126 (2004). https://doi.org/10.1007/s00428-003-0949-1

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  • DOI: https://doi.org/10.1007/s00428-003-0949-1

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