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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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
Abrebanel P, Sarfaty S, Gal R, Chaimoff C, Kessler E (1984) Plasma cell granuloma of the pancreas. Arch Pathol Lab Med 108:531–532
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
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
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
Broughan TA, Fischer WL, Tuthill RJ (1993) Vascular invasion by hepatic inflammatory pseudotumor. A clinicopathologic study. Cancer 71:2934–2940
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
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
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
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
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
Dehner LP (2000) The enigmatic inflammatory pseudotumours: the current state of our understanding, or misunderstanding. J Pathol 192:277–279
Dehner LP, Coffin CM (1998) Idiopathic fibrosclerotic disorders and other inflammatory pseudotumors. Semin Diagn Pathol 15:161–173
Dent GA, Baird DB, Ross DW (1991) Systemic idiopathic fibrosis with T-cell receptor gene rearrangement. Arch Pathol Lab Med 115:80–83
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
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
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
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
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
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
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
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
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
Kloppel G, Luttges J, Lohr M, Zamboni G, Longnecker D (2003) Autoimmune pancreatitis: pathological, clinical, and immunological features. Pancreas 27:14–19
Koning GA, Schiffelers RM, Storm G (2002) Endothelial cells at inflammatory sites as target for therapeutic intervention. Endothelium 9:161–171
Kroft SH, Stryker SJ, Winter JN, Ergun G, Rao MS (1995) Inflammatory pseudotumor of the pancreas. Int J Pancreatol 18:277–283
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
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
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
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
Simms RW, Korn JH (2002) Cytokine directed therapy in scleroderma: rationale, current status, and the future. Curr Opin Rheumatol 14:717–722
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
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
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
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
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
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
Zanger P, Kronsbein U, Merkle P, Bosse A (2002) Inflammatory myofibroblastic tumor of the pancreas with regional lymph node involvement. Pathologe 23:161–166
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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