Original Article| Volume 130, ISSUE 5, e316-e323, November 2020

Download started.


Inflammatory myofibroblastic tumor in the head and neck—a neoplasm with both tumor features and inflammation


      The aim of this study was to unveil the reciprocal relation of tumor characteristics and inflammation in inflammatory myofibroblastic tumor in the head and neck.

      Study Design

      The study included a retrospective cohort of patients with inflammatory myofibroblastic tumors treated between 2005 and 2017 in a tertiary hospital. Tumor features and inflammation were assessed through the expression of anaplastic lymphoma kinase (ALK), the degree of inflammation and cyclooxygenase-2 (COX-2) expression. The prognostic factors were analyzed for overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses.


      Forty-one patients diagnosed with inflammatory myofibroblastic tumors were followed up, and 41 paraffin sections were obtained. The positive rate of ALK expression was 21 (51.2%) of 41 patients. Nineteen patients had high-grade ALK expression, and 22 patients had low-grade ALK expression. Thirty-nine patients had high-grade inflammation, and 2 had low-grade inflammation. The positive rate of COX-2 expression was 100%. Tumors with both high-grade ALK expression and inflammation had worse DFS (P = .015). The multivariate Cox analysis showed that the grades of ALK expression and inflammation (P = .004) were independent risk factors for DFS.


      Because of the latent synergistic effects of ALK and inflammation in the tumorigenesis of inflammatory myofibroblastic tumor, the combined therapy of ALK and COX-2 inhibitors shows promise.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


        • Rosenberg A.E.
        WHO Classification of Soft Tissue and Bone, fourth edition: Summary and commentary.
        Curr Opin Oncol. 2013; 25: 571-573
        • Al-Humidi A.
        • Al-Khamiss A.
        Inflammatory myofibroblastic tumor arising in the external ear: unexpected location. (case report).
        Int J Health Sci (Qassim). 2015; 9: 201-205
        • Ong H.S.
        • Ji T.
        • Zhang C.P.
        • et al.
        Head and neck inflammatory myofibroblastic tumor (IMT): evaluation of clinicopathologic and prognostic features.
        Oral Oncol. 2012; 48: 141-148
        • Coffin C.M.
        • Dehner L.P.
        • Meis-Kindblom J.M.
        Inflammatory myofibroblastic tumor, inflammatory fibrosarcoma, and related lesions: an historical review with differential diagnostic considerations.
        Semin Diagn Pathol. 1998; 15: 102-110
        • Meis-Kindblom J.M.
        • Kjellstrom C.
        • Kindblom L.G.
        Inflammatory fibrosarcoma: update, reappraisal, and perspective on its place in the spectrum of inflammatory myofibroblastic tumors.
        Semin Diagn Pathol. 1998; 15: 133-143
        • Brunn H.
        Two interesting benign lung tumors of contradictory histopathology.
        Am J Surg. 1939; 9: 119-131
        • Sciot R.
        • Dal Cin P.
        • Fletcher C.D.
        • et al.
        Inflammatory myofibroblastic tumor of bone: report of two cases with evidence of clonal chromosomal changes.
        Am J Surg Pathol. 1997; 21: 1166-1172
        • Butrynski J.E.
        • D'Adamo D.R.
        • Hornick J.L.
        • et al.
        Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor.
        N Engl J Med. 2010; 363: 1727-1733
        • Kusunoki-Nakamoto F.
        • Matsukawa T.
        • Tanaka M.
        • et al.
        Successful treatment of an unresectable inflammatory myofibroblastic tumor of the frontal bone using a cyclooxygenase-2 inhibitor and methotrexate.
        Intern Med. 2013; 52: 623-628
        • Bennett J.A.
        • Nardi V.
        • Rouzbahman M.
        • Morales-Oyarvide V.
        • Nielsen G.P.
        • Oliva E.
        Inflammatory myofibroblastic tumor of the uterus: a clinicopathological, immunohistochemical, and molecular analysis of 13 cases highlighting their broad morphologic spectrum.
        Mod Pathol. 2017; 30: 1489-1503
        • Guillou L.
        • Coindre J.M.
        • Bonichon F.
        • et al.
        Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma.
        J Clin Oncol. 1997; 15: 350-362
        • Marino-Enriquez A.
        • Wang W.L.
        • Roy A.
        • et al.
        Epithelioid inflammatory myofibroblastic sarcoma: an aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK.
        Am J Surg Pathol. 2011; 35: 135-144
        • Hutarew G.
        • Hauser-Kronberger C.
        • Strasser F.
        • Llenos I.C.
        • Dietze O.
        Immunohistochemistry as a screening tool for ALK rearrangement in NSCLC: evaluation of five different ALK antibody clones and ALK FISH.
        Histopathology. 2014; 65: 398-407
        • Scholzen T.
        • Gerdes J.
        The Ki-67 protein: from the known and the unknown.
        J Cell Physiol. 2000; 182: 311-322
        • Affara N.I.
        • Coussens L.M.
        IKKalpha at the crossroads of inflammation and metastasis.
        Cell. 2007; 129: 25-26
        • Wang L.
        • Kang F.
        • Li J.
        • Zhang J.
        • Shan B.
        Overexpression of p65 attenuates celecoxib-induced cell death in MDA-MB-231 human breast cancer cell line.
        Cancer Cell Int. 2013; 13: 14
        • Wang G.
        • Li J.
        • Zhang L.
        • Huang S.
        • Zhao X.
        • Zhao X.
        Celecoxib induced apoptosis against different breast cancer cell lines by down-regulated NF-kappaB pathway.
        Biochem Biophys Res Commun. 2017; 490: 969-976
        • Yang S.
        • Wang X.
        • Jiang H.
        • Wang Y.
        • Li Z.
        • Lu H.
        Effective treatment of aggressive fibromatosis with celecoxib guided by genetic testing.
        Cancer Biol Ther. 2017; 18: 757-760
        • de Moraes E.
        • Dar N.A.
        • de Moura Gallo C.V.
        • Hainaut P.
        Cross-talks between cyclooxygenase-2 and tumor suppressor protein p53: balancing life and death during inflammatory stress and carcinogenesis.
        Int J Cancer. 2007; 121: 929-937
        • Krawczyk M.
        • Emerson B.M.
        p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-kappaB complexes.
        Elife. 2014; 3: e01776
        • Zhai B.
        • Yang H.
        • Mancini A.
        • He Q.
        • Antoniou J.
        • Di Battista J.A.
        Leukotriene B(4) BLT receptor signaling regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of Ras/Raf/ERK/p42 AUF1 pathway.
        J Biol Chem. 2010; 285: 23568-23580
        • Mano H.
        ALKoma: a cancer subtype with a shared target.
        Cancer Discov. 2012; 2: 495-502
        • Morris S.W.
        • Kirstein M.N.
        • Valentine M.B.
        • et al.
        Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
        Science. 1995; 267: 316-317
        • Barreca A.
        • Lasorsa E.
        • Riera L.
        • et al.
        Anaplastic lymphoma kinase in human cancer.
        J Mol Endocrinol. 2011; 47: R11-R23
        • Lin J.J.
        • Riely G.J.
        • Shaw A.T.
        Targeting ALK: precision medicine takes on drug resistance.
        Cancer Discov. 2017; 7: 137-155
        • Coffin C.M.
        • Patel A.
        • Perkins S.
        • Elenitoba-Johnson K.S.
        • Perlman E.
        • Griffin C.A.
        ALK1 and p80 expression and chromosomal rearrangements involving 2 p23 in inflammatory myofibroblastic tumor.
        Mod Pathol. 2001; 14: 569-576
        • Coffin C.M.
        • Hornick J.L.
        • Fletcher C.D.
        Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases.
        Am J Surg Pathol. 2007; 31: 509-520
        • Li Q.
        • Liu N.
        • Shen B.
        • et al.
        Helicobacter pylori enhances cyclooxygenase 2 expression via p38 MAPK/ATF-2 signaling pathway in MKN45 cells.
        Cancer Lett. 2009; 278: 97-103
        • Katayama R
        • Shaw AT
        • Khan TM
        • et al.
        Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers.
        Sci Transl Med. 2012; 4: 117-120
        • Dzierba CD
        • Takvorian AG
        • Rafalski M
        • et al.
        Synthesis, structure-activity relationships, and in vivo properties of 3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-ones as corticotropin-releasing factor-1 receptor antagonists.
        J Med Chem. 2004; 47: 5783-5790
        • Minoo P
        • Wang HY.
        ALK-immunoreactive neoplasms.
        Int J Clin Exp Pathol. 2012; 5: 397-410