Inflammatory myofibroblastic tumor with predominant anaplastic lymphoma kinase-positive cells lacking a myofibroblastic phenotype

Pathol Int. 2003 Jun;53(6):376-81. doi: 10.1046/j.1440-1827.2003.01484.x.


Inflammatory myofibroblastic tumor (IMT), synonymously referred to as inflammatory pseudotumor, is a distinctive mesenchymal lesion composed of spindle cells displaying morphological features of myofibroblasts admixed with considerable numbers of inflammatory cells. Recent genetic and molecular studies have shown that a subset of IMT is characterized by the expression of altered anaplastic lymphoma kinase (ALK) protein mostly resulting from rearrangements of the ALK gene such as TPM3-ALK, TPM4-ALK and CLTC-ALK fusion genes. We analyzed the ALK status in nine cases of IMT arising in various anatomical locations. Six cases showed immunohistochemical expression of the ALK protein, and two ALK-positive lesions examined by reverse transcription-polymerase chain reaction and a subsequent sequencing analysis harbored the TPM4-ALK fusion gene. Of note, the majority of ALK-positive tumor cells in four of the six lesions lacked the coexpression of myogenic markers including alpha-smooth muscle actin, a cytoskeletal protein indicating myofibroblastic differentiation, whereas a substantial number of tumor cells in the remaining two cases coexpressed ALK and alpha-smooth muscle actin and/or desmin. In an ultrastructural study of the lesion with predominant ALK-positive/actin-negative cells, spindle cells failed to demonstrate features of myofibroblasts such as intracytoplasmic bundles of thin filaments and dense bodies. The current findings suggest that ALK-positive cells in IMT are not always myofibroblastic but might be immature primitive mesenchymal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anaplastic Lymphoma Kinase
  • Child
  • Child, Preschool
  • DNA / analysis
  • Female
  • Fibroblasts / enzymology*
  • Fibroblasts / ultrastructure
  • Granuloma, Plasma Cell / enzymology*
  • Granuloma, Plasma Cell / pathology
  • Humans
  • Immunohistochemistry
  • Infant
  • Male
  • Myocytes, Smooth Muscle / enzymology*
  • Myocytes, Smooth Muscle / ultrastructure
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Phenotype
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Receptor Protein-Tyrosine Kinases
  • Reverse Transcriptase Polymerase Chain Reaction


  • Oncogene Proteins, Fusion
  • DNA
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases