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

• Published in: Pathology international 2003-06, Vol.53 (6), p.376-381
• Main Authors: Hisaoka, Masanori, Shimajiri, Shohei, Matsuki, Yasumasa, Meis-Kindblom, Jeanne M., Kindblom, Lars-Gunnar, Li, Xiao-Qiu, Wang, Jian, Hashimoto, Hiroshi
• Format: Article
• Language: English
• Subjects: 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; inflammatory myofibroblastic tumor; inflammatory pseudotumor; 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
• ISSN: 1320-5463; 1440-1827
• 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 α‐smooth muscle actin, a cytoskeletal protein indicating myofibroblastic differentiation, whereas a substantial number of tumor cells in the remaining two cases coexpressed ALK and α‐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.