1. ¹Laboratory of Pathology, National Institutes of Health, National Cancer Institute, Bethesda, Maryland
2. ²Pediatric Oncology Branch, National Institutes of Health, National Cancer Institute, Bethesda, Maryland
3. ³Thoracic Oncology Section, Surgery Branch, National Institutes of Health, National Cancer Institute, Bethesda, Maryland
4. ⁴Laboratory of Immunopathology, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rockville, Maryland

Correspondence: Dr. Larisa V. Debelenko, Department of Pathology, Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115-5737. E-mail: Larisa.Debelenko@childrens.harvard.edu

Received 7 July 2003.

Abstract

Inflammatory myofibroblastic tumor (IMT) is a rare childhood neoplasm. The natural history of this disease is poorly understood. Recently chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene have been implicated in this tumor. We have studied a case of ALK-positive soft tissue IMT showing clinical and morphologic features of malignancy. Interphase fluorescence in situ hybridization demonstrated ALK rearrangements in both primary and metastatic lesions. Rapid amplification of cDNA ends (5'RACE) identified cysteinyl-tRNA synthetase (CARS) gene fused to ALK, which predicts an in-frame chimeric protein with the preserved functional catalytic domain of ALK at the C terminus. Amplification and sequencing of tumor DNA confirmed the breakpoint at the genomic level. Restriction analysis of DNA from primary soft tissue and recurrent lung tumors showed identical patterns, indicating the same clonal origin of both lesions. Western blot analysis with C-terminus ALK antibody showed expression of an aberrantly sized chimeric protein of approximately 130 kd in tumor tissue. This is the second case of IMT demonstrating CARS as the ALK fusion partner, which confirms the recurring involvement of ALK in IMT by a common genetic mechanism. Moreover, identical clonality of separate lesions involving different sites supports metastasis in IMT.