Crizotinib in ALK-Rearranged Inflammatory Myofibroblastic Tumor

• Published in: The New England journal of medicine Vol. 363; no. 18; pp. 1727 - 1733
• Main Authors: Butrynski, James E, D'Adamo, David R, Hornick, Jason L, Dal Cin, Paola, Antonescu, Cristina R, Jhanwar, Suresh C, Ladanyi, Marc, Capelletti, Marzia, Rodig, Scott J, Ramaiya, Nikhil, Kwak, Eunice L, Clark, Jeffrey W, Wilner, Keith D, Christensen, James G, Jänne, Pasi A, Maki, Robert G, Demetri, George D, Shapiro, Geoffrey I
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 28.10.2010
• Subjects: Abdominal Neoplasms - drug therapy; Abdominal Neoplasms - genetics; Adult; Biological and medical sciences; General aspects; Granuloma, Plasma Cell - drug therapy; Granuloma, Plasma Cell - genetics; Humans; Male; Medical sciences; Mutation; Neoplasms, Muscle Tissue - drug therapy; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins c-met - antagonists & inhibitors; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyridines - adverse effects; Pyridines - therapeutic use; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor - antagonists & inhibitors; Young Adult; Medicine; C-Onc gene; Myofibroblast; Tumor; Inflammation; Anaplastic lymphoma kinase; Protooncogene
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1007056

A subgroup of inflammatory myoblastic tumors (IMTs) have gene rearrangements that activate anaplastic lymphoma kinase (ALK). The authors report a case of IMT in which ALK was aberrantly expressed and the tumor had a response to crizotinib, an ALK kinase inhibitor. Inflammatory myofibroblastic tumors (IMTs) occur primarily during the first two decades of life and typically arise in the lung, retroperitoneum, or abdominopelvic region. 1 , 2 Abdominal tumors may be multifocal. Lesional cells are predominantly myofibroblasts in a myxoid to collagenous stroma admixed with inflammatory cells. 2 , 3 Local recurrence may occur after initial surgery, with a low risk of distant metastases, 1 , 2 so that IMTs are considered to be soft-tissue tumors of intermediate biologic potential, with a small fraction behaving aggressively. 4 Rearrangements involving the ALK locus on chromosome 2p23 have been documented in approximately 50% of IMTs. 5 , 6 ALK aneuploidy has also . . .