Inflammatory myofibroblastic tumor (IMT) is a rare benign cancer that can express a more aggressive phenotype related to the genetic mutation of the anaplastic lymphoma kinase receptor (ALK).
We advocate scrutinizing patients with presumptive single organ IgG4-RD for IMT and the diagnostic algorithm should include ALK and ROS1 immunohistochemistry and, in selected cases, a next-generation sequencing-based fusion assay that covers known IMT-associated gene fusions.
ALK is a receptor tyrosine kinase, associated with many tumor types as diverse as anaplastic large cell lymphomas, inflammatory myofibroblastic tumors, breast and renal cell carcinomas, non-small cell lung cancer, neuroblastomas, and more.
Our results indicate that ALK expression in AFH is common, particularly with the highly sensitive D5F3 and 5A4 antibodies and enhanced detection systems, and may be a potential source of diagnostic confusion with IMT.
Of note, 1 tumor previously diagnosed as leiomyosarcoma was established as inflammatory myofibroblastic tumor along this study with a novel ALK-TNS1 fusion.
We report two emblematic cases of IMT in pediatric patients, treated with the second-generation ALK inhibitor ceritinib in the context of a clinical trial (NCT01742286).
One exceptional case of a RANBP2-ALK-positive epithelioid inflammatory myofibroblastic sarcoma (an aggressive variant of IMT) showed moderate cytoplasmic staining for pan-Trk.
One PD-L1, CD8-enriched leiomyosarcoma showed an ALK overexpression suggesting possible classification as inflammatory myofibroblastic tumor, but otherwise lacked morphologic features of this entity.
A molecular-targeted drug (anaplastic lymphoma kinase inhibitor) was found to be extremely effective as selective therapy for inflammatory myofibroblastic tumor with anaplastic lymphoma kinase translocation.
IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL).
Herein, we report the first case of IMT which harbors an ALK gene amplification rather than a rearrangement thus resulting in overexpression of the protein, arising from the femur of a 24-year-old man.
Inflammatory myofibroblastic tumor has ALK gene rearrangements and is considered a neoplasm as opposed to PCG, which is a reactive polyclonal plasma cell proliferation.
As preliminary data are promising, a prospective study evaluating crizotinib treatment in patients with unresectable/multifocal ALK<sup>+</sup> IMT/EIMS is warranted.
All 14 IMTs were confirmed to harbor ALK genetic fusion by RNA sequencing, and ALK immunostaining in the form of granular cytoplasmic positivity with paranuclear accentuation was observed in all 14 cases.
Anaplastic lymphoma kinase (ALK) gene activation is involved in the carcinogenesis process of several human cancers such as anaplastic large cell lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression.
We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations.