A clinical and genomic profile of inflammatory myofibroblastic tumors.

Abstract

1538 Background: Inflammatory Myofibroblastic Tumors (IMT) are tumors that morphologically traverse the neoplastic and inflammatory realms. With a predilection for children and young adults, many patients present with systemic symptoms and the tumors demonstrate local invasiveness and even metastasis. IMTs are composed of fascicles of myofibroblastic spindle cells with a marked lymphoplasmacytic infiltrate. Methods: Integrated genomic profiling of DNA and RNA from IMTs in 30 patients was performed using a hybrid capture, paired-end NGS sequencing method and customized pipeline analysis. Results: 23 patients were children or young adults ( < 30y), overall the age ranged from 7 months to 72 years. The tumor was clinically aggressive in 10 patients; 3 metastatic, 5 multifocal and 2 locally invasive. Epithelioid morphology was documented in 2 cases, one demonstrated the ALK-RANBP2 fusion. ALK rearrangements were detected in 13 patients, with 7 different fusion partners. ALK IHC or FISH was performed in 23 patients and were all concordant with the genomic results. 22 gene fusions were detected in 21 patients, 4 tumors had ROS1-TFG fusions, 2 had NTRK3-ETV6 fusions. 3 had novel fusions in JAK1-PML, PDGFRB-NOTCH1 and MUTYH-TESK2 respectively. Intact tyrosine kinase domains (TKD) in JAK1 are transposed to the promoter coiled-coil motif in PML, in the rearrangement. While the TKDs are preserved in the PDGRB and TESK2 rearrangements, the functional roles of their partners are yet to be elucidated. The prevalence of rearrangements was higher in patients below 30 years of age (20/23) compared to that above 30y (3/7). All 10 aggressive tumors were detected to have rearrangements. Conclusions: IMTs are seen predominantly in younger age groups. Gene rearrangements are seen more frequently in patients with younger age and also in more aggressive tumors, in a statistically significant manner. Alterations in genes associated with hematopoietic neoplasms such as JAK1 among others, are interesting, given the hematologic component of the lesion, and the presence of novel tyrosine kinase rearrangements warrant further investigations to elucidate mechanistic models.