Abstract
Thymic epithelial tumors (TET) are rare and large molecular studies are therefore difficult to perform. However, institutional case series and rare multi-institutional studies have identified a number of interesting molecular aberrations in TET, including gene fusions in a subset of these tumors. These gene fusions can aid in the diagnosis, shed light on the pathogenesis of a subset of tumors, and potentially may provide patients with the opportunity to undergo targeted therapy or participation in clinical trials. Gene fusions that have been identified in TET include MAML2 rearrangements in 50% to 56% of mucoepidermoid carcinomas (MAML2::CRTC1), 77% to 100% of metaplastic thymomas (YAP1::MAML2), and 6% of B2 and B3 thymomas (MAML2::KMT2A); NUTM1 rearrangements in NUT carcinomas (most commonly BRD4::NUTM1); EWSR1 rearrangement in hyalinizing clear cell carcinoma (EWSR1::ATF1); and NTRK rearrangement in a thymoma (EIF4B::NTRK3). This review focuses on TET in which these fusion genes have been identified, their morphologic, immunophenotypic, and clinical characteristics and potential clinical implications of the fusion genes. Larger, multi-institutional, global studies are needed to further elucidate the molecular characteristics of these rare but sometimes very aggressive tumors in order to optimize patient management, provide patients with the opportunity to undergo targeted therapy and participate in clinical trials, and to elucidate the pathogenesis of these tumors.