Taylor MS, et al. - In this study, the morphologic overlap between inflammatory myofibroblastic tumor (IMT) and immunoglobulin (Ig)G4-related diseases was highlighted. In addition, researchers emphasized the significance of a multiplex fusion assay in the distinction of IgG4-related disease (IgG4-RD) from IMT. Seven IMTs with morphologic and immunohistochemical features of IgG4-RD were identified; 3 patients were originally diagnosed with IgG4-RD. In addition, 56 patients with IgG4-RD were reevaluated. They noted a dense lymphoplasmacytic infiltrate and storiform-type fibrosis in all 7 IMTs, with obliterative phlebitis in 3 cases. Less than 5% of overall cellularity displayed the neoplastic stromal cells; either absent or focal and mild stromal atypia was noted. All cases displayed elevated numbers of IgG4 positive cells and increased IgG4 to IgG ratio. ALK related abnormalities were noted in 4 cases: 3 fusions and one alternative transcription initiation; while 2 patients displayed ROS1 and NTRK3 fusions. On immunohistochemistry, all 56 IgG4-RD cases were negative for ALK and ROS1; 6 cases were negative on the fusion assay. Both histologically and on immunohistochemistry for IgG4, highly inflamed IMTs could not be distinguished from IgG4-RD. They suggest examining thoroughly the patients with presumptive single organ IgG4-RD for IMT and including ALK and ROS1 immunohistochemistry in the diagnostic algorithm. In selected cases, they suggest performing a next-generation sequencing-based fusion assay that covers known IMT-associated gene fusions.