A Novel CASC15-ALK and TFG-ROS1 Fusion Observed in Uterine Inflammatory Myofibroblastic Tumor

Abstract

The majority of inflammatory myofibroblastic tumors (IMTs) in the gynecologic tract occur in the uterine corpus and harbor anaplastic lymphoma kinase ( ALK ) rearrangement. Herein, we report 1 uterine IMT case with a novel fusion involving ALK and 1 uterine IMT case with ROS1 rearrangement. The ages of the patients were 56 and 57 yr, respectively. The tumor size was 10.0 and 8.0 cm, respectively. Both patients had stage IB disease. Histologically, the 2 IMT cases had classic morphologic features and predominantly comprised bland spindle cells with hypercellular (fascicular/storiform) and hypocellular (myxoid rich) areas admixed with variably prominent lymphoplasmacytic infiltration. Immunohistochemically, the ALK -rearranged case was positive for ALK , and the ROS1 -rearranged case was positive for ROS1 . Both cases were diffusely positive for desmin. The tumor cells were variably positive for estrogen receptor (1/2 cases, 50.0%) and progesterone receptor (1/2 cases, 50.0%). Targeted RNA sequencing revealed one case each with either a novel CASC15-ALK or TFG-ROS 1 fusion. We identified a novel ALK fusion partner CASC15 in IMT and described the first uterine IMT with a TFG-ROS1 fusion. This study improves our understanding of molecular events in IMT.