Uterine inflammatory myofibroblastic tumor harboring novel NUDCD3-ROS1 and NRP2-ALK fusions: clinicopathologic features of 4 cases and literature review.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate biologic potential, which occurs mostly in the lung and abdomen cavity of children and young adults. Uterine IMTs are rare. Herein, we presented clinicopathologic features of 4 uterine IMTs. All four patients were initially diagnosed as leiomyosarcoma by other hospitals and corrected to uterine IMT after pathological consultation. Patient age ranged from 44 to 64 years old. Two cases demonstrated multiple masses. Microscopically, three tumors were composed of fascicular spindled cells with eosinophilic cytoplasm, and the other one was densely composed of spindled and epithelioid cells with bizarre and multinucleated cells. Tumor cells showed variable nuclear atypia, ranging from mild to severe. Prominent inflammatory cell infiltration was found in one case, and necrosis in two tumors. Immunochemistry staining revealed expression of smooth muscle markers in all four tumors, including a-SMA and desmin. Three tumors were positive for ALK protein expression. FISH analysis demonstrated ROS1 rearrangement in one tumor and ALK rearrangement in the other 3 tumors. NGS analysis showed novel NUDCD3-ROS1 and NRP2-ALK fusions in two tumors and TNS1-ALK fusion in the other two tumors. Gene aberrations involving p53 signaling pathway were identified in all four cases. All patients received surgery as primary treatment, and one had neoadjuvant chemotherapy. Three patients recurred within 12 months, and the other one recurred after 7 years. Patients with recurrence were treated with a combination of chemotherapy, targeted therapy, or surgery. In conclusion, the diagnosis of uterine IMTs can be challenging. Ancillary studies including ALK IHC, FISH, and NGS are helpful to establish diagnosis and to discover novel gene rearrangement potentially for targeted therapy.