The First Case Treated with Larotrectinib of a Novel TMTC2-NTRK3 Fusion Undifferentiated High-Grade Pleomorphic Sarcoma of the Chest

Abstract

Undifferentiated high-grade pleomorphic sarcoma (UPS) is a rare soft tissue sarcoma (STS) of mesenchymal origin, particularly the extremities and retroperitoneum, meanwhile it has been reported in almost all parts of the body. UPS is highly invasive and has a poor prognosis due to its clinical manifestations of painless mass and deep tumor site, which are usually found at an advanced stage. Patients with UPS tend to have a lower 5-year survival rate than patients with other types of STS. Recently, NTRK fusions were detected in many cancer types, such as thyroid cancer, colorectal cancer, non-small cell lung cancer, soft tissue tumors, uterine sarcomas, and melanomas. However, the mutation frequency of NTRK fusion in all cancers is only 0.1-1%. Targeted therapy with NTRK inhibitors, such as Larotrectinib and Entrectinib, leads to a response in most patients with NTRK1/2/3 gene fusion-positive tumors. Herein, we present a 68-years old man diagnosed with stage IIIA (T2N0M0G3) UPS. Next-generation sequencing (NGS) revealed a novel TMTC2-NTRK3 fusion. The NTRK3 positivity was also detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). He had a response to Larotrectinib. This report broadens the spectrum of NTRK fusions in UPS and highlights a new target for treatment.