Late Recurrence of Spindle Cell Sarcoma in Association with TPM3::NTRK1 Fusion

We report a 31-year-old woman with a history of low-grade, undifferentiated spindle cell sarcoma of the hand diagnosed at 10 years of age and subsequently amputated. The patient remained under surveillance without recurrence for over 20 years before she presented with multiple new masses in the skin of the head and neck. Biopsies confirmed recurrent sarcoma. Imaging studies revealed metastases within the lungs and peri-pancreatic tissue. Molecular analysis of these lesions showed a TPM3::NTRK1 fusion, and the patient started treatment on larotrectinib, on which she now remains, relapse and recurrence-free at 40 months. In presenting this patient, we hope to draw attention to the potentially overlooked provisional category of NTRK-rearranged spindle cell neoplasms that has been added to the fifth edition of the World Health Organization (WHO) classifications of pediatric tumors and soft tissue and bone tumors. While these neoplasms constitute only an estimated 1% of pediatric soft tissue neoplasms, discovering NTRK abnormalities in these lesions opens an important line of targeted therapy options, i.e., NTRK inhibitors. We hope to also show the community the potential for NTRK-rearranged spindle cell neoplasms to present with late local recurrence and metastases.