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Alexander Drilon, MD

Gregory J. Riely, MD, PhD


NTRK Gene Fusions in Undifferentiated Sarcomas in Pediatric Patients

By: Justine Landin, PhD
Posted: Tuesday, May 24, 2022

NTRK gene fusions may be more common in undifferentiated round cell sarcomas of soft tissue and bone as well as tumors of uncertain differentiation in pediatric patients than previously thought, according to Filippo Nozzoli, MD, of the University of Florence, Italy, and colleagues. In fact, multiple undifferentiated round cell sarcomas tumor biopsies were positive for NTRK expression, and two were found to express the ETV6-NTRK3 fusion. The findings of this retrospective study were published in the journal Pathology and Oncology Research.

“The histological pattern of the two positive cases, together with the demonstration of the NTRK rearrangement, led to reclassify these previously not otherwise specified sarcomas with uncertain differentiation into the emerging category of NTRK-rearranged neoplasms,” stated the study investigators.

Biopsies of bone or soft-tissue tumors from pediatric patients diagnosed with undifferentiated round cell sarcomas or tumors of uncertain differentiation were chosen based upon histopathologic review and diagnosis review from the World Health Organization classification scheme (n = 105). Pan-Trk immunohistochemistry was performed, and RNA was isolated using next-generation sequencing to identify NTRK gene fusions. Positive results were confirmed using real-time polymerase chain reaction (PCR).

Of the 105 tumors tested, 11.4% were positive for NTRK expression and exhibited several staining patterns, although most of the positive staining was observed within the cytoplasm. Confirmation of these immunohistochemistry results via real-time PCR indicated that in two cases, there was evidence of the ETV6-NTRK3 fusion.

One of these patients was a 13-year-old boy with a prior diagnosis of Ewing-like sarcoma who was rediagnosed with undifferentiated soft-tissue sarcoma. This patient received chemotherapy and has exhibited disease-free survival and no viable tumor cells within the past 4 years. The second patient was an 11-year-old boy who was diagnosed with undifferentiated soft-tissue sarcoma; he received adjuvant multiagent chemotherapy and has also experienced continuous disease-free survival for the past 6 years.

Disclosure: For full disclosures of the study authors, visit

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