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NTRK-rearranged mesenchymal tumours: diagnostic challenges, morphological patterns and proposed testing algorithm.

Daniel D Wong¹, Ana Cristina Vargas², Fiona Bonar³

¹Anatomical Pathology, PathWest, QEII Medical Centre, Nedlands, WA, Australia; School of Medicine, The University of Western Australia, Crawley, WA, Australia.

|April 13, 2020

Summary

Oncogenic NTRK gene fusions are found in rare mesenchymal tumors, posing diagnostic challenges. Early detection is crucial for effective targeted therapy in advanced sarcomas.

Keywords:

NTRK TRK entrectinib larotrectinib mesenchymal tumours pan-TRK sarcoma soft tissue tumours

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Area of Science:

Oncology
Pathology
Genetics

Background:

Neurotrophic receptor tyrosine kinase (NTRK) gene fusions are increasingly recognized in various mesenchymal tumors beyond their initial description.
These NTRK-rearranged neoplasms present diagnostic difficulties for pathologists due to non-specific clinical and pathological features.

Observation:

This study details six rare NTRK-rearranged mesenchymal neoplasms from an Australian multi-institutional series.
Key morphological patterns and immunoprofiles aiding in routine diagnosis are highlighted.

Findings:

The study addresses the diagnostic challenges posed by NTRK-rearranged mesenchymal tumors.
It emphasizes the importance of recognizing these fusions for targeted therapy in advanced and metastatic sarcomas.

Implications:

Accurate identification of NTRK fusions is critical for guiding treatment decisions with targeted therapies.
The proposed diagnostic algorithm aims to assist pathologists, acknowledging limitations of current ancillary studies like IHC, FISH, and NGS.