Evaluation of pan-TRK immunostaining in malignant peripheral nerve sheath tumours: does its positivity indicate NTRK rearrangements or neural differentiation?

Aims Histological features of conventional malignant peripheral nerve sheath tumour (C-MPNST) resemble those of neurotrophic tropomyosin or tyrosine receptor kinase gene ( NTRK )-rearranged spindle cell neoplasm, a new entity of soft-tissue tumour. Pan-TRK immunohistochemistry has recently become popular for detecting NTRK rearrangements cost-effectively, but its positivity can also reflect neural differentiation. We investigated what pan-TRK positivity truly indicates in a large case series of neurogenic tumours. Methods Pan-TRK, S100, SOX10 and histone 3 lysine 27 trimethylation (H3K27me3) immunohistochemical analyses were performed on 99 C-MPNSTs, 17 malignant triton tumours, 8 epithelioid MPNSTs (E-MPNSTs), 2 atypical neurofibromatous neoplasms with uncertain biologic potential (ANNUBPs) and 1 glandular MPNST. For pan-TRK-positive cases, NTRK rearrangements were examined by molecular methods. Results 15 cases (11 C-MPNSTs, 3 E-MPNSTs and 1 ANNUBP) were positive for pan-TRK. Clinically, the positivity rates were significantly higher in older patients (≥50 years, 21.3% vs