Detection of NTRK1/2/3 rearrangements in pigmented spindle cell naevus of Reed: a comparative study of optimized pan-TRK immunohistochemistry, FISH and RNA-NGS.

Authors

Costantino Ricci, Barbara Corti, Sara Coluccelli, Giulia Calafato, Debora Anconelli, Francesco Vasuri, Martina Lambertini, Federico Venturi, Biagio Scotti, Alessia Grillini, Eugenia Franchini, Thais Maloberti, Antonio De Leo, Giovanni Tallini, Elisa Gruppioni, Annalisa Altimari, Michelangelo Fiorentino, Gerardo Cazzato, Emi Dika, Dario de Biase

Published in

Histopathology. Oct 09, 2026. Epub Oct 09, 2026.

Abstract

Pigmented spindle cell naevus of Reed (PSCN) is mainly characterized by MYO5A::NTRK3 fusion. However, the prevalence of NTRK fusions/rearrangements in PSCNs ranges from 15.8% to 57% in the literature, and the agreement among techniques for detecting these alterations has not been analysed. Here, we analysed NTRK fusions/rearrangements in a series of PSCNs using an optimized pan-TRK protocol, RNA-NGS fusion panel and FISH (NTRK1/2/3).
Seventy-nine PSCNs were collected, reclassified (2025 WHO criteria and negative for BRAF V600E/RAS Q61R stains), and stained with a modified version of a recently proposed pan-TRK protocol (additional amplification steps and Red chromogen). In 64 and 57 cases with available material, we performed RNA-NGS and FISH (NTRK1/2/3) analyses, respectively. Pan-TRK was positive in 16 (20.3%) cases, all showing diffuse, granular, cytoplasmic staining of moderate intensity. In 59 cases with evaluable RNA-NGS data, 33 (55.9%) harboured MYO5A::NTRK3 fusion, 3 (5.1%) had NTRK3 imbalance, and 1 (1.7%) case each showed MYO5A::ROS1 and ESR1::CCDC170 fusion. In 51 cases with evaluable FISH (NTRK3) data, 33 (64.7%) were positive for NTRK3 rearrangement. Both the comparison of pan-TRK versus RNA-NGS and versus FISH (NTRK3) revealed high values of specificity (SP) and positive predictive value (PPV) (92.3%-96.2%) for the detection of NTRK3 fusions/rearrangements, despite a limited sensitivity (SE) of 36.4%. In the comparison of pan-TRK versus RNA-NGS and FISH (NTRK3), both SP and PPV were 100%, with a SE of 33.3%.
Our 'optimized' pan-TRK protocol achieved high SP and PPV for the detection of NTRK3 fusions/rearrangements in PSCNs, despite a limited sensitivity compared to molecular assay. These results suggest that this protocol may serve as a diagnostic tool in routine practice, effectively guiding molecular testing and refining the diagnostic workflow for PSCNs.

PMID:
42851163
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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