Abstract
Aims
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).
Methods and results
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%.
Conclusions
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.