Design: Diagnostic comparison of pan-TRK IHC, FISH and RNA-NGS
Population: 79 pigmented spindle cell naevi of Reed
Primary outcome: Agreement of pan-TRK IHC with molecular detection of NTRK3 rearrangement
Effect: Specificity and PPV 92-100%; sensitivity 33-36%

A Histopathology study (9 October 2026) reclassified 79 pigmented spindle cell naevi of Reed under 2025 WHO criteria and tested them with an optimised pan-TRK immunohistochemistry protocol, RNA-NGS and FISH.

RNA-NGS found MYO5A::NTRK3 fusion in 56% of evaluable cases, and FISH showed NTRK3 rearrangement in 65%. Pan-TRK was positive in 20%, with diffuse granular cytoplasmic staining. Against molecular testing it was highly specific, with positive predictive value of 92-100%, but sensitivity was only about 33-36%.

The practical reading is that a positive pan-TRK stain with that pattern in the right morphology strongly supports an NTRK3-rearranged Reed naevus, while a negative stain says little. Where the distinction from a spitzoid or other melanocytic tumour matters, molecular testing remains necessary.

Use a positive pan-TRK stain as supportive evidence of NTRK3 rearrangement in a suspected Reed naevus
Do not treat a negative pan-TRK stain as excluding an NTRK fusion
Send RNA-NGS or FISH where the diagnosis would change management
Look for diffuse, granular cytoplasmic staining - the pattern seen in positive cases

Why it matters

It defines what a cheap stain can and cannot do before a costly molecular test.

The statistics, in plain English

High specificity and PPV mean a positive result is almost always right. Sensitivity of about a third means two out of three fusion-positive lesions will stain negative. The protocol was optimised in one laboratory, so performance elsewhere may differ.