Design: Diagnostic accuracy study comparing 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 fusion
Effect: Specificity and PPV 92–100%; sensitivity 33–36%

This study examined 79 pigmented spindle cell naevi of Reed, reclassified to 2025 WHO criteria and negative for BRAF V600E and RAS Q61R, using an optimised pan-TRK immunohistochemistry protocol, an RNA-NGS fusion panel and NTRK FISH.

Pan-TRK was positive in 20% of cases, with diffuse granular cytoplasmic staining. RNA-NGS found MYO5A::NTRK3 fusion in 56% of evaluable cases, and FISH found NTRK3 rearrangement in 65%. Against the molecular tests, pan-TRK had specificity and positive predictive value of about 92% to 100%, but sensitivity of only about 33% to 36%.

A positive stain is a reliable pointer to an NTRK3 fusion and can support the diagnosis of a Reed naevus. A negative stain, however, is common in fusion-positive lesions and should not be read as excluding one. Where molecular testing is limited, as in many Indian laboratories, the stain can triage cases but cannot replace FISH or NGS when the diagnosis depends on finding the fusion.

Treat a positive pan-TRK stain in a pigmented spindle cell lesion as strong support for an NTRK3 fusion.
Do not use a negative pan-TRK stain to exclude NTRK3 rearrangement.
Send FISH or RNA-NGS when the diagnosis hinges on demonstrating a fusion.
Exclude BRAF V600E and RAS Q61R before labelling a lesion as a Reed naevus.

Why it matters

Stained-negative Reed naevi may be wrongly treated as fusion-negative, which can push a benign diagnosis towards an atypical one.

The statistics, in plain English

Specificity near 100% means a positive stain almost always reflects a real fusion. Sensitivity of about a third means two of every three fusion-positive lesions stained negative. The study is a single series, so these figures may vary with different protocols and laboratories.