- Design
- Comparative diagnostic accuracy study of pan-TRK immunohistochemistry, FISH and RNA sequencing
- Population
- 79 pigmented spindle cell naevi of Reed (64 sequenced, 57 with FISH)
- Primary outcome
- Pan-TRK performance for NTRK3 fusion or rearrangement
- Effect
- Specificity and PPV 92.3% to 96.2%; sensitivity 36.4%
In pigmented spindle cell naevus of Reed, NTRK3 fusions, mainly MYO5A::NTRK3, are common but published rates vary widely. A study collected 79 cases, reclassified them by 2025 WHO criteria and BRAF and RAS stains, and stained them with an optimised pan-TRK protocol with extra amplification and red chromogen. RNA sequencing was run on 64 and FISH on 57.
Pan-TRK was positive in 16 cases (20.3%). Of 59 with evaluable sequencing, 33 (55.9%) had MYO5A::NTRK3. Against sequencing and FISH, pan-TRK showed specificity and positive predictive value of 92.3% to 96.2% but sensitivity of only 36.4%.
So a positive stain supports a fusion, but a negative stain misses most. The authors suggest the stain can guide molecular testing; in a lesion where the diagnosis matters, a negative result should not stop confirmatory sequencing. Cost and access to sequencing differ across Indian laboratories, which makes a clear reporting comment more useful.
- Treat a positive pan-TRK stain in this setting as supporting an NTRK3 fusion.
- Do not treat a negative stain as excluding a fusion; sensitivity was 36.4%.
- Send for molecular confirmation when the diagnosis depends on it.
- State the protocol used in the report, because this was an optimised variant.
Why it matters
It sets out when a cheaper stain is helpful and when it can mislead.
Don't overread it
Findings come from a single protocol in one study of 79 cases; it is not a validated replacement for molecular assays.
The statistics, in plain English
Specificity and positive predictive value show how often a positive stain is right; sensitivity shows how many true fusions it picks up. With sensitivity near one third, about two in three fusions would be missed by the stain alone.
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