TRBC1 immunohistochemistry first for suspected cutaneous T-cell lymphoma

Design

Large retrospective diagnostic accuracy cohort with paired TCR clonality testing

Population

665 skin biopsies from 566 patients with suspected cutaneous T-cell infiltrates

Primary outcome

Agreement of TRBC1 immunohistochemistry with TCR clonality

Effect

Sensitivity 85.8%, specificity 79.8%; polytypic negative likelihood ratio 0.18

This study assessed TRBC1 immunohistochemistry, which shows whether an αβ T-cell population uses one T-cell receptor β constant region or both, in 665 skin biopsies from 566 patients, each with paired TCR clonality testing. Cases spanned mycosis fungoides stages and variants, Sézary syndrome, other cutaneous lymphoproliferative disorders and reactive infiltrates.

Using below 15% or above 85% TRBC1-positive cells as monotypic, sensitivity was 85.8% and specificity 79.8%, with positive and negative predictive values of 86.0% and 79.5%. Polytypic staining was strongly associated with reactive disease (OR 53.65; negative likelihood ratio 0.18) and was seen in every biopsy of a separate 270-case reactive cohort. Three readers agreed closely overall (κ 0.943), less so in reflexed difficult cases (κ 0.776). Digital quantification matched the manual read in 87.6%. Errors were predictable: patch-stage mycosis fungoides tended to read polytypic despite a clonal TCR, and reactive infiltrates sometimes read monotypic.

The authors propose staining for TRBC1 first and sending TCR clonality testing only for borderline staining or when the result does not fit the clinical and histological picture. In settings where molecular clonality testing is costly or slow, as in much of India, a one-slide stain that resolves most cases would be valuable. Antibody availability should be checked locally.

• Consider TRBC1 immunohistochemistry as the first clonality test in suspected cutaneous T-cell lymphoma.
• Send TCR clonality testing when TRBC1 is borderline or conflicts with the clinical picture.
• Be cautious with a polytypic result in early patch-stage disease, where false negatives clustered.
• Be cautious with a monotypic result in a sparse reactive infiltrate, where false positives clustered.
• Use the 15% and 85% thresholds the study validated if you adopt the stain.

Why it matters

A single immunostain could replace molecular testing for most suspected cutaneous lymphoma biopsies.

Don't overread it

TRBC1 missed about one clonal case in seven, mostly early patch-stage disease, so it does not replace clinicopathological correlation.

The statistics, in plain English

A negative likelihood ratio of 0.18 means a polytypic result lowers the odds of clonality to about a fifth of what they were, a strong but not absolute rule-out. Sensitivity of 85.8% means about one clonal case in seven reads as polytypic, mostly in patch-stage disease.

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