Track

Clinical Studies

Abstract

TRBC1 immunohistochemistry establishes cutaneous T-cell lymphoma clonality. However, as CD30+lymphoproliferative disorders (CD30+LPDs) often have infiltrating reactive cells and/or loss of CD3 and/or TCRβ, TRBC1 IHC interpretation can be difficult. We recently described improved identification of T-cell receptor proteins in CTCLs using TCRα IHC and hypothesized that TRBC1 clonality interpretations would improve against TCRα. Using 26 clinicopathologically confirmed αβ+ primary cutaneous CD30+LPDs (11 LYP, 15 ALCL), we compared TRBC1-defined clonality using baseline CD3, TCRβ, and TCRα. Strong, diffuse expression of CD3 was present in 19/26 cases (9/11 LYP, 10/15 ALCL) while 22/26 cases expressed TCRα (11/11 LYP, 11/15 ALCL) and 1/21 cases expressed TCRβ (0/10 LYP, 1/11 ALCL). Using previously designated cut-offs (>70% or <25%), 25/26 cases were monoclonal by TRBC1/CD3, 24/26 by TRBC1/TCRα, and 16/21 by TRBC1/TCRβ; 5 cases showed TRBC1>TCRβ, complicating interpretation but confirming TCR aberrancy. Unusual scenarios included: low CD3, TCRβ, and TCRα (ALCL, monoclonal); low CD3, high TCRβ and TCRα (LyP, monoclonal); low CD3, high TCRα (ALCL, monoclonal); or low CD3 and TCRβ, high TCRα (1 LyP and 3 ALCL, monoclonal). In such cases, percentages could be gauged. No differences were noted between LYP vs. ALCL (p=0.39). TCRα IHC robustly detects TCRα protein and can be used to define TRBC1 clonality in CD30+LPDs. TCRα and CD3 synergize in determining TRBC1 clonality despite displaying different patterns versus TCRβ. Importantly, relative reduction in TCRβ may reflect biological differences, not technical artifact, suggesting that high TRBC1:TCRβ ratios are an independent marker of clonality; additional study of this concept is warranted.