TRBC1 Immunohistochemistry Utilization in Formalin-fixed Paraffin-embedded Tissue as an Adjunct to T-cell Clonality Testing in the Assessment of Cutaneous Lymphoproliferative Disorders.

Abstract

T-cell receptor β chain constant region 1 (TRBC1) immunohistochemistry (IHC) has emerged as a novel tool for identifying T-cell clonality in skin biopsies. Its performance in routine formalin-fixed, paraffin-embedded (FFPE) skin specimens across the spectrum of cutaneous T-cell lymphoma (CTCL), however, remains an area of active investigation. We evaluated TRBC1 IHC in 36 cases of cutaneous T-cell lymphoproliferative disorders and 31 polyclonal controls. TRBC1 was assessed relative to CD3 by blinded consensus interpretation followed by semiquantitative estimation of TRBC1-positive cells as a percentage of CD3-positive T-cells. Results were compared with molecular clonality test data, and subtype-specific analyses were performed. Overall concordance of TRBC1 consensus interpretation with clonality testing was 79% (sensitivity 64%, specificity 97%, positive predictive value 96%, negative predictive value 70%). Sensitivity was higher (72%) when analysis was restricted to cases of mycosis fungoides (MF) and controls, but sensitivity decreased (50%) when assessment was restricted to only the intraepithelial T-cells. Sensitivity was also lower (56%) with the assessment of non-MF CTCL. Thresholds of ≤20% or ≥80% and ≤30% or ≥70% TRBC1-positive cells permitted optimal discrimination between monoclonality and polyclonality. As anticipated, lymphoproliferative disorders composed of T-cells that did not express a β chain, including those composed of TCR-ɣ/δ T-cells, lacked TRBC1 expression. Overall, TRBC1 IHC demonstrated modest utility as an adjunctive marker of T-cell clonality in FFPE skin biopsies, with greatest diagnostic value in MF when evaluation is not restricted to intraepithelial lymphocytes.