TRBC1/TRBC2 Immunophenotyping Provides Added Value During the Diagnostic Workup of T-Cell Lymphoma

Abstract

Background: Molecular T-cell receptor (TCR) clonality testing cannot link clonality to immunophenotype, limiting discrimination between malignant and clonal reactive T-cell expansions. Method(s): We evaluated TRBC1/TRBC2 immunophenotyping in 50 consecutive cases with suspected T-cell malignancy, assessing restriction (ratio > 10) across T-cell subsets. Result(s): TRBC immunophenotyping showed 100% sensitivity for T-cell malignancy if assessed within subsets or phenotypically abnormal populations. Malignant clones predominantly showed CD4alphabeta/CD8alphabeta restriction (18/21), while reactive clones predominantly showed gammadelta/dual-positive/dual-negative restriction (15/16), enabling enhanced discrimination. Conclusion(s): TRBC immunophenotyping provides sensitive clonality detection with phenotypic lineage assignment, adding diagnostic clarity beyond molecular testing and supporting integration into routine workflows. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission. Copyright © 2025 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.