Immunohistochemical Evaluation of T Cell Receptor and T Cell Receptor Beta Constant 1 Expression Distinguishes Benign and Neoplastic Immature T Cell Populations and Reveals Discrete TRBC1/TCR Phenotypes

Background: Expression of TRBC1 and TRBC2 is increasingly assessed in the evaluation for clonal T-cell populations. While flow cytometry has repeatedly shown utility in evaluating TRBC 1/2 expression, immunohistochemical (IHC) methods have not been extensively examined, particularly in immature T-cell populations. Purpose: This study evaluated TRBC1 IHC staining in formalin-fixed paraffin-embedded (FFPE) tissue, encompassing benign thymic tissue, thymomas, and T-lymphoblastic leukemias/lymphomas (T-LL). Methods: IHC for TRBC1, CD3, TCR-BF1, and TCR-δ was performed in all cases; TdT was performed on all T-LLs. TRBC1 was scored as positively restricted (≥ 85%), negatively restricted (≤ 15%), or polytypic (16–84%) in T-cells, using CD3 and/or TdT staining as the denominator. Results: All thymic tissues (n = 6) and thymomas (n = 5) showed polytypic TRBC1 staining patterns. Twenty-four T-LL specimens were identified from 21 patients, to include bone marrow (n = 16), lymph node (n = 7), and bone (n = 1) biopsies. All T-LL cases showed positively (n = 3 patients, 14%) or negatively (n = 18 patients, 86%) restricted TRBC1 expression. Patients with multiple specimens showed consistent TRBC1 staining across tissue sites and sampling time points. Coexpression analysis of TRBC1, TCR-BF1, and TCR-δ staining revealed frequent TRBC1-negative cases with either TCR-δ+ (n = 6, 29%) or TCR null (n = 7, 33%) phenotypes. TRBC1 IHC restriction and molecular methods for clonality assessment were concordant in 13 of 15 evaluated cases (87%). Conclusions: T-LL showed restricted patterns of TRBC1 expression by IHC, whereas benign immature T-cell populations showed polytypic staining. The observed TCR and TRBC1 phenotypes of T-LL are distinct from those of mature T-cell neoplasms and warrant further study.