Expanding the use of T cell receptor beta constant 1 immunohistochemistry in formalin-fixed paraffin-embedded tissues in assessing T cell clonality in mature and immature T cell neoplasms

Abstract

Aims: Demonstration of clonality is important in the diagnosis of a T cell neoplasm. Allelic exclusion of T cell receptor beta constant chains (TRBC) ensures restricted TRBC1 or 2 expression in T cells. Here, we extend the applicability of TRBC1 immunohistochemistry (IHC) in assessing T cell clonality in formalin-fixed paraffin-embedded (FFPE) tissue sections, with a particular focus on peripheral T cell lymphoma and lymphoblastic lymphoma/leukaemia. Methods and results: TRBC1 and CD3 IHCs were performed on benign lymph nodes (BLN; n = 21), mature T cell lymphomas (TCL; n = 34), thymic tissues (n = 12) and T lymphoblastic lymphoma/leukaemia (T-ALL; n = 21). TRBC1 usage in CD3+ cells [TRBC1/CD3(%)] was scored manually and computationally. Non-restricted TRBC1 patterns in reactive T cells, as measured by TRBC1/CD3(%), are normally distributed (BLN average = 59.4%; thymocyte average = 58.5%). TRBC1 staining patterns, as measured by TRBC1/CD3(%), distribute into three clusters, reflecting the monotypic populations (TRBC1+ and TRBC1–) at two ends and a third cluster with a non-restricted pattern (due to increased reactive T cells). Based on the distribution patterns, we suggest TRBC1/CD3(%) ≤ 0.25 and ≥ 0.75 as a guide to establish monotypic patterns in mature T cells. Our T-ALL cohort, selected for high blast burden, exhibits monotypic TRBC1 patterns. Conclusion: TRBC1 IHC is a useful tool that can complement molecular TCR gene rearrangement studies in assessing clonality in mature and immature T cell populations, and can be compatible with decalcified tissue.