A practical approach to risk stratification of incidental T cell clonality

Because T cell neoplasms often present with nonspecific findings, T cell clonality assessment is performed across many clinical scenarios, including the workup of cytopenias, lymphocytosis, eosinophilia, and suspected lymphoma. Sensitive assays, including flow cytometric staining of the T cell receptor (TCR) constant region and molecular-based TCR clonality testing, have enhanced our ability to detect T cell neoplasms, but these techniques frequently identify T cell clones in patients without suspicion of T cell malignancy. These incidentally detected clones, sometimes called T cell clones of uncertain significance (TCUS), do not clearly have universal potential for progression to overt T cell neoplasia. However, their detection can prompt unnecessary diagnostic procedures, generate unwarranted patient anxiety, and even lead to inappropriate therapeutic interventions. Here, we propose a practical framework for risk stratification of unexpected T cell clones in peripheral blood that minimizes the risk of unnecessary intervention while maintaining vigilance for true T cell malignancy.