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, 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.