T-cell clones of uncertain significance are highly prevalent and show close resemblance to T-cell large granular lymphocytic leukemia. Implications for laboratory diagnostics

Benign clonal T-cell expansions in reactive immune responses often complicate the laboratory diagnosis T-cell neoplasia. We recently introduced a novel flow cytometry assay to detect T-cell clones in blood and bone marrow, based on the identification of a monophasic T-cell receptor (TCR) β chain constant region-1 (TRBC1) expression pattern within a phenotypically distinct TCRαβ T-cell subset. In routine laboratory practice, T-cell clones of uncertain significance (T-CUS) were detected in 42 of 159 (26%) patients without T-cell malignancy, and in 3 of 24 (13%) healthy donors. Their phenotype (CD8+/CD4−: 78%, CD4−/CD8−: 12%, CD4+/CD8+: 9%, or CD4+/CD8−: 2%) closely resembled that of 26 cases of T-cell large granular lymphocytic leukemia (T-LGLL) studied similarly, except for a much smaller clone size (p