How to establish the diagnosis of LGL leukemia. The diagnosis is based on a LGL peripheral expansion (> 0.5 × 10⁹/L). Specific criteria for T-LGL leukemia include expression of LGL surface markers compatible with an activated T-cell (commonly CD3⁺/CD8⁺/CD57⁺ and/or CD16⁺) phenotype and clonal rearrangement of the TCR-γ gene using PCR or specific and clonal Vβ expression using flow cytometry. Specific criteria for NK-LGL leukemia and NK-LGL lymphocytosis include expression of LGL surface markers compatible with an NK-cell (commonly CD3⁻/CD8⁺/CD16⁺ and/or CD16⁺/CD56⁺) phenotype. The term chronic NK-LGL lymphocytosis is used for patients with relatively few symptoms and chronic illness, whereas patients with massive tissue LGL infiltration of the spleen, liver, and BM and presenting aggressive clinical behavior are considered to have NK-LGL leukemia. Reproduced with permission from Lamy and Loughran.⁶