Unusual immunophenotype of T-cell large granular lymphocytic leukemia: Report of two cases

Large granular lymphocytes (LGL) leukemias are commonly of the T-cell or NK-cell type. T-cell LGL leukemia is typically a disorder of mature CD3, CD8 and T-cell receptor TCR (TCR - T cell receptor)-αβ positive cytotoxic T-cells. Rare variants include TCRγδ⁺ variants and CD4 ⁺ TCRαβ⁺ cases. We report a case of each of these rare variants. An 83-year-old female presented with anemia and lymphocytosis with LGLs on peripheral smear. Six-color multiparametric flowcytometric analysis showed expression of CD3, heterogeneous CD7, dim CD2 and TCRγδ and lacked expression of CD5, TCRαβ, CD56, CD4 and CD8. A final diagnosis of TCRγδ⁺ T-cell LGL leukemia was made. Differentiation between TCRγδ⁺ T-cell LGL leukemia and other γδ⁺ T-cell malignancies is of utmost importance due to the indolent nature of the former as compared to the highly aggressive behavior of the latter. An 85-year-old male diagnosed with liposarcoma was identified to have lymphocytosis during preoperative evaluation. Peripheral smear showed presence of LGLs. Flowcytometric immunophenotyping showed expression of TCRαβ, CD3, CD2, CD5, CD4, dim CD8, CD56 with aberrant loss of CD7 expression. Vβ repertoire analysis by flowcytometry showed 97% cells with Vβ14 clonality. A final diagnosis of TCRαβ⁺ CD4 ⁺ T-cell LGL leukemia was made. CD4 ⁺ T-cell large granular lymphocytic leukemias have an indolent, less aggressive course when compared to their CD8 ⁺ counterparts and are not necessarily associated with cytopenias. However, their association with secondary neoplasia (29% of the cases) warrants a high degree of suspicion in the diagnosis as also noted in the index case. Use of a wide panel of antibodies and newer modalities such as Vβ repertoire analysis helps in accurate subtyping of LGL leukemia.