Indolent γδ CD4−/CD8− double negative T-large granular lymphocytic leukemia with a STAT5B T628S mutation: a case report

T-large granular lymphocytic leukemia (T-LGLL) is an uncommon clonal lymphoproliferative disorder, predominantly originating from CD8 + αβ T cells. γδ T-cell and CD4 − /CD8 − double negative variants are uncommon, with their molecular characteristics and clinical behavior not yet fully elucidated. STAT5B mutations have been reported in specific subsets of T-LGLL and may correlate with aggressive disease in certain variants. We report the case of a 58-year-old woman with persistent lymphocytosis for more than four years. The patient had no B symptoms, lymphadenopathy, hepatosplenomegaly, autoimmune disease, or abnormal inflammatory markers. Peripheral blood contained 3.65 × 10 9 /L large granular lymphocytes (50% of leukocytes), with abnormal lymphocytes accounting for 11.2% of bone marrow nucleated cells. Immunophenotyping demonstrated a γδ CD4 − /CD8 − double negative T-cell population with CD16/CD56 co-expression. T-cell receptor γ gene rearrangement analysis revealed T-cell clonality, while cytogenetic analysis revealed a normal karyotype. Targeted next-generation sequencing of whole bone marrow DNA identified a STAT5B c.1883 C > G (T628S) mutation with a variant allele frequency (VAF) of 6.5%, along with a CCND3 variant of uncertain significance. Despite the STAT5B mutation, the patient remained clinically stable without treatment. Serial complete blood count analyses indicated persistent lymphocytosis without progressive leukocytosis, stable hemoglobin concentrations, and stable platelet counts. This case illustrates that the presence of a STAT5B mutation was not associated with aggressive clinical behavior, as the patient maintained an indolent clinical course.