38

Large granular lymphocytic leukemias (LGLs) are rare lymphoproliferative syndromes characterized by the clonal expansion of T or NK lymphocytes in 85 and 15% of cases respectively. Interestingly, T- and NK- LGL leukemias share a common pathophysiology and similar clinical and biological presentations. This lymphoproliferative syndrome is characterized by cytopenias and a frequent association with autoimmune diseases or manifestations. It is an indolent disease that in most cases allows for an abstinence-only strategy at diagnosis. However, the majority of patients will require initiation of treatment during follow-up. As NK cells lack a TCR, obtaining evidence of clonality in NK-LGL leukemias is difficult. This is crucial in view of possible reactive expansions in the context of viral infections or dysimmune diseases. The diagnostic approach has been facilitated by the progress made in recent years in the understanding of the pathophysiology and the recent identification of recurrent mutations. In this review, we will discuss the pathophysiology of NK-LGL leukemias and present recent advances in diagnostic strategies before discussing therapeutic management.