Large granular lymphocyte (LGL) leukemia is characterized by a clonal proliferation of LGLs. LGLs comprise 5 percent of the population of peripheral blood mononuclear cells, are larger than most circulating lymphocytes, and have characteristic azurophilic granules containing acid hydrolases (picture 1). They may be either T cells (T-LGL), the more common type, or natural killer cells (NK-LGL) .
LGL leukemia is a heterogeneous disorder characterized by peripheral blood and marrow lymphocytic infiltration with LGLs, splenomegaly, and cytopenias, most commonly neutropenia. Up to one-third of patients with T-LGL leukemia also have rheumatoid arthritis (RA) . LGL leukemia can also occur in association with Sjögren’s syndrome in the absence of RA  and with other autoimmune disorders, including inflammatory bowel disease, systemic lupus, and autoimmune thyroid disease [3,4].
The pathogenesis, clinical manifestations, diagnosis, and differential diagnosis of LGL leukemia in the setting of RA are discussed here. Detailed discussions of T-LGL leukemia, NK-LGL leukemia, and their treatment are presented separately. (See "Clinical manifestations, pathologic features, and diagnosis of T cell large granular lymphocyte leukemia" and "Natural killer (NK) cell large granular lymphocyte leukemia" and "Treatment of large granular lymphocyte leukemia".)
T-cell large granular lymphocyte (T-LGL) leukemia is very uncommon among patients with rheumatoid arthritis (RA), despite the frequency of RA among patients with this disorder. In one study of over 1000 patients with RA, the prevalence of neutropenia that could not be attributed to other causes was 1.7 percent; one-third of the patients with neutropenia (0.6 percent of all patients with RA) exhibited LGL proliferation on bone marrow examination .
The mean age of onset of T-LGL leukemia in RA is 60 years, with no gender differences, which is similar to patients without arthritis . (See "Clinical manifestations, pathologic features, and diagnosis of T cell large granular lymphocyte leukemia", section on 'Clinical features'.)