Clinical, hematologic, and immunophenotypic characterization of canine large granular lymphocytosis

Clinical, hematologic, and immunophenotypic data were studied in 25 dogs with large granular lymphocyte (LGL) lymphocytosis. Primarily large-breed dogs were affected, with an average age at initial diagnosis of 10 years (range 5-14 years). All dogs had persistent (>4 months) LGL lymphocytosis except for three that were euthanized with aggressive disease. Splenomegaly was reported in 12 of 20 dogs in which splenic size was evaluated. The clinical course was heterogeneous and dogs were divided into four groups based on similar clinical and hematologic findings: acute leukemia (3/25), persistent lymphocytosis with anemia (12/25), persistent lymphocytosis without anemia (8/25), and reactive lymphocytosis (2/25). Immunophenotypes varied within groups but were homogeneous among cells from the same patient except in the two dogs classified as reactive LGL lymphocytosis. Analysis of T-cell receptor (TCR) usage identified three main LGL lineages. TCR alpha beta was expressed in 15/25 (60%) cases. TCR gamma delta was expressed in 8/25 (32%) cases, and 2/25 (8%) cases were CD3(-), compatible with NK cells. beta (2) integrin expression was distinctive. CD11a was consistently expressed, while CD11b was absent. CD11c was expressed only weakly in 16/25 (64%) cases. The leukointegrin alpha (d)beta (2) was highly prevalent on all LGL lineages, being expressed in 23/25 (92%) cases. Prominent involvement of the spleen, relative sparing of bone marrow, an unexpectedly large proportion of gamma delta T-cell LGLs, and the distinctive beta (2) integrin expression pattern on diverse lineages of LGLs suggest the disease arises from unique populations of lymphocytes that preferentially localize in the splenic red pulp.