CD3(+), CD56(+) AGGRESSIVE VARIANT OF LARGE GRANULAR LYMPHOCYTE LEUKEMIA

Clonal expansions of CD3(+) large granular lymphocytes (LGL) have been classified as T-LGL leukemia. The majority of patients with T-LGL leu kemia have a chronic disease (years) manifested often by severe neutro penia, rheumatoid arthritis, and mild-to-moderate splenomegaly. The ch aracteristic phonotype of the leukemic LGL is CD3(+), CD8(+), CD16(+), CD57(+), and CD56(-). In this report we describe an aggressive varian t of T-LGL leukemia in which leukemic LGL also expressed CD56, as iden tified by two-color flow-cytometry analysis. In contrast to the chroni c nature typical of T-LGL leukemia, these patients presented with a se vere systemic illness that was rapidly progressive and resistant to tr eatment. Atypical clinical features included rapidly increasing spleen size to massive proportions, extensive lymphadenopathy, and the prese nce of B symptoms (fever, nightsweats. weight loss). Hematologic and p athologic features were also unusual for T-LGL leukemia. These patient s had very high LGL counts at diagnosis (range 11,692 to 26,312 mu L), which increased rapidly despite treatment. Histopathologic examinatio n of splenic sections showed extensive infiltration of red pulp cords and sinuses by leukemic cells with atrophy of the white pulp. These cl inicopathologic features are similar to those described for patients w ith natural killer cell (NK)-LGL leukemia, whose cells are also CD56(). However, unlike NK-LGL leukemia, we could not show a direct pathoge nic role for Epstein-Barr virus (EBV), as Southern-blot analyses using an EBV-joined termini probe were negative in these patients. Our find ings suggest that CD3(+), CD56(+) LGL leukemia is a distinct clinicopa thologic entity separate from the usual CD3(+), CD56(-) T-LGL leukemia . The expression on leukemic LGL of CD56, an adhesion molecule, may de termine the aggressive biologic nature of this newly described disease . (C) 1994 by The American Society of Hematology.