Frequent expression of CD3 epsilon in CD3 (Leu 4)-negative nasal T-cell lymphomas

Adult natural killer (NK) cells had not generally been thought to express CD3 proteins other than zeta; however they were recently demonstrated to express CD3 epsilon in an activated condition. This prompted us to investigate the tumor tissues from 17 patients with Leu4-negative peripheral T-cell lymphoma, including eight with nasal T-cell lymphoma (NTCL), for the expression of CD3 epsilon. The tissues were immunohistologically stained with rabbit anti-human CD3 epsilon antibody. The expression of CD3 epsilon was more frequent in the tissues of nasal lymphoma than in the non-nasal lymphoma tissues: specimens from six of eight of the NTCL patients expressed CD3 epsilon, while only one of nine of the non-NTCL patients did so. The NTCL patients presented clinically with lethal midline granuloma, had histologic findings of tumor necrosis and angioinvasion, and had a peculiar CD2+, Leu4-, CD3 epsilon+, CD5-, CD7+, CD45RO+, CD4-, CD8-, beta F1-, T-cell receptor (TRC) delta 1-, CD56+ phenotype. This peculiar phenotype seems to be closely associated with NTCL. No clonal rearrangement of the TCR genes was detected in three NTCL patients examined. The NK cell origin of NTCL has been suggested by previous investigators. The phenotypic correspondence of our nasal tumors to adult activated NK cells supports this possibility, together with their lack of clonal rearrangement of the TCR genes.