CLONAL CD3(-ASSOCIATED (NKA) EXPANSIONS - PRIMARY MALIGNANCIES OR SECONDARY REACTIVE PHENOMENA()CD8(+) LARGE GRANULAR LYMPHOCYTE (LGL) NK)

This study reports the clinical, haematological and immunophenotypic f eatures of a series of 25 patients with clonal expansions of large gra nular lymphocytes (LGL)/NK-associated (NKa) cells. These showed a male predominance (16:9) with a median age of 67 (range 38-91) years; four had a documented history of rheumatoid arthritis, a further 18 had di verse clinical disorders, and the remaining three were clinically well . Mild anaemia was found in approximately half the patients and a lymp hocytosis (seen in approximately 70% of the cases) was usually modest (< 10.0 x 10(9)/l). Neutropenia was the most frequently observed featu re, and this was typically persistent in nature. Serum studies reveale d few consistent features although positive rheumatoid factor and incr eased soluble CD8 levels were noted in 67% and 87% of those cases test ed. Phenotypically, all cases were CD2(+)CD3(+)CD8(+) and expressed me mbrane TCR alpha beta chains; most (17/22) were additionally CD5(+) an d (19/22) CD7(+). The staining intensities of CD5 and CD7 antigens wer e however lower than that of normal CD4(+) and CD8(+) blood lymphocyte s. Expression of NKa antigens was variable although 16/22 cases were C D16(+)CD56(-) and 19/22 were CD57(+). Clonal CD3(+)CD8(+) LGL/NKa expa nsions with a CD16(+)CD56(+) composite phenotype were not seen in this patient series. Analyses of 'activation' antigens showed a consistent lack of CD25 expression by CD3(+) cells, but increased CD3/Ia co-expr ession was found in a high proportion (19/25) of cases. Studies of CD4 5R isoform expression by CD8(+) LGL/NKa cell fractions revealed a cons istent CD45RA(+)RO(-) profile for all cases tested. It is suggested th at the clinical and cellular findings in these patients raise the dist inct possibility that most of these clonal LGL/NKa disorders have a ch ronic reactive rather than neoplastic aetiology.