Syndrome de sézary

Abstract

The Sezary cell is a mature lymphocyte with a convoluted, cerebriform nucleus on cytomorphologic and ultrastructural samples. It is a major diagnostic feature of Sezary syndrome, clinically defined by the rapid onset of a pruriginous erythroderma with diffused adenopathies. Sezary cells can also reveal blood involvement by tumor cells in patients with mycosis fungoides. In a suggestive clinical context, peripheral blood smear examination is essential, whatever the results of the total blood count, to identify a significant percentage of characteristic cells. Most Sezary cells have a phenotype of mature memory T-lymphocytes, CD2 +, CD3 +, CD4 +, CD5 +, CD8 −, CD45RO +, CD45RA −, TCR α/β +, but rarely they can also exhibit a CD8 +CD4 − or CD4 +CD8 + phenotype, and/or a lack of expression of CD2, CD3, CD4, or CD5 antigens. Patients with a Sezary syndrome often have an increase in CD4 + lymphocytes. The CD4 +CD7 − population is also increased, but tumor cells have been identified both in the CD4 +CD7 + and in the CD4 +CD7 − populations. Sezary cells are found in the CD4 +CD26 − population, but there are yet no specific phenotypic markers of Sezary cells. IL-7 is a growth factor for Sezary cells, and can induce the establishment of long-term tumor T-cell lines. We recently identified three other surface antigens on Sezary cells. The Natural Killer (NK) receptor CD158k/KIR3DL2/p140, normally expressed by NK and CD8 + T-cells was detected on the surface of CTCL cell lines as well as on freshly isolated CD4 + peripheral blood lymphocytes from SS patients. SC5 is a newly described activation-related intracellular inhibitory receptor expressed on the surface of a minor PBL subset. We found that SC5 expression was significantly increased in SS cells and correlated to p140 expression, ILT-2/CD85j is another inhibitory receptor expressed by tumor T-lymphocytes. Both SC5 and ILT-2 molecules are functional on CTCL cells, as their triggering in vitro leads to the recruitement of SHP-1 and to the specific inhibition of CTCL malignant cell proliferation induced by CD3/TCR stimulation. The expression of these antigens and the cytokine-induced upregulation of bcl-2 could partly explain the survival and the inhibition of the apoptosis of Sezary cells. Their identification on circulating SS tumor cells might be of importance both for the understanding of CTCL pathophysiology and for the treatment of SS patients.