Sezary syndrome: cutaneous immunoperoxidase double-labeling technique demonstrates CD4/CD8 ratio non-specificity

Background: Sezary syndrome (SS) is an erythrodermic cutaneous T-cell lymphoma with a leukemic component. Biopsies from these patients may suggest erythrodermic mycosis fungoides or SS but most often are not diagnostic. Additional methods are therefore usually needed to diagnose SS. These include a peripheral blood morphological assessment, flow cytometry, and gene rearrangement studies. The Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer has proposed criteria for the diagnosis of SS based on peripheral blood analysis. These include an increased T-cell count with a CD4/CD8 ratio of greater than or equal to10, in conjunction with evidence of a T-cell clone in the blood (Willemze et al., Blood 1997; 90: 354-371). Methods: We have conducted a study designed to obtain CD4/CD8 ratios by immunoperoxidase staining of skin biopsies, as opposed to flow cytometry. Fourteen biopsies from eight patients with SS and 14 control biopsies were evaluated for CD4/CD8 ratio via double immunostaining. Results: A CD4/CD8 ratio of >10 : 1 was seen in 85% of SS biopsies and 43% of controls with horseradish peroxidase used as the CD4 antibody. With alkaline phosphotase used as the CD4 antibody, 54% of SS biopsies and 21% of control biopsies exhibited a >10 : 1 ratio. We demonstrate that double-labeling immunoperoxidase staining with antibodies to CD4 and CD8 on skin biopsies is not specific for SS. By comparing the CD4/CD8 ratios from skin biopsies in Sezary cases with those from biopsies in inflammatory dermatoses cases, we conclude that flow cytometry remains the most specific method for determining the CD4/CD8 ratios in patients with cutaneous eruptions. Although immunohistochemistry would be useful for laboratories with limited access to flow cytometry, we dismiss such a use, as CD4/CD8 ratios greater than or equal to10 were also found in 21-43% of non-Sezary cases examined. Conclusions: We conclude that a CD4/CD8 ratio >10 : 1 on skin biopsy is not sufficiently specific to support a diagnosis of SS.