T-cell receptor gene analysis in the diagnosis of Sezary syndrome

Diagnosing Sezary syndrome (SS) on clinicopathological grounds alone is far from straightforward, particularly in the early stages of the disease. Aty pical lymphocytes may be seen in the peripheral blood of patients with reac tive forms of erythroderma, so additional criteria are needed to establish the diagnosis of a T-cell leukemia/lymphoma. A wide variety of confirmatory tests have been proposed in the literature, but there has been no systemat ic attempt to compare the specificity and sensitivity of these different me thods. Recent data indicate that T-cell receptor (TCR) gene analysis is the most useful test currently available and that methods based on polymerase chain reaction are more sensitive than Southern blot analysis. We propose t hat the diagnostic criteria for SS should include erythroderma, atypical ci rculating mononuclear cells, and evidence of a clonal T-cell population in the peripheral blood. Clonality can be established with certainty by cytoge netic or TCR gene analysis, but only the latter is sufficiently sensitive t o be of value in routine diagnosis. Immunophenotypic data showing an expand ed CD4(+)/CD7(-) population, an elevated CD4/CD8 ratio, or restricted V bet a expression are nor specific to T-cell malignancy and should not be used a s a sole diagnostic criteria in SS. Entry criteria for future clinical stud ies will need to be more rigorous if meaningful comparisons are to be made between different treatment options.