The Evolution of Sézary Syndrome: Past, Present and Future

Abstract

In this review, the author discusses the changes that have occurred in our understanding of Sézary syndrome and erythrodermic mycosis fungoides, which are currently regarded as ‘leukemic’ and ‘non-leukemic’ expressions of erythrodermic cutaneous T cell lymphoma, respectively. The neoplastic cells have highly infolded ‘cerebriform’ nuclei (neoplastic Sézary cells), and display properties of central memory T cells of skin-associated lymphoid tissue. Although Sézary syndrome is characterized by a myriad of genetic and epigenetic abnormalities, no one fundamental defect is common to all cases. Cytokines and colonization of the skin by Staphylococcus aureus promote phenotypic plasticity and tumor progression. The prognostic significance of blood involvement is now recognized as B ratings in a revised tumor-node-metastasis (TNM) classification system for cutaneous T cell lymphoma. Flow cytometry and evolving molecular genetic methods to quantify blood involvement are replacing traditional visual counts of Sézary cells on blood smears. Patients without erythroderma and blood findings that are typical for Sézary syndrome have been reported. The author predicts that revisions to the TNMB ratings will be required in the future.