Mycosis fungoides and Sézary syndrome: Pathophysiology and pathology

Cutaneous T cell lymphoma (CTCL) encompasses a wide range of disorders with various manifestations, clinical courses and therapeutic considerations. Mycosis fungoides (MF) is the most common form of CTCL in which the skin may be variably affected by flat patches, thin plaques or tumors. Sézary syndrome (SS) is a more aggressive form of CTCL in which there is diffuse skin involvement (erythroderma) and substantial peripheral blood involvement. MF/SS is a malignancy of the skin-homing population of T lymphocytes. The fact that a proportion of patients with MF will eventually progress to SS, as well as the corollary observation that after treatment, a patient previously with SS may demonstrate lesions typical of MF, indicates that MF and SS are different manifestations of the same malignancy. Fundamental to their clinical manifestations, the clonal T cells in MF/SS utilize the same mechanisms as normal T lymphocytes to infiltrate/populate the skin. Especially relevant in more advanced disease, like normal recirculating T cells, MF/SS cells may also traffic to variably involve the lymph nodes and peripheral blood. MF/SS cells will express a particular T cell receptor (TCR) and demonstrate an activated, memory phenotype. Within the compartments of skin, lymph nodes, and blood, MF/SS cells are further characterized by their resistance to apoptosis, clonal expansion, and capacity to exert regulatory effects on the remaining T cell repertoire/populations. Hence, a detailed consideration of normal T cell physiology is fundamental to the understanding of the pathogenesis of CTCL.