Cutaneous T-cell Lymphoma: Mycosis Fungoides and Sézary Syndrome

Introduction

Cutaneous T-cell lymphoma (CTCL) is a group of non-Hodgkin lymphomas with primary cutaneous manifestation but can also involve the blood, lymph nodes, and visceral organs. Mycosis fungoides (MF) is the most common variant and accounts for 54–72% of all cases of CTCL. Sézary syndrome (SS) represents 2.5% of all cases of CTCL and is an aggressive, leukemic variant of CTCL. MF and SS are considered different presentations of the same disease and, therefore, are referred to as MF/SS and included in a single staging system. However, recently published studies using gene expression analysis revealed a different expression profile for MF and SS.

MF/SS is characterized by a predominance of memory helper T cells (CD4 ⁺ /CD45R0 ⁺ ) with loss of mature T-cell antigens. Clinically, MF presents with lesions limited to the skin and follows an indolent course over several years; SS presents with generalized erythroderma, lymphadenopathy and blood involvement. Other cutaneous lymphomas, in order of decreasing frequency, include primary cutaneous peripheral T-cell lymphoma, CD30 ⁺ lymphoproliferative disorders (lymphomatoid papulosis and anaplastic large T-cell lymphoma), subcutaneous panniculitic T-cell lymphoma, NK/T-cell lymphoma, angioimmunoblastic T-cell lymphoma, and adult T-cell leukemia/lymphoma (HTLV-1 ⁺ ). Since MF and SS are the most common type of CTCL, they will be the focus of this chapter.

History

Mycosis fungoides was first described by Alibert in 1806 through a case series of patients with mushroom-like cutaneous lesions. Sézary later described a patient with erythroderma, leukocytosis, and lymphadenopathy in 1936.

Epidemiology

MF/SS is rare, with an annual incidence of 6.4 per million patient-years in the United States from 1973 to 2002. MF is substantially more common in blacks than whites (incidence rate ratio 1.6) and even less common in Asians (incidence rate ratio of 0.6 compared to whites). Conversely, SS occurs more commonly in whites than blacks. The onset of disease increases in incidence with age (median age at diagnosis, 57–61 years). However, MF/SS has been described in patients of all ages. Epidemiologic data accumulated between 1973 and 2002 appeared to show an increased incidence of MF/SS. CTCL incidence positively correlates with high physician density, high density of medical specialists, high median family income, and high percentage of adults with a bachelor's degree or higher. These data indicate that the true incidence of CTCL is likely underrepresented with current epidemiological data.