Primary cutaneous T-cell lymphoma (CTCL) is a group of lymphoproliferative disorders characterized by malignant T cells localizing and proliferating in the skin causing different types of skin lesions. CTCLs are classified as a clinically and biologically heterogeneous group of non-Hodgkin lymphomas (NHLs), and account for approximately 70% to 85% of all cutaneous lymphomas. Two subtypes, mycosis fungoides (MF) and Sézary syndrome (SS), are the most common types representing approximately 57% to 75% of all CTCLs. Mycosis fungoides tends to be indolent, that is, not rapidly progressing, and can sometimes mimic benign skin conditions such as psoriasis and chronic eczema. In its early form MF’s appearance is like a patch or a plaque, however, it can progress to a more advanced stage with tumor, erythroderma, or lymph node involvement. Sézary syndrome, the leukemic form of CTCL, appears as a diffuse rash (erythroderma) in addition to having malignant lymphocytes in the blood. It can pursue an aggressive course following dissemination to nodal or other extracutaneous sites. Both SS and MF compromises the integrity of the patient’s skin, resulting in itch, inflammation, breakdown in the skin barrier, chronic open sores, and susceptibility to infection.
The incidence of CTCL is on the rise with 4–8 people per million currently diagnosed with this disease. Patients with stage IA disease exhibit median survival times comparable to healthy controls. Patients with patches or plaques limited to the skin enjoy lengthy median survival times in the 15.8 to 21.5 year range. Patients with more advanced systemic disease including tumor-stage disease or erythrodermic (Sézary) disease experience highly abbreviated median overall survival times in the 1.4 to 4.7 year range. Furthermore, the occurrence of large cell transformation significantly worsens the risk of disease progression in MF and SS.
Cutaneous T-cell lymphomas follow a chronic, relapsing course with patients frequently undergoing multiple consecutive therapies. Design of therapeutic strategies are primarily based on disease stage and history of prior response to treatment. Since currently available evidence indicates that MF and SS are incurable, great consideration is given to the sequencing of drug treatment administered during palliation. Early stage disease (IA-IIA) with limited skin involvement is generally treated with skin-directed therapies intended to minimize recurrence as well as preserve quality of life. Patients with advanced and erythrodermic stage IIB-IVB MF and SS can have profound immunosuppression, with treatments targeting tumor cells aimed for immune reconstitution. Biologic agents or targeted therapies either alone or in combination are used first, with more immunosuppressive chemotherapies being reserved for refractory, metastatic or rapidly progressive disease.