Cutaneous T-cell lymphomas are a group of extra-nodal non-Hodgkin’s lymphomas that originate in the skin and consist of a group of diseases with varying clinical presentation, histologic features, and prognosis. Cutaneous T-cell lymphomas account for approximately 80% of all primary cutaneous lymphomas, with mycosis fungoides being the most common type accounting for approximately 70% of cutaneous T-cell lymphomas. Cutaneous T-cell lymphoma, being an extremely difficult disease to cure, requires a chronic disease treatment regimen that includes biological and cytokine drugs, photochemotherapy, and monoclonal antibody drugs directed at new molecular targets.
Classification of cutaneous T-cell lymphoma.
In 2005 the World Health Organization (WHO) classification of malignant lymphomas and the European Organization for Research and Treatment of Cancer (EORTC) classification of cutaneous lymphomas were merged and a new classification system (WHO- EORTC) classification system was proposed at the meeting. The most significant change is that previously Sezary syndrome was often classified as a variant of mycosis fungoides, but the WHO- EORTC classification The WHO-EORTC classification system treats the two diseases as separate categories with their own clinical features.
WHO-EORTC classification of cutaneous T-cell lymphoma 2005:
Mycosis fungoides granulomatosis.
Variants and subtypes of mycosis fungoides.
Mycosis fungoides granulomas of pro-follicular origin.
Paget-like reticulocytosis.
Granulomatous skin laxity.
Sezary’s syndrome.
Adult T-cell leukemia/lymphoma.
Primary cutaneous CD30+ lymphoproliferative disorders.
Primary cutaneous progressive large cell lymphoma.
Lymphomatoid papulosis.
Subcutaneous lipofuscinosis-like T-cell lymphoma.
Extra-nodal NK/T-cell lymphoma, nasal type.
Primary cutaneous peripheral T-cell lymphoma, unspecified type.
Primary cutaneous aggressive pro-epidermal CD8+ T-cell lymphoma.
Cutaneous T-cell lymphoma.
Primary cutaneous CD4+ small/moderate size pleomorphic T-cell lymphoma.
Pathogenesis.
The pathogenesis of cutaneous T-cell lymphoma is currently unknown. The viral etiology of mycosis fungoides has been proposed by some research groups who have found short sequences of human T-cell lymphoma virus (HTLV)-1 in mycosis fungoides tissue specimens. Other investigators have suggested that the pathogenesis of mycosis fungoides is associated with cytomegalovirus (CMV) and EBV, but there is still a lack of sufficient evidence.
Clinical manifestations of mycosis fungoides and Sezary’s syndrome.
Mycosis fungoides lesions are varied; the initial lesions are erythematous, patchy, scaly plaques that may be associated with pruritus; the lesions are often confined to non-light areas of the trunk and may present with skin color changes (skin atrophy with capillary dilation) or with hair loss. As the lesions progress, they may become infiltrative plaques, more widespread, occurring on light areas such as the face, and further become tumor nodules or ulcers. Patients usually undergo a prolonged period of lesions, ranging from months to years, and Sezary’s syndrome, which usually has a generalized erythrodermic appearance with severe atrophy or mossy skin changes, more pronounced pruritus and desquamation, plaques or tumor nodules that may coexist, usually with enlarged lymph nodes and greater than 5% cerebral gyrus-like malignant T cells in the peripheral blood. When the disease progresses further it can cause hair loss, nail atrophy, and damage to the eye.
Advances in treatment.
Because mycosis fungoides and Sezary syndrome are difficult to cure, the goal of treatment is to control the progression of the disease while ensuring that the toxic side effects of the drugs are kept to a minimum. Many topical therapeutic agents (nitrogen mustard, steroids, bexarotene) as well as UV-based therapies provide rapid relief of plaques and plaques in the disease, and systemic therapy is indicated for patients who are difficult to control by local treatment or for patients with disseminated plaques and tumorigenic forms. In some patients with progressive disease or where single therapy has failed, a combination of phototherapy, steroid hormones, and biologic agents has been shown to be more effective for patients.
IFN-α has become a first-line therapeutic agent for the treatment of cutaneous T-cell lymphoma.
Medium-wave ultraviolet light (UVB) has shown good results in early plaque and plaque stage mycosis fungoides
Histone deacetylase inhibitors, vorinostat and peptidoglutethimide have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of cutaneous T-cell lymphoma.