Mycosis Fungoides

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL), a rare type of cancer derived from malignant T-cells of the skin. It results in erythematous patches and plaques with fine scales and tumors commonly on the sun-protected areas of the body (e.g., buttocks, trunk, and limbs).  

Generally speaking, lymphomas are tumors derived from white blood cells called lymphocytes, which include B cells and T cells. Typically, lymphomas affect lymph nodes; however, they can also develop in organs or tissues, a condition referred to as extra-nodal lymphoma. Lymphomas can be categorized into two main groups: Hodgkin lymphoma and non-Hodgkin lymphoma, where non-Hodgkin refers to the absence of the Reed-Sternberg cell, a characteristic cell found in Hodgkin lymphoma. Mycosis fungoides is a rare type of non-Hodgkin lymphoma that affects the skin. 

Individuals with mycosis fungoides may present with non-specific signs and symptoms years before the development of the classic features of the disease. Most commonly, these early symptoms consist of itchy skin and scaly lesions that may come and go over years, leading to frequent misdiagnoses (e.g., psoriasis, eczema). In some individuals, these initial lesions may never progress to mycosis fungoides, whereas in others they may follow the usual evolution of the disease.  

The first stage of mycosis fungoides is the patch stage, characterized by irregular, erythematous skin lesions with overlying scaly, wrinkled skin. These lesions typically develop in sun-protected areas, such as the chest, lower abdomen, and buttocks, and can vary in size. As the disease progresses, patches may evolve into thickened plaques that are often red, purplish, or brown and have a rough appearance. Initially, plaques are confined to certain skin areas, but over time they may affect the whole body. The final stage of mycosis fungoides is the development of tumors, which can appear over healthy skin or on top of patches and plaques. 

Malignant T-cells may sometimes leave the skin and start to circulate in the blood, resulting in a leukemic form of cutaneous T-cell lymphoma (CTCL) known as Sezary syndrome. Sezary syndrome is a rare and aggressive condition that presents with erythroderma, a red, itchy rash that affects almost the whole body surface. In addition to the bloodstream, malignant T-cells can travel to nearby lymph nodes and more rarely, to the liver, spleen, or gastrointestinal tract. This can result in swelling of the lymph nodes and hepatosplenomegaly, or enlargement of the liver and spleen.  

Treatment of mycosis fungoides varies depending on the stage of the disease and the risk of progression. Current treatments can help minimize the symptoms and improve quality of life, however, they are not curative in the majority of cases.  

Early-stage disease can be managed with topical treatments, such as corticosteroids (e.g., betamethasone, triamcinolone) or immunomodulators like imiquimod. Additionally, total body phototherapy such as psoralen with ultraviolet A (PUVA) therapy is commonly used. PUVA combines psoralen, a photosensitizing agent, with UVA rays to treat skin lesions by inducing death of the malignant cells. Because mycosis fungoides is highly radiosensitive, radiation therapy is also used to treat individual skin lesions or the entire skin surface. 

Systemic therapy is reserved for individuals with advanced stages of disease or poor response to topical treatments. Treatment options include retinoids (e.g., bexarotene), immunotherapy with interferon-alpha, low-dose methotrexate, and monoclonal antibodies, such as brentuximab vedotin. Monoclonal antibodies are medications designed to recognize and bind to specific proteins on the surface of cancer cells, helping to destroy them. Conventional chemotherapy (e.g., bleomycin, vincristine) is not as effective in treating mycosis fungoides as it is in other types of cancer, however, it may be used in combination with other systemic therapies in individuals with refractory disease. Finally, individuals with advanced disease may benefit from a bone marrow transplant, where blood-forming stem cells from a healthy donor are infused into the affected individual’s bloodstream to replace their affected bone marrow.