Mycosis fungoides and Sézary syndrome are rare forms of non-Hodgkin lymphoma that primarily impact the skin. These conditions are classified as cutaneous T-cell lymphoma (CTCL), malignancies originating from specific white blood cells.
Understanding Cutaneous T-Cell Lymphoma
Cutaneous T-cell lymphoma (CTCL) refers to a group of cancers that arise from T-lymphocytes, a type of white blood cell that normally plays a role in the body’s immune system. These cancerous T-cells primarily accumulate in the skin, causing various skin-related symptoms. While the skin is the primary site of involvement, in some cases, these abnormal T-cells can also affect the blood, lymph nodes, and even internal organs.
T-cells are a component of the immune system, responsible for recognizing and fighting off infections and abnormal cells. In CTCL, these T-cells undergo genetic changes in their DNA, leading to uncontrolled growth and multiplication. This accumulation of cancerous T-cells in the skin results in the characteristic skin lesions associated with CTCL. Although the precise cause of these cellular transformations is not fully understood, the resulting buildup of abnormal T-cells is the underlying mechanism of CTCL.
Mycosis Fungoides and Sézary Syndrome Defined
Mycosis fungoides (MF) is the most common type of CTCL, accounting for approximately 50% to 70% of all cases. This lymphoma typically presents as slow-growing skin lesions, appearing as flat, scaly patches, thicker raised plaques, or tumors. MF usually follows an indolent, chronic course, often remaining confined to the skin for many years before potentially progressing.
In contrast, Sézary syndrome (SS) is a more aggressive, leukemic variant of CTCL, affecting typically 3% to 5% of all CTCL diagnoses. SS is characterized by widespread skin redness (erythroderma), often covering 80% or more of the body surface. This condition often includes severe itching, enlarged lymph nodes, and the presence of cancerous T-cells, called Sézary cells, circulating in the blood. While Sézary syndrome can sometimes develop as an advanced form of mycosis fungoides, it can also arise independently.
Recognizing the Signs
Mycosis fungoides often begins with characteristic skin lesions. These typically include patches, which are flat, scaly, and often itchy areas. These patches commonly appear on areas of the body not usually exposed to the sun, such as the lower abdomen, upper thighs, buttocks, and breasts. Over time, these patches can evolve into plaques, which are thicker, raised lesions that are often reddish or brownish and itchy.
The disease may progress to form tumors, which are raised lumps or nodules, thicker and deeper than plaques. These tumors can develop from pre-existing patches or plaques, or appear on their own, often in areas like the upper thighs, groin, armpits, and the crook of the elbow. Most patients with mycosis fungoides experience itching.
Sézary syndrome presents with more severe symptoms, most notably generalized erythroderma, which is widespread redness covering most of the body, often with severe itching. Other common signs include palmoplantar keratoderma, a thickening of skin on the palms and soles. Hair loss (alopecia), nail abnormalities, and outward turning of the lower eyelids (ectropion) can also occur. Individuals with Sézary syndrome often have enlarged lymph nodes and may experience systemic symptoms such as fever, fatigue, and unexplained weight loss.
Diagnosis and Treatment Pathways
Diagnosing mycosis fungoides and Sézary syndrome involves a multi-faceted approach, combining clinical assessment with laboratory and imaging tests. A skin biopsy is typically a primary diagnostic tool, where a small piece of affected skin is removed for microscopic examination by a pathologist. This helps to identify the presence of cancerous T-cells in the skin.
Blood tests are also performed, especially for Sézary syndrome, to detect Sézary cells circulating in the bloodstream. A lymph node biopsy may be necessary if lymph nodes are enlarged, to determine if the cancer has spread beyond the skin. Imaging tests, such as PET/CT scans, may be used for disease staging to assess for potential involvement of internal organs. The staging of both conditions uses a TNMB system, evaluating the extent of skin involvement (T), lymph node involvement (N), presence of metastasis (M), and blood involvement (B).
Treatment strategies for mycosis fungoides and Sézary syndrome are individualized, depending on the disease stage, specific type, and overall patient health. For early-stage disease, skin-directed therapies are often employed. These include topical corticosteroids to reduce inflammation and kill lymphoma cells, and topical chemotherapy agents like mechlorethamine or carmustine. Phototherapy, involving exposure to specific wavelengths of ultraviolet (UV) light, is another common skin-directed approach. Localized radiation therapy can also be used for specific lesions or tumors.
For more advanced stages or when skin-directed therapies are not sufficient, systemic therapies are considered. These treatments affect the entire body and may include chemotherapy, targeted therapies that attack cancer cells, or immunotherapy that boosts the body’s immune response against the cancer. Extracorporeal photopheresis, a procedure where blood is treated outside the body with a light-sensitizing medication and then returned, is another option, particularly for Sézary syndrome. While there is no known cure for mycosis fungoides or Sézary syndrome, treatments aim to manage symptoms, control disease progression, and improve quality of life.