Mycosis fungoides

Overview

Mycosis fungoides is the most common form of cutaneous T-cell lymphoma (CTCL), a rare type of non-Hodgkin lymphoma that primarily affects the skin. Despite its name, mycosis fungoides is not a fungal infection. Instead, it is a type of cancer that involves malignant T-lymphocytes (a type of white blood cell) infiltrating the skin, causing various dermatologic manifestations such as patches, plaques, or tumors.

The disease progresses slowly and often starts with skin symptoms that may resemble eczema or psoriasis, making early diagnosis challenging. Over time, it can involve deeper layers of skin, lymph nodes, blood, and internal organs. Mycosis fungoides typically affects adults over the age of 50, with a higher incidence in males and people of African descent. Though it is a chronic condition, many patients can manage it effectively for years with appropriate therapy.

Causes

The exact cause of mycosis fungoides remains unknown. It is not contagious, and there is no known infectious or environmental trigger that consistently explains its development. Most cases are sporadic, meaning they occur without a family history or identifiable risk factor.

Possible Contributing Factors

• Genetic mutations: Abnormalities in T-cell genes or pathways that regulate immune function and cell growth may play a role.

• Chronic immune stimulation: Ongoing antigenic stimulation has been hypothesized to contribute, though evidence is inconclusive.

• Viral infections: Some researchers have investigated the role of viruses such as HTLV (human T-lymphotropic virus), but no definitive link has been established.

Unlike other lymphomas, there is no strong evidence linking mycosis fungoides to chemical exposures, radiation, or other environmental toxins.

Symptoms

Mycosis fungoides typically progresses through three clinical stages: patch stage, plaque stage, and tumor stage. However, not all patients follow this linear progression, and the disease may remain confined to one stage for years.

1. Patch Stage

• Flat, scaly, red or pink patches

• Often mistaken for eczema, psoriasis, or dermatitis

• Commonly affects sun-protected areas like the buttocks, thighs, or lower back

• May be itchy or asymptomatic

2. Plaque Stage

• Thicker, raised lesions with more defined borders

• Darker red or violaceous in color

• Itching and discomfort often increase

3. Tumor Stage

• Nodules or tumors develop on the skin, often ulcerating

• May appear on top of plaques or independently

• Higher risk of infection and pain

Advanced Symptoms

• Involvement of lymph nodes and internal organs

• Sezary syndrome (a leukemic variant) characterized by widespread redness (erythroderma), circulating malignant T-cells (Sezary cells), and severe itching

• Fatigue, weight loss, or night sweats in advanced stages

The appearance and distribution of lesions vary between individuals, and misdiagnosis is common in early stages.

Diagnosis

Diagnosing mycosis fungoides can be difficult, especially in early stages when it mimics common skin disorders. A combination of clinical examination, histopathology, immunohistochemistry, and molecular testing is usually required.

Diagnostic Steps

• Skin biopsy: Multiple biopsies over time may be needed to identify malignant T-cells in the skin.

• Immunophenotyping: Tests to determine T-cell markers (e.g., CD3, CD4, CD8) and detect clonal T-cell populations.

• Molecular testing: T-cell receptor (TCR) gene rearrangement studies to identify monoclonality.

• Blood tests: To evaluate Sezary cells in advanced cases or Sezary syndrome.

• Imaging studies: CT or PET scans to assess lymph node or internal organ involvement if disease is advanced.

Differential Diagnosis

• Psoriasis

• Chronic eczema

• Drug eruptions

• Other cutaneous lymphomas or inflammatory dermatoses

Given the diagnostic complexity, referral to a dermatologist or oncologist specializing in cutaneous lymphomas is often necessary.

Treatment

Treatment for mycosis fungoides is based on the stage and extent of the disease, as well as the patient’s overall health. While early-stage disease is often indolent and can be managed with skin-directed therapies, advanced disease may require systemic treatment.

1. Skin-Directed Therapies

• Topical corticosteroids: To reduce inflammation and lesion size in early-stage disease

• Topical chemotherapy: Such as mechlorethamine (nitrogen mustard)

• Phototherapy: Narrow-band UVB or PUVA (psoralen plus UVA) light therapy

• Total skin electron beam therapy (TSEB): A form of radiation used for widespread skin involvement

2. Systemic Therapies (for advanced disease)

• Oral retinoids: Bexarotene, acitretin

• Interferon-alpha: Immunomodulatory effects

• Histone deacetylase inhibitors: Vorinostat, romidepsin

• Monoclonal antibodies: Brentuximab vedotin (anti-CD30), mogamulizumab (anti-CCR4)

• Chemotherapy: For aggressive or refractory cases

• Stem cell transplant: Considered in select advanced cases

Supportive Care

• Moisturizers and anti-itch medications

• Infection prevention and management

• Pain control for ulcerated tumors

Treatment is typically chronic and may involve a combination of therapies over time to maintain disease control and minimize side effects.

Prognosis

The prognosis for mycosis fungoides depends on the stage at diagnosis, extent of skin and systemic involvement, and response to treatment. Early-stage disease generally has a good prognosis, while advanced stages are more difficult to treat and associated with lower survival rates.

Prognostic Indicators

• Stage I: Localized patches or plaques—median survival exceeds 15 years

• Stage II–III: More extensive skin involvement or lymphadenopathy—median survival varies

• Stage IV: Blood, lymph node, or organ involvement—median survival may drop to 1–4 years

Factors Associated with Better Prognosis

• Early-stage disease

• Good response to skin-directed therapies

• No blood or visceral involvement

Challenges

• Risk of disease progression to more aggressive forms

• Chronic symptoms such as itching and skin breakdown

• Psychological impact due to long-term visible skin disease

With ongoing advancements in targeted therapies and early detection, the management of mycosis fungoides continues to improve, helping patients maintain a better quality of life and extended survival.