Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL), a rare type of non-Hodgkin lymphoma that primarily affects the skin. It is characterized by the malignant proliferation of CD4+ T-helper lymphocytes, which infiltrate the skin and cause progressive skin lesions. Despite its misleading name, MF is not a fungal infection—the term originated in the 19th century when tumors were described as resembling mushrooms. 

The disease typically progresses slowly over years or decades, moving from patch-like skin changes to plaques and, in some cases, tumor formation. While many patients remain in early stages for years, advanced disease can spread to lymph nodes, blood, and internal organs, significantly impacting prognosis and quality of life. Understanding its clinical features, progression, and management is essential for both patients and healthcare providers. 

This article provides a comprehensive overview of mycosis fungoides, covering its causes, signs and symptoms, diagnosis, treatment, complications, and prognosis. 

Mycosis fungoides is a cutaneous T-cell lymphoma that primarily affects the skin, caused by malignant CD4+ T-lymphocytes. It typically begins with skin involvement but can later spread to the lymph nodes, blood, and visceral organs in advanced cases. MF has several recognized subtypes, including folliculotropic mycosis fungoides, pagetoid reticulosis, and granulomatous slack skin. 

MF is distinct from Sézary syndrome, another type of CTCL characterized by generalized skin redness (erythroderma), lymph node enlargement, and the presence of malignant T-cells in the blood. 

Mycosis fungoides is considered rare in the general population, but among cutaneous lymphomas it stands out as the most frequently diagnosed form. It accounts for the majority of primary cutaneous T-cell lymphomas, making it a key condition within this group. Although its incidence is relatively low compared to other cancers, its impact is significant because of its chronic course and potential to affect quality of life. Recognizing its prevalence among skin lymphomas helps clinicians prioritize awareness and early detection in dermatology and oncology practice. 

• Incidence: 0.3–1 cases per 100,000 people per year 

• Accounts for 50–60% of all primary cutaneous lymphomas 

• Most common in adults aged 50–70 years 

• Male predominance (approximately 2:1 ratio) 

Higher incidence and more advanced presentation seen in African American populations 

The exact cause of MF is still not fully understood, and researchers believe it likely arises from a combination of influences rather than a single trigger. Studies suggest that immune system irregularities, genetic mutations, and long-term environmental exposures may all contribute to disease development. Although no definitive cause has been identified, several contributing factors have consistently been proposed in medical literature. This uncertainty makes it important to explore the possible pathways that could lead to MF. Below are some of the leading hypotheses that help explain how this condition might arise: 

• Chronic antigenic stimulation: Persistent skin inflammation may drive abnormal T-cell proliferation. 

• Genetic changes: Somatic mutations in genes regulating cell survival and immune function (e.g., STAT3, PLCG1, CDKN2A). 

• Environmental factors: Exposure to chemicals, pesticides, or chronic infections may play a role, though evidence is inconclusive. 

• Viral factors: Viruses such as HTLV-1 have been studied, but no consistent link has been proven. 

Mycosis fungoides does not appear suddenly but instead evolves gradually over time as malignant T-cells accumulate in the skin. Understanding how this process unfolds is important for recognizing the disease in its earliest stages. Researchers have outlined the step-by-step way abnormal immune cells begin to target the skin and eventually spread to other areas of the body. This staged progression helps explain why MF often mimics common skin conditions before becoming more advanced and recognizable. 

• Malignant T-helper cells (CD4+, CLA+, CCR4+) migrate to the skin. 

• In early stages, they localize in the epidermis (epidermotropism). 

• Over time, infiltration thickens the skin, leading to plaques and eventually tumor nodules. 

• Advanced disease may spread to lymph nodes, blood, and organs. 

MF typically follows a slow, stepwise progression through three clinical stages, which can be summarized in a brief overview. These stages include the patch stage, the plaque stage, and finally the tumor stage. Each step reflects increasing severity and distinct changes in the skin’s appearance and symptoms. Understanding this progression is key to recognizing the disease and monitoring its development. 

Patch Stage 

• Red, scaly, or atrophic patches with variable borders 

• Often appear on sun-protected areas (buttocks, flanks, thighs) 

• Frequently misdiagnosed as eczema or psoriasis 

Plaque Stage 

• Thickened, raised, reddish-brown plaques 

• May show poikiloderma (skin thinning, pigment changes, visible blood vessels) 

• Can be itchy and uncomfortable 

Tumor Stage 

• Large nodules or tumors that may ulcerate 

• Risk of rapid progression and secondary infections 

Other Features 

• Severe itching (pruritus) 

• Lymph node swelling in advanced stages 

• Hair loss and follicular papules in folliculotropic MF 

• Erythroderma if disease progresses to Sézary syndrome 

Staging is determined using the TNMB classification system: 

T (Skin): 

• T1: Patches/plaques <10% body surface area (BSA) 

• T2: Patches/plaques ≥10% BSA 

• T3: One or more tumors (≥1 cm) 

• T4: Erythroderma covering ≥80% BSA 

N (Nodes): Ranges from no abnormal nodes to significant lymphoma involvement 

• M (Metastasis): M0 = no visceral involvement; M1 = visceral disease 

• B (Blood): Reflects presence and degree of Sézary cells 

Diagnosing mycosis fungoides often requires careful attention to subtle clinical clues, since early signs can resemble common skin conditions. Physicians usually begin considering MF when patients present with persistent rashes or plaques that do not respond to typical treatments. Because the disease evolves slowly, repeated evaluations are often necessary to build suspicion. A thorough history, examination, and attention to resistant or unusual lesions can guide clinicians toward ordering further tests. This stage of evaluation is critical because early recognition can significantly improve management and outcomes. 

MF should be considered when patients present with persistent, treatment-resistant skin lesions. 

Skin Biopsy 

• Gold standard for diagnosis 

• Multiple biopsies may be needed due to patchy involvement 

• Findings include atypical T-cells with cerebriform nuclei and epidermotropism 

Immunophenotyping 

• MF cells typically express CD3+, CD4+, CD45RO+, with loss of CD7/CD26 

• T-cell receptor (TCR) gene rearrangement confirms clonality 

Other Tests 

• Complete blood count (CBC) to assess for Sézary cells 

• LDH levels (tumor burden marker) 

• Flow cytometry for blood involvement 

• Imaging (CT or PET-CT) for advanced disease 

Differential Diagnosis 

Conditions that mimic MF include psoriasis, eczema, lichen planus, parapsoriasis, drug reactions, and other skin lymphomas. 

Treatment for mycosis fungoides is guided by the stage of disease and the extent of involvement. The primary goals are to relieve symptoms such as itching or discomfort, slow or stop the progression of skin lesions, and help patients maintain their overall quality of life. Approaches may range from topical therapies and light-based treatments in early stages to systemic therapies in advanced disease. While cures are rare, many patients achieve long-term control with the right combination of therapies. Ongoing follow-up is essential to adjust treatment as the disease evolves. 

Skin-Directed Therapies (Early Stages) 

• Topical corticosteroids 

• Topical chemotherapy (mechlorethamine, carmustine) 

• Topical retinoids (bexarotene) 

• Phototherapy (narrowband UVB, PUVA) 

• Localized radiation therapy 

Systemic Therapies (Advanced Disease) 

• Retinoids (oral bexarotene) 

• Interferon-alpha 

• Histone deacetylase inhibitors (vorinostat, romidepsin) 

• Methotrexate (low-dose) 

• Chemotherapy (for refractory disease) 

• Extracorporeal photopheresis (ECP) 

• Monoclonal antibodies (mogamulizumab, brentuximab vedotin for CD30+ cases) 

Stem Cell Transplantation 

Allogeneic stem cell transplant may be considered for advanced or refractory MF. 

Complications from mycosis fungoides often develop as the disease progresses, and they can significantly impact both physical health and emotional well-being. Because the skin barrier is weakened, patients become more vulnerable to outside irritants, infections, and chronic discomfort. In advanced stages, systemic complications may arise that require intensive medical management. Recognizing these possible complications early helps clinicians address them promptly and provide supportive care. Below are some of the more common complications associated with this condition. 

• Skin infections due to barrier disruption 

• Ulceration and bleeding from tumors 

• Transformation to large-cell lymphoma (worse prognosis) 

• Psychological impact from chronic disease and visible skin lesions 

Outcomes in mycosis fungoides are closely tied to the stage at diagnosis, with earlier detection generally leading to better results. In early-stage MF, patients often have a near-normal life expectancy and can live for many years with appropriate treatment. By contrast, those in the tumor stage face a more guarded outlook, with five-year survival rates estimated around 40–60%. If the disease spreads to internal organs (visceral involvement), survival is significantly shortened, typically ranging from one to four years. Other factors such as patient age, elevated LDH levels, and transformation to large-cell lymphoma can also strongly influence prognosis. 

There are no proven ways to prevent MF due to its uncertain cause. However, early recognition and treatment can help slow disease progression and improve quality of life. 

Patients require long-term follow-up with regular skin checks, lymph node exams, and monitoring for systemic involvement. Supportive care includes: 

• Emollients for dry skin 

• Antihistamines for itching 

• Psychosocial support and counseling 

Mycosis fungoides is a rare but chronic form of cutaneous T-cell lymphoma with a highly variable course. While it is often slow-growing, some patients progress to advanced stages with systemic involvement. Early recognition, stage-based treatment, and ongoing follow-up are key to improving outcomes and maintaining quality of life. Although MF is usually incurable, many patients live for decades with careful management. 

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2. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Primary Cutaneous Lymphomas. Version 1.2025. 

3. Agar NS, Wedgeworth E, Crichton S, et al. Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised ISCL/EORTC staging proposal. J Clin Oncol. 2010;28(31):4730–4739. 

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