Mycosis fungoides, also known as Alibert-Bazin syndrome or granuloma fungoides, is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time. Symptoms include rash, tumors, skin lesions, and itchy skin.
While the cause remains unclear, most cases are not hereditary. Most cases are in people over 20 years of age, and it is more common in men than women. Treatment options include sunlight exposure, ultraviolet light, topical corticosteroids, chemotherapy, and radiotherapy.
Signs and symptoms
thumb|270px|Plaque of mycosis fungoides
thumb|270px|Plaque of mycosis fungoides on foot treated with [[imiquimod at Penn Medicine in Philadelphia, and then radiation at Lehigh Valley Hospital–Cedar Crest in Allentown]]
thumb|Tumour stage mycosis fungoides seen on the head and neck
The symptoms of mycosis fungoides are categorized into three clinical stages: the patch stage, the plaque stage, and the tumour stage. The patch stage is defined by flat, reddish patches of varying sizes that may have a wrinkled appearance. They can also look yellowish in people with darker skin. It is characterized by the presence of raised lesions that appear reddish-brown; in darker skin tones, plaques may have a greyish or silver appearance. Both patch and plaque stages are considered early-stage mycosis fungoides.
The symptoms displayed are progressive, with early stages consisting of lesions presented as scaly patches. Lesions often initially develop on the trunk of the body in places that are rarely exposed to the sun, such as the buttocks. Hypopigmentation (when the skin is lighter than normal) of lesions are less common but can be found in children, adolescents and/or dark-skinned individuals.
The advanced stage of mycosis fungoides is characterized by generalized erythroderma (red rash covering most of the body) with severe pruritus (itching) and scaling. Those that experience intense pruritus commonly indicate that it negatively affects their quality of life emotionally, functionally and physically.
Mycosis fungoides (MF) and Sézary syndrome (SS) are related conditions, with the same type of cancer T-lymphocytes, that initially grow in different body compartments. SS cells are found mainly in the blood, whereas MF typically involves the skin. In advanced stages of MF, the cancer cells move from the skin into other organs and the bloodstream; this progression is referred to as "leukemic mycosis fungoides", "Sézary syndrome preceded by mycosis fungoides", or "secondary mycosis fungoides".
Cause
Mycosis fungoides is caused by abnormal white blood cells (T-lymphocytes). These abnormal cells have a preference for localizing and proliferating uncontrolled in the outer layer of the skin (epidermis). The abnormal cells may later involve other organs such as the lymph nodes. It is hypothesized that the genetic mutations in these cancer cells lead to increased growth and escape from programmed cell death.
Additionally, the disease is an unusual expression of CD4 T cells, a part of the immune system. These T cells are skin-associated, meaning they are biochemically and biologically most related to the skin, in a dynamic manner. Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL), but there are many other types of CTCL that have nothing to do with mycosis fungoides and these disorders are treated differently.
Diagnosis
Diagnosis often requires a combination of clinical and pathological studies. Diagnosis is sometimes difficult because the early phases of the disease often resemble inflammatory dermatoses (such as eczema, psoriasis, lichenoid dermatoses including lichen planus, vitiligo, and chronic cutaneous lupus erythematosus), as well as other cutaneous lymphomas. Misdiagnosis is common for this condition and dermatologists who mistakenly identify early-stage MF as common inflammatory skin conditions, such as psoriasis, may administer prolonged treatment with topical steroids or immunosuppressive drugs without obtaining a biopsy or proper follow-up, which can obscure the underlying disease. Similarly, general practitioners, who manage skin conditions, may incorrectly treat non-classical MF lesions with antifungal creams, further complicating the diagnosis when the lesions fail to respond to the treatment. Although data on childhood MF is limited, a 2021 systematic review observed that there is a significant delay in the diagnosis of childhood MF which may negatively affect a child's prognosis. Notably, most pediatric persons with MF present with early-stage disease. A review of the National Cancer Database revealed that women with MF have higher 5- and 10-year survival rates compared to men.
- Presence of cancer cells with twisted contours (cerebriform nuclei)
- In the patch and plaque stages, the cancer cells are seen in the epidermis (the most superficial layer of skin). This is referred to as epidermotropism.
- Pautrier's microabcesses, aggregates of four or more atypical lymphocytes arranged in the epidermis. Pautrier microabcesses are characteristic of mycosis fungoides but are generally absent.
- In the tumour stage, the cancer cells move into the dermis (the deeper layer of skin)
To stage the disease, various tests may be ordered, to assess nodes, blood and internal organs, but most patients present with disease apparently confined to the skin, as patches (flat spots) and plaques (slightly raised or 'wrinkled' spots).
Peripheral smear will often show buttock cells.
Laboratory Tests
The laboratory diagnosis of MF includes a comprehensive metabolic panel (CMP) and complete blood count (CBC) with differential, with a manual slide review to detect Sézary cells, which show characteristic cerebriform nuclei. Liver function tests assess potential extracutaneous involvement, while uric acid and lactate dehydrogenase (LDH) levels serve as markers for aggressive disease. Flow cytometry identifies malignant T-cell clones, and T-cell receptor (TCR) gene rearrangement testing confirms clonal expansion if blood involvement is suspected.
- Positron emission tomography-computed tomography (PET-CT) may be used for additional disease monitoring. Staging is based on the tumor, node, metastasis, blood (TNMB) classification proposed by the Mycosis Fungoides Cooperative Group and revised by the International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer. Systemic treatments of mycosis fungoides often lead to resistance; as such, additional treatment options are often necessary in advanced disease.
Other treatments have been suggested, however, larger and more extensive research is needed to identify effective treatment strategies for this disease. Mogamulizumab is a CCR4 monoclonal antibody which has been shown to improve progression-free survival. It was approved by the US FDA in 2018 for use in people with relapsed or refractory mycosis fungoides or Sézary disease. The complete remission rate in children is nearly 30%. The incidence of mycosis fungoides was seen to be increasing between 2000 and 2020, although certain regions have demonstrated some stabilization.
The global age adjusted incidence of Mycosis Fungoides is approximately 6-7 cases for every 1 million people, with rates varying across regions and ethnicities. Racial disparities amongst Mycosis Fungoides diagnosis have been seen to be higher in African American populations when compared to Caucasian populations in America.
Research indicates that early-onset MF cases are less likely to occur with approximately 0.5% - 5% of all MF cases being diagnosed before the age of 20. Gender disparities are present in juvenile cases as well, with there being a male-to-female ratio of 2:1, indicating a higher rate amongst males in this age demographic. The name mycosis fungoides is very misleading—it loosely means "mushroom-like fungal disease". The disease, however, is not a fungal infection but rather a type of non-Hodgkin's lymphoma. It was so named because Alibert described the skin tumors of a severe case as having a mushroom-like appearance.
In 1814, Alibert named the disease Pian fungicides because of the visual similarity to the treponemal disease Yaws, also known as Pian.
See also
- Cutaneous T-cell lymphoma
- Pagetoid reticulosis
- Premycotic phase
- Sézary's disease
- Secondary cutaneous CD30+ large cell lymphoma
- Angiocentric lymphoma
- List of cutaneous conditions