Mycosis Fungoides
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
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. The plaque stage follows the patch stage of mycosis fungoides. 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 tumour stage typically shows large irregular lumps. Tumours can develop form plaques or normal skin in any region of the body, including the face and head regions.
Itching (pruritus) is common, perhaps in 20 percent of patients, but is not universal. 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. The advanced stage of mycosis fungoides is characterized by generalized erythroderma (red rash covering most of the body) with severe pruritus (itching) and scaling. The key difference between Sézary syndrome and the other stages of mycosis fungoides is the large number of cancer cells found in the blood (leukemic disease). When mycosis fungoides develops to meet the criteria for Sézary syndrome, it is referred to as leukemic mycosis fungoides, Sézary syndrome preceded by mycosis fungoides, or secondary mycosis fungoides.
Cause
The cause of mycosis fungoides is still unknown. However, there are a few current hypothesized causes of the disease. One of these hypotheses is that mycosis fungoides is caused by genetic and cellular signalling abnormalities. Examples of these abnormalities include clonal abnormalities and altered expression of adhesion molecules and/or cytokins.
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 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. Several biopsies are recommended, to be more certain of the diagnosis.
The criteria for the disease are established on the skin biopsy:
- the superficial papillary dermis is infiltrated by a bandlike lymphocyte infiltrate
- epidermotropism
- presence of atypical T-cells with cerebriform nuclei in the dermal and epidermal infiltrates.
Pautrier's microabcesses are aggregates of four or more atypical lymphocytes arranged in the epidermis. Pautrier microabcesses are characteristic of mycosis fungoides but are generally absent.
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.
Staging
Traditionally, mycosis fungoides has been divided into three stages: premycotic, mycotic and tumorous. The premycotic stage clinically presents as an erythematous (red), itchy, scaly lesion. Microscopic appearance is non-diagnostic and represented by chronic nonspecific dermatosis associated with psoriasiform changes in epidermis.
In the mycotic stage, infiltrative plaques appear and biopsy shows a polymorphous inflammatory infiltrate in the dermis that contains small numbers of frankly atypical lymphoid cells. These cells may line up individually along the epidermal basal layer. The latter finding if unaccompanied by spongiosis is highly suggestive of mycosis fungoides. In the tumorous stage a dense infiltrate of medium-sized lymphocytes with cerebriform nuclei expands the dermis.
Accurate staging of Mycosis Fungoides is essential to determine appropriate treatment and prognosis. 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. This staging system examines the extent of skin involvement (T), presence of lymph node (N), visceral disease (M), and presence of Sezary cells in the peripheral blood (B).
Most patients with Mycosis Fungoides have early-stage disease (Stage IA-IIA) at the time of their initial diagnosis. These patients with early stage disease that is primarily confined to the skin have a favorable prognosis. Patients with advanced stage (Stage IIB-IVB) are often refractory to treatment and have an unfavorable prognosis. Treatment of patients with advanced stage disease is designed to reduce tumor burden, delay disease progression, and preserve quality of life.
Prognosis
A 1999 US-based study of patient records observed a 5-year relative survival rate of 77%, and a 10-year relative survival rate of 69%. After 11 years, the observed relative survival rate remained around 66%. Poorer survival is correlated with advanced age and black race. Superior survival was observed for married women compared with other gender and marital-status groups.
Treatment
Mycosis fungoides can be treated in a variety of ways. Common treatments include simple sunlight, ultraviolet light (mainly NB-UVB 312 nm), topical steroids, topical and systemic chemotherapies, local superficial radiotherapy, the histone deacetylase inhibitor vorinostat, total skin electron radiation, photopheresis and systemic therapies (e.g. interferons, retinoids, rexinoids) or biological therapies. Treatments are often used in combination.
There is limited evidence for the efficacy of topical and systemic therapies for mycosis fungoides. Due to the possible adverse effects of these treatments in early disease it is recommended to begin therapy with topical and skin-directed treatments before progressing to more systemic therapies. Larger and more extensive research is needed to identify effective treatment strategies for this disease.
In 2010, the U.S. Food and Drug Administration granted orphan drug designation for naloxone lotion, a topical opioid receptor competitive antagonist used as a treatment for pruritus in cutaneous T-cell lymphoma.
The US FDA approved the drug mogamulizumab (trade name Poteligeo) in August 2018 for treatment of relapsed or refractory mycosis fungoides and Sézary disease.
Epidemiology
It is rare for the disease to appear before age 20, and it appears to be noticeably more common in males than females, especially over the age of 50, where the incidence of the disease (the risk per person in the population) does increase. The average age of onset is between 45 and 55 years of age for patients with patch and plaque disease only, but is over 60 for patients who present with tumours, erythroderma (red skin) or a leukemic form (the Sézary syndrome). The incidence of mycosis fungoides was seen to be increasing till the year 2000 in the United States, thought to be due to improvements in diagnostics. However, the reported incidence of the disease has since then remained constant, suggesting another unknown reason for the jump seen before 2000.
History
Mycosis fungoides was first described in 1806 by French dermatologist Jean-Louis-Marc Alibert. 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.
Notable cases
In 1995 actor Mr. T was diagnosed with a cutaneous T-cell lymphoma, or mycosis fungoides. Once in remission, he joked about the coincidence: "Can you imagine that? Cancer with my name on it — personalized cancer!"
Popular British television actor Paul Eddington died of mycosis fungoides after living with the condition for four decades.
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