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Mycosis fungoides and Sézary syndrome are neoplasias of malignant T lymphocytes that usually possess the helper/inducer cell surface phenotype. These kinds of neoplasms initially present as skin involvement and, as such, have been classified as cutaneous T-cell lymphomas. Cutaneous T-cell lymphomas should be distinguished from other T-cell lymphomas that involve the skin, such as anaplastic large cell lymphoma (CD30 positive), peripheral T-cell lymphoma (CD30 negative, with no epidermal involvement), adult T-cell leukemia/lymphoma (usually with systemic involvement), or subcutaneous panniculitic T-cell lymphoma.[2,3] These histologic types of T-cell lymphomas are discussed in another PDQ summary. (Refer to the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.)
Typically, the natural history of mycosis fungoides is indolent. Symptoms of the disease may present for long periods, in a range of 2 to 10 years, because cutaneous eruptions wax and wane before they receive a biopsy confirmation. Mycosis fungoides and Sézary syndrome are treatable with available topical therapy, systemic therapy, or both. To date, curative modalities have proven elusive, with the possible exception of patients with minimal disease confined to the skin.
In addition, several benign or indolent conditions can be confused with mycosis fungoides. Consultation with a pathologist who has expertise in distinguishing these conditions is important.
Prognosis and Survival
The prognosis of patients with mycosis fungoides and Sézary syndrome is based on the extent of disease (stage) at presentation. The presence of lymphadenopathy and involvement of peripheral blood and viscera increase in likelihood with worsening cutaneous involvement and define poor prognostic groups.[5,6,7,8] The Cutaneous Lymphoma International Consortium retrospectively reviewed 1,275 patients and found the following four independent prognostic markers indicate a worse survival:
The median survival following diagnosis varies according to stage. Patients with stage IA disease have a median survival of 20 years or more. Most deaths for this group are not caused by, nor are they related to, mycosis fungoides.[10,11] In contrast, more than 50% of patients with stage III through stage IV disease die of mycosis fungoides, with a median survival of approximately 5 years.[7,9,12,13] The Cutaneous Lymphoma International Prognostic index used male gender, age older than 60 years, plaques, lymph nodes, blood involvement, and visceral involvement as poor prognostic factors to define predicted overall survival (OS) and progression-free survival in both early-stage and advanced-stage groups.
A report on 1,798 patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database found an increase in second malignancies (standardized incidence ratio, 1.32; 95% confidence interval [CI], 1.15–1.52), especially for Hodgkin lymphoma, non-Hodgkin lymphoma, and myeloma. Another report on 4,459 patients from the SEER database found that the 19.2% of African Americans with mycosis fungoides have a shorter OS, potentially attributable to disease characteristics, socioeconomic status, and type of therapy (hazard ratio, 1.47; 95% CI, 1.25–1.74; P < .001).
Cutaneous disease can manifest itself as an eczematous patch or plaque stage covering less than 10% of the body surface (T1), a plaque stage covering 10% or more of the body surface (T2), or as tumors (T3) that frequently undergo necrotic ulceration.[17,18] Several retrospective studies showed that 20% of patients progress from stage I or II disease to stage III or IV disease.[19,20,21] Sézary syndrome presents with generalized erythroderma (T4) and peripheral blood involvement. However, there is some disagreement about whether mycosis fungoides and Sézary syndrome are actually variants of the same disease. The same retrospective study with a median follow-up of 14.5 years found that only 3% of 1,422 patients progressed from mycosis fungoides to Sézary syndrome.
There is consensus that patients with Sézary syndrome (leukemic involvement) have a poor prognosis (median survival, 4 years), with or without the typical generalized erythroderma.[23,24] Cytologic transformation from a low-grade lymphoma to a high-grade lymphoma (large cell transformation) occurs rarely (<5%) during the course of these diseases and is associated with a poor prognosis.[25,26,27] A retrospective analysis of 100 cases with large cell transformation found reduced disease-specific survival with extracutaneous transformation, increased extent of skin lesions, and CD30 negativity. A common cause of death during the tumor phase is septicemia caused by chronic skin infection with staph species, herpes simplex, herpes zoster, and fungal skin infections.[29,30]
Folliculotropic mycosis fungoides is a variant of mycosis fungoides marked by folliculotropic, rather than epidermotropic, neoplastic infiltrates, with preferential location in the head and neck area. Early plaque-stage folliculotropic mycosis fungoides have a very indolent prognosis, while extracutaneous disease portends a very poor prognosis.
The histologic diagnosis of mycosis fungoides and Sézary syndrome is usually difficult to determine in the initial stages of the disease and may require the review of multiple biopsies by an experienced pathologist.
A definitive diagnosis from a skin biopsy requires the presence of mycosis fungoides and Sézary syndrome cells (convoluted lymphocytes), a band-like upper dermal infiltrate, and epidermal infiltrations with Pautrier abscesses (collections of neoplastic lymphocytes). A definitive diagnosis of Sézary syndrome may be made from a peripheral blood evaluation when skin biopsies are consistent with the diagnosis. Supportive evidence for circulating Sézary cells is provided by T-cell receptor gene analysis, identification of the atypical lymphocytes with hyperconvoluted or cerebriform nuclei, and flow cytometry with the characteristic deletion of cell surface markers such as CD7 and CD26. However, none of these is individually pathognomonic for lymphoma.[1,2]
The American Joint Committee on Cancer (AJCC) has designated staging by TNM (tumor, node, metastasis) classification to define mycosis fungoides. Peripheral blood involvement with mycosis fungoides or Sézary syndrome cells is correlated with more advanced skin stage, lymph node and visceral involvement, and shortened survival.
Mycosis fungoides and Sézary syndrome also have a formal staging system proposed by the International Society for Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC).[2,3]
Treatment options for patients with mycosis fungoides and Sézary syndrome include the following:[1,2]
Other Drug Therapy
These types of treatments produce remissions, but long-term remissions are uncommon. Treatment, therefore, is considered palliative for most patients, although major symptomatic improvement is regularly achieved. Survival in excess of 8 years, however, is common for patients with early stages of disease. All patients with mycosis fungoides and Sézary syndrome are candidates for clinical trials evaluating new approaches to treatment.
Because several forms of treatment can produce complete resolution of skin lesions in this stage, the choice of therapy is dependent on local expertise and the facilities available. With therapy, the survival of patients with stage IA disease can be expected to be the same as for age- and gender-matched controls.[1,2,3]
There is no curative therapy and no clear difference in overall survival (OS) among the treatment options for patients with stage I and stage II mycosis fungoides.
A randomized study of 103 patients compared combined total-skin electron-beam radiation (TSEB) plus combination chemotherapy with sequential topical therapies. In the latter group, combination chemotherapy was reserved for symptomatic extracutaneous disease or for disease that was refractory to topical therapies. Patients with any disease stage were eligible. Although the complete response rate was higher with combined therapy, toxic effects were considerably greater, and no difference was seen in disease-free or OS between the two groups.[Level of evidence: 1iiA]
Treatment Options for Stage I and Stage II Mycosis Fungoides
Treatment options for stages I and II mycosis fungoides include the following:
(Refer to the Treatment Option Overview for Mycosis Fungoides [Including Sézary Syndrome] section of this summary for more information on these treatment options.)
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
There is no curative therapy and no clear difference in overall survival (OS) among the treatment options for patients with stage III and stage IV disease.
The use of single alkylating agents has produced objective responses in 60% of patients, with a duration of less than 6 months. One of the alkylating agents (e.g., mechlorethamine [nitrogen mustard], cyclophosphamide, or chlorambucil), or the antimetabolite methotrexate is the most frequently used. Single agents have not been shown to cure any patients, and insufficient data exist to determine whether these agents prolong survival. Combination chemotherapy is not definitely superior to single agents. Even in stage IV disease, treatments directed at the skin may provide significant palliation.
A randomized study of 103 patients compared combined total-skin electron-beam radiation (TSEB) plus combination chemotherapy with conservation therapy consisting of sequential topical therapies. In the latter group, combination chemotherapy was reserved for symptomatic extracutaneous disease or for disease refractory to topical therapies. Patients with any stage were eligible. Although the complete response rate was higher with combined therapy, toxic effects were considerably greater, and no difference was seen in disease-free survival or OS between the two groups.[Level of evidence: 1iiA]
Sézary Syndrome is a rare leukemic variant of cutaneous T-cell lymphoma characterized by erythroderma, circulating Sézary cells with cerebriform nuclei, lymphadenopathy, and pruritus. This condition typically progresses rapidly with only short duration of response to most therapies. A retrospective review of 176 patients with SS identified the following poor prognostic factors:
Remissions attained by using extracorporeal photophoresis, alpha interferon, or retinoids may be followed by allogeneic stem cell transplantation. In an anecdotal series of 16 patients with Sézary syndrome after allogeneic transplant, 9 were in complete remission after 4 years.
Treatment Options for Stage III and Stage IV Mycosis Fungoides (Including Sézary Syndrome)
Treatment options for stages III and IV mycosis fungoides and Sézary syndrome include the following (note that in this clinical setting, the skin is easily injured; any of the topical therapies must be administered with extreme caution):[2,5]
The treatment of relapsed patients with mycosis fungoides and Sézary syndrome who have cutaneous T-cell lymphomas involves the joint decisions of the dermatologist, medical oncologist, and radiation oncologist. It may be possible to re-treat localized areas of relapse in the skin with additional electron-beam radiation or possibly to repeat total-skin electron-beam radiation therapy (TSEB). Photon radiation to bulky skin or nodal masses may prove beneficial. If these options are not possible, then continued topical treatment with other modalities such as mechlorethamine or psoralen and ultraviolet A radiation (PUVA) may be warranted to relieve cutaneous symptoms.
Clinical trials, if possible, should be considered as the next therapeutic option.
Treatment Options for Recurrent Mycosis Fungoides (Including Sézary Syndrome)
Treatment options under clinical evaluation for recurrent mycosis fungoides and Sézary syndrome include the following:[2,3]
These references have been identified by members of the PDQ Adult Treatment Editorial Board as significant in the field of mycosis fungoides and Sézary syndrome (MF/SS) treatment. This list is provided to inform users of important studies that have helped shape the current understanding of and treatment options for MF/SS. Listed after each reference are the sections within this summary where the reference is cited.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Mycosis Fungoides (Including Sézary Syndrome)
Revised text to state that a common cause of death during the tumor phase is septicemia caused by chronic skin infection with staph species, herpes simplex, herpes zoster, and fungal skin infections (added Talpur et al. as reference 29 and Lebas et al. as reference 30).
Treatment Option Overview for Mycosis Fungoides (Including Sézary Syndrome)
Revised text to state that therapeutic trials with psoralen and ultraviolet A radiation (PUVA) have shown an 80% to 90% complete remission rate with early cutaneous stages achieving the best responses.
Added text to state that single-arm and retrospective comparisons confirm narrowband ultraviolet B with 80% to 90% complete remission rates, especially for patients with early cutaneous stages (added Almohideb et al. as reference 8 and Elcin et al. as reference 9).
Added text to state that in a prospective randomized trial, 372 previously treated patients received either mogamulizumab, a monoclonal antibody directed against C-C chemokine receptor 4, or vorinostat, the histone deacetylase inhibitor. With a median follow-up of 17 months, the median progression-free survival favored mogamulizumab at 7.7 months versus 3.1 months for vorinostat (added Kim et al. as reference 46 and level of evidence 1iiDiii).
Stage I and Stage II Mycosis Fungoides Treatment
Added narrowband ultraviolet B radiation as a photodynamic therapy treatment option (added Almohideb et al. as reference 11 and Elcin et al. as reference 12).
Stage III and Stage IV Mycosis Fungoides (Including Sézary Syndrome) Treatment
Recurrent Mycosis Fungoides (Including Sézary Syndrome) Treatment
Added narrowband ultraviolet B radiation as a photodynamic therapy treatment option (added Almohideb et al. as reference 6 and Elcin et al. as reference 7).
Added mogamulizumab as a targeted therapy treatment option (added Kim et al. as reference 34).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of mycosis fungoides (including Sézary Syndrome). It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewer for Mycosis Fungoides (Including Sézary Syndrome) Treatment is:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Mycosis Fungoides (Including Sézary Syndrome) Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/lymphoma/hp/mycosis-fungoides-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389288]
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Last Revised: 2019-09-20
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