National Cancer Institute


Expert-reviewed information summary about the treatment of mycosis fungoides (including Sézary syndrome).

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.

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).

Mycosis Fungoides (Including Sézary Syndrome) Treatment

Mycosis Fungoides (Including Sézary Syndrome) Treatment

General Information About Mycosis Fungoides (Including Sézary Syndrome) Treatment

Clinical Presentation

Mycosis fungoides (MF) and Sézary syndrome (SS) 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. 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 MF 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. MF/SS is 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, a number of benign or indolent conditions can be confused with MF. Consultation with a pathologist who has expertise in distinguishing these conditions is important.

Prognosis and Survival

The prognosis of patients with MF/SS is based on the extent of disease at presentation (stage). The presence of lymphadenopathy and involvement of peripheral blood and viscera increase in likelihood with worsening cutaneous involvement and define poor prognostic groups. The Cutaneous Lymphoma International Consortium retrospectively reviewed 1,275 patients and found the following four independent prognostic markers indicate a worse survival:

  • Stage IV disease.
  • Age older than 60 years.
  • Large cell transformation.
  • Elevated lactate dehydrogenase (LDH).

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, MF. In contrast, more than 50% of patients with stage III through stage IV disease die of MF, with a median survival of approximately 5 years. 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 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 Program (SEER) database found an increase in second malignancies (standardized incidence ratio, 1.32; 95% confidence interval, 1.15–1.52), especially for Hodgkin lymphoma, non-Hodgkin lymphoma, and myeloma.

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. Several retrospective studies showed that 20% of patients progress from stage I or II disease to stage III or IV disease. SS presents with generalized erythroderma (T4) and peripheral blood involvement. However, there is some disagreement about whether the MF and SS 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 MF to SS.

There is consensus that patients with SS have a poor prognosis (median survival, 4 years). 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. 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 sepsis from or caused by chronic skin infection with staph species and subsequent systemic infections.

Cellular Classification of Mycosis Fungoides (Including Sézary Syndrome)

The histologic diagnosis of mycosis fungoides and Sézary syndrome (MF/SS) 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 MF/SS cells (convoluted lymphocytes), a band-like upper dermal infiltrate, and epidermal infiltrations with Pautrier abscesses (collections of neoplastic lymphocytes). A definitive diagnosis of SS 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.

Stage Information for Mycosis Fungoides (Including Sézary Syndrome)

The stages that follow are defined by TNM classification. Peripheral blood involvement with mycosis fungoides or Sézary syndrome (MF/SS) cells is correlated with more advanced skin stage, lymph node and visceral involvement, and shortened survival.

MF/SS 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).

Definitions of TNM

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define MF.

Clinical trials have assessed the extent of skin involvement using detailed scoring systems such as the modified Severity-Weighted Assessment Tool (mSWAT).

Treatment Option Overview for Mycosis Fungoides (Including Sézary Syndrome)

Treatment options for patients mycosis fungoides and Sézary syndrome (MF/SS) include the following:

Photodynamic Therapy

Radiation Therapy

Biologic Therapy

Chemotherapy

Other Drug Therapy

Targeted Therapy

Transplantation

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 MF/SS are candidates for clinical trials evaluating new approaches to treatment.

Stage I and Stage II Mycosis Fungoides

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 age and gender-matched controls.

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 (MF).

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 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.[]

Treatment Options for Stage I and Stage II Mycosis Fungoides

Treatment options for stages I and II MF include the following:

(Refer to the Treatment Option Overview for Mycosis Fungoides (Including Sézary Syndrome) for more information on these treatment options.)

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage I mycosis fungoides/Sezary syndrome and stage II mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Stage III and Stage IV Mycosis Fungoides (Including Sézary Syndrome)

Mycosis Fungoides

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, 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 or OS between the two groups.[]

Sézary Syndrome

Sézary Syndrome (SS) 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:

  • High lactate dehydrogenase.
  • Previous diagnosis of mycosis fungoides (MF).
  • Presence of T-cell receptor gene rearrangements in skin, blood, or both.

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 SS 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 (MF) (including SS) 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):

(Refer to the Treatment Option Overview for Mycosis Fungoides (Including Sézary Syndrome) for more information on these treatment options.)

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage III mycosis fungoides/Sezary syndrome and stage IV mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Recurrent Mycosis Fungoides (Including Sézary Syndrome)

The treatment of relapsed patients with mycosis fungoides (MF) (including Sézary syndrome [SS]) with 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 Under Clinical Evaluation for Recurrent Mycosis Fungoides (Including Sézary Syndrome)

Treatment options under clinical evaluation for recurrent mycosis fungoides and Sézary Syndrome (MF/SS) include the following:

(Refer to the Treatment Option Overview for Mycosis Fungoides (Including Sézary Syndrome) for more information on these treatment options.)

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with recurrent mycosis fungoides/Sezary syndrome. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Key References for Mycosis Fungoides (Including Sézary Syndrome) Treatment

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 and SS. Listed after each reference are the sections within this summary where the reference is cited.

  • Agar NS, Wedgeworth E, Crichton S, et al.: Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol 28 (31): 4730-9, 2010.[PUBMED Abstract]

    Cited in:

    • General Information About Mycosis Fungoides (Including Sézary Syndrome)
    • Stage Information for Mycosis Fungoides (Including Sézary Syndrome)
  • Hughes CF, Khot A, McCormack C, et al.: Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. Blood 125 (1): 71-81, 2015.[PUBMED Abstract]

    Cited in:

    • Stage I and Stage II Mycosis Fungoides
    • Stage III and Stage IV Mycosis Fungoides (Including the Sézary Syndrome)
    • Recurrent Mycosis Fungoides (Including the Sézary Syndrome)
  • Kadin ME, Hughey LC, Wood GS: Large-cell transformation of mycosis fungoides-differential diagnosis with implications for clinical management: a consensus statement of the US Cutaneous Lymphoma Consortium. J Am Acad Dermatol 70 (2): 374-6, 2014.[PUBMED Abstract]

    Cited in:

    • General Information About Mycosis Fungoides (Including Sézary Syndrome)
  • Quaglino P, Pimpinelli N, Berti E, et al.: Time course, clinical pathways, and long-term hazards risk trends of disease progression in patients with classic mycosis fungoides: a multicenter, retrospective follow-up study from the Italian Group of Cutaneous Lymphomas. Cancer 118 (23): 5830-9, 2012.[PUBMED Abstract]

    Cited in:

    • General Information About Mycosis Fungoides (Including Sézary Syndrome)
  • Talpur R, Singh L, Daulat S, et al.: Long-term outcomes of 1,263 patients with mycosis fungoides and Sézary syndrome from 1982 to 2009. Clin Cancer Res 18 (18): 5051-60, 2012.[PUBMED Abstract]

    Cited in:

    • General Information About Mycosis Fungoides (Including Sézary Syndrome)

Changes to This Summary (07/12/2017)

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 (MF) (Including Sézary Syndrome [SS])

Revised text to state that the cutaneous T-cell lymphomas should be distinguished from other T-cell lymphomas that involve the skin, such as anaplastic large cell lymphoma, peripheral T-cell lymphoma, adult T-cell leukemia/lymphoma, or subcutaneous panniculitic T-cell lymphoma.

Added Alberti-Violetti et al. as reference 9. Added text to state that the Cutaneous Lymphoma International Consortium retrospectively reviewed 1,275 patients and found four independent prognostic markers that indicate a worse survival, including stage IV disease, age older than 60 years, large cell transformation, and elevated lactate dehydrogenase (cited Scarisbrick et al. as reference 10).

Added R. Volmer as reference 12. Revised text to state that in contrast, more than 50% of patients with stage III through stage IV disease die of MF, with a median survival of approximately 5 years. Also added that 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 groups and advanced-stage groups (cited Benton et al. as reference 15).

Revised text to state that cutaneous disease can manifest itself as an eczematous patch or plaque stage covering less than 10% of the body surface, a plaque stage covering 10% or more of the body surface, or as tumors that frequently undergo necrotic ulceration. Also revised the text about several retrospective studies, which showed that 20% of patients progressed from stage I or II disease to stage III or IV disease (cited Wernham et al. as reference 19 and Desai et al. as reference 20).

Treatment Option Overview for MF (Including SS)

Added Olsen et al. as reference 4.

Added text to state that total-skin electron-beam radiation therapy can provide excellent palliation, with complete response rates of as much as 80%, and may be combined with systemic treatment. Also added ultraviolet B radiation or ultraviolet A radiation as radiation therapy options.

Added Targeted Therapy as a new subsection.

Added text to state that among these highly selected patients, the 5-year OS rate ranges from 30% to 50%, with a relapse-free survival rate of 15% to 25% (cited Lechowicz et al. as reference 50).

Stage I and Stage II MF

This section was extensively revised.

Stage III and Stage IV MF (Including SS)

This section was extensively revised.

Recurrent MF (Including SS)

Revised text to include allogeneic bone marrow or stem cell transplantation for the transplantation treatment option under clinical evaluation (cited Lechowich et al. as reference 30).

Added text to include brentuximab vedotin, a targeted therapy, as a treatment option under clinical evaluation (cited Kim et al. as reference 31 and Duvic et al. as reference 32).

Key References for MF (Including SS)Treatment

Editorial changes were made to this section.

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.

About This PDQ Summary

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:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

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:

  • Eric J. Seifter, MD (Johns Hopkins University)

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.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

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 . Available at: https://www.cancer.gov/types/lymphoma/hp/mycosis-fungoides-treatment-pdq. Accessed . [PMID: 26389288]

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