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Clinical Presentation
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.[
Typically, the natural history of mycosis fungoides is indolent.[
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 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.[
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.[
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.[
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.[
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.[
References:
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.[
References:
The American Joint Committee on Cancer (AJCC) has designated staging by TNM (tumor, node, metastasis) classification to define mycosis fungoides.[
Mycosis fungoides and Sézary syndrome also have a formal staging system proposed by the International Society for Cutaneous Lymphomas (ISCL) and the European Organisation for Research and Treatment of Cancer (EORTC).[
EORTC Classification | Dutch System | NCI-VA Classification |
---|---|---|
DL = dermatopathic lymphadenopathy; EORTC = European Organisation for Research and Treatment of Cancer; LN = lymph nodes; N = regional lymph node; NCI = National Cancer Institute; VA = U.S. Department of Veterans Affairs. | ||
a Reprinted with permission from AJCC: Primary Cutaneous Lymphomas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 967–72. | ||
N1 | Grade 1: DL | LN0: No atypical lymphocytes. |
LN1: Occasional and isolated atypical lymphocytes (not arranged in clusters). | ||
LN2: Many atypical lymphocytes or lymphocytes in 3-6‒cell clusters. | ||
N2 | Grade 2: DL; early involvement by mycosis fungoides (presence of cerebriform nuclei <7.5 µm [micrometer]). | LN3: Aggregates of atypical lymphocytes; nodal architecture preserved. |
N3 | Grade 3: Partial effacement of lymph node architecture; many atypical cerebriform mononuclear cells. | LN4: Partial/complete effacement of nodal architecture by atypical lymphocytes or frankly neoplastic cells. |
Grade 4: Complete effacement. |
Stage | TNM | Description | B | Peripheral Blood Involvement Criteria |
---|---|---|---|---|
T = primary tumor; N = regional lymph node; M = distant metastasis; B = peripheral blood involvement. | ||||
a Reprinted with permission from AJCC: Primary Cutaneous Lymphomas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 967–72. | ||||
The explanations for superscripts b through f are at the end of Table 5. | ||||
IA | T1, N0, M0 | T1 = Limited patches,b papules, and/or plaquesc covering <10% of the skin surface. | B0,1 | B0 = Absence of significant blood involvement: ≤5% of peripheral blood lymphocytes are atypical (Sézary) cells.d |
–T1a = T1a (patch only). | ||||
–T1b = T1b (plaque ± patch). | –B0a = Clone negativee | |||
–B0b = Clone positivee | ||||
N0 = No clinically abnormal peripheral lymph nodes;f biopsy not required. | B1 = Low blood tumor burden: >5% of peripheral blood lymphocytes are atypical (Sézary) cells, but does not meet the criteria of B2. | |||
M0 = No visceral organ involvement. | –B1a = Clone negativee | |||
–B1b = Clone positivee | ||||
IB | T2, N0, M0 | T2 = Patches, papules, or plaques covering ≥10% of the skin surface. | B0,1 | See B0, B1 descriptions above in this table, Stage IA. |
–T2a = T2a (patch only). | ||||
–T2b = T2b (plaque ± patch). | ||||
N0 = No clinically abnormal peripheral lymph nodes;f biopsy not required. | ||||
M0 = No visceral organ involvement. |
Stage | TNM | Description | B | Peripheral Blood Involvement Criteria |
---|---|---|---|---|
T = primary tumor; N = regional lymph node; M = distant metastasis; B = peripheral blood involvement; LN = lymph nodes; NCI = National Cancer Institute. | ||||
a Reprinted with permission from AJCC: Primary Cutaneous Lymphomas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 967–72. | ||||
The explanations for superscripts e through g are at the end of Table 5. | ||||
IIA | T1,2; N1,2; M0 | See T1–2 descriptions above in Table 2, Stages IA, IB. | B0,1 | See B0, B1 descriptions above in Table 2, Stage IA. |
N1 = Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0–2. | ||||
–N1a = Clone negative.e | ||||
–N1b = Clone positive.e | ||||
N2 = Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. | ||||
–N2a = Clone negative.e | ||||
–N2b = Clone positive.e | ||||
M0 = No visceral organ involvement. | ||||
IIB | T3, N0–2, M0 | T3 = One or more tumorsg(≥1 cm in diameter). | B0,1 | See B0, B1 descriptions above in Table 2, Stage IA. |
–T3a = Multiple lesions involving 2 noncontiguous body regions. | ||||
–T3b = Multiple lesions involving ≥3 body regions. | ||||
N0 = No clinically abnormal peripheral lymph nodes;f biopsy not required. | ||||
See N1–2 descriptions above in this table, Stage IIA | ||||
M0 = No visceral organ involvement. |
Stage | TNM | Description | B | Peripheral Blood Involvement Criteria |
---|---|---|---|---|
T = primary tumor; N = regional lymph node; M = distant metastasis; B = peripheral blood involvement. | ||||
a Reprinted with permission from AJCC: Primary Cutaneous Lymphomas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 967–72. | ||||
III | T4, N0–2, M0 | T4 = Confluence of erythema covering ≥80% of body surface area. | B0,1 | See B0, B1 descriptions above in Table 2, Stage IA. |
See N0–2 descriptions above in Table 3, Stages IIA, IIB. | ||||
M0 = No visceral organ involvement. | ||||
IIIA | T4, N0–2, M0 | T4 = Confluence of erythema covering ≥80% of body surface area. | B0 | See B0 description above in Table 2, Stage IA. |
See N0–2 descriptions above in Table 3, Stages IIA, IIB. | ||||
M0 = No visceral organ involvement. | ||||
IIIB | T4, N0–2, M0 | T4 = Confluence of erythema covering ≥80% of body surface area. | B1 | See B1 description above in Table 2, Stage IA. |
See N0–2 descriptions above in Table 3, Stages IIA, IIB. | ||||
M0 = No visceral organ involvement. |
Stage | TNM | Description | B | Peripheral Blood Involvement Criteria |
---|---|---|---|---|
T = primary tumor; N = regional lymph node; M = distant metastasis; B = peripheral blood involvement; LN = lymph nodes; NCI = National Cancer Institute. | ||||
a Reprinted with permission from AJCC: Primary Cutaneous Lymphomas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 967–72. | ||||
b For skin,patch indicates any size skin lesion without significant elevation or induration. Presence/absence of hypo- or hyperpigmentation, scale, crusting, and/or poikiloderma should be noted. | ||||
c For skin,plaque indicates any size skin lesion that is elevated or indurated. Presence/absence of scale, crusting, and/or poikiloderma should be noted. Histologic features such as folliculotropism, large cell transformation (>25% large cells) and CD30 positivity or negativity, as well as clinical features such as ulceration, are important to document. | ||||
d For blood, Sézary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei. If Sézary cells cannot be used to determine tumor burden for B2, then one of the following modified ISCL criteria, along with a positive clonal rearrangement of the T-cell receptor (TCR), may be used instead: (1) expanded CD4+ or CD3+ cells with a CD4/CD8 ratio of >10, or (2) expanded CD4+ cells with abnormal immunophenotype, including loss of CD7 or CD26. | ||||
e A T-cell clone is defined by polymerase chain reaction (PCR) or Southern blot analysis of the TCR gene. | ||||
f For node,abnormal peripheral lymph node(s) indicates any palpable peripheral node that on physical examination is firm, irregular, clustered, fixed or ≥1.5 cm in diameter. Node groups examined on physical examination include cervical, supraclavicular, epitrochlear, axillary, and inguinal. Central nodes, which generally are not amenable to pathological assessment, currently are not considered in the nodal classification unless used to establish N3 histopathologically. | ||||
g For skin,tumor indicates at least one 1-cm diameter solid or nodular lesion with evidence of depth and/or vertical growth. Note the total number of lesions, total volume of lesions, largest size lesion, and region of body involved. Also note whether there is histologic evidence of large cell transformation. Phenotyping for CD30 is encouraged. | ||||
h For viscera, spleen and liver may be diagnosed by imaging criteria. | ||||
IVA1 | T1–4, N0–2, M0 | See T1‒2 descriptions above in Table 2, Stages IA, IB. | B2 | B2 = High blood tumor burden: ≥1,000 mcg/L Sézary cellsd with positive clone.e |
T3 = One or more tumorsg(≥1 cm in diameter). | ||||
–T3a = Multiple lesions involving 2 noncontiguous body regions. | ||||
–T3b = Multiple lesions involving ≥3 body regions. | ||||
T4 = Confluence of erythema covering ≥80% of body surface area. | ||||
See N0–2 descriptions above in Table 3, Stages IIA, IIB. | ||||
M0 = No visceral organ involvement. | ||||
IVA2 | T1–4, N3, M0 | See T1‒2 descriptions above in Table 2, Stages IA, IB and see T3–4 descriptions above in this table, Stage IVA1. | B0–2 | See B0, B1 descriptions above in Table 2, Stage IA and see B2 description above in this table, Stage IVA1. |
N3 = Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3–4 or NCI LN4; clone positive or negative. | ||||
M0 = No visceral organ involvement. | ||||
IVB | T1–4, N0–3, M1 | See T1‒2 descriptions above in Table 2, Stages IA, IB and see T3–4 descriptions above in this table, Stage IVA1. | B0–2 | See B0, B1 descriptions above in Table 2, Stage IA and see B2 description above in this table, Stage IVA1. |
See N0–2 descriptions above in Table 3, Stages IIA, IIB. | ||||
N3 = Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3–4 or NCI LN4; clone positive or negative. | ||||
M1 = Visceral involvement (must have pathology confirmation,h and organ involved should be specified). |
References:
Treatment options for patients with mycosis fungoides and Sézary syndrome include the following:[
Photodynamic Therapy
Radiation Therapy
Biologic Therapy
Chemotherapy
Other Drug Therapy
Targeted Therapy
Transplantation
Checkpoint Inhibitors
Anecdotal responses, some lasting for months, can be seen with aggressive antibiotic treatment of Staphylococcus aureus, with corresponding decreased expression of interleukin-2 receptors, STAT signaling, and T-cell proliferation.[
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.
References:
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.[
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.[
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.
References:
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 [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.[
Sézary Syndrome
Sézary syndrome is a rare leukemic variant of cutaneous T-cell lymphoma characterized by erythroderma, circulating Sézary cells with cerebriform nuclei, lymphadenopathy, and pruritus.[
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):[
(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.
References:
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).[
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:[
(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.
References:
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.
Cited in:
Cited in:
Cited in:
Cited in:
Cited in:
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.
Editorial changes were made to this summary.
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® Cancer Information for Health Professionals 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 in the care of their 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 reviewers for Mycosis Fungoides (Including Sézary Syndrome) Treatment are:
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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: 2023-06-27
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