Mycosis Fungoides (Including Sézary Syndrome) Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Mycosis Fungoides (Including Sézary Syndrome) Treatment (PDQ®)–Health Professional Version

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General Information About Mycosis Fungoides (Including Sézary Syndrome)

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.[1] 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.[4] 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, a number of benign or indolent conditions can be confused with mycosis fungoides. Consultation with a pathologist who has expertise in distinguishing these conditions is important.[1]

Prognosis and Survival

The prognosis of patients with mycosis fungoides and Sézary syndrome is based on the extent of disease (stage) at presentation.[5] The presence of lymphadenopathy and involvement of peripheral blood and viscera increase in likelihood with worsening cutaneous involvement and define poor prognostic groups.[5-8] The Cutaneous Lymphoma International Consortium retrospectively reviewed 1,275 patients and found the following four independent prognostic markers indicate a worse survival:[9]

Stage IV disease.
Age older than 60 years.
Large cell transformation.
Elevated lactate dehydrogenase.

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.[14]

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.[15] 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).[16]

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.[19-21] 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.[22] 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.[19]

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.[25-27] 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.[28] A common cause of death during the tumor phase is sepsis from Pseudomonas aeruginosa or Staphylococcus aureus caused by chronic skin infection with staph species and subsequent systemic infections.[18]

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.[29] Early plaque-stage folliculotropic mycosis fungoides have a very indolent prognosis, while extracutaneous disease portends a very poor prognosis.[29]

References

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Willemze R, Kerl H, Sterry W, et al.: EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 90 (1): 354-71, 1997. [PUBMED Abstract]
Harris NL, Jaffe ES, Stein H, et al.: A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84 (5): 1361-92, 1994. [PUBMED Abstract]
Diamandidou E, Cohen PR, Kurzrock R: Mycosis fungoides and Sezary syndrome. Blood 88 (7): 2385-409, 1996. [PUBMED Abstract]
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]
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]
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Scarisbrick JJ, Prince HM, Vermeer MH, et al.: Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. J Clin Oncol 33 (32): 3766-73, 2015. [PUBMED Abstract]
Kim YH, Jensen RA, Watanabe GL, et al.: Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol 132 (11): 1309-13, 1996. [PUBMED Abstract]
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Su C, Nguyen KA, Bai HX, et al.: Racial disparity in mycosis fungoides: An analysis of 4495 cases from the US National Cancer Database. J Am Acad Dermatol 77 (3): 497-502.e2, 2017. [PUBMED Abstract]
Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell lymphoma: review and current concepts. J Clin Oncol 18 (15): 2908-25, 2000. [PUBMED Abstract]
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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]
Wernham AG, Shah F, Amel-Kashipaz R, et al.: Stage I mycosis fungoides: frequent association with a favourable prognosis but disease progression and disease-specific mortality may occur. Br J Dermatol 173 (5): 1295-7, 2015. [PUBMED Abstract]
Desai M, Liu S, Parker S: Clinical characteristics, prognostic factors, and survival of 393 patients with mycosis fungoides and Sézary syndrome in the southeastern United States: a single-institution cohort. J Am Acad Dermatol 72 (2): 276-85, 2015. [PUBMED Abstract]
Olsen EA, Rook AH, Zic J, et al.: Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC). J Am Acad Dermatol 64 (2): 352-404, 2011. [PUBMED Abstract]
Kubica AW, Davis MD, Weaver AL, et al.: Sézary syndrome: a study of 176 patients at Mayo Clinic. J Am Acad Dermatol 67 (6): 1189-99, 2012. [PUBMED Abstract]
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