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Mycosis Fungoides and the Sézary Syndrome Treatment (PDQ®)

Health Professional Version
Last Modified: 01/24/2014

General Information About Mycosis Fungoides and the Sézary Syndrome

Clinical Presentation
Prognosis and Survival



Clinical Presentation

Mycosis fungoides and the Sézary syndrome (MF/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.[1] These types of lymphomas are included in the Revised European-American Lymphoma classification as low-grade T-cell lymphomas, which 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.) In addition, a number of benign or very indolent conditions can be confused with mycosis fungoides. Consultation with a pathologist who has expertise in distinguishing these conditions is important.[4]

Prognosis and Survival

The prognosis of patients with MF/SS is based on the extent of disease at presentation (stage).[5] The presence of lymphadenopathy and involvement of peripheral blood and viscera increase in likelihood with worsening cutaneous involvement and define poor prognostic groups.[5-7] The median survival following diagnosis varies according to stage. Patients with stage IA disease have a median survival of 20 or more years. The majority of deaths for this group are not caused by, nor are they related to, MF.[8] In contrast, more than 50% of patients with stage III through stage IV disease die of MF, with a median survival of less than 5 years.[7,9,10] 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 of 1.32; 95% confidence interval, 1.15–1.52), especially for Hodgkin and non-Hodgkin lymphoma and for myeloma.[11]

Typically, the natural history of MF is indolent.[12] Symptoms of the disease may present for long periods, an average of 2 to 10 years, as waxing and waning cutaneous eruptions prior to biopsy confirmation. MF/SS is treatable with available topical and/or systemic therapies. Curative modalities, however, have thus far proven elusive, with the possible exception of patients with minimal disease confined to the skin.

Cutaneous disease typically progresses from an eczematous patch/plaque stage covering less than 10% of the body surface (T1) to plaque stage covering 10% or more of the body surface (T2), and finally to tumors (T3) that frequently undergo necrotic ulceration.[4,13] A retrospective study with a median follow-up of 14.5 years showed that 20% of the 1,422 patients progressed from stage I or II disease to stage III or IV disease.[14] 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.[15] 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.[14] There is consensus that patients with SS have a poor prognosis (median survival of 4 years).[16] 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.[17,18] 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.[19] 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.[13]

References
  1. Girardi M, Heald PW, Wilson LD: The pathogenesis of mycosis fungoides. N Engl J Med 350 (19): 1978-88, 2004.  [PUBMED Abstract]

  2. 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]

  3. 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]

  4. 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]

  5. 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]

  6. 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]

  7. Kim YH, Liu HL, Mraz-Gernhard S, et al.: Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol 139 (7): 857-66, 2003.  [PUBMED Abstract]

  8. 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]

  9. Zackheim HS, Amin S, Kashani-Sabet M, et al.: Prognosis in cutaneous T-cell lymphoma by skin stage: long-term survival in 489 patients. J Am Acad Dermatol 40 (3): 418-25, 1999.  [PUBMED Abstract]

  10. de Coninck EC, Kim YH, Varghese A, et al.: Clinical characteristics and outcome of patients with extracutaneous mycosis fungoides. J Clin Oncol 19 (3): 779-84, 2001.  [PUBMED Abstract]

  11. Huang KP, Weinstock MA, Clarke CA, et al.: Second lymphomas and other malignant neoplasms in patients with mycosis fungoides and Sezary syndrome: evidence from population-based and clinical cohorts. Arch Dermatol 143 (1): 45-50, 2007.  [PUBMED Abstract]

  12. Diamandidou E, Cohen PR, Kurzrock R: Mycosis fungoides and Sezary syndrome. Blood 88 (7): 2385-409, 1996.  [PUBMED Abstract]

  13. Lorincz AL: Cutaneous T-cell lymphoma (mycosis fungoides) Lancet 347 (9005): 871-6, 1996.  [PUBMED Abstract]

  14. 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]

  15. 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]

  16. 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]

  17. Kim YH, Bishop K, Varghese A, et al.: Prognostic factors in erythrodermic mycosis fungoides and the Sézary syndrome. Arch Dermatol 131 (9): 1003-8, 1995.  [PUBMED Abstract]

  18. Arulogun SO, Prince HM, Ng J, et al.: Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation. Blood 112 (8): 3082-7, 2008.  [PUBMED Abstract]

  19. Benner MF, Jansen PM, Vermeer MH, et al.: Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood 119 (7): 1643-9, 2012.  [PUBMED Abstract]