Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Clinical manifestations, pathologic features, and diagnosis of mycosis fungoides

Richard T Hoppe, MD
Youn H Kim, MD
Section Editors
Timothy M Kuzel, MD, FACP
John A Zic, MD
Deputy Editor
Alan G Rosmarin, MD


Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T cell lymphoma (CTCL).

MF is a mature T cell non-Hodgkin lymphoma with presentation in the skin but with potential involvement of the nodes, blood, and viscera. Skin lesions include patches or plaques that may be localized or widespread, tumors, and erythroderma.

SS is defined as a distinctive erythrodermic CTCL with a leukemic involvement of malignant T cells clonally matching that in the skin.

This group of disorders differs from other primary cutaneous T cell lymphomas by virtue of unique clinical features and histopathology. This topic review will discuss the clinical features, diagnosis, and staging of MF. The diagnosis of SS and the management of these disorders are discussed separately. (See "Clinical presentation, pathologic features, and diagnosis of Sézary syndrome" and "Treatment of early stage (IA to IIA) mycosis fungoides" and "Treatment of advanced stage (IIB to IV) mycosis fungoides" and "Treatment of Sézary syndrome".)


The cause of MF is unclear. Current hypotheses include genetic and epigenetic abnormalities [1-6]. Although environmental and occupational exposure to solvents and chemicals has been implicated in the etiology of the disease, a large case-controlled study failed to support this hypothesis [7]. An infectious etiology for MF has been suggested, but no relation has been confirmed [8]. Human T-lymphotropic virus type I (HTLV-I) has been reported in the peripheral blood or cutaneous lesions of some patients with MF [9,10]. However, an equal number of studies have evidence against a role of HTLV-I [11,12].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Dec 2016. | This topic last updated: Mon Oct 03 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. van Doorn R, Zoutman WH, Dijkman R, et al. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J Clin Oncol 2005; 23:3886.
  2. Shin J, Monti S, Aires DJ, et al. Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome. Blood 2007; 110:3015.
  3. Wong HK, Mishra A, Hake T, Porcu P. Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome). Br J Haematol 2011; 155:150.
  4. Wilcox RA. Cutaneous T-cell lymphoma: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol 2011; 86:928.
  5. Whittaker S. Biological insights into the pathogenesis of cutaneous T-cell lymphomas (CTCL). Semin Oncol 2006; 33:S3.
  6. Wong HK. Novel biomarkers, dysregulated epigenetics, and therapy in cutaneous T-cell lymphoma. Discov Med 2013; 16:71.
  7. Whittemore AS, Holly EA, Lee IM, et al. Mycosis fungoides in relation to environmental exposures and immune response: a case-control study. J Natl Cancer Inst 1989; 81:1560.
  8. Mirvish ED, Pomerantz RG, Geskin LJ. Infectious agents in cutaneous T-cell lymphoma. J Am Acad Dermatol 2011; 64:423.
  9. Hall WW, Liu CR, Schneewind O, et al. Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. Science 1991; 253:317.
  10. Ghosh SK, Abrams JT, Terunuma H, et al. Human T-cell leukemia virus type I tax/rex DNA and RNA in cutaneous T-cell lymphoma. Blood 1994; 84:2663.
  11. Wood GS, Salvekar A, Schaffer J, et al. Evidence against a role for human T-cell lymphotrophic virus type I (HTLV-I) in the pathogenesis of American cutaneous T-cell lymphoma. J Invest Dermatol 1996; 107:301.
  12. Li G, Vowels BR, Benoit BM, et al. Failure to detect human T-lymphotropic virus type-I proviral DNA in cell lines and tissues from patients with cutaneous T-cell lymphoma. J Invest Dermatol 1996; 107:308.
  13. Karenko L, Hahtola S, Päivinen S, et al. Primary cutaneous T-cell lymphomas show a deletion or translocation affecting NAV3, the human UNC-53 homologue. Cancer Res 2005; 65:8101.
  14. Zhang Y, Wang Y, Yu R, et al. Molecular markers of early-stage mycosis fungoides. J Invest Dermatol 2012; 132:1698.
  15. Choi J, Goh G, Walradt T, et al. Genomic landscape of cutaneous T cell lymphoma. Nat Genet 2015; 47:1011.
  16. Ungewickell A, Bhaduri A, Rios E, et al. Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2. Nat Genet 2015; 47:1056.
  17. Ballabio E, Mitchell T, van Kester MS, et al. MicroRNA expression in Sezary syndrome: identification, function, and diagnostic potential. Blood 2010; 116:1105.
  18. Campbell JJ, Clark RA, Watanabe R, Kupper TS. Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood 2010; 116:767.
  19. Laharanne E, Oumouhou N, Bonnet F, et al. Genome-wide analysis of cutaneous T-cell lymphomas identifies three clinically relevant classes. J Invest Dermatol 2010; 130:1707.
  20. Ralfkiaer U, Hagedorn PH, Bangsgaard N, et al. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL). Blood 2011; 118:5891.
  21. Karenko L, Kähkönen M, Hyytinen ER, et al. Notable losses at specific regions of chromosomes 10q and 13q in the Sézary syndrome detected by comparative genomic hybridization. J Invest Dermatol 1999; 112:392.
  22. van Doorn R, van Kester MS, Dijkman R, et al. Oncogenomic analysis of mycosis fungoides reveals major differences with Sezary syndrome. Blood 2009; 113:127.
  23. Vermeer MH, van Doorn R, Dijkman R, et al. Novel and highly recurrent chromosomal alterations in Sézary syndrome. Cancer Res 2008; 68:2689.
  24. Girardi M, Heald PW, Wilson LD. The pathogenesis of mycosis fungoides. N Engl J Med 2004; 350:1978.
  25. Hwang ST, Janik JE, Jaffe ES, Wilson WH. Mycosis fungoides and Sézary syndrome. Lancet 2008; 371:945.
  26. Kim EJ, Hess S, Richardson SK, et al. Immunopathogenesis and therapy of cutaneous T cell lymphoma. J Clin Invest 2005; 115:798.
  27. López-Lerma I, Estrach MT. A distinct profile of serum levels of soluble intercellular adhesion molecule-1 and intercellular adhesion molecule-3 in mycosis fungoides and Sézary syndrome. J Am Acad Dermatol 2009; 61:263.
  28. Bernengo MG, Fierro MT, Novelli M, et al. Soluble interleukin-2 receptor in Sézary syndrome: its origin and clinical application. Br J Dermatol 1993; 128:124.
  29. Wasik MA, Vonderheid EC, Bigler RD, et al. Increased serum concentration of the soluble interleukin-2 receptor in cutaneous T-cell lymphoma. Clinical and prognostic implications. Arch Dermatol 1996; 132:42.
  30. Yamanaka K, Clark R, Rich B, et al. Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma. Blood 2006; 107:2440.
  31. Kakinuma T, Sugaya M, Nakamura K, et al. Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. J Am Acad Dermatol 2003; 48:23.
  32. Criscione VD, Weinstock MA. Incidence of cutaneous T-cell lymphoma in the United States, 1973-2002. Arch Dermatol 2007; 143:854.
  33. Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010; 116:3724.
  34. Korgavkar K, Xiong M, Weinstock M. Changing incidence trends of cutaneous T-cell lymphoma. JAMA Dermatol 2013; 149:1295.
  35. Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood 2009; 113:5064.
  36. Fujita A, Hamada T, Iwatsuki K. Retrospective analysis of 133 patients with cutaneous lymphomas from a single Japanese medical center between 1995 and 2008. J Dermatol 2011; 38:524.
  37. Sun G, Berthelot C, Li Y, et al. Poor prognosis in non-Caucasian patients with early-onset mycosis fungoides. J Am Acad Dermatol 2009; 60:231.
  38. Hinds GA, Heald P. Cutaneous T-cell lymphoma in skin of color. J Am Acad Dermatol 2009; 60:359.
  39. Wu XC, Andrews P, Chen VW, Groves FD. Incidence of extranodal non-Hodgkin lymphomas among whites, blacks, and Asians/Pacific Islanders in the United States: anatomic site and histology differences. Cancer Epidemiol 2009; 33:337.
  40. Klein RS, Dunlop JD, Samimi SS, et al. Improvement in peripheral blood disease burden in patients with Sézary syndrome and leukemic mycosis fungoides after total skin electron beam therapy. J Am Acad Dermatol 2013; 68:972.
  41. Crowley JJ, Nikko A, Varghese A, et al. Mycosis fungoides in young patients: clinical characteristics and outcome. J Am Acad Dermatol 1998; 38:696.
  42. Quaglino P, Zaccagna A, Verrone A, et al. Mycosis fungoides in patients under 20 years of age: report of 7 cases, review of the literature and study of the clinical course. Dermatology 1999; 199:8.
  43. Pope E, Weitzman S, Ngan B, et al. Mycosis fungoides in the pediatric population: report from an international Childhood Registry of Cutaneous Lymphoma. J Cutan Med Surg 2010; 14:1.
  44. Hodak E, Klein T, Gabay B, et al. Familial mycosis fungoides: report of 6 kindreds and a study of the HLA system. J Am Acad Dermatol 2005; 52:393.
  45. Demierre MF, Gan S, Jones J, Miller DR. Significant impact of cutaneous T-cell lymphoma on patients' quality of life: results of a 2005 National Cutaneous Lymphoma Foundation Survey. Cancer 2006; 107:2504.
  46. Morales MM, Olsen J, Johansen P, et al. Viral infection, atopy and mycosis fungoides: a European multicentre case-control study. Eur J Cancer 2003; 39:511.
  47. Zackheim HS, McCalmont TH. Mycosis fungoides: the great imitator. J Am Acad Dermatol 2002; 47:914.
  48. Guitart J, Magro C. Cutaneous T-cell lymphoid dyscrasia: a unifying term for idiopathic chronic dermatoses with persistent T-cell clones. Arch Dermatol 2007; 143:921.
  49. Smoller BR, Bishop K, Glusac E, et al. Reassessment of histologic parameters in the diagnosis of mycosis fungoides. Am J Surg Pathol 1995; 19:1423.
  50. Pimpinelli N, Olsen EA, Santucci M, et al. Defining early mycosis fungoides. J Am Acad Dermatol 2005; 53:1053.
  51. Kazakov DV, Burg G, Kempf W. Clinicopathological spectrum of mycosis fungoides. J Eur Acad Dermatol Venereol 2004; 18:397.
  52. 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 2003; 139:857.
  53. Kim YH, Jensen RA, Watanabe GL, et al. Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol 1996; 132:1309.
  54. Kodama K, Fink-Puches R, Massone C, et al. Papular mycosis fungoides: a new clinical variant of early mycosis fungoides. J Am Acad Dermatol 2005; 52:694.
  55. Monopoli A, Annessi G, Lombardo GA, et al. Purely follicular mycosis fungoides without mucinosis: report of two cases with review of the literature. J Am Acad Dermatol 2003; 48:448.
  56. Abbott RA, Sahni D, Robson A, et al. Poikilodermatous mycosis fungoides: a study of its clinicopathological, immunophenotypic, and prognostic features. J Am Acad Dermatol 2011; 65:313.
  57. Boulos S, Vaid R, Aladily TN, et al. Clinical presentation, immunopathology, and treatment of juvenile-onset mycosis fungoides: a case series of 34 patients. J Am Acad Dermatol 2014; 71:1117.
  58. Uhlenhake EE, Mehregan DM. Annular hypopigmented mycosis fungoides: a novel ringed variant. J Cutan Pathol 2012; 39:535.
  59. Bi MY, Curry JL, Christiano AM, et al. The spectrum of hair loss in patients with mycosis fungoides and Sézary syndrome. J Am Acad Dermatol 2011; 64:53.
  60. Ahern K, Gilmore ES, Poligone B. Pruritus in cutaneous T-cell lymphoma: a review. J Am Acad Dermatol 2012; 67:760.
  61. Vij A, Duvic M. Prevalence and severity of pruritus in cutaneous T cell lymphoma. Int J Dermatol 2012; 51:930.
  62. Vonderheid EC, Diamond LW, van Vloten WA, et al. Lymph node classification systems in cutaneous T-cell lymphoma. Evidence for the utility of the Working Formulation of Non-Hodgkin's Lymphomas for Clinical Usage. Cancer 1994; 73:207.
  63. Baser S, Onn A, Lin E, et al. Pulmonary manifestations in patients with cutaneous T-cell lymphomas. Cancer 2007; 109:1550.
  64. Swerdlow A, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissue, International Agency for Research on Cancer Press, Lyon 2008.
  65. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
  66. Epstein EH Jr, Levin DL, Croft JD Jr, Lutzner MA. Mycosis fungoides. Survival, prognostic features, response to therapy, and autopsy findings. Medicine (Baltimore) 1972; 51:61.
  67. Stein M, Farrar N, Jones GW, et al. Central neurologic involvement in mycosis fungoides: ten cases, actuarial risk assessment, and predictive factors. Cancer J 2006; 12:55.
  68. Krejsgaard T, Odum N, Geisler C, et al. Regulatory T cells and immunodeficiency in mycosis fungoides and Sézary syndrome. Leukemia 2012; 26:424.
  69. Mallo-García S, Coto-Segura P, Suárez-Casado H, et al. Fatal outcome due to bacterial superinfection of eczema herpeticum in a patient with mycosis fungoides. Dermatol Online J 2008; 14:21.
  70. Talpur R, Bassett R, Duvic M. Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sézary syndrome. Br J Dermatol 2008; 159:105.
  71. Lee J, Richardson SK, Melhem ER, et al. Progressive multifocal leukoencephalopathy from JC virus in a patient with advanced mycosis fungoides. J Am Acad Dermatol 2007; 57:893.
  72. 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 2007; 143:45.
  73. Herro E, Dicaudo DJ, Davis MD, et al. Review of contemporaneous mycosis fungoides and B-cell malignancy at Mayo Clinic. J Am Acad Dermatol 2009; 61:271.
  74. Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007; 110:1713.
  75. Marschalkó M, Erős N, Kontár O, et al. Folliculotropic mycosis fungoides: clinicopathological analysis of 17 patients. J Eur Acad Dermatol Venereol 2015; 29:964.
  76. Diamandidou E, Colome-Grimmer M, Fayad L, et al. Transformation of mycosis fungoides/Sezary syndrome: clinical characteristics and prognosis. Blood 1998; 92:1150.
  77. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL (Eds), IARC Press, Lyon 2008.
  78. 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 2014; 70:374.
  79. Sausville EA, Worsham GF, Matthews MJ, et al. Histologic assessment of lymph nodes in mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma): clinical correlations and prognostic import of a new classification system. Hum Pathol 1985; 16:1098.
  80. Kern DE, Kidd PG, Moe R, et al. Analysis of T-cell receptor gene rearrangement in lymph nodes of patients with mycosis fungoides. Prognostic implications. Arch Dermatol 1998; 134:158.
  81. Oshtory S, Apisarnthanarax N, Gilliam AC, et al. Usefulness of flow cytometry in the diagnosis of mycosis fungoides. J Am Acad Dermatol 2007; 57:454.
  82. Wood G, Weiss L, Warnke R, et al. The immunopathology of cutaneous lymphomas: Immunophenotypic and immunogenotypic characteristics. Semin Dermatol 1986; 5:334.
  83. Smoller BR, Santucci M, Wood GS, Whittaker SJ. Histopathology and genetics of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am 2003; 17:1277.
  84. Swerdlow SH, Campo E, Harris NL, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues, IARC Press, Lyon 2008.
  85. Benner MF, Jansen PM, Vermeer MH, Willemze R. Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood 2012; 119:1643.
  86. Edinger JT, Clark BZ, Pucevich BE, et al. CD30 expression and proliferative fraction in nontransformed mycosis fungoides. Am J Surg Pathol 2009; 33:1860.
  87. Ashton-Key M, Diss TC, Du MQ, et al. The value of the polymerase chain reaction in the diagnosis of cutaneous T-cell infiltrates. Am J Surg Pathol 1997; 21:743.
  88. Muche JM, Lukowsky A, Asadullah K, et al. Demonstration of frequent occurrence of clonal T cells in the peripheral blood of patients with primary cutaneous T-cell lymphoma. Blood 1997; 90:1636.
  89. Delfau-Larue MH, Laroche L, Wechsler J, et al. Diagnostic value of dominant T-cell clones in peripheral blood in 363 patients presenting consecutively with a clinical suspicion of cutaneous lymphoma. Blood 2000; 96:2987.
  90. Weng WK, Armstrong R, Arai S, et al. Minimal residual disease monitoring with high-throughput sequencing of T cell receptors in cutaneous T cell lymphoma. Sci Transl Med 2013; 5:214ra171.
  91. Vega F, Luthra R, Medeiros LJ, et al. Clonal heterogeneity in mycosis fungoides and its relationship to clinical course. Blood 2002; 100:3369.
  92. Thurber SE, Zhang B, Kim YH, et al. T-cell clonality analysis in biopsy specimens from two different skin sites shows high specificity in the diagnosis of patients with suggested mycosis fungoides. J Am Acad Dermatol 2007; 57:782.
  93. Guitart J. Beyond clonal detection: defining the T-cell clone. Arch Dermatol 2005; 141:1159.
  94. Khan N, Shariff N, Cobbold M, et al. Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol 2002; 169:1984.
  95. Fung MA, Murphy MJ, Hoss DM, Grant-Kels JM. Practical evaluation and management of cutaneous lymphoma. J Am Acad Dermatol 2002; 46:325.
  96. www.nccn.org (Accessed on April 27, 2012).
  97. Simon HU, Plötz SG, Dummer R, Blaser K. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med 1999; 341:1112.
  98. Lober CW. Should the patient with generalized pruritus be evaluated for malignancy? J Am Acad Dermatol 1988; 19:350.
  99. Pujol RM, Gallardo F, Llistosella E, et al. Invisible mycosis fungoides: a diagnostic challenge. J Am Acad Dermatol 2002; 47:S168.
  100. Guitart J, Weisenburger DD, Subtil A, et al. Cutaneous γδ T-cell lymphomas: a spectrum of presentations with overlap with other cytotoxic lymphomas. Am J Surg Pathol 2012; 36:1656.
  101. Swerdlow SH, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.