Abstract
Mycosis fungoides (MF), and the associated leukemic variant Sezary Syndrome (SS), are the most common group of cutaneous T-cell lymphomas. MF/SS is a non-Hodgkin’s lymphoma of mature, skin-homing, clonal, malignant T lymphocytes that initially presents in the skin as patches, plaques, tumors, or generalized erythema (erythroderma) and can involve the lymph nodes and peripheral blood. Much progress has been made in recent years in understanding the origin of the malignant T cell in MF/SS and the pathophysiology and immunology of the disease. This recent work has made a great impact on diagnosis, prognostication, and treatment. In this review, we survey the MF/SS published literature over the past year and highlight some of the important advances.
Similar content being viewed by others
References and Recommended Reading
Girardi, M, Heald PW, Wilson LD: The pathogenesis of mycosis fungoides. N Engl J Med 2004, 35:1978–1988. A lucid, comprehensive review of the basic science advances in MF/SS.
WHO-EORTC classification for cutaneous lymphomas. Blood 2005, 105:3768–3785. The new joint classification system is a step in the right direction for clarifying cutaneous lymphomas.
Pimpinelli N, Olsen EA, Santucci M, et al.: Defining early mycosis fungoides. J Am Acad Dermatol 2005, 53:1053–1063.
Wood GS, Tung RM, Haeffner AC, et al.: Detection of clonal T-cell receptor gamma gene rearrangements in early mycosis fungoides/Sezary syndrome by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR/DGGE). J Invest Dermatol 1994, 103: 34–41.
Ponti R, Quaglino P, Novelli M, et al.: T-cell receptor gamma gene rearrangement by multiplex polymerase chain reaction/heteroduplex analysis in patients with cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome) and benign inflammatory disease: correlation with clinical, histological and immunophenotypical findings. Br J Dermatol 2005, 153:565–573.
Alessi E, Coggi A, Venegoni L, et al.: The usefulness of clonality for the detection of cases clinically and/or histopathologically not recognized as cutaneous T-cell lymphoma. Br J Dermatol 2005, 153: 368–371.
Guitart J: Beyond clonal detection: defining the T-cell clone. Arch Dermatol 2005, 141(9):1159–1160. A concise summary of the current role of T-cell receptor clonality in MF/SS diagnosis and prognosis.
Cordel N, Lenormand B, Courville P, et al.: Usefulness of cutaneous T-cell clonality analysis for the diagnosis of cutaneous T-cell lymphoma in patients with erythroderma. Arch Pathol Lab Med 2005, 129:372–376.
Tracey L, Villuendas R, Dotor AM, et al.: Mycosis fungoides shows concurrent deregulation of multiple genes involved in the TNF signaling pathway: an expression profile study. Blood 2003, 102:1042–1050. One of three studies that demonstrate the power of microarray analysis as applied to MF/SS. See [10,11].
Kari L, Loboda A, Nebozhyn M, et al.: Classification and prediction of survival in patients with the leukemic phase of cutaneous T cell lymphoma. J Exp Med 2003, 197:1477–1488. One of three studies that demonstrate the power of microarray analysis as applied to MF/SS. See [9,11].
Nebozhyn M, Loboda A, Kari L, et al.: Quantitative PCR on 5 genes reliably identifies CTCL patients with 5–99% circulating tumor cells with 90% accuracy. Blood 2006, 107:3189–3196. One of three studies that demonstrate the power of microarray analysis as applied to MF/SS. See [9,10].
Vonderheid EC, Bernengo MG: The Sezary syndrome: hematologic criteria. Hematol Oncol Clin North Am 2003, 17:1367–1389, viii. An update of the B classification system for MF/SS that reflects the newer diagnostic techniques.
Beylot-Barry M, Parrens M, Delaunay M, et al.: Is bone marrow biopsy necessary in patients with mycosis fungoides and Sezary syndrome? A histological and molecular study at diagnosis and during follow-up. Br J Dermatol 2005, 152:1378–1379.
Morton LM, Wang SS, Devesa SS, et al.: Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006, 107:265–276.
Morales MM, Putcha V, Evans HS, et al.: Survival of mycosis fungoides in patients in the Southeast of England. Dermatology 2005, 211:325–329.
Gupta RK, Ramble J, Tong CY, et al.: Cytomegalovirus seroprevalence is not higher in patients with mycosis fungoides/Sezary syndrome. Blood 2006, 107:1241–1242.
Tothova SM, Bonin S, Trevisan G, Stanta G: Mycosis fungoides: is it a Borrelia burgdorferi-associated disease? Br J Cancer 2006, 94:879–883.
Trento E, Castilletti C, Ferraro C, et al.: Human herpesvirus 8 infection in patients with cutaneous lymphoproliferative diseases. Arch Dermatol 2005, 141:1235–1242.
Morales-Suarez-Varela MM, Olsen J, Johansen P, et al.: Occupational exposures and mycosis fungoides. A European multicentre case-control study (Europe). Cancer Causes Control 2005, 16:1253–1259.
Schmidt A, Robbins J, Zic J: Transformed mycosis fungoides developing after treatment with alefacept. J Am Acad Dermatol 2005, 53:355–356.
Dalle S, Balme B, Berger F, et al.: Mycosis fungoides-associated follicular mucinosis under adalimumab. Br J Dermatol 2005, 153:207–208.
Abeni D, Frontani M, Sampogna F, et al.: Circulating CD8+ lymphocytes, white blood cells, and survival in patients with mycosis fungoides. Br J Dermatol 2005, 153:324–330.
Juarez T, Isenhath SN, Polissar NL, et al.: Analysis of T-cell receptor gene rearrangement for predicting clinical outcome in patients with cutaneous T-cell lymphoma: a comparison of Southern blot and polymerase chain reaction methods. Arch Dermatol 2005, 141:1107–1113.
Assaf C, Hummel M, Steinhoff M, et al.: Early TCR-beta and TCR-gamma PCR detection of T-cell clonality indicates minimal tumor disease in lymph nodes of cutaneous T-cell lymphoma: diagnostic and prognostic implications. Blood 2005, 105:503–510.
Klemke CD, Mansmann U, Poenitz N, et al.: Prognostic factors and prediction of prognosis by the CTCL Severity Index in mycosis fungoides and Sezary syndrome. Br J Dermatol 2005, 153:118–124. This paper offers a revised severity index that, if further validated, could be a valuable tool in future clinical trials and outcome studies.
Kupper TS, Fuhlbrigge RC: Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 2004, 4:211–222. Excellent review of the role of skin-homing T cells.
Sokolowska-Wojdylo M, Wenzel J, Gaffal E, et al.: Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7. Br J Dermatol 2005, 152:258–264.
Kagami S, Sugaya M, Minatani Y, et al.: Elevated serum CTACK/CCL27 levels in CTCL. J Invest Dermatol 2006, 126:1189–1191.
Sokolowska-Wojdylo M, Wenzel J, Gaffal E, et al.: Absence of CD26 expression on skin-homing CLA+ CD4+ T lymphocytes in peripheral blood is a highly sensitive marker for early diagnosis and therapeutic monitoring of patients with Sezary syndrome. Clin Exp Dermatol 2005,30:702–706.
Introcaso CE, Hess SD, Kamoun M, et al.: Association of change in clinical status and change in the percentage of the CD4+CD26-lymphocyte population in patients with Sezary syndrome. J Am Acad Dermatol 2005, 53:428–434.
Narducci MG, Scala E, Bresin A, et al.: Skin homing of Sezary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV. Blood 2006, 107:1108–115. This paper elucidates the role of CD26 loss in SS.
Vonderheid EC, Boselli CM, Conroy M, et al.: Evidence for restricted Vbeta usage in the leukemic phase of cutaneous T cell lymphoma. J Invest Dermatol 2005, 124:651–661.
Talpur R, Jones DM, Alencar AJ, et al.: CD25 expression is correlated with histological grade and response to denileukin diftitox in cutaneous T-cell lymphoma. J Invest Dermatol 2006, 126:575–583.
Fontenot JD, Gavin MA, Rudensky AY: Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003, 4:330–336.
Karube K, Ohshima K, Tsuchiya T, et al.: Expression of FoxP3, a key molecule in CD4CD25 regulatory T cells, in adult T-cell leukaemia/lymphoma cells. Br J Haematol 2004, 126:81–84.
Walsh PT, Benoit BM, Wysocka M, et al.: A role for regulatory T cells in cutaneous T-cell lymphoma: induction of a CD4 + CD25 + Foxp3+ T-cell phenotype associated with HTLV-1 infection. J Invest Dermatol 2006, 126:690–692. One of two papers that explore the relationship between Treg cells and MF/SS, an emerging area of research. See [37].
Berger CL, Tigelaar R, Cohen J, et al.: Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells. Blood 2005, 105:1640–1647. One of two papers that explore the relationship between Treg cells and MF/SS, an emerging area of research. See [36].
Wong HK, Wilson AJ, Gibson HM, et al.: Increased expression of CTLA-4 in malignant T-cells from patients with mycosis fungoides—cutaneous T cell lymphoma. J Invest Dermatol 2006, 126:212–219.
Szabo SJ, Jacobson NG, Dighe AS, et al.: Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. Immunity 1995, 2:665–675.
Showe LC, Fox FE, Williams D, et al.: Depressed IL-12-mediated signal transduction in T cells from patients with Sezary syndrome is associated with the absence of IL-12 receptor beta 2 mRNA and highly reduced levels of STAT4. J Immunol 1999, 163:4073–4079.
Wysocka M, Zaki MH, French LE, et al.: Sezary syndrome patients demonstrate a defect in dendritic cell populations: effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines. Blood 2002, 100:3287–3294.
Kim EJ, Hess S, Richardson SK, et al.: Immunopathogenesis and therapy of cutaneous T cell lymphoma. J Clin Invest 2005, 115:798–812. This review summarizes the immunobiology of MF/SS and the rationale behind combination therapy.
Yamanaka K, Clark R, Dowgiert R, et al.: Expression of interleukin-18 and caspase-1 in cutaneous T-cell lymphoma. Clin Cancer Res 2006, 12:376–382.
Okamura H, Tsutsi H, Komatsu T, et al.: Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 1995, 378:88–91.
Yoshimoto T, Tsutsui H, Tominaga K, et al.: IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils. Proc Natl Acad Sci U S A 1999, 96:13962–13966.
Dalloul A, Laroche L, Bagot M, et al.: Interleukin-7 is a growth factor for Sezary lymphoma cells. J Clin Invest 1992, 90:1054–1060.
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, 107:2440–2445.
Yawalkar N, Ferenczi K, Jones DA, et al.: Profound loss of T-cell receptor repertoire complexity in cutaneous T-cell lymphoma. Blood 2003, 102:4059–4066. One of two papers that demonstrate that MF/SS profoundly decreased normal T-cell repertoire, which may contribute to the immunosuppression observed in these patients. See [49].
Yamanaka K, Yawalkar N, Jones DA, et al.: Decreased Tcell receptor excision circles in cutaneous T-cell lymphoma. Clin Cancer Res 2005, 11:5748–5755. One of two papers that demonstrate that MF/SS profoundly decreased normal T-cell repertoire, which may contribute to the immunosuppression observed in these patients. See [48*].
Rosato RR, Grant S: Histone deacetylase inhibitors: insights into mechanisms of lethality. Expert Opin Ther Targets 2005, 9:809–824.
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, 23:3886–3896.
Nagasawa T, Zhang Q, Raghunath PN, et al.: Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing. Leuk Res 2006, 30:303–312.
Sors A, Jean-Louis F, Pellet C, et al.: Down-regulating constitutive activation of the NF-kappaB canonical pathway overcomes the resistance of cutaneous T-cell lymphoma to apoptosis. Blood 2006, 107:2354–2363.
Querfeld C. Rosen ST, Kuzel TM, et al.: Long-term followup of patients with early-stage cutaneous T-cell lymphoma who achieved complete remission with psoralen plus UV-A monotherapy. Arch Dermatol 2005, 141:305–311.
Rupoli S, Goteri G, Pulini S, et al.: Long-term experience with low-dose interferon-alpha and PUVA in the management of early mycosis fungoides. Eur J Haematol 2005, 75:136–145.
Duvic M, Martin AG, Kim Y, et al.: Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol 2001, 137:581–593.
Budgin JB, Richardson SK, Newton SB, et al.: Biological effects of bexarotene in cutaneous T-cell lymphoma. Arch Dermatol 2005, 141:315–321.
Gorgun G, Foss F: Immunomodulatory effects of RXR rexinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox. Blood 2002, 100:1399–1403.
Foss F, Demierre MF, DiVenuti G: A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood 2005, 106:454–457.
Bouwhuis SA, Davis MD, el-Azhary RA, et al.: Bexarotene treatment of late-stage mycosis fungoides and Sezary syndrome: development of extracutaneous lymphoma in 6 patients. J Am Acad Dermatol 2005, 52:991–996.
McGinnis KS, Junkins-Hopkins JM, Crawford G, et al.: Low-dose oral bexarotene in combination with lowdose interferon alfa in the treatment of cutaneous T-cell lymphoma: clinical synergism and possible immunologic mechanisms. J Am Acad Dermatol 2004, 50:375–379.
Hino R, Shimauchi T, Tokura Y: Treatment with IFNgamma increases serum levels of Th1 chemokines and decreases those of Th2 chemokines in patients with mycosis fungoides. J Dermatol Sci 2005, 38:189–195.
Marchi E, Alinari L, Tani M, et al.: Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients. Cancer, 2005. 104(11): 2437–2441.
Molina A, Zain J, Arber DA, et al.: Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol 2005, 23:6163–6171. A retrospective review of eight patients treated with bone marrow/ stem cell transplantation, which is increasingly considered for MF/SS patients with refractory disease.
Zhang C, Richon V, Ni X, et al.: Selective induction of apoptosis by histone deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. J Invest Dermatol 2005, 125:1045–1052.
Olsen E, Kim YH, Kuzel T, et al.: Vorinostat (suberoylanilide hydroxamic acid, SAHA) is clinically active in advanced cutaneous T-cell lymphoma (CTCL): Results of a phase IIb trial [abstract]. Proc ASCO 2006 24:7500.
Salskov-Iversen M, Berger CL, Edelson RL: Rapid construction of a dendritic cell vaccine through physical perturbation and apoptotic malignant T cell loading. J Immune Based Ther Vaccines 2005, 3:4.
Lamberg SI, Bunn PA Jr: Proceedings of the Workshop on Cutaneous T-cell Lymphomas (mycosis fungoides and Sezary syndrome). Cancer Treat Rep 1979, 63:561–568.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, E.J., Lin, J., Hopkins, J.M.J. et al. Mycosis fungoides and sezary syndrome: An update. Curr Oncol Rep 8, 376–386 (2006). https://doi.org/10.1007/s11912-006-0061-1
Issue Date:
DOI: https://doi.org/10.1007/s11912-006-0061-1