Cutaneous T-cell Lymphoma

https://doi.org/10.1016/j.hoc.2008.07.014Get rights and content

Cutaneous T-cell lymphoma comprises a heterogeneous group of lymphoproliferative disorders characterized by clonal expansions of mature, post-thymic T cells that infiltrate the skin. This article discusses the staging, prognosis, and treatment of mycosis fungoides and Sézary syndrome.

Section snippets

Staging and prognosis of mycosis fungoides/SÉzary syndrome

Staging systems for MF have been developed based on clinical features of skin involvement as well as infiltration of lymph nodes and viscera. The most commonly used staging system for MF/SS is based on a tumor (T)-node (N)-metastasis (M)-blood (B) classification (Table 2).15 Skin involvement is defined by the type and extent of lesion. T1 and T2 disease are patches or plaques involving less than or more than 10% of the skin surface, respectively. T3 disease is the presence of at least one

Treatment

The diagnosis and initial treatment of CTCL usually takes place in the dermatologist's office. Because of the panoply of therapies available and the chronic progressive clinical course in most patients, management of the disease ideally involves a multidisciplinary team incorporating expertise in skin-directed therapy, radiation therapy, photopheresis, infusional and oral anti-neoplastic therapies, and combined-modality treatment. The therapeutic decision should incorporate the disease stage,

Summary

Although a number of treatments have shown efficacy in the symptomatic management of CTCL, cure remains elusive for most patients. The overall goals of treatment for most patients are to provide palliation for symptoms of pruritus and compromised skin integument and to prevent further immunosuppression. Given the low overall incidence of CTCL, the disease chronicity, the morbidity, and the lack of effective cure, enrollment in clinical trials should be encouraged so that more effective agents

References (97)

  • E.C. Vonderheid et al.

    Long-term efficacy, curative potential, and carcinogenicity of topical mechlorethamine chemotherapy in cutaneous T cell lymphoma

    J Am Acad Dermatol

    (1989)
  • P. Heald et al.

    Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial

    J Am Acad Dermatol

    (2003)
  • C.L. Berger et al.

    The growth of cutaneous T-cell lymphoma is stimulated by immature dendritic cells

    Blood

    (2002)
  • R.C. Gathers et al.

    Narrowband UVB phototherapy for early-stage mycosis fungoides

    J Am Acad Dermatol

    (2002)
  • G. Jones et al.

    Combined treatment with oral etretinate and electron beam therapy in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)

    J Am Acad Dermatol

    (1992)
  • G. Jones et al.

    Total skin electron beam radiotherapy for patients who have mycosis fungoides

    Hematol Oncol Clin North Am

    (2003)
  • C.L. Berger et al.

    The immune response to class I-associated tumor-specific cutaneous T-cell lymphoma antigens

    J Invest Dermatol

    (1996)
  • M. Girardi et al.

    Selective immunotherapy through extracorporeal photochemotherapy: yesterday, today, and tomorrow

    Hematol Oncol Clin North Am

    (2003)
  • L.D. Wilson et al.

    Systemic chemotherapy and extracorporeal photochemotherapy for T3 and T4 cutaneous T-cell lymphoma patients who have achieved a complete response to total skin electron beam therapy

    Int J Radiat Oncol Biol Phys

    (1995)
  • G. Saed et al.

    Mycosis fungoides exhibits a Th1-type cell-mediated cytokine profile whereas Sezary syndrome expresses a Th2-type profile

    J Invest Dermatol

    (1994)
  • E.A. Olsen et al.

    Interferon alfa-2a in the treatment of cutaneous T cell lymphoma

    J Am Acad Dermatol

    (1989)
  • E. Dippel et al.

    Extracorporeal photopheresis and interferon-alpha in advanced cutaneous T-cell lymphoma

    Lancet

    (1997)
  • K.M. Chin et al.

    Biologic correlates of response and survival in patients with cutaneous T-cell lymphoma treated with denileukin diftitox

    Clin Lymphoma Myeloma

    (2006)
  • R. Talpur et al.

    CD25 expression is correlated with histological grade and response to denileukin diftitox in cutaneous T-cell lymphoma

    J Invest Dermatol

    (2006)
  • G. Gorgun et al.

    Immunomodulatory effects of RXR retinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox

    Blood

    (2002)
  • F. Foss et al.

    A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma

    Blood

    (2005)
  • J.M. McGregor et al.

    Spectrum of p53 gene mutations suggests a possible role for ultraviolet radiation in the pathogenesis of advanced cutaneous lymphomas

    J Invest Dermatol

    (1999)
  • J. Shin et al.

    Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome

    Blood

    (2007)
  • J.J. Scarisbrick et al.

    Microsatellite instability is associated with hypermethylation of the hMLH1 gene and reduced gene expression in mycosis fungoides

    J Invest Dermatol

    (2003)
  • J.J. Scarisbrick et al.

    Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and Sezary syndrome

    J Invest Dermatol

    (2002)
  • R.L. Piekarz et al.

    Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report

    Blood

    (2001)
  • C. Zhang 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)
  • M. Duvic et al.

    Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL)

    Blood

    (2007)
  • V.L. Schramm

    Development of transition state analogues of purine nucleoside phosphorylase as anti-T-cell agents

    Biochim Biophys Acta

    (2002)
  • M. Duvic et al.

    Response to oral forodesine in refractory cutaneous t-cell lymphoma: interim results of a phase I/II study

    ASH Annual Meeting Abstracts

    (2007)
  • S.J. Whittaker et al.

    Efficacy and tolerability of currently available therapies for the mycosis fungoides and Sezary syndrome variants of cutaneous T-cell lymphoma

    Cancer Treat Rev

    (2007)
  • J. Lundin et al.

    Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome

    Blood

    (2003)
  • M. Duvic et al.

    Phase II evaluation of gemcitabine monotherapy for cutaneous T-cell lymphoma

    Clin Lymphoma Myeloma

    (2006)
  • M. Girardi et al.

    The pathogenesis of mycosis fungoides

    N Engl J Med

    (2004)
  • V.D. Criscione et al.

    Incidence of cutaneous T-cell lymphoma in the United States, 1973–2002

    Arch Dermatol

    (2007)
  • G. Burg et al.

    WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects

    J Cutan Pathol

    (2005)
  • A.S. Whittemore et al.

    Mycosis fungoides in relation to environmental exposures and immune response: a case-control study

    J Natl Cancer Inst

    (1989)
  • E. Tuyp et al.

    A case-control study of possible causative factors in mycosis fungoides

    Arch Dermatol

    (1987)
  • J.T. Abrams et al.

    Association between Sezary T cell-activating factor, Chlamydia pneumoniae, and cutaneous T cell lymphoma

    Ann N Y Acad Sci

    (2001)
  • M.J. Rossler et al.

    No evidence of skin infection with Chlamydia pneumoniae in patients with cutaneous T cell lymphoma

    Clin Microbiol Infect

    (2003)
  • B.A. Pancake et al.

    The difficulty of detecting HTLV-1 proviral sequences in patients with mycosis fungoides

    J Acquir Immune Defic Syndr Hum Retrovirol

    (1996)
  • D. Zucker-Franklin et al.

    Detection of human T-lymphotropic virus-like particles in cultures of peripheral blood lymphocytes from patients with mycosis fungoides

    Proc Natl Acad Sci U S A

    (1991)
  • P.A.J. Bunn et al.

    Report of the Committee on Staging and Classification of Cutaneous T-cell Lymphomas

    Cancer Treat Rep

    (1979)
  • Cited by (30)

    • Cutaneous T Cell Lymphoma: A Difficult Diagnosis Demystified

      2019, Dermatologic Clinics
      Citation Excerpt :

      The combination of methotrexate with this treatment modality increases the overall efficacy by inhibiting the inactivation of the FAS promoter.90 Allogeneic stem cell transplantation has been shown to be highly efficacious for the treatment of CTCL, providing a sustained immune-mediated graft-versus-lymphoma effect.11 Although morbidity and mortality after this therapy is relatively high, possibly given the advanced age of CTCL patients and the immunosuppression typical of the disease and its treatment, stem cell transplantation can provide long-term remission in a subset of patients.91

    • Romidepsin for the treatment of relapsed/refractory cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome): Use in a community setting

      2016, Critical Reviews in Oncology/Hematology
      Citation Excerpt :

      Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphomas (NHL) in which malignant, mature, post-thymic T cells initially arise in the skin (Lansigan et al., 2008).

    • Sézary syndrome: A study of 176 patients at Mayo Clinic

      2012, Journal of the American Academy of Dermatology
      Citation Excerpt :

      Another prognostic factor was the presence of TCR gene rearrangements in skin and blood. In the literature, the prognostic factors associated with worse outcomes include advanced age, enlargement of peripheral lymph nodes, increased leukemic burden in the blood, increased LDH levels, low percentage of CD8+ cells in lymph nodes, and large-cell transformation.2,3,8,10,24,35 Because of a lack of data on the disease course of many patients, we were not able to assess for certain prognostic factors, such as large-cell transformation.

    • Pocket Guide to Diagnostic Hematopathology

      2019, Pocket Guide to Diagnostic Hematopathology
    View all citing articles on Scopus
    View full text