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Mycosis Fungoides☆
Mycosis Fungoides☆ L Hansen, Creighton University School of Medicine, Omaha, NE, USA ã 2014 Elsevier Inc. All rights reserved.
Introduction Definition Classification Consequences Associated Disorders Etiology Epidemiology Pathophysiology Signs and Symptoms Standard Therapies Experimental Therapies Animal Models References
1 1 1 1 1 2 2 2 2 2 3 3 3
Introduction Mycosis fungoides is a form of cutaneous lymphoma in which the skin is infiltrated with neoplastic T cells. Mycosis fungoides often develops slowly over many years, often presenting with a generalized erythroderma, skin patches, or skin plaques. The skin patches and plaques can develop into ulcerating or fungating tumors. Mycosis fungoides can also spread extracutaneously. Mycosis fungoides does not affect the life expectancy of those with limited involvement of the skin in patches and plaques (Kim and Hoppe, 2000; Weedon, 1998). Generalized involvement of the skin in patch/plaque disease, tumor development, and extracutaneous disease results in increasingly shorter survival times (Connors et al., 2002; Kim and Hoppe, 2000).
Definition Mycosis fungoides is a form of cutaneous T-cell lymphoma in which neoplastic lymphocytes infiltrate the skin.
Classification Mycosis fungoides is the most common type of cutaneous T-cell lymphoma.
Consequences Mycosis fungoides most commonly presents as a generalized erythroderma, skin patches, or skin plaques, frequently with accompanying pruritus. The skin patches and plaques can develop into ulcerating or fungating tumors. Mycosis fungoides can spread to regional lymphatics and then to viscera. Mycosis fungoides has an overall 5 year survival of 68%, although survival varies depending on the stage of the disease (Kim et al., 2003). Although it is incurable, mycosis fungoides does not affect the life expectancy of those with limited involvement of the skin in patches and plaques (Kim and Hoppe, 2000; Weedon, 1998). Generalized involvement of the skin in patch/plaque disease, tumor development, and extracutaneous disease result in increasingly shorter survival times (Connors et al., 2002; Kim and Hoppe, 2000). Advanced disease (T3/T4) is associated with a 5 year survival rate of less than 50% (Kim et al., 2003).
Associated Disorders Sezary syndrome is an erythrodermic leukemic version of mycosis fungoides (Zackheim, 2003). ☆ Change History: August 2014. LA Hansen updated abstract, introduction, etiology, consequences, pathophysiology, standard therapies, experimental therapies, and references.
Reference Module in Biomedical Research
http://dx.doi.org/10.1016/B978-0-12-801238-3.05166-7
1
2
Mycosis Fungoides
Etiology While the precise etiology of mycosis fungoides is unknown, environmental chemicals or viruses might contribute to the development of this condition (Kim and Hoppe, 2000).
Epidemiology Mycosis fungoides is most commonly encountered in middle aged and elderly males. It is more common in African-American patients.
Pathophysiology Mycosis fungoides is characterized by the infiltration of mononuclear cells, characterized by a hyperconvoluted nuclear surface, in the papillary dermis and epidermis (Kim and Hoppe, 2000; Weedon, 1998). The lymphocytes are denser and more often atypical in plaques compared to patches. In tumors, the infiltrating cells are large and atypical with mitotic figures, and can extend throughout the dermis as well as into the subcutis (Weedon, 1998). Mycosis fungoides cells often retain CD4 immunoreactivity, frequently lose reactivity to other mature T-cell antigens, and sustain monoclonal rearrangements of the T-cell receptor gene (Connors et al., 2002; Kim and Hoppe, 2000). Histopathological analysis of enlarged lymph nodes associated with extracutaneous mycosis fungoides often reveals dermatopathic lymphadenitis and atypical lymphocytes (Kim and Hoppe, 2000).
Signs and Symptoms Mycosis fungoides most commonly presents as a generalized erythroderma, ill-defined skin patches, or well-demarcated red or violet plaques. Erythroderma is associated with intense pruritus. The skin patches and plaques appear most often over the trunk and extremities and are slightly scay, erythematous, and often pruritic. They can develop into ulcerating or fungating tumors that are red to violet in color with a shiny surface (Connors et al., 2002; Weedon, 1998).
Standard Therapies A variety of treatments, including chemotherapy, radiation therapy, corticosteroids, and phototherapy are employed for the treatment of mycosis fungoides. Most often the cutaneous forms of mycosis fungoides are treated topically. Those with refractory or extracutaneous disease may also receive systemic chemotherapy. Agent name
Discussion
Corticosteroids Phototherapy
Topical corticosteroids are very effective for the treatment of early stage mycosis fungoides (Connors et al., 2002). When administered together, psoralen and ultraviolet A irradiation (PUVA) inhibit DNA synthesis. Phototherapy is very effective for the treatment of early-stage mycosis fungoides (Connors et al., 2002; Kim and Hoppe, 2000). Topical nitrogen mustard (HN2) is an effective and FDA-approved treatment for cutaneous mycosis fungoides (Connors et al., 2002; Kim and Hoppe, 2000). Electron beam irradiation is used to deliver a total body, cutaneous treatment for patients with widespread patch/plaque or skin tumorous mycosis fungoides (Kim and Hoppe, 2000). Single agent systemic chemotherapy, which is typically used to treat refractory mycosis fungoides, is characterized by low response rates of short duration (Connors et al., 2002). Combination therapy involving both systemic chemotherapy and topical treatment results in high, but short-lived response rates (Connors et al., 2002; Kim and Hoppe, 2000). Topical treatment with the retinoid bexarotene, alone or in combination with other agents, is reportedly effective in the treatment of mycosis fungoides, particularly in early patch/plaque stages (Connors et al., 2002). Bexarotene. Extracorporeal photopheresis, which involves psoralen and ultraviolet A irradiation of leukapheresed mononuclear cells, is effective in the treatment of erythrodermic mycosis fungoides (Connors et al., 2002). Interferon and retinoids increase the response rate to this therapy (Connors et al., 2002). Immunotherapy together with alemtuzumab, a monoclonal antibody, has been found to induce some partial and complete responses as a treatment of T cell lymphoma (Lundin et al., 1998; Vonderheid et al., 2002). Alemtuzumab recognizes the CD52 antigen expressed on all lymphocytes. Topical imiquimod increases interferon-alpha and is an effective treatment for mycosis fungoides (reviewed in Fernandez-Guarino, 2013).
Nitrogen mustard (mechlorethamine) Electron beam irradiation Systemic chemotherapy
Bexarotene Extracorporeal photopheresis (ECP) Alemtuzumab
Imiquimod
Mycosis Fungoides
3
Experimental Therapies A variety of agents are being tested as treatments for refractory mycosis fungoides. Agent name 90Y-T101
Discussion 90Y-T101, a radioimmunoconjugate that targets CD5+ lymphocytes, has displayed some efficacy as a treatment of skin lymphomas (Connors et al., 2002).
Animal Models Although mycosis fungoides has been reported in the mouse (Lohmiller et al., 1999), there is no generally accepted animal model of this condition. The mouse C6VL thymoma model is used as a tool for developing T cell-targeted immunotherapy for the treatment of mycosis fungoides (Reddy et al., 2001).
References Connors JM, Hsi ED, and Foss FM (2002) Lymphoma of the skin. Hematology Am Soc Hematol Educ Program 263–282. Fernandez-Guarino M (2013) Emerging treatment options for early mycosis fungoides. Clinical, Cosmetic and Investigational Dermatology 6: 61–69. Kim YH and Hoppe RT (2000) Mycosis Fungoides and the Sezary syndrome. In: Bast RC Jr., Kufe DW, Pollock RE, Weichselbaum RR, Holland JF, Frei E III, and Gansler TS (eds.) Cancer medicine, 5th edn. Hamilton, ON: B.C. Decker, Inc. Kim YH, Liu HL, Mraz-Gernhard S, Varghese A, and Hoppe RT (2003) Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Archives of Dermatology 139(7): 857–866. Lohmiller JJ, Swing SP, Valli VE, and Li X (1999) Epidermotropic lymphoma (mycosis fungoides) in an ICR mouse. Contemporary Topics in Laboratory Animal Science 38(5): 47–49. Lundin J, Osterborg A, Brittinger G, Crowther D, Dombret H, Engert A, Epenetos A, Gisselbrecht C, Huhn D, Jaeger U, Thomas J, Marcus R, Nissen N, Poynton C, Rankin E, Stahel R, Uppenkamp M, Willemze R, and Mellstedt H (1998) CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin’s lymphomas: a phase II multicenter study. Journal of Clinical Oncology 16(10): 3257–3263. Reddy SA, Okada C, Wong C, Bahler D, and Levy R (2001) T cell antigen receptor vaccines for active therapy of T cell malignancies. Annals of the New York Academy of Sciences 941: 97–105. Vonderheid EC, Bernengo MG, Burg G, Duvic M, Heald P, Laroche L, Olsen E, Pittelkow M, Russell-Jones R, Takigawa M, and Willemze R (2002) Update of erythrodermic cutaneous T-cell lymphoma: Report of the international society for cutaneous lymphomas. Journal of the American Academy of Dermatology 1: 95–106. Weedon D (1998) Cutaneous infiltrates – Lymphoid and leukemic skin pathology. Scotland: Churchill Livingstone Edinburgh, pp. 897–929. Zackheim HS (2003) Treatment of mycosis fungoides/Sezary syndrome: The University of California, San Francisco (UCSF) approach. International Journal of Dermatology 42(1): 53–56.
Relevant Websites http://www.mffoundation.org/ – This website is maintained by the Mycosis Fungoides Foundation. It provides general information about the disease, its treatment, and meetings of interest to investigators in this area. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call¼bv.View.ShowSection&rid¼cmed – This site is an online version of Cancer Medicine. http://www.sidnet.org – This website is maintained by the Society of Investigative Dermatology. It provides information on research funding, scientific meetings and journals, and links to other sites related to skin diseases research. http://www.skincancer.org/ – This website is maintained by The Skin Cancer Foundation, an organization that funds research related to skin cancer. The site also provides general information about these disorders.
Introduction Definition Classification Consequences Associated Disorders Etiology Epidemiology Pathophysiology Signs and Symptoms Standard Therapies Experimental Therapies Animal Models References
1 1 1 1 1 2 2 2 2 2 3 3 3
Introduction Mycosis fungoides is a form of cutaneous lymphoma in which the skin is infiltrated with neoplastic T cells. Mycosis fungoides often develops slowly over many years, often presenting with a generalized erythroderma, skin patches, or skin plaques. The skin patches and plaques can develop into ulcerating or fungating tumors. Mycosis fungoides can also spread extracutaneously. Mycosis fungoides does not affect the life expectancy of those with limited involvement of the skin in patches and plaques (Kim and Hoppe, 2000; Weedon, 1998). Generalized involvement of the skin in patch/plaque disease, tumor development, and extracutaneous disease results in increasingly shorter survival times (Connors et al., 2002; Kim and Hoppe, 2000).
Definition Mycosis fungoides is a form of cutaneous T-cell lymphoma in which neoplastic lymphocytes infiltrate the skin.
Classification Mycosis fungoides is the most common type of cutaneous T-cell lymphoma.
Consequences Mycosis fungoides most commonly presents as a generalized erythroderma, skin patches, or skin plaques, frequently with accompanying pruritus. The skin patches and plaques can develop into ulcerating or fungating tumors. Mycosis fungoides can spread to regional lymphatics and then to viscera. Mycosis fungoides has an overall 5 year survival of 68%, although survival varies depending on the stage of the disease (Kim et al., 2003). Although it is incurable, mycosis fungoides does not affect the life expectancy of those with limited involvement of the skin in patches and plaques (Kim and Hoppe, 2000; Weedon, 1998). Generalized involvement of the skin in patch/plaque disease, tumor development, and extracutaneous disease result in increasingly shorter survival times (Connors et al., 2002; Kim and Hoppe, 2000). Advanced disease (T3/T4) is associated with a 5 year survival rate of less than 50% (Kim et al., 2003).
Associated Disorders Sezary syndrome is an erythrodermic leukemic version of mycosis fungoides (Zackheim, 2003). ☆ Change History: August 2014. LA Hansen updated abstract, introduction, etiology, consequences, pathophysiology, standard therapies, experimental therapies, and references.
Reference Module in Biomedical Research
http://dx.doi.org/10.1016/B978-0-12-801238-3.05166-7
1
2
Mycosis Fungoides
Etiology While the precise etiology of mycosis fungoides is unknown, environmental chemicals or viruses might contribute to the development of this condition (Kim and Hoppe, 2000).
Epidemiology Mycosis fungoides is most commonly encountered in middle aged and elderly males. It is more common in African-American patients.
Pathophysiology Mycosis fungoides is characterized by the infiltration of mononuclear cells, characterized by a hyperconvoluted nuclear surface, in the papillary dermis and epidermis (Kim and Hoppe, 2000; Weedon, 1998). The lymphocytes are denser and more often atypical in plaques compared to patches. In tumors, the infiltrating cells are large and atypical with mitotic figures, and can extend throughout the dermis as well as into the subcutis (Weedon, 1998). Mycosis fungoides cells often retain CD4 immunoreactivity, frequently lose reactivity to other mature T-cell antigens, and sustain monoclonal rearrangements of the T-cell receptor gene (Connors et al., 2002; Kim and Hoppe, 2000). Histopathological analysis of enlarged lymph nodes associated with extracutaneous mycosis fungoides often reveals dermatopathic lymphadenitis and atypical lymphocytes (Kim and Hoppe, 2000).
Signs and Symptoms Mycosis fungoides most commonly presents as a generalized erythroderma, ill-defined skin patches, or well-demarcated red or violet plaques. Erythroderma is associated with intense pruritus. The skin patches and plaques appear most often over the trunk and extremities and are slightly scay, erythematous, and often pruritic. They can develop into ulcerating or fungating tumors that are red to violet in color with a shiny surface (Connors et al., 2002; Weedon, 1998).
Standard Therapies A variety of treatments, including chemotherapy, radiation therapy, corticosteroids, and phototherapy are employed for the treatment of mycosis fungoides. Most often the cutaneous forms of mycosis fungoides are treated topically. Those with refractory or extracutaneous disease may also receive systemic chemotherapy. Agent name
Discussion
Corticosteroids Phototherapy
Topical corticosteroids are very effective for the treatment of early stage mycosis fungoides (Connors et al., 2002). When administered together, psoralen and ultraviolet A irradiation (PUVA) inhibit DNA synthesis. Phototherapy is very effective for the treatment of early-stage mycosis fungoides (Connors et al., 2002; Kim and Hoppe, 2000). Topical nitrogen mustard (HN2) is an effective and FDA-approved treatment for cutaneous mycosis fungoides (Connors et al., 2002; Kim and Hoppe, 2000). Electron beam irradiation is used to deliver a total body, cutaneous treatment for patients with widespread patch/plaque or skin tumorous mycosis fungoides (Kim and Hoppe, 2000). Single agent systemic chemotherapy, which is typically used to treat refractory mycosis fungoides, is characterized by low response rates of short duration (Connors et al., 2002). Combination therapy involving both systemic chemotherapy and topical treatment results in high, but short-lived response rates (Connors et al., 2002; Kim and Hoppe, 2000). Topical treatment with the retinoid bexarotene, alone or in combination with other agents, is reportedly effective in the treatment of mycosis fungoides, particularly in early patch/plaque stages (Connors et al., 2002). Bexarotene. Extracorporeal photopheresis, which involves psoralen and ultraviolet A irradiation of leukapheresed mononuclear cells, is effective in the treatment of erythrodermic mycosis fungoides (Connors et al., 2002). Interferon and retinoids increase the response rate to this therapy (Connors et al., 2002). Immunotherapy together with alemtuzumab, a monoclonal antibody, has been found to induce some partial and complete responses as a treatment of T cell lymphoma (Lundin et al., 1998; Vonderheid et al., 2002). Alemtuzumab recognizes the CD52 antigen expressed on all lymphocytes. Topical imiquimod increases interferon-alpha and is an effective treatment for mycosis fungoides (reviewed in Fernandez-Guarino, 2013).
Nitrogen mustard (mechlorethamine) Electron beam irradiation Systemic chemotherapy
Bexarotene Extracorporeal photopheresis (ECP) Alemtuzumab
Imiquimod
Mycosis Fungoides
3
Experimental Therapies A variety of agents are being tested as treatments for refractory mycosis fungoides. Agent name 90Y-T101
Discussion 90Y-T101, a radioimmunoconjugate that targets CD5+ lymphocytes, has displayed some efficacy as a treatment of skin lymphomas (Connors et al., 2002).
Animal Models Although mycosis fungoides has been reported in the mouse (Lohmiller et al., 1999), there is no generally accepted animal model of this condition. The mouse C6VL thymoma model is used as a tool for developing T cell-targeted immunotherapy for the treatment of mycosis fungoides (Reddy et al., 2001).
References Connors JM, Hsi ED, and Foss FM (2002) Lymphoma of the skin. Hematology Am Soc Hematol Educ Program 263–282. Fernandez-Guarino M (2013) Emerging treatment options for early mycosis fungoides. Clinical, Cosmetic and Investigational Dermatology 6: 61–69. Kim YH and Hoppe RT (2000) Mycosis Fungoides and the Sezary syndrome. In: Bast RC Jr., Kufe DW, Pollock RE, Weichselbaum RR, Holland JF, Frei E III, and Gansler TS (eds.) Cancer medicine, 5th edn. Hamilton, ON: B.C. Decker, Inc. Kim YH, Liu HL, Mraz-Gernhard S, Varghese A, and Hoppe RT (2003) Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Archives of Dermatology 139(7): 857–866. Lohmiller JJ, Swing SP, Valli VE, and Li X (1999) Epidermotropic lymphoma (mycosis fungoides) in an ICR mouse. Contemporary Topics in Laboratory Animal Science 38(5): 47–49. Lundin J, Osterborg A, Brittinger G, Crowther D, Dombret H, Engert A, Epenetos A, Gisselbrecht C, Huhn D, Jaeger U, Thomas J, Marcus R, Nissen N, Poynton C, Rankin E, Stahel R, Uppenkamp M, Willemze R, and Mellstedt H (1998) CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin’s lymphomas: a phase II multicenter study. Journal of Clinical Oncology 16(10): 3257–3263. Reddy SA, Okada C, Wong C, Bahler D, and Levy R (2001) T cell antigen receptor vaccines for active therapy of T cell malignancies. Annals of the New York Academy of Sciences 941: 97–105. Vonderheid EC, Bernengo MG, Burg G, Duvic M, Heald P, Laroche L, Olsen E, Pittelkow M, Russell-Jones R, Takigawa M, and Willemze R (2002) Update of erythrodermic cutaneous T-cell lymphoma: Report of the international society for cutaneous lymphomas. Journal of the American Academy of Dermatology 1: 95–106. Weedon D (1998) Cutaneous infiltrates – Lymphoid and leukemic skin pathology. Scotland: Churchill Livingstone Edinburgh, pp. 897–929. Zackheim HS (2003) Treatment of mycosis fungoides/Sezary syndrome: The University of California, San Francisco (UCSF) approach. International Journal of Dermatology 42(1): 53–56.
Relevant Websites http://www.mffoundation.org/ – This website is maintained by the Mycosis Fungoides Foundation. It provides general information about the disease, its treatment, and meetings of interest to investigators in this area. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call¼bv.View.ShowSection&rid¼cmed – This site is an online version of Cancer Medicine. http://www.sidnet.org – This website is maintained by the Society of Investigative Dermatology. It provides information on research funding, scientific meetings and journals, and links to other sites related to skin diseases research. http://www.skincancer.org/ – This website is maintained by The Skin Cancer Foundation, an organization that funds research related to skin cancer. The site also provides general information about these disorders.