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1
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Singh GK, Das P, Srivastava S, Singh K, Singh V, Barui S, Mulajkar D, Dubey IP. Mycosis fungoides and Sezary syndrome - Simplifying the approach for dermatologists. Part 2: Evaluation, staging, prognosis and treatment. Indian J Dermatol Venereol Leprol 2025; 91:180-187. [PMID: 39912186 DOI: 10.25259/ijdvl_754_2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 07/19/2024] [Indexed: 02/07/2025]
Abstract
Cutaneous T-cell lymphoma is a heterogeneous group of T-cell neoplasms, of which mycosis fungoides and Sezary syndrome are the most common. The prognosis depends on the stage of the disease. The early stage follows a protracted course with a five-year disease-specific survival of greater than 95% and is treated with skin-directed topical therapies, phototherapy, and oral drugs like methotrexate. Advanced disease has a five-year overall survival of less than 25% and requires management by systemic chemotherapeutic agents. This review article is the second part out of the two covering the staging, prognosis, and treatment from a dermatologist's perspective.
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Affiliation(s)
- Gautam Kumar Singh
- Department of Dermatology, Bharati Vidyapeeth's Medical College, Pune, India
| | - Pankaj Das
- Department of Dermatology, Armed Forces Medical College, Pune, India
| | - Shailendra Srivastava
- Department of Dermatology, Base Hospital Delhi Cantonment and Army College of Medical Sciences, Delhi Cantt, India
| | - Kanwaljeet Singh
- Department of Pathology, Army Hospital, Research and Referral, Kolkata, India
| | - Vikram Singh
- Department of Pathology, Armed Forces Medical College, Pune, India
| | - Sanghita Barui
- Department of Pathology, Base Hospital, Delhi Cantonment and Army College of Medical Sciences, Delhi Cantt, India
| | - Deepak Mulajkar
- Department of Medical Oncology, Army Hospital Research and Referral, Delhi, India
| | - Indra Prakash Dubey
- Department of Nuclear Imaging, Army Hospital Research and Referral, Delhi, India
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2
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Huang TC, Chang CH, Hsiao PF, Hsu CK, Lin CY, Wu CS, Yeh SP, Tsai TF. Cutaneous T-cell lymphoma: Consensus on diagnosis and management in Taiwan. J Formos Med Assoc 2024:S0929-6646(24)00517-5. [PMID: 39496538 DOI: 10.1016/j.jfma.2024.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/17/2024] [Accepted: 11/01/2024] [Indexed: 11/06/2024] Open
Abstract
Cutaneous T cell lymphomas (CTCLs), with mycosis fungoides (MF) and Sézary syndrome (SS) as the classic types, are the commonest group of primary cutaneous lymphomas. The diverse clinical manifestation and non-specific histologic findings of early lesions in CTCLs render diagnosis challenging. Treatment modalities also vary and include topical and oral medications, chemotherapy, phototherapy, and radiation therapies. Local dermatological, hemato-oncologic and radiotherapeutical experts in Taiwan convened meetings in 2023 to review and discuss the latest evidence and updates regarding diagnosis and management of CTCLs. A consensus was developed with the aim to raise awareness and understanding, provide practical guidance for early diagnosis and appropriate management, and ultimately optimize care to maximize benefits of patients.
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Affiliation(s)
- Tai-Chung Huang
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chung-Hsing Chang
- Skin Institute, Department of Dermatology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Institute of Medical Sciences, College of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Pa-Fan Hsiao
- Department of Dermatology, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
| | - Chao-Kai Hsu
- Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chien-Yio Lin
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou and Taipei, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chien-Shan Wu
- Department of Dermatology, Pingtung Veterans General Hospital, Pingtung, Taiwan
| | - Su-Peng Yeh
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; China Medical University, Taichung, Taiwan
| | - Tsen-Fang Tsai
- Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
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3
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Fay CJ, Awh KC, LeBoeuf NR, Larocca CA. Harnessing the immune system in the treatment of cutaneous T cell lymphomas. Front Oncol 2023; 12:1071171. [PMID: 36713518 PMCID: PMC9878398 DOI: 10.3389/fonc.2022.1071171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 12/01/2022] [Indexed: 01/15/2023] Open
Abstract
Cutaneous T cell lymphomas are a rare subset of non-Hodgkin's lymphomas with predilection for the skin with immunosuppressive effects that drive morbidity and mortality. We are now appreciating that suppression of the immune system is an important step in the progression of disease. It should come as no surprise that therapies historically and currently being used to treat these cancers have immune modulating functions that impact disease outcomes. By understanding the immune effects of our therapies, we may better develop new agents that target the immune system and improve combinatorial treatment strategies to limit morbidity and mortality of these cancers. The immune modulating effect of therapeutic drugs in use and under development for cutaneous T cell lymphomas will be reviewed.
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4
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Crimp C, Gangal A, Tarabadkar ES, Shinohara MM. Mechlorethamine Hydrochloride Gel in the Treatment of Mycosis Fungoides–Type Cutaneous T-Cell Lymphoma (MF-CTCL): A Focus on Patient Selection and Special Considerations. Cancer Manag Res 2022; 14:3271-3279. [DOI: 10.2147/cmar.s351420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 11/08/2022] [Indexed: 11/23/2022] Open
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Increased Chlormethine-Induced DNA Double-Stranded Breaks in Malignant T Cells from Mycosis Fungoides Skin Lesions. JID INNOVATIONS 2022; 2:100069. [PMID: 34977846 PMCID: PMC8683611 DOI: 10.1016/j.xjidi.2021.100069] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 01/16/2023] Open
Abstract
Mycosis fungoides (MF) is a type of cutaneous T-cell lymphoma. Chlormethine (CL) is recommended as first-line therapy for MF, with a major purpose to kill tumor cells through DNA alkylation. To study the extent of treatment susceptibility and tumor specificity, we investigated the gene expression of different DNA repair pathways, DNA double-stranded breaks, and tumor cell proliferation of clonal TCR Vβ+ tumor cell populations in cutaneous T-cell lymphoma skin cells on direct exposure to CL. Healthy human T cells were less susceptible to CL exposure than two T-lymphoma cell lines, resulting in higher proportions of viable cells. Interestingly, in T cells from MF lesions, we observed a downregulation of several important DNA repair pathways, even complete silencing of RAD51AP1, FANC1, and BRCA2 involved in homologous recombination repair. In the presence of CL, the double-stranded DNA breaks in malignant MF skin T cells increased significantly as well as the expression of the apoptotic gene CASP3. These data point toward an important effect of targeting CL on MF skin tumor T cells, which support CL use as an early cutaneous lymphoma treatment and can be of synergistic use, especially beneficial in the setting of combination skin-directed therapies for cutaneous T-cell lymphoma.
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Brumfiel CM, Patel MH, Puri P, Besch-Stokes J, Lester S, Rule WG, Khera N, Sluzevich JC, DiCaudo DJ, Comfere N, Bennani NN, Rosenthal AC, Pittelkow MR, Mangold AR. How to Sequence Therapies in Mycosis Fungoides. Curr Treat Options Oncol 2021; 22:101. [PMID: 34570278 DOI: 10.1007/s11864-021-00899-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/13/2021] [Indexed: 12/11/2022]
Abstract
OPINION STATEMENT Choice of therapy in mycosis fungoides is based on both patient- and lymphoma-specific factors, such as disease characteristics, comorbidities, symptoms and effect on quality of life, potential associated toxicities of therapy, response and tolerance to prior lines of therapy, and convenience and practicality. Generally, we sequence therapies from least toxic, targeted, nonimmunosuppressive to more toxic, immunosuppressive and from single agent to multiple agents, as necessary. If more toxic, immunosuppressive agents are required to alleviate disease burden or symptoms, we generally use them just long enough to control the disease, then transition to a maintenance regimen with less toxic, less immunosuppressive agents.
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Affiliation(s)
- Caitlin M Brumfiel
- Department of Dermatology, Mayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ, 85259, USA
| | - Meera H Patel
- Department of Dermatology, Mayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ, 85259, USA
| | - Pranav Puri
- Department of Dermatology, Mayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ, 85259, USA
| | - Jake Besch-Stokes
- Department of Dermatology, Mayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ, 85259, USA
| | - Scott Lester
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA
| | - William G Rule
- Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA
| | - Nandita Khera
- Division of Hematology Oncology, Mayo Clinic, Phoenix, AZ, USA
| | | | - David J DiCaudo
- Department of Dermatology, Mayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ, 85259, USA
| | - Nneka Comfere
- Department of Dermatology, Mayo Clinic, Rochester, MN, USA
| | - N Nora Bennani
- Division of Hematology Oncology, Mayo Clinic, Rochester, MN, USA
| | | | - Mark R Pittelkow
- Department of Dermatology, Mayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ, 85259, USA
| | - Aaron R Mangold
- Department of Dermatology, Mayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ, 85259, USA.
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Prag Naveh H, Amitay-Laish I, Zidan O, Leshem YA, Sherman S, Noyman Y, Taieb J, Didkovsky E, Hodak E. Real-life experience with chlormethine gel for early-stage mycosis fungoides with emphasis on types and management of cutaneous side-effects . J DERMATOL TREAT 2021;33:2364-2370. [PMID: 34427536 DOI: 10.1080/09546634.2021.1967266] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND Real-life efficacy data on the recently approved once daily application of chlormethine gel (CG) for mycosis fungoides (MF) is limited, and detailed characterization of the side effects and their management are strikingly sparse. OBJECTIVE To evaluate the efficacy and particularly the side effect profile of CG in early-stage MF patients in a real-life setting. METHODS We performed a single-center retrospective analysis of 66 early-stage MF adult patients treated with CG in 2016-2019. RESULTS Treatment with a once-daily application (52%), or at lower frequencies (48%), in some with topical corticosteroids (TCS) (40%), resulted in an overall response rate of 50%, with no significant difference between stage IA and IB. Cutaneous side effects (56%) included irritant or allergic contact dermatitis (36%, mostly mild/moderate and manageable by reducing application frequency and/or adding TCS or interrupting treatment), unmasking effect (9%), hyperpigmentation (14%), and pruritus (9%). Withdrawal due to side effects occurred in 19.6% of patients (15% for contact dermatitis). CONCLUSION In real-life management, flexible regimens of CG sometimes with TCS, show efficacy in early-stage MF and may reduce the rate of contact dermatitis, the main treatment-limiting side effect. Practical recommendations with emphasis of the types, time of appearance, and management of side effects are provided.
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Affiliation(s)
- Hadas Prag Naveh
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Iris Amitay-Laish
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Omri Zidan
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Yael A Leshem
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shany Sherman
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yehonatan Noyman
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Joseph Taieb
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Elena Didkovsky
- Institute of Pathology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Emmilia Hodak
- Division of Dermatology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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8
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Querfeld C, Kim YH, Guitart J, Scarisbrick J, Quaglino P. Use of chlormethine 0.04% gel for mycosis fungoides after treatment with topical chlormethine 0.02% gel: A phase 2 extension study. J Am Acad Dermatol 2021; 87:209-211. [PMID: 34333079 DOI: 10.1016/j.jaad.2021.06.896] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 06/09/2021] [Accepted: 06/13/2021] [Indexed: 11/19/2022]
Affiliation(s)
| | - Youn H Kim
- Department of Dermatology, Stanford Cancer Center, Stanford, California
| | - Joan Guitart
- Northwestern University Feinberg School of Medicine, Chicago, Illinois
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9
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Ohtsuka M, Hamada T, Miyagaki T, Shimauchi T, Yonekura K, Kiyohara E, Fujita H, Izutsu K, Okuma K, Kawai K, Koga H, Sugaya M. Outlines of the Japanese guidelines for the management of primary cutaneous lymphomas 2020. J Dermatol 2020; 48:e49-e71. [PMID: 33245165 DOI: 10.1111/1346-8138.15707] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 10/31/2020] [Indexed: 01/06/2023]
Abstract
Since the publication of the Japanese "Guidelines for the management of cutaneous lymphomas" in 2011, the World Health Organization (WHO) classification of hematolymphoid neoplasms and the WHO-European Organisation for Research and Treatment of Cancer classification for primary cutaneous lymphomas were updated and a number of novel systemic drugs for cutaneous T-cell lymphoma had been approved in Japan. In 2020, we revised the Japanese guidelines for the management of cutaneous lymphomas with consideration of the recent advances in the understanding of the pathophysiology and classification of cutaneous lymphomas together with the update of treatment strategies reflecting the advent of novel drugs. In addition to a brief explanation of epidemiology, diagnosis, staging system, prognosis and management of each subtype of cutaneous lymphomas, the recommendations for nine clinical questions regarding treatment options that can vary even among experts are also described. A systematic review process and determination of recommendations in answer to each clinical question have been performed in accordance with the Grading of Recommendations, Assessment, Development and Evaluation scheme by a multidisciplinary expert panel consisting of dermatologists, a hematologist and a radiation oncologist. In this article, we present the outlines of the revised Japanese "Guidelines for the management of cutaneous lymphomas".
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Affiliation(s)
- Mikio Ohtsuka
- Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Toshihisa Hamada
- Department of Dermatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Tomomitsu Miyagaki
- Department of Dermatology, St Marianna University School of Medicine, Kawasaki, Japan
| | - Takatoshi Shimauchi
- Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Kentaro Yonekura
- Department of Dermatology, Imamura General Hospital, Kagoshima, Japan
| | - Eiji Kiyohara
- Department of Dermatology, Osaka University School of Medicine, Suita, Japan
| | - Hideki Fujita
- Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Koji Izutsu
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Kae Okuma
- Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuhiro Kawai
- Department of Dermatology, Kido Hospital, Niigata, Japan
| | - Hiroshi Koga
- Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Makoto Sugaya
- Department of Dermatology, International University of Health and Welfare, Narita, Japan
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10
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Tarabadkar ES, Shinohara MM. Skin Directed Therapy in Cutaneous T-Cell Lymphoma. Front Oncol 2019; 9:260. [PMID: 31032224 PMCID: PMC6470180 DOI: 10.3389/fonc.2019.00260] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Accepted: 03/22/2019] [Indexed: 11/16/2022] Open
Abstract
Skin directed therapies (SDTs) serve important roles in the treatment of early stage cutaneous T-cell lymphoma (CTCL)/mycosis fungoides (MF), as well as managing symptoms and improving quality of life of all stages. There are now numerous options for topical therapies that demonstrate high response rates, particularly in early/limited MF. Phototherapy retains an important role in treating MF, with increasing data supporting efficacy and long-term safety of both UVB and PUVA as well as some newer/targeted methodologies. Radiation therapy, including localized radiation and total skin electron beam therapy, continues to be a cornerstone of therapy for all stages of MF.
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Affiliation(s)
- Erica S Tarabadkar
- Division of Dermatology, University of Washington, Seattle, WA, United States
| | - Michi M Shinohara
- Division of Dermatology, University of Washington, Seattle, WA, United States
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11
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Tomczyk MD, Walczak KZ. l,8-Naphthalimide based DNA intercalators and anticancer agents. A systematic review from 2007 to 2017. Eur J Med Chem 2018; 159:393-422. [PMID: 30312931 DOI: 10.1016/j.ejmech.2018.09.055] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 09/17/2018] [Accepted: 09/20/2018] [Indexed: 11/28/2022]
Abstract
In this review, we describe a detailed investigation about the structural variations and relative activity of 1,8-naphthalimide based intercalators and anticancer agents. The 1,8-naphthalimides binds to the DNA via intercalation, and exert their antitumor activities through Topoisomerase I/II inhibition, photoinduced DNA damage or related mechanism. Here, our discussion focused on works published over the last ten years (2007-2017) related to therapeutic applications, in the order of cancer treatment followed by other properties of 1,8-naphthalimides. In preparing for this review, we considered that several seminal reviews have appeared over the last fifteen years and focused on closely related subjects, however, none of them is exhaustive.
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Affiliation(s)
- Mateusz D Tomczyk
- Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100, Gliwice, Poland
| | - Krzysztof Z Walczak
- Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100, Gliwice, Poland.
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12
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van Santen S, Vermeer MH, Willemze R. Classification and recommended treatment options for folliculotropic mycosis fungoides. Expert Opin Orphan Drugs 2017. [DOI: 10.1080/21678707.2018.1406796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Suzanne van Santen
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Maarten H. Vermeer
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Rein Willemze
- Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
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13
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Melasma treatment: A novel approach using a topical agent that contains an anti-estrogen and a vascular endothelial growth factor inhibitor. Med Hypotheses 2017; 101:1-5. [DOI: 10.1016/j.mehy.2017.01.020] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 01/07/2017] [Accepted: 01/21/2017] [Indexed: 12/17/2022]
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14
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Aberrant microRNA expression in tumor mycosis fungoides. Tumour Biol 2016; 37:14667-14675. [DOI: 10.1007/s13277-016-5325-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 09/06/2016] [Indexed: 01/12/2023] Open
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15
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16
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Hu SCS. Mycosis fungoides and Sézary syndrome: Role of chemokines and chemokine receptors. World J Dermatol 2015; 4:69-79. [DOI: 10.5314/wjd.v4.i2.69] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Revised: 03/16/2015] [Accepted: 04/09/2015] [Indexed: 02/06/2023] Open
Abstract
Mycosis fungoides is the most common form of cutaneous T-cell lymphoma (CTCL), and is characterized by a clonal expansion of malignant CD4+ T lymphocytes with skin-homing properties. Clinically and pathologically, mycosis fungoides can be categorized into patch, plaque and tumor stages. The clinical course of mycosis fungoides is usually chronic and indolent, but a proportion of patients may develop progressive disease with peripheral blood, lymph node and visceral organ involvement. Sézary syndrome is an aggressive leukemic form of CTCL characterized by a clonal population of malignant T cells in the peripheral blood. Various forms of skin-directed and systemic treatments are available for mycosis fungoides and Sézary syndrome. However, current treatments are generally not curative, and can only control the disease. Currently, the etiology and pathogenesis of mycosis fungoides and Sézary syndrome are not well defined. Proposed mechanisms include chronic antigenic stimulation by infectious agents, expression of specific adhesion molecules, altered cytokine production, mutations of oncogenes and tumor suppressor genes, and avoidance of apoptosis. In recent years, a number of chemokine receptors and their corresponding chemokine ligands have been found to contribute to the migration and survival of lymphoma cells in mycosis fungoides and Sézary syndrome, including CC chemokine receptor 4 (CCR4), CCR10, C-X-C chemokine receptor type 4 (CXCR4), CCR7, CCR3 and CXCR3. Since chemokines and chemokine receptors have been found to play important roles in the pathophysiology of mycosis fungoides and Sézary syndrome, they may be potentially useful targets for the development of new treatments for these diseases in the future.
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17
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Clinical presentation, immunopathology, and treatment of juvenile-onset mycosis fungoides: A case series of 34 patients. J Am Acad Dermatol 2014; 71:1117-26. [DOI: 10.1016/j.jaad.2014.07.049] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2012] [Revised: 06/30/2014] [Accepted: 07/25/2014] [Indexed: 11/21/2022]
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18
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Hernández Z, Peñate Y, Hernández-Machín B, Pérez-Méndez L, Suárez-Hernández J, Hernández J, Fernández-de-Misa R. Treatment of stage Ia and Ib mycosis fungoides with psoralen UVA monotherapy: an observational study in tertiary hospitals in the Canary Islands. Int J Dermatol 2014; 53:1417-22. [DOI: 10.1111/ijd.12425] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Zaida Hernández
- Department of Dermatology; Complejo Hospitalario Universitario Insular Materno-Infantil; Maternity and Children's Hospital; University Hospital Complex; Las Palmas de Gran Canaria Spain
| | - Yeray Peñate
- Department of Dermatology; Complejo Hospitalario Universitario Insular Materno-Infantil; Maternity and Children's Hospital; University Hospital Complex; Las Palmas de Gran Canaria Spain
| | | | - Lina Pérez-Méndez
- Dermatology Research Unit; University of La Laguna; San Cristóbal de la Laguna; Tenerife Spain
- Department of Dermatology; University Hospital Nuestra Señora de Candelaria; Santa Cruz de Tenerife Spain
| | - Jose Suárez-Hernández
- Department of Dermatology; University Hospital Nuestra Señora de Candelaria; Santa Cruz de Tenerife Spain
| | - Javier Hernández
- Department of Dermatology; Complejo Hospitalario Universitario Insular Materno-Infantil; Maternity and Children's Hospital; University Hospital Complex; Las Palmas de Gran Canaria Spain
| | - Ricardo Fernández-de-Misa
- Dermatology Research Unit; University of La Laguna; San Cristóbal de la Laguna; Tenerife Spain
- Department of Dermatology; University Hospital Nuestra Señora de Candelaria; Santa Cruz de Tenerife Spain
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19
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Mazzeo E, Rubino L, Buglione M, Antognoni P, Magrini SM, Bertoni F, Parmiggiani M, Barbieri P, Bertoni F. The current management of mycosis fungoides and Sézary syndrome and the role of radiotherapy: Principles and indications. Rep Pract Oncol Radiother 2014; 19:77-91. [PMID: 24936325 PMCID: PMC4054991 DOI: 10.1016/j.rpor.2013.07.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Revised: 06/17/2013] [Accepted: 07/16/2013] [Indexed: 10/26/2022] Open
Abstract
AIM To evaluate the current treatment of mycosis fungoides (MF) and Sézary syndrome (SS) focusing on the role of radiotherapy (RT), its principles and indications, and the perspectives of the novel irradiation technologies. BACKGROUND MF and SS are rare lymphoproliferative diseases whose incidence is increasing. For a long time RT has been used as a single modality or in integrated treatment programs for these diseases. MATERIALS AND METHODS The latest systematic reviews, primary studies and new diagnostic and treatment guidelines on MF and SS were analyzed. Clinical outcomes together with the technical aspects and the role of RT were also evaluated. RESULTS New data are available on pathogenesis, diagnostic criteria, classification and staging procedures for MF and SS and several local and systemic therapies are proposed. Localized RT can cure "minimal stage" MF while total skin electron beam irradiation (TSEI) may cure initial-stage disease and may offer important symptom relief (itch, erythroderma) in a more advanced setting. Despite its efficacy, RT is not largely used, mainly because of some technical difficulties but new RT technologies may be proposed to treat large skin surfaces. CONCLUSIONS New treatment programs offer good results, with median survival of more than 12 years in early-stage MF, but the median survival of 2.5 years or less in advanced stages is still a challenge. RT remains an option for all stages with a good cost/effectiveness ratio in a curative or palliative setting. New RT technologies can overcome some technical problems of treating large skin surfaces.
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Affiliation(s)
- Ercole Mazzeo
- Department of Radiation Oncology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy
| | - Laura Rubino
- Department of Radiation Oncology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy
| | - Michela Buglione
- Department of Radiation Oncology, Brescia University, Istituto del Radio “O. Alberti”, Brescia, Italy
| | - Paolo Antognoni
- Department of Radiotherapy, Azienda Ospedaliera Universitaria Ospedale di Circolo e Fondazione Macchi, Varese, Italy
| | - Stefano Maria Magrini
- Department of Radiation Oncology, Brescia University, Istituto del Radio “O. Alberti”, Brescia, Italy
| | - Francesco Bertoni
- Department of Radiation Oncology, Brescia University, Istituto del Radio “O. Alberti”, Brescia, Italy
| | - Manuela Parmiggiani
- Department of Radiation Oncology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy
| | - Paola Barbieri
- Department of Radiation Oncology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy
| | - Filippo Bertoni
- Department of Radiation Oncology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy
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Li JY, Horwitz S, Moskowitz A, Myskowski PL, Pulitzer M, Querfeld C. Management of cutaneous T cell lymphoma: new and emerging targets and treatment options. Cancer Manag Res 2012; 4:75-89. [PMID: 22457602 PMCID: PMC3308634 DOI: 10.2147/cmar.s9660] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Cutaneous T cell lymphomas (CTCL) clinically and biologically represent a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the most common subtypes. Over the last decade, new immunological and molecular pathways have been identified that not only influence CTCL phenotype and growth, but also provide targets for therapies and prognostication. This review will focus on recent advances in the development of therapeutic agents, including bortezomib, the histone deacetylase inhibitors (vorinostat and romidepsin), and pralatrexate in CTCL.
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Affiliation(s)
- Janet Y Li
- College of Physicians and Surgeons, Columbia University, New York, NY, USA
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Goujon E, Truc G, Pétrella T, Maingon P, Jeudy G, Collet E, Galliot C, Dalac-Rat S. [Total skin electron beam therapy for early-stage mycosis fungoides: immediate results and long-term follow-up in 68 patients]. Ann Dermatol Venereol 2009; 136:249-55. [PMID: 19328307 DOI: 10.1016/j.annder.2008.11.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2008] [Accepted: 11/05/2008] [Indexed: 11/28/2022]
Abstract
BACKGROUND Our aim was to evaluate the efficacy of total skin electron beam therapy (TSEB) in the management of early-stage mycosis fungoides in order to assess its position in relation to other skin-directed therapies. PATIENTS AND METHODS A retrospective study of 68 patients (30 in stage T1 and 38 in stage T2). RESULTS The median treatment duration was 6 weeks. Three months after the end of TSEB, a complete clinical response occurred in 66 patients (97%). The most marked effects of acute toxicity included localized ulcerations in 13 patients (13.2%) not requiring hospitalization. Mean follow-up was 6.5 years (1.6 to 28.7). The overall survival rates at 5 and 10 years were 86% and 71%, respectively. Thirty-nine patients (57.4%) experienced relapse with a mean disease-free interval of 1.8 years. The disease-free survival rates at 5 and 10 years were 41% and 31%, respectively. This rate was higher when TSEB was performed early (p=0.031). Twenty-one years after TSEB, only one case of cutaneous malignancy (basal cell carcinoma) was noted. DISCUSSION Because of its high response rates and rapidity of action, TSEB should be considered as first-line therapy in the management of early-stage mycosis fungoides.
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Affiliation(s)
- E Goujon
- Service de dermatologie, centre hospitalier William-Morey, 7, quai de l'Hôpital, 71100 Chalon-sur-Saône, France.
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Abstract
Cutaneous T-cell lymphoma (CTCL) is an uncommon and complex malignancy of the immune system with a wide range of clinical presentations primarily involving the skin. An extensive menu of skin-directed and/or systemic treatment options exists. Best practices in management involve multidisciplinary collaboration. Nursing care for patients who have CTCL is a critical component in the successful management of the disease and requires special attention to the patient's physical, emotional, and spiritual needs. Nurses can make a significant impact by being accessible, offering emotional support, demonstrating advocacy, and providing ongoing education for the patient and family.
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Affiliation(s)
- Sue A McCann
- Department of Dermatology, University of Pittsburgh Medical Center, Suite 145 Lothrop Hall, Pittsburgh, PA 15213, USA.
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Abstract
BACKGROUND Mycosis fungoides (MF) is the most common clinicopathologic subtype of primary cutaneous T-cell lymphoma. OBJECTIVE The therapy of MF is highlighted in this overview. RESULTS AND CONCLUSIONS Skin-directed MF therapies include topical corticosteroids, nitrogen mustard, carmustine (BCNU), topical bexarotene gel, imiquimod cream, radiotherapy, total skin electron beam therapy, and phototherapy. Systemic therapies include extracorporeal photopheresis, interferon, oral bexarotene, denileukin diftitox, monoclonal antibodies and cytokine therapy, and other systemic chemotherapy. Finally, some investigative therapeutic modalities are presented.
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Abstract
Granulomatous slack skin (GSS) is a rare variant of mycosis fungoides in which inflammation leads to elastolysis manifested by pendulous skin folds with a predilection for flexural areas. Histologic findings include many multinucleated giant cells with large numbers of nuclei and loss of dermal elastic tissue. Definitive therapy has yet to be established, but recently interferon-alpha and radiation, interferon-gamma, and pentostatin have shown some success in the treatment of GSS. We present two cases of GSS treated with topical nitrogen mustard (chlormethine; mechlorethamine; mustine), one of whom has long-term remission and the other partial remission. Topical nitrogen mustard appears to be an effective skin-directed therapy for this rare condition.
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Affiliation(s)
- Tricia L Hultgren
- Department of Dermatology, MD Anderson Cancer Center, Houston, TX , USA.
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Barzilai A, Trau H, David M, Feinmesser M, Bergman R, Shpiro D, Schiby G, Rosenblatt K, Or R, Hodak E. Mycosis fungoides associated with B-cell malignancies. Br J Dermatol 2006; 155:379-86. [PMID: 16882178 DOI: 10.1111/j.1365-2133.2006.07346.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse. OBJECTIVES To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms. METHODS Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period. RESULTS Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled. CONCLUSIONS This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.
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Affiliation(s)
- A Barzilai
- Dermatology, Sheba Medical Center, Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Amitay-Layish I, David M, Kafri B, Barzilai A, Feinmesser M, Hodak E. Early-stage mycosis fungoides, parapsoriasis en plaque, and pregnancy. Int J Dermatol 2006; 46:160-5. [PMID: 17269968 DOI: 10.1111/j.1365-4632.2006.02963.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Non-Hodgkin's lymphoma (NHL) coincident with pregnancy is rare, and the literature regarding mycosis fungoides (MF), the most common primary cutaneous NHL, and pregnancy is strikingly sparse. The effect of pregnancy on MF, or on parapsoriasis en plaque (PPP), and the effect of these diseases on pregnancy, are still unknown. OBJECTIVE To study the effect of pregnancy on MF and PPP and the impact of these diseases on pregnancy. METHODS The files of the MF and PPP patients seen during the past 12 years in our department were reviewed to search for patients who had been pregnant during the course of their disease. RESULTS Nine women who met the study criteria were identified, seven with early-stage MF and two with PPP. A total of 12 pregnancies was recorded: nine in patients with MF and three in patients with PPP. In none of the patients was there any indication that pregnancy changed the course of MF or PPP. Of the 12 pregnancies, 11 were normal; one was naturally aborted. Two of the patients were treated with topical steroids during pregnancy. One patient was treated with narrow-band ultraviolet-B combined with topical steroids. The rest preferred to avoid any therapy. CONCLUSIONS Pregnancy appeared to have no impact on the course of early MF or PPP, and no adverse effect was noted on pregnancy. Further studies are needed to clarify the interplay between pregnancy and MF or PPP.
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Affiliation(s)
- Iris Amitay-Layish
- Department of Dermatology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel
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Williams LE, Rassnick KM, Power HT, Lana SE, Morrison-Collister KE, Hansen K, Johnson JL. CCNU in the Treatment of Canine Epitheliotropic Lymphoma. J Vet Intern Med 2006. [DOI: 10.1111/j.1939-1676.2006.tb02833.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Abstract
As one of the most important vesicant agents, the destructive properties of mustards on the skin, eyes and respiratory system, combined with a lack of antidote, makes them effective weapons. Such weapons are inexpensive, easily obtainable and frequently stockpiled. Sulphur mustard (mustard gas) has been used as a chemical warfare agent in at least 10 conflicts. In this article, the use of mustard as a potential agent of chemical warfare and terrorism is outlined. The dose-dependent effects of acute sulphur mustard exposure on the skin, eyes, and respiratory system are described, as well as the possible extents of injuries, the mechanisms of action and the long-term complications. Prevention and management of mustard exposure are briefly discussed. The need for awareness and preparedness in the dermatological community regarding mustard exposure is emphasized.
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Affiliation(s)
- R N Saladi
- Department of Dermatology, Mount Sinai Medical Center, New York, NY 10029-6574, USA.
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