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Frontiers in Oncology 2023Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas. MF is the most common cutaneous lymphoma, and it is classified into classic... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas. MF is the most common cutaneous lymphoma, and it is classified into classic Alibert-Bazin MF, folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin, each with characteristic clinical presentation, histopathological findings, and distinct clinical behaviors. SS is an aggressive leukemic variant of cutaneous lymphoma, and it is characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by malignant cells. There is a wide range of dermatological manifestations of MF/SS, and prompt recognition is essential for early diagnosis. Skin biopsy for histopathology and immunohistochemical analysis is imperative to confirm the diagnosis of MF/SS. Histopathology may also provide information that may influence prognosis and treatment. Staging follows the TNMB system. Besides advanced stage, other factors associated with poorer prognosis are advanced age, male gender, folliculotropism in histopathology of patients with infiltrated plaques and tumors in the head and neck region, large cell transformation, and elevated lactate dehydrogenase. Treatment is divided into skin-directed therapies (topical treatments, phototherapy, radiotherapy), and systemic therapies (biological response modifiers, targeted therapies, chemotherapy). Allogeneic bone marrow transplantation and extracorporeal photopheresis are other treatment modalities used in selected cases. This review discusses the main clinical characteristics, the histopathological/immunohistochemical findings, the staging system, and the therapeutic management of MF/SS.
PubMed: 37124514
DOI: 10.3389/fonc.2023.1141108 -
Blood Research Apr 2023Mycosis fungoides (MF) and Sézary syndrome (SS) are a distinct disease entity of cutaneous T-cell lymphoma with heterogenous clinical features and prognosis. MF mainly... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are a distinct disease entity of cutaneous T-cell lymphoma with heterogenous clinical features and prognosis. MF mainly involves skin and usually shows an indolent and favorable clinical course. In patients with advanced-stage disease, extracutaneous involvement including lymph nodes, viscera, and blood, or large cell transformation may be observed. SS is a leukemic form of advanced-stage MF, characterized by generalized erythroderma. Early-stage MF can be treated with skin-directed therapy. However, patients with refractory or advanced-stage disease are associated with severe symptoms or poor prognosis, requiring systemic therapy. Recent progress in understanding the pathogenesis of MF/SS has contributed to advances in the management of these rare diseases. This review aims to describe the clinical manifestations, diagnosis, risk stratification, and treatment strategy of MF/SS, focusing on the recent updates in the management of these diseases.
PubMed: 37105561
DOI: 10.5045/br.2023.2023023 -
Clinical Lymphoma, Myeloma & Leukemia Jun 2023The term cutaneous T-cell lymphoma (CTCL) is a general term for T-cell lymphomas that are found primarily in skin. The most common CTCL entities, mycosis fungoides and... (Review)
Review
The term cutaneous T-cell lymphoma (CTCL) is a general term for T-cell lymphomas that are found primarily in skin. The most common CTCL entities, mycosis fungoides and Sezary syndrome are incurable diseases with a plethora of conventional treatment options. In the past treatment options have been selected primarily according to stage. Given newer targeted therapies with varied response in different body compartments, we suggest a compartment-guided algorithm that may enhance response rates directing the selection of the most efficacious treatment options.
Topics: Humans; Skin Neoplasms; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin
PubMed: 37061415
DOI: 10.1016/j.clml.2023.03.003 -
Frontiers in Immunology 2023Germline CARD11 gain-of-function (GOF) mutations cause B cell Expansion with NF-κB and T cell Anergy (BENTA) disease, whilst somatic GOF CARD11 mutations recur in...
INTRODUCTION
Germline CARD11 gain-of-function (GOF) mutations cause B cell Expansion with NF-κB and T cell Anergy (BENTA) disease, whilst somatic GOF CARD11 mutations recur in diffuse large B cell lymphoma (DLBCL) and in up to 30% of the peripheral T cell lymphomas (PTCL) adult T cell leukemia/lymphoma (ATL), cutaneous T cell lymphoma (CTCL) and Sezary Syndrome. Despite their frequent acquisition by PTCL, the T cell-intrinsic effects of CARD11 GOF mutations are poorly understood.
METHODS
Here, we studied B and T lymphocytes in mice with a germline Nethyl-N-nitrosourea (ENU)-induced Card11 mutation identical to a mutation identified in DLBCL and modifying a conserved region of the CARD11 coiled-coil domain recurrently mutated in DLBCL and PTCL.
RESULTS AND DISCUSSION
Our results demonstrate that CARD11.M365K is a GOF protein that increases B and T lymphocyte activation and proliferation following antigen receptor stimulation. Germline Card11 mutation was insufficient alone to cause B or T-lymphoma, but increased accumulation of germinal center (GC) B cells in unimmunized and immunized mice. Card11 mutation caused cell-intrinsic over-accumulation of activated T cells, T regulatory (T), T follicular (T) and T follicular regulatory (T) cells expressing increased levels of ICOS, CTLA-4 and PD-1 checkpoint molecules. Our results reveal CARD11 as an important, cell-autonomous positive regulator of T, T and T cells. They highlight T cell-intrinsic effects of a GOF mutation in the CARD11 gene, which is recurrently mutated in T cell malignancies that are often aggressive and associated with variable clinical outcomes.
Topics: Mice; Animals; Gain of Function Mutation; CARD Signaling Adaptor Proteins; Programmed Cell Death 1 Receptor; Guanylate Cyclase; Apoptosis Regulatory Proteins; Mutation; Lymphoma, Large B-Cell, Diffuse; Inducible T-Cell Co-Stimulator Protein
PubMed: 36960072
DOI: 10.3389/fimmu.2023.1095257 -
International Journal of Molecular... Feb 2023Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18,...
Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of and , whereas the pathway analysis indicated a further downregulation of -associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.
Topics: Humans; Dermatitis, Exfoliative; Inflammasomes; Interleukin-18; Leukocytes, Mononuclear; Sezary Syndrome; Skin; Skin Neoplasms
PubMed: 36902104
DOI: 10.3390/ijms24054674 -
Oncology (Williston Park, N.Y.) Feb 2023Cutaneous T-cell lymphomas (CTCLs) are clinically heterogeneous T-cell lymphomas that arise in the skin and are characterized by their clinical and pathological... (Review)
Review
Cutaneous T-cell lymphomas (CTCLs) are clinically heterogeneous T-cell lymphomas that arise in the skin and are characterized by their clinical and pathological features. This review will focus on mycosis fungoides (MF) and Sézary syndrome (SS), which represent 60% to 80% and less than 10% of CTCL cases, respectively. While most patients with MF present with patches and plaques and can be successfully treated with skin-directed therapies, a minority of patients progress from early to advanced stages or undergo large cell transformation. SS is defined as erythroderma, lymphadenopathy, and more than 1000 circulating atypical T-cells/uL with cerebriform nuclei. It has a poor overall survival of 2.5 years. Given the overall rarity of CTCLs, it is notable that clinical trials of treatments for MF/SS have been successfully completed, resulting in FDA approvals of novel therapies with increasing overall response rates. This review outlines the current multidisciplinary approach to diagnosing and treating MF/SS, with a focus on combining skin-directed therapies with emerging targeted and investigational systemic therapies. Integrating these anticancer therapies with skin care and bacterial decolonization is critical for comprehensive management. Curing patients with MF/SS may be possible by using a personalized medicine approach including novel combination strategies, restoration of T helper 1 cytokines, and avoidance of immunosuppressive regimens.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Precision Medicine; Therapies, Investigational; Cytokines; Skin Neoplasms
PubMed: 36862846
DOI: 10.46883/2023.25920984 -
International Journal of Molecular... Feb 2023Transmembrane protein 244 (TMEM244) was annotated to be a member of the TMEM family, which are is a component of cell membranes and is involved in many cellular...
Transmembrane protein 244 (TMEM244) was annotated to be a member of the TMEM family, which are is a component of cell membranes and is involved in many cellular processes. To date, the expression of the TMEM244 protein has not been experimentally confirmed, and its function has not been clarified. Recently, the expression of the gene was acknowledged to be a diagnostic marker for Sézary syndrome, a rare cutaneous T-cell lymphoma (CTCL). In this study, we aimed to determine the role of the gene in CTCL cells. Two CTCL cell lines were transfected with shRNAs targeting the transcript. The phenotypic effect of knockdown was validated using green fluorescent protein (GFP) growth competition assays and AnnexinV/7AAD staining. Western blot analysis was performed to identify the TMEM244 protein. Our results indicate that is not a protein-coding gene but a long non-coding RNA (lncRNA) that is necessary for the growth of CTCL cells.
Topics: Humans; Cell Cycle; Lymphoma, T-Cell, Cutaneous; RNA, Long Noncoding; Sezary Syndrome; Skin Neoplasms
PubMed: 36834942
DOI: 10.3390/ijms24043531 -
Cureus Jan 2023Background Prior quantitative studies have described the diminished health-related quality of life (HRQoL) faced by the overall mycosis fungoides (MF)/Sézary syndrome...
Background Prior quantitative studies have described the diminished health-related quality of life (HRQoL) faced by the overall mycosis fungoides (MF)/Sézary syndrome (SS) population; yet, little is known about how the disease affects HRQoL in skin of color (SOC) patients. This qualitative study sought to explore the lived experiences of SOC patients with MF/SS and gain deeper insights into the impact the disease has on various facets of HRQoL. Methodology Interviews with SOC patients with MF/SS ≥18 were recruited from a cutaneous lymphoma clinic. A thematic analysis was performed to identify overarching themes. Results Ten patients were invited to participate from July to September 2021. One patient with SS and seven patients with MF (four in the early stage and four in the advanced stage), with a median age of 60.5 years, agreed to participate. Emerging themes included diagnostic and therapeutic delays frequently due to initial misdiagnoses with other skin conditions. Physical and functional burdens significantly hindered participants' abilities to carry out daily responsibilities and maintain employment, and impacts on physical appearance (e.g., darkened skin) led to increased self-consciousness and lack of social acceptance. Participants regarded family and faith as main sources of support in addition to developing healthy coping strategies, such as self-acceptance and adaptability. All participants reported feeling satisfied with their access to healthcare information and the quality of care received. Conclusions Our findings provide greater insights into how HRQoL is impacted across SOC patients with MF/SS, which can help raise awareness among healthcare providers and assist with creating interdisciplinary healthcare approaches to better support the needs of this population.
PubMed: 36824562
DOI: 10.7759/cureus.34054 -
Cancers Jan 2023Mycosis fungoides and Sézary syndrome are epidermotropic cutaneous lymphomas, and both of them are rare diseases. Mycosis fungoides is the most frequent primary... (Review)
Review
Mycosis fungoides and Sézary syndrome are epidermotropic cutaneous lymphomas, and both of them are rare diseases. Mycosis fungoides is the most frequent primary cutaneous lymphoma. In about 25% of patients with mycosis fungoides, the disease may progress to higher stages. The pathogenesis and risk factors of progression in mycosis fungoides and Sézary syndrome are not yet fully understood. Previous works have investigated inter- and intrapatient tumor cell heterogeneity. Here, we overview the role of the tumor microenvironment of mycosis fungoides and Sézary syndrome by describing its key components and functions. Emphasis is put on the role of the microenvironment in promoting tumor growth or antitumor immune response, as well as possible therapeutic targets. We focus on recent advances in the field and point out treatment-related alterations of the microenvironment. Deciphering the tumor microenvironment may help to develop strategies that lead to long-term disease control and cure.
PubMed: 36765704
DOI: 10.3390/cancers15030746