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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... Mar 2024Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell... (Review)
Review
Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell lymphoma, such as Sezary's syndrome and mycosis fungoides. Over the past three decades, its immunotherapeutic properties have been tested on a variety of autoimmune conditions, including many dermatologic diseases. There is ample evidence of ECP's ability to modify leukocytes and alter cytokine production for certain dermatologic diseases that have been refractory to first-line treatments, such as atopic dermatitis. However, the evidence on the efficacy of ECP for the treatment of these dermatologic diseases is unclear and/or lacks sufficient evidence. The purpose of this paper is to review the literature on the utilization and clinical efficacy of ECP in the treatment of several [autoimmune] dermatologic diseases and discuss its applications, guidelines, recommendations, and future implementation for dermatologic diseases.
Topics: Humans; Photopheresis; Skin Neoplasms; Mycosis Fungoides; Blood Component Removal; Sezary Syndrome
PubMed: 38474257
DOI: 10.3390/ijms25053011 -
Cancers Apr 2021Primary cutaneous T-cell lymphomas (CTCLs) constitute a heterogeneous group of diseases that affect the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) account... (Review)
Review
Primary cutaneous T-cell lymphomas (CTCLs) constitute a heterogeneous group of diseases that affect the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) account for the majority of these lesions and have recently been the focus of extensive translational research. This review describes and discusses the main pathobiological manifestations of MF/SS, the molecular and clinical features currently used for diagnosis and staging, and the different therapies already approved or under development. Furthermore, we highlight and discuss the main findings illuminating key molecular mechanisms that can act as drivers for the development and progression of MF/SS. These seem to make up an orchestrated constellation of genomic and environmental alterations generated around deregulated T-cell receptor (TCR)/phospholipase C, gamma 1, (PLCG1) and Janus kinase/ signal transducer and activator of transcription (JAK/STAT) activities that do indeed provide us with novel opportunities for diagnosis and therapy.
PubMed: 33923722
DOI: 10.3390/cancers13081931 -
Frontiers in Oncology 2020Cutaneous T cell lymphomas (CTCL) comprise of a heterogeneous group of non-Hodgkin lymphomas derived from skin-homing T cells. Variation in clinical presentation and... (Review)
Review
Cutaneous T cell lymphomas (CTCL) comprise of a heterogeneous group of non-Hodgkin lymphomas derived from skin-homing T cells. Variation in clinical presentation and lack of definitive molecular markers make diagnosis especially challenging. The biology of CTCL remains elusive and clear links between genetic aberrations and epigenetic modifications that would result in clonal T cell expansion have not yet been identified. Nevertheless, in recent years, next generation sequencing (NGS) has enabled a much deeper understanding of the genomic landscape of CTCL by uncovering aberrant genetic pathways and epigenetic dysregulations. Additionally, single cell profiling is rapidly advancing our understanding of patients-specific tumor landscape and its interaction with the surrounding microenvironment. These studies have paved the road for future investigations that will explore the functional relevance of genetic alterations in the progression of disease. The ultimate goal of elucidating the pathogenesis of CTCL is to establish effective therapeutic targets with more durable clinical response and treat relapsing and refractory CTCL.
PubMed: 32477957
DOI: 10.3389/fonc.2020.00765 -
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 -
Diagnostics (Basel, Switzerland) Jun 2022Mycosis fungoides (MF) and Sezary syndrome (SS) are the two most common type of cutaneous T-cell lymphoma (CTCL). Currently, no markers can be clearly related to...
Mycosis fungoides (MF) and Sezary syndrome (SS) are the two most common type of cutaneous T-cell lymphoma (CTCL). Currently, no markers can be clearly related to prognosis or to differential diagnosis between early stages and inflammatory benign diseases (IBD). The thymocyte selection-associated high mobility group box factor (TOX), has been proposed as a possible marker in differential diagnosis between early CTCL stages and IBD. Recently TOX has been related to prognosis. We aimed to investigate whether TOX may be a diagnostic or prognostic marker. MF and SS biopsies between 2010 and 2020 were retrieved. New tissues slides were stained with an anti-TOX antibody, (Clone NAN448B). On each slide, 5 fields were examined at high magnification (400×), to evaluate the percentage of marker-positivity in a quantitative way. Thirty-six patients (12 females and 24 males) and 48 biopsies were collected. Nine patients had multiple biopsies. TOX expression in MF/SS cases showed an increase from early to advanced phases. TOX was not regarded as a prognostic marker due to the absence of significant changes by comparing early MF cases with reactive conditions. TOX statistical significance increased in patients alive with disease and in those dead of disease ( = 0.013 and = 0.0005, respectively) as compared with patients in complete remission. Our results show that TOX should be regarded more as a prognostic than a diagnostic marker.
PubMed: 35885488
DOI: 10.3390/diagnostics12071582 -
Anais Brasileiros de Dermatologia 2021Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis... (Review)
Review
Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Quality of Life; Sezary Syndrome; Skin Neoplasms
PubMed: 34053802
DOI: 10.1016/j.abd.2020.12.007 -
Italian Journal of Dermatology and... Aug 2022The mechanisms involved in mycosis fungoides, and Sezary Syndrome progression are largely unknown. Over the last decade the interest in immune system contrast of...
BACKGROUND
The mechanisms involved in mycosis fungoides, and Sezary Syndrome progression are largely unknown. Over the last decade the interest in immune system contrast of neoplasm has grown owing to the introduction of immunotherapy. PD-1 and its ligand (PD-L1) are the target of several immunotherapy treatment. In the literature reports on the expression of PD-1 and PD-L1 have provided contrasting results.
METHODS
In our analysis we investigated PD-1 expression in neoplastic cells and in tumor infiltrating lymphocytes (TILs) as well as PD-L1 expression in tumor cells and in tumor associated macrophages (TAMs). PD-L1 and PD-1 positive cells were counted in 5 high-power fields (HPF) and scored as the average number of positive neoplastic cells/TILs/TAMs per HPF.
RESULTS
From databases of two institutions (Bologna and Florence) thirty-five patients corresponding to 43 biopsies were retrieved. In seven instances sequential biopsies were present. No statistically significant expression was observed comparing early to advanced stages by analysing PD-1 by tumor cells and TILs and of PD-L1 by tumor cells and TAMs.
CONCLUSIONS
Our results corroborate that PD-1 and PD-L1 expression is not stage-dependent in mycosis fungoides and Sezary syndrome. However, PD-1 and PD-L1 expression in affected patients provides a rationale to schedule anti PD-1/PD-L1 drugs.
Topics: B7-H1 Antigen; Humans; Lymphocytes, Tumor-Infiltrating; Mycosis Fungoides; Programmed Cell Death 1 Receptor; Sezary Syndrome; Skin Neoplasms
PubMed: 35373781
DOI: 10.23736/S2784-8671.22.07275-9 -
Skin Therapy Letter Sep 2022Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US... (Review)
Review
Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US FDA in 1988 for the treatment of Sézary syndrome, a leukemic form of cutaneous T-cell lymphoma (CTCL). Although CTCL remains the only FDA-approved indication, ECP has since been used off-label for numerous other conditions, including graft-versus-host disease (GvHD), systemic sclerosis, autoimmune bullous dermatoses, Crohn's disease, and prevention of solid organ transplant rejection. In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis. Herein, we review the current concepts regarding ECP mechanism of action, treatment considerations and protocols, and efficacy.
Topics: Humans; Photopheresis; Graft vs Host Disease; Dermatology; Lymphoma, T-Cell, Cutaneous; Scleroderma, Systemic; Skin Neoplasms
PubMed: 36469458
DOI: No ID Found