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Dermatologic Clinics Oct 2015Primary cutaneous lymphomas (PCLs) are an extremely heterogeneous group of non-Hodgkin lymphomas that manifest in the skin. Their diagnosis is complex and based on... (Review)
Review
Primary cutaneous lymphomas (PCLs) are an extremely heterogeneous group of non-Hodgkin lymphomas that manifest in the skin. Their diagnosis is complex and based on clinical lesion type and evaluation of findings on light microscopic examination, immunohistochemistry and molecular analysis of representative skin biopsies. The evaluation, classification, and staging system is unique for mycosis fungoides (MF) and Sézary syndrome (SS), the most common subtypes of cutaneous T-cell lymphoma (CTCL) versus the other subtypes of Non-MF/Non-SS CTCL and the subtypes of cutaneous B-cell lymphoma (CBCL). Since current treatment is stage-based, it is particularly important that the correct diagnosis and stage be ascertained initially. The purpose of this article is to review the current evaluation, diagnosis, classification, staging, assessment techniques, and response criteria for the various types of both T-cell and B-cell PCLs.
Topics: Humans; Lymphoma, B-Cell; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Neoplasm Staging; Prognosis; Sezary Syndrome; Skin Neoplasms
PubMed: 26433839
DOI: 10.1016/j.det.2015.06.001 -
Journal Der Deutschen Dermatologischen... Aug 2016Primary cutaneous CD30(+) lymphoproliferative disorders are the second most common group of cutaneous T-cell lymphomas (CTCL) and include lymphomatoid papulosis (LyP)... (Review)
Review
Primary cutaneous CD30(+) lymphoproliferative disorders are the second most common group of cutaneous T-cell lymphomas (CTCL) and include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large T-cell lymphoma (cALCL). Both disease entities share overlapping clinical, histopathological, and molecular features, thus representing a spectrum of cutaneous CD30(+) lymphoproliferative disorders. LyP may be distinguished from cALCL by clinicopathological correlation. In some patients, both diseases may coexist at initial diagnosis or develop over the course of the disease. Mycosis fungoides (MF), the most common CTCL, is not considered a primary cutaneous CD30(+) lymphoproliferative disorder, but may occur in some LyP patients. In addition, LyP-like lesions may develop in MF patients. However, this is frequently a manifestation of MF rather than a representation of two different disease entities. Caution also has to be taken in the setting of transformed MF with lesions expressing CD30, as they may be mistaken for either LyP or cALCL, resulting in an inadequate therapeutic approach.
Topics: Humans; Ki-1 Antigen; Lymphoma, T-Cell, Cutaneous; Lymphomatoid Papulosis; Mycosis Fungoides; Skin Neoplasms
PubMed: 27509411
DOI: 10.1111/ddg.13117 -
Journal of Clinical Pathology Dec 2015Primary cutaneous T-cell lymphomas (CTCLs) represent a number of extranodal lymphomas arising from a malignant population of lymphocytes in the skin, with the most... (Review)
Review
Primary cutaneous T-cell lymphomas (CTCLs) represent a number of extranodal lymphomas arising from a malignant population of lymphocytes in the skin, with the most common type being mycosis fungoides (MF) representing half of all primary CTCLs. Despite advances in immunohistochemistry and molecular methodology, significant diagnostic challenges remain due to phenotypic overlap of primary CTCLs with several inflammatory dermatoses, secondary lymphomas, among other conditions. Clinical features such as presentation and morphology, staging, histology, immunophenotype and molecular features must be considered in detail before a diagnosis is made in order to minimise false-positive, false-negative and indeterminate diagnoses. Herein, we review primary CTCLs, including epidemiological data, a brief summary of clinical presentations, immunophenotype, molecular signatures and differential diagnoses.
Topics: Diagnosis, Differential; Female; Humans; Immunohistochemistry; Immunophenotyping; Lymphoma, T-Cell, Cutaneous; Male; Mycosis Fungoides; Skin; Skin Neoplasms
PubMed: 26602417
DOI: 10.1136/jclinpath-2015-203133 -
Journal of the American Academy of... Nov 2021Primary cutaneous T-cell lymphomas (CTCLs) other than mycosis fungoides (MF) and Sézary syndrome (SS) encompass a heterogenous group of non-Hodgkin lymphomas with... (Review)
Review
Primary cutaneous T-cell lymphomas (CTCLs) other than mycosis fungoides (MF) and Sézary syndrome (SS) encompass a heterogenous group of non-Hodgkin lymphomas with variable clinical courses, prognoses, and management approaches. Given the morphologic and histologic overlap among the CTCL subtypes and other T-cell lymphomas with cutaneous manifestations, thorough evaluation with clinicopathologic correlation and exclusion of systemic involvement are essential prior to initiating therapy. Staging and treatment recommendations vary, depending on the subtype, clinical behavior, and treatment response. Generally, for subtypes in which staging is recommended, Ann Arbor or tumor, node, metastasis staging specific to CTCL other than MF or SS are used. For many subtypes, there is no standard treatment to date. Available recommended treatments range widely, from no active or minimal intervention with skin-directed therapy to aggressive systemic therapies that include multi-agent chemotherapy with consideration for hematopoietic stem cell transplant. Emerging targeted therapies, such as brentuximab, a chimeric antibody targeting CD30, show promise in altering the disease course of non-MF/SS CTCLs.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Prognosis; Sezary Syndrome; Skin Neoplasms
PubMed: 33945836
DOI: 10.1016/j.jaad.2021.04.081 -
Dermatologic Clinics Oct 2015Primary cutaneous CD30⁺ lymphoproliferative disorders (LPDs) account for approximately 25% of cutaneous lymphomas. Although these LPDs are clinically heterogeneous,... (Review)
Review
Primary cutaneous CD30⁺ lymphoproliferative disorders (LPDs) account for approximately 25% of cutaneous lymphomas. Although these LPDs are clinically heterogeneous, they can be indistinguishable histologically. Lymphomatoid papulosis rarely requires systemic treatment; however, multifocal primary cutaneous anaplastic large cell cutaneous lymphoma and large cell transformation of mycosis fungoides are typically treated systemically. As CD30⁺ LPDs are rare, there is little published evidence to support a specific treatment algorithm. Most studies are case reports, small case series, or retrospective reviews. This article discusses various treatment choices for each of the CD30⁺ disorders and offers practical pearls to aid in choosing an appropriate regimen.
Topics: Antineoplastic Agents; Cell Transformation, Neoplastic; Combined Modality Therapy; Diagnosis, Differential; Humans; Ki-1 Antigen; Lymphoma, Primary Cutaneous Anaplastic Large Cell; Lymphomatoid Papulosis; Mycosis Fungoides; Prognosis; Skin Neoplasms
PubMed: 26433852
DOI: 10.1016/j.det.2015.05.013 -
Chinese Clinical Oncology Feb 2019Mycosis fungoides (MF) and Sézary syndrome (SS) are two well-characterized skin limited and leukemic subtypes of cutaneous T-cell lymphoma (CTCL), respectively.... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are two well-characterized skin limited and leukemic subtypes of cutaneous T-cell lymphoma (CTCL), respectively. Progressive global immune dysfunction and a multitude of specific immunological abnormalities have long been recognized as features of MF and SS. Therefore, a variety of immune-based therapies have been explored and used in the clinic for decades in the attempt to restore the immune imbalance in these malignancies. With recent advances in the development of novel immunotherapies in cancer treatment, new treatment modalities have emerged to complement the existing repertoire. Herein, we provide a comprehensive review of immune evasive mechanisms in MF/SS and summarize the established and emerging immunotherapies for these malignancies. We explain the underlying mechanisms of these immune-based therapies and derive recommendation from results of major clinical trials.
Topics: Humans; Immunotherapy; Mycosis Fungoides; Sezary Syndrome
PubMed: 30691274
DOI: 10.21037/cco.2019.01.01 -
Journal of the American Academy of... Jun 2023
Topics: Humans; Mycosis Fungoides; Antibodies, Monoclonal, Humanized; Skin Neoplasms; Sezary Syndrome
PubMed: 36858155
DOI: 10.1016/j.jaad.2023.01.047 -
Frontiers in Immunology 2020Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have...
BACKGROUND
Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have been inconsistent. To gain insight into the immunogenicity of MF we characterized the neoantigen landscape of this lymphoma, focusing on the known predictors of responses to immunotherapy: the quantity, HLA-binding strength and subclonality of neoantigens.
METHODS
Whole exome and whole transcriptome sequences were obtained from 24 MF samples (16 plaques, 8 tumors) from 13 patients. Bioinformatic pipelines (Mutect2, OptiType, MuPeXi) were used for mutation calling, HLA typing, and neoantigen prediction. PhyloWGS was used to subdivide malignant cells into stem and clades, to which neoantigens were matched to determine their clonality.
RESULTS
MF has a high mutational load (median 3,217 non synonymous mutations), resulting in a significant number of total neoantigens (median 1,309 per sample) and high-affinity neoantigens (median 328). In stage I disease most neoantigens were clonal but with stage progression, 75% of lesions had >50% subclonal antigens and 53% lesions had CSiN scores <1. There was very little overlap in neoantigens across patients or between different lesions on the same patient, indicating a high degree of heterogeneity.
CONCLUSIONS
The neoantigen landscape of MF is characterized by high neoantigen load and significant subclonality which could indicate potential challenges for immunotherapy in patients with advanced-stage disease.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; Clonal Evolution; Computational Biology; Disease Management; Disease Progression; Disease Susceptibility; Female; Gene Expression Profiling; Humans; Male; Mutation; Mycosis Fungoides; Neoplasm Staging; Peptides; Transcriptome; Exome Sequencing
PubMed: 33329522
DOI: 10.3389/fimmu.2020.561234 -
The Journal of Investigative Dermatology Feb 2024Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic...
Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic large-cell lymphoma (pcALCL). We investigated the differences in spatially resolved transcriptome profiles of MF-LCT and pcALCL using CD30 morphology markers and 28 and 24 regions of interest (ROIs) in MF-LCT and pcALCL, respectively. Differentially expressed genes, pathway analysis, and immune-cell deconvolution by selective analysis of CD30-positive tumor cells and CD30-negative extratumoral areas were undertaken. In CD30-positive ROIs of MF-LCT, 190 differentially expressed genes were upregulated (29 were directly or indirectly associated with extracellular matrix remodeling), whereas 255 differentially expressed genes were downregulated, compared with those of pcALCL. Except for cornified envelope formation and keratinization, all six pathways enriched in CD30-positive ROIs of MF-LCT were associated with extracellular matrix remodeling. In CD30-positive ROIs in MF-LCT compared with those in pcALCL, immune-cell deconvolution revealed significantly increased fibroblasts and M2 macrophages (P = 0.012 and P = 0.023, respectively) but decreased M1 macrophages (P = 0.031). In CD30-negative ROIs in MF-LCT compared with those in pcALCL, memory B (P = 0.021), plasma (P = 0.023), and CD8 memory T (P = 0.001) cells significantly decreased, whereas regulatory T cells (P = 0.024) increased. Predomination of extracellular matrix remodeling pathways and immunosuppressive microenvironment in MF-LCT indicates pathophysiological differences between MF-LCT and pcALCL.
Topics: Humans; Lymphoma, Large-Cell, Anaplastic; Transcriptome; Ki-1 Antigen; Mycosis Fungoides; Skin Neoplasms; Tumor Microenvironment
PubMed: 37544586
DOI: 10.1016/j.jid.2023.05.030 -
Leukemia & Lymphoma Mar 2018Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common cutaneous T-cell lymphomas (CTCLs). Both lack curative options, and advanced-stage carries a poor... (Review)
Review
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common cutaneous T-cell lymphomas (CTCLs). Both lack curative options, and advanced-stage carries a poor prognosis. Whilst there are a number of treatments available, achieving and maintaining a durable remission remains challenging. We review current systemic treatment options as monotherapy for advanced-stage MF (IIB-IV), appraising their mechanism of action, analyzing their efficacy, and describing toxicities. Individually, reported overall response rates (ORR) vary widely in the literature and duration of responses are typically short, ranging from 7.5 to 22.4 months. Combined therapy is frequently used in an effort to boost responses, although prospective studies comparing combinations to single agent therapies are rarely conducted. While recent translational research has led to increased understanding of the immunopathogenesis of MF and SS and the development of new treatments, current standard of care therapies are not curative and have low ORR for advanced-stage disease.
Topics: Antineoplastic Agents; Humans; Mycosis Fungoides; Prognosis; Sezary Syndrome; Skin Neoplasms
PubMed: 29308723
DOI: 10.1080/10428194.2017.1347650