-
Seminars in Diagnostic Pathology Nov 2020While the lung is frequently involved by systemic lymphoma, primary pulmonary lymphoma accounts for less than 1% of all extranodal ymphomas. In particular, T-cell... (Review)
Review
While the lung is frequently involved by systemic lymphoma, primary pulmonary lymphoma accounts for less than 1% of all extranodal ymphomas. In particular, T-cell lymphoma is very rare in the lung, as a primary or secondary lesion. Patients with pulmonary T-cell lymphoma usually present with cough, dyspnea, pain, fever, recurrent infections, and hemoptysis. Typical radiologic features include pulmonary nodules, consolidation, solid pulmonary opacities, cystic changes, hilar adenopathy, and pleural effusions. Patients with these clinical and radiologic findings are frequently presumed to have pneumonia and initially treated with empirical antibiotics. Therefore, CT-guided needle biopsy, bronchoscopic examination, or even wedge biopsy should be considered when clinical symptoms show deterioration despite adequate antibiotic therapy. Precise pathologic diagnosis and molecular characterization are recommended in all cases, following the World Health Organization (WHO) classification. Principles of treatment typically vary with the different histologic types of T-cell lymphoma.
Topics: Biopsy; Biopsy, Needle; Bronchoscopy; Diagnosis, Differential; Humans; Killer Cells, Natural; Lung; Lung Neoplasms; Lymphoma; Lymphoma, T-Cell; Pathology, Molecular; Sezary Syndrome; T-Lymphocytes
PubMed: 32448591
DOI: 10.1053/j.semdp.2020.04.003 -
Dermatologie (Heidelberg, Germany) Oct 2022Primary cutaneous lymphomas (CL) are highly radiosensitive. Therefore, radiotherapy is an integral part of multimodality treatment. (Review)
Review
BACKGROUND
Primary cutaneous lymphomas (CL) are highly radiosensitive. Therefore, radiotherapy is an integral part of multimodality treatment.
AIM
The present work provides an overview of indications, technical developments, and dose concepts for total skin electron beam therapy (TSEBT), local radiotherapy as well as maintenance therapy, and current combination studies regarding cutaneous T‑ and B‑cell lymphomas.
MATERIALS AND METHODS
We performed a selective literature search in the PubMed database on the topic of radiotherapy for CL and a search for current studies using clinicaltrials.gov. Furthermore, we describe our own treatment strategies and summarize national and international guidelines.
RESULTS
Low-dose TSEBT is nationally and internationally recommended as an alternative to conventional 36 Gy TSEBT. The main advantages are better tolerability, the possibility of retreatment, a shorter treatment course (approximately 3 weeks), and a short time to response. In current studies, TSEBT is usually delivered to a total dose of 12 Gy and combined with immunotherapy and epigenetic therapy. Local radiotherapy is indicated for mycosis fungoides (MF) tumors and is a curative treatment regimen for other CL, particularly primary cutaneous B‑cell lymphomas.
CONCLUSION
TSEBT is a very effective treatment for MF and is a highly effective palliative treatment, leading to rapid symptom relief and improvement in quality of life. It is an important treatment option, especially in patients with extensive generalized lesions or advanced tumor stage. Local radiation is used as part of TSEBT for tumors and as a boost to undertreated areas. Other CLs are primarily curable with local radiotherapy.
Topics: Humans; Lymphoma, B-Cell; Mycosis Fungoides; Quality of Life; Skin; Skin Neoplasms
PubMed: 36018330
DOI: 10.1007/s00105-022-05046-w -
Expert Review of Clinical Immunology Mar 2024Primary cutaneous T cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas derived from skin-homing T cells. These include mycosis fungoides and its... (Review)
Review
INTRODUCTION
Primary cutaneous T cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas derived from skin-homing T cells. These include mycosis fungoides and its leukemic variant Sezary syndrome, as well as the CD30+ lymphoproliferative disorders.
AREAS COVERED
In this review, we provide a summary of the current literature on CTCL, with a focus on the immunopathogenesis and treatment of mycosis fungoides and Sezary syndrome.
EXPERT OPINION
Recent advances in immunology have provided new insights into the biology of malignant T cells. This in turn has led to the development of new therapies that modulate the immune system to facilitate tumor clearance or target specific aspects of tumor biology.
PubMed: 38450476
DOI: 10.1080/1744666X.2024.2326035 -
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 -
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 -
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 -
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 -
Cancer Management and Research 2023Cutaneous T-Cell Lymphoma (CTCL) is a heterogenous disease that consists of distinct clinicopathologic entities and presentations requiring a unique and expert approach... (Review)
Review
Cutaneous T-Cell Lymphoma (CTCL) is a heterogenous disease that consists of distinct clinicopathologic entities and presentations requiring a unique and expert approach to management. The most common subtype is mycosis fungoides, in which local disease has an excellent prognosis and is often managed with topical therapy alone. More extensive cutaneous involvement as well as involvement of lymph nodes and the peripheral blood (Sezary syndrome) require systemic therapies. Recent years have brought an expansion of therapeutic options, specifically with immune-based approaches that were developed using the knowledge gained regarding the biology and molecular pathology of CTCL. Previous systemic therapies such as retinoids, histone deacetylase inhibitors, and chemotherapeutic agents come with significant toxicity and only short-term response. Newer agents such as mogamulizumab and brentuximab vedotin use a targeted immune-based approach leading to longer periods of response with less systemic toxicity. While still in its infancy, the use of immune checkpoint inhibitors such as nivolumab and pembrolizumab appears promising, and while their current clinical application is limited, early data suggest possible future areas for research of immune manipulation to treat CTCL. Herein, we review these novel immune-based treatment strategies, their superiority over prior systemic options, and the ongoing need for further research and clinical trial enrollment.
PubMed: 37700809
DOI: 10.2147/CMAR.S330908 -
Current Hematologic Malignancy Reports Jun 2023Cutaneous T cell lymphomas (CTCLs) exhibit a wide variety of clinical features, histologic characteristics, and genetic drivers. We review novel molecular findings that... (Review)
Review
PURPOSE OF REVIEW
Cutaneous T cell lymphomas (CTCLs) exhibit a wide variety of clinical features, histologic characteristics, and genetic drivers. We review novel molecular findings that inform our understanding of the pathogenesis of CTCL, with a focus on the tumor microenvironment (TME).
RECENT FINDINGS
There is increasing evidence challenging the model of T:mycosis fungoides (MF) and T:Sézary syndrome (SS) phenotype. Phylogenetic analysis performed using whole-exome sequencing (WES) raises the possibility that MF can arise without a common ancestral T cell clone. The detection of ultraviolet (UV) marker signature 7 mutations in the blood of patients with SS raises questions about the role of UV exposure in CTCL pathogenesis. There is also increasing interest on the role of the TME in CTCL. Existing therapies such as the RXR retinoid bexarotene and the anti-CCR4 monoclonal antibody mogamulizumab may act through the CTCL TME by impacting the CCL22:CCR4 axis, while cancer-associated fibroblasts (CAFs) in the CTCL TME contribute to drug resistance, as well as a Th2 milieu and tumor growth via secretion of pro-tumorigenic cytokines. Staphylococcus aureus (SA) is a frequent cause of morbidity among CTCL patients. SA may positively select for malignant T cells through adaptive downregulation of alpha-toxin surface receptors and promotion of tumor growth via upregulation of the JAK/STAT pathway. Recent molecular advancements have contributed to our understanding of the pathogenesis of CTCL and shed light into the potential mechanisms of existing therapies. Further understanding of the CTCL TME may fuel the discovery of novel therapies for CTCL.
Topics: Humans; Janus Kinases; Phylogeny; Skin Neoplasms; STAT Transcription Factors; Signal Transduction; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Biomarkers; Tumor Microenvironment
PubMed: 37017872
DOI: 10.1007/s11899-023-00692-w -
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