-
Frontiers in Cell and Developmental... 2024This review systematically describes the application of mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the... (Review)
Review
This review systematically describes the application of mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the diverse research approaches essential for understanding CTCL's intricate pathogenesis and evaluating potential treatments. The review categorizes various mouse models, including xenograft, syngeneic transplantation, and genetically engineered mouse models (GEMMs), emphasizing their contributions to understanding tumor-host interactions, gene functions, and studies on drug efficacy in CTCL. It acknowledges the limitations of these models, particularly in fully replicating human immune responses and early stages of CTCL. The review also highlights novel developments focusing on the potential of skin-targeted GEMMs in studying natural skin lymphoma progression and interactions with the immune system from onset. In conclusion, a balanced understanding of these models' strengths and weaknesses are essential for accelerating the deciphering of CTCL pathogenesis and developing treatment methods. The GEMMs engineered to target specifically skin-homing CD4 T cells can be the next top mouse models that pave the way for exploring the effects of CTCL-related genes.
PubMed: 38665428
DOI: 10.3389/fcell.2024.1372881 -
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 -
Dermatology Research and Practice 2024To review the scientific literature related to human microbiota and cutaneous T-cell lymphoma. . An exploratory and systematic review of the articles retrieved from the... (Review)
Review
OBJECTIVE
To review the scientific literature related to human microbiota and cutaneous T-cell lymphoma. . An exploratory and systematic review of the articles retrieved from the bibliographic databases MEDLINE (PubMed), Embase, The Cochrane Library, and Scopus, published in the last 10 years with the following descriptors: "lymphoma, T-cell, cutaneous," "microbiota," "Mycosis Fungoides," "Sézary Syndrome," "lymphoma, primary cutaneous anaplastic large cell," "Lymphomatoid Papulosis" and "Microbiota," "microbiota," "Microbial Community," and "Microbial Communities."
RESULTS
Of the 87 references retrieved, after applying the inclusion and exclusion criteria, 21 articles were selected. Most studies linking cutaneous T-cell lymphoma and the microbiota focus on the cutaneous microbiome, with being the main related agent. Skin colonization by this bacterium could be involved in the hyperactivation of the STAT3 inflammatory pathway and in the overproduction of IL-17, both of which are widely related to the development of more aggressive and advanced forms of cutaneous T-cell lymphoma. We also found evidence of a possible relationship between intestinal dysbiosis and the development of cutaneous T-cell lymphoma, observing a decrease in taxonomic variability and an increase in certain genera such as in the intestinal microbiome of patients with cutaneous T-cell lymphoma. The possible etiopathogenic mechanism underlying this relationship could be explained by an increase in systemic cytokine release, promoting the hyperactivation of STAT3 at the skin level.
CONCLUSION
There appears to be a relationship between cutaneous T-cell lymphoma and the cutaneous and intestinal microbiome, as well as a possible pathophysiological pathway involved. The possible modulation of the cutaneous and intestinal microbiome or the action on the signaling inflammatory pathway, using pharmacological tools such as JAK inhibitors or IL-17 inhibitors in the latter case, could open the possibility for future therapeutic studies for cutaneous T-cell lymphoma.
PubMed: 38435536
DOI: 10.1155/2024/9919225 -
Cells Mar 2024Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)-the most common variant of... (Review)
Review
Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)-the most common variant of CTCL-often presents with skin lesions around the abdomen and buttocks ("bathing suit" distribution), i.e., in skin areas devoid of sun-induced vitamin D. For decades, sunlight and vitamin D have been connected to CTCL. Thus, vitamin D induces apoptosis and inhibits the expression of cytokines in malignant T cells. Furthermore, CTCL patients often display vitamin D deficiency, whereas phototherapy induces vitamin D and has beneficial effects in CTCL, suggesting that light and vitamin D have beneficial/protective effects in CTCL. Inversely, vitamin D promotes T helper 2 (Th2) cell specific cytokine production, regulatory T cells, tolerogenic dendritic cells, as well as the expression of immune checkpoint molecules, all of which may have disease-promoting effects by stimulating malignant T-cell proliferation and inhibiting anticancer immunity. Studies on vitamin D treatment in CTCL patients showed conflicting results. Some studies found positive effects, others negative effects, while the largest study showed no apparent clinical effect. Taken together, vitamin D may have both pro- and anticancer effects in CTCL. The balance between the opposing effects of vitamin D in CTCL is likely influenced by treatment and may change during the disease course. Therefore, it remains to be discovered whether and how the effect of vitamin D can be tilted toward an anticancer response in CTCL.
Topics: Humans; Skin Neoplasms; Vitamin D; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Skin; Skin Diseases; Vitamins
PubMed: 38534347
DOI: 10.3390/cells13060503 -
JAAD Case Reports Aug 2023
PubMed: 37600734
DOI: 10.1016/j.jdcr.2023.05.025 -
Journal of Clinical Medicine Mar 2024: The umbilicus is a fibrous remnant located in the centre of the abdomen. Various entities may be encountered in this special anatomical location; however, little is... (Review)
Review
: The umbilicus is a fibrous remnant located in the centre of the abdomen. Various entities may be encountered in this special anatomical location; however, little is known about their dermoscopic presentation. The aim of this study was to provide a comprehensive summary of existing evidence on dermoscopic features of umbilical lesions. : Studies assessing dermoscopic images of umbilical lesions were included in this study. No age, ethnicity or skin phototype restrictions were applied. Papers assessing lesions outside of the umbilical area, lacking dermoscopic images and/or dermoscopic description and not related to the topic were excluded. Embase, Medline and Cochrane Library were searched from inception to the end of May 2023. The Joanna Briggs Institute critical appraisal tools were used to evaluate the risk of bias of the selected studies. The quality and the level of evidence of included studies were assessed according to the Oxford 2011 Levels of Evidence. Thirty-four studies reporting a total of 39 lesions met the inclusion criteria and were included in qualitative analysis. : A qualitative synthesis of the following entities was performed: melanoma, nevi, basal cell carcinoma, fibroepithelioma of Pinkus, Sister Mary Joseph nodule, mycosis fungoides, dermatofibroma, endometriosis, epidermal cyst, granuloma, intravascular papillary endothelial hyperplasia, lichen planus, omphalolith, seborrheic keratosis, and syringoma. : Dermoscopy is a non-invasive technique that may be useful in the differential diagnosis of umbilical lesions. The main limitations of this study were lack of a high level of evidence in the studies and the lack of uniformity in applied dermoscopic terminology between included studies.
PubMed: 38542014
DOI: 10.3390/jcm13061790 -
Human Pathology Aug 2023Cutaneous T-cell lymphomas are an heterogeneous group of uncommon lymphoid neoplasms that are challenging to diagnose and require close collaboration between...
Cutaneous T-cell lymphomas are an heterogeneous group of uncommon lymphoid neoplasms that are challenging to diagnose and require close collaboration between dermatologists, pathologists and hematologists/oncologists. This article reviews the most common cutaneous T-cell lymphomas: mycosis fungoides (both classic and variant forms) as well as its leukemic counterpart Sézary syndrome, CD30+ T-cell lymphoproliferative disorders including the ever-expanding group of lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, and primary cutaneous CD4+ small/medium lymphoproliferative disorder. We discuss the classic clinical and histopathologic features of these lymphomas and review how they can be distinguished from reactive entities. In particularly, updates to these diagnostic categories and current controversies in classification are highlighted. Moreover, we review the prognosis and treatment for each entity. These lymphomas exhibit variable prognosis, and therefore it is important to correctly classify atypical cutaneous T-cell infiltrates for appropriate patient treatment and prognosis. Cutaneous T-cell lymphomas are at the interface of several medical specialties; this review seeks to summarize key features of these lymphomas and highlight new and emerging insights into these lymphomas.
PubMed: 37307932
DOI: 10.1016/j.humpath.2023.06.001 -
Journal of the European Academy of... Nov 2023Histopathological differentiation of early mycosis fungoides (MF) from benign chronic inflammatory dermatoses remains difficult and often impossible, despite the...
BACKGROUND
Histopathological differentiation of early mycosis fungoides (MF) from benign chronic inflammatory dermatoses remains difficult and often impossible, despite the inclusion of all available diagnostic parameters.
OBJECTIVE
To identify the most impactful histological criteria for a predictive diagnostic model to discriminate MF from atopic dermatitis (AD).
METHODS
In this multicentre study, two cohorts of patients with either unequivocal AD or MF were evaluated by two independent dermatopathologists. Based on 32 histological attributes, a hypothesis-free prediction model was developed and validated on an independent patient's cohort.
RESULTS
A reduced set of two histological features (presence of atypical lymphocytes in either epidermis or dermis) was trained. In an independent validation cohort, this model showed high predictive power (95% sensitivity and 100% specificity) to differentiate MF from AD and robustness against inter-individual investigator differences.
LIMITATIONS
The study investigated a limited number of cases and the classifier is based on subjectively evaluated histological criteria.
CONCLUSION
Aiming at distinguishing early MF from AD, the proposed binary classifier performed well in an independent cohort and across observers. Combining this histological classifier with immunohistochemical and/or molecular techniques (such as clonality analysis or molecular classifiers) could further promote differentiation of early MF and AD.
Topics: Humans; Dermatitis, Atopic; Skin Neoplasms; Mycosis Fungoides; Epidermis
PubMed: 37422709
DOI: 10.1111/jdv.19325 -
European Journal of Dermatology : EJD Oct 2023This article reviews the 2022 European Society for Photodynamic Therapy (Euro-PDT) Annual Congress. PDT has been investigated for the treatment of a broad number of... (Review)
Review
This article reviews the 2022 European Society for Photodynamic Therapy (Euro-PDT) Annual Congress. PDT has been investigated for the treatment of a broad number of oncologic, infectious and inflammatory indications. New studies confirm the potential for wider use of topical PDT for acne and photoaging, as well as several uncommon conditions including tinea capitis, Mycobacterium marinum, cutaneous alternariosis, resistant acral warts, eyelid Bowen's disease, mycosis fungoides, pseudolymphoma, and graft-versus-host disease. Hidradenitis suppurativa patients may also benefit from intra-lesional PDT. Several methods of delivering PDT have been validated, including conventional, daylight and artificial daylight PDT. Light-emitting fabrics have emerged as an innovative solution to the delivery of uniform light over the scalp as well as anatomically-challenging sites, with opportunities now to control and monitor these devices via mobile phone applications. Pre-treatment of patients with thicker, more difficult-to-treat actinic keratoses (AK) with calcitriol appears to be a practical approach to increasing efficacy, although this is associated with increased local skin reactions. Sequential treatment of AK and photoaging with daylight-PDT and injectable NASHA gel indicates that these two therapeutic approaches offer complementary effects. Potential biomarkers may help predict responsiveness of patients with field cancerization and AK receiving daylight PDT. Over-expression of the proto-oncogene, Myc, has been observed in poor responders, whilst the tumour suppressor gene, PTEN, showed under-expression. The potential for use and methods of delivery of topical PDT for dermatological indications continue to expand the enhanced choice of treatment offered to patients.
Topics: Humans; Photosensitizing Agents; Photochemotherapy; Keratosis, Actinic; Skin Neoplasms; Skin; Aminolevulinic Acid; Treatment Outcome
PubMed: 38297922
DOI: 10.1684/ejd.2023.4562