-
Cancers Aug 2023Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides and belongs to the spectrum of... (Review)
Review
Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides and belongs to the spectrum of cutaneous CD30+ T-cell lymphoproliferative disorders. Although primary cutaneous ALCL usually presents as a localized nodule or papule with or without ulceration, multifocal lesions may occur in up to 20% of cases. Histologically, primary cutaneous ALCL consists of a diffuse dermal infiltrate of medium to large anaplastic/pleomorphic cells with abundant amphophilic-to-eosinophilic cytoplasm, horseshoe-shaped nuclei, strong and diffuse expression of CD30, and with focal or no epidermotropism. The neoplastic infiltrate may show angiocentric distribution and may extend to the subcutis. Patients with localized or multifocal disease have a similar prognosis with a 10-year overall survival rate of 90%. Approximately 30% of primary cutaneous ALCLs harbor a (6p25.3) gene rearrangement that results in decreased expression of this dual-specific phosphatase, decreased STAT3 activation, and decreased activity of immune and autoimmune-mediated mechanisms regulated by T-cells.
PubMed: 37627126
DOI: 10.3390/cancers15164098 -
Cells Jul 2023Mycosis fungoides (MF) is the most common cutaneous lymphoma characterized by an indolent course. Prognosis is stage-based but this approach does not reflect the...
Mycosis fungoides (MF) is the most common cutaneous lymphoma characterized by an indolent course. Prognosis is stage-based but this approach does not reflect the different outcomes within stages. Considering that tumor microenvironment is known to be involved in MF pathogenesis and progression, we decided to investigate 99 MF cases by using the PanCancer Immune Profiling Panel. We identified and validated a signature of 9 genes able to predict MF survival and distinguish a high-risk group with a worse outcome from a low-risk group of cases with a better outcome. At the molecular level, low-risk vs. high-risk cases reported a global upregulation of immune genes, enriched in cytokines, and a higher density of dendritic cells and mast cells, possibly associated with a more favorable clinical course.
Topics: Humans; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; Risk Factors; Lymphoma, Non-Hodgkin; Tumor Microenvironment
PubMed: 37566023
DOI: 10.3390/cells12151944 -
Frontiers in Immunology 2023Mycosis fungoides (MF) is an indolent T-cell lymphoma that mainly affects the skin and presents with itch in more than half of the patients. Recently, the expression of...
BACKGROUND
Mycosis fungoides (MF) is an indolent T-cell lymphoma that mainly affects the skin and presents with itch in more than half of the patients. Recently, the expression of Mas-related G protein-coupled receptor X2 (MRGPRX2), a receptor of mast cell (MC) responsible for the IgE-independent non-histaminergic itch, has been shown in lesional skin of patients with pruritic skin diseases, including chronic urticaria, prurigo, and mastocytosis. As of yet, limited knowledge exists regarding the MRGPRX2 expression in the skin of patients with MF.
OBJECTIVES
To investigate the number of MRGPRX2-expressing (MRGPRX2+) cells in the skin of patients with MF and its correlation with clinical and laboratory characteristics of the disease.
METHODS
MRGPRX2 was analyzed in lesional and non-lesional skin of MF patients and healthy skin tissues by immunohistochemistry. Co-localization of MRGPRX2 with the MC marker tryptase was assessed by immunofluorescence. Public single-cell RNAseq data was reanalyzed to identify the MRGPRX2 expression on the distinct cell types.
RESULTS
In lesional skin of MF patients, MRGPRX2+ cell number was higher than in non-lesional skin and healthy control skin (mean:15.12 vs. 6.84 vs. 5.51 cells/mm, p=0.04), and correlated with MC numbers (r=0.73, p=0.02). MC was the primary cell type expressing MRGPRX2 in MF patients. The ratio of MRGPRX2+ MCs to MRGPRX2+ cells in lesional and non-lesional skin correlated with the severity of disease (r=0.71, p=0.02 and r=0.67, p=0.03, respectively).
CONCLUSIONS
Our findings point to the role of MRGPRX2 and MC in the pathogenesis of MF that should be investigated in further studies.
Topics: Humans; Mycosis Fungoides; Skin; Receptors, G-Protein-Coupled; Skin Neoplasms; Pruritus; Cell Count; Nerve Tissue Proteins; Receptors, Neuropeptide
PubMed: 38022672
DOI: 10.3389/fimmu.2023.1197821 -
Life (Basel, Switzerland) Feb 2024The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated... (Review)
Review
The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL.
PubMed: 38398754
DOI: 10.3390/life14020245 -
Clinical and Experimental Medicine Dec 2023Primary cutaneous T-cell lymphomas (CTCL), which include mycosis fungoides (MF) and Sézary syndrome (SS), are a group of lymphoproliferative disorders characterized by... (Review)
Review
Primary cutaneous T-cell lymphomas (CTCL), which include mycosis fungoides (MF) and Sézary syndrome (SS), are a group of lymphoproliferative disorders characterized by clonal accumulation of neoplastic T-lymphocytes in the skin. Severe pruritus, one of the most common and distressing symptoms in primary CTCL, can significantly impair emotional well-being, physical functioning, and interpersonal relationships, thus greatly reducing quality of life. Unfortunately, effectively managing pruritus remains challenging in CTCL patients as the underlying mechanisms are, as of yet, not fully understood. Previous studies investigating the mechanisms of itch in CTCL have identified several mediators and their corresponding antagonists used for treatment. However, a comprehensive overview of the mediators and receptors contributing to pruritus in primary CTCL is lacking in the current literature. Here, we summarize and review the mediators and receptors that may contribute to pruritus in primary CTCL to explore the mechanisms of CTCL pruritus and identify effective therapeutic targets using the PubMed and Web of Science databases. Studies were included if they described itch mediators and receptors in MF and SS. Overall, the available data suggest that proteases (mainly tryptase), and neuropeptides (particularly Substance P) may be of greatest interest. At the receptor level, cytokine receptors, MRGPRs, and TRP channels are most likely important. Future drug development efforts should concentrate on targeting these mediators and receptors for the treatment of CTCL pruritus.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Quality of Life; Skin Neoplasms; Mycosis Fungoides; Pruritus; Sezary Syndrome
PubMed: 37555911
DOI: 10.1007/s10238-023-01141-x -
Dermatopathology (Basel, Switzerland) Oct 2023Programmed cell death protein 1 (PD-1) plays a pivotal role in immune system regulation, with its expression levels linked to malignancy prognosis. However, existing...
Programmed cell death protein 1 (PD-1) plays a pivotal role in immune system regulation, with its expression levels linked to malignancy prognosis. However, existing reports on PD-1 staining in mycosis fungoides (MF) present conflicting findings, and little attention has been given to PD-1 staining in different MF variants. To address this, we conducted a retrospective study, employing immunohistochemistry to examine PD-1 expression in cases of folliculotropic MF and non-folliculotropic MF. We analyzed 24 cases of folliculotropic MF and 18 cases of non-folliculotropic MF, and recorded both the percentage of PD-1-labeled tumor cells and the intensity score (negative, weak, medium, or strong). Our results revealed significant disparity in PD-1 labeling between patch/plaque MF and folliculotropic MF ( = 0.028). Non-folliculotropic MF exhibited higher PD-1 labeling in tumor cells (58.3%) compared to folliculotropic MF (40.2%). Notably, there was no significant difference in PD-1 staining between folliculotropic MF and non-folliculotropic MF when both were in the early stage/indolent disease category. However, when considering the tumor stage, folliculotropic MF exhibited PD-1 staining in tumor cells at a rate of 21.1%, while non-folliculotropic MF showed PD-1 staining in tumor cells at a rate of 46.6% ( = 0.005). Additionally, among folliculotropic MF cases, 13 out of 24 cases displayed differing PD-1 expression patterns between epidermal and dermal components, with preserved PD-1 staining in the epidermal component and loss of staining in the dermal component. Furthermore, consistent with the prior literature, tumor cells with large cell transformations exhibited significantly lower PD-1 labeling ( = 0.017). Our findings showcase the unique PD-1 staining patterns in MF.
PubMed: 37873805
DOI: 10.3390/dermatopathology10040038 -
Journal of the European Academy of... Sep 2023Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is characterized by proliferation of malignant skin-tropic T cells. Progression from... (Review)
Review
Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is characterized by proliferation of malignant skin-tropic T cells. Progression from early-stage disease (skin patches and/or plaques) to more advanced stages (cutaneous tumours, erythroderma or extracutaneous involvement) occurs slowly and can be discontinuous. Prognosis is poor for the ~25% of patients who progress to advanced disease. Patients at any stage of MF may experience reduced health-related quality of life (QoL) via a spectrum of physically and psychologically debilitating symptoms that can impact many aspects of daily life. Allogeneic stem-cell transplantation is a curative treatment option for some patients with advanced disease, but otherwise there is currently no cure for MF; patients are often refractory to several treatments and require lifelong management. The goals of therapy are symptom control, prevention of disease progression, avoidance of treatment-related toxicity and maintenance/improvement of QoL. Although treatment regimens exist it can be difficult to know how to prioritize them, hence therapies are tailored according to patient needs and drug availabilities, following clinical recommendations. International consensus guidelines recommend skin-directed therapies (SDTs) as first-line treatment for early-stage disease, and SDTs combined with systemic therapy for advanced stages. Chlormethine (CL), also known as mechlorethamine, chlorethazine, mustine, HN2, caryolysine and embichin, is a synthetic deoxyribonucleic acid-alkylating agent that was used as a chemical weapon (mustard gas) during the First World War. Subsequent investigation revealed that survivors of mustard gas exposure had lymphocytopenia, and that CL could inhibit rapidly proliferating malignant T cells. CL has since been developed as a topical treatment for MF and prescribed as such for over 70 years. This review aims to summarize the current knowledge regarding the mechanism of action of CL in the cutaneous micro-environment, in the specific context of MF treatment.
Topics: Humans; Mechlorethamine; Quality of Life; Mustard Gas; Mycosis Fungoides; Skin Neoplasms; Tumor Microenvironment
PubMed: 37262305
DOI: 10.1111/jdv.19237 -
Journal of the American Academy of... Nov 2023
PubMed: 37321484
DOI: 10.1016/j.jaad.2023.05.082 -
Journal of Drugs in Dermatology : JDD Dec 2023Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody that appears to be more effective against CD30-expressing cutaneous T-cell lymphoma (CTCL) compared to...
BACKGROUND
Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody that appears to be more effective against CD30-expressing cutaneous T-cell lymphoma (CTCL) compared to current standard-of-care treatments. Objective: To determine the real-world efficacy and adverse effects of BV use in patients with mycosis fungoides (MF) who were treated with BV at Atrium Health Wake Forest Baptist Medical Center.
METHODS
Study staff performed a retrospective chart review of patients diagnosed with MF who were prescribed BV at Atrium Health Wake Forest Baptist Comprehensive Cancer Center.
RESULTS
Regardless of their response to BV, all patients in our cohort had higher CD30 positivity on subsequent biopsies compared to their initial skin biopsy. Conclusions: Improved understanding of appropriate CD30 testing and evaluation will allow for quicker invention of patients with BV responsive CTCL. J Drugs Dermatol. 2023;22(12):e33-e34. doi:10.36849/JDD.6981e.
Topics: Humans; Brentuximab Vedotin; Retrospective Studies; Immunoconjugates; Skin Neoplasms; Ki-1 Antigen; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous
PubMed: 38051830
DOI: 10.36849/JDD.6981 -
The Australasian Journal of Dermatology Nov 2023Eyelids may be affected in systemic, ocular adnexal and primary cutaneous lymphomas (PCLs). The frequency of eyelid involvement in PCLs is still not well known and it is... (Review)
Review
Eyelids may be affected in systemic, ocular adnexal and primary cutaneous lymphomas (PCLs). The frequency of eyelid involvement in PCLs is still not well known and it is not a predilection site for any type. While primary cutaneous T-cell lymphomas (CTCLs) are more commonly seen than primary cutaneous B-cell lymphomas (CBCLs), especially mycosis fungoides (MF) as by far the most frequent type, B cell lymphomas are reported to be the commonest type in eyelid localization on the contrary. PCLs may be located on the eyelids, as the sole manifestation or in association with the involvement of other parts of the eye and elsewhere of the body. MF may present with a rich spectrum of clinical features on the eyelids mostly seen in folliculotropic subtype and advanced-stage disease. Erythematous scaly patches or plaques representing the most commonly encountered eyelid MF lesions may mimic many other dermatological conditions. Diffuse thickening, oedema, poikilodermic changes, atrophy and wrinkling are other suggestive findings of eyelid MF. Milia-like papules, madarosis and ectropion are also seen in the folliculotropic variant of MF, as ectropion is more typical for Sezary syndrome. Eyelids are also a typical location for tumoural MF which has been suggested as a poor prognostic indicator in MF. Papulonodular lesions, large tumours, ulceration, diffuse infiltration, oedema and subcutaneous atrophy on the eyelids may also be seen in other types of PCLs. Keep in mind, the rich clinical spectrum of PCLs on the eyelids may be crucial in early diagnosis in this special localization.
Topics: Humans; Ectropion; Mycosis Fungoides; Skin Neoplasms; Eyelids; Atrophy; Edema; Lymphoma, T-Cell, Cutaneous
PubMed: 37435706
DOI: 10.1111/ajd.14131