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European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022.European Journal of Cancer (Oxford,... Jul 2022Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary... (Review)
Review
Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed with dermatoscopy. If a melanoma is suspected, a histopathological examination is always required. Sequential digital dermatoscopy and full body photography can be used in high-risk patients to improve the detection of early melanoma. Where available, confocal reflectance microscopy can also improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the American Joint Committee on Cancer classification. Thin melanomas up to 0.8 mm tumor thickness do not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC onwards whole-body examinations with computed tomography (CT) or positron emission tomography CT (PET-CT) in combination with brain magnetic resonance imaging are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to define the frequency and extent of examinations. A stage-based follow-up scheme is proposed which, according to the experience of the guideline group, covers the optimal requirements, but further studies may be considered. This guideline is valid until the end of 2024.
Topics: Consensus; Humans; Melanoma; Neoplasm Recurrence, Local; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35570085
DOI: 10.1016/j.ejca.2022.03.008 -
Journal of Immunology Research 2020Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both... (Review)
Review
Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy. The use of immunotherapy in the treatment of metastatic melanoma is a relatively late discovery for this malignancy. Recent studies have shown a significantly higher success rate with combination of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Immunotherapy is associated to a panel of dysimmune toxicities called immune-related adverse events that can affect one or more organs and may limit its use. Future directions in the treatment of metastatic melanoma include immunotherapy with anti-PD1 antibodies or targeted therapy with BRAF and MEK inhibitors.
Topics: Animals; Combined Modality Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Melanoma; Molecular Targeted Therapy; Neoplasm Metastasis; Protein Kinase Inhibitors; Skin Neoplasms
PubMed: 32671117
DOI: 10.1155/2020/9235638 -
CA: a Cancer Journal For Clinicians Mar 2020
Review
Topics: Adult; Combined Modality Therapy; Diagnosis, Differential; Humans; Lung Neoplasms; Male; Melanoma; Neoplasm Metastasis; Pneumonectomy; Skin Neoplasms; Thoracic Surgery, Video-Assisted
PubMed: 32101327
DOI: 10.3322/caac.21599 -
Journal of the European Academy of... Jan 2022The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing. A growing part of this patient group is formed by immunocompromised patients, for... (Review)
Review
The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing. A growing part of this patient group is formed by immunocompromised patients, for example organ-transplant recipients (OTR). Although over 90% of the cSCC show a relatively harmless clinical behaviour, there is also a chance of developing advanced cSCC and metastases. Locally advanced cSCC are defined as cSCC that have locally advanced progression and are no longer amenable to surgery or radiation therapy. Better understanding of the clinical behaviour of cSCC is essential to discriminate between low- and high-risk cSCC. Staging systems are important and have recently been improved. Genetic characterisation of SCC will likely become an important tool to help distinguish low and high-risk cSCC with an increased potential to metastasise in the near future. Available treatments for high-risk and advanced cSCC include surgery, radiotherapy, chemotherapy and targeted therapy with epidermal growth factor receptors inhibitors. Anti-PD-1 antibodies show promising results with response rates of up to 50% in both locally advanced and metastatic cSCC but, in its present form, is not suitable for OTR.
Topics: Carcinoma, Squamous Cell; Humans; Immunocompromised Host; Neoplasm Staging; Skin Neoplasms
PubMed: 34855246
DOI: 10.1111/jdv.17728 -
American Journal of Hematology Jan 2023Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary...
DISEASE OVERVIEW
Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS).
DIAGNOSIS
The diagnosis of MF or SS requires the integration of clinical and histopathologic data.
RISK-ADAPTED THERAPY
TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a "risk-adapted," multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or the blood involvement are generally approached with systemic therapies, including biologic-response modifiers, histone deacetylase inhibitors, or antibody-based strategies, in an escalating fashion. In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Neoplasm Staging; Sezary Syndrome; Skin Neoplasms
PubMed: 36226409
DOI: 10.1002/ajh.26760 -
Surgical Pathology Clinics Jun 2021PRAME (PReferentially expressed Antigen in MElanoma) is a melanoma-associated antigen expressed in cutaneous and ocular melanomas and some other malignant neoplasms,... (Review)
Review
PRAME (PReferentially expressed Antigen in MElanoma) is a melanoma-associated antigen expressed in cutaneous and ocular melanomas and some other malignant neoplasms, while its expression in normal tissue and benign tumors is limited. Detection of PRAME protein expression by immunohistochemistry in a cohort of 400 melanocytic tumors showed diffuse nuclear immunoreactivity for PRAME in most metastatic and primary melanomas. In contrast, most nevi were negative for PRAME or showed nondiffuse immunoreactivity. The difference in the extent of immunoreactivity for PRAME in unambiguous melanocytic tumors prompted the study of PRAME as an ancillary tool for evaluating melanocytic lesions in more challenging scenarios.
Topics: Antigens, Neoplasm; Humans; Immunohistochemistry; Melanoma; Skin Neoplasms
PubMed: 34023098
DOI: 10.1016/j.path.2021.01.001 -
Cell Jun 2022Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to...
Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.
Topics: Animals; Heterografts; Humans; Melanoma; Mice; Neoplasm Transplantation; Nevus, Pigmented; Skin Neoplasms
PubMed: 35561684
DOI: 10.1016/j.cell.2022.04.025 -
ESMO Open Jun 2021Cutaneous melanoma is the most lethal form of skin cancer and its incidence has been increasing in the past 30 years. Although this is completely resectable in most... (Review)
Review
Cutaneous melanoma is the most lethal form of skin cancer and its incidence has been increasing in the past 30 years. Although this is completely resectable in most cases, thicker melanoma and those with regional lymph-node involvement are at a high risk of relapse. In recent years, the management of locoregional disease has drastically changed. In particular, in the 8th Edition of the American Joint Committee on Cancer (AJCC), subgroup classification of TNM (tumor-node-metastasis) has been modified, with the addition of the IIID stage. Furthermore, in recent randomized trials, completion lymph node dissection in case of sentinel lymph node biopsy positivity has not been shown to offer any improvement in overall survival versus observation. Consequently, radical dissection has been recommended as the standard treatment, but only in patients with palpable nodal metastases. However, the major novelty in the treatment of locally advanced melanoma has been the introduction of drugs, already used for metastatic disease, that have also shown clinical efficacy in the adjuvant setting. In fact, immunotherapies and, in the case of BRAF V600E/K-mutated melanoma, combination treatment of BRAF and MEK inhibitors have improved recurrence-free survival in these patients. In this paper, we will describe the current management of a patient with radically resectable melanoma and discuss the key points in light of the latest scientific evidence.
Topics: Humans; Lymph Node Excision; Melanoma; Neoplasm Recurrence, Local; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 33930656
DOI: 10.1016/j.esmoop.2021.100136 -
Briefings in Bioinformatics Jul 2021NLRP3 inflammasome was introduced as a double-edged sword in tumorigenesis and influenced immunotherapy response by modulating host immunity. However, a systematic...
NLRP3 inflammasome was introduced as a double-edged sword in tumorigenesis and influenced immunotherapy response by modulating host immunity. However, a systematic assessment of the NLRP3-inflammasome-related genes across human cancers is lacking, and the predictive role of NLRP3 inflammasome in cancer immunotherapy (CIT) response remains unexplored. Thus, in this study, we performed a pan-cancer analysis of NLRP3-inflammasome-related genes across 24 human cancers. Out of these 24 cancers, 15 cancers had significantly different expression of NLRP3-inflammasome-related genes between normal and tumor samples. Meanwhile, Cox regression analysis showed that the NLRP3 inflammasome score could be served as an independent prognostic factor in skin cutaneous melanoma. Further analysis indicated that NLRP3 inflammasome may influence tumor immunity mainly by mediating tumor-infiltrating lymphocytes and macrophages, and the effect of NLRP3 inflammasome on immunity is diverse across tumor types in tumor microenvironment. We also found that the NLRP3 inflammasome score could be a stronger predictor for immune signatures compared with tumor mutation burden (TMB) and glycolytic activity, which have been reported as immune predictors. Furthermore, analysis of the association between NLRP3 inflammasome and CIT response using six CIT response datasets revealed the predictive value of NLRP3 inflammasome for immunotherapy response of patients in diverse cancers. Our study illustrates the characterization of NLRP3 inflammasome in multiple cancer types and highlights its potential value as a predictive biomarker of CIT response, which can pave the way for further investigation of the prognostic and therapeutic potentials of NLRP3 inflammasome.
Topics: Databases, Factual; Disease-Free Survival; Humans; Immunotherapy; Inflammasomes; Melanoma; NLR Family, Pyrin Domain-Containing 3 Protein; Neoplasm Proteins; Skin Neoplasms; Survival Rate; Tumor Microenvironment; Melanoma, Cutaneous Malignant
PubMed: 33212483
DOI: 10.1093/bib/bbaa345 -
The FEBS Journal Mar 2022Epithelial-to-mesenchymal transition (EMT), a process through which epithelial tumor cells acquire mesenchymal phenotypic properties, contributes to both metastatic... (Review)
Review
Epithelial-to-mesenchymal transition (EMT), a process through which epithelial tumor cells acquire mesenchymal phenotypic properties, contributes to both metastatic dissemination and therapy resistance in cancer. Accumulating evidence indicates that nonepithelial tumors, including melanoma, can also gain mesenchymal-like properties that increase their metastatic propensity and decrease their sensitivity to therapy. In this review, we discuss recent findings, illustrating the striking similarities-but also knowledge gaps-between the biology of mesenchymal-like state(s) in melanoma and mesenchymal state(s) from epithelial cancers. Based on this comparative analysis, we suggest hypothesis-driven experimental approaches to further deepen our understanding of the EMT-like process in melanoma and how such investigations may pave the way towards the identification of clinically relevant biomarkers for prognosis and new therapeutic strategies.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Cell Differentiation; Drug Resistance, Neoplasm; Epithelial Cells; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Melanoma; Mesenchymal Stem Cells; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Proteins; Neoplastic Stem Cells; Skin Neoplasms; Transcription Factors
PubMed: 33999497
DOI: 10.1111/febs.16021