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Skin Cancer: Recent Advances in Diagnosis, Treatment, and Prevention
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Skin Cancer: Recent Advances in Diagnosis, Treatment, and Prevention

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 14157

Special Issue Editor

Prof. Dr. Alexander Kreuter

E-Mail Website
Guest Editor
1. Department of Dermatology, Venereology and Allergology, Helios St. Elisabeth Hospital Oberhausen, University Witten/Herdecke, 46045 Oberhausen, Germany
2. Department of Dermatology, Venereology and Allergology, Helios St. Johannes Hospital Duisburg, 47166 Duisburg, Germany
Interests: epithelial skin cancer; melanoma; cutaneous T-cell lymphoma; cutaneous sarcoma

Special Issue Information

Dear Colleagues,

Skin cancer is by far the most common malignancy worldwide, affecting men and women of every skin color. The incidence of both melanoma and non-melanoma skin cancer (keratinocyte skin cancer such as basal cell carcinoma and squamous cell carcinoma) has increased in recent decades. According to the World Health Organisation (WHO), between 2 and 3 million non-melanoma skin cancers and approximately 132,000 melanoma skin cancers are diagnosed globally each year. One in every three cancers diagnosed annually is a skin cancer. 

The continuously rising incidence rates of both melanoma and non-melanoma skin cancer are largely attributed to behavior changes and increased exposure to ultraviolet (UV) radiation during outdoor activities. Approximately 90 percent of all non-melanoma skin cancers are associated with UV exposure. If detected early, the prognosis of skin cancer is often excellent. Nevertheless, more than 5,400 people worldwide die of advanced non-melanoma skin cancer every month.    

Tremendous progress has been achieved in recent years in the understanding of the molecular pathogenesis of skin cancer, leading to the development of new therapeutic strategies. In the last decade, there has been a paradigm shift in how we approach the treatment of skin cancer, especially advanced melanoma, due to the unprecedented success of MAPK pathway and immune checkpoint inhibitors. The latter have revolutionized the treatment landscape of many hematological and solid tumors.

For this Special Issue of Cancers, we welcome original research and review articles that provide an overview of the most recent advances and future challenges for the diagnosis, treatment and prevention of skin cancer. Research areas may include (but are not limited to) the following skin tumours: melanoma, cutaneous squamous cell carcinoma and basal cell carcinoma, Merkel cell carcinoma, cutaneous sarcoma (atypical fibroxanthoma, pleomorphic dermal sarcoma, angiosarcoma) and cutaneous T- and B-cell lymphoma.

I look forward to receive your contributions to this Special Issue.

Prof. Dr. Alexander Kreuter
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Melanoma
  • cutaneous squamous cell carcinoma and basal cell carcinoma
  • merkel cell carcinoma
  • cutaneous sarcoma (atypical fibroxanthoma, pleomorphic dermal sarcoma, angiosarcoma)
  • cutaneous T and B cell lymphoma
  • immunotherapy
  • targeted therapy
  • chemotherapy
  • radiotherapy
  • clinical study
  • translational study

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Published Papers (7 papers)

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Research

Jump to: Review, Other

11 pages, 1915 KiB  
Article
ATOH1, TFAP2B, and CEACAM6 as Immunohistochemical Markers to Distinguish Merkel Cell Carcinoma and Small Cell Lung Cancer
by Serena M. Vilasi, Jannett Nguyen, Catherine J. Wang, Lingling Miao, Kenneth Daily, Mary Eid, Joon Seon Song, Hong Jiang, Kris Ylaya, Klaus J. Busam, Maria R. Gaiser, Stephen M. Hewitt and Isaac Brownell
Cancers 2024, 16(4), 788; https://doi.org/10.3390/cancers16040788 - 15 Feb 2024
Cited by 3 | Viewed by 1663
Abstract
Merkel cell carcinoma (MCC) and small cell lung cancer (SCLC) can be histologically similar. Immunohistochemistry (IHC) for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF-1) are commonly used to differentiate MCC from SCLC; however, these markers have limited sensitivity and specificity. To [...] Read more.
Merkel cell carcinoma (MCC) and small cell lung cancer (SCLC) can be histologically similar. Immunohistochemistry (IHC) for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF-1) are commonly used to differentiate MCC from SCLC; however, these markers have limited sensitivity and specificity. To identify new diagnostic markers, we performed differential gene expression analysis on transcriptome data from MCC and SCLC tumors. Candidate markers included atonal BHLH transcription factor 1 (ATOH1) and transcription factor AP-2β (TFAP2B) for MCC, as well as carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) for SCLC. Immunostaining for CK20, TTF-1, and new candidate markers was performed on 43 MCC and 59 SCLC samples. All three MCC markers were sensitive and specific, with CK20 and ATOH1 staining 43/43 (100%) MCC and 0/59 (0%) SCLC cases and TFAP2B staining 40/43 (93%) MCC and 0/59 (0%) SCLC cases. TTF-1 stained 47/59 (80%) SCLC and 1/43 (2%) MCC cases. CEACAM6 stained 49/59 (83%) SCLC and 0/43 (0%) MCC cases. Combining CEACAM6 and TTF-1 increased SCLC detection sensitivity to 93% and specificity to 98%. These data suggest that ATOH1, TFAP2B, and CEACAM6 should be explored as markers to differentiate MCC and SCLC. Full article
(This article belongs to the Special Issue Skin Cancer: Recent Advances in Diagnosis, Treatment, and Prevention)
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17 pages, 4719 KiB  
Article
Kinase Insert Domain Receptor Q472H Pathogenic Germline Variant Impacts Melanoma Tumor Growth and Patient Treatment Outcomes
by Milad Ibrahim, Irineu Illa-Bochaca, Faisal Fa’ak, Kelsey R. Monson, Robert Ferguson, Chen Lyu, Eleazar Vega-Saenz de Miera, Paul Johannet, Margaret Chou, Justin Mastroianni, Farbod Darvishian, Tomas Kirchhoff, Judy Zhong, Michelle Krogsgaard and Iman Osman
Cancers 2024, 16(1), 18; https://doi.org/10.3390/cancers16010018 - 19 Dec 2023
Viewed by 1564
Abstract
Background: We previously reported a higher incidence of a pathogenic germline variant in the kinase insert domain receptor (KDR) in melanoma patients compared to the general population. Here, we dissect the impact of this genotype on melanoma tumor growth kinetics, tumor phenotype, and [...] Read more.
Background: We previously reported a higher incidence of a pathogenic germline variant in the kinase insert domain receptor (KDR) in melanoma patients compared to the general population. Here, we dissect the impact of this genotype on melanoma tumor growth kinetics, tumor phenotype, and response to treatment with immune checkpoint inhibitors (ICIs) or targeted therapy. Methods: The KDR genotype was determined and the associations between the KDR Q472H variant (KDR-Var), angiogenesis, tumor immunophenotype, and response to MAPK inhibition or ICI treatment were examined. Melanoma B16 cell lines were transfected with KDR-Var or KDR wild type (KDR-WT), and the differences in tumor kinetics were evaluated. We also examined the impact of KDR-Var on the response of melanoma cells to a combination of VEGFR inhibition with MAPKi. Results: We identified the KDR-Var genotype in 81/489 (37%) patients, and it was associated with a more angiogenic (p = 0.003) and immune-suppressive tumor phenotype. KDR-Var was also associated with decreased PFS to MAPKi (p = 0.022) and a trend with worse PFS to anti-PD1 therapy (p = 0.06). KDR-Var B16 murine models had increased average tumor volume (p = 0.0027) and decreased CD45 tumor-infiltrating lymphocytes (p = 0.0282). The anti-VEGFR treatment Lenvatinib reduced the tumor size of KDR-Var murine tumors (p = 0.0159), and KDR-Var cells showed synergistic cytotoxicity to the combination of dabrafenib and lenvatinib. Conclusions: Our data demonstrate a role of germline KDR-Var in modulating melanoma behavior, including response to treatment. Our data also suggest that anti-angiogenic therapy might be beneficial in patients harboring this genotype, which needs to be tested in clinical trials. Full article
(This article belongs to the Special Issue Skin Cancer: Recent Advances in Diagnosis, Treatment, and Prevention)
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11 pages, 3372 KiB  
Article
Subtypes of Melanomas Associated with Different Degrees of Actinic Elastosis in Conventional Histology, Irrespective of Age and Body Site, Suggesting Chronic Ultraviolet Light Exposure as Driver for Lentigo Maligna Melanoma and Nodular Melanoma
by Konstantin Drexler, Veronika Zenderowski, Laura Schreieder, Kevin Koschitzki, Sigrid Karrer, Mark Berneburg, Sebastian Haferkamp and Dennis Niebel
Cancers 2024, 16(1), 1; https://doi.org/10.3390/cancers16010001 - 19 Dec 2023
Cited by 2 | Viewed by 1283
Abstract
(1) Background: Ultraviolet (UV) radiation and sunburns are associated with an increased incidence of acquired nevi and melanomas. However, the data are controversial as to whether chronic UV exposure or high intermittent UV exposure is the major carcinogenic factor in melanocytic tumors. In [...] Read more.
(1) Background: Ultraviolet (UV) radiation and sunburns are associated with an increased incidence of acquired nevi and melanomas. However, the data are controversial as to whether chronic UV exposure or high intermittent UV exposure is the major carcinogenic factor in melanocytic tumors. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure in nevi and different clinical melanoma subtypes (i.e., superficial spreading melanoma (SSM), nodular malignant melanoma (NMM), acral lentiginous melanoma (ALM), and lentigo maligna melanoma (LMM)) with respect to clinical variables (age, sex, and body site). (2) Methods: We defined a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 595 melanocytic lesions from 559 patients with their clinical variables. (3) Results: The TEG was correlated with age and UV-exposed body sites. Furthermore, the TEG was significantly higher in LMM than in all other types of melanomas and the TEG in NMM was higher than in SSM, irrespective of patient age and tumor site. (4) Conclusions: High cumulative UV exposure is more strongly associated with LMM and NMM than with other melanoma subtypes. Full article
(This article belongs to the Special Issue Skin Cancer: Recent Advances in Diagnosis, Treatment, and Prevention)
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9 pages, 941 KiB  
Article
Insights into Melanoma Clinical Practice: A Perspective for Future Research
by Giang T. Lam, Carmela Martini, Tiffany Brooks, Sarita Prabhakaran, Ashley M. Hopkins, Ben S.-Y. Ung, Jingying Tang, Maria C. Caruso, Robert D. Brooks, Ian R. D. Johnson, Alexandra Sorvina, Shane M. Hickey, Litsa Karageorgos, Sonja Klebe, John J. O’Leary, Douglas A. Brooks and Jessica M. Logan
Cancers 2023, 15(18), 4631; https://doi.org/10.3390/cancers15184631 - 19 Sep 2023
Cited by 3 | Viewed by 1515
Abstract
Background: Early diagnosis is the key to improving outcomes for patients with melanoma, and this requires a standardized histological assessment approach. The objective of this survey was to understand the challenges faced by clinicians when assessing melanoma cases, and to provide a perspective [...] Read more.
Background: Early diagnosis is the key to improving outcomes for patients with melanoma, and this requires a standardized histological assessment approach. The objective of this survey was to understand the challenges faced by clinicians when assessing melanoma cases, and to provide a perspective for future studies. Methods: Between April 2022 and February 2023, national and international dermatologists, pathologists, general practitioners, and laboratory managers were invited to participate in a six-question online survey. The data from the survey were assessed using descriptive statistics and qualitative responses. Results: A total of 54 responses were received, with a 51.4% (n = 28) full completion rate. Of the respondents, 96.4% reported ambiguity in their monthly melanoma diagnosis, and 82.1% routinely requested immunohistochemistry (IHC) testing to confirm diagnosis. SOX10 was the most frequently requested marker, and most respondents preferred multiple markers over a single marker. Diagnostic and prognostic tests, as well as therapeutic options and patient management, were all identified as important areas for future research. Conclusions: The respondents indicated that the use of multiple IHC markers is essential to facilitate diagnostic accuracy in melanoma assessment. Survey responses indicate there is an urgent need to develop new biomarkers for clinical decision making at multiple critical intervention points. Full article
(This article belongs to the Special Issue Skin Cancer: Recent Advances in Diagnosis, Treatment, and Prevention)
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9 pages, 869 KiB  
Article
Model for End-Stage Liver Disease Correlates with Disease Relapse and Death of Patients with Merkel Cell Carcinoma
by Thilo Gambichler, Jürgen C. Becker, Laura Susok, Riina Käpynen and Nessr Abu Rached
Cancers 2023, 15(12), 3195; https://doi.org/10.3390/cancers15123195 - 15 Jun 2023
Cited by 2 | Viewed by 2052
Abstract
Merkel cell carcinoma (MCC) is a highly malignant skin tumor that occurs mainly in elderly and/or immunosuppressed patients. MCC prognosis has been significantly improved by the introduction of immune checkpoint inhibitor treatment. Recently, blood-based biomarkers have been investigated that can potentially predict the [...] Read more.
Merkel cell carcinoma (MCC) is a highly malignant skin tumor that occurs mainly in elderly and/or immunosuppressed patients. MCC prognosis has been significantly improved by the introduction of immune checkpoint inhibitor treatment. Recently, blood-based biomarkers have been investigated that can potentially predict the outcome of MCC patients. In this context, parameters of liver scores have not yet been investigated. We retrospectively recruited 47 MCC patients with available relevant laboratory data at primary diagnosis. At this time, we investigated blood-based scores as follows: model for end-stage liver disease (MELD), aspartate aminotransferase/platelet count ratio index (APRI), and the alanine transaminase/aspartate aminotransferase ratio (De Ritis ratio). MCC relapse was negatively correlated with the De Ritis score (r = −0.3, p = 0.024) and positively correlated with the MELD score (r = 0.3, p = 0.035). Moreover, MCC-specific death positively correlated with CCI score (r = 0.4, p = 0.01) and MELD score (r = 0.4, p = 0.003). In multivariable analysis, the MELD score remained in the regression model as significant independent predictor for MCC relapse (hazard ratio: 1.16 (95% CI 1.04 to 1.29; p = 0.008) and MCC-specific death (hazard ratio: 1.2 (95% CI 1.04 to 1.3; p = 0.009). We observed for the first time that the MELD score appears to independently predict both MCC relapse and MCC-specific death. These results should be further investigated in larger prospective studies. Full article
(This article belongs to the Special Issue Skin Cancer: Recent Advances in Diagnosis, Treatment, and Prevention)
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Review

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24 pages, 404 KiB  
Review
Risk Factors and Innovations in Risk Assessment for Melanoma, Basal Cell Carcinoma, and Squamous Cell Carcinoma
by K. Wunderlich, M. Suppa, S. Gandini, J. Lipski, J. M. White and V. Del Marmol
Cancers 2024, 16(5), 1016; https://doi.org/10.3390/cancers16051016 - 29 Feb 2024
Cited by 8 | Viewed by 3152
Abstract
Skin cancer is the most frequently diagnosed cancer globally and is preventable. Various risk factors contribute to different types of skin cancer, including melanoma, basal cell carcinoma, and squamous cell carcinoma. These risk factors encompass both extrinsic, such as UV exposure and behavioral [...] Read more.
Skin cancer is the most frequently diagnosed cancer globally and is preventable. Various risk factors contribute to different types of skin cancer, including melanoma, basal cell carcinoma, and squamous cell carcinoma. These risk factors encompass both extrinsic, such as UV exposure and behavioral components, and intrinsic factors, especially involving genetic predisposition. However, the specific risk factors vary among the skin cancer types, highlighting the importance of precise knowledge to facilitate appropriate early diagnosis and treatment for at-risk individuals. Better understanding of the individual risk factors has led to the development of risk scores, allowing the identification of individuals at particularly high risk. These advances contribute to improved prevention strategies, emphasizing the commitment to mitigating the impact of skin cancer. Full article
(This article belongs to the Special Issue Skin Cancer: Recent Advances in Diagnosis, Treatment, and Prevention)

Other

Jump to: Research, Review

13 pages, 599 KiB  
Perspective
Immunotherapy and Hypofractionated Radiotherapy in Older Patients with Locally Advanced Cutaneous Squamous-Cell Carcinoma of the Head and Neck: A Proposed Paradigm by the International Geriatric Radiotherapy Group
by Nam P. Nguyen, Juliette Thariat, Olena Gorobets, Vincent Vinh-Hung, Lyndon Kim, Sergio Calleja Blanco, Maria Vasileiou, Meritxell Arenas, Thandeka Mazibuko, Huan Giap, Felix Vincent, Alexander Chi, Gokoulakrichenane Loganadane, Mohammad Mohammadianpanah, Agata Rembielak, Ulf Karlsson, Ahmed Ali, Satya Bose and Brandi R. Page
Cancers 2023, 15(20), 4981; https://doi.org/10.3390/cancers15204981 - 13 Oct 2023
Cited by 2 | Viewed by 1908
Abstract
Cutaneous skin carcinoma is a disease of older patients. The prevalence of cutaneous squamous-cell carcinoma (cSCC) increases with age. The head and neck region is a frequent place of occurrence due to exposure to ultraviolet light. Surgical resection with adjuvant radiotherapy is frequently [...] Read more.
Cutaneous skin carcinoma is a disease of older patients. The prevalence of cutaneous squamous-cell carcinoma (cSCC) increases with age. The head and neck region is a frequent place of occurrence due to exposure to ultraviolet light. Surgical resection with adjuvant radiotherapy is frequently advocated for locally advanced disease to decrease the risk of loco-regional recurrence. However, older cancer patients may not be candidates for surgery due to frailty and/or increased risk of complications. Radiotherapy is usually advocated for unresectable patients. Compared to basal-cell carcinoma, locally advanced cSCC tends to recur locally and/or can metastasize, especially in patients with high-risk features such as poorly differentiated histology and perineural invasion. Thus, a new algorithm needs to be developed for older patients with locally advanced head and neck cutaneous squamous-cell carcinoma to improve their survival and conserve their quality of life. Recently, immunotherapy with checkpoint inhibitors (CPIs) has attracted much attention due to the high prevalence of program death ligand 1 (PD-L1) in cSCC. A high response rate was observed following CPI administration with acceptable toxicity. Those with residual disease may be treated with hypofractionated radiotherapy to minimize the risk of recurrence, as radiotherapy may enhance the effect of immunotherapy. We propose a protocol combining CPIs and hypofractionated radiotherapy for older patients with locally advanced cutaneous head and neck cancer who are not candidates for surgery. Prospective studies should be performed to verify this hypothesis. Full article
(This article belongs to the Special Issue Skin Cancer: Recent Advances in Diagnosis, Treatment, and Prevention)
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