Skin Cancer: From Molecular Basis to Therapy

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (19 April 2024) | Viewed by 7634

Special Issue Editor


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Guest Editor
Lega italiana per la Lotta contro i Tumori (LILT) – Associazione Provinciale di Padova, Padua, Italy
Interests: dermatology; atopic dermatitis; skin cancer; autoimmune bullous disorders
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Special Issue Information

Dear Colleagues,

Keratinocyte tumors, commonly referred to as nonmelanoma skin cancer (NMSC), constitute a heavy burden of disease, being the leading malignancy in terms of frequency for Caucasian individuals. Specifically, in subjects with lighter skin phototypes, basal cell carcinoma (BCC) is the most common cancer. On the other hand, melanoma is a global health concern, being among the most common malignancies responsible for years of life lost in young adults. Additionally, rarer types of cancer arise in the skin: cutaneous lymphomas are a group of malignant lymphocyte proliferations that feature striking skin-homing even during dissemination, which sets them apart from nodal forms of lymphoma. Finally, Kaposi sarcoma is a multifocal systemic disease that challenges the traditional dogma of cancer clonality.

This Special Issue welcomes contributions that highlight a multidisciplinary approach to the diagnosis and management of skin cancer and will focus on the following:

- Basic science research providing novel insights into signal transduction pathways in cutaneous carcinogenesis and into the role of “mutator phenotypes” in individuals with hereditary tumor predisposition syndromes; 
- Recent updates in the early detection of skin cancers and in strategies aimed at reducing UV radiation exposure;
- Innovative approaches in the surgical or skin-directed treatments of skin cancer;
- While the breakthrough therapies that have revolutionized the management of advanced skin cancer are beyond the current scope, contributions emphasizing the significance of a multidisciplinary approach in this setting as well as the patients’ perspective, are an appreciated addition to this issue.

This Special Issue is now open to the submission of new research papers, reviews, commentaries, and case reports. Prospective contributors are encouraged to share a brief abstract or provisional title with the Editorial Office to discuss with the Editors.

Dr. Alvise Sernicola
Guest Editor

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Keywords

  • nonmelanoma skin cancer
  • melanoma
  • cutaneous lymphoma
  • Kaposi sarcoma
  • skin directed therapy
  • carcinogenesis
  • UV radiation
  • tumor predisposition syndrome

Published Papers (6 papers)

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Research

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22 pages, 1202 KiB  
Article
Pattern Analysis of Benign and Malignant Atypical Melanocytic Skin Lesions of Palms and Soles: Variations of Dermoscopic Features According to Anatomic Site and Personal Experience
by Linda Tognetti, Alessandra Cartocci, Elvira Moscarella, Aimilios Lallas, Emi Dika, Maria Concetta Fargnoli, Caterina Longo, Gianluca Nazzaro, John Paoli, Ignazio Stanganelli, Serena Magi, Francesco Lacarrubba, Paolo Broganelli, Jean-Luc Perrot, Mariano Suppa, Roberta Giuffrida, Elisa Cinotti, Lo Conte Sofia, Gennaro Cataldo, Gabriele Cevenini and Pietro Rubegniadd Show full author list remove Hide full author list
Life 2024, 14(6), 659; https://doi.org/10.3390/life14060659 - 22 May 2024
Viewed by 249
Abstract
Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. [...] Read more.
Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. Aims: To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. Methods: A dataset of 471 aMPPLs—excised in the suspect of malignancy—was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. Results: A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the “fingers area” (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most “difficult” to diagnose, the parallel ridge pattern was poorly recognized and irregular/regular fibrillar patterns often misinterpreted. Regarding the aMPPL of the “heel area”, the parallel furrow pattern (p = 0.014) and lattice-like pattern (p = 0.001) significantly discriminated benign cases, while asymmetry of colors (p = 0.002) and regression structures (p = 0.025) malignant ones. In aMPPLs of the “plantar arch”, the lattice-like pattern (p = 0.012) was significant for benignity and asymmetry of structures, asymmetry of colors, regression structures, or blue-white veil for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. Conclusions: This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Basis to Therapy)
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28 pages, 6894 KiB  
Article
Recent Updates Regarding the Antiproliferative Activity of Galium verum Extracts on A375 Human Malignant Melanoma Cell Line
by Alexandra-Denisa Semenescu, Elena-Alina Moacă, Andrada Iftode, Cristina-Adriana Dehelean, Diana-Simona Tchiakpe-Antal, Laurian Vlase, Slavita Rotunjanu, Delia Muntean, Sorin Dan Chiriac and Raul Chioibaş
Life 2024, 14(1), 112; https://doi.org/10.3390/life14010112 - 11 Jan 2024
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Abstract
The biological activity of Galium verum herba was exerted on various tumor cell lines with incredible results, but their potential effect on malignant melanoma has not been established yet. Therefore, the current study was structured in two directions: (i) the investigation of the [...] Read more.
The biological activity of Galium verum herba was exerted on various tumor cell lines with incredible results, but their potential effect on malignant melanoma has not been established yet. Therefore, the current study was structured in two directions: (i) the investigation of the phytochemical profile of diethyl ether (GvDEE) and butanol (GvBuOH) extracts of G. verum L. and (ii) the evaluation of their biological profile on A375 human malignant melanoma cell line. The GvDEE extract showed an FT-IR profile different from the butanol one, with high antioxidant capacity (EC50 of GvDEE = 0.12 ± 0.03 mg/mL > EC50 of GvBuOH = 0.18 ± 0.05 mg/mL). The GvDEE extract also showed antimicrobial potential, especially against Gram-positive bacteria strains, compared to the butanol extract, which has no antimicrobial activity against any bacterial strain tested. The results regarding the antitumor potential showed that both extracts decreased A375 cell viability largely (69% at a dose of 55 µg/mL of the GvDEE extract). Moreover, both extracts induce nuclear fragmentation by forming apoptotic bodies and slight chromatin condensation, which is more intense for GvDEE. Considering the results, one can state that the Galium verum herba possesses antitumor effects on the A375 human malignant melanoma cell line, a promising phytocompound for the antitumor approach to skin cancer. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Basis to Therapy)
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14 pages, 6906 KiB  
Article
UVA/UVB Irradiation Exerts a Distinct Phototoxic Effect on Human Keratinocytes Compared to Human Malignant Melanoma Cells
by Otilia Gag, Ștefania Dinu, Horațiu Manea, Iasmina Marcovici, Iulia Pînzaru, Ramona Popovici, Zorin Crăiniceanu, Zsolt Gyori, Gheorghe Iovănescu and Sorin Chiriac
Life 2023, 13(5), 1144; https://doi.org/10.3390/life13051144 - 8 May 2023
Cited by 1 | Viewed by 2225
Abstract
Solar ultraviolet radiation (UVR) is responsible for the development of many skin diseases, including malignant melanoma (MM). This study assessed the phototoxic effects of UVA, and UVB radiations on healthy and pathologic skin cells by evaluating the behavior of human keratinocytes (HaCaT) and [...] Read more.
Solar ultraviolet radiation (UVR) is responsible for the development of many skin diseases, including malignant melanoma (MM). This study assessed the phototoxic effects of UVA, and UVB radiations on healthy and pathologic skin cells by evaluating the behavior of human keratinocytes (HaCaT) and MM cells (A375) at 24 h post-irradiation. The main results showed that UVA 10 J/cm2 exerted no cytotoxicity on HaCaT and A375 cells, while UVB 0.5 J/cm2 significantly reduced cell viability and confluence, induced cell shrinkage and rounding, generated nuclear and F-actin condensation, and induced apoptosis by modulating the expressions of Bax and Bcl-2. The association of UVA 10 J/cm2 with UVB 0.5 J/cm2 (UVA/UVB) induced the highest cytotoxicity in both cell lines (viability < 40%). However, the morphological changes were different—HaCaT cells showed signs of necrosis, while in A375 nuclear polarization and expulsion from the cells were observed, features that indicate enucleation. By unraveling the impact of different UVR treatments on the behavior of normal and cancer skin cells and describing enucleation as a novel process involved in the cytotoxicity of UVA/UVB irradiation, these findings bridge the gap between the current and the future status of research in the field. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Basis to Therapy)
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Review

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12 pages, 471 KiB  
Review
Role of IL-4 and IL-13 in Cutaneous T Cell Lymphoma
by Roberto Mazzetto, Paola Miceli, Jacopo Tartaglia, Christian Ciolfi, Alvise Sernicola and Mauro Alaibac
Life 2024, 14(2), 245; https://doi.org/10.3390/life14020245 - 9 Feb 2024
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Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Basis to Therapy)
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Other

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12 pages, 6539 KiB  
Case Report
Madelung’s Disease Evolving to Liposarcoma: An Uncommon Encounter
by Mihaiela Lungu, Violeta Diana Oprea, Gabriela Stoleriu, Ana-Maria Ionescu, Andrei Lucian Zaharia, Ana Croitoru, Bianca Stan and Elena Niculet
Life 2024, 14(4), 521; https://doi.org/10.3390/life14040521 - 17 Apr 2024
Viewed by 658
Abstract
(1) Background: Madelung’s disease—known also as Benign Symmetric Adenolipomatosis (BSA) or Multiple Symmetric Lipomatosis (MSL), is a rare subcutaneous tissue disease characterized by the proliferation of non-encapsulated fat tissue with mature adipocytes. Patients develop symmetrical fatty deposits of varying sizes, (located particularly around [...] Read more.
(1) Background: Madelung’s disease—known also as Benign Symmetric Adenolipomatosis (BSA) or Multiple Symmetric Lipomatosis (MSL), is a rare subcutaneous tissue disease characterized by the proliferation of non-encapsulated fat tissue with mature adipocytes. Patients develop symmetrical fatty deposits of varying sizes, (located particularly around the neck, shoulders, upper and middle back, arms, abdomen, and thighs), having clinical, esthetic, and psychiatric repercussions. (2) Methods: We report a case diagnosed with BSA upon admission to the Neurological and Internal Medicine Departments of the Emergency Clinical Hospital of Galati. (3) Results: This patient developed compressive phenomena and liposarcoma with liver metastasis, followed by death shortly after hospital presentation. The histopathology examination confirmed right latero-cervical liposarcoma and round cell hepatic metastasis. The specific metabolic ethiopathogenic mechanism has not been elucidated, but the adipocytes of BSA are different from normal cells in proliferation, hormonal regulation, and mitochondrial activity; a rare mitochondrial gene mutation, together with other interacting genetic or non-genetic factors, have been considered in recent studies. A thorough literature search identified only three cases reporting malignant tumors in BSA patients. (4) Conclusions: The goal of our paper is to present this rare case in the oncogenic synergism of two tumors. In the management of this BSA disorder, possible malignant transformation should be considered, although only scarce evidence was found supporting this. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Basis to Therapy)
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8 pages, 16951 KiB  
Case Report
Poorly Differentiated Cutaneous Squamous Cell Carcinoma (cSCC) or Lymphoepithelioma-like Carcinoma of the Skin (LELCS) with Squamous Pearls: A Case Presentation with Emphasis on Histomorphological Features and Classification Debates
by Sonia Maniglio, Gerardo Cazzato, Concetta Caporusso, Anna Colagrande, Eleonora Nacchiero, Michele Maruccia, Jacqueline Valerio, Eugenio Maiorano, Leonardo Resta, Andrea Marzullo, Giuseppe Giudice and Giuseppe Ingravallo
Life 2023, 13(12), 2265; https://doi.org/10.3390/life13122265 - 27 Nov 2023
Viewed by 1037
Abstract
Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare primary skin cancer, with an annual incidence of 1/100,000 and about 85 cases published in the literature. It is considered the cutaneous counterpart of undifferentiated nasopharyngeal carcinoma (UNC, Schmincke–Regaud tumor) but has no association [...] Read more.
Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare primary skin cancer, with an annual incidence of 1/100,000 and about 85 cases published in the literature. It is considered the cutaneous counterpart of undifferentiated nasopharyngeal carcinoma (UNC, Schmincke–Regaud tumor) but has no association with EBV. We present an interesting case with features of LELCS in a 93-year-old man, right frontal–orbital region, diagnosed histologically and with immunohistochemical features. We also emphasize contrasting morphologic features for correct nosographic classification and address current issues, suggesting potential insights. Finally, we briefly reviewed other cases described in the literature. Full article
(This article belongs to the Special Issue Skin Cancer: From Molecular Basis to Therapy)
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