Special Issue "Current Advances on Non-Melanoma Skin Cancer"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Dermatology".

Deadline for manuscript submissions: closed (31 August 2020).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Constantin Caruntu
E-Mail Website
Guest Editor
Department of Physiology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
Interests: physiology and physiopathology of the skin and oral mucosa; dermato-oncology; in vivo reflectance confocal microscopy
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Special Issue Information

Dear Colleagues,

Non‑melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and several rare skin tumors and is the most common malignancy affecting humans worldwide. It accounts for the vast majority of skin cancers and a large percentage of all malignant tumors. Despite the growing public awareness and scientific interest regarding the risk of skin cancer, the incidence of NMSC is still rapidly increasing. Even if most NMSCs are associated with a less aggressive behavior, they can still be locally invasive and may produce extensive destruction of neighboring structures, inducing significant morbidity. Moreover, different types or subtypes of NMSCs are associated with frequent recurrence and may carry a significant metastatic potential. As a direct consequence, NMSC has become a major burden on healthcare systems with a significant socio‑economic impact.

Hence, there is no doubt as to why these keratinocyte-derived tumors are in the spotlight of scientific interest for both fundamental research and clinical practice, and this Special Issue aims to bring together the most recent and relevant scientific research on NMSC. Studies regarding the complex inherited and environmental factors that can trigger tumor initiation and progression may offer a new perspective on skin cancer prevention. Investigation of new markers of skin carcinogenesis may contribute to the development of novel diagnostic, staging, and prognosis strategies for skin cancer and could lead to the design of more sophisticated and individually tailored treatment protocols. Improvements related to non-invasive or minimally invasive diagnostic tools and treatment methods may ameliorate the discomfort of patients while also reducing the costs associated with therapy. Moreover, the development of new techniques for early diagnosis of NMSCs could reduce morbidity, ensuring more efficient treatment with better aesthetic and functional results.

Dr. Constantin Caruntu
Guest Editor

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Keywords

  • non-melanoma skin cancer
  • basal cell carcinoma
  • squamous cell carcinoma
  • prevention
  • early diagnosis
  • treatment
  • new technologies

Published Papers (7 papers)

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Research

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Article
In Vivo Reflectance Confocal Microscopy-Diagnostic Criteria for Actinic Cheilitis and Squamous Cell Carcinoma of the Lip
J. Clin. Med. 2020, 9(6), 1987; https://doi.org/10.3390/jcm9061987 - 25 Jun 2020
Cited by 2 | Viewed by 855
Abstract
Actinic cheilitis (AC) is one of the most frequent pathologies to affect the lips. Studies show that the most commonplace oral malignancy, squamous cell carcinoma (SCC), often emerges from AC lesions. Invasive diagnostic techniques performed on the lips carry a high risk of [...] Read more.
Actinic cheilitis (AC) is one of the most frequent pathologies to affect the lips. Studies show that the most commonplace oral malignancy, squamous cell carcinoma (SCC), often emerges from AC lesions. Invasive diagnostic techniques performed on the lips carry a high risk of complications, but reflectance confocal microscopy (RCM), a non-invasive skin imaging technique, may change the current diagnostic pathway. This retrospective study was aimed at consolidating the RCM diagnostic criteria for AC and lip SCC. The study was conducted in two tertiary care centers in Bucharest, Romania. We included adults with histopathologically confirmed AC and SCC who also underwent RCM examination. Of the twelve lesions included in the study, four were AC and eight were SCC. An atypical honeycomb pattern and the presence of target cells in the epidermis were RCM features associated with AC. SCC was typified by the presence of complete disruption of the epidermal architecture and dermal inflammatory infiltrates. The mean blood vessel diameter in SCC was 18.55 µm larger than that in AC (p = 0.006) and there was no significant difference (p = 0.64) in blood vessel density, as measured by RCM, between SCC and AC. These data confirm that RCM can be useful for the in vivo distinction between AC and lip SCC. Full article
(This article belongs to the Special Issue Current Advances on Non-Melanoma Skin Cancer)
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Article
Use of Cytology in the Diagnosis of Basal Cell Carcinoma Subtypes
J. Clin. Med. 2020, 9(3), 612; https://doi.org/10.3390/jcm9030612 - 25 Feb 2020
Cited by 1 | Viewed by 1129
Abstract
Background: Basal cell carcinoma (BCC) is the most common skin cancer in the white population. Nonsurgical treatments are first-line alternatives in superficial BCC (sBCC); therefore, differentiating between sBCC and non-sBCC is of major relevance for the clinician. Scraping cytology possesses several advantages, such [...] Read more.
Background: Basal cell carcinoma (BCC) is the most common skin cancer in the white population. Nonsurgical treatments are first-line alternatives in superficial BCC (sBCC); therefore, differentiating between sBCC and non-sBCC is of major relevance for the clinician. Scraping cytology possesses several advantages, such as an earlier diagnosis and scarring absence, in comparison to a biopsy. Nevertheless, previous studies reported difficulties in differentiating the different BCC subtypes. The objective of this study was to determine the capability and accuracy of scraping cytology to differentiate between sBCC and non-sBCC. Methods: In this retrospective study, cytological samples of histologically confirmed BCC were examined. Select cytological features were correlated to BCC subtypes (sBCC or non-sBCC). Results: A total of 84 BCC samples were included (29 sBCC; 55 non-sBCC). An inverse correlation between the diagnosis of sBCC and the presence of mucin, dehiscence, and grade of atypia in the basal cells was observed. The presence of medium and large basal cell clusters correlated directly to a sBCC diagnosis. The presence of clear cells is strongly associated with sBCC. Therefore, Conclusion: Scraping cytology is reliable in differentiating sBCC from other BCC subtypes. Full article
(This article belongs to the Special Issue Current Advances on Non-Melanoma Skin Cancer)
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Article
Influence of Serum Vitamin D Level in the Response of Actinic Keratosis to Photodynamic Therapy with Methylaminolevulinate
J. Clin. Med. 2020, 9(2), 398; https://doi.org/10.3390/jcm9020398 - 01 Feb 2020
Cited by 2 | Viewed by 1364
Abstract
In mouse models of squamous cell carcinoma, pre-treatment with calcitriol prior to photodynamic therapy with aminolevulinic acid (ALA) enhances tumor cell death. We have evaluated the association between vitamin D status and the response of actinic keratoses to photodynamic therapy with methylaminolevulinate. Twenty-five [...] Read more.
In mouse models of squamous cell carcinoma, pre-treatment with calcitriol prior to photodynamic therapy with aminolevulinic acid (ALA) enhances tumor cell death. We have evaluated the association between vitamin D status and the response of actinic keratoses to photodynamic therapy with methylaminolevulinate. Twenty-five patients with actinic keratoses on the head received one session of photodynamic therapy with methylaminolevulinate. Biopsies were taken at baseline and six weeks after treatment. Immuno-histochemical staining was performed for VDR, P53, Ki67 and β-catenin. Basal serum 25(OH)D levels were determined. Cases with a positive histological response to treatment had significantly higher serum 25(OH)D levels (26.96 (SD 7.49) ngr/mL) than those without response (18.60 (SE 7.49) ngr/mL) (p = 0.05). Patients with a complete clinical response displayed lower basal VDR expression (35.71% (SD 19.88)) than partial responders (62.78% (SD 16.735)), (p = 0.002). Our results support a relationship between vitamin D status and the response of actinic keratoses to photodynamic therapy with methylaminolevulinate. Full article
(This article belongs to the Special Issue Current Advances on Non-Melanoma Skin Cancer)
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Review

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Review
Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma
J. Clin. Med. 2020, 9(9), 3010; https://doi.org/10.3390/jcm9093010 - 18 Sep 2020
Cited by 2 | Viewed by 738
Abstract
Basal cell carcinoma (BCC) is the most common malignant skin tumor. BCC displays a different behavior compared with other neoplasms, has a slow evolution, and metastasizes very rarely, but sometimes it causes an important local destruction. Chronic ultraviolet exposure along with genetic factors [...] Read more.
Basal cell carcinoma (BCC) is the most common malignant skin tumor. BCC displays a different behavior compared with other neoplasms, has a slow evolution, and metastasizes very rarely, but sometimes it causes an important local destruction. Chronic ultraviolet exposure along with genetic factors are the most important risk factors involved in BCC development. Mutations in the PTCH1 gene are associated with Gorlin syndrome, an autosomal dominant disorder characterized by the occurrence of multiple BCCs, but are also the most frequent mutations observed in sporadic BCCs. PTCH1 encodes for PTCH1 protein, the most important negative regulator of the Hedgehog (Hh) pathway. There are numerous studies confirming Hh pathway involvement in BCC pathogenesis. Although Hh pathway has been intensively investigated, it remains incompletely elucidated. Recent studies on BCC tumorigenesis have shown that in addition to Hh pathway, there are other signaling pathways involved in BCC development. In this review, we present recent advances in BCC carcinogenesis. Full article
(This article belongs to the Special Issue Current Advances on Non-Melanoma Skin Cancer)
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Review
Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer
J. Clin. Med. 2020, 9(9), 2868; https://doi.org/10.3390/jcm9092868 - 04 Sep 2020
Cited by 6 | Viewed by 1210
Abstract
Skin cancer represents the most common type of cancer among Caucasians and presents in two main forms: melanoma and non-melanoma skin cancer (NMSC). NMSC is an umbrella term, under which basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC) [...] Read more.
Skin cancer represents the most common type of cancer among Caucasians and presents in two main forms: melanoma and non-melanoma skin cancer (NMSC). NMSC is an umbrella term, under which basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC) are found along with the pre-neoplastic lesions, Bowen disease (BD) and actinic keratosis (AK). Due to the mild nature of the majority of NMSC cases, research regarding their biology has attracted much less attention. Nonetheless, NMSC can bear unfavorable characteristics for the patient, such as invasiveness, local recurrence and distant metastases. In addition, late diagnosis is relatively common for a number of cases of NMSC due to the inability to recognize such cases. Recognizing the need for clinically and economically efficient modes of diagnosis, staging, and prognosis, the present review discusses the main etiological and pathological features of NMSC as well as the new and promising molecular biomarkers available including telomere length (TL), telomerase activity (TA), CpG island methylation (CIM), histone methylation and acetylation, microRNAs (miRNAs), and micronuclei frequency (MNf). The evaluation of all these aspects is important for the correct management of NMSC; therefore, the current review aims to assist future studies interested in exploring the diagnostic and prognostic potential of molecular biomarkers for these entities. Full article
(This article belongs to the Special Issue Current Advances on Non-Melanoma Skin Cancer)
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Review
Deciphering the Molecular Landscape of Cutaneous Squamous Cell Carcinoma for Better Diagnosis and Treatment
J. Clin. Med. 2020, 9(7), 2228; https://doi.org/10.3390/jcm9072228 - 14 Jul 2020
Cited by 3 | Viewed by 804
Abstract
Cutaneous squamous cell carcinoma (cSCC) is a common type of neoplasia, representing a terrible burden on patients’ life and clinical management. Although it seldom metastasizes, and most cases can be effectively treated with surgical intervention, once metastatic cSCC displays considerable aggressiveness leading to [...] Read more.
Cutaneous squamous cell carcinoma (cSCC) is a common type of neoplasia, representing a terrible burden on patients’ life and clinical management. Although it seldom metastasizes, and most cases can be effectively treated with surgical intervention, once metastatic cSCC displays considerable aggressiveness leading to the death of affected individuals. No consensus has been reached as to which features better characterize the aggressive behavior of cSCC, an achievement hindered by the high mutational burden caused by chronic ultraviolet light exposure. Even though some subtypes have been recognized as high risk variants, depending on certain tumor features, cSCC that are normally thought of as low risk could pose an increased danger to the patients. In light of this, specific genetic and epigenetic markers for cutaneous SCC, which could serve as reliable diagnostic markers and possible targets for novel treatment development, have been searched for. This review aims to give an overview of the mutational landscape of cSCC, pointing out established biomarkers, as well as novel candidates, and future possible molecular therapies for cSCC. Full article
(This article belongs to the Special Issue Current Advances on Non-Melanoma Skin Cancer)
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Review
A Systematic Review and Meta-Analysis of the Accuracy of in Vivo Reflectance Confocal Microscopy for the Diagnosis of Primary Basal Cell Carcinoma
J. Clin. Med. 2019, 8(9), 1462; https://doi.org/10.3390/jcm8091462 - 13 Sep 2019
Cited by 9 | Viewed by 1416
Abstract
Basal cell carcinoma (BCC) is the most common cancer worldwide and its incidence is constantly rising. Early diagnosis and treatment can significantly reduce patient morbidity and healthcare costs. The value of reflectance confocal microscopy (RCM) in non-melanoma skin cancer diagnosis is still under [...] Read more.
Basal cell carcinoma (BCC) is the most common cancer worldwide and its incidence is constantly rising. Early diagnosis and treatment can significantly reduce patient morbidity and healthcare costs. The value of reflectance confocal microscopy (RCM) in non-melanoma skin cancer diagnosis is still under debate. This systematic review and meta-analysis were conducted to assess the diagnostic accuracy of RCM in primary BCC. PubMed, Google Scholar, Scopus, and Web of Science databases were searched up to July 05, 2019, to collect articles concerning primary BCC diagnosis through RCM. The studies’ methodological quality was assessed by the QUADAS-2 tool. The meta-analysis was conducted using Stata 13.0, RevMan 5.0, and MetaDisc 1.4 software. We included 15 studies totaling a number of 4163 lesions. The pooled sensitivity and specificity were 0.92 (95% CI, 0.87–0.95; I2 = 85.27%) and 0.93 (95% CI, 0.85–0.97; I2 = 94.61%), the pooled positive and negative likelihood ratios were 13.51 (95% CI, 5.8–31.37; I2 = 91.01%) and 0.08 (95% CI, 0.05–0.14; I2 = 84.83%), and the pooled diagnostic odds ratio was 160.31 (95% CI, 64.73–397.02; I2 = 71%). Despite the heterogeneity and risk of bias, this study demonstrates that RCM, through its high sensitivity and specificity, may have a significant clinical impact on the diagnosis of primary BCC. Full article
(This article belongs to the Special Issue Current Advances on Non-Melanoma Skin Cancer)
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