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Background/Objectives: Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are non-melanoma skin cancers (NMSCs) and the most prevalent cancers in the United States. Image-guided superficial radiotherapy (IGSRT) is a relatively new treatment option that uses high-resolution dermal ultrasound integrated with superficial radiotherapy to improve tumor visualization. IGSRT is a clinically equivalent non-surgical alternative to Mohs micrographic surgery at 2 years of follow-up in early-stage NMSC, but larger cohort studies with longer follow-up periods that allow for analysis of patient outcomes by demographic and disease characteristics are needed. Methods: This large, retrospective cohort study was conducted to determine the effect of risk factors (tumor location, tumor stage, and sex) on 2-, 4-, and 6-year freedom from recurrence rates in 19,988 NMSC lesions treated with IGSRT, including lesions with complete treatment courses. Results: Overall freedom from recurrence rates were 99.68% at 2 years, 99.54% at 4 years, and 99.54% at 6 years; rates did not differ significantly by tumor location (head/neck versus other locations, p = 0.9) or sex (male versus female, p = 0.4). In contrast, there was a significant difference in freedom from recurrence rates when analyzed by tumor stage (p = 0.004). Conclusions: There was no significant effect of tumor location or sex on freedom from recurrence in IGSRT-treated NMSC. Although there was a significant difference according to tumor stage, freedom from recurrence rates exceeded 99% at all stages. [ABSTRACT FROM AUTHOR]

Non-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), are increasingly common and present significant healthcare challenges. Neutrophil extracellular traps (NETs), chromatin fibers expulsed by neutrophil granulocytes, can promote immunotherapy resistance via an impairment of CD8+ T cell-mediated cytotoxicity. Here, to identify a potential therapeutic target, we investigate the expulsion of NETs and their relation to CD8+ T cell infiltration in NMSC. Immunofluorescence staining for neutrophils (CD15) and NETs (H3cit), as well as immunohistochemistry for cytotoxic T cells (CD8+) on human cSCCs (n = 24), BCCs (n = 17) and MCCs (n = 12), revealed a correlation between neutrophil infiltration and ulceration diameter in BCC and MCC, but not in cSCC. In BCC and cSCC, neutrophil infiltration also correlated with the cross-sectional area (CSA). NETs were not associated with established risk factors but with the presence of an ulceration, and, in cSCC, with abscess-like structures. CD8+ T cell infiltration was not reduced in tumors that were NET-positive nor in those with a denser neutrophil infiltration. This study is the first to report and characterize NETs in NMSC. Thus, it gives an incentive for further research in this relevant yet understudied topic. [ABSTRACT FROM AUTHOR]

Background: Basal Cell Carcinoma (BCC) is the most common type of skin carcinoma and is considered an epidemic disease due to its increasing frequency in many countries. The most important problem of BCC is local invasion It grows in a "silent" way into immediately adjacent tissue. It rarely metastasizes. The early tumors are commonly small, translucent or pearly, raised and rounded areas located on a few dilated, superficial vessels. There are six subtypes of BCC that include nodular, pigmented, superficial, morphea form, cystic. The most important risk factor for basal cell carcinoma is exposure to UV-radiation. Outdoor workers with a long history of workrelated UV-exposure are at increased risk of developing BCC. Other risk factors include family history of skin carcinoma, light skin phototypes, advanced age. Objective: The current study investigated pathological and histological changes in tissue sections to identify the factors contributing to the infection frequency. Patients and Methods: Thirty-three BCC patients' samples have been collected from the main care center at al-Baquba Teaching Hospital of Diyala Province, Iraq. All patient groups were clinically diagnosed as BCC by dermatologists. Results: The study showed macroscopic and microscopic histological changes. An ulcerated macroscopic appearance of the lesion was shown. The tumor lesions are located on the face. It was noted that the percentage of patients was higher in men than women and higher in light skin than dark skin. The study also showed that the age group 66-74 years had a higher infection percentage, while the lower percentage was of the age group > 83 years. Conclusion: These findings pave the way for future research endeavors aimed at prevention, early detection, and targeted treatment strategies for this prevalent skin carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: This research explored a new method to evaluate surgical margins when removing non-melanoma skin cancer, aiming to reduce the time patients need to stay in the hospital. Typically, surgeons use 3D histology to ensure all cancer tissues have been removed, but this process is time-consuming. This study suggests using ex vivo reflectance confocal microscopy (evRCM), which allows for quicker margin assessments. While evRCM showed high accuracy in confirming cancer-free areas, it was not as effective in detecting small remaining cancer cells as histology. Despite this limitation, evRCM significantly reduced patients' time in the hospital. These findings suggest that evRCM could become a valuable tool for improving the speed and accuracy of skin cancer surgery; however, its effectiveness is limited. Close collaboration between surgeons and pathologists is mandatory to achieve good patient outcomes. Background/Objectives: To ensure that non-melanoma skin cancer (NMSC) is completely removed in healthy tissue, micrographically controlled surgery (3D histology) is often performed, which can prolong the inpatient stay. This study examined ex vivo reflectance confocal microscopy (evRCM) for perioperative assessment of surgical margins, specifically in cases where re-excision was necessary due to incomplete removal of cutaneous tumor tissue. Methods: NMSC re-excisions were evaluated using evRCM by a cutaneous surgeon, with retrospective review by an independent pathologist when results differed from histology. Results: evRCM demonstrated high specificity (0.96; 95% CI, 0.90–0.99) but low sensitivity (0.20; 95% CI, 0.06–0.51). Unlike pathology, which discards outer surgical margins, evRCM examined the true surgical margins. Retrospective pathology analysis of the misdiagnosed cases confirmed that 25% (n = 2/8) were false negative and 75% (n = 6/8) were potentially false positive, resulting in a sensitivity of 0.2–0.8. Notably, evRCM led to a 113-day reduction in in-hospital stays, probably resulting in increased patient satisfaction and cost-effectiveness. Conclusions: evRCM was valuable for speeding up the assessment of surgical margins in patients with re-excised NMSC. Proper tissue preparation and assessment require interdisciplinary collaboration between cutaneous surgeons, pathologists, and physician assistants, emphasizing the need for standardized operating procedures. [ABSTRACT FROM AUTHOR]

Background: Innovative treatments for non‐melanoma skin cancers (NMSCs) are required to enhance patient outcomes. Aims: This review examines the effectiveness and safety of receptor tyrosine kinase inhibitors (RTKIs). Methods: A comprehensive review was conducted on the treatment potential of several RTKIs, namely cetuximab, erlotinib, gefitinib, panitumumab, and lapatinib. Results: The findings indicate that these targeted therapies hold great promise for the treatment of NMSCs. However, it is crucial to consider relapse rates and possible adverse effects. Further research is needed to improve treatment strategies, identify patient groups that would benefit the most, and assess the long‐term efficacy and safety, despite the favorable results reported in previous studies. Furthermore, it is crucial to investigate the potential benefits of integrating RTKIs with immunotherapy and other treatment modalities to enhance the overall efficacy of therapy for individuals with NMSC. Conclusions: Targeted therapies for NMSCs may be possible with the use of RTKIs. The majority of studies focused on utilizing epidermal growth factor receptor inhibitors as the primary class of RTKIs for the treatment of NMSC. Other RTKIs were only employed in experimental investigations. Research indicates that RTKIs could potentially serve as a suitable alternative for elderly patients who are unable to undergo chemotherapy and radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Skin cancer shows geographic and ethnic variation. New Zealand—with a predominantly fair-skinned populations, high UV indices and outdoor lifestyles—has high rates of skin cancer. However, population prevalence data is lacking. This study aimed to determine the demographics and socioeconomic disease trends of non-melanoma skin cancer prevalence in New Zealand from a large targeted-screening study. Methods: A targeted screening programme was conducted among 32,839 individuals, Fitzpatrick Skin Types I to IV in Auckland, New Zealand during the 2008–2022 period. This data was analyzed retrospectively. Linear regression models were used to assess statistical trends of skin cancer prevalence over time, along with associated factors that included demographics, disease trends and overall prevalence. Results: A total of 32,839 individuals were screened and 11,625 skin cancers were detected. 16,784 individuals were females who had 4,378 skin cancers. 16,055 individuals were males who had 5,777 skin cancers. 54 males and 65 females had multiple skin cancers. The article presents detailed descriptions of tumour types and subtypes detected, age groups, demographic and socioeconomic information. regarding the non-melanoma skin cancers detected. Conclusion: Overall men have more non-melanoma skin cancer (NMSC) than females; however females develop more BCC on the lips. BCC is three times more common in the 31-50 age group, whereas SCC are significantly more prevalent after age 80. Prevalence of BCC has not changed over the 15-year timeframe of the study but SCC has increased. Older ages and higher incomes are associated with higher rates of NMSC in New Zealand. [ABSTRACT FROM AUTHOR]

Purpose: Long‐term use of hydrochlorothiazide increases the risk of non‐melanoma skin cancer. We aimed to evaluate potential changes in the use of hydrochlorothiazide in Switzerland after a direct healthcare professional communication (DHPC) in November 2018 by Swissmedic. Methods: We performed interrupted time‐series analyses using a large Swiss healthcare claims database (2015–2021). Within monthly intervals, we quantified the total number of claims and the total dispensed 'defined daily doses' (DDD) for preparations containing (1) hydrochlorothiazide, (2) angiotensin‐converting enzyme (ACE) inhibitors and angiotensin‐II‐receptor blockers (ARB), (3) calcium‐channel blockers (CCB) and (4) thiazide‐like diuretics per 10 000 persons. Using segmented linear regression, we quantified the pre‐DHPC trend, the immediate change and the post‐DHPC change in trend for total claims and DDD for the four drug classes weighted for the demographic distribution of the Swiss population. Results: ACE inhibitors and ARB were the most frequently claimed antihypertensive drugs with 300–400 claims per 10 000 persons, which increased by 5.4% during the study period. The average number of hydrochlorothiazide claims (157/10 000 persons in 2015) declined by 35% between 2015 and 2021. The decrease started prior to the DHPC, but the DHPC was associated with an immediate 6.1% decline and an accelerated decline in claims over time after the DHPC (similar results for DDD). This coincided with a 23% increase in claims of CCB (dihydropyridine type) over 7 years, whereas use of other antihypertensives increased less. Conclusion: Our results suggest that the DHPC by Swissmedic in 2018 accelerated a pre‐existing decline in the use of hydrochlorothiazide in Switzerland. [ABSTRACT FROM AUTHOR]

Abstract Background Skin cancer is the most common form of cancer in Ireland with over 13,000 new cases diagnosed annually. People with inflammatory bowel disease are at higher risk of developing skin cancer. Objectives The aim of this study is to assess inflammatory bowel disease (IBD) patients' awareness around skin cancer risk and photoprotection practices and to identify gaps in patient education regarding skin cancer prevention in IBD patients. Methods IBD patients >18 years old were invited to fill out a questionnaire while waiting for their outpatient appointment. Results A total of 87 patients (52% women) with IBD (Crohn's disease 62.8%, UC 35%,) were included. A total of 38 patients were diagnosed before age 25 (44%). Most patients were on active treatment for their IBD (96.5%, n = 85). Four patients had a personal history, and seven patients had a family history of skin cancer. Nearly half of participants (47.6%) were unaware or unsure of an increased risk of skin cancer associated with IBD and 42.5% were unaware or unsure of an increased risk with some IBD treatments. Behaviours around sun‐cream were generally good, however, other sun protective methods were suboptimal. Conclusions Only half (52.4%) of IBD patients surveyed were aware of a link between skin cancer and IBD. Skin cancer knowledge was generally good, however, photoprotection practices were suboptimal. This underscores the role of healthcare professionals in re‐enforcing sun safety information and skin cancer education in the IBD population.

Image-guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high-resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for dermatologists from a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of HRDUS used in conjunction with SRT for NMSC. Medical records from 7 dermatology clinics of 883 patients with 1507 cases of NMSC treated with IGSRT between 2017 and 2018 were retrospectively reviewed. In total, 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. In total, 83% of NMSC lesions were labeled as high risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF, and dose will result in more efficacy and less toxicity, respectively.

Abstract Background Skin cancer shows geographic and ethnic variation. New Zealand—with a predominantly fair-skinned populations, high UV indices and outdoor lifestyles—has high rates of skin cancer. However, population prevalence data is lacking. This study aimed to determine the demographics and socioeconomic disease trends of non-melanoma skin cancer prevalence in New Zealand from a large targeted-screening study. Methods A targeted screening programme was conducted among 32,839 individuals, Fitzpatrick Skin Types I to IV in Auckland, New Zealand during the 2008–2022 period. This data was analyzed retrospectively. Linear regression models were used to assess statistical trends of skin cancer prevalence over time, along with associated factors that included demographics, disease trends and overall prevalence. Results A total of 32,839 individuals were screened and 11,625 skin cancers were detected. 16,784 individuals were females who had 4,378 skin cancers. 16,055 individuals were males who had 5,777 skin cancers. 54 males and 65 females had multiple skin cancers. The article presents detailed descriptions of tumour types and subtypes detected, age groups, demographic and socioeconomic information. regarding the non-melanoma skin cancers detected. Conclusion Overall men have more non-melanoma skin cancer (NMSC) than females; however females develop more BCC on the lips. BCC is three times more common in the 31-50 age group, whereas SCC are significantly more prevalent after age 80. Prevalence of BCC has not changed over the 15-year timeframe of the study but SCC has increased. Older ages and higher incomes are associated with higher rates of NMSC in New Zealand.

In fair-skinned populations worldwide, skin cancer is a serious public health threat. A significant percentage of all reported occupational diseases fall back on skin cancer. Over the past few decades, there has been a rise in the frequency of skin cancer diagnoses among outdoor workers. The main cause of non-melanoma skin cancer is solar ultraviolet radiation (UVR), which is also the most common occupational carcinogenic exposure in terms of the number of exposed workers (i.e., outdoor workers). Sun protection—and concomitantly the prevention of occupational skin cancer—is a component of workplace safety. The risks of solar UVR exposure at work are often disregarded in practice, despite the recent recognition of the need for measures to support outdoor workers’ sun protection behavior. It is anticipated that occupational dermatology will become increasingly focused on sun safety in the coming decades. To handle current hurdles in a sustainable manner, the full range of preventive measures should be utilized. Existing strategies for the prevention of occupational skin cancer might be evolved and enriched by new (educational) concepts, methods, and/or technologies. In this, not only components of general prevention and individual prevention but also setting-based prevention and behavior-based prevention might be freshly thought through.

We present a case of a 49-year-old man with a giant basal cell carcinoma of the back, with metastases in the lungs, liver, mediastinum and both adrenal glands. Neoadjuvant vismodegib was administered, after which wide local resection of the tumour was performed. There have been no signs of local recurrence.

Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed the transcriptomic changes observed in epidermal PPARγ-deficient mice (Pparg-/-epi). A gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis, and cell survival. Single-cell sequencing of Pparg-/-epi mice verified changes to the stromal compartment, including increased inflammatory cell infiltrates, particularly neutrophils, and an increase in fibroblasts expressing myofibroblast marker genes. A comparison of transcriptomic data from Pparg-/-epi and publicly available human and/or mouse actinic keratoses (AKs) and cutaneous squamous cell carcinomas (SCCs) revealed a strong correlation between the datasets. Importantly, PPAR signaling was the top common inhibited canonical pathway in AKs and SCCs. Both AKs and SCCs also had significantly reduced PPARG expression and PPARγ activity z-scores. Smaller reductions in PPARA expression and PPARα activity and increased PPARD expression but reduced PPARδ activation were also observed. Reduced PPAR activity was also associated with reduced PPARα/RXRα activity, while LPS/IL1-mediated inhibition of RXR activity was significantly activated in the tumor datasets. Notably, these changes were not observed in normal sun-exposed skin relative to non-exposed skin. Finally, Ppara and Pparg were heavily expressed in sebocytes, while Ppard was highly expressed in myofibroblasts, suggesting that PPARδ has a role in myofibroblast differentiation. In conclusion, these data provide strong evidence that PPARγ and possibly PPARα represent key tumor suppressors by acting as master inhibitors of the inflammatory changes found in AKs and SCCs. [ABSTRACT FROM AUTHOR]

The keratinocyte carcinomas, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs, assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment. [ABSTRACT FROM AUTHOR]

Since the scrotum is rarely exposed to sunlight, basal cell carcinoma (BCC) development in this area is an uncommon occurrence. As result, there is a scarcity of research covering this particular presentation, which poses a diagnostic and therapeutic challenge for clinicians. The objective of this systematic review is to provide a thorough overview of scrotal BCC, including a summary of its clinical characteristics, and microscopic subtypes. It also seeks to discuss the many techniques used in the management of this uncommon clinical presentation. Utilizing data from 1957 to October 2023, a systematic review of PubMed and Wiley Online Library was conducted to identify all cases of scrotal BCC with various presentations and managements. A total of 73 patients were included. The median patient age was 65.9 years (range 42 to 87). All studies were either case reports or case series. Our review shows that treatment with Mohs micrographic surgery (MMS), leads to a superior patient outcome based on anecdotal evidence in select cases. To deepen our understanding of Mohs surgery’s efficacy in treating scrotal BCC, it is imperative to conduct more robust research in the form of randomized clinical trials. [ABSTRACT FROM AUTHOR]

Skin cancer is the most common cancer type in the USA, with over five million annually treated cases and one in five Americans predicted to develop the disease by the age of 70. Skin cancer can be classified as melanoma or non-melanoma (NMSC), the latter including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC). Development of BCC and SCC is impacted by environmental, behavioral, and genetic risk factors and the incidence is on the rise, with the associated number of deaths surpassing those caused by melanoma, according to recent reports. Substantial morbidity is related to both BCC and SCC, including disfigurement, loss of function, and chronic pain, driving high treatment costs, and representing a heavy financial burden to patients and healthcare systems worldwide. Clinical presentations of BCC and SCC can be diverse, sometimes carrying considerable phenotypic similarities to benign lesions, and underscoring the need for the development of disease-specific biomarkers. Skin biomarker profiling plays an important role in deeper disease understanding, as well as in guiding clinical diagnosis and patient management, prompting the use of both invasive and non-invasive tools to evaluate specific biomarkers. In this work, we review the known and emerging biomarkers of BCC and SCC, with a focus on molecular and histologic biomarkers relevant for aspects of patient management, including prevention/risk assessments, tumor diagnosis, and therapy selection. [ABSTRACT FROM AUTHOR]

Background: Seeding of skin cancer cells following diagnostic or therapeutic surgical procedures can occur and might cause local recurrences. As current preferred therapy for skin malignancy is surgical excision, seeding of tumour cells by manipulating malignant tissue or suturing can be another factor leading to recurrences. Objective: To evaluate whether genetic material and malignant cells adhere to standard suture materials. Methods: This prospective study included patients who underwent excision of skin lesions. Monofilament and braided sutures were examined. Sutures were passed through the observed tumour or healthy skin margins and were examined for DNA material and cells by cytological analysis, cell culture and characterization, and DNA analysis. Results: Twenty-two patients and 148 sutures were included. DNA quantification showed DNA material on all sutures, with no significant difference between braided and monofilament sutures. Cytological analysis showed that all slides prepared from cell blocks contained normal squamous and atypical cells. Cell culture and characterization showed viable cells adhering to the sutures under direct light microscopy. Cell cultures showed rapid proliferation of epithelial cells from squamous cell carcinoma specimens. Conclusion: Suture materials carry DNA material and cells, including malignant cells of cutaneous origin and may seed them at distant sites. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma is particularly common and its incidence is increasing. Effective treatment is needed to prevent local recurrence and metastasis. The aim of our systematic review was to assess the potential added value of Mohs micrographic surgery compared with conventional excision. The majority of included studies showed a lower risk of recurrence when Mohs micrographic surgery was used to treat cutaneous squamous cell carcinoma. In addition, Mohs micrographic surgery offers advantages for tumors located in aesthetically or anatomically challenging areas. However, this technique requires a certain level of expertise and additional time and resources. Background: The first-line treatment of the localized form of cutaneous squamous cell carcinoma (cSCC) remains surgical excision. Either conventional excision (CE) with margins or Mohs micrographic surgery (MMS) may be preferred, depending on the risk factors of cSCC, the characteristics of the tumor, and the available technical facilities. Methods: This article presents a systematic review of the current literature spanning from 1974 to 2023, comparing outcomes of cSCC treated with MMS versus cSCC treated with conventional excision. Results: Out of the 6821 records identified through the database search, a total of 156 studies were screened, of which 10 were included in the review. The majority of the included studies showed that treatment of cSCC with MMS consistently exhibits a significantly lower risk of recurrence compared to treatment with CE. In addition, MMS is emerging as the preferred technique for the resection of cSCC located in aesthetically or functionally challenging anatomical areas. Conclusion: The studies generally demonstrate that MMS is a safer and more effective treatment of cSCC than CE. Nevertheless, outcomes such as recurrence rates and cost-effectiveness should be assessed more precisely, in order to allow for a more tailored approach in determining the appropriate indication for the use of MMS. [ABSTRACT FROM AUTHOR]

Opinion statement: Neoadjuvant immunotherapy will change the standard of care for advanced resectable cutaneous squamous cell carcinoma (cSCC) and possibly other non-melanoma skin cancers. With pathological complete response rates around 50% for cSCC in early studies, neoadjuvant therapy allows patients the possibility of significant reduction in tumor size, de-escalation of adjuvant therapy, and improved long-term outcomes. Patients must be carefully selected to ensure that there is a margin of safety with respect to resectability, such that if a tumor progresses on neoadjuvant therapy, there remains a curative surgical option that is acceptable to the patient. The optimal treatment paradigm is an area of active research, with many researchers questioning whether adjuvant therapy, or even local therapy, is necessary in patients who seem to have a complete response. The ability to predict who will respond will become even more critical to answer, as a significant number of patients do not want to risk their disease progressing, especially in cosmetically sensitive areas of the head and neck. Recent studies in melanoma show promise for improved response rates using combination therapies, and these strategies may apply to cSCC as well. The use of LAG-3 inhibitors or mRNA vaccine technology may further improve the utility of neoadjuvant strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Anti-cancer treatments often entail a spectrum of adverse effects, and among these, skin cancers have been under significant scrutiny. From traditional immunosuppressants such as methotrexate to chemotherapeutic agents such as fludarabine and hydroxyurea, as well as from new targeted therapies such as ibrutinib and JAK inhibitors to MAP kinase pathway inhibitors and sonic hedgehog pathway inhibitors, each treatment modality poses unique mechanisms of action and associated risks of skin cancer. In addition, the role of radiotherapy in inducing secondary skin cancers underscores the long-term consequences of therapeutic interventions. It is crucial to ascertain whether a specific therapy increases the risk of skin cancer so that appropriate screening measures can be implemented before and during treatment. Our comprehensive review not only investigates various medications and treatment modalities linked with heightened skin cancer risks, elucidating their mechanisms of action and relevant properties, but also proposes effective strategies for managing patients undergoing such therapies. Skin cancers involve a significant concern in cancer therapy due to their association with various treatment modalities. This comprehensive review explores the increased risk of skin cancers linked to different anti-cancer treatments, including classic immunosuppressants such as methotrexate (MTX), chemotherapeutic agents such as fludarabine and hydroxyurea (HU), targeted therapies like ibrutinib and Janus Kinase inhibitors (JAKi), mitogen-activated protein kinase pathway (MAPKP) inhibitors, sonic hedgehog pathway (SHHP) inhibitors, and radiotherapy. MTX, a widely used immunosuppressant in different fields, is associated with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous melanoma (CM), particularly at higher dosages. Fludarabine, HU, and other chemotherapeutic agents increase the risk of non-melanoma skin cancers (NMSCs), including cSCC and BCC. Targeted therapies like ibrutinib and JAKi have been linked to an elevated incidence of NMSCs and CM. MAPKP inhibitors, particularly BRAF inhibitors like vemurafenib, are associated with the development of cSCCs and second primary melanomas (SPMs). SHHP inhibitors like vismodegib have been linked to the emergence of cSCCs following treatment for BCC. Additionally, radiotherapy carries carcinogenic risks, especially for BCCs, with increased risks, especially with younger age at the moment of exposure. Understanding these risks and implementing appropriate screening is crucial for effectively managing patients undergoing anti-cancer therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) ranks among the malignancies with the most pronounced mutation burdens. Understanding its genetic aspects is crucial for improving patient care. This retrospective case-control study compares the molecular profiles of cSCCs in the head and neck regions prone to local recurrence against those without relapse, aiming to identify predictive markers for prognosis and therapy. Using a next-generation sequencing (NGS) array, histological samples from cSCC patients were analyzed, highlighting the most frequently mutated genes in cSCC. Controls displayed a higher mutation count, thus potentially enhancing tumor antigen presentation for the immune system. This immune response might prevent future recurrences, emphasizing the immune system's role in cSCC. The study underscores the importance of novel therapies that leverage the immune system. Cutaneous squamous cell carcinoma is a prevalent malignancy with a rising incidence and a notably high mutational load. Exploring the genetic nuances of cSCC and investigating molecular approaches stands as a potential avenue for improving outcomes in high-risk patients. This retrospective case-control study involved two cohorts, one of 14 patients (the "discovery cohort") and the other of 12 patients (the "validation cohort"), with cSCC located in the head/neck anatomical region and diagnosed at the pT2 stage. Overall, cases developed early local relapses of the disease, whereas controls never relapsed during the entire follow-up period. A next-generation sequencing (NGS) approach conducted on histological samples revealed that TP53 and CDKN2A were the most frequently mutated genes in our series. No specific mutations were identified as potential prognostic or therapeutic targets. Controls exhibited a tendency toward a higher mutational rate compared to cases. It is possible that an increased number of mutations could prompt the cSCC to expose more antigens, becoming more immunogenic and facilitating recognition by the immune system. This could enhance and sustain the immunological response, potentially preventing future recurrences. [ABSTRACT FROM AUTHOR]

Common therapeutics in relation to melanoma and non-melanoma cancers include the use of kinase inhibitors. The long-term benefits of kinases, however, are limited by development of drug resistance. An alternative approach for treatment would be to focus on transcription factors. Cyclic AMP-regulatory element-binding protein (CREB) is a transcription factor that is commonly overactivated or overexpressed in many different cancers including skin cancer. Ultraviolet radiation (UVR), one of the main causes of skin cancer, can activate CREB in both melanocytes and keratinocytes. In addition, CREB has been found to be activated in skin cancers. Considering the prominent role that CREB plays in skin cancers, the studies reviewed herein raise the possibility of CREB as a potential prognostic and diagnostic marker of skin cancer and a novel target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

It has long been recognized that a history of skin cancer puts one at risk for additional primary skin cancers. However, more variable data exists for the risk of developing a non-cutaneous primary cancer following a diagnosis of skin cancer. The data are most variable for Basal Cell Carcinoma (BCC), the most common and least aggressive type of skin cancer. While early studies imply that BCC does not impart a larger risk of other primary non-cutaneous cancers, more recent studies with larger populations suggest otherwise. The cancers most significantly associated with BCC are lip, oropharyngeal, and salivary gland cancer. There is also burgeoning evidence to suggest a link between BCC and prostate, breast, and colorectal cancer, but more data are needed to draw a concrete conclusion. Squamous Cell Carcinoma (SCC), the second most common type of skin cancer, has a slightly more defined risk to other non-cutaneous primary malignancies. There is a notable link between SCC and non-Hodgkin's lymphoma (NHL), possibly due to immunosuppression. There is also an increased risk of other cancers derived from squamous epithelium following SCC, including oropharyngeal, lip, and salivary gland cancer. Some studies also suggest an increased risk of respiratory tract cancer following SCC, possibly due to shared risk factors. Melanoma, a more severe type of skin cancer, shows a well-defined risk of additional primary non-cutaneous malignancies. The most significant of these risks include NHL, thyroid cancer, prostate cancer, and breast cancer along with a host of other cancers. Each of these three main skin cancer types has a profile of genetic mutations that have also been linked to non-cutaneous malignancies. In this review, we discuss a selection of these genes to highlight the complex interplay between different tumorigenesis processes. [ABSTRACT FROM AUTHOR]

Non-melanoma skin cancer (NMSC) mainly includes basal cell carcinoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma, showing a low mortality rate but the highest incidence worldwide. In recent decades, research has focused on understanding the pathogenesis and clinical treatments of NMSC, leading to significant advances in our knowledge of these diseases and the development of novel therapies, including immunotherapy. Nevertheless, the low to moderate objective response rate, high recurrence, and therapeutic resistance remain persistent challenges, which are partly attributable to the intratumoral heterogeneity. This heterogeneity indicates that tumor cells, immune cells, and stromal cells in the tumor microenvironment can be reshaped to a series of phenotypic and transcriptional cell states that vary in invasiveness and treatment responsiveness. The advent of single-cell RNA sequencing (scRNA-seq) has enabled the comprehensive profiling of gene expression heterogeneity at the single-cell level, which has been applied to NMSC to quantify cell compositions, define states, understand tumor evolution, and discern drug resistance. In this review, we highlight the key findings, with a focus on intratumoral heterogeneity and the mechanism of drug resistance in NMSC, as revealed by scRNA-seq. Furthermore, we propose potential avenues for future research in NMSC using scRNA-seq.

Background: Basal Cell Carcinoma (BCC) is the most common type of skin carcinoma and is considered an epidemic disease due to its increasing frequency in many countries. The most important problem of BCC is local invasion It grows in a “silent” way into immediately adjacent tissue. It rarely metastasizes. The early tumors are commonly small, translucent or pearly, raised and rounded areas located on a few dilated, superficial vessels. There are six subtypes of BCC that include nodular, pigmented, superficial, morphea form, cystic. The most important risk factor for basal cell carcinoma is exposure to UV-radiation. Outdoor workers with a long history of work-related UV-exposure are at increased risk of developing BCC. Other risk factors include family history of skin carcinoma, light skin phototypes, advanced age. Objective: The current study investigated pathological and histological changes in tissue sections to identify the factors contributing to the infection frequency. Patients and Methods: Thirty-three BCC patients' samples have been collected from the main care center at al-Baquba Teaching Hospital of Diyala Province, Iraq. All patient groups were clinically diagnosed as BCC by dermatologists. Results: The study showed macroscopic and microscopic histological changes. An ulcerated macroscopic appearance of the lesion was shown. The tumor lesions are located on the face. It was noted that the percentage of patients was higher in men than women and higher in light skin than dark skin. The study also showed that the age group 66-74 years had a higher infection percentage, while the lower percentage was of the age group > 83 years. Conclusion: These findings pave the way for future research endeavors aimed at prevention, early detection, and targeted treatment strategies for this prevalent skin carcinoma.

Abstract Background With the increasing incidence of skin cancer and limited access to specialised care, teledermoscopy (TDS) may represent a useful triage tool for skin cancer detection. Objectives An evaluation of a 3‐year TDS project in primary healthcare centres (PHCs) in Belgium (TELESPOT project). Methods A total of nine PHCs were trained to use an in‐house developed smartphone‐based application for macroscopic and dermoscopic acquisition of skin lesions, subsequently analysed independently by two investigators in a tertiary university skin cancer centre. The primary outcome was the proportion of high‐priority management (HPM) recommendations. Secondary outcomes included the TDS diagnoses, the quality of image acquisition, the mean time between HPM recommendations and subsequent surgery, the correlation between HPM reports and histopathology after surgery as well as patient and general practitioner satisfaction scores. All the endpoints were compared between the initial year of the TDS project and the subsequent 2‐year extension period of the study. Results Over 3 years, a total of 478 lesions were analysed in 335 patients: initial phase (105 lesions from 76 patients in six PHCs) and extension phase (373 lesions from 259 patients in nine PHCs). An HPM was recommended in 9.2% (initial and extension phases: 7.6% and 15.7%, respectively). The dermoscopic‐histological correlation achieved 84.1%. The median delay between HPM and surgery was 9 days. Conclusions This TDS project avoided unnecessary tertiary care visits in about 9 out of 10 cases, increased the HPM by a ninefold in comparison with the conventional care pathway and provided excellent satisfaction levels for PHCs and patients. Long‐term participation improved the triage quality for suspect skin lesions by 2.24‐fold.

Background: Non-melanoma skin cancers (NMSCs) are responsible for up to one-third of all human malignancies. Surgery is usually the treatment of choice, but patients often experience pain during the procedure. Topical rhenium-188 resin skin cancer treatment (RSCT) may be a valid therapeutic alternative. Methods: In this monocentric pilot study, 19 patients suffering from NMSC were treated with RSCT. Most of these patients had also experienced surgery, either because they developed a new NMSC in aftercare, or they had suffered previously from NMSC. Three RSCT-treated patients, who had no exposure to surgery so far, were paired with three matched patients, who had received surgery. We sought to evaluate and compare the patients' experience with both treatments. A questionnaire assessed patients' perceptions regarding side effects, aesthetic outcomes, wound care, fear of complications, and personal treatment preferences. Patients evaluated the different parameters of their either RSCT- or surgery-treated lesions on a scale from 0–10. Results: Patients were more afraid of complications before surgery than before RSCT (p = 0.04). Treatment with RSCT caused significantly less pain on treatment day (mean 0.56) than surgery (mean 2.32) (0 no pain, 10 maximum pain) (p = 0.02) and 14 days after the procedure (mean 0.89 versus mean 2.47) (p = 0.02). On day 14, RSCT-treated lesions were also significantly less itchy (mean 0.34) than after surgery (mean 1.50). Most patients were very satisfied with the aesthetic outcome after both RSCT (mean 8.42) and surgery (mean 8.31) (p = 0.89). In the case of a new NMSC, the majority of patients who experienced both treatments would rather be treated primarily with RSCT (44%) or would consider both options (31%); only 19% preferred surgery. Conclusion: Patients evaluated RSCT as less painful than surgery. The aesthetic outcomes of both treatments were comparable. For pain-sensitive patients, RSCT might be a preferable treatment option. [ABSTRACT FROM AUTHOR]

The prevalence of two major types of skin cancer, melanoma and non-melanoma skin cancer, has been increasing worldwide. Skin cancer incidence is estimated to rise continuously over the next 20 years due to ozone depletion and an increased life expectancy. Chemotherapeutic agents could affect healthy cells, and thus may be toxic to them and cause numerous side effects or drug resistance. Phytochemicals that are naturally occurring in fruits, plants, and herbs are known to possess various bioactive properties, including anticancer properties. Although the effects of phytochemicals are relatively milder than chemotherapeutic agents, the long-term intake of phytochemicals may be effective and safe in preventing tumor development in humans. Diverse phytochemicals have shown anti-tumorigenic activities for either melanoma or non-melanoma skin cancer. In this review, we focused on summarizing recent research findings of the natural and dietary terpenoids (eucalyptol, eugenol, geraniol, linalool, and ursolic acid) that have anticancer activities for both melanoma and non-melanoma skin cancers. These terpenoids may be helpful to protect skin collectively to prevent tumorigenesis of both melanoma and nonmelanoma skin cancers. [ABSTRACT FROM AUTHOR]

Ultrasound and high-frequency ultrasound assessment of melanoma and non-melanoma skin cancer in the pre-therapeutical setting is becoming increasingly popular in the field of dermatosurgery and dermatooncology, as it can provide clinicians with relevant, "in vivo" parameters regarding tumor lateral and depth extension as well as potential locoregional spread, cancelling the need of more extensive imaging methods and avoiding a delay in diagnosis. Furthermore, preoperative sonography and color Doppler can aid in orienting the clinical diagnosis, being able in numerous situations to differentiate between benign and malignant lesions, which require a different therapeutic approach. This preoperative knowledge is of paramount importance for planning an individualized treatment regimen. Using sonography at the time of diagnosis, important surgical complications, such as neurovascular damage, can be avoided by performing a preoperative neurovascular mapping. Furthermore, sonography can help reduce the number of surgical steps by identifying the lesions' extent prior to surgery, but it can also spare unnecessary surgical interventions in cases of locally advanced lesions, which infiltrate the bone or already present with locoregional metastases, which usually require modern radiooncological therapies in accordance to European guidelines. With this review, we intend to summarize the current indications of sonography in the field of skin cancer surgery, which can help us improve the therapeutic attitude toward our patients and enhance patient counseling. In the era of modern systemic radiooncological therapies, sonography can help better select patients who qualify for surgical procedures or require systemic treatments due to tumoral extension. [ABSTRACT FROM AUTHOR]

Objective: Skin cancers are the most common malignant cancers. For the surgical treatment of skin cancer, there are cases where axillary dissection should be performed, and secondary lymphedema after axillary dissection is not uncommon. The study examined the number of lymph nodes removed in the dissection materials to evaluate the factors that may predict the development of lymphedema. Material and Method: Our study included patients who underwent axillary lymph node dissection for malignant skin tumors originating from the upper extremities between 2019 and 2022. Age, gender, type of primary malignancy, localization of the lesion, total number of lymph nodes removed in the dissection material, number of metastatic lymph nodes detected in the dissection material, history of SLNB, and the difference in measurements between the operated and non-operated extremity were recorded preoperatively and at the first year postoperatively. Result: In our study, there was a statistically significant positive correlation between the total number of lymph nodes removed and the diameter difference between the dissected and non-dissected arms. At the same time, there was a statistically significant positive correlation between the number of metastatic lymph nodes and the diameter difference between the dissected limb and the metacarpophalangeal joints of the other limb. Conclusion: Lymphedema is a complication that is difficult to treat and whose prognosis can be alleviated if detected early. By evaluating the number of excised and metastatic lymph nodes in the dissection materials, it may be possible to take early precautions, educate patients, develop individual treatment modalities, and avoid unwanted complications in patients who may develop lymphedema. [ABSTRACT FROM AUTHOR]

Immunosuppression is a known risk factor for the development of cutaneous squamous cell carcinoma (CSCC), especially in solid organ transplant recipients and chronic lymphocytic leukemia. However, this risk is less well defined in autoimmune and inflammatory conditions. Assess the impact that disease-type, duration of immunosuppression, and systemic medications have on CSCC accrual rates, defined as the number of CSCCs a patient develops per year, in autoimmune and inflammatory conditions. Retrospective review of 94 immunosuppressed (rheumatoid arthritis: 31[33.0%], inflammatory bowel disease: 17[18.1%], psoriasis: 11[11.7%], autoimmune other (AO): 24[25.5%], inflammatory other: 21[22.3%]) and 188 immunocompetent controls to identify all primary, invasive CSCCs diagnosed from 2010 to 2020. Immunosuppressed patients had higher CSCC accrual rates than immunocompetent controls (0.44 ± 0.36): total cohort (0.82 ± 0.95, P <.01), rheumatoid arthritis (0.88 ± 1.10, P <.01), inflammatory bowel disease (0.94 ± 0.88, P <.01), psoriasis (1.06 ± 1.58, P <.01), AO (0.72 ± 0.56, P <.01), and inflammatory other (0.72 ± 0.61, P <.01). There was an association between increased tumor accrual rates and exposure to systemic medications including, immunomodulators, tumor necrosis factor-alpha inhibitors, non-tumor necrosis factor inhibitor biologics, and corticosteroids, but not with number of systemic medication class exposures or duration of immunosuppression. Retrospective, singlecenter study. Patients with autoimmune and inflammatory conditions accrue CSCCs at higher rates than immunocompetent patients. [ABSTRACT FROM AUTHOR]

Transforming Growth Factor‐Beta (TGF‐β) signalling pathway is of paramount importance in the processes of wound healing, epidermal integrity maintenance and development of skin cancer. The objective of this research endeavour was to clarify the impact of gene mutations and variations in expression within TGF‐β family on mechanisms of tissue repair, as well as to identify potential targets for therapeutic purposes in non‐melanoma skin cancer (NMSC). The methods utilized in this study involved obtaining RNA‐seq data from 224 NMSC patients and paired normal skin tissues from the PRJNA320473 and PRJEB27606 databases. The purpose of the differential gene expression analysis was to identify genes whose expression had changed significantly. In order to evaluate the effects and interrelationships of identified gene variants, structural analysis with AlphaFold and PDB data and network analysis with the STRING database were both utilized. Critical gene expression was externally validated through the utilization of the GEPIA database. Tumour tissues exhibited a notable upregulation of genes associated with the TGF‐β pathway, specifically MMP1, MMP3, MMP9, EGF, COL3A1 and COL1A2, in comparison with normal tissues. As indicated by the central node status of these genes in the network analysis, they play a crucial role in the progression of NMSCs. The results of the structural analysis suggested that mutations might cause functional disruptions. External validation of the upregulation confirmed the expression trends and emphasized the biomarker potential of the upregulated genes. In conclusion, this research offered thorough examination of molecular modifications that occur in TGF‐β family genes, which are linked to cutaneous wound healing and NMSC. The modified expression of the identified hub genes may represent innovative targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Bowen's disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3–5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen's disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase. [ABSTRACT FROM AUTHOR]

Simple Summary: Skin cancer represents a prevalent and significant global health concern. Our study focused on comprehending cutaneous squamous cell carcinoma in the Mexican population through the examination of genetic variants of the PTCH1 gene, the assessment of its mRNA's relative expression, and the utilization of bioinformatics tools. Despite the absence of statistically significant associations in the experimental results, integrating bioinformatics was imperative to understand the impact of the analyzed variants on protein function, splicing, expression, and disease-related aspects. This contributes to our overarching comprehension of non-melanoma skin cancer development. Further investigation is crucial to gain a comprehensive understanding of the in vivo role of these genetic variants. Background: Skin cancer is one of the most frequent types of cancer, and cutaneous squamous cell carcinoma (cSCC) constitutes 20% of non-melanoma skin cancer (NMSC) cases. PTCH1, a tumor suppressor gene involved in the Sonic hedgehog signaling pathway, plays a crucial role in neoplastic processes. Methods: An analytical cross-sectional study, encompassing 211 cSCC patients and 290 individuals in a control group (CG), was performed. A subgroup of samples was considered for the relative expression analysis, and the results were obtained using quantitative real-time PCR (qPCR) with TaqMan® probes. The functional, splicing, and disease-causing effects of the proposed variants were explored via bioinformatics. Results: cSCC was predominant in men, especially in sun-exposed areas such as the head and neck. No statistically significant differences were found regarding the rs357564, rs2236405, rs2297086, and rs41313327 variants of PTCH1, or in the risk of cSCC, nor in the mRNA expression between the cSCC group and CG. A functional effect of rs357564 and a disease-causing relation to rs41313327 was identified. Conclusion: The proposed variants were not associated with cSCC risk in this Mexican population, but we recognize the need for analyzing larger population groups to elucidate the disease-causing role of rare variants. [ABSTRACT FROM AUTHOR]

5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm2) formulated with various chemical permeation enhancers. The patches containing Transcutol® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm2 and 82.56 ± 8.2 µg/cm2, respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles. [ABSTRACT FROM AUTHOR]

Simple Summary: This systematic review concludes that a higher neutrophil-to-lymphocyte ratio (NLR), a robust indicator of adverse prognosis across the common metastatic cancers including malignant melanoma, is also a promising biomarker of tumor aggressiveness in all advanced stage non-melanoma skin cancers. A distinct exception with still inconclusive evidence is the cutaneous T-cell lymphoma, although there are some data indicating that higher NLR may predict poorer prognosis in patients with earlier stages mycosis fungoides. Finally, given the promising data concerning the impact of NLR as a prognosticator of the outcome of the treatment with the current immunotherapies, there is presently a need for studies focusing on the role of NLR in the framework of the treatment of advanced non-melanoma skin cancer. With the ongoing progress of basic research along with the introduction of new pharmaceutical options spanning almost all therapeutic areas, the need for biomarkers that will be implemented into the personalized medical approach is higher than ever. Their use can be incorporated into clinical practice and can be applied to the classification of disorders and the evaluation of disease severity but also to the monitoring of the progress of therapeutic/pharmaceutical interventions. This systematic review collects the findings of hematologic biomarkers in various cutaneous malignancies, excluding malignant melanoma, to support their potential use in the prognosis but also in the assessment of therapeutic strategies for the specific category of skin disorders. [ABSTRACT FROM AUTHOR]

Standard non-melanoma skin cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in cases of advanced tumors. EVs, including exosomes, are integral to carcinogenesis, and are found in NMSC releasing mediators impacting tumor progression. Nevertheless, the precise intercellular signaling role of NMSC-derived EVs remains unclear. This review aims to elucidate their potential role in NMSC diagnosis and treatment. This systematic review encompassed literature searches in electronic databases from inception to September 2023, based on certain inclusion and exclusion criteria, addressing NMSC-derived EVs, their molecular cargo, and their implications in the diagnosis, prognosis, and treatment of NMSC. Key components were identified. Extracellular vesicle (EV) proteins and RNA have emerged as diagnostic biomarkers in EV-based liquid biopsy. Circular RNA CYP24A1, known for its molecular stability, holds promise as a diagnostic biomarker. Long noncoding RNAs (lincRNA-PICSAR) and Desmoglein 2 (DSg2) are linked to drug resistance, serving as prognostic biomarkers. EV mediators are being actively investigated for their potential role as drug delivery agents. In conclusion, this systematic review showed that NMSC-derived EVs display promise as therapeutic targets and diagnostic biomarkers. Further research is imperative to fully comprehend EV mechanisms and explore their potential in cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background/Aim: This study aimed to analyze the dosimetric effects of jaw tracking during Volumetric Modulated Arc Therapy (VMAT) planning for facial nonmelanoma skin cancer (NMSC). Patients and Methods: This study included 50 patients with facial NMSC who underwent VMAT planning with or without jaw tracking. The target volume (TV) included the primary skin lesion with a 1-cm margin around the surface and a depth of 4 mm. A total of 55 Gy in 20 fractions was prescribed, and the plans were considered acceptable if the TV was covered by 95-105% of the isodose curve. A dosimetric comparison was performed for the volumes of the low-dose regions, which were defined as <50% of the prescription dose (V10-50%). Target coverage was evaluated using the homogeneity index (HI) and conformity index (CI). Results: The patients' mean TV was 5.137 cc (range=1.03-15.89 cc). Jaw tracking resulted in mean volume reduction rates of 3.9%, 6.6% 10.6% and 13.8% for V40%, V30%, V20%, and V10%, respectively (all p<0.001). The volume change in V50% between the two groups was 2.7% (p=0.006). No significant differences were observed in HI (p=0.449) or CI (p=0.127). Conclusion: The application of jaw tracking during VMAT for facial NMSC is associated with a significant reduction in the volume of low dose delivered in the radiation field (V10-50%), while maintaining target coverage. Future analyses should assess whether this volume difference affects treatment-related cosmetic outcomes. [ABSTRACT FROM AUTHOR]

In Caucasians, basal cell carcinoma, the predominant non-melanoma skin cancer type, poses challenges for surgeons due to anatomical and aesthetic concerns, particularly when located on the nose. The study aimed to evaluate tumor distribution, size, morphological subtypes, surgical outcomes, radicality levels, and their correlation with recurrence rates. A retrospective analysis encompassed 343 cases of nasal skin cancer over a four-year period from 1 January 2019 to 31 December 2022. The research cohort comprised 252 female and 91 male participants, averaging 75.2 years old. Tumors were most found on the left sidewall of the nose (25.4%) and the dorsum (24.8%). The infiltrative morphological subtype was predominant (70.8%). Standard surgical excision with fasciocutaneous plastic was the preferred surgical procedure. Radical excision, defined by the absence of tumor cells in a resection margin, was accomplished in 79.0% of lesions, whereas 16.9% demonstrated incomplete excision, signifying the presence of tumor cells in the resection margin. Non-radically excised tumors exhibited a significantly higher recurrence rate (24.1%) compared to those with radical excision (6.3%). In nasal reconstruction, diverse surgical techniques are essential for precise adaptation based on factors like tumor characteristics and patient needs. Despite surgeons' careful adherence to excision margin guidelines, the possibility of non-radical outcome cannot be eliminated. [ABSTRACT FROM AUTHOR]

Keratinocyte-derived skin cancers comprise basal cell carcinoma, squamous cell carcinoma, its precursor actinic keratosis, and Bowen’s disease. Historically, this group of neoplasms has been subsumed under the term non-melanoma skin cancer. However, the term non-melanoma skin cancer can be misleading and lacks precision. Therefore, more precise and reasonable terminology, valuing the relevance of keratinocyte-derived cancer, appears pertinent to meet its clinical and scientific significance. A group of experienced dermato-oncologists initiated a consensus approach to promote the use of the term “keratinocyte cancer” instead of “non-melanoma skin cancer” when referring to carcinomas and their precursors that are derived from keratinocytes. The vote among members of the consensus group indicated unanimous agreement on the consistent use of the term “keratinocyte cancer” instead of “non-melanoma skin cancer”. International delegates also voted in favour of the revised terminology. The more precise and, by means of etiopathogenesis, correct term “keratinocyte cancer” should be consistently used for malignancies originated from keratinocytes. This is expected to have a positive impact on patient–physician communication and gives better justice to this important group of keratinocyte-derived cancers.

BackgroundMethodsResultsConclusionPrior research has shown a positive association of pseudoexfoliative glaucoma (PXG) in patients with non-melanoma skin cancer (NMSC), likely due to an increase in ultraviolet exposure associated with both. However, the role of NMSC as a genetic risk factor for PXG has not been examined. Thus, the goal of this study is to utilize Mendelian randomization with genome-wide association studies to evaluate for genetic causality while controlling for environmental confounders.We conducted a MR using the inverse variance weighted method (MR-IVW) as our primary analysis. Genomic data was sourced from GWASs for patients with NMSC (10,382 cases, 208,410 controls) and PXG (1,515 cases and 210,201 controls), originating from the FinnGen Biobank.Despite previous association of history of NMSC with occurrence of PXG, we found no evidence for a causal association between SNPs associated with NMSC and risk of PXG following MR analysis (MR-IVW, odds ratio (OR): 0.98, 95% CI: 0.85-1.14, P = 0.87).Here, we found no evidence for a causal association between SNPs associated with NMSC and the risk of PXG following a MR analysis. [ABSTRACT FROM AUTHOR]

Circumscribed palmar hypokeratosis (CPH) is a localized disorder of epidermal keratinization that is presented as a well‐delimited, depressed, erythematous plaque on the palms or on the soles. It is histopathologically characterized by an abrupt thinning of the corneal epidermal layer. CPH is considered a benign condition, but a few cases with dysplastic changes/carcinoma in situ in the hypokeratotic epidermis have been described. We report hereby a case of invasive squamous cell carcinoma developed within a plaque of CPH. The pathogenesis of the malignant changes in this disorder remains to be clarified. Clinicians should be aware of the potential for developing malignancy in CPH and carry out a closer follow‐up of this disorder. [ABSTRACT FROM AUTHOR]

AbstractObjective To assess the trends in non-melanoma skin cancer (NMSC) incidence in Hong Kong from 1990 to 2019 and the associations of age, calendar period, and birth cohort, to make projections to 2030, and to examine the drivers of NMSC incidence.Methods We assessed the age, calendar period, and birth cohort effects of NMSC incidence in Hong Kong between 1990 and 2019 using an age-period-cohort model. Using Bayesian age-period-cohort analysis with integrated nested Laplace approximations, we projected the incidence of NMSC in Hong Kong to 2030.Results From 1990 to 2019, the age-standardized incidence rate of NMSC increased from 6.7 per 100,000 population to 8.6 per 100,000 population in men and from 5.4 per 100,000 to 5.9 per 100,000 population in women, among the 19,568 patients in the study (9812 male patients [50.14%]). The annual net drift was 2.00% (95% confidence interval [CI]: 1.50–2.50%) for men and 1.53% (95% CI: 0.95–2.11%) for women. Local drifts increased for both sexes above the 35–39-year age group. The period and cohort risk of developing NMSC tended to rise but slowed gradually in the most recent period and post-1975 birth cohort. From 2019 to 2030, it is projected that the number of newly diagnosed NMSC cases in Hong Kong will increase from 564 to 829 in men and from 517 to 863 in women. Population aging, population growth, and epidemiologic changes contributed to the increase in incident NMSCs, with population aging being the most significant contributor.Conclusion The slowing of the period and cohort effects suggests that the rising incidence of NMSC is partly attributable to increased awareness and diagnosis. The increasing prevalence of NMSC among the elderly and an aging population will significantly impact the clinical workload associated with NMSC for the foreseeable future.

Non-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), are increasingly common and present significant healthcare challenges. Neutrophil extracellular traps (NETs), chromatin fibers expulsed by neutrophil granulocytes, can promote immunotherapy resistance via an impairment of CD8+ T cell-mediated cytotoxicity. Here, to identify a potential therapeutic target, we investigate the expulsion of NETs and their relation to CD8+ T cell infiltration in NMSC. Immunofluorescence staining for neutrophils (CD15) and NETs (H3cit), as well as immunohistochemistry for cytotoxic T cells (CD8+) on human cSCCs (n = 24), BCCs (n = 17) and MCCs (n = 12), revealed a correlation between neutrophil infiltration and ulceration diameter in BCC and MCC, but not in cSCC. In BCC and cSCC, neutrophil infiltration also correlated with the cross-sectional area (CSA). NETs were not associated with established risk factors but with the presence of an ulceration, and, in cSCC, with abscess-like structures. CD8+ T cell infiltration was not reduced in tumors that were NET-positive nor in those with a denser neutrophil infiltration. This study is the first to report and characterize NETs in NMSC. Thus, it gives an incentive for further research in this relevant yet understudied topic.

Non-melanoma skin cancers (NMSCs) are a significant cause of morbidity and mortality; their incidence is increasing most in older patients. NMSCs have traditionally been treated with surgical excision, curettage, Mohs micrographic surgery (MMS), and superficial radiotherapy (SRT). Image-guided SRT (IGSRT) is a treatment option for poor surgical candidates or patients with low- or high-risk, early-stage NMSC who prefer to avoid surgery. This large retrospective cohort study compared 2-, 4-, and 6-year freedom from recurrence in biopsy-proven NMSC lesions treated with IGSRT (n = 20,069 lesions) between patients aged < 65 years (n = 3158 lesions) and ≥65 years (n = 16,911 lesions). Overall freedom from recurrence rates were 99.68% at 2 years, 99.57% at 4 years, and 99.57% at 6 years. Rates did not differ significantly by age (p = 0.8) nor by sex among the two age groups (p > 0.9). There was a significant difference in recurrence among older patients when analyzed by stage (p = 0.032), but no difference by stage in younger patients (p = 0.7). For early-stage NMSCs, IGSRT is a clinically equivalent alternative to MMS and statistically significant in superiority to non-image-guided SRT. This study demonstrates that there is no significant effect of age on 2-, 4-, or 6-year freedom from recurrence in patients with IGSRT-treated NMSC.

The elevated occurrence of non-melanoma skin cancer (NMSC) and the adverse effects associated with available treatments adversely impact the quality of life in multiple dimensions. In connection with this, there is a necessity for alternative approaches characterized by increased tolerance and lower side effects. Natural compounds could be employed due to their safety profile and effectiveness for inflammatory and neoplastic skin diseases. These anti-cancer drugs are often derived from natural sources such as marine, zoonotic, and botanical origins. Natural compounds should exhibit anti-carcinogenic actions through various pathways, influencing apoptosis potentiation, cell proliferation inhibition, and metastasis suppression. This review provides an overview of natural compounds used in cancer chemotherapies, chemoprevention, and promotion of skin regeneration, including polyphenolic compounds, flavonoids, vitamins, alkaloids, terpenoids, isothiocyanates, cannabinoids, carotenoids, and ceramides. [ABSTRACT FROM AUTHOR]