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.

The exact incidence of cutaneous squamous cell carcinoma (CSCC) or nonmelanoma skin cancer is unknown, and it is believed that the rate of occurrence is increasing with the growing elderly population and sun exposure, and it is more prevalent in males than in females. In this article, we describe the case of an 81-year-old woman who presented with a lesion on the right upper eyebrow. The patient had been consulting a dermatologist and undergoing treatment for three months. However, the lesion did not show any signs of improvement, and the dermatologist speculated that it might be a common wound that was healing slowly because of her diabetes. Imaging revealed an ulcerating skin lesion on the right upper eyebrow without connection to the deeper structures. Surgical intervention was chosen with the patient\'s consent. This rare case of CSCC on a woman\'s eyebrow showed that skin cancer can occur in unusual locations and in people without risk factors.

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.

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.

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.
CONCLUSIONS: 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.

Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide. Skin exposure is the leading risk factor for initiating NMSC. Ultraviolet (UV) light induces various genomic aberrations in both tumor-promoting and tumor-suppressing genes in epidermal cells. In conjunction with interactions with a changed stromal microenvironment and local immune suppression, these aberrations contribute to the occurrence and expansion of cancerous lesions. Surgical excision is still the most common treatment for these lesions; however, locally advanced or metastatic disease significantly increases the chances of morbidity or death. In recent years, numerous pharmacological targets were found through extensive research on the pathogenic mechanisms of NMSCs, leading to the development of novel treatments including Hedgehog pathway inhibitors for advanced and metastatic basal cell carcinoma (BCC) and PD-1/PD-L1 inhibitors for locally advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC). Despite the efficacy of these new drugs, drug resistance and tolerability issues often arise with long-term treatment. Ongoing studies aim to identify alternative strategies with reduced adverse effects and increased tolerability. This review summarizes the current and emerging therapies used to treat NMSC.

Background: The COVID-19 era has been a bleak period for both cancer and non-cancer patients, with delayed non-emergency treatments, such as for non-melanoma skin cancer (NMSC). This study aimed to evaluate how the treatment of NMSC patients was influenced by the management of the COVID-19 pandemic in an Eastern European Maxillofacial Surgery center. Materials and Methods: A total of 176 patients with a histopathological diagnosis of head and neck NMSC who were surgically treated in Cluj-Napoca Emergency County Hospital between 2016 and 2022 were included in this study, and divided into two samples, pre-pandemic (2016-2019) and COVID-19 (2020-2022) periods. Results: The pandemic presented with a decrease of 46.15% in patients\' hospitalization, with wealthy and educated patients being prevalent. Even if the waiting time for surgery was increased, the stage of cancer and preference method for reconstruction did not differ. Despite the lower addressability of NMSC patients during the pandemic, there were no changes in surgical treatment. Conclusions: During COVID-19, the number of patients was reduced, with a longer waiting time for surgery, but without any changes in tumor stage and treatment preferences. However, the benefit of removing a cancer tumor is higher compared to the risk of developing COVID-19 infection during hospitalization.

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.

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.

This case report covers the case of a 56-year-old woman with two separate occurrences of squamous cell neoplasms, one arising in pink tattoo pigment and another arising in orange tattoo pigment. A review of the literature was conducted to evaluate the prevalence of malignancy occurring in tattoos. This is rare and there are a limited number of case reports and no large studies done on this condition. Most malignancies in tattoos occur in red, black, or blue tattoo inks and no cases have been reported thus far of malignancy in pink or orange tattoo pigments. Due to the limited number of cases, more case studies are needed to determine the prevalence, risk, and epidemiology of malignancy arising within tattoos.