Search Results (1,046)

Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer entity in Germany, following basal cell carcinoma. Its incidence has increased fourfold over the past three decades. Early diagnosis and treatment are essential for achieving favorable outcomes. Our study aims to identify prognostic factors based on real-world data to improve follow-up protocols and raise clinical vigilance. Methods: We conducted a retrospective, monocenter analysis with a total of 124 patients with at least one cSCC thicker than 3 mm, treated at the Department of Dermatology, University Medical Center Mainz, between 2010 and 2020. Tumor-specific criteria were correlated with patient-specific data, such as gender, age, immunosuppression, UV exposure and mortality. Results: A higher incidence of cSCC was found on UV-exposed skin (91.1%); however, tumors on non-UV-exposed skin were on average thicker (6.55 mm vs. 9.25 mm, p = 0.011) and associated with higher metastasis rates (10.6% vs. 63.3%, p < 0.001). Immunosuppression was strongly associated with a younger age at diagnosis (74 years vs. 81 years), a higher metastasis rate (29% vs. 10.8%, p = 0.021) and a worse 5Y-OS-rate (36.1% vs. 97.8%, p = 0.04). SLNB was performed in eight patients, with one positive SLN identified (12.5%). Local recurrence was observed in 18.1% (n = 21) of patients who did not experience SLNB, whereas no local recurrences (0%) were reported in patients with SLNB (p = 0.349). Discussion: Tumors on non-UV-exposed areas were thicker and more often metastatic, suggesting delayed detection or more aggressive tumor subtypes. Immunosuppression was associated with worse outcomes, underscoring the need for intensified follow-up. SLNB was rarely performed, and larger studies are needed to assess its role. Full article

Background: Merkel cell polyomavirus (MCPyV) has been established as an etiological agent in Merkel cell carcinoma (MCC), yet its role in other cutaneous neoplasms remains under investigation. The impact of the host’s immunogenetic characteristics on the persistence of Merkel cell polyomavirus (MCPyV) in non-melanoma skin cancer (NMSC) is not yet well understood. Objective: Our aim was to investigate the presence of MCPyV in various skin lesions, particularly NMSC, and its association with cytokine gene polymorphisms related to immune regulation. Methods: We analyzed 274 skin biopsies (lesional, perilesional, and healthy skin) from 84 patients undergoing dermatological evaluation. MCPyV DNA and polymorphisms in IL-6, IL-10, IFN-γ, and TNF-α genes were detected using PCR-based assays. Results: MCPyV was significantly more prevalent in NMSC and non-cancerous lesions than in surgical margins or healthy skin (p = 0.050 and 0.048, respectively). Concordance between lesion and margin samples was low (κ = 0.305), suggesting microenvironment-specific viral persistence. Notably, high-expression IL-10 genotypes (-1082 GG) and low-expression IL-6 genotypes (-174 AA) were significantly associated with MCPyV detection (p = 0.048 and p = 0.015, respectively). Conclusions: MCPyV preferentially localizes to NMSC lesions, particularly in individuals with immunogenetic profiles favoring viral persistence. Since the role of MCPyV in the pathogenesis of NMSC remains uncertain, our results highlight the need for further studies to clarify whether the lesion’s microenvironment supports viral persistence or indicates a more intricate interaction between the virus and the host, which could be significant for the development of skin cancer. Full article

Background/Objectives: The increasing incidence rates of keratinocyte carcinoma (KC), particularly in fair-skinned populations, call for efforts to intensify health education of the general population in addressing this prevalent skin cancer type. As a preparatory step, this systematic review summarizes the published research on the knowledge and risk perception regarding KC among individuals without medical training. Methods: The review was registered in PROSPERO (CRD42024618851) and adheres to PRISMA guidelines. The databases PubMed, Scopus, Web of Science, PsycArticles, and PsycINFO were searched on 30 July 2024. Studies were eligible if knowledge and/or risk perception was assessed in lay people. Risk of bias (ROB) was assessed with the Joanna Briggs Institute checklist for prevalence studies. Comparable outcomes (e.g., awareness of terms for KC) were meta-analyzed. Results: Included reports (n = 17) were published between 1991 and 2024 with 16,728 individuals assessed. Awareness for the most common type of KC, basal cell carcinoma (BCC), was low (20.75% of respondents (95% confidence interval (CI): 15.24–27.61)), while more respondents were familiar with colloquial terms (60.9–72.8%). Meta-analysis indicated an underestimation of the frequency of KC, with only 7.21% (CI: 4.03–12.58) identifying BCC as the most common type of skin cancer. Furthermore, concern about developing KC as assessed in only two overlapping studies was reported by only 25–30% of respondents, indicating a significant gap in risk awareness and a lack of research on risk perception regarding KC. Conclusions: This review highlights the need for targeted health education interventions to improve knowledge and preventive behaviors regarding KC. Given the limitations of the included studies, characterized by high ROB, heterogeneity of results, and a lack of standardized assessment tools, further research is essential to enhance the understanding and awareness of KC in diverse populations. Full article

Feline mammary carcinoma (FMC) exhibits aggressive behavior, with limited treatment options. Given the relevance of the PD-1/PD-L1/PD-L2 axis in human breast cancer immunotherapy, this study assessed PD-1 and its ligands in rare FMC histotypes (n = 48) using immunohistochemistry on tumor cells (TCs), intratumoral lymphocytes (iTILs), and stromal tumor-infiltrating lymphocytes (sTILs). PD-1 was expressed in 13% of TCs, 85% of iTILs, and 94% of sTILs, while PD-L1 was observed in 46% of TCs, 96% of iTILs, and 100% of sTILs. PD-L2 was expressed in 79% of TCs and 100% of both iTILs and sTILs, with PD-L1/PD-L2 co-expression in 42% of TCs. Higher PD-1 IHC scores in TCs were associated with a less aggressive biological behavior; PD-L1 in iTILs was linked to skin ulceration, whereas PD-L2 in TCs was associated with its absence. Our findings highlight the relevance of the PD-1/PD-L1/PD-L2 immune checkpoint in rare FMC subtypes and support further investigation into checkpoint-blockade therapies. Full article

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Recent preclinical and clinical studies have confirmed the essential role of interferons in the host’s immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, the role of innate immune signaling, particularly interferon-γ (IFN γ) and its downstream pathways, remains underexplored. This review summarizes recent findings on IFN-γ in MCC, highlighting its dual role in promoting both antitumor immunity and immune evasion. IFN-γ enhances cytotoxic T cell responses, upregulates MHC class I/II expression, and induces tumor cell apoptosis. Transcriptomic studies have shown that IFN-γ treatment upregulates immune-regulatory genes including PD-L1, HLA-A/B/C, and IDO1 by over threefold; it also activates APOBEC3B and 3G, contributing to antiviral defense and tumor editing. Clinically, immune checkpoint inhibitors (ICIs) such as pembrolizumab and avelumab yield objective response rates of 30–56% and two-year overall survival rates exceeding 60% in advanced MCC. However, approximately 50% of patients do not respond, in part due to IFN-γ signaling deficiencies. This review further discusses IFN-γ’s crosstalk with the STAT1/3/5 pathways and emerging combination strategies aimed at restoring immune sensitivity. Understanding these mechanisms may inform personalized immunotherapeutic approaches and guide the development of IFN-γ–based interventions in MCC. Full article

Background/Objectives: This study investigated the timing of adverse events (AEs) after carbon-ion radiotherapy (CIRT) for hepatocellular carcinoma (HCC) and identified the risk factors for biliary stricture post CIRT. Methods: This retrospective study included 103 patients with HCC who had undergone CIRT (60 Gy/4 fractions). The onset, frequency, and grade of AEs after CIRT were analyzed. HCC was classified into perihilar and distal types to assess the frequency of biliary stricture, and the risk factors for biliary stricture were investigated. Results: AEs after CIRT were more frequent in patients with liver dysfunction, skin redness/dermatitis, and pigmentation. Biliary stricture occurred long after CIRT (3.0–17.0 months). Most AEs were of grade 1–2. Grade ≥ 3 AEs included biliary stricture (2.9%) and radiation gastric ulcer (1.0%), whereas grade 5 AEs included biliary stricture (1.9%). Biliary stricture was exclusively observed in patients with perihilar-type HCC. Among patients with perihilar-type HCC, those having a tumor in the portal vein trunk branch area were more prone to biliary stricture than those with a tumor in the primary portal vein branch area (p = 0.0018), and all grade ≥ 3 biliary strictures (2.9%) were observed in the portal vein trunk branch area. Patients with perihilar-type HCC and biliary stricture were more likely to have macrovascular invasion (p = 0.0052) and previous local therapy targeting the perihilar region (p = 0.0371) than those without biliary stricture. Conclusions: This study reported the detailed data of AEs post CIRT for HCC and the risk factors for biliary stricture post CIRT. Full article

Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment of actinic keratoses (AK), pre-malignant entities that have the risk of transformation into skin carcinomas. The hypothesis that diclofenac increases granular layer development in the mice tail model, having an anti-psoriatic effect, was demonstrated in a previous study in which 1% and 2% diclofenac ointment was evaluated. The aim of the present study was to perform experimental research on the topical effect of diclofenac in the mice tail model, by testing 4% and 8% diclofenac ointment, which is presented in the first part of the manuscript. In the second part of the manuscript, we also aimed to conduct a literature review regarding topical diclofenac uses in specific dermatological entities by evaluating the articles published in PubMed and Scopus databases during 2014–2025. The studies regarding the efficacy of topical diclofenac in dermatological diseases such as AK and field cancerization, actinic cheilitis, basal cell carcinoma, Bowen disease, Darier disease, seborrheic keratoses, and porokeratosis, were analyzed. The results of the experimental work showed a significant effect of 4% and 8% diclofenac ointment on orthokeratosis degree when compared to the negative control groups. Diclofenac in the concentration of 4% and 8% significantly increased the orthokeratosis degree compared to the negative control with untreated mice (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test) and to the negative control with vehicle (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test). The mean epidermal thickness was increased for the diclofenac groups, but not significantly when compared to the control groups. The results are concordant with our previous experiment, emphasizing the need for future clinical trials on the use of topical diclofenac in psoriasis. Full article

Non-melanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), represents the most common type of cancer worldwide, particularly among Caucasians. While BCC is locally invasive with minimal metastatic potential, cSCC is a highly aggressive tumor with a significant potential for metastasis, particularly in elderly populations. Tumor development and progression and the metastasis of cSCC are influenced by a complex interplay between tumor cells and the tumor microenvironment. Recent research highlights the importance of various immune cell subsets, including T cells, tumor-associated macrophages (TAMs), and dendritic cells, in influencing tumor progression, immune evasion, and treatment resistance. This review outlines key regulatory mechanisms in the immune tumor microenvironment (TME) of cSCC and explores the role of cytokines, immune checkpoints, and stromal interactions. We further discuss the relevance of three-dimensional (3D) in vitro models such as spheroids, organoids, and tumor-on-chip systems as tools to mimic immune–tumor interactions with higher physiological relevance, such as macrophage activation and polarization against cSCC cells. Globally, 3D models offer new opportunities for immunotherapy screening and mechanistic studies. Understanding the immune landscape in cSCC through advanced modeling techniques holds strong clinical potential for improving diagnostic and therapeutic strategies. Full article

Background: Huriez syndrome is a rare hereditary skin disorder marked by early-onset sclerodactyly, hyperkeratosis of the palms and soles, and nail dysplasia. A key concern is the early and aggressive development of cutaneous squamous cell carcinoma (SCC), typically affecting the dorsal aspects of the hands. Methods: This narrative review summarizes clinical features, genetic aspects, and oncologic implications of Huriez syndrome. A systematic search was conducted in PubMed and Scopus, including English-language articles published up to May 2025. Relevant case reports and small case series were analyzed. Results: Seven patients (58.3%) underwent multiple surgeries due to recurrent or bilateral disease. Six patients (50%) required amputations, including finger, hand, and arm amputations, with no foot amputations reported. Reconstruction after oncological resection was performed in six patients (50%) using skin grafts (3), pedicled flaps (2), or free flaps (1). Amputation was mainly for advanced disease, with radial forearm flaps used for reconstruction. All flaps remained disease-free. Five cases (41.6%) had a history of local recurrence. Conclusions: The early diagnosis of Huriez syndrome is crucial to enable the surveillance and timely treatment of SCC. A multidisciplinary team including dermatologists, oncologists, plastic surgeons, and geneticists is recommended. Further research is needed to clarify genetic mechanisms and develop early detection strategies to improve outcomes. Full article

Basal cell carcinoma (BCC), the most common skin cancer, is primarily driven by Hedgehog (Hh) and TP53 pathway alterations. Although additional pathways were implicated, the mutational landscape in Asian populations, particularly Koreans, remains underexplored. We performed whole-exome sequencing of BCC tumor tissues from Korean patients and analyzed mutations in 11 established BCC driver genes (PTCH1, SMO, GLI1, TP53, CSMD1/2, NOTCH1/2, ITIH2, DPP10, and STEAP4). Mutational profiles were compared with Caucasian cohort profiles to identify ethnicity-specific variants. Ultraviolet (UV)-exposed and non-UV-exposed tumor sites were compared; genes unique to non-UV-exposed tumors were further analyzed with protein–protein interaction analysis. BCCs in Koreans exhibited distinct features, including fewer truncating and more intronic variants compared to Caucasians. Korean-specific mutations in SMO, PTCH1, TP53, and NOTCH2 overlapped with oncogenic gain-of-function/loss-of-function (GOF/LOF) variants annotated in OncoKB, with some occurring at hotspot sites. BCCs in non-exposed areas showed recurrent mutations in CSMD1, PTCH1, and NOTCH1, suggesting a UV-independent mechanism. Novel mutations in TAS1R2 and ADCY10 were exclusive to non-exposed BCCs, with protein–protein interaction analysis linking them to TP53 and NOTCH2. We found unique ethnic-specific and UV-independent mutational profiles of BCCs in Koreans. TAS1R2 and ADCY10 may contribute to tumorigenesis of BCC in non-exposed areas, supporting the need for population-specific precision oncology. Full article

Exosomes, small extracellular vesicles secreted by various cell types, have gained significant attention in cancer investigations. Isolation and characterization of exosomes derived from DOK (dysplastic oral keratinocyte), SCC (squamous cell carcinoma) and HaCaT (normal skin keratinocyte) cell lines and microRNA profiling were conducted. Magnetic sorting was applied to obtain pure exosomes. Morphology and size were characterized by transmission electron microscopy and nanoparticle tracking analysis. Validation of membrane exosomal markers (CD9, CD63) was performed via Western blotting. MiR-21, miR-31, and miR-133 levels were analyzed in exosomes and parent cells by qPCR. Biological effects of the exosomes were tested by adding them to fibroblast cultures and determining the expression of relevant carcinogenesis markers by qPCR. Exosomes appeared as cup-shaped nano-sized particles, and there was no difference regarding particle diameter and concentration between the three types of exosomes. The oncogenic miR-21 was significantly upregulated both in SCC and SCC-derived exosomes compared to DOK and HaCaT cells and their respective exosomes. However, miR-31 unexpectedly showed the highest expression in normal cells and the lowest in HaCaT exosomes. MiR-133, the tumor suppressor miRNA, was downregulated in both SCC and DOK cells compared to normal (HaCaT) cells, while the opposite situation was observed in exosomes, with HaCaT cells showing the lowest levels of miR-133. The differences in exosome content were reflected in signaling pathway activation in exosome-treated fibroblasts, with SCC exosomes exerting the most potent effect on several cancer-related pathways, notably PIK3/AKT, PTEN, and NOTCH signaling cascades. Full article

Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as pivotal regulators in both inflammatory and neoplastic skin disorders. Their implications in numerous biological processes, including gene expression, immune responses, and epidermal homeostasis, suggest potential applications as diagnostic and prognostic markers, as well as therapeutic targets. Methods: We conducted a literature search on lncRNAs involved in both psoriasis and cutaneous squamous cell carcinoma (cSCC), highlighting overlapping pathogenic mechanisms. Results: Several lncRNAs, such as HOTAIR, MALAT-1, H19, and uc.291, display dysregulated expression in both psoriasis and cSCC, influencing keratinocyte proliferation and apoptosis, immune modulation, cytokine signaling, and the synthesis of epidermal proteins. Conclusions: The intersection of lncRNA function in chronic inflammation and skin carcinogenesis underscores their role in mediating the transition from psoriatic inflammation to tumorigenesis, offering new insights into disease susceptibility; further investigation through functional studies and clinical validation are required. The study of lncRNA-mediated molecular pathways is particularly relevant given the increased risk of non-melanoma skin cancers and lymphoproliferative disorders among patients with chronic and severe forms of psoriasis. Full article

Background/Objectives: The gold standard of treatment for both melanoma and non-melanoma skin cancers is wide surgical resection to obtain oncological radicality, which occasionally results in functional or aesthetic impairment, potentially affecting quality of life. Despite the increased complexity of the technique, extended duration of hospitalization, and prolonged surgical operative times, microsurgery can facilitate the reconstruction of locally invasive skin cancers following ablative surgery and may yield superior functional and aesthetic outcomes. Consequently, microsurgical reconstruction is more likely to be necessary if a large skin tumor requires excision. However, the impact of this extensive and complex procedure on patients with skin cancer has not yet been fully elucidated. The objective of this research was to critically analyze the utilization of free flap reconstruction subsequent to skin cancer therapy. Through a comprehensive examination of published data, this study aimed to assess the potential benefits and drawbacks associated with this reconstructive approach. Methods: A systematic review of studies that were published from January 2004 to May 2024 was conducted using the MEDLINE online database search. To present an evidence summary and provide a systematic approach and quality assessment, the GRADE^® rating was applied to the results. Results: This review summarizes the oncological and clinical data, including previous interventions, adjuvant and neoadjuvant therapies, nodal status, distant metastasis, and follow-up time. Surgical outcome parameters such as healing time, flap survival, revision rate success, and minor and major complications were documented. Along with the findings, a quality assessment of the studies was also provided. Conclusions: This systematic review underscores the extensive use and efficacy of microsurgery for reconstruction after skin cancer excision; however, the literature remains limited by inconsistent reporting of oncological outcomes and the lack of a standardized approach to evaluate the impact of free flap reconstruction on both immediate and long-term cancer-specific results. Full article

Recently, there has been a rise in skin cancer cases, for which early detection is highly relevant, as it increases the likelihood of a cure. In this context, this work presents a benchmarking study of standard Convolutional Neural Network (CNN) architectures for automated skin lesion classification. A total of 38 CNN architectures from ten families (ConvNeXt, DenseNet, EfficientNet, Inception, InceptionResNet, MobileNet, NASNet, ResNet, VGG, and Xception) were evaluated using transfer learning on the HAM10000 dataset for seven-class skin lesion classification, namely, actinic keratoses, basal cell carcinoma, benign keratosis-like lesions, dermatofibroma, melanoma, melanocytic nevi, and vascular lesions. The comparative analysis used standardized training conditions, with all models utilizing frozen pre-trained weights. Cross-database validation was then conducted using the ISIC 2019 dataset to assess generalizability across different data distributions. The ConvNeXtXLarge architecture achieved the best performance, despite having one of the lowest performance-to-number-of-parameters ratios, with 87.62% overall accuracy and 76.15% F1 score on the test set, demonstrating competitive results within the established performance range of existing HAM10000-based studies. A proof-of-concept multiplatform mobile application was also implemented using a client–server architecture with encrypted image transmission, demonstrating the viability of integrating high-performing models into healthcare screening tools. Full article