Epiplakin expression in non-melanoma skin cancer: associations with epithelial-mesenchymal transition markers and tumor invasion.

Efficacy and safety of electrochemotherapy in the treatment of cutaneous and sub-cutaneous recurrence from breast cancer: A single-center cohort study.

Background/Objectives: Vitamin D (VD), through the interaction with its receptor (VDR), plays essential roles in the skin. VDR-mediated signaling prevents cancer development and improves prognosis, making it an appealing target for therapy. However, VD cutaneous synthesis begins with solar exposure, which is the first etiological factor for cutaneous cancer and increases oxidative stress (OS). This complicates the dermatologist's perspective when advising photoprotective strategies while aiming to consider the benefits of VD signaling. In this context, and in the absence of cutaneous data to date, this research aims to address VDR dynamics in skin cells and tissue subjected to OS. It also explores the potential of a natural photoprotectant with antioxidant properties (a specific combination of Polypodium leucotomos and Aspalathus linearis extracts) in preventing VDR depletion. Methods: HaCaT cell cultures and skin explants were used as experimental models. OS was induced by treatments with hydrogen peroxide (H2O2). The proteins of interest (VDR and Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)) were analyzed by immunostaining. Cell viability, nuclear counterstaining, and Haematoxylin/Eosin staining were used as cyto/histochemical controls. Results: In both experimental models, we observed the reduction of VDR under OS. Pre-treatments with the botanical ingredient preserved VDR levels from that decline, probably through a mechanism involving NRF2. Conclusions: Cutaneous VDR levels are altered under oxidative stress, and certain photoprotectants could preserve them. This opens the door to preserving the benefits of VDR signaling while preventing solar radiation damage, bringing a new viewpoint for designing future strategies in skin cancer prevention and treatment.

Pigments used in tattoos represent a unique case of voluntary, long-term exposure to particles trapped in the skin. Evidence is accumulating that these compounds, and in particular red pigments, are associated with skin disorders and possibly cutaneous cancers. In the present work, we tested the hypothesis of degradation of pigments in the dermis that would lead to the release of diffusible nanoparticles or soluble degradation products. These species could then reach the epidermis and trigger physiological responses by impacting keratinocytes. Two degradation pathways of tattoo pigments were investigated in the present work, which combined physicochemical characterization and toxicological assessment in the HaCaT human keratinocyte cell line. The first pathway was the photodegradation of pigments that we explored in a previous work on Pigment orange 13 (PO13) and extended here to Pigment red 254 (PR254) and Pigment red 122 (PR122). While PR254 was photostable, PR122 was found to release toxic photoproducts. The second studied pathway was the possible degradation in the phagolysosomes of macrophages where pigment particles are stored in the skin. We did not observe degradation upon incubation in reconstructed phagolysosomal medium but rather found that the added immunoglobulins completely inhibited the cytotoxicity of PO13, PR254, and PR122. The observation of a drastic decrease in ζ potential strongly suggested the creation of a protein corona, which led to a decrease in cellular toxicity.

Abstract Background: Cutaneous metastases in breast cancer (CMBC) are clinically challenging and associated with poor prognosis and limited therapeutic options. Conventional treatments offer minimal survival benefit and often fail to control skin lesions. Emerging data suggest that immunotherapy, particularly adoptive cell therapy, may offer therapeutic promise. This study evaluates the feasibility and immunologic impact of cytokine-induced killer (CIK) cells in preclinical models of CMBC. Methods: We established in vitro and in vivo models using murine breast cancer cells with cutaneous metastatic potential. CIK cells were generated from peripheral blood mononuclear cells of murine splenocytes. Cytotoxicity assays, flow cytometry, transcriptomic profiling, and immunohistochemistry were used to assess anti-tumor effects and immune-related changes. The impact of CIK therapy alone or in combination with a TLR7 agonist was also examined. Results: Transcriptomic analysis of cutaneous lesions revealed upregulation of immune effector molecules (CXCL9/10/11, B2M, CD27) and checkpoint pathways (PD-L1). CMBC cells showed heightened sensitivity to CIK-mediated cytotoxicity compared to non-cutaneous metastatic cells. In vivo, CIK therapy significantly reduced cutaneous tumor burden and prolonged survival. Co-administration of a TLR7 agonist enhanced tumor cell apoptosis, reduced PD-L1 expression, and increased T-cell infiltration, suggesting a synergistic immunomodulatory effect. Conclusions: CIK cell therapy demonstrates strong preclinical efficacy against breast cancer cutaneous metastases and reshapes the tumor immune microenvironment. These findings support further development of CIK-based immunotherapy, potentially in combination with innate immune modulators, for patients with CMBC—a clinical subgroup with high unmet need. Citation Format: M. Hou, S. Chang, F. Chen, M. Pan, C. Luo. Cik cell therapy remodels the immune microenvironment and suppresses cutaneous metastatic breast cancer in preclinical models [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-01.

Background: Cutaneous squamous cell carcinoma (cSCC) represents one of the most common keratinocyte-derived malignancies encountered in clinical practice; however, its genomic landscape remains far less comprehensively characterized than that of other cutaneous cancers. This study aims to identify key molecular drivers and potential therapeutic targets by comprehensively characterizing the genomic landscape of cSCC using data from the American Association for Cancer Research (AACR) Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) consortium. Methods: A retrospective cohort analysis of cSCC samples was performed utilizing AACR Project GENIE data accessed via the cBioPortal platform (v18.0-public) on 22 November 2025. Analyses included identification of recurrent somatic and copy-number alterations, pairwise gene-gene co-occurrence testing using Fisher's exact tests with Benjamini-Hochberg False Discovery Rate (FDR) correction, and exploratory subgroup comparisons by sex and race, with statistical significance defined as p < 0.05. Results: Recurrent mutations were identified in TP53 (83.5%), NOTCH1 (56.3%), KMT2D (47.0%), CDKN2A (44.4%), TERT (41.4%), ROS1 (34.3%), FAT1 (33.3%), NOTCH2 (31.2%), ERBB4 (28.4%), and KMT2A (24.3%), reflecting disruption of the p53 pathway, cell-cycle control, Notch signaling, epigenetic regulation, telomere maintenance, RTK/MAPK pathways, and Wnt signaling. Statistically significant co-occurrence patterns were observed, and exploratory subgroup analyses evaluated mutation frequency differences by sex and race. Conclusions: This large, multi-institutional genomic analysis defines recurrent mutational and structural alterations in cSCC and highlights an integrated pattern of pathway disruption involving genomic integrity, differentiation, epigenetic control, and proliferative signaling. These findings enhance current understandings of the molecular architecture underlying this common yet genomically understudied malignancy and provide a foundation for future mechanistic studies and development of targeted diagnostic and therapeutic strategies.

Cutaneous metastatic breast cancer (CMBC) exhibits aggressive behavior driven by tumor adaptation to the skin microenvironment, yet research specifically addressing breast cancer metastasis to the skin remains limited, representing a significant unmet clinical need. In this study, transcriptomic profiling, functional assays, and mouse models revealed that CMBC is associated with poor prognosis and upregulation of angiogenesis, inflammatory signaling, and lipid metabolism, particularly arachidonic and linoleic acid pathways. Adipocyte-derived signals enhanced cutaneous metastasis through STAT3 activation, leading to increased Angpt2, Vegfc, and Ptgis expression. Pharmacologic inhibition of STAT3 suppressed metastasis in vitro and in vivo. Elevated STAT3, ANGPT2, and PTGIS levels correlated with reduced progression-free and disease-free survival. These findings highlight STAT3-mediated signaling and metabolic reprogramming as key drivers of CMBC progression and suggest a promising therapeutic target for this understudied and clinically challenging condition.

Prurigo nodularis (PN) is a chronic inflammatory skin disorder associated with various systemic disorders. However, its potential link to increased malignancy risk remains unclear. We conducted a retrospective cohort study using the US Collaborative Network in the TriNetX database, encompassing data from January 1, 2016 to January 1, 2022. Adults diagnosed with PN (n = 10 941) were matched 1:1 with controls without PN (n = 10 941) based on demographics, comorbidities, and medication use. The primary outcome was the hazard ratio (HR) for malignancy occurring between 3 months and 5 years after the index date. The HRs and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Patients with PN exhibited a significantly increased risk of developing malignancies compared with the controls (HR 2.10; 95% CI 1.81-2.43). Notably, higher risks were observed for cutaneous squamous cell carcinoma (HR 4.24; 95% CI 2.69-6.69), basal cell carcinoma (HR 2.49; 95% CI 1.68-3.69), hematopoietic cancers (HR 1.97; 95% CI 1.26-3.06), gastrointestinal cancers (HR 1.87; 95% CI 1.24-2.81), respiratory system cancers (HR 1.86; 95% CI 1.23-2.82), and female genital cancers (HR 2.77; 95% CI 1.29-5.95). In conclusion, PN is associated with a significantly elevated risk of malignancy, particularly cutaneous cancers. These preliminary findings underscore the necessity for heightened clinical vigilance. Further prospective studies are needed to confirm this association, elucidate the underlying mechanisms, and evaluate the potential benefits of routine cancer screening in this high-risk population.

HIV-related exclusion criteria in cutaneous cancer clinical trials.

Epithelia maintain their barrier function through the proliferative and plastic behavior of stem cells that drive continuous tissue regeneration. However, these same properties render epithelia susceptible to tumorigenesis. The skin, the largest epithelial barrier, is the source of the most prevalent human cancers, yet the molecular mechanisms by which stem cells and their microenvironment cooperate to promote cutaneous cancer development remain incompletely defined. Previous work demonstrated that genotoxic injury in normal skin activates epithelial-dermal inflammasome signaling that drives epithelial stem cell hyperproliferation and misspecification. Here, we investigated whether this mechanism also operates in diseased skin. We found that stem cell misspecification is a broadly conserved feature across pathological skin conditions but is absent in normally proliferating tissue. Notably, inflammasome activation is detected in both epithelial and dermal compartments of cutaneous squamous cell carcinoma (cSCC), but not in other skin pathologies. Mechanistically, oncogenic KRAS expression in keratinocytes triggers inflammasome activation before tumor formation non-cell autonomously. Furthermore, IL-1 signaling is activated in fibroblasts adjacent to the cSCC tumor interface, but not in the overlying epithelium. Taken together, these findings support a model in which KRAS-driven epithelial-fibroblast inflammasome crosstalk establishes a feed-forward IL-1 signaling loop that enhances the tumor-promoting microenvironment in cSCC.

Background: The rising incidence of cutaneous non-melanoma skin cancers underscores the need for individualized reconstruction, particularly for cheek defects that pose distinctive anatomic and functional challenges. This study aimed to analyze reconstructive patterns for cheek skin lesions and to develop a simple, site- and size-based algorithm for small- to medium-sized defects. Methods: We retrospectively reviewed 129 consecutive patients treated between 2022 and 2025 for primary basal cell carcinoma, squamous cell carcinoma, or benign cheek skin tumors. After excision, defects were reconstructed with primary closure, local flaps, or skin grafts. Associations between the largest clinically measured lesion diameter (used as a proxy for the post-excision defect size), anatomical subsite, histopathology, and reconstructive technique were evaluated using ANOVA or Kruskal-Wallis tests, chi-square tests, and Spearman's correlation. Results: The mean lesion diameter was 19.75 ± 12.93 mm. Reconstruction was performed using local flaps in 62 patients (48.06%), primary closure in 53 (41.09%), and skin grafts in 14 (10.85%). Larger defects were more frequently managed with grafts or flaps (F(2,110) = 4.84, p = 0.010), and lesion size correlated with reconstructive complexity (Spearman's ρ = 0.229, p = 0.015). Lesion location was also significantly associated with the reconstruction method (χ2(10) = 48.29, p < 0.001; Cramér's V = 0.44). Margin-negative (R0) excision was achieved in 95.35% of cases, with a low recurrence rate (3.91%) and complication rate (1.56%). Conclusions: Lesion size and anatomical location are key determinants of reconstructive strategy for cheek skin defects. In this cohort, lesions ≤ 20 mm were predominantly managed with primary closure, whereas lesions > 20 mm more frequently required flap reconstruction or skin grafting. This size-based split is cohort-derived and should be interpreted as a pragmatic framework that requires external validation.

Recent advances in ENT are transforming clinical practice. In audiology, bone conduction stimulation alleviates tinnitus, even in normal-hearing patients. The new European consensus on congenital CMV infection optimizes follow-up by trimester of maternal infection. In phoniatrics, EMG-controlled electrolarynx devices improve intonation, while cell therapy and AI (>90 % sensitivity) transform laryngeal regeneration and lesion analysis. In thyroid surgery, nerve monitoring, fluorescence, and 3D exoscopes enhance safety ; thermoablation allows personalized de-escalation. Airway reconstructions guided by 3D imaging improve voice and swallowing recovery. Finally, immunotherapy (pembrolizumab, cemiplimab) redefines head and neck and cutaneous cancer care.

The Nurse's Role in the Practical Management of Lymphocele after Inguinal Dissection for Cutaneous Cancer: Tunisian Study

Background/Objectives: Actinic keratosis (AK) is a precancerous lesion that may progress into cutaneous cancer. However, the progression potential of individual lesions remains unpredictable. The histological basal proliferation pattern of AKs may serve as a risk marker for progression, yet it cannot be assessed clinically. The objective was to evaluate whether Olsen grading (hyperkeratosis of AKs) and pain as clinical markers correlate with the histological basal proliferation (PRO) and different histological aspects. Methods: In this retrospective two-center study, 380 clinically diagnosed AKs were graded according to the clinical Olsen classification (I-III) and assessed for pain upon palpation. Histologically, they were classified based on their basal- (PRO I-III) and upward-directed (AK I-III) growth patterns, and additional histopathological features, such as acantholysis, were documented. Results: Olsen grading showed weak correlation with the PRO classification (Spearman's rho = 0.136, p = 0.008), with exact agreement of 36.3% (κ = 0.07). Pain was significantly associated with higher PRO grades (p = 0.005) and acantholysis (p = 0.023) but not with Olsen grades or upward-directed growth (AK I-III). Conclusions: Olsen grading does not allow reliable prediction of basal proliferation patterns in AKs. Its use as a clinical severity scale may suggest progression relevance; however, no substantiated association with histological indicators of transformation could be demonstrated in this study. The presence of pain, however, correlated with high PRO grades and the presence of acantholysis.

Minimally invasive treatments are increasingly needed for low to intermediate risk cutaneous squamous cell carcinoma (cSCC), particularly in patients with high disease burden. To evaluate the efficacy and tolerability of intralesional talimogene laherparepvec (TVEC) as a novel immunotherapeutic approach for cSCC in patients seeking non-surgical options. Up to 5 histologically confirmed invasive low to intermediate risk cSCC tumors per patient were treated and referred to as target lesions injected (TLIs). Intralesional TVEC was administered every 2 weeks, up to 4 injections per lesion. Response rate was assessed by subject and individual TLIs. Eleven patients with 24 cSCC tumors were enrolled. ORR was 100% by patient (11/11) and by tumor (24/24) (95% CI = 76.2%). A confirmed complete response occurred in 90.9% of patients (10/11; 95% CI = 58.7%, 99.8%) involving 23 of 24 tumors. Median duration of response was 212 days (range = 140-236 days). Two years post-treatment, patients showed no recurrence and significantly fewer new primary invasive cSCCs. Nonrandomized, small sample size, and lesion site exclusions. Intralesional TVEC demonstrated promising efficacy and tolerability as a minimally invasive treatment for low to intermediate risk cSCC with potential to reduce subsequent incidence rates.

Basosquamous carcinoma (BSC) is a rare and aggressive cutaneous cancer with an increased risk of recurrence and metastasis. There are no specific clinical presentations of BSC, and the diagnosis is only made after biopsy. We report a case of histologically confirmed basosquamous carcinoma. We Report: A 70-year-old female patient with a personal history of treated nasopharyngeal tumor presented with a two-year history of a linear, ulcerated, bleeding-on-contact lesion on her face. A biopsy was performed, and histology revealed a tumor with mixed features of basal cell carcinoma combined with an area of squamous cell carcinoma, consistent with the morphological appearance of basosquamous carcinoma.

ABSTRACT Background Hematopoietic stem cell transplant (HSCT) recipients face an increased risk of cutaneous malignancies. Chronic cutaneous graft‐versus‐host disease (cGVHD), specific to allogeneic HSCT (alloHSCT), has been proposed to further elevate this risk, though its impact on skin cancer latency and distribution remains unclear. Objectives To evaluate the timeline and characteristics of post‐transplant skin cancers in HSCT recipients, stratified by transplant type and presence of cutaneous cGVHD. Methods A retrospective cohort study of HSCT recipients with documented cutaneous malignancies treated at Duke University Medical Center from 2010 to 2020. Patients with solid organ transplants were excluded. Primary outcomes were time to first and second skin cancer post‐transplant. Secondary outcomes included cancer type, number, and anatomic location. Results Among 192 patients, 96 underwent alloHSCT with cutaneous cGVHD, 20 alloHSCT without cGVHD, and 76 autoHSCT. Time to first skin cancer was significantly longer in the cGVHD group (mean 2131 days) compared to alloHSCT without cGVHD (1686 days) and autoHSCT (1287 days; p = 0.047). However, time to second malignancy was shorter in the cGVHD cohort (2871 days) than in alloHSCT without cGVHD (4231 days) but longer than autoHSCT recipients (1954 days; p = 0.02). SCC was the most prevalent malignancy, though patients with cGVHD had higher rates of BCC and melanoma. Cutaneous cancers predominantly involved UV‐exposed areas, but truncal involvement was more common in cGVHD patients. Conclusions HSCT recipients with cutaneous cGVHD demonstrate delayed onset of first skin cancer but accelerated development of subsequent malignancies. These findings suggest dynamic immune shifts over time and emphasize the need for tailored dermatologic surveillance protocols based on transplant type and cGVHD status.

Cutaneous cancer is a constantly progressive health challenge as life-threatening in men and women around the world. This study addressed repurposed ciclopirox olamine (COA) through the utilization of different essential oils limonene (LIM), eugenol (EU), and olive oil (OLO) as natural lipids possessing innate anticancer potential. HSPiP software provided preliminary screening of oils and solvents based on the theoretical solubility of COA. Placebo microemulsions (ME1-ME3) were prepared after optimizing Smix at varied ratios (surfactant to co-surfactant ratio) and evaluated for size, zeta potential, and polydispersity index (PDI). EU, LIM, and OLO (as microemulsions) were used to assess anticancer potential against A431, A375, and B16-F10 cell lines. Moreover, HSF (human fibroblast cells) was used to assess the safety of these excipients at the same concentrations. It was required to carry out concentration-dependent cytotoxic potential of EU and LIM against A431 and B16-F10 as compared to COA. Finally, an apoptosis study was conducted to understand the mechanistic perspective of EU and LIM against A431 and B16-F10. Results showed an excellent correlation (r2 = 0.97) of the predicted theoretical solubility of COA in the explored excipients to the experimental solubility data. UV scanning of the COA-solubilized oils negated any chemical interactions. ME1-ME3 showed tween-80 (10.9–21.6%) dependent size reduction (510–339 nm) and PDI values (0.28–0.31). In the cytotoxicity study, EU, LIM, and OLO elicited concentration-dependent cellular killing. LIM was found to be relatively sensitive to A431 and B16-F10 compared to EU. Notably, LIM resulted in dramatically aggressive induced early and late apoptosis in both cell lines at the explored IC50. Thus, the topical nanoformulations of COA containing anticancer essential oils can offer a promising approach for treating cutaneous melanoma.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-18141-4.

Economic and environmental benefits of greening a Mohs surgery clinic: A comprehensive intervention and analysis.

Breast cancer is the most common non cutaneous cancer in Irish women. Diagnosis offers a key opportunity to promote lifestyle change. This study assessed awareness of modifiable lifestyle risk factors and acceptability of secondary risk reduction services amongst breast cancer survivors and healthcare professionals.A cross-sectional study was conducted between September and December 2021. Surveys were developed using previously validated questionnaires: the Mitchelstown Cohort Survey and the International Physical Activity Questionnaire. A survey was offered to healthcare professionals working in and patients attending the early breast cancer outpatient clinic at the South Infirmary Victoria and Cork University Hospitals', Ireland.322 patients and 29 healthcare professionals participated. Many patients met at-risk lifestyle factors; body mass index >25kg/m2 (66 % [n = 203/313]), low physical activity (19 % [n = 60/322]), frequent consumption of high fat, sugar and salt containing foods (42 % [n = 135/320]), increased alcohol consumption (39 % [n = 125/322]) and current smoker (5 % [n = 17/322]). 83 % of patients and HCPs agreed that modifiable lifestyle risk factors are important in cancer prevention. Only 17 % (n=5/29) of HCPs had training in secondary risk reduction; however, 90 % were willing to refer to services. Patients who had increased alcohol intake or weight gain since diagnosis were more likely to engage with services (44 %, n = 15/34 [p=<0.008]) and (74 %, n = 99/134, [p = <0.001]).A large proportion of patients met at-risk lifestyle criteria. Gaps in knowledge of at-risk lifestyle behaviours exist. Patients intended engagement with some secondary risk reduction services was associated with their lifestyle behaviours. Our study highlights the challenges of implementing survivorship health promotion programs.