Transplant recipients have an elevated risk of actinic keratosis (AK), a precursor for squamous cell carcinoma (SCC). We assessed whether an AK polygenic risk score (PRS) can identify transplant-naive individuals and transplant recipients at risk of multiple AKs who may benefit from early prevention. Using genome-wide association data (140,339 cases; 1,430,776 controls), we developed an AK PRS and evaluated it in cohort studies of European descent individuals in QSkin (N=12,843), STAR (N=357), UK Biobank (N=963), and All of Us (N=1,859). The PRS was strongly associated with high AK burden in transplant-naive individuals, conferring a five-fold increased risk of developing ≥20 AKs (OR per standard deviation (SD) increase in the PRS =5.06, 95%CI=4.69-5.46). In transplant recipients, it was associated with up to a 2.5-fold increased risk of developing ≥1 AK (UKB OR per SD =2.49, 95%CI=1.91-3.23; STAR OR per SD=1.79, 95%CI=1.10-2.91; All of Us OR per SD=1.52, 95%CI=1.35-1.70). The PRS improved prediction of ≥20 AKs by 13% beyond age and sex (AUC 0.90 vs 0.77) and identified the highest-risk 20% with a 9-fold increased risk in transplant-naive individuals (OR=8.61, 95%CI=7.26-10.22) and a 2-fold increased risk in transplant recipients (OR=2.23, 95%CI=1.26-4.20), compared to the middle-risk 60%. Incorporating PRS into pre- and post-transplant care could enable earlier, personalised prevention.

Keratinocyte carcinoma (KC) places a considerable and growing burden on healthcare systems. Given the KC population's heterogeneity, tailored clinical pathways are needed to accommodate diverse management needs. This study applied machine learning (ML)-based phenomapping to identify distinct real-world subgroups within a national KC population using demographic and medical history variables. The study included KC patients treated in publicly-funded, office-based dermatology practices and registered in the Danish Skin Cancer Registry (2014-2022). In 106,490 KC patients, 7 ML-derived clusters were identified. One cluster (22.2%; n=23,590) consisted primarily of young, well educated high-income medically noncomplex females presenting with low-risk basal cell carcinomas (BCCs). Four clusters (55.2%; n=58,736) comprised patients with a greater dermatological disease burden, characterized by facial BCCs, multiple BCCs, a greater proportion of squamous cell carcinomas (SCCs), a history of skin cancer or previous actinic keratosis-related treatment. The remaining 2 clusters (22.7%; n=24,164) comprised highly comorbid patients with a greater proportion of SCCs, a high number of KCs on the head and neck and high immunosuppressive drug exposure. ML-derived phenomapping of a national KC population identified distinct, clinically relevant KC subgroups, providing a basis for tailored clinical pathways with differentiated resource needs.

Bowen's disease and bowenoid actinic keratosis share overlapping clinical and histopathological features, and there is no clear consensus regarding their differential diagnosis. This study aimed to identify clinicopathological differences between the two diseases and to develop a diagnostic prediction model in a Korean population. We retrospectively analyzed 253 patients pathologically diagnosed with Bowen's disease or bowenoid actinic keratosis at a single institution in South Korea. Clinical and histopathological variables were compared between the two groups, and significant variables were incorporated into a multivariable logistic regression model. The model was externally validated using an independent cohort of 207 patients from another institution in South Korea. In the development cohort, variables significantly associated with diagnosis included lesion location, adjacent pigmented lesions, solar elastosis, pathologically identical lesions in the same region, and the number of atypical cells within a 3 mm width of the epidermis. The prediction model showed good discriminative performance, with an area under the receiver operating characteristic curve of 0.897. In the external validation cohort, the model demonstrated excellent performance, with an area under the curve of 0.994 and an accuracy of 95.17%. These findings suggest that integration of clinical and histopathological features may help differentiate Bowen's disease from bowenoid actinic keratosis in Korean clinical settings. Further validation in ethnically and geographically diverse populations is needed before broader application of the proposed model.

Although the association between diabetes and cutaneous squamous cell carcinoma (cSCC) is well recognized, the specific role of insulin resistance (IR) as an independent driver of cSCC pathogenesis remains underexplored. This review synthesized emerging evidence on the ultraviolet (UV)-independent molecular mechanisms by which IR promotes cSCC initiation and progression. Hyperinsulinemia activates the insulin-like growth factor-1 receptor (IGF-1R), which triggers both the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways, stimulating keratinocyte proliferation and suppressing apoptosis. In parallel, hyperglycemia-driven formation of advanced glycation end products (AGEs) and oxidative stress cause deoxyribonucleic acid (DNA) damage and impair tumor suppressor functions, notably that of tumor protein p53 (TP53). The resulting reactive oxygen species (ROS) activate nuclear factor-kappa B (NF-κB), establishing a chronic inflammatory milieu that remodels the tumor microenvironment through cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and by upregulating matrix metalloproteinases (MMPs). These processes collectively facilitate the malignant transformation of actinic keratosis (AK) to invasive cSCC. The analysis in the present study identified novel therapeutic targets and reaffirmed the importance of further studies on microbiome interactions and lifestyle interventions for IR-associated cSCC.

Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer, and primarily diagnosed by invasive and time-consuming histopathological biopsy, highlighting the need for rapid, non-invasive adjunctive tools. We report the case of a 93-year-old patient presenting with a suspicious scalp lesion who underwent dermoscopy, Wood's lamp examination, and in vivo Raman spectroscopy prior to biopsy. Conventional clinical examinations suggested a malignant lesion but were unable to determine the specific tumor type, whereas Raman spectra displayed high similarity to former BCC cases and clear separation from actinic keratosis cases by principal component analysis. Characteristic Raman peaks associated with collagen (936 and 1657 cm[-1]), glycine (1204 cm[-1]), and phospholipids (1445 cm[-1]) were identified, consistent with molecular alterations reported in BCC. Although the initial histopathological assessment suggested a benign lesion, subsequent expert review together with immunohistochemical analysis confirmed BCC, aligning with the Raman spectroscopy findings. This case further demonstrates the potential of Raman spectroscopy to complement conventional histopathology and assist in the identification of diagnostically challenging BCC cases.

Recent studies have linked modifiable risk factors (RFs) to melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). This study aimed to investigate the causal relationships between 11 modifiable RFs and these skin cancers and to identify novel therapeutic targets using multi-omics approaches.

Ultraviolet (UV) light exposure is a recognised risk factor for dermal haemangiosarcoma (HSA) in dogs and dermal squamous cell carcinoma (SCC) in dogs and cats. These tumours cause substantial local disease and often require repeated surgery due to recurrence or de novo lesions, creating a notable welfare and financial burden. Research on preventing harmful UV exposure in pets is still in its infancy, particularly in relation to the safety of UV filters used in sunscreens. This review summarises the current evidence on UV-induced carcinogenesis, strategies to reduce UV exposure, and the safety of sunscreen ingredients in dogs and cats. UV light is strongly implicated in a range of dermatoses, from actinic keratosis to dermal HSA and SCC in dogs and cats, and the risk is likely higher in Australian pets. Indoor confinement during peak UV periods, shade, and sun-protective clothing can reduce exposure, with sunscreen an additional strategy. Sunscreen is relevant because UV-associated cancers typically develop in sparsely haired or hairless regions such as the nose and ventrum, making these areas suitable for targeted sunscreen application. Sunscreens containing non-nanoparticle zinc oxide appear safe for dogs and cats when ingestion is prevented or minimised, whereas the safety of organic UV filters remains unclear due to limited safety data in both humans and animals. Non-nanoparticle titanium dioxide is a possible alternative to zinc oxide and organic filters, but there is currently little information on its safety when ingested by dogs and cats. Overall, the available evidence supports sunscreen as a necessary component of UV-reduction strategies in pets, but substantial research is needed to determine the safety profiles of different UV filters and to establish evidence-based guidelines for their safe use.

Photodynamic therapy (PDT) is a cornerstone non-invasive modality for keratinocytic precancers and non-melanoma skin cancer (NMSC), leveraging selective photosensitizer accumulation, light activation, and reactive oxygen species (ROS) generation. This narrative review synthesized literature from major databases (2010-2025) to comprehensively evaluate PDT's molecular mechanisms, innovative optimization protocols, and clinical efficacy across actinic keratosis (AK), field cancerization, Bowen's disease (BD), basal cell carcinoma (BCC), and invasive squamous cell carcinoma (cSCC). The evidence highlights frontline clinical maturity and excellent cosmetic outcomes for superficial lesions (AK, field cancerization, superficial BCC, and BD), with daylight PDT offering a virtually painless alternative for widespread dysplasia. However, therapeutic reliability decreases in thick nodular, pigmented, or high-risk lesions due to optical barriers and tissue hypoxia. To overcome these limitations, advanced physical and chemical enhancements-such as ablative fractional lasers, iron chelators, epigenetically enhanced PDT (ePDT), and targeted nanocarriers-are actively reshaping drug delivery and cellular susceptibility. Furthermore, cyclic PDT serves as an indispensable tissue-sparing intervention for organ transplant recipients and Gorlin syndrome patients. In conclusion, while PDT is highly effective for superficial neoplasias, precise histopathological stratification and the integration of nanomedicine are critical to overcoming current biological barriers in aggressive dermatological malignancies.

Photodynamic therapy (PDT) is an established treatment for actinic keratosis, with adverse effects usually limited to transient phototoxic reactions. Allergic contact dermatitis (ACD) to topical photosensitizers is rare and has mainly been reported in association with methyl aminolevulinate (MAL). Data on allergic reactions following laser-assisted PDT remain limited. A 67-year-old male patient with a history of previously well-tolerated laser-assisted PDT developed a severe eczematous skin reaction after laser-assisted PDT with 5-aminolevulinic acid (ALA) for the treatment of actinic keratoses of the scalp and arms. Patch testing after complete clinical healing revealed positive reactions to both ALA and MAL, while the vehicle and standard allergens remained negative, confirming the diagnosis of ACD to ALA. As only ALA had been applied clinically during the current and previous PDTs, the reaction to MAL was interpreted as cross-sensitization rather than evidence of clinical exposure. This case highlights ACD as a rare yet clinically relevant adverse effect of laser-assisted PDT and demonstrates cross-sensitization between ALA and MAL in the absence of prior clinical MAL exposure.