Basal cell carcinoma (BCC), the most common keratinocyte cancer, presents a substantial public health challenge due to its high prevalence. Traditional diagnostic methods, which rely on visual examination and histopathological analysis, do not include metabolomic data. This exploratory study aims to molecularly characterize BCC and diagnose tumour tissue by applying matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and machine learning (ML). BCC tumour development was induced in a mouse model and tissue sections containing BCC (n = 12) were analysed. The study design involved three phases: (i) Model training, (ii) Model validation and (iii) Metabolomic analysis. The ML algorithm was trained on MS data extracted and labelled in accordance with histopathology. An overall classification accuracy of 99.0% was reached for the labelled data. Classification of unlabelled tissue areas aligned with the evaluation of a certified Mohs surgeon for 99.9% of the total tissue area, underscoring the model\'s high sensitivity and specificity in identifying BCC. Tentative metabolite identifications were assigned to 189 signals of importance for the recognition of BCC, each indicating a potential tumour marker of diagnostic value. These findings demonstrate the potential for MALDI-MSI coupled with ML to characterize the metabolomic profile of BCC and to diagnose tumour tissue with high sensitivity and specificity. Further studies are needed to explore the potential of implementing integrated MS and automated analyses in the clinical setting.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.

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BACKGROUND: Psoralen + ultraviolet-A (PUVA) is associated with photocarcinogenesis. However, carcinogenic risk with other ultraviolet phototherapies remains unclear.
OBJECTIVE: Evaluate whether phototherapy without psoralens increases skin cancer risk.
METHODS: Retrospective cohort study of patients treated at a teaching-hospital phototherapy center (1977-2018). Skin cancer records were validated against pathology reports. Age-standardized incidence rates (ASIRs) of skin cancer were evaluated for gender, skin phototype, diagnosis, ultraviolet modality, anatomical site; and compared to provincial population incidence rates (2003).
RESULTS: In total, 3506 patients treated with broadband-ultraviolet-B, narrowband-UVB and/or combined UVAB were assessed with a mean follow-up of 7.3 years. Majority of patients had psoriasis (60.9%) or eczema (26.4%). Median number of treatments was 43 (1-3598). Overall, 170 skin cancers (17 melanoma, 33 squamous cell carcinoma and 120 basal cell carcinoma) occurred in 79 patients. Patient-based and tumor-based ASIR of skin cancer was 149 (95% CI: 112-187)/100,000 and 264 (219-309)/100,000 person-years, respectively. There was no significant difference between tumor-based ASIRs for melanoma, squamous cell carcinoma, and basal cell carcinoma compared to the general population; or in phototherapy patients with-psoriasis or eczema; or immunosuppressants. No cumulative dose-response correlation between UVB and skin cancer was seen.
CONCLUSIONS: Treatment and follow-up duration.
CONCLUSIONS: No increased risk of melanoma and keratinocyte cancer was found with phototherapy.

Giant keratinocyte tumors, in particular basal cell carcinomas of the scalp area, are a serious challenge for dermatosurgeons, oncologists, and maxillofacial and reconstructive surgeons. The scalp area is limited in terms of skin mobility, and its elasticity decreases with age. The size of the tumors in this area and the degree of infiltration of the underlying tissues are important for the therapeutic choice, from surgical removal, waiting for granulations to form, and placing a split skin mesh graft (at a later stage) to performing complex rotational/transpositional or advancement flaps. Achieving an optimal aesthetic result is often the consequence of interventions carried out or based on the decisions of multidisciplinary teams. Alternatives, such as radiotherapy and targeted therapy with vismodegib, could be administered both preoperatively and postoperatively or as first-line therapy, depending on the tumor board decisions. We present the case of a 69-year-old female patient with a histopathologically proven preoperative giant basal cell carcinoma of the scalp that did not infiltrate the tabula externa. A preoperative ultrasound was performed to preserve the feeding flap arteries. Surgical treatment under general anesthesia was planned and subsequently carried out. During surgery, the surgical resection lines were in close proximity to the arterial vessels, but they remained preserved and ensured a subsequently unproblematic healing process. After the application of the rotational advancement flap technique under general anesthesia, an optimal cosmetic effect was achieved.

BACKGROUND: Skin cancer rates are at all-time highs, but the shortage of dermatologists compels patients to seek medical advice from general practitioners. A new referral pathway called the Suspected Skin Cancer (SSC) service was established to provide general practitioners in Waikato, New Zealand, with rapid diagnosis and treatment advice for lesions suspicious for skin cancer.
OBJECTIVE: The aim of this study was to assess the quantity, quality, and characteristics of referrals to the SSC teledermatology service during its first 6 months.
METHODS: A retrospective chart review of all referrals sent to the SSC teledermatology service during the first 6 months of its operation was conducted. Time to advice, diagnoses, diagnostic discordance, adherence to advice, and time to treatment were recorded. Diagnostic discordance between general practitioners, dermatologists, and pathologists was calculated.
RESULTS: The SSC service received 340 referrals for 402 lesions. Dermatologists diagnosed 256 (63.7%) of these lesions as benign; 56 (13.9%) were histologically confirmed as malignant, including 19 (4.7%) melanomas. The overall discordance between referrer and dermatologist on specific and broad (ie, benign or malignant) diagnoses for 402 lesions was 47% and 26% (κ=0.58, SD 0.07), respectively; 44% and 26% (κ=0.61, SD 0.15) between referrer and pathologist; and 18% and 12% (κ=0.82, SD 0.12) between dermatologist and pathologist. The mean time between referral submission and receiving advice was 1.02 days. The average time to action (eg, excision) was 64.8 days.
CONCLUSIONS: An electronic referral system can be an effective form of teledermatology for providing prompt diagnosis and management advice for benign and malignant skin lesions.

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Because of long-term immunosuppression, solid organ transplant recipients are at increased risk for keratinocyte cancer. We matched solid organ transplant patients (n = 150), cases with keratinocyte cancers and tumor-free controls, considering the most important risk factors for keratinocyte cancer in solid organ transplant recipients. Using whole exome data of germline DNA from this patient cohort, we identified several genetic loci associated with the occurrence of multiple keratinocyte cancers. We found one genome-wide significant association of a common single nucleotide polymorphism located in EXOC3 (rs72698504). In addition, we found several variants with a p-value of less than 10-5 associated with the number of keratinocyte cancers. These variants were located in the genes CYB561, WASHC1, PITRM1-AS1, MUC8, ABI3BP, and THBS2-AS1. Using whole exome sequencing data, we performed groupwise tests for rare missense variants in our dataset and found robust associations (p < 10-6, Burden Zeggini test) between MC1R, EPHA8, EPO, MYCT1, ADGRG3, and MGME1 and keratinocyte cancer. Thus, overall, we detected genes involved in pigmentation/UV protection, tumor suppression, immunomodulation, intracellular traffic, and response to UV as genetic risk factors for multiple keratinocyte cancers in solid organ transplant recipients. We also grouped selected genes to pathways and found a selection of genes involved in the \"cellular response to UV\" to be significantly associated with multiple keratinocyte cancers.

(1) Background: Keratinocyte cancer (KC) is associated with exposure to ultraviolet (UV) radiation. However, data are controversial as to whether chronic UV exposure or high intermittent UV exposure are key drivers of carcinogenesis in cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC). Prolonged sun exposure of the skin causes photo-aging, which is associated with actinic elastosis, a condition characterized by the degeneration of elastin in the upper dermis, which is assessable via conventional histology. In this study, we aimed to compare the degree of actinic elastosis in different types of KC with regard to various patient characteristics. (2) Methods: We defined a semiquantitative score for the degree of actinic elastosis ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration). The extent was measured histometrically by two independent dermatohistopathologists in the immediate vicinity of 353 KC. The scores were merged and matched with tumor types (cSCC and BCC with subtypes), and clinical variables such as body site, sex and age. (3) Results: As expected, the degree of actinic elastosis correlated with age. However, it was significantly higher in cSCC compared to BCC irrespective of age, sex, body site and tumor subtypes. (4): Conclusions: Lifetime sun exposure may be estimated via routine histology using this scoring technique for actinic elastosis as a surrogate marker. cSCCs are more strongly associated with chronic UV exposure than BCCs, even in sun-exposed localizations such as the face.