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Paired related homeobox 1 (PRRX1) is an inducer of epithelial‐to‐mesenchymal transition (EMT) in different types of cancer cells. We detected low PRRX1 expression in nevus but increased levels in primary human melanoma and cell lines carrying the BRAFV600E mutation. High expression of PRRX1 correlates with invasiveness and enrichment of genes belonging to the EMT programme. Conversely, we found that loss of PRRX1 in metastatic samples is an independent prognostic predictor of poor survival for melanoma patients. Here, we show that stable depletion of PRRX1 improves the growth of melanoma xenografts and increases the number of distant spontaneous metastases, compared to controls. We provide evidence that loss of PRRX1 counteracts the EMT phenotype, impairing the expression of other EMT‐related transcription factors, causing dysregulation of the ERK and signal transducer and activator of transcription 3 (STAT3) signaling pathways, and abrogating the invasive and migratory properties of melanoma cells while triggering the up‐regulation of proliferative/melanocytic genes and the expression of the neural‐crest‐like markers nerve growth factor receptor (NGFR; also known as neurotrophin receptor p75NTR) and neural cell adhesion molecule L1 (L1CAM). Overall, our results indicate that loss of PRRX1 triggers a switch in the invasive programme, and cells de‐differentiate towards a neural crest stem cell (NCSC)‐like phenotype that accounts for the metastatic aggressiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: We conducted a study at the Melanoma Unit of the Hospital Clinic of Barcelona to investigate brain metastases in patients with cutaneous melanoma. We collected data from patients diagnosed between January 1998 and September 2023. Patients with melanoma in situ or those with prior lung or breast cancer were excluded. Our aim was to identify factors associated with the development and survival outcomes of brain metastases. We analyzed patient demographics, tumor characteristics, and survival data. The diagnosis of brain metastases was confirmed using imaging techniques, and biopsies were performed when feasible. Our study followed strict guidelines for reporting observational studies. We found that younger age and larger primary tumor thickness increased the risk of developing brain metastases. Additionally, the presence of ulceration and microscopic satellitosis in the primary tumor were associated with a higher risk. Melanomas located on the trunk had a higher risk compared to those on the extremities. Patients with brain metastases had a median survival of around six months. Neurological symptoms and leptomeningeal involvement were associated with poorer survival outcomes. Higher number of brain lesions and elevated levels of lactate dehydrogenase (LDH) also predicted worse survival. Our findings highlight the importance of early detection and monitoring of melanoma patients, especially those at higher risk of brain metastases. Understanding these factors can aid in personalized treatment approaches and improving patient outcomes. Background: Melanoma is the cancer with the highest risk of dissemination to the central nervous system (CNS), one of the leading causes of mortality from this cancer. Objective: To identify patients at higher risk of developing CNS metastases and to evaluate associated prognostic factors. Methods: A cohort study (1998–2023) assessed patients who developed CNS melanoma metastases. Multivariate logistic regression was used to identify predictive factors at melanoma diagnosis for CNS metastasis. Cox regression analysis evaluated the CNS-independent metastasis-related variables impacting survival. Results: Out of 4718 patients, 380 (8.05%) developed CNS metastases. Multivariate logistic regression showed that a higher Breslow index, mitotic rate ≥ 1 mm2, ulceration, and microscopic satellitosis were significant risk factors for CNS metastasis development. Higher patient age and the location of the primary tumor in the upper or lower extremities were protective factors. In survival analysis, post-CNS metastasis, symptomatic disease, prior non-CNS metastases, CNS debut with multiple metastases, elevated LDH levels, and leptomeningeal involvement correlated with poorer survival. Conclusion: Predictive factors in the primary tumor independently associated with brain metastases include microscopic satellitosis, ulceration, higher Breslow index, and trunk location. Prognostic factors for lower survival in CNS disease include symptomatic disease, multiple CNS metastases, and previous metastases from different sites. [ABSTRACT FROM AUTHOR]

Background: As the use of smartphones continues to surge globally, mobile applications (apps) have become a powerful tool for healthcare engagement. Prominent among these are dermatology apps powered by Artificial Intelligence (AI), which provide immediate diagnostic guidance and educational resources for skin diseases, including skin cancer. Objective: This article, authored by the EADV AI Task Force, seeks to offer insights and recommendations for the present and future deployment of AI‐assisted smartphone applications (apps) and web‐based services for skin diseases with emphasis on skin cancer detection. Methods: An initial position statement was drafted on a comprehensive literature review, which was subsequently refined through two rounds of digital discussions and meticulous feedback by the EADV AI Task Force, ensuring its accuracy, clarity and relevance. Results: Eight key considerations were identified, including risks associated with inaccuracy and improper user education, a decline in professional skills, the influence of non‐medical commercial interests, data security, direct and indirect costs, regulatory approval and the necessity of multidisciplinary implementation. Following these considerations, three main recommendations were formulated: (1) to ensure user trust, app developers should prioritize transparency in data quality, accuracy, intended use, privacy and costs; (2) Apps and web‐based services should ensure a uniform user experience for diverse groups of patients; (3) European authorities should adopt a rigorous and consistent regulatory framework for dermatology apps to ensure their safety and accuracy for users. Conclusions: The utilisation of AI‐assisted smartphone apps and web‐based services in diagnosing and treating skin diseases has the potential to greatly benefit patients in their dermatology journeys. By prioritising innovation, fostering collaboration and implementing effective regulations, we can ensure the successful integration of these apps into clinical practice. [ABSTRACT FROM AUTHOR]

Acral melanoma is the fourth most common subtype of cutaneous melanoma in Caucasians, representing 2-3% of all melanomas,1 but is the most frequent histological subtype among non-Caucasians and dark-skinned populations.2 It is found on glabrous skin of the soles, palms and nailbeds, with 80% appearing on the feet. Compared to other subtypes of cutaneous melanoma, it has a worse prognosis, with significantly lower 5-year melanoma-specific survival rates.1 This fact has been mainly attributed to delayed diagnosis, which is well documented in the literature, and can average as much as 18 months.2 Moreover, the diagnosis of acral melanoma remains challenging for many reasons. Dermoscopy training course improves podiatrists' accuracy in diagnosing lesions suggestive of acral melanoma: A cross-sectional study. [Extracted from the article]

(c) Histopathology: Shows an infundibulocystic basal cell carcinoma characterized by a relatively well-circumscribed neoplasm showing cystic areas as well as a cleft in the adjacent dermis (hematoxylin-eosin stain original magnification ×10) gl The patient's mother was a 77-year-old woman with a medical history of a single facial nodular BCC, a frontobasal meningioma, and a mandibular plexiform ameloblastoma. Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome (GS), is a tumor predisposing disorder with an autosomal dominant inheritance.1,2 It is caused by mutations in the hedgehog pathway, being I PTCH1 i the most commonly affected gene. Many other syndromes are also associated with the development of multiple facial papules and solid organ neoplasias and should be considered in the differential diagnosis (Table 2).2,10 Patients with I SUFU i mutations also seem to develop less odontogenic keratocysts when compared with patients harboring I PATCHED i mutations. [Extracted from the article]

Background: Bullous pemphigoid affects elderly individuals with multiple comorbidities, making conventional treatments unsuitable., Objective: Evaluate the effectiveness and safety of dupilumab in the treatment of bullous pemphigoid., Methods: A multicenter ambispective cohort study was conducted in 34 hospitals. Patients with bullous pemphigoid treated with Dupilumab were included. Most of patients (97.1%) received an initial 600 mg dose followed by 300 mg every two weeks., Outcomes and Measures: The primary outcome was the proportion of patients achieving complete remission within 4 weeks, defined as Investigator Global Assessment score of 0 or 1. Complete remission at weeks 16, 24, and 52, adverse events, reductions in peak pruritus numerical rating scale, and systemic glucocorticoid use were also assessed., Results: The study included 103 patients with a median age of 77.3 years, 58.0% male. Complete remission was achieved by 53.4% within 4 weeks and 95.7% by week 52. Peak pruritus scale reduced by 70.0% by week 4 and was completely controlled by week 24. Thirteen patients presented adverse events, most of which were mild. Systemic glucocorticoid use reduced by 82.1% by week 52. Shorter disease duration and exclusive cutaneous involvement predicted better response at 16 weeks. No differences in response rates to dupilumab were observed between drug-associated bullous pemphigoid and idiopathic cases. No significant difference in response rates was observed between patients treated with dupilumab in monotherapy and those receiving dupilumab with concomitant treatments., Conclusions: Dupilumab is effective, rapid, and safe in managing bullous pemphigoid, reducing the need for corticosteroids and other treatments. Early initiation and exclusive skin involvement predict better outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis., Objectives: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence., Methods: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined., Results: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%., Conclusions: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)