Background/Objectives: Sinonasal mucosal melanomas (SNMMs) are rare and aggressive malignancies with poor survival outcomes. Our systematic review and meta-analysis aim to evaluate overall survival (OS) rates in patients with SNMM; Methods: We conducted a systematic search, following PRISMA guidelines across PubMed, Web of Science (WOS), and citation searching for studies reporting survival and prognosis outcomes for SNMMs. Inclusion criteria included studies with 5-year OS rates. Studies were excluded if they included tumor sites other than the paranasal sinuses or nasal cavity, were published in languages other than English and Spanish, or had a sample size of fewer than 15 patients. Two reviewers independently screened studies, extracted data, and assessed study quality using the Joanna Briggs Institute (JBI) critical appraisal checklist. Analyses of survival probabilities were conducted. Meta-analyses were performed using a random-effects model. PROSPERO ID CRD42024565137; Results: A total of 515 articles were identified after removing duplicates, and 99 reports were assessed for eligibility. Of these, 35 studies were included in the meta-analysis, encompassing a total of 2383 SNMM patients, of whom 1192 (50%) were female, with a weighted mean age of 65.4 years (SD = 5.4). Fifteen studies were from Europe (42.9%), six (17.1%) were from America, eleven (31.4%) were from Asia, two (5.7%) were from Australia, and one (2.9%) combined European, United Kingdom, and American populations. The 5-year OS was 34.8 [95% CI = 30.6–39.5], with the highest OS in America at 40.5 [95% CI = 34.1–48.1], followed by Europe at 36.6 [95% CI = 30.6–43.7], Australia at 32.3 [95% CI = 12.5–83.8], and Asia at 28.1 [95% CI = 19.5–40.7]. The age-standardized incidence rate (ASIR) for SNMM ranges was between 0.07 and 0.14 per 100,000 persons/year, with a slightly higher incidence in women than in men; Conclusions: This meta-analysis, one of the largest to date on SNMM, confirms the aggressive nature of this melanoma subtype with poor survival outcomes. Despite geographic differences in survival rates, the overall 5-year survival remains low, highlighting the urgent need for improved treatment strategies and more research to improve patient outcomes.

Actinic keratosis (AK) is the main risk factor for the development of cutaneous invasive squamous cell carcinoma (SCC). It represents the first sign of severe chronic ultraviolet radiation exposure, which has a clear significant effect. Nevertheless, the skin is exposed to many other exposome factors which should be thoroughly considered. Our aim was to assess the impact of exposome factors other than ultraviolet radiation (UVR) on the etiopathology of AK and Bowen’s disease (BD) and progression of AK to SCC and to design tailored prevention strategies. We performed an exhaustive literature search in September 2021 through PubMed on the impact of exposome factors other than UVR on AK, BD and SCC. We conducted several parallel searches combining terms of the following topics: AK, BD, SCC and microbiome, hormones, nutrition, alcohol, tobacco, viral infections, chemical contaminants and air pollution. Notably, skin microbiome studies have shown how Staphylococcus aureus infections are associated with AK and AK-to-SCC progression by the production of chronic inflammation. Nutritional studies have demonstrated how a caloric restriction in fat intake, oral nicotinamide and moderate consumption of wine significantly reduce the number of premalignant keratoses and SCC. Regarding lifestyle factors, both alcohol and smoking are associated with the development of SCC in a dose-dependent manner. Relevant environmental factors are viral infections and chemical contaminants. Human papillomavirus infections induce deregulation of cellular proliferation and are associated with AK, BD and SCC. In addition to outdoor jobs, occupations such as industrial processing and farming also increase the risk of developing keratoses and SCC. The exposome of AK will undoubtedly help the understanding of its etiopathology and possible progression to SCC and will serve as a basis to design tailored prevention strategies.

Introduction Most skin disorders, such as atopic dermatitis, psoriasis, skin cancer or age-related skin issues, are the result of a complex interaction between genetic and environmental factors over time. As an external organ, the skin provides the opportunity to study the link between exposure to the environment and several specific biological responses using an exposome approach. The aim of this review was to identify the state of the art of exposome approaches and elucidate the impact of the new era of exposomics on dermatology. Methods Two parallel and independent bibliometric analyses were conducted based on documents extracted from the Core Collection and the Science Citation Index Expanded (SCI-Expanded) databases from the Clarivate Analytics’ Web of Science (WOS) platform by using the following search terms “exposome” and “skin exposome”. In both searches, we used the topic field that includes title, abstract, author keywords and keywords plus terms and the following filters: “English language” and all documents published up to 30 September 2021. We further analysed and interpreted documents extracted in plain text format. Results Based on the defined searches, 910 documents were identified as being related to “exposome” and 45 as being related to “skin exposome”. Environmental sciences and toxicology were the most impacted research areas, and aging, cancer and respiratory allergies were the most documented diseases while, surprisingly, dermatology was much less impacted. Krutmann et al. were the pioneers in implementing this new concept in dermatology with publication of “The skin aging exposome” in 2017 (J Dermatol Sci. 2017;85:152–61). After this tipping point, the number of publications in dermatology evaluating the impact of exposome factors in many skin disorders has steadily increased. Conclusions Exposome studies are rapidly attracting interest in dermatology. The results of these studies will undoubtedly improve our understanding of why and under which circumstances some individuals develop skin disorders and help design tailored prevention strategies for patients suffering from these disorders.

Background/Objectives: Sinonasal mucosal melanoma (SNMM) is a rare and aggressive melanoma subtype with a notably poor prognosis compared to cutaneous melanoma (CM). Despite advances in molecular characterization, SNMM remains underexplored, posing a clinical challenge and highlighting the need for detailed molecular profiling. This study aimed to identify the molecular features of SNMM, elucidate its clinical behavior and prognostic implications, and provide insights for improved therapeutic strategies. Methods: This retrospective study analyzed 37 primary melanoma tumors diagnosed at the Hospital Clinic of Barcelona. Gene expression was examined using 1402 immuno-oncology-related probes through next-generation sequencing. Hierarchical clustering analysis (HCA), differentially expressed genes (DEGs), gene set enrichment analysis (GSEA), and the xCell algorithm were performed. The statistical methods comprised descriptive statistics, clinical variable associations, and survival analyses. Results: HCA revealed two primary clusters. Cluster A exclusively contained CM tumors (20/24), while cluster B included all SNMMs (13/13) and some CMs (4/24). Cluster B showed a higher average age at diagnosis (p = 0.018), higher mitotic index (p = 0.0478), fewer BRAF mutations (p = 0.0017), and poorer melanoma-specific survival (p = 0.0029). Cluster B showed 602 DEGs with cell cycle pathways enriched, immune pathways diminished, lower immune scores (p < 0.0001), and higher stromal scores (p = 0.0074). Conclusions: This study revealed distinct molecular characteristics and an altered tumor microenvironment in SNMMs and certain aggressive CMs. Identifying specific genes and pathways involved in cell cycle progression and immune evasion suggests potential prognostic markers, offering new avenues for enhancing treatment strategies and improving patient survival rates.

Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized advanced melanoma treatment, yet many patients fail to achieve sustained clinical benefit. Several biomarkers, including tumor microenvironment (TME) signature, PD-1/PD-L1 expression, and IFN-γ signaling, have been proposed. However, robust predictive markers remain elusive. This study aimed to identify molecular markers of response by analyzing tumor and peripheral immune signatures. Methods: This study analyzed 21 advanced melanoma patients treated with ICIs. Formalin-fixed, paraffin-embedded tumors underwent RNA-sequencing targeting 1392 immuno-oncology probes. Genes significantly associated with progression-free survival (PFS) by log-rank test underwent hierarchical clustering analysis (HCA). Differential expression and xCell analyses were then performed on the resulting clusters. Cox multivariate analysis was applied to identify independent PFS predictors. Pre-treatment peripheral blood mononuclear cells were analyzed by mass cytometry, followed by FlowSOM and UMAP clustering. Results: Fifty-five genes significantly associated with PFS identified two molecular clusters via HCA. Cluster A demonstrated prolonged PFS (59.4 vs. 2.4 months, p = 0.0004), while Cluster B was characterized by downregulated IFN-γ signaling, antigen presentation pathways, and reduced immune score. Multivariate Cox analysis confirmed molecular cluster as an independent PFS predictor (p < 0.001). Mass cytometry revealed higher frequencies of circulating PD-1+ CD4+ effector memory (EM) T subpopulations among responders. Conclusions: This study highlights the potential role of molecular and immune profiling in predicting ICI response in advanced melanoma. The identification of distinct molecular clusters underscores significant TME heterogeneity, with immune-cold tumor clusters associated with poorer outcomes. Furthermore, circulating PD-1+ T subpopulations emerged as potential markers of ICI response, suggesting their value in improving patient stratification.

Background: Sinonasal mucosal melanoma (SNMM) is a rare and aggressive melanoma subtype with a notably poor prognosis. Despite molecular characterization advances, SNMM remains clinically challenging, highlighting the need for detailed molecular profiling. This study aimed to identify the molecular features of SNMM, elucidate its prognostic implications, and provide insights for improved therapies.Methods: Sixteen SNMM tumors were retrospectively analyzed at the Hospital Clinic of Barcelona. Next‐generation sequencing targeted 1392 immuno‐oncology‐related probes. Log‐rank test, hierarchical clustering analysis (HCA), Cox regression, differentially expressed genes, gene set enrichment analysis, and the xCell algorithm were performed. Statistical analyses comprised descriptive statistics, clinical variable associations, and survival analyses.Results: Among 16 tumors, 107 genes significantly correlated with melanoma‐specific survival (MSS) (p < 0.05). HCA based on these genes revealed two clusters: Cluster B showed poorer prognosis (median MSS: 11.73 months; Q1: 8.74, Q3: 30.78) compared to Cluster A (median MSS: 81.74 months; Q1: 32.82, Q3: 92.44; p = 0.0051). Cox regression identified staging and molecular clustering as independent MSS predictors, with Cluster B exhibiting a hazard ratio of 13.23 (95% confidence intervals [CI]: 1.503–116.48, p = 0.02). Cluster B tumors displayed upregulated cell cycle genes and reduced infiltration of CD4+, CD8+, Th1, and B cells.Conclusions: Molecular profiling in SNMM provides prognostic information beyond standard clinical parameters. Cell cycle and immune‐related gene expression patterns, together with decreased infiltration of CD4+, CD8+, Th1, and B cells, correlate with poorer MSS. Integrating molecular profiling with clinical staging could improve risk assessment and help identify high‐risk patients for tailored therapeutic approaches.