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Keywords = primary cutaneous melanoma

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12 pages, 556 KB  
Article
Sentinel Node Biopsy for Head and Neck Melanoma: A 12-Year Experience from a Medium-Volume Regional Center
by Péter Lázár, Kristóf Boa, Noémi Mezőlaki, Zoltán Varga, Zsuzsanna Besenyi, Erika Varga, István Balázs Németh, Eszter Baltás, Judit Oláh, Erika Gabriella Kis, József Piffkó and Róbert Paczona
J. Clin. Med. 2026, 15(2), 763; https://doi.org/10.3390/jcm15020763 (registering DOI) - 17 Jan 2026
Viewed by 83
Abstract
Background: Head and neck (H&N) cutaneous melanomas have poorer outcomes than melanomas at other sites, yet sentinel lymph node biopsy (SLNB)—a key prognostic tool in clinically node-negative disease—is less frequently performed, particularly outside tertiary centers. We evaluated the feasibility and prognostic relevance [...] Read more.
Background: Head and neck (H&N) cutaneous melanomas have poorer outcomes than melanomas at other sites, yet sentinel lymph node biopsy (SLNB)—a key prognostic tool in clinically node-negative disease—is less frequently performed, particularly outside tertiary centers. We evaluated the feasibility and prognostic relevance of SLNB in a medium-volume regional institution. Methods: We retrospectively reviewed patients with primary H&N cutaneous melanoma who underwent SLNB at the Department of Oral and Maxillofacial Surgery, University of Szeged, between 2010 and 2022. Clinicopathological features, nodal outcomes, recurrence patterns, recurrence-free survival (RFS), and overall survival (OS) were analyzed using Kaplan–Meier methods and univariate Cox regression. Results: Thirty-eight patients underwent SLNB, with a 100% sentinel lymph node identification rate and no major complications. Positive sentinel lymph nodes were identified in 8 patients (21.1%). Two false-negative events occurred, resulting in a false-omission rate of 6.7% and a negative predictive value of 93.3%. SLN-negative patients demonstrated longer RFS and OS, although differences were not statistically significant. Among patients with intermediate-risk melanoma (pT1b–pT3a), 18.5% had a positive SLN. Conclusions: SLNB is a safe and clinically meaningful staging procedure for H&N melanoma in a medium-volume regional center. Sentinel node status provides important prognostic information and supports appropriate patient selection for contemporary adjuvant therapy. Full article
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18 pages, 1383 KB  
Article
Site- and Size-Based Algorithm for Reconstruction of Cheek Skin Defects: A Single-Center Retrospective Study
by Emilia Lis, Anna Lato, Julia Miaśkiewicz, Michał Gontarz, Tomasz Marecik, Krzysztof Gąsiorowski, Grażyna Wyszyńska-Pawelec and Jakub Bargiel
J. Clin. Med. 2026, 15(1), 331; https://doi.org/10.3390/jcm15010331 - 1 Jan 2026
Viewed by 213
Abstract
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- [...] Read more.
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. Full article
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19 pages, 2992 KB  
Article
Ephrin Receptors and Ephrin Ligands in Uveal Melanoma: A Big Data Analysis Using Web Resources
by Georgios Mandrakis, Christina-Maria Flessa, Panoraia Keratsa, Apostolos Zaravinos, Stamatios Theocharis and Alexandros G. Sykaras
Int. J. Mol. Sci. 2026, 27(1), 442; https://doi.org/10.3390/ijms27010442 - 31 Dec 2025
Viewed by 604
Abstract
Uveal melanoma (UVM) is a rare cancer that represents the second most common melanoma (after the cutaneous) and the most common primary intraocular malignancy in adults. Despite recent advances in the understanding of UVM pathogenesis, its prognosis remains unchanged, with half of patients [...] Read more.
Uveal melanoma (UVM) is a rare cancer that represents the second most common melanoma (after the cutaneous) and the most common primary intraocular malignancy in adults. Despite recent advances in the understanding of UVM pathogenesis, its prognosis remains unchanged, with half of patients dying because of liver metastasis. Erythropoietin-producing human hepatocellular receptors (EPHs) constitute the largest known family of tyrosine receptors, and, along with their ligands, EFNs, regulate key physiological processes and are implicated in cancer pathogenesis. In this study, we used open-access web bioinformatics platforms to explore and analyze big datasets provided by The Cancer Genome Atlas (TCGA) UVM cohort of patients. We profiled the genomic alterations present in a subset of UVM patients, highlighting a likely pathogenic deep deletion of EPHA7. Survival analysis showed that overexpression levels of EPHA4, EPHA5, EPHA8, EPHB2, and EFNB2 are significantly associated with poor overall survival. Additionally, high expression levels of EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2 correlate with reduced progression-free interval and disease-free survival. Finally, we identified the EPHs (EPHA2, EPHA4, EPHA8, and EPHB4) and EFNs (EFNA1, EFNA3, EFNA4, and EFNB2) that are significantly overexpressed in the aggressive epithelioid histological subtype and revealed that the majority of EPHs/EFNs are overexpressed in metastatic disease. In conclusion, our results highlight that a subset of EPHs and EFNs may be associated with worse clinical outcomes (EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2), and an aggressive histological subtype (EPHA2, EPHA4, EPHA8, EPHB4, EFNA1, EFNA3, EFNA4, and EFNB2). The potential correlation of these genes with clinicopathological parameters of UVM need to be evaluated and validated with bioinformatic and experimental approaches in well-characterized cohorts of UVM patients. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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19 pages, 1452 KB  
Article
Neoadjuvant Therapy in Resectable Advanced Melanoma: Swiss Real-World Data
by Ann-Kathrin Blumenröther, Yongxing Fang, Tamara El Saadany, Egle Ramelyte, Omar Hasan Ali, Thomas Kündig, Daniela Mihic-Probst, Sarah Steiner, Alexander Maurer, Reinhard Dummer, Joanna Mangana and Lara V. Maul
Cancers 2026, 18(1), 98; https://doi.org/10.3390/cancers18010098 - 28 Dec 2025
Viewed by 410
Abstract
Background/Objectives: Neoadjuvant and perioperative treatment regimens for melanoma have demonstrated significantly longer event-free survival (EFS) compared with adjuvant therapy in the NADINA and SWOG S1801 trials. While these studies yielded promising results, real-world effectiveness and safety remain to be clarified. Methods: [...] Read more.
Background/Objectives: Neoadjuvant and perioperative treatment regimens for melanoma have demonstrated significantly longer event-free survival (EFS) compared with adjuvant therapy in the NADINA and SWOG S1801 trials. While these studies yielded promising results, real-world effectiveness and safety remain to be clarified. Methods: We performed a retrospective, real-world study of all patients with advanced, resectable cutaneous or mucosal melanoma stage III/IV who received neoadjuvant treatment at the Department of Dermatology, University Hospital Zurich, Switzerland between April 2023 and September 2025. Primary endpoints were pathologic and radiologic response, EFS, recurrence-free survival (RFS), and safety. Results: In total, 31 patients were analyzed (52% female; median age 65 years), including 5 patients without lymph node involvement. Eighteen patients (58%) with cutaneous melanoma received neoadjuvant immunotherapy according to the NADINA protocol, three patients (10%) with mucosal melanoma received ipilimumab (1 mg/kg) and nivolumab (3 mg/kg), and ten patients (32%) were treated according to the SWOG S1801 protocol. A major pathologic response (MPR) was achieved in 12 of 31 patients (38%) overall, including 5 of 18 (28%) in the NADINA cohort, 6 of 10 (60%) in the SWOG S1801 cohort, and 1 of 3 (33%) in the mucosal cohort. We observed a pathologic partial response (pPR) in 7 of 31 patients (23%) overall, including 6 of 18 (33%) in the NADINA cohort and 1 of 3 (33%) in the mucosal cohort. A pathologic non-response (pNR) was seen in 9 of 31 patients (29%) overall, including 5 of 18 (28%) in the NADINA cohort, 3 of 10 (30%) in the SWOG S1801 cohort, and 1 of 3 (33%) in the mucosal cohort. Among all patients without lymph node involvement, 1 of 5 achieved MPR (20%), 2 had pPR (40%), and 2 showed pNR (40%). At data cutoff (median follow-up, 9.2 months), the 9-month EFS was 77% in the NADINA cohort, 74% in the SWOG S1801 cohort, and 33% in the mucosal cohort. In the whole cohort, 6-month RFS for the subgroups of MPR, pPR and pNR was 72.9%, 85.7% and 72.9%. Radiologic response evaluation with FDG-PET/CT after neoadjuvant therapy correlated significantly with pathologic response (p = 0.02). No patient with complete metabolic response (CMR) or partial metabolic response (PMR) recurred until data cutoff. In total, 6 of 31 patients (19%) showed stable metabolic disease (SMD), and 8 of 31 patients (26%) showed progressive metabolic disease (PMD). The 6-month RFS in the subgroups of SMD and PMD was 62.5% in each case. Adverse events (AEs) of grade 3 or higher were reported in 13 of 31 patients (42%) in the total real-world cohort, 8 of 18 in the NADINA cohort (44%), 2 of 10 (20%) in the SWOG S1801 cohort (20%), and 3 of 3 (100%) in the mucosal cohort. The most frequent grade 3/4 toxicities were immune-related (ir) Colitis (n = 3, 10%), irHepatitis (n = 2, 6%) and irMyocarditis (n = 2, 6%). Conclusions: Neoadjuvant immunotherapy is effective in real-world practice with a similar safety profile as shown in the clinical studies. Nevertheless, MPR rates in the NADINA real-world cohort were lower compared to the phase III trial. Larger multicenter studies are needed to validate our findings and to better understand response patterns, even in patients without lymph node involvement and in rare melanoma subtypes. Full article
(This article belongs to the Special Issue Immunotherapy for Skin Cancers)
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19 pages, 1996 KB  
Article
Recombinant RGD-Apoptins Decrease Human Melanoma Cell Viability
by Dmitriy Shirokov, Daria Lepekhina, Valentin Manuvera, Margarita Bogomiakova, Aleksandra Strokach, Anastasia Kazakova, Georgij Arapidi and Vassili Lazarev
Int. J. Mol. Sci. 2025, 26(24), 12016; https://doi.org/10.3390/ijms262412016 - 13 Dec 2025
Viewed by 323
Abstract
Cutaneous melanoma is an extremely dangerous tumor disease with poor prognosis at advanced stages. Accounting for a small percentage of all skin tumors, malignant melanoma leads the mortality rate in this group of cancers. Clearly, the search for new drugs and therapeutic approaches [...] Read more.
Cutaneous melanoma is an extremely dangerous tumor disease with poor prognosis at advanced stages. Accounting for a small percentage of all skin tumors, malignant melanoma leads the mortality rate in this group of cancers. Clearly, the search for new drugs and therapeutic approaches for the treatment of cutaneous melanoma is a highly pressing issue in modern medicine. In this study, novel recombinant proteins with anti-melanoma activity, called RGD-apoptins, were produced in an E. coli expression system, and their properties were evaluated in human cell models. These chimeric proteins consist of two parts, each tumor-specific. One part of the chimeric molecule is the RGD peptide, which binds to αVβ3 integrins widely expressed on the surface of malignant melanocytes. The other part is the viral protein apoptin, known to induce programmed cell death in tumor cells but not in normal cells. This molecular design aims to enhance the specificity of potential therapeutic agent toward malignant melanoma cells while reducing cytolytic effects on healthy tissue. In a resazurin assay, RGD-apoptins decreased the viability of MeWo human melanoma cells and did not affect the viability of HaCaT human keratinocyte cell line and primary skin fibroblasts. Using an annexin V assay, we confirmed that malignant melanocytes death occurs via apoptosis. Transcriptomic analysis allowed us to dynamically evaluate the spectrum of differentially expressed genes 24 and 48 h after treating melanoma cells with recombinant RGD-apoptin. Full article
(This article belongs to the Section Molecular Oncology)
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9 pages, 1236 KB  
Communication
A Novel Germline Frameshift Variant in the Tumor Suppressor Gene OBSCN in a Melanoma Patient
by Barbara Anna Bokor, Aliasgari Abdolreza, Margit Pál, Zita Battyani, Márta Széll and Nikoletta Nagy
Int. J. Mol. Sci. 2025, 26(21), 10553; https://doi.org/10.3390/ijms262110553 - 30 Oct 2025
Viewed by 427
Abstract
Malignant melanoma is a complex malignancy with genetic, environmental, and lifestyle factors in its etiology. While germline variants in melanoma predisposition genes have been described, many patients remain genetically unexplained after panel testing. We previously analyzed a Hungarian melanoma cohort (n = 17), [...] Read more.
Malignant melanoma is a complex malignancy with genetic, environmental, and lifestyle factors in its etiology. While germline variants in melanoma predisposition genes have been described, many patients remain genetically unexplained after panel testing. We previously analyzed a Hungarian melanoma cohort (n = 17), identifying variants in predisposing or susceptibility genes in 58.82% of patients. For individuals negative on this melanoma-specific panel, we expanded testing to a 19-gene panel associated with multiple cancer types. Next-generation sequencing was performed, followed by Sanger sequencing for confirmation. Variants were classified according to ACMG guidelines. In a 58-year-old female patient with a history of primary cutaneous melanoma, we identified a novel heterozygous frameshift variant in the tumor suppressor gene OBSCN (c.21322_21323insCTGG, p.G7108AfsTer10; NM_001386125.1). This insertion introduces a premature stop codon in exon 89 within the immunoglobulin-like domain, predicting protein truncation. Classified as likely pathogenic (PVS1, PM2), the variant is absent from population databases. To date, somatic OBSCN mutations have been reported in melanoma. This first report of a germline OBSCN frameshift variant in melanoma expands the genetic landscape of melanoma predisposition and suggests that OBSCN may represent a candidate gene contributing to melanoma risk. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment in Skin Cancer)
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19 pages, 2497 KB  
Article
Multi-Modal Biomarker Profiling of Tumor Microenvironment and Genomic Alterations to Enhance Immunotherapy Stratification in Melanoma
by Meshack Bida, Thabiso Victor Miya, Tebogo Marutha, Rodney Hull, Mohammed Alaouna and Zodwa Dlamini
Curr. Issues Mol. Biol. 2025, 47(10), 821; https://doi.org/10.3390/cimb47100821 - 3 Oct 2025
Viewed by 1008
Abstract
Tumor mutational burden (TMB) and tumor-infiltrating lymphocytes (TILs) are key biomarkers for predicting immunotherapy responses in cutaneous melanoma. The discordance between brisk TIL morphology and absent cytokine signals complicates immune profiling. We examined the interactions between TMB, TIL patterns, cytokine expression, and genomic [...] Read more.
Tumor mutational burden (TMB) and tumor-infiltrating lymphocytes (TILs) are key biomarkers for predicting immunotherapy responses in cutaneous melanoma. The discordance between brisk TIL morphology and absent cytokine signals complicates immune profiling. We examined the interactions between TMB, TIL patterns, cytokine expression, and genomic alterations to uncover immune escape mechanisms and refine prognostic tools. A structure-based BRAF druggability analysis was performed to anchor the genomic findings in a therapeutic context. Primary cutaneous melanoma cases (N = 205) were classified as brisk (n = 65), non-brisk (n = 60), or absent TILs (n = 80) according to the American association for cancer research (AACR) guidelines. Inter-observer concordance was measured using intraclass correlation. Tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were graded using immunohistochemistry. Eleven brisk TIL cases lacking TNF-α expression were analyzed using the (Illumina TruSight Oncology 500, Illumina-San Diego, CA, USA). Dabrafenib docking to the BRAF ATP site was performed with Glide SP/XP and rescored with Prime MM-GBSA. Brisk TILs lacking cytokine signals suggested post-translational silencing of TNF-α/IFN-γ. Among the 11 profiled cases, eight exhibited high TMB and copy number alterations, with enrichment of nine metastasis/immune regulation genes. Inter-observer concordance was high (absent TILs, 95%; brisk TILs, 90.7%). BRAF docking yielded a canonical type-I pose and strong ATP pocket engagement (ΔG_bind −84.93 kcal·mol−1). Single biomarkers are insufficient for diagnosis. A multiparametric framework combining histology, cytokine immunohistochemistry (IHC), and genomic profiling enhances stratification and reveals immune escape pathways, with BRAF modeling providing a mechanistic anchor for the targeted therapy. Full article
(This article belongs to the Section Molecular Medicine)
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25 pages, 730 KB  
Review
Treatment-Related Adverse Events in Individuals with BRAF-Mutant Cutaneous Melanoma Treated with BRAF and MEK Inhibitors: A Systematic Review and Meta-Analysis
by Silvia Belloni, Rosamaria Virgili, Rosario Caruso, Cristina Arrigoni, Arianna Magon, Gennaro Rocco and Maddalena De Maria
Cancers 2025, 17(19), 3152; https://doi.org/10.3390/cancers17193152 - 28 Sep 2025
Viewed by 2368
Abstract
Objectives: We conducted a systematic review of clinical trials and case reports analyzing the safety of the currently approved BRAF and MEK inhibitors in adults with cutaneous melanoma (CM), and a meta-analysis to estimate the pooled prevalence of treatment-related adverse events (TRAEs). [...] Read more.
Objectives: We conducted a systematic review of clinical trials and case reports analyzing the safety of the currently approved BRAF and MEK inhibitors in adults with cutaneous melanoma (CM), and a meta-analysis to estimate the pooled prevalence of treatment-related adverse events (TRAEs). Methods: We systematically searched six databases for studies published since 2009. The TRAE absolute frequencies reported in primary studies were aggregated using the Metaprop command in Stata 17, which calculates 95% confidence intervals (CIs) incorporating the Freeman–Tukey double arcsine transformation of proportions to stabilize variances within random-effect models. Methodological quality was assessed using the RoB 2 tool for randomized controlled trials (RCTs) and the ROBINS-I tool for non-randomized studies. Results: Twelve RCTs, thirteen prospective cohort studies (PCSs), and ten case reports were included. Meta-analysis was feasible for two regimens: vemurafenib 960 mg monotherapy and dabrafenib 150 mg twice daily plus trametinib 1–2 mg daily. The most common TRAEs during vemurafenib treatment were musculoskeletal and connective-tissue disorders (24%, 95% CI: 6–41%, p = 0.01), with arthralgia as the most prevalent (44%, 95% CI: 29–59%, p < 0.001), followed by rash (39%, 95% CI: 22–56%, p < 0.001). The most common TRAEs during dabrafenib plus trametinib were constitutional toxicities (classified in CTCAE as ‘General disorders and administration site conditions’; 25%, 95% CI: 14–37%, p < 0.001), with fatigue as the most prevalent (47%, 95% CI: 38–56%, p < 0.001), followed by pyrexia (40%, 95% CI: 26–54%, p < 0.001). Squamous cell carcinoma and keratoacanthoma were among the most frequent grade ≥ 3 cutaneous adverse events observed with vemurafenib therapy. Conclusions: Although additional large-scale studies are needed to corroborate these findings, each treatment has a distinct toxicity profile that should be considered when developing personalized risk-stratified treatment plans and in guiding healthcare resource allocation in melanoma care. Full article
(This article belongs to the Section Cancer Therapy)
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14 pages, 1399 KB  
Article
Cytokine and Chemokine-Associated Signatures Underlying Dermal Invasion and Skin Metastasis in Melanoma
by Viktória Koroknai, István Szász, Tünde Várvölgyi, Gabriella Emri, Ádám Fodor and Margit Balázs
Int. J. Mol. Sci. 2025, 26(19), 9334; https://doi.org/10.3390/ijms26199334 - 24 Sep 2025
Viewed by 784
Abstract
Metastatic spread remains the primary cause of mortality in melanoma. Our aim was to investigate the role of dermal endothelial cells in modulating melanoma cell invasiveness and cytokine/chemokine pattern. Primary melanoma cell lines were co-cultured with human dermal endothelial cells and assessed using [...] Read more.
Metastatic spread remains the primary cause of mortality in melanoma. Our aim was to investigate the role of dermal endothelial cells in modulating melanoma cell invasiveness and cytokine/chemokine pattern. Primary melanoma cell lines were co-cultured with human dermal endothelial cells and assessed using Matrigel invasion assays. Invasive and non-invasive subpopulations were separated for gene expression analyses, and candidate molecules were further evaluated in patient tissue and plasma samples. Co-culture of melanoma and dermal endothelial cells revealed altered expression of several cytokine receptor genes (CCR5, CXCR7, IL1RAPL2, IL4R, IL6ST, IL18R1, IL22RA2, TNFRSF10A, TNFRSF11B, and TNFRSF21). Analysis of clinical melanoma samples showed significant downregulation of IL1RAPL2 and TNFRSF10A in cutaneous metastases, whereas IL6ST expression correlated with Breslow thickness of the primary tumor rather than metastatic site. Proteome profiling of dermal endothelial cells revealed alterations in Midkine, GROα, MIP-3α, IL-8, and SDF-1 following co-culture with melanoma cells. Plasma measurements in melanoma patients confirmed elevated Midkine levels in skin metastases and decreased MIP-3α in metastatic disease. These results highlight potential cytokine and chemokine-mediated pathways involved in melanoma dermal invasion and cutaneous metastasis. While some findings did not reach statistical significance, concordant trends between in vitro and patient-derived data suggest their relevance and warrant further investigation in larger cohorts. Full article
(This article belongs to the Section Molecular Oncology)
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19 pages, 11762 KB  
Article
Metastatic Head and Neck Non-Melanoma Skin Cancer: A Retrospective Analysis of Clinico-Pathologic Features and Reconstructive Approach
by Victor Vlad Costan, Otilia Boișteanu, Delia Gabriela Ciobanu Apostol, Ștefan Vasile Toader, Cristina Colac Boțoc, Alin Gabriel Colac, Mihai-Liviu Ciofu and Mihaela Paula Toader
J. Clin. Med. 2025, 14(18), 6650; https://doi.org/10.3390/jcm14186650 - 21 Sep 2025
Viewed by 891
Abstract
Background/Objectives: Non-melanoma skin cancer (NMSC) is the most common malignancy globally, with cutaneous squamous cell carcinoma (cSCC) posing a significant risk of regional metastasis, especially in high-risk anatomical areas such as the head and neck. While general risk factors for metastasis are well [...] Read more.
Background/Objectives: Non-melanoma skin cancer (NMSC) is the most common malignancy globally, with cutaneous squamous cell carcinoma (cSCC) posing a significant risk of regional metastasis, especially in high-risk anatomical areas such as the head and neck. While general risk factors for metastasis are well known, few studies have directly compared the clinical and pathological features of synchronous versus metachronous metastatic behavior. This study aimed to evaluate the clinicopathological characteristics and reconstructive implications associated with these two metastatic patterns in head and neck NMSC. Methods: We conducted a retrospective observational study of 46 patients with histologically confirmed metastatic NMSC of the head and neck, treated between January 2022 and May 2024 at a tertiary care center. Patients were stratified into synchronous or metachronous metastasis groups. Clinical data, histopathological features, metastatic sites, and surgical approaches were analyzed. Comparative statistics were applied using chi-square and t-tests, with significance set at p < 0.05. Results: Of the 46 patients, 50% had synchronous and 50% had metachronous metastases. The lower lip was the most common primary tumor site in both groups. Perineural and lymphovascular invasion were more frequent in synchronous metastases. Metachronous cases often required more complex reconstructive procedures, including free flap reconstructions and mandibular resections. Patients with metachronous metastases were significantly older (p = 0.024), and approximately one-third developed metastases more than four years after initial treatment. Conclusions: Head and neck NMSC, particularly involving the lower lip, may exhibit late-onset metastatic potential. Risk-adapted surveillance extending beyond current guidelines is warranted to improve long-term outcomes in high-risk patients. Full article
(This article belongs to the Special Issue Clinical Advances in Skin Cancer: A Closer Look at Non-Melanoma Types)
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21 pages, 6628 KB  
Article
Development of Nomograms to Predict the Probability of Recurrence at Specific Sites in Patients with Cutaneous Melanoma
by Eszter Anna Janka, Imre Lőrinc Szabó, Tünde Toka-Farkas, Lilla Soltész, Zita Szentkereszty-Kovács, Beatrix Ványai, Tünde Várvölgyi, Anikó Kapitány, Andrea Szegedi and Gabriella Emri
Cancers 2025, 17(18), 3080; https://doi.org/10.3390/cancers17183080 - 21 Sep 2025
Cited by 1 | Viewed by 854
Abstract
Background: Risk assessment models are increasingly being used in oncology to improve therapeutic and follow-up decisions for individual patients. Methods: In our study, we used a university hospital registry database containing data on patients diagnosed with invasive cutaneous melanoma between 2000 and 2019 [...] Read more.
Background: Risk assessment models are increasingly being used in oncology to improve therapeutic and follow-up decisions for individual patients. Methods: In our study, we used a university hospital registry database containing data on patients diagnosed with invasive cutaneous melanoma between 2000 and 2019 (training cohort: N = 1402; validation cohort: N = 601). Using multivariate Cox regression models, we identified clinicopathological variables that are independent risk factors for melanoma recurrence at specific sites. We then constructed nomograms to predict the probability of recurrence at 3, 5, and 10 years. Results: Age, sex, primary tumor location, histological subtype, Clark invasion level and AJCC pT category were independent prognostic factors for melanoma recurrence in regional lymph nodes. Age, sex, primary tumor location, Clark level of invasion, AJCC pT stage and regional lymph node metastasis were risk factors for skin/soft tissue (including muscle)/non-regional lymph node metastases. We found that AJCC pT category and sex were also independent prognostic factors for melanoma recurrence in the lung, visceral sites, and brain. Furthermore, the nomogram predicting recurrence in the lung and visceral sites incorporated the presence of regional lymph node and skin/soft tissue/non-regional lymph node metastases. ROC curves showed good performance of the nomograms in both the training and validation cohorts. The calibration curve showed a good fit. Conclusion: Our results support the high prognostic value of AJCC pT stage and patient sex, which remained consistent across all melanoma stages, and demonstrate the feasibility of creating nomogram models to predict recurrence risk in melanoma patients. Full article
(This article belongs to the Special Issue Skin Cancer: Epidemiology, Management and New Therapies)
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18 pages, 560 KB  
Review
Melanoma in Primary Care: A Narrative Review of Training Interventions and the Role of Telemedicine in Medical Education
by Ignazio Stanganelli, Edoardo Mora, Debora Cantagalli, Serena Magi, Laura Mazzoni, Matelda Medri, Cesare Massone, Davide Melandri, Federica Zamagni, Ines Zanna, Gianluca Pistore, Saverio Caini, Salvatore Amato, Vincenzo De Giorgi, Pietro Quaglino, Maria Antonietta Pizzichetta, Giovanni Luigi Tripepi, Giorgia Ravaglia and Sofia Spagnolini
Curr. Oncol. 2025, 32(9), 522; https://doi.org/10.3390/curroncol32090522 - 18 Sep 2025
Viewed by 1284
Abstract
General practitioners play a crucial role in the early detection and prevention of cutaneous melanoma. However, structured training on skin cancer diagnosis and management is often lacking. This narrative review aims to map the current educational interventions for general practitioners focused on melanoma, [...] Read more.
General practitioners play a crucial role in the early detection and prevention of cutaneous melanoma. However, structured training on skin cancer diagnosis and management is often lacking. This narrative review aims to map the current educational interventions for general practitioners focused on melanoma, assess their methodological approaches and outcomes, and explore the contribution of e-learning and telemedicine in medical education. A comprehensive literature search identified 54 relevant studies published between 1 January 1995 and 31 December 2024. Data were extracted and categorized by topics covered, training methodology, interactivity, and clinical outcomes. Training programs varied widely in duration, delivery, and content. Interventions that integrated dermoscopy and interactive methodologies demonstrated improved diagnostic accuracy and clinical impact. E-learning, particularly asynchronous models, emerged as a flexible and effective modality, although few studies evaluated long-term retention or clinical practice changes. Educational programs tailored to general practitioners and enriched with dermoscopy and telemedicine tools show promise in improving melanoma detection and care. Structured, interactive, and blended/hybrid learning models should be prioritized to support effective primary and secondary prevention. Full article
(This article belongs to the Special Issue Advances in Melanoma: From Pathogenesis to Personalized Therapy)
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14 pages, 3326 KB  
Case Report
Multifocal Oral Mucosal Melanoma with an Atypical Clinical Presentation
by Klaudia Podlińska, Monika Monist, Magdalena Sławińska and Wojciech Popowski
Dent. J. 2025, 13(9), 432; https://doi.org/10.3390/dj13090432 - 18 Sep 2025
Cited by 2 | Viewed by 1279
Abstract
Background: Oral mucosal melanoma (oral malignant melanoma—OMM) is a rare malignant neoplasm. It arises from the proliferation of atypical melanocytes—cells derived from the neural crest that produce melanin. Unlike cutaneous melanomas, which are etiologically linked to ultraviolet (UV) radiation exposure, the risk [...] Read more.
Background: Oral mucosal melanoma (oral malignant melanoma—OMM) is a rare malignant neoplasm. It arises from the proliferation of atypical melanocytes—cells derived from the neural crest that produce melanin. Unlike cutaneous melanomas, which are etiologically linked to ultraviolet (UV) radiation exposure, the risk factors for mucosal melanomas remain poorly defined. According to the World Health Organization (WHO), these tumors predominantly affect older individuals, with peak incidence occurring in the seventh decade of life and are rarely observed in the first three decades. The primary treatment modality for patients with mucosal melanoma is radical surgical excision with clear margins. The 5-year overall survival rate for OMM ranges from 20% to 50%. Case Presentation: This article reports an atypical clinical manifestation of oral mucosal melanoma in a 99-year-old patient who presented to the Department of Oral Surgery at the University Dental Center, Medical University of Warsaw. The nonspecific clinical appearance did not initially suggest a melanocytic lesion. A definitive diagnosis was established through histopathological examination, which subsequently guided the treatment plan. Conclusions: This report highlights the necessity of performing microscopic evaluation even for lesions with a nonspecific or non-suspicious appearance, underlines the importance of regular dental check-ups, and stresses the need to strengthen oncological vigilance among dental practitioners. Full article
(This article belongs to the Special Issue Dental Oncology)
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17 pages, 299 KB  
Review
Indications and Mechanisms of Action of the Main Treatment Modalities for Non-Melanoma Skin Cancer
by Marcio F. Chedid, Aline C. Tregnago, Floriano Riva, Lucas Prediger, Anisha Agarwal and Jane Mattei
Life 2025, 15(9), 1447; https://doi.org/10.3390/life15091447 - 16 Sep 2025
Viewed by 1504
Abstract
Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or [...] Read more.
Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or other rare tumors (1%). Given the high cure rates and the ability to histologically confirm tumor clearance, surgical therapy is the gold standard for the treatment of skin cancer. Conventional surgery is the most employed technique for the removal of non-melanoma skin cancer (NMSCs). Mohs Micrographic Surgery (MMS) is the most precise surgical method for the treatment of non-melanoma skin cancer, allowing for 100% margin evaluation, being the gold-standard method for surgical treatment of non-melanoma skin cancer. Whenever it is possible to obtain wide margins (4 to 6 mm), cure rates vary from 70% to 99%. Imiquimod, a synthetic imidazoquinolinone amine, is a topical immune response modifier approved by the U.S. Food and Drug Administration (FDA) for the treatment of external anogenital warts, actinic keratosis (AK), and superficial basal cell carcinoma (sBCC). The efficacy of imiquimod is primarily attributed to its ability to modulate both innate and adaptive immune responses, as well as its direct effects on cancer cells. Imiquimod exerts its immunomodulatory effects by activating Toll-like receptors 7 and 8 (TLR7/8) on various immune cells, including dendritic cells, macrophages, and natural killer (NK) cells. Upon binding to these receptors, imiquimod triggers the MyD88-dependent signaling pathway, leading to the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). This cascade leads to the production of pro-inflammatory cytokines, including interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). These cytokines enhance local inflammation, recruit additional immune cells to the tumor site, and stimulate antigen presentation, thereby promoting an anti-tumor immune response. Radiation therapy (RTh) may be employed as a primary treatment to BCC. It may also be employed as an adjuvant treatment to surgery for SCC and aggressive subtypes of BCC. RTh triggers both direct and indirect DNA damage on cancer cells and generates reactive oxygen species (ROS) within cells. ROS trigger oxidative damage to DNA, proteins, and lipids, exacerbating the cellular stress and contributing to tumor cell death. Recently, immunotherapy emerged as a revolutionary treatment for all stages of SCC. Cemiplimab is a human programmed cell death 1 (PD-1)-blocking antibody that triggers a response to over 50% of patients with locally advanced and metastatic SCC. A randomized clinical trial (RCT) published in 2022 revealed that cemiplimab was highly effective in the neoadjuvant treatment of large SCCs. The drug promoted a significant tumor size decrease, enabling organ-sparing operations and a much better cosmetic effect. A few months ago, a RCT of cemiplimab on adjuvant therapy for locally aggressive SCC was published. Interestingly, cemiplimab was administered to patients with local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features, revealed that cemiplimab led to much lower risks both of locoregional recurrence and distant recurrence. Full article
5 pages, 1163 KB  
Abstract
Raman Spectroscopy Diagnosis of Melanoma
by Gianmarco Lazzini, Daniela Massi, Davide Moroni, Ovidio Salvetti, Paolo Viacava, Marco Laurino and Mario D’Acunto
Proceedings 2025, 129(1), 10; https://doi.org/10.3390/proceedings2025129010 - 12 Sep 2025
Viewed by 658
Abstract
Cutaneous melanoma is an aggressive form of skin cancer and a leading cause of cancer-related mortality. In this sense, Raman Spectroscopy (RS) could represent a fast and effective method for melanoma-related diagnosis. We therefore introduced a new method based on RS to distinguish [...] Read more.
Cutaneous melanoma is an aggressive form of skin cancer and a leading cause of cancer-related mortality. In this sense, Raman Spectroscopy (RS) could represent a fast and effective method for melanoma-related diagnosis. We therefore introduced a new method based on RS to distinguish Compound Naevi (CN) from Primary Cutaneous Melanoma (PCM) from ex vivo solid biopsies. To this aim, integrating Confocal Raman Micro-Spectroscopy (CRM) with four Machine Learning (ML) algorithms: Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Support Vector Machine (SVM), and Random Forest Classifier (RFC). We focused our attention on the comparison between traditional pre-processing operations with Continuous Wavelet Transform (CWT). In particular, CWT led to the maximum classification accuracy, which was ∼89.0%, which highlighted the method as promising in view of future implementations in devices for everyday use. Full article
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