Melanoma Research最新文献

{"title":"An atypical Spitz tumor with metastasis in an adolescent patient.","authors":"Michela Tabanelli, Enrico Morelli, Vanna Chiarion Sileni, Emilia Crisanti, Nicola Pannacci, Francesco Savoia","doi":"10.1097/CMR.0000000000001081","DOIUrl":"10.1097/CMR.0000000000001081","url":null,"abstract":"<p><p>Despite the large number of studies published in the dermatologic and anatomopathologic literature, there are still many doubts and controversies regarding the natural history and behavior of atypical Spitz tumors (ASTs) in children. We report the case of an AST that developed metastases 5 years after the first surgical excision. In 2012, a 12-year-old boy underwent surgical excision of a melanocytic lesion of the right forearm, which was histologically classified as an AST. After multidisciplinary evaluation, a wide local excision was performed, avoiding sentinel lymph node biopsy. During follow-up, metastatic disease was diagnosed in 2017, leading to a diagnosis of stage IV melanoma. Despite multimodal treatments, including therapies that were off-label at the time due to the patient's age, disease progression occurred and the patient died in 2021. The management of AST remains controversial, reflecting the clinicopathologic gray zone occupied by borderline spitzoid tumors, in which morphology alone may be inadequate to predict biological behavior.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"139-142"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanoma: a genetics guide for surgeons.","authors":"Ferdia J Browne, Stephanie M Bollard, Patrick Ormond, Fergal Kelleher, Terri P McVeigh, Shirley M Potter","doi":"10.1097/CMR.0000000000001082","DOIUrl":"10.1097/CMR.0000000000001082","url":null,"abstract":"<p><p>Melanoma is considered the most lethal cutaneous malignancy when not detected early and treated at early stages. Whilst up to 90% of new melanoma diagnoses are attributable to excess ultraviolet radiation, genetic predisposition plays a pivotal role in melanomagenesis, making it imperative for surgeons, at the forefront of melanoma diagnosis and management, to thoroughly grasp this concept. Identification of genetically high-risk patients enables targeted surveillance, earlier diagnosis, and timely intervention, reducing melanoma-related morbidity and mortality despite the complexity of the underlying genetic landscape. However, in recent years, there have been several pathogenic variants identified that increase the risk of melanoma development. These pathogenic variants also contribute to the development of other cancers, constituting several cancer syndromes. As such, it is becoming increasingly important for surgeons to appreciate the fundamentals of genetic predisposition and to also consider non-melanomatous cancers in their practice. This article aims to outline the contribution of various pathogenic variants to the development of melanoma and other cancers, and in turn, how carriers of these variants should be managed, whilst highlighting the indications for genetic screening for some variants. Melanoma-dominant syndromes, such as CDKN2A , CDK4 , and POT1 , and melanoma-subordinate syndromes are described herein. Knowledge of these conditions will enable surgeons to incorporate these genetic insights into clinical practice and offer more personalised and effective care to patients with melanoma.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"81-91"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tebentafusp-associated dermatological adverse events in patients with metastatic uveal melanoma: a single-center retrospective cohort study.","authors":"Maggie H Zhou, Wei Li, Austin K Carpenter, Shari R Lipner","doi":"10.1097/CMR.0000000000001078","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001078","url":null,"abstract":"","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"36 2","pages":"143-144"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosome 1p13.2 gene cluster upregulation in neuroblastoma RAS viral oncogene homolog pathogenic variant melanoma: a potential biomarker axis.","authors":"Sophie M Bilik, Olivia M Burke, Scott A Elman","doi":"10.1097/CMR.0000000000001080","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001080","url":null,"abstract":"<p><p>Neuroblastoma RAS viral oncogene homolog (NRAS) mutations occur in 20-30% of cutaneous melanomas, defining a distinct molecular subtype. While NRAS mutations drive unique gene expression programs, locus-specific transcriptional regulation has not been systematically explored. This study characterized coordinated transcriptional upregulation in NRAS-mutant melanoma, focusing on chromosome 1p13.2. RNA-seq and mutation data for 472 melanoma samples from The Cancer Genome Atlas Skin Cutaneous Melanoma were analyzed. Differential expression, coexpression assessment, and copy number variation (CNV) correlation were performed for 45 protein-coding genes within 1p13.2. Findings were validated in MSK-IMPACT 2021 ( n  = 696). In NRAS-mutant melanomas, 56% of 1p13.2 genes were upregulated (false discovery rate < 0.05) versus 12% genome-wide ( P  < 0.001), including TRIM33, AMPD1, GNAI3, and SLC25A24. Upregulation was NRAS-specific: 84% showed higher expression versus BRAF-mutant tumors. Six of the 10 most NRAS-correlated genes localized to 1p13.2. CNV gains showed dose-dependent effects (gains: 1.8-3.2 fold; amplifications: 3.5-5.4 fold), with strong correlations (AMPD1 ρ = 0.68, GNAI3 ρ = 0.62, TRIM33 ρ = 0.58; P  < 0.001). MSK-IMPACT validation confirmed 1p13.2 upregulation. As these findings are based on transcriptomic and copy number analyses, additional protein-level and functional studies across independent cohorts are required to confirm biological significance. NRAS-mutant melanomas harbor a coordinated transcriptional program within 1p13.2, driven by CNV gains. This locus contains genes with potential druggability, offering new avenues for combinatorial targeting alongside mitogen-activated protein kinase pathway inhibition.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"36 2","pages":"134-138"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival and toxicity profile of elderly melanoma patients treated with immune checkpoint inhibitors: a retrospective study from a tertiary care center.","authors":"Mónica Pozuelo-Ruiz, Blanca de Unamuno-Bustos, Fernando Navarro-Blanco, Rodolfo D Palacios-Diaz, Rafael Botella-Estrada","doi":"10.1097/CMR.0000000000001076","DOIUrl":"10.1097/CMR.0000000000001076","url":null,"abstract":"<p><p>The use of immune checkpoint inhibitors (ICI) in the elderly population remains challenging because of age-related factors and lack of evidence due to underrepresentation in clinical trials. This retrospective study aimed to assess the efficacy and safety of ICI in elderly melanoma patients compared with younger individuals, to describe their toxicity profile, and to analyze the influence of health status. We included 93 melanoma patients treated with ICI from January 2016 to July 2024 at a single institution. Patients were grouped by age: less than 65, 65-74, and greater than or equal to 75 years. Baseline characteristics, treatment data, progression-free survival (PFS), overall survival (OS), adverse events and geriatric assessments (ECOG Performance Status, Charlson Comorbidity Index and G8 Frailty Scale) were analyzed. Statistical analyses included Kaplan-Meier and regression models. Survival outcomes were comparable across age groups. In advanced disease, patients over 65 showed improved mean PFS [40.2 vs. 17.1 months, P  = 0.036; hazard ratio: 0.49, 95% confidence interval (CI): 0.25-0.95]. OS did not differ significantly. Older patients had lower overall toxicity rates (46-50 vs. 74% in <65 years, P  = 0.008; odds ratio: 0.31, 95% CI: 0.13-0.75), with fewer grade 3 adverse events. No association was found between comorbidity indices or frailty status and increased toxicity. Adverse events were predominantly mild-to-moderate, mainly skin-related and constitutional; grade 3 adverse events and gastrointestinal symptoms were more frequent in less than 65 years. In conclusion, immunotherapy is effective and well-tolerated in elderly melanoma patients, neither advanced age nor frailty status alone should restrict its use.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"115-121"},"PeriodicalIF":1.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants of adjuvant treatment choice between immunotherapy (immune checkpoint inhibitor) and targeted therapy in resected stage III BRAF V600-mutated cutaneous melanoma: a multicenter observational study: MELADJ3.","authors":"Aurore Devoldere, Olivier Bouche, Coralie Barbe, Kevin Didier, Sixtine Colbach, Florence Granel Brocard, Claire Carlier","doi":"10.1097/CMR.0000000000001083","DOIUrl":"10.1097/CMR.0000000000001083","url":null,"abstract":"<p><p>In resected stage III BRAF V600-mutated melanoma, patients are eligible for adjuvant targeted therapy or immune checkpoint inhibitors (ICIs), but no comparative data guide this choice. Understanding factors shaping patient preferences is essential for shared decision-making. To identify factors associated with patient choice between adjuvant ICI or targeted therapy in resected stage III BRAF V600-mutated cutaneous melanoma. This multicenter, prospective, questionnaire-based, cross-sectional study was conducted from November 2024 to July 2025 across oncology centers in France concerning adults with completely resected AJCC8 stage III BRAF V600-mutant melanoma. Patients received standardized information from their oncologist regarding two adjuvant options - anti-PD1 immunotherapy (nivolumab or pembrolizumab) and targeted therapy (dabrafenib plus trametinib) - before making their treatment choice. The primary outcome was treatment selection (ICI vs. targeted therapy). Secondary outcomes consisted of describing determinants of patient decision-making using a structured questionnaire. Among 45 participants, 25 chose ICI and 20 selected targeted therapy. Questionnaire analysis showed that younger, professionally active patients with dependent children were more likely to prefer targeted therapy, valuing autonomy in treatment administration and reduced hospital visits. In contrast, older or nonworking patients more often favored ICI, citing reassurance from regular medical follow-up and the ability to delegate treatment management. Age and employment status were significantly associated with therapeutic choice. Identifying drivers of treatment preference may support more personalized adjuvant strategies. The finding that targeted therapy is favored by younger patients reinforces the relevance of sentinel lymph node biopsy in BRAF-mutated melanoma, despite expanding indications for immunotherapy in earlier stages.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"107-114"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of tranexamic acid in patients with stage III melanoma undergoing lymph node dissection: a retrospective cohort study.","authors":"Karoline Assifuah Kristjansen, Camilla Mensel, Marie Øbo Larsen, Gertrud Dam-Dalgeir, Kathrine Wulf Munk, Abdullah Maarouf, Peder Ikander, Toke Alstrup, Louise Mahncke Guldbrandt, Marie Louise Bønnelykke-Behrndtz","doi":"10.1097/CMR.0000000000001084","DOIUrl":"10.1097/CMR.0000000000001084","url":null,"abstract":"<p><p>Tranexamic acid (TXA) is widely used off-label and increasingly explored for drug repurposing as an anticancer agent within melanoma surgery, mandating safety evaluation from existing data. Although TXA is safe in surgical populations, its safety profile has not been specifically evaluated in melanoma surgery. Concerns arise from preclinical models suggesting that antifibrinolytic therapy may facilitate micrometastatic spread. Other drug-related adverse effects, such as thromboembolic events and seizure risk, must also be considered in this context. This study evaluates the safety of perioperative TXA in melanoma surgery. Patients ( n  = 155) with stage III cutaneous melanoma undergoing complete lymph node dissection at Aarhus and Aalborg University Hospital between 1 May 2020 and 31 July 2024, were identified, and clinical data were extracted retrospectively. Outcomes included recurrence (local, regional or systemic), thromboembolic events, and seizures. Recurrences were analyzed using a cause-specific Cox proportional hazards model, adjusting for age and adjuvant therapy. Fisher's exact test was used to compare metastatic patterns by recurrence location (local, regional, or systemic), thromboembolic events, and seizures between groups. Among 155 patients, 44 (28%) were exposed to TXA. Recurrences were recorded in 87 patients (56%), with similar proportions across exposure groups. TXA was not associated with recurrence (hazard ratio 0.94, 95% confidence interval: 0.57-1.54), nor with differences in the metastatic pattern. No association between risk of thromboembolic events or seizure and TXA exposure was detected. Perioperative TXA is not associated with recurrence, thromboembolic events, or seizures in patients with stage III melanoma undergoing complete lymph node dissection.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"92-97"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor DNA accelerates diagnosis and treatment guidance for metastatic uveal melanoma with hepatic lesions not amenable to biopsy.","authors":"Claire R Kissinger, Devin J Miller, Zhenteng Li, Usman M Ashraf, Gretchen Hubbard, Melissa A Wilson","doi":"10.1097/CMR.0000000000001077","DOIUrl":"10.1097/CMR.0000000000001077","url":null,"abstract":"<p><p>Uveal melanoma is a common intraocular tumor in which up to 50% of patients develop metastasis. Uveal melanoma often presents asymptomatically and is usually diagnosed by clinical examination and imaging, as tissue biopsy is not feasible. Recently, analysis of circulating tumor DNA has enabled diagnosis and mutation analysis in such tumors where tissue sampling cannot be performed. In our case study report, we demonstrate the use of the Caris Assure Assay for the diagnosis of metastatic uveal melanoma in a patient where tissue biopsy was not feasible. Plasma analysis identified a pathogenic SPEN variant and human leukocyte antigen (HLA) genotype (HLA-A*02:17 and HLA-A*02:01 alleles), conferring therapeutic eligibility for tebentafusp, and molecular evidence supportive of metastatic uveal melanoma, enabling initiation of appropriate systemic therapy before additional tissue sampling. Subsequent tissue biopsy from the liver (56 days after liquid biopsy) confirmed canonical GNAQ and SF3B1 driver mutations, reinforcing the diagnosis and clarifying the molecular underpinnings of the metastatic lesion itself. While the liquid biopsy and ablation of one of the lesions confirmed the diagnosis, the liquid biopsy was a key first step that provided a comprehensive diagnostic and prognostic picture without the need for an invasive procedure. This case highlights how integrating liquid biopsy into the diagnostic pathway for uveal melanoma can lead to earlier, more informed treatment decisions.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"36 2","pages":"129-133"},"PeriodicalIF":1.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment effect of neoadjuvant immunotherapy in melanoma correlates with tumor burden: meta-analysis of reported clinical trials.","authors":"Daniela Duarte-Bateman, Joseph M Escandón, Alan Shen, Yanwen Chen, Jennifer Ko, Jan Joseph Melenhorst, Anthony Tufaro, Lucy B Kennedy, James Isaacs, Brian R Gastman","doi":"10.1097/CMR.0000000000001079","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001079","url":null,"abstract":"<p><p>Neoadjuvant immune checkpoint inhibition (Neo-ICI) in melanoma is an emerging therapeutic strategy that induces pathologic responses with significant prognostic implications for survival. Tumor burden in nonresectable melanoma has a major impact on immunotherapy efficacy, yet little is known on its impact in the Neo-ICI setting. We evaluated the association between tumor burden, measured by the sum of diameters (SoD), and pathological response in melanoma patients treated with Neo-ICI. A meta-analysis of published trials in resectable stage III/IV melanoma was conducted, extracting data on patient characteristics, treatment regimens, pathological response, and survival outcomes. A total of 451 patients were included in the meta-analysis. The pooled pathological complete response (pCR) rate was 47% (95% confidence interval: 35-58%; P  < 0.001). Meta-regression demonstrated a significant association between SoD and pCR (moderator = -0.36; P = 0.032), with greater tumor burden associated with lower pCR rates. No significant association was observed between SoD and recurrence-free survival (RFS). This study identifies higher tumor burden as a potential risk factor for lower pathologic response rates to neoadjuvant therapy, underscoring the need to incorporate tumor burden into future clinical research and potentially clinical decision-making.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"36 2","pages":"98-106"},"PeriodicalIF":1.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant therapy in mucosal melanoma: a single-center experience and review of the literature.","authors":"Jane Mattei, Lin Ruitao, Michael A Davies, Michael K Wong, Adi Diab, Laura E Haydu, Sapna P Patel, Robade N Amaria, Jennifer L McQuade, Hussein Tawbi, Elizabeth M Burton, Isabella C Glitza","doi":"10.1097/CMR.0000000000001073","DOIUrl":"10.1097/CMR.0000000000001073","url":null,"abstract":"<p><p>Mucosal melanoma (MM) is an aggressive and rare subtype of melanoma, and it is associated with poor prognosis. Surgical resection remains the mainstay of the treatment for localized disease, and different from cutaneous melanoma, the impact of adjuvant therapy has not been clearly established. We retrospectively analyzed patients with surgically resected MM from the MD Anderson Cancer Center melanoma database from January 2000 to December 2019. The univariate log-rank test and multivariate Cox regression model were used to analyze the impact of adjuvant therapy on overall survival (OS) and relapse-free survival. A total of 246 patients with localized or locally advanced MM who underwent surgical resection were included. The median OS for all patients was 4.8 years [95% confidence interval (CI), 3.6-6], with median OS for the 125 patients who received adjuvant systemic therapy was 5.7 years (95% CI, 4.0-10.2) and 4.0 years (95% CI, 2.8-6.6) for the 121 patients who had only surgery or surgery plus radiation in the subanalysis, chemotherapy was associated with a longer OS (7.3 years; 95% CI, 4.4-NA) compared to immunotherapy (5.5 years; 95% CI, 2.8-NA). Cox regression analysis demonstrated lymph node involvement, Breslow thickness, and use of adjuvant systemic therapy were considered independent factors for OS. Adjuvant systemic therapy was associated with a significant survival benefit in patients with resected MM (HR 0.53; 95% CI, 0.34-0.82; P  = 0.004). However, due to the retrospective nature of the study, prospective clinical trials are warranted to determine the optimal adjuvant treatment strategy for this patient population.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"31-42"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}