A 60-year-old woman underwent evaluation for a 6-year history of Parkinsonism. One year earlier, she had been diagnosed with malignant melanoma of the left palpebral conjunctiva, which recurred despite treatment. For the assessment of Parkinson disease, 123 I FP-CIT and Tc-99m ECD SPECT were performed. Unexpectedly, intense 123 I FP-CIT uptake was observed in the left eyelid lesion, whereas 99m Tc-ECD showed no uptake. CT and MRI demonstrated a corresponding mass consistent with recurrent malignant melanoma. This first report underscores the need to recognize extrastriatal tracer uptake.

CAP2 promotes skin cutaneous melanoma progression by targeting epithelial-mesenchymal transition-like processes through the TLR4/NF-κB pathway.

Melanoma of the foot and nail unit carries a worse prognosis than cutaneous melanoma elsewhere because lesions are frequently hidden, misdiagnosed, and therefore diagnosed at more advanced stages. Traditional ABCDE criteria are often insufficient for foot and nail presentations; the CUBED recognition tool was developed to improve detection of atypical plantar and subungual lesions. To evaluate four consecutive cases of foot melanoma seen in a single NHS community podiatry department, compare case characteristics against ABCDE and CUBED recognition tools, and describe service responses that aimed to improve early detection. A retrospective case series of four patients diagnosed with foot melanoma between 2019 and 2022 in one community podiatry service. Clinical features, referral timelines, diagnostic pathways, treatments, and outcomes were extracted and mapped against ABCDE and CUBED criteria. Shared-learning interventions developed by the department following these cases are described. All four cases were toe-based melanomas (one lentigo maligna, one nail-bed malignant melanoma, two acral melanomas). Presentations commonly included irregular colour, bleeding or ulceration, delayed healing, diagnostic uncertainty, and lesion enlargement. CUBED criteria more consistently identified concerning features across the series than ABCDE criteria, prompting urgent dermatology referral in each case. Outcomes varied: one patient remains disease-free after excision, one developed distant metastasis and died, two underwent toe amputation and received systemic treatment. Departmental responses included case-based teaching and a poster campaign promoting CUBED and ABCDE recognition across local clinical networks. Podiatrists are pivotal in early detection of foot melanoma. The CUBED tool demonstrated greater sensitivity for atypical foot and nail lesions in this series. Wider education and adoption of CUBED alongside ABCDE may reduce misdiagnosis, shorten diagnostic delay, and improve clinical outcomes.

Pet dogs with naturally occurring cancers provide valuable models for comparative oncology and pathology tumour registries offer a powerful resource for onco-epidemiological research. Here, we analysed the Small Animal Veterinary Surveillance Network (SAVSNET) pathology-based tumour registry (PTR), one of the largest veterinary tumour registries to date, focusing on four major canine tumours: mast cell tumour (MCT), osteosarcoma (OSA), haemangiosarcoma (HSA), and melanoma (MEL). A case-control study was conducted using a subset of 130 998 histologically confirmed tumours drawn from the pathology tumour registry containing over 1.1 million canine tumour records from 1.02 million dogs collected in the UK between 2010 and 2023. Case-control analyses were performed for melanoma, haemangiosarcoma, OSA and MCT using a denominator population of dogs attending first-opinion veterinary practices. Additionally for MCT, comparisons were made against dogs diagnosed with other tumour types ('tumour denominator' approach). Breed-specific risks were identified, including high odds ratios (OR) for Bulldog-related breeds and Retrievers with mast cell tumours (MCTs) (OR up to 6.8, 95% CI 6.0, 7.6), Rottweilers, Shar Pei and Giant-Schnauzer with melanoma (OR up to 50.3, 95% CI 24.7, 102.5), and German Shepherd Dogs, Mastiffs, and Bullmastiffs with haemangiosarcoma (OR up to 28.0, 95% CI 10.6, 40.9). Higher-grade MCT were diagnosed at older ages and certain breeds were more predisposed to higher-grade MCT (Shar Pei, Rottweiler) while others were more prone to low-grade MCTs (Boxer, Boston Terrier). Neutered dogs generally had higher tumour odds than entire dogs; for example, in MCTs, female-neutered vs. female-entire showed OR 1.81 (95% CI 1.6, 2.0) in ages 3-6, with similar patterns across older age bands. In general, the difference in OR values between entire and neutered dogs was consistently more pronounced in females than in males. These findings demonstrate the value of the SAVSNET PTR as a comprehensive resource for canine tumour surveillance, with potential to support health initiatives and cancer research by identifying breed-specific and demographic risk factors as well as a foundational tool for comparative cancer epidemiology.

Epidemiology, clinical characteristics, and survival of acral and non-acral melanoma in Colombia.

Given the therapeutic challenges posed by the unique molecular genetic mechanisms and immune-privileged microenvironment of uveal melanoma, this review aims to systematically evaluate the latest research on the molecular genetics and immune microenvironment of uveal melanoma, providing insights for translational research and the development of clinical treatment strategies. In gene therapy, a recombinant adeno-associated viral vector engineered to target the oncogenic GNAQ Q209L mutation achieved single-base-pair precision knockdown, offering a novel approach to overcoming the complex therapeutic challenges posed by downstream signaling in this pathway. Regarding tumor metastasis, BAP1 inactivation induces a low-metabolic state by inhibiting the mTORC1/p70S6K1 pathway, enabling tumor cells to adapt to nutritional stress during metastasis. Concurrently, BAP1 mutations regulate cell adhesion molecules and suppress the nuclear factor-κB pathway, collectively establishing an immunosuppressive microenvironment that drives the highly metastatic nature of uveal melanoma. The predictive value of chromosome 8q amplification was shown to be context-dependent, with high-risk subgroups exhibiting extremely poor prognosis, particularly in BAP1-mutant cases. At the epigenetic level, miR-181a-5p demonstrates therapeutic potential by inducing uveal melanoma apoptosis through targeting GNAQ and AKT3. Clinically, the bispecific T-cell redirection drug Tebentafusp has achieved a major breakthrough in metastatic uveal melanoma immunotherapy. This review systematically elucidates key driver gene mutations, chromosomal abnormalities, epigenetic alterations, and the unique immunosuppressive microenvironment of uveal melanoma, providing new insights into mechanisms of treatment resistance and guiding the development of innovative therapeutic strategies.

Valeriana wallichii-loaded tin oxide nanoparticle gel for targeted melanoma therapy: cytotoxicity, antioxidant activity, and cellular uptake evaluation.

While many studies have been conducted on mortality in nuclear workers, morbidity remains less studied in these populations. This study aimed to assess the algorithm-derived incidence of cancer in a population of French nuclear workers, by using medico-administrative data from the National Health Data System (SNDS) as no national cancer registry is available, and to compare it with a general population sample. The study cohort included permanent workers with at least 1 year's work history in the company Electricité de France, monitored for ionizing radiation exposure at least once over the period 1961-2003. The comparison population was a representative random sample of 2% of the French population receiving outpatient healthcare. Cancer incidences were estimated over the 2009-2018 period using data collected from the SNDS and validated algorithms. Standardized incidence ratios and 95% Confidence Interval (SIR [CI95%]) were calculated. The cohort comprised 27,473 workers, while the comparison population included 611,953 persons. Incidences in the cohort were significantly higher for prostate cancer (SIR=1.09 [CI95% 1.01-1.18]), malignant melanoma of the skin (1.33 [1.08-1.60]), and breast cancer in women (1.35 [1.03-1.73]) compared with that of the comparison population. Significant deficits were observed for liver, larynx, trachea-bronchus-lung and bladder cancers. This study is the first to use the SNDS in a cohort of workers to assess cancer incidence. In the absence of linkage with individual radiation dose information, it should not be interpreted as evidence of radiation causality. The next step will be to investigate exposure-risk analyses when data access will be completed.

Multicentric malignant melanoma in a grey mare: A case report.

Metastatic cancer, particularly metastatic melanoma, poses a significant therapeutic challenge due to its resistance to standard treatments and a low five-year survival rate of 20-27%. Recent advances in cancer vaccine research show great promise in reducing disease recurrence, but these approaches still face challenges pertaining to antigen selection, ease of production, and programmability. To address some of these challenges, we have adapted the DoriVac platform to serve as a cancer vaccine against metastatic melanoma. DoriVac is a DNA origami-based vaccine platform that allows for the codelivery of antigens of choice and the CpG immune adjuvant at an optimal nanospacing to promote Th1 immune polarization. In our study, we observed a significant reduction in lung tumor nodules in the B16OVA and B16F10 melanoma models for DoriVac-treated mice. DoriVac also appears to be a safe treatment, as we did not observe any significant increase in antinanoparticle (i.e., anti-dsDNA) antibodies. Importantly, we observed an enhanced effect when DoriVac was combined with an αPD-L1 immune checkpoint blockade, leading to an even greater reduction in metastatic lung tumor nodules. Our results also indicate an increased activation of antigen-presenting cells, NK cells, CD4+ T cells, and CD8+ T cells in comparison to the control groups. These findings suggest that DoriVac, particularly in combination with the αPD-L1 immune checkpoint blockade, can serve as a promising immunotherapy against metastatic cancer.

We describe the case of a man in his 60s with metastatic melanoma on encorafenib/binimetinib and nivolumab/relatlimab, with a history of immune checkpoint inhibitor (ICI)-induced acute interstitial nephritis, who presented with acute-onset nausea, vomiting and profuse watery diarrhoea. Investigations excluded infectious causes, and flexible sigmoidoscopy with biopsy demonstrated lymphocytic colitis. His symptoms persisted despite discontinuation of Braftovi-Mektovi (BRAF-MEK) therapy and required escalation of corticosteroid therapy and budesonide initiation. This case highlights the diagnostic challenges of differentiating ICI-mediated colitis from adverse events of targeted therapy and underscores the importance of endoscopic and histological confirmation in guiding treatment.

Though major advancements have been made within the realm of targeted and immune-based therapies, metastatic melanoma still remains one of the most notoriously incurable malignancies due to early drug tolerance and eventual resistance. Increasing evidence has started to show drug-tolerant persister cells as a critical nongenetic mechanism that allows survival under MAPK pathway inhibition. While genetically resistant clones support stable mutations, persister cells enter reversible, slow-cycling states which are triggered by stressful conditions. This review synthesizes current research on the various molecular and cellular mechanisms which support melanoma persister cell formation, focusing specifically on phenotype plasticity, selective translational control, metabolic rewiring, redox buffering, and compensatory signaling pathways. We highlight how dynamic transitions among MITF-low, SOX10-low, and KDM5B-high states enable persistence under therapeutic pressure, and how epitranscriptomic regulation and metabolic shifts toward oxidative/lipid-dependent processes help decouple and focus on survival rather than proliferation. Furthermore, we examine microenvironment-driven activation of RhoA-FAK-AKT signaling and redox-adaptive sulfur metabolism as unique adaptive resistance mechanisms. Finally, our paper emphasizes persister states serving as evolutionary intermediates from which stable resistance can eventually emerge, and outline therapeutic strategies which exploit the transient persister vulnerability and help prevent melanoma drug-resistance.

We introduce Longitudinal-CT, a publicly available resource of whole-body computed tomography (CT) studies with exhaustive expert manual annotations of tumor lesions across two timepoints. The dataset comprises 600 CT studies from 300 patients diagnosed with metastatic malignant melanoma, each including a baseline and a follow-up examination acquired during systemic therapy at the University Hospital Tübingen, Germany. In total, it contains 7,182 manually segmented tumor lesions - 4,079 at baseline and 3,103 at follow-up - each labeled with anatomical location, volume, and longitudinal correspondence to capture lesion evolution such as persistence, regression, merging, or new appearance. All CT data are provided in anonymized NIfTI format with corresponding segmentation masks and lesion metadata. Longitudinal-CT establishes a standardized foundation for developing and validating artificial intelligence methods for automated lesion detection, segmentation, and temporal tracking in oncology. As a reference, a baseline deep learning segmentation model trained using nnU-Net v2 demonstrates the dataset's potential for advancing research in automated oncologic whole-body CT lesion segmentation.

Although PD-1 inhibitors have significantly reduced metastatic melanoma patients' mortality, only a small proportion of these patients actually benefit. We aim to develop some parsimonious predictive models for identifying those patients' survival outcome under anti-PD-1 treatment. Based on the genomic mutation and copy number variation data of metastatic melanoma patients in the Liu and Shoushtari cohorts, we developed and validated three different nomograms to identify their survival outcomes under anti-PD-1 monotherapy. Patients without anti-PD-1 monotherapy in the TCGA and MSK cohorts were employed as negative controls to assess the applicability of our models to anti-PD-1 monotherapy. All predictive models developed in this study are accessible and available for use at https://yyw0505.shinyapps.io/nomogram_app/. The first nomogram, and also the one we most recommend, built on five genes including NID1 amplification, TYRP1 deletion, mutations of PIK3C2G, FLT1 and IKZF1, classified patients into the High-Risk and Low-Risk group, and patients in the High-Risk group exhibited shorter overall survival (OS) and progression-free survival (PFS). However, there was no difference of OS between the two groups in both the TCGA and MSK cohorts, indicated the first nomogram was a predictive model rather than prognostic model. Similar results were also observed in the second and third nomogram. The parsimonious and robust predictive model could provide valuable assistance for clinical practice.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with immune-related adverse events (irAEs), including musculoskeletal symptoms. We report a case of rapid exacerbation of bilateral hip osteoarthritis (OA) induced by nivolumab. A 56-year-old woman with a history of developmental hip dysplasia and malignant melanoma was treated with nivolumab. Following nivolumab administration, she developed severe bilateral hip pain and polyarthralgia, with necessitating drug discontinuation. Despite cessation of the ICI, her symptoms persisted, accompanied by elevated C-reactive protein levels. Imaging showed end-stage OA with joint space narrowing and increased 18F-FDG uptake in both hip joints. She underwent staged bilateral total hip arthroplasty. Intraoperative pathology showed marked synovial hyperplasia. Immunohistochemical analysis showed diffuse positivity for CD68, TNF-α, IL-6, PD-1, and PD-L1, findings consistent with an immune-mediated inflammatory process superimposed on degenerative changes. Postoperatively, her hip pain and associated symptoms gradually improved, accompanied by normalization of inflammatory markers during follow-up. Histological evidence suggests that PD-1/PD-L1 blockade may locally amplify inflammation within the osteoarthritic joint. Clinicians must be vigilant regarding the potential for ICIs to rapidly worsen underlying joint disease, warranting timely surgical intervention when conservative management fails.

Melanoma, originating from the malignant change in skin melanocytes, is highly metastatic, yet effective treatments to prevent its spread are still lacking. Lysine-specific histone demethylase 1 (LSD1) functions as an epigenetic modifier; however, its role in melanoma remains incompletely elucidated. In this study, we determined that LSD1 expression is upregulated in metastatic melanoma relative to primary melanoma, which is indicative of a poor prognosis. Subsequent experiments revealed that targeting LSD1 effectively suppresses melanoma metastasis in both in vitro and in vivo models. Mechanistically, the pharmacological or genetic inhibition of LSD1 induces the phosphorylation and subsequent degradation of Yes-associated protein (YAP), a critical component of the Hippo signaling pathway that is strongly linked to tumor metastasis. Furthermore, ChIP-qPCR analysis indicates that the LSD1 inhibition enhances H3K4me2 modification at the promoter regions of NF2 and LATS1/2, thereby promoting their transcriptional activation. This results in increased expression of NF2 (encoded by NF2) and LATS1/2, ultimately activating the Hippo pathway. These findings not only enhance our understanding of the molecular mechanisms driving melanoma metastasis but also establish a novel theoretical basis for the development of LSD1 inhibitors and targeted therapeutic strategies for melanoma.

In medical image analysis, skin lesion diagnosis remains a complicated task. Skin lesions are a prevalent form of skin disease that exists globally. A malignant skin cancer, otherwise called melanoma, usually starts after melanocyte cells begin to grow uncontrollably. Among several forms of cancer, malignant melanoma is the deadliest form as it has a high vulnerability to spread into deeper tissues and because of its high death rate as well. Early identification of skin tumours is essential to permit advanced treatment. In general, the manual inspection of dermatologists is time-consuming, subjective, and tedious, resulting in dissimilar recognition precision based on their experience. In recent times, many investigators have studied the application of deep learning (DL) methods to skin lesion segmentation. In this study, the DL-driven entropy-curvature attention mechanism for enhanced segmentation and classification of skin lesions (DLECAM-ESCSL) model is proposed in medical imaging techniques. The primary purpose of the DLECAM-ESCSL model is to develop an effective approach for precise skin lesion segmentation to assist in early and reliable skin disease diagnosis using advanced techniques. At first, the image pre-processing step involves various levels, such as image resizing, hair removal, and noise removal, to improve the quality of raw images by eliminating the noise. Furthermore, the attention mechanism-based entropy-curvature (ECA) method is employed for the segmentation process. For the feature extraction process, the DLECAM-ESCSL model utilises the vision transformer (ViT) model to recognise and isolate the most relevant information from raw data. Finally, the Wasserstein autoencoder (WAE) model is used for classification. The performance valuation of the DLECAM-ESCSL approach portrayed a superior accuracy value of 99.16% over existing methods under the Skin Cancer ISIC dataset.

Despite therapeutic advancements, approximately 50% of advanced melanoma patients succumb to metastatic disease. Molecular tumor boards (MTB) aim to identify targetable molecular alterations to guide individualized treatment strategies. Yet, real-world data on patient selection, referral timing, recommendation rates, implementation, and clinical impact remain limited. In this exploratory retrospective bicenter analysis, we evaluated 80 patients with advanced melanoma who presented at institutional MTBs of two comprehensive cancer centers. Clinical and molecular tumor data were analyzed using bioinformatic tools to characterize mutation profiles, treatment recommendations, and their real-world implementation. Most patients (88.3%) had stage IV melanoma at the time of presentation and had received a median of three prior systemic treatment lines. Actionable treatment recommendations were formulated in 77.9% of eligible cases, yet only 33.7% of recommendations were implemented. Non-implementation was most commonly attributable to early patient death or regulatory barriers. Importantly, when recommended therapies were applied, patients experienced significantly improved progression-free survival (7.85 vs. 4.34 months; PFS ratio 1.8) and overall survival (10.64 vs. 5.06 months) compared with patients in whom recommended treatments were not implemented. Among patients with implemented MTB recommendations (n = 26), the median intra-patient PFS ratio was 1.68, and 14 of 26 patients (53.8%) achieved a PFS ratio ≥ 1.3. These findings indicate that MTBs frequently generate clinically actionable recommendations for metastatic melanoma, but late-stage referral substantially limits their real-world implementation. When applied, molecularly guided treatment strategies may confer meaningful clinical benefit, underscoring the importance of earlier integration of MTBs into melanoma care pathways.

Melanoma is an aggressive skin cancer with limited durable responses despite therapeutic advances. Comprehensive characterization of genomic alterations may improve understanding of disease progression and inform therapeutic strategies. We aimed to characterize genomic alterations in cutaneous melanoma and compare mutation prevalences between primary and metastatic tumors to improve therapeutic strategies. We conducted a systematic review and meta-analysis of genomic data from primary and metastatic cutaneous melanomas to assess the prevalence of gene mutations and copy number alterations. Relevant studies were identified in MEDLINE and Embase up to October 2024 using the search algorithm ((Mutation) OR "Genomics"[Mesh]) AND ("Melanoma"[Mesh]). Data were synthesized using random-effects meta-analyses to estimate the pooled prevalence of gene mutations and copy number variations, with heterogeneity assessed using I2 statistics. This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ninety-nine publications were included, encompassing 10,386 primary cutaneous melanoma samples and 4273 metastatic samples. The most frequently mutated genes in both settings were BRAF, TERT, TP53, NRAS, and NF1. The prevalence of BRAF, NRAS, TERT, CDKN2A, and PTEN mutations was significantly higher in metastatic lesions. NRAS mutations were more common in central nervous system metastases than in other metastatic sites. In contrast, KIT mutations were more common in primary tumors. Acral melanoma exhibited a distinct molecular profile, with an overall lower mutation prevalence, particularly involving BRAF. Chromosomal losses at 9p21.3 and 9p21 were commonly observed in both primary and metastatic tumors, with higher prevalence in primary tumors. Our findings highlight distinct genomic differences between primary and metastatic melanoma, underscoring the value of metastatic tumor biopsies in informing molecularly guided treatment decisions.

Metastatic cutaneous melanoma (MCM) is primarily treated with BRAF/MEK inhibitors and immune checkpoint inhibitors (ICIs), but the long-term efficacy of these therapies is often limited by acquired resistance. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD biosynthesis, is frequently upregulated in MCM, supporting metabolic rewiring and targeted therapy resistance. Interferon-γ (IFN-γ) signaling plays a central role in melanoma biology, exerting both antitumor and immunoregulatory effects, linked with the onset of therapeutic resistance. Emerging evidence suggests that metabolic pathways may critically modulate IFN-γ responses; however, the functional interplay between NAD/NAMPT metabolism and IFN-γ signaling in melanoma cells remains poorly defined. We integrated transcriptomic, bioinformatic, biochemical, and functional approaches in human and murine melanoma cell lines, together with analyses of TCGA datasets and a tissue microarray (TMA) cohort. Mechanistic studies included pharmacological and genetic perturbation of Bromodomain and Extra-Terminal motif (BET) epigenetic factor BRD4, Interferon Regulatory Factor 1 (IRF1), and NAMPT, chromatin immunoprecipitation (ChIP) assays, and metabolic analyses. Tumor-T cell co-culture systems were used to assess the impact of melanoma-cell NAMPT modulation on T-cell behavior. IFN-γ induced NAMPT expression through a BRD4/IRF1-dependent transcriptional program. In turn, NAMPT activity was required to sustain IFN-γ signaling, as its inhibition impaired STAT1 activation and downstream transcriptional responses. Mechanistically, NAMPT-dependent NAD metabolism supported mitochondrial complex I activity and oxidative metabolism and was required for efficient BRD4 recruitment to IFN-responsive promoters, including CD274/PD-L1 and NAMPT itself. Across melanoma datasets and patient samples, NAMPT expression correlated with IFN-γ-responsive genes, including PD-L1. Functionally, modulation of NAMPT in melanoma cells influenced T-cell cytotoxicity and migration in co-culture systems. Overall, these findings identify NAMPT as a key metabolic component of the IFN-γ response network in melanoma cells, establishing a feed-forward regulatory circuit linking cytokine signaling, chromatin regulation, and mitochondrial metabolism. This work provides a framework to investigate how metabolic control of IFN-γ signaling shapes tumor-immune interactions.