Dermalogical Onclogy -Pumed

Skin cutaneous melanoma (SKCM) continues to pose significant therapeutic challenges owing to its aggressive nature and evolving resistance mechanisms. This study investigates the under-characterized role of Hippo pathway effector TEAD4 in SKCM pathogenesis through integrated multiomics analysis of clinical cohorts (TCGA, GEO, immunotherapy cohorts) combined with functional validation in A375 cell models and xenograft systems. Our pan-cancer analysis identified TEAD4 overexpression as a strong...

Tumor clonal evolution and spatiotemporal heterogeneity are key drivers of therapeutic resistance in melanoma, often driven by selection pressures generated by systemic therapy. Genetic testing plays a key role in guiding targeted therapies, but a single biopsy may not fully reflect the mutational landscape. This paper reports a case of metastatic acral melanoma that demonstrated dynamic branching clonal evolution under systemic therapeutic stress. The patient first underwent genetic testing in...

A 43-year-old woman presented with multiple exophytic lesions on both eyelids of the left eye. The patient underwent excisional biopsy of the lesions, and later 2 more interventions were necessary for the excision of the affected margins. She was followed by dermatology and medical oncology specialists, as she presented several skin tumors in other locations. Two years after the intervention, she developed a lower corneal abscess in the left eye, with cultures positive for Candida spp....

The incidence of basal cell carcinoma is increasing globally, with Denmark showing a 220% rise between 2013 and 2021, underscoring the need to optimize treatment strategies. Curettage with or without electrodesiccation (C±E) is commonly used, yet updated tumour-specific recurrence data are limited. Using the Danish Skin Cancer Registry, we assessed long-term recurrence after C±E for 47,358 basal cell carcinomas treated in office-based dermatological practices between 2013 and 2022. Follow-up...

Over the past decade, the therapeutic paradigm of cutaneous melanoma has been transformed strongly, driven by advances in immuno-oncology and precision medicine. Building on the success of immune checkpoint blockade and targeted therapy, new treatment strategies now aim to improve efficacy, overcome resistance, and prolong the durability of responses. Clinical trials on neoadjuvant therapy supporting its clinical use are presented. Furthermore, the latest progress in combinatorial immune...

Melanoma is one of the most aggressive and treatment-resistant skin cancers, and its long-term response to conventional therapies and systemic immune checkpoint blockade has limited efficacy because of immunosuppression induced by tumors and off-target toxicity. Transdermal microneedle (MN)-based drug delivery systems have emerged as an interesting alternative for localized, minimally invasive melanoma immunotherapy in recent years. This review is a critical analysis of the recent breakthroughs...

This study aims to identify potential biomarkers for retinal detachment secondary to choroidal melanoma (CM). Mendelian randomisation (MR) analysis, immunohistochemistry, cell proliferation and migration assays, co-culture experiments involving human microglial cells (HMC3) and CM cells, and tube formation assay were employed to validate the role of IL-8 in retinal detachment secondary to choroidal melanoma. Mendelian randomisation analysis identified four inflammatory mediators causally linked...

Mast cells are emerging players in malignant conditions, but the underlying molecular mechanisms remain poorly defined. Based on previous studies showing that steroids can impact on tumour progression in various settings, we here investigated whether mast cell-derived steroid synthesis can have an impact on tumour metastasis in a melanoma model. To this end, we used mice with mast cell-specific ablation of Cyp11a1, a key enzyme in steroid synthesis. We show that lung colonization of melanoma...

CONCLUSIONS: We created a reliable melanocytic lesion detection model without task-specific fine-tuning, achieving high accuracy, sensitivity, and specificity.

Increased sialylation of tumour cells, which favours tumour growth and immune evasion, has been described using in vitro and in vivo models, leading to the first in-human clinical trial targeting sialylation in cancer. One important limitation is that the biology of sialic acids and their receptors (Siglecs), which have been considered as immune checkpoints, is different between mice and human. Hence, it is crucial to fully describe and investigate sialic acids and Siglecs expression in animal...

Acral lentiginous melanoma (ALM) is characterized by a low mutational burden, frequent chromosomal rearrangements, and profound epigenetic dysregulation, distinguishing it from ultraviolet (UV)-induced melanoma. Among the epigenetic regulators, Enhancer of Zeste Homolog 2 (EZH2), the catalytic component of the Polycomb Repressive Complex 2 (PRC2), plays a central role in chromatin compaction and transcriptional repression through trimethylation of histone H3 on lysine 27 (H3K27me3). EZH2...

CONCLUSIONS: Our results highlight that both hypoxia and therapeutic pressure modulate tumor progression in a complex, context-dependent manner.

Vasoactive intestinal peptide (VIP) plays a multifaceted role in cancer biology, yet its prognostic and immunological implications in melanoma remain underexplored. This study aimed to construct a VIP-related gene signature for risk stratification and to explore its potential associations with the tumor immune microenvironment and drug sensitivity in melanoma. RNA-sequencing data and clinical information were obtained from TCGA-SKCM (n = 477, training set) and GSE65904 (n = 209, validation set)....

CONCLUSIONS: Despite substantial improvements in detection rates, SLNB in head and neck melanoma demonstrates clinically relevant limitations in diagnostic sensitivity. The observed false-negative rate highlights a risk of understaging, which may affect eligibility for adjuvant systemic therapies. SLNB findings should therefore be interpreted in the context of anatomical risk patterns and integrated into individualized follow-up strategies. The lack of an association between sentinel lymph node...

CONCLUSION: This exploratory study introduces ENLIGHT-DP as a digital pathology biomarker shown to significantly predict clinical outcomes in patients with cSCC treated with PD-1 inhibitors.

Immunotherapy based on the adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) has proven effective in treating human metastatic melanoma patients, but success in tumors with lower mutational burdens remains a challenge. Preclinical evaluation of cellular therapies commonly relies on murine models, which often require implantation of tumors into immunocompromised mice and thus do not accurately reflect the complex tumor-immune interactions seen in patients. Alternatively, spontaneous...

CONCLUSION: GLP receptor agonists were associated with a significantly reduced risk of postoperative inflammatory complications after dermatologic surgery, supporting their perioperative safety and potential beneficial role in wound healing.

CONCLUSIONS: Melanoma education increased the specificity of primary care clinicians' e-consults without increasing in-person dermatology referrals or unnecessary biopsies. While this intervention has promise for improving skin cancer care in primary care, efforts are needed to increase clinician engagement in this education.

T cell exhaustion remains a significant barrier to effective adoptive cell therapy in solid tumors. Here, we demonstrate that in vitro treatment with the PI3Kδ inhibitor CAL-101 generates T cells with enhanced stemness and metabolic fitness. These cells show increased mitochondrial dependence and spare respiratory capacity while maintaining normal basal metabolism. Under chronic antigen stimulation, CAL-101-treated T cells, including human T cells, resist terminal exhaustion and maintain...

Melanoma is a highly aggressive skin cancer, with mortality largely driven by the development of resistance to BRAF-targeted therapies such as vemurafenib. Although several combination strategies have been explored, durable responses in resistant disease remain limited, highlighting the need for new therapeutic approaches. δ-tocotrienol (δ-TT), a member of the vitamin E family, has shown anticancer activity in different tumor models, but its effects in BRAF inhibitor-resistant melanoma remain...

CONCLUSIONS AND RELEVANCE: Among adults with non-small cell lung cancer, melanoma, or renal cell carcinoma receiving ICIs, PCSK9I use was associated with improved survival and reduced levels of acute health care utilization without significant differences in cardiovascular events, warranting further prospective investigation.

Objective To investigate the heterogeneity characteristics of cancer-associated fibroblasts (CAF) in acral melanoma (AM) and their functional roles in the tumor microenvironment (TME), providing a theoretical basis for developing effective therapeutic strategies. Methods The single-cell RNA sequencing data used in this study were previously generated by our research group and have been deposited in the HRA001804 dataset of the National Genomics Data Center (NGDC). Five AM patient samples were...

CONCLUSIONS: These findings suggest that the designation of MMs as benign lesions may underestimate the oncologic potential of intramedullary or invasive disease. Consideration of aRT on an individualized basis for patients with intramedullary or invasive disease is reasonable, regardless of extent of resection.

Background: Germline CDKN2A variants are associated with Familial Atypical Mole-Malignant Melanoma (FAMMM) syndrome. This syndrome involves an increased risk of melanoma, pancreatic cancer, and, in specific populations, duodenal cancer, breast cancer, and astrocytoma. The CDKN2A (c.146T>C) variant has been found in hereditary cancer patients within the Mexican population. Furthermore, the phenotype linked to this variant in Mexico differs from that observed in other groups. This study aims to...

Background and Objectives: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin malignancy associated with high rates of recurrence and disease-specific mortality. Although adjuvant platinum-etoposide chemotherapy is used in high-risk disease, the optimal number of treatment cycles has not been established. Materials and Methods: This multicenter retrospective cohort study included 104 patients with resected high-risk MCC (pathological stage IIB-III) treated at Israeli...

Cutaneous melanoma remains a highly lethal malignancy once metastatic. Current prognostic stratification relies primarily on staging and serum lactate dehydrogenase (LDH), which incompletely captures inter-patient biological heterogeneity. Increasing evidence highlights the importance of tumour-immune interactions in melanoma progression and response to therapy. This narrative review summarises and critically evaluates current evidence on circulating cytokines as prognostic and biologically...

Fanconi anemia (FA) is a rare inherited disorder associated with impaired DNA repair, characterized by congenital anomalies, bone marrow failure, and a significantly increased risk of developing malignancies, particularly squamous cell carcinoma (SCC) of the head and neck. Treatment options for advanced SCC in FA are limited due to hypersensitivity to DNA-damaging agents. This article presents a unique case of SCC that developed in a 17-year-old patient with FA caused by a homozygous mutation in...

Compounds of plant origin have increasingly emerged as anticancer agents through direct cytotoxicity and sensitizing mechanisms. Melanoma remains the most aggressive form of skin cancer that exhibits a steadily increasing number of new cases globally each year, thus urgently requiring more effective therapeutic strategies. Therefore, phytochemicals can be considered promising candidates, particularly when used in combination with immune checkpoint inhibitors. Their ability to optimize...

Targeted inhibition of the MAPK pathway with BRAF and MEK inhibitors (BRAFi/MEKi) produces rapid tumor regressions in BRAF V600-mutant melanoma, yet most patients ultimately develop acquired resistance. Resistance is not solely a tumor-cell-intrinsic phenomenon; it is accompanied by time-dependent remodeling of the tumor immune microenvironment (TIME) that can shape sensitivity to immune checkpoint inhibitors (ICIs) and inform rational combination or sequencing strategies. Early during MAPK...

High lactate concentration is a hallmark of the tumor microenvironment (TME). Regulatory T cells (Tregs) exhibit unique metabolic adaptability to this lactate-rich environment, yet the underlying mechanisms remain incompletely understood. Here, we demonstrate that the monocarboxylate transporter MCT4 is upregulated in tumor-infiltrating Tregs and mediates direct lactate uptake. Using Treg-specific conditional knockout (cKO) mice, we show that MCT4 deficiency does not affect basal Treg...

Melanoma is a highly aggressive skin malignancy characterized by early metastasis, marked therapeutic resistance, and poor clinical outcomes in advanced disease. Increasing evidence indicates that immune dysregulation within the tumor microenvironment (TME) is a central determinant of melanoma progression, metastatic dissemination, and treatment failure. The melanoma immune microenvironment is shaped by complex interactions among tumor-associated macrophages, tumor-infiltrating lymphocytes,...

Cutaneous squamous cell carcinoma (cSCC) is a common malignant skin tumor with invasive potential and risk of recurrence. This study investigated the anti-cSCC effects of luteolin in vitro and in vivo and explored the associated molecular mechanisms. The effects of luteolin on A431 cell viability were assessed by CCK-8 assay, and apoptosis was analyzed by Annexin V-FITC/propidium iodide (PI) double staining. qRT-PCR and Western blot analyses were performed to evaluate apoptosis-related factors...

In the last decades, melanoma incidence has been rising in many countries, e.g., in Northern Europe, where rates are among the highest despite high latitudes. Using population incidence and demographic data from the NORDCAN database, we estimate the 5-year probability of melanoma diagnosis in 1973-1999. We consider individuals aged 30-54 years, grouped by calendar year and 5-year age group. We analyse temporal patterns to detect possible differences among countries and local deviations from the...

Cutaneous squamous cell carcinoma (CSCC) is a highly prevalent malignancy with rising incidence, particularly among elderly and immunosuppressed individuals. Although most early-stage cases are cured with surgery, a relevant minority present with high-risk features or anatomically complex disease. Immune checkpoint inhibitors (ICIs) have transformed the management of advanced CSCC and are increasingly being evaluated in perioperative settings. This review critically examines current evidence for...

Merkel cell carcinoma (MCC) is a rare, aggressive neurocutaneous malignancy associated with ultraviolet damage, immunosuppression, and Merkel cell polyoma virus infection. Periocular MCC is uncommon but has high rates of local recurrence and metastasis and presents unique therapeutic challenges due to functional and cosmetic considerations. Immune checkpoint inhibitor (ICI) therapy has shown efficacy in systemic MCC; however, evidence for periocular use is limited to small case series and...

Perineural spread (PNS) from cutaneous squamous cell carcinoma (cSCC) to the skull base is increasingly recognised as a route of cancer spread. Management historically involved definitive radiotherapy to treat PNS at the skull base. In the endemic region with modern magnetic resonance neurogram (MRN) and skull base surgical expertise, the outcome has improved over the years. With the advent of immunotherapy, the outcome may be maintained while preserving critical organs in the head and neck...

CONCLUSIONS: There were differences as well as similarities in the reasons for indoor and outdoor tanning. This indicates that overarching prevention strategies could be effective. Additionally, targeted measures specifically for indoor and outdoor tanning could also be beneficial in raising awareness about the risks of UV radiation and, in the long term, reducing the incidence of skin cancer.

Combined immune checkpoint inhibition (ICI) and multitargeted tyrosine kinase inhibition (TKI) improve outcomes in advanced melanoma, especially in heavily pretreated patients, but introduce complex, overlapping toxicities. Although immune-related adverse events and TKI-specific toxicities are well characterized individually, their concurrent presentation is uncommon and can obscure diagnosis. Capillary leak syndrome (CLS), a rare but potentially life-threatening complication of ICIs, further...

Head and neck non-melanoma skin cancers (H&N NMSCs) account for most head and neck malignancies. While primary treatment comprises surgery, adjuvant radiation is recommended in advanced tumors. Radiation oncology practice patterns for resected locally advanced (rLA) and locoregional (rLR) H&N NMSCs have not been well characterized. Using data from the Institute for Clinical Evaluative Sciences (ICES) between 2003 and 2019, we conducted a longitudinal, population-based study characterizing...

To quantify national trends in the incidence, treatment patterns, and direct medical costs of malignant melanoma (MM) and non-melanoma skin cancer (NMSC) in South Korea between 2011 and 2019. We analyzed data from the National Health Insurance Service and Korea Central Cancer Registry and also identified incident cases of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and MM. Age-standardized incidence rates (ASIRs; Segi World Standards) were calculated. Surgical procedures (wide...

CONCLUSION: Local flaps provide a reliable and aesthetically effective solution for nasal reconstruction after skin cancer ablation. Precise flap selection based on defect geometry and subunit involvement is key to minimizing complications and achieving optimal structural and cosmetic outcomes.

CONCLUSION: Management of sectoral schwannomatosis is individual, although surgical treatment involving total nerve-sparing tumor resection is preferable. Further data collection is necessary for a more detailed analysis of segmental schwannomatosis.

AIM: To evaluate pathological response and safety outcomes of neoadjuvant immunotherapy in a real-world cohort of patients with locally advanced resectable melanoma.

CONCLUSION: The majority of patients with infantile hemangioma can be safely managed with oral propranolol in an outpatient setting.

CONCLUSIONS: Both the standard and alternate regimens of ipilimumab plus nivolumab treatment resulted in biochemical evidence for endocrinopathy in 54.6% and 38.9% of treated patients, respectively. Endocrinopathy always presented during or shortly following active treatment. Delayed onset of endocrinopathy was uncommon. Prompt replacement therapy allowed continuation of immune checkpoint inhibitors and minimized the risk for hospitalizations. Due to the high incidence of hypopituitarism,...

CONCLUSION: This case illustrates a novel immunosuppressive strategy for management of pembrolizumab-induced AIHA, a rare but serious hematologic adverse effect associated with immunotherapy. We describe the clinical presentation and report that the combination of CTX and 5-FU in addition to corticosteroids and IVIG was successful in treating severe AIHA. Further investigation in larger cohorts is warranted to validate this approach for intervention in AIHA. With appropriate and prompt...

BACKGROUND AND PURPOSE: Radiotherapy (RT) is effective for cutaneous T-cell lymphoma (CTCL), but the optimal focal dose remains debated. We evaluated lesion response, local control, toxicity and patient satisfaction after 2 × 4 Gy compared with higher-dose regimens. Patient/material and methods: This single-centre retrospective study included CTCL patients treated with RT between 1990 and 2019 at a German university hospital. Lesions receiving 2 × 4 Gy (low-dose) were compared with lesions...

Malignant melanoma has a high mortality rate and is aggressive. The development, metastasis, and angiogenesis of melanoma have all been connected to toll-like receptor 4 (TLR4). However, signal transduction mediated by TLR4 for accelerating melanoma progression is fully unclear. Because of this, the current research has been carried out to explore drug candidate possibility using 3'-Sialyllactose (3'-SL). We investigated the inhibitory effect of 3'-SL on migration and invasion, which are...

CONCLUSION: Years of life lost in cSCC increase in the presence of desmoplasia, bone invasion, immunosuppression, and tumor progression. YLL complements conventional survival measures and highlights a clinically meaningful disease burden despite low disease-specific mortality.

BACKGROUND Infantile hemangiomas (IH) are the most common benign vascular tumors in infants. While most of these lesions undergo spontaneous involution or respond favorably to propranolol, some cases present with early ulceration, aggressive progression, or resistance to standard therapy. Managing such complex cases remains challenging and requires individualized, multidisciplinary strategies and timely escalation to alternative modalities. Here, we report a medically refractory case of...