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This document is an editorial published in the journal Frontiers in Oncology titled "Recent advances in boron neutron capture therapy in radiation oncology." The editorial discusses four papers that were published in a research topic on boron neutron capture therapy (BNCT) in radiation oncology. The papers cover topics such as developing a tumor control probability model for recurrent head and neck cancer, investigating the impact of BNCT on the immune system, the use of accelerator-based BNCT for cutaneous malignant melanoma, and the concern of out-of-field leakage in AB-BNCT systems. The editorial highlights the potential of BNCT as a treatment modality and suggests future research directions. [Extracted from the article]

Cutaneous melanoma, Immunohistochemistry, Lymph node metastases, Nevi, Nicotinamide N-methyltransferase 1 Immunohistochemical expression of NNMT in dermal melanocytic nevi (a; the scale bar corresponds to 100 m), primary cutaneous melanomas (b; the scale bar corresponds to 50 m) and lymph node metastases from cutaneous melanoma (c; the scale bar corresponds to 30 m). Keywords: Cutaneous melanoma; Immunohistochemistry; Lymph node metastases; Nevi; Nicotinamide N-methyltransferase EN Cutaneous melanoma Immunohistochemistry Lymph node metastases Nevi Nicotinamide N-methyltransferase 480 482 3 01/06/23 20230101 NES 230101 Davide Sartini and Elisa Molinelli have contributed equally to this work. [Extracted from the article]

Cutaneous malignant melanoma is a rapidly progressing skin tumor accounting for most deaths from skin malignancies. Four morphological variants (nodular, superficial spreading, lentigo maligna, and acral lentiginous) are described in the literature. Here we are reporting malignant melanoma in a 35-year-old male who presented with depigmented plaques with few hyperpigmented areas and extensive overlying scaling. The patient progressed to the nodular stage within 2 weeks and succumbed to death during chemotherapy. We are reporting such rare presentation of malignant melanoma to create awareness among dermatologists to avoid misdiagnosis and delayed treatment which can lead to rapid progression and fatal outcome.

The second most common mutation in melanoma occurs in NRAS oncogene, being a more aggressive disease that has no effective approved treatment. Besides, cellular plasticity limits better outcomes of the advanced and therapy-resistant patients. Peroxiredoxins (PRDXs) control cellular processes through direct hydrogen peroxide oxidation or by redox-relaying processes. Here, we demonstrated that PRDX2 could act as a modulator of multiple EMT markers in NRAS-mutated melanomas. PRDX2 knockdown lead to phenotypic changes towards invasion in human reconstructed skin and the treatment with a PRDX mimetic (gliotoxin), decreased migration in PRDX2-deficient cells. We also confirmed the favorable clinical outcome of patients expressing PRDX2 in a large primary melanoma cohort. This study contributes to our knowledge about genes involved in phenotype switching and opens a new perspective for PRDX2 as a biomarker and target in NRAS-mutated melanomas. [Display omitted] • NRAS-mutated melanoma cells did not express PRDX2 are more invasive. • Knockdown PRDX2 in melanoma cells increased invasion potential. • Melanoma cells did not express PRDX2 showed more EMT markers. • Mimetic of PRDX2 is able to change migration capability. • PRDX2 correlated with better prognosis in primary melanoma cohort. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of obesity-associated protein (FTO) and human homeobox protein 13(HOXB13) in cutaneous malignant melanoma (CMM) invasion and proliferation. Methods From January 2019 to December 2020, the expression of FTO and HOXB13 in CMM cells was detected by real-time polymerase chain reaction (RT-PCR). The expression and correlation of FTO and HOXB13 was analyzed by TCGA. The changes in expressionof n6-methyladenosine (m6A) of HOXB13 were detected by immunoprecipitation. The biological effects of FTO and HOXB13 on CMM cells proliferation and invasion was analyzed by CCK-8 and Transwell. Results Compared with normal cutaneous malignant melanoma, the expression level of FTO and HOXB13 in CMM cells was significantly increased (P<0.05). The methylation level of m6A of HOXB13 was regulated by FTO. After knocking down FTO in CMM cells, the proliferation and invasion ability was significantly reduced (P<0.05). After overexpression of HOXB13, the proliferation and invasion ability was significantly restored (P<0.05). The effect of FTO on malignant phenotype of CMM was achieved through HOXB13. Conclusion FTO can promote the proliferation and invasion of CMM cells by removing methylation modification of m6A of HOXB13 and up-regulating the expression of HOXB13. [ABSTRACT FROM AUTHOR]

The occurrence of cutaneous malignant melanoma in exotic felids is poorly reported. A 6-year-old, unneutered, solitary, female white Bengal tiger (Panthera tigris tigris), living in a suitable environment, was evaluated for the presence of a mass near the left eye. Histopathology of the referred biopsy showed the presence of melanocytes with anaplastic features (pleomorphism, cytomegaly, karyomegaly, binucleation), hemorrhagic area and fibrinous inflammatory focus. The histopathological diagnosis was malignant melanoma. Two months after diagnosis, the tigress manifested considerable deterioration with weight loss and the presence of a round mass on the neck. At that time, because of its size, the melanoma totally obstructed vision. Based on this, and for humane reasons, the animal was euthanized. At the time of necropsy, metastasis was observed in the lungs, pleura and kidneys. This case demonstrates the importance of raising awareness of melanomas in underreported species. [ABSTRACT FROM AUTHOR]

Introduction: Dermoscopy is one of the most commonly used methods in early diagnosis of melanoma. It is conducted to differentiate between benign and malignant patterns in melanocytic lesions. Aim: To determine if there is a predominance of one dermoscopic pattern in patients with melanoma and if there is a significant difference in dominant global dermoscopic pattern in patients with cutaneous melanomas correlated with patients' sex and the location of the primary tumor. Material and methods: The study included 162 patients with prior diagnosis of cutaneous melanoma. Dermoscopic and videodermoscopic pictures and patient data were analyzed with regard to the pattern: reticular, globular, homogeneous and mixed pattern (two-component pattern; reticular-globular pattern) with central or peripheral globules and multicomponent (mixed -- at least 3 types of structures in one nevus). Results: The reticular pattern was significantly more prevalent in male patients (38.57%, 27 patients) in comparison to female patients (18.45%, 17 patients). We also found a statistically significant lower prevalence of reticular pattern in patients diagnosed with melanomas located on upper limbs. The homogeneous pattern was statistically significantly more prevalent in patients in whom primary tumors were located on the head and upper limbs. Conclusions: Our study suggests that predominant complex patterns are more commonly observed in patients diagnosed with cutaneous melanoma, although there is a significant number of patients with predominant reticular and homogeneous patterns, which are not often associated with an increased risk of development of melanoma. [ABSTRACT FROM AUTHOR]

Background: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown.Methods: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models.Results: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment.Conclusions: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients.Lay Summary: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma. [ABSTRACT FROM AUTHOR]

Krüppel-like transcription factor 6 (KLF6) is a ubiquitous tumor suppressor gene involved in regulating cell growth, proliferation, differentiation and angiogenesis. The objective of the study was to investigate the clinical and prognostic significance of KLF6 expression in cutaneous malignant melanoma (CMM) patients. A total of CMM 67 patients were enrolled in this study. The specimens were evaluated by immunohistochemistry to detect KLF6. The positive KLF6 expression in CMM tissues was significantly lower than in normal skin tissues (p < 0.01). The presence of KLF6 in CMM was correlated with ulceration (p < 0.01), lymph node metastasis (p < 0.01) and clinical stage (p < 0.01). The overall 5-year survival rate of the 67 patients was 13.4%. The 5-year survival rate of patients with negative KLF6 expression was correlated with KLF6 expression (p < 0.01), ulceration (p < 0.01), lymph node metastasis (p < 0.01), clinical stage (p < 0.01) and operation type (p < 0.01). Ulceration and clinical staging were independent relevant factors. In conclusion, the presence of KLF6 in CMM was correlated with ulceration, lymph node metastasis, clinical stage and poor prognosis. [ABSTRACT FROM AUTHOR]

A systematic review published in the British Journal of Dermatology examines the risk factors for developing multiple primary melanomas in patients diagnosed with melanoma. The study analyzes data from 27 studies over the past 40 years, including 388,244 patients with a single melanoma and 24,757 patients with multiple primary melanomas. The review finds that the highest risk of subsequent melanoma is associated with inherited CDKN2A mutation, high naevus count, and the presence of one or more atypical naevi. Other risk factors include family history of melanoma, male sex, older age at diagnosis, light skin color, moderate naevus count, first lesions occurring on the head or neck, and inadequate sun protection. The study suggests that patients with these risk factors should be made aware of their likelihood of developing subsequent melanoma and receive appropriate education and instruction for self-examination of the skin. Patients at the highest risk, such as those with hereditary melanoma due to CDKN2A mutation, may be recommended to undergo long-term periodic skin examination by a dermatologist. However, the review also raises the question of whether long-term dermatological surveillance for all patients with high naevus density or atypical naevi is an efficient use of healthcare resources. Overall, the study provides valuable information for improving secondary prevention of melanoma. [Extracted from the article]

The article discusses the use of teledermoscopy for the triage of cutaneous melanomas in Northern Sweden, where access to dermatology specialists is limited. The study evaluated the reliability and accuracy of teledermoscopy in diagnosing suspected melanomas, showing a high sensitivity of 98.9%. The results indicate that teledermoscopy is a safe and efficient method for diagnosing and triaging cutaneous melanomas, contributing to more rapid diagnosis and treatment, with a focus on accurate image and information transfer to minimize errors. [Extracted from the article]

The article focuses on the utility of ultrasound (US) in diagnosing and treating primary and metastatic melanoma, addressing the challenges in oncology. Topics include the advantages of US over other imaging methods in assessing tumor depth; guiding therapeutic decisions; and improving early detection of locoregional metastases, ultimately enhancing patient outcomes and treatment efficiency in melanoma management.

Aberrant expression of long non‐coding RNA (lncRNA) zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2‐AS1) has been identified in many tumors, but its role in cutaneous malignant melanoma remains largely obscure. Our present study was intended to unveil the role and potential mechanism of ZFPM2‐AS1 in cutaneous malignant melanoma. RT‐qPCR was utilized to analyze ZFPM2‐AS1 expression in cutaneous malignant melanoma cells. Cell counting kit‐8 (CCK‐8), colony formation, flow cytometry, and transwell analyses were utilized to assess ZFPM2‐AS1 function on cell proliferation, apoptosis, and migration. Luciferase reporter, RNA immunoprecipitation, and RNA‐pull down assays were applied to probe the regulatory mechanism of ZFPM2‐AS1 in cutaneous malignant melanoma cells. Up‐regulation of ZFPM2‐AS1 was discovered in cutaneous malignant melanoma cells. ZFPM2‐AS1 deletion restrained cell proliferation, migration, and elevated cell apoptosis in cutaneous malignant melanoma. ZFPM2‐AS1 regulated notch receptor 1 (NOTCH1) to activate the NOTCH pathway. ZFPM2‐AS1 acted as a competing endogenous RNA (ceRNA) to affect NOTCH1 expression via sponging miR‐650. Collectively, ZFPM2‐AS1 exerted an oncogenic role in cutaneous malignant melanoma progression via targeting miR‐650/NOTCH1 signaling. Our study might offer a novel sight for cutaneous malignant melanoma treatment. [ABSTRACT FROM AUTHOR]

Background: In Italy, the incidence of cutaneous malignant melanoma is two-fold higher in the north than in the south. This gradient might be associated with differences in incidence trends and disease surveillance. We compared the time trends in incidence rates, mortality rates, dermatologic office visit rates and skin biopsy rates between the Emilia-Romagna Region (northern Italy) and the Sicily Region (southern Italy)., Methods: The cancer registries of Parma, Modena, Ferrara and Romagna (current population, 2,606,465) and Catania-Messina-Enna, Siracusa and Ragusa (2,775,019) provided incidence and mortality records for the years 2008-2017. The records of outpatient services delivered in public health facilities were obtained from the two Regional Administrations. Trends in rates were assessed with the estimated average annual percent change. North-south differences were expressed as age-standardised rate ratios., Results: In the context of a generalised increasing incidence trend, which was more moderate in the female population of the Sicily Region, the standardised rate ratios were: 5.31 (males) and 5.20 (females) for in situ cutaneous malignant melanoma; 2.10 and 2.07 for invasive cutaneous malignant melanoma, with an excess incidence concentrated in lesions ⩽1.00 mm thick (3.58 and 3.05); 3.00 and 2.44 for dermatologic office visits; and 5.25 and 5.02 for skin biopsies. Mortality was stable in both Regions., Conclusions: In the Emilia-Romagna Region, as compared with the Sicily Region, a higher incidence of cutaneous malignant melanoma -especially of in situ and early invasive cutaneous malignant melanoma- coexisted with a higher level of clinical surveillance. The question of the direction of the cause-effect relationship between increased incidence and increased diagnostic scrutiny remains open., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Observational studies have identified a dual effect of circulating inflammatory proteins and immune cells on cancer progression. However, the specific mechanisms of action have not been clarified in the exacerbation of cutaneous-origin tumors. Therefore, this study aims to investigate whether the causal relationship between circulating inflammatory factors and basal cell carcinoma (BCC), cutaneous malignant melanoma (SKCM), and cutaneous squamous cell carcinoma (cSCC) is regulated by immune cells., Methods: This study employed the Two-Sample Mendelian Randomization (TSMR) approach to investigate the causal relationships between 91 circulating inflammatory factors and three prevalent types of skin cancer from a genetic perspective. Bayesian Weighted Mendelian Randomization (BWMR) was also used to validate correlation and reverse MR to assess inverse relationships. Subsequent sensitivity analyses were conducted to limit the impact of heterogeneity and pleiotropy. Finally, the two-step Mendelian Randomization (two-step MR) method was utilized to ascertain the mediating effects of specific immune cell traits in the causal pathways linking circulating inflammatory factors with BCC, SKCM, and cSCC., Results: The Inverse Variance Weighted (IVW) method and the Bayesian Weighted Algorithm collectively identified nine inflammatory factors causally associated with BCC, SKCM, and cSCC. The results from Cochran's Q test, mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger intercept were not statistically significant (p < 0.05). Additionally, the proportions mediated by CD4+ CD8dim T cell %leukocyte, CD4-CD8-Natural Killer T %T cell, and CD20 on IgD-CD38-B cell for FIt3L, CCL4, and OSM were 9.26%, 8.96%, and 10.16%, respectively., Conclusion: Immune cell levels potentially play a role in the modulation process between circulating inflammatory proteins and cutaneous-origin exacerbated tumors. This finding offers a new perspective for the in-depth exploration of cutaneous malignancies., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Introduction: Cutaneous malignant melanoma (CMM) incidence has risen rapidly in the last 50 years. Poor progression and high mortality characterize CMM, making a thorough understanding of progression and associated factors essential for optimizing care. Aims: We assessed the association between the Neutrophil-to-Lymphocyte Ratio (NLR) and mortality in adults with CMM from an entirely mixed-race Hispanic population during 12 consecutive years of extensive follow-up. Material & Methods: We performed a retrospective cohort study in a tertiary hospital in Peru. NLR was categorized with a cutoff value higher or equal than 3. We collected demographic variables, laboratory results and treatments at baseline of follow-up. Cox regression analysis was performed, and we calculated crude and adjusted hazard ratios (HR) and their 95% confidence interval (95%CI). Results: The analysis was from 615 CMM cases, and there were 378 deaths. Most melanomas (63.6%) were acral lentiginous. The crude analysis showed that high NLR is a risk factor for mortality, HR = 2.52; 95%CI (2.03–3.14). High NRL ratio remains statistically significant after adjusting for confounding variables, aHR = 1.61; 95%CI (1.16–2.24). Other risk factors for mortality were clinical stages III and IV, older than 60 years, females and greater Breslow thickness. Conclusions: We concluded that high NRL ratio is a risk factor for mortality and should be monitored in every patient who is diagnosed with malignant melanoma during their first blood count. It should then be carried out in follow-up controls for patients of clinical stage III and IV only, or in patients who present a relapse.

In Oceania, North America and north‐western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty‐one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age‐standardised rates were analysed using joinpoint regression models and age‐period‐cohort models. Age‐standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2‐4.0] among men and 2.5 [2.0‐3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low‐risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949—the median cohort with respect to the number of cases for both genders—as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth‐cohort‐dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long‐term upward incidence trend of CMM is extending to southern Europe. What's new? After increasing for many years, malignant melanoma rates began to stabilise or decline in many regions before 2000. Is this also true for southern Europe? In the current study, the authors found that melanoma rates have also began to decline in Italy. The reversal of the long‐term, worldwide increase in melanoma risk seen in other Caucasian populations thus appears to extend to southern Europe. These results indicate that primary prevention strategies have been effective in modifying sun‐exposure habits in this region, and should continue to be reinforced via public health messaging. [ABSTRACT FROM AUTHOR]

Background: The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only.Methods: The TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/- whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group.Discussion: This is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM.Results: The first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden.Trial Registration: ClinicalTrials.gov , NCT03116412 . Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412. [ABSTRACT FROM AUTHOR]

Background. Epithelial splicing regulatory protein 1 (ESRP1) has been described as an RNA-binding protein involved in cancer development. However, the expression and regulatory network of ESRP1 in cutaneous malignant melanoma (CMM) remain unclear. Methods. From the sequencing data of 103 CMM samples in The Cancer Genome Atlas database, the expression level of ESRP1 and its correlation with the clinicopathological characteristics were analyzed using the Oncomine 4.5, Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN tools, while LinkedOmics was used to identify differential gene expression with ESRP1 and to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Gene enrichment analysis examined target networks of kinases, miRNAs, and transcription factors. Finally, TIMER was used to analyze the relationship between ESRP1 and tumor immune cell infiltration. Results. We found that ESRP1 was lowly expressed in CMM tissues, and a low level of ESRP1 expression correlated with better overall survival. Expression of this gene was linked to functional networks involving the condensed chromosomes, epidermal development, and translation initiation. Functional network analysis suggested that ESRP1 regulated ribosome metabolism, drug metabolism, and chemical carcinogenesis via pathways involving several cancer-related kinases, miRNAs, and transcription factors. Furthermore, our results suggested that ESRP1 played an important role in regulating tumor-associated macrophage polarization, dendritic cell infiltration, Treg cells, and T cell exhaustion. Conclusion. Our study demonstrates ESRP1 expression, prognostic value, and potential regulatory networks in CMM, thereby shedding light on the clinical significance of ESRP1, and provides a novel biomarker for determining prognosis and immune infiltration in CMM. [ABSTRACT FROM AUTHOR]

Introduction: Due to the rising incidence of cutaneous melanoma there is a great need for the development of new diagnostic techniques as well as the improvement of those that are already well known, such as dermoscopy. Since early detection and a proper technique for excising the tumor are crucial for patients' survival, early staging of the tumor is very important. Aim: To investigate whether there is a significant difference between the presence of selected dermoscopic features compared to the location on the skin and pathology results: Breslow's depth, mitotic index and ulceration. Material and methods: We examined videodermoscopic images of cutaneous melanomas in 81 patients and compared their features with the histological results such as Breslow's depth, mitotic index and ulceration. In the study, we divided and compared the tumors in groups: in situ and invasive, ≤ 1.0 mm and > 1.0 mm thick on the Breslow scale. Results: In the study we observed statistically significantly higher prevalence of pseudopods (30.5%) and multicomponent pattern (69.5%) in invasive melanomas in comparison to in situ melanomas (9.1% and 36.4% respectively). White regression structures were more commonly described in invasive melanomas thicker than 1.0 mm on Breslow's scale. Atypical blood vessels and nodules were more specific to invasive melanomas with ulcerations and mitotic index ≥ 1. The atypical pigment network was more specific for thin invasive melanomas. Conclusions: Presence of pseudopods, a multicomponent pattern, white regression structures, atypical blood vessels and nodules on dermoscopy suggest invasive (high stage) melanoma. [ABSTRACT FROM AUTHOR]

Citrus products are rich sources of furocoumarins, a class of photoactive compounds. Certain furocoumarins combined with ultraviolet radiation can induce skin cancer. We examined the relationship between citrus consumption and cutaneous melanoma risk among 56,205 Caucasian postmenopausal women in the Women's Health Initiative. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma by citrus intake level. During a mean follow-up of 15.7 years, 956 incident melanoma cases were documented. In multivariable adjusted models, the HR (95% CI) for melanoma was 1.12 (0.91, 1.37) among the highest citrus consumers (1.5+ servings/day of fruit or juice) versus the lowest (<2 servings/week), 0.95 (0.76, 1.20) among the highest citrus fruit consumers (5+ servings/week) versus non-consumers, and was 1.13 (0.96, 1.32) for the highest citrus juice consumers (1+ servings/day) versus the lowest (<1 serving/week). In stratified analyses, an increased melanoma risk associated with citrus juice intake was observed among women who spent the most time outdoors in summer as adults; the HR for the highest versus lowest intake was 1.22 (1.02, 1.46) (p trend = 0.03). Further research is needed to explore the association of melanoma with citrus juices among women with high sun exposure. [ABSTRACT FROM AUTHOR]

The role of Sentinel Lymph Node Biopsy (SLNB) is pivotal in the contemporary staging of cutaneous melanoma. In this review, we examine advanced molecular testing platforms like gene expression profiling (GEP) and immunohistochemistry (IHC) as tools for predicting the prognosis of sentinel lymph nodes. We compare these innovative approaches with traditional staging assessments. Additionally, we delve into the shared genetic and protein markers between GEP and IHC tests and their relevance to melanoma biology, exploring their prognostic and predictive characteristics. Finally, we assess alternative methods to potentially obviate the need for SLNB altogether. Progress in adjuvant melanoma therapy has diminished the necessity of Sentinel Lymph Node Biopsy (SLNB) while underscoring the importance of accurately identifying high-risk stage I and II melanoma patients who may benefit from additional anti-tumor interventions. The clinical application of testing through gene expression profiling (GEP) or immunohistochemistry (IHC) is gaining traction, with platforms such as DecisionDx, Merlin Assay (CP-GEP), MelaGenix GEP, and Immunoprint coming into play. Currently, extensive validation studies are in progress to incorporate routine molecular testing into clinical practice. However, due to significant methodological limitations, widespread clinical adoption of tissue-based molecular testing remains elusive at present. While various tissue-based molecular testing platforms have the potential to stratify the risk of sentinel lymph node positivity (SLNP), most suffer from significant methodological deficiencies, including limited sample size, lack of prospective validation, and limited correlation with established clinicopathological variables. Furthermore, the genes and proteins identified by individual gene expression profiling (GEP) or immunohistochemistry (IHC) tests exhibit minimal overlap, even when considering the most well-established melanoma mutations. However, there is hope that the ongoing prospective trial for the Merlin Assay may safely reduce the necessity for SLNB procedures if successful. Additionally, the MelaGenix GEP and Immunoprint tests could prove valuable in identifying high-risk stage I-II melanoma patients and potentially guiding their selection for adjuvant therapy, thus potentially reducing the need for SLNB. Due to the diverse study designs employed, effective comparisons between GEP or IHC tests are challenging, and to date, there is no study directly comparing the clinical utility of these respective GEP or IHC tests. • Sentinel lymph node biopsy (SLNB) is currently crucial for the staging of melanoma. • Tissue-based molecular tests are effective in identifying high-risk melanoma. • These are gene expression profiling (GEP)- or immunohistochemistry (IHC)-based. • roboTissue-based molecular tests could reduce the need for SLNB. • roboThey could lead to early initiation of adjuvant therapy. [ABSTRACT FROM AUTHOR]

The survival in patients diagnosed with cutaneous malignant melanoma (CMM) has improved in the Nordic countries in the last decades. It is of interest to know if these improvements are observed in all ages and for both women and men. Patients diagnosed with CMM in the Nordic countries in 1990–2016 were identified in the NORDCAN database. Flexible parametric relative survival models were fitted, except for Iceland where a non-parametric Pohar-Perme approach was used. A range of survival metrics were estimated by sex, both age-standardised and age-specific. The 5-year relative survival improved in all countries, in both women and men and across age. While the improvement was more pronounced in men, women still had a higher survival at the end of the study period. The survival was generally high, with age-standardised estimates of 5-year relative survival towards the end of the study period ranging from 85% in Icelandic men to 95% in Danish women. The age-standardised and reference-adjusted 5-year crude probability of death due to CMM ranged from 5% in Danish and Swedish women to 13% in Icelandic men. Although survival following CMM was relatively high in the Nordic countries in 1990, continued improvements in survival were observed throughout the study period in both women and men and across age. • Survival following cutaneous malignant melanoma is high in the Nordic countries. • The survival has continuously improved between 1990 and 2016. • Survival improvements were observed across age and in both men and women. [ABSTRACT FROM AUTHOR]

This article, published in the Australasian Journal of Dermatology, examines the association between ultraviolet radiation (UVR) and skin cancer. The study used data from the Stockholm Public Health Cohort, including self-reported questionnaire data and information from Swedish national registers. The results showed that UVR-related factors, such as sunbed use and being diagnosed with actinic keratosis or melanocytic nevi, were significantly associated with an increased risk of skin cancer. The study did not find any other preventable causes for the rising incidence of skin cancer, even after adjusting for various factors. [Extracted from the article]

Dysregulation of the kynurenine pathway has been regarded as a mechanism of tumor immune escape by the enzymatic activity of indoleamine 2, 3 dioxygenase and kynurenine production. However, the immune-modulatory properties of other kynurenine metabolites such as kynurenic acid, 3-hydroxykynurenine, and anthranilic acid are poorly understood. In this study, plasma from patients diagnosed with metastatic cutaneous malignant melanoma (CMM) was obtained before (PRE) and during treatment (TRM) with inhibitors of mitogen-activated protein kinase pathway (MAPKIs). Immuno-oncology related protein profile and kynurenine metabolites were analyzed by proximity extension assay (PEA) and LC/MS-MS, respectively. Correlation network analyses of the data derived from PEA and LC/MS-MS identified a set of proteins that modulate the differentiation of Th1 cells, which is linked to 3-hydroxykynurenine levels. Moreover, MAPKIs treatments are associated with alteration of 3-hydroxykynurenine and 3hydroxyanthranilic acid (3HAA) concentrations and led to higher “CXCL11,” and “KLRD1” expression that are involved in T and NK cells activation. These findings imply that the kynurenine pathway is pathologically relevant in patients with CMM.

Background: Obesity is associated with chronic low-grade inflammation, which is linked to cancer development. Abdominal obesity (a body mass index, ABSI), however, has unusually been associated inversely with cutaneous malignant melanoma (CMM), while general obesity (body mass index, BMI) is associated positively. Leucocytes participate in inflammation and are higher in obesity, but prospective associations of leucocytes with cutaneous malignant melanoma are unclear., Methods: We examined the prospective associations of neutrophil, lymphocyte, and monocyte counts (each individually), as well as the prospective associations of ABSI and BMI, with cutaneous malignant melanoma in UK Biobank. We used multivariable Cox proportional hazards models and explored heterogeneity according to sex, menopausal status, age (≥ 50 years at recruitment), smoking status, ABSI (dichotomised at the median: ≥73.5 women; ≥79.8 men), BMI (normal weight, overweight, obese), and time to diagnosis., Results: During a mean follow-up of 10.2 years, 2174 CMM cases were ascertained in 398,450 participants. There was little evidence for associations with neutrophil or lymphocyte counts. Monocyte count, however, was associated inversely in participants overall (HR = 0.928; 95%CI: 0.888-0.971; per one standard deviation increase; SD = 0.144*10 9 /L women; SD = 0.169*10 9 /L men), specifically in older participants (HR = 0.906; 95%CI: 0.862-0.951), and more clearly in participants with low ABSI (HR = 0.880; 95%CI: 0.824-0.939), or with BMI ≥ 25 kg/m 2 (HR = 0.895; 95%CI: 0.837-0.958 for overweight; HR = 0.923; 95%CI: 0.848-1.005 for obese). ABSI was associated inversely in pre-menopausal women (HR = 0.810; 95%CI: 0.702-0.935; SD = 4.95) and men (HR = 0.925; 95%CI: 0.867-0.986; SD = 4.11). BMI was associated positively in men (HR = 1.148; 95%CI: 1.078-1.222; SD = 4.04 kg/m 2 ). There was little evidence for heterogeneity according to smoking status. The associations with monocyte count and BMI were retained to at least 8 years prior to diagnosis, but the association with ABSI was observed up to 4 years prior to diagnosis and not for longer follow-up time., Conclusions: Monocyte count is associated prospectively inversely with the risk of developing CMM in older individuals, while BMI is associated positively in men, suggesting a mechanistic involvement of factors related to monocytes and subcutaneous adipose tissue in melanoma development. An inverse association with ABSI closer to diagnosis may reflect reverse causality or glucocorticoid resistance., (© 2024. The Author(s).)