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Simple Summary: Nevoid melanoma is a rare melanoma subtype that closely resembles a common nevus clinically and histologically. For this reason, diagnosis is easily missed. Both dermatologists and pathologists should be aware of this entity since its recognition might avoid severe consequences for the patient and medicolegal issues. Only a few papers on clinical and dermoscopic characteristics of nevoid melanoma are available. This study analyzes the clinical and pathological characteristics of nevoid melanoma in a population of patients affected by this rare subtype. It compares the prognosis and survival of these patients to data from classical melanoma featured in the literature. Additionally, by analyzing available dermoscopic images of nevoid melanoma, we aim to identify dermoscopic features that might help clinicians to suspect nevoid melanoma, reducing misdiagnosis. Background: Diagnosis of nevoid melanoma (NeM) is often difficult because NeM closely resembles a common nevus clinically and histologically. Methods: A retrospective study was conducted on 110 patients diagnosed with and/or treated for primary nevoid melanoma at the Veneto Institute of Oncology and at the University Hospital of Padua from August 1999. Results: Mean Breslow thickness was of 1.4 mm. Sentinel lymph node biopsy was conducted in nearly half of the patients, and positivity was detected in 16.7% of them. Twenty-four clinical and 23 dermoscopic pictures were collected. Papular and macular lesions prevailed over nodular and plaque-type lesions. Different hues of brown, pink, and red color were most represented. Twenty nevus-like NeMs and four multicomponent-pattern NeMs were observed. The Most frequent dermoscopic patterns for nevus-like NeM were atypical pigmented reticulum, irregular globules and dots, and hyperpigmented blotches. Atypical vessels, asymmetric peripheric striae, blue-white veil, and areas of regression were less frequent and prevailed in multicomponent pattern NeM. A structureless pattern was also featured. Many patients in the series had multiple melanomas. However, none of them had numerous multiple nevoid melanomas. Conclusions: NeM should not be regarded as a separate biological entity from classical melanoma, and the same histological and clinical prognostic factors apply to NeM. Clinically and dermoscopically, it often resembles benign nevi, although some clues such as evolution and some dermoscopic patterns could suggest malignancy. Clinical suspicion might prove crucial to further pathological analysis and recognition. [ABSTRACT FROM AUTHOR]

Simple Summary: Kaposi's sarcoma (KS) is a low-grade, vascular tumor associated with human herpesvirus 8 (HHV8) infection. There are four widely recognized types of KS including classic, endemic, iatrogenic, and epidemic forms. Although in most cases, KS is an indolent disease limited to the skin, it may have a more aggressive behavior resulting in locally aggressive disease and/or involving the mucosae or visceral organs, especially in immunosuppressed patients. The main risk factors are HHV-8 infection and immunosuppression status. The treatment is very heterogenous, because there is still no unified strategy for the treatment of KS. The aim of this study is to describe the demographic and clinical features, treatment outcomes, and prognosis of a cohort of patients affected by KS treated at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV) between 1993 and 2022. Kaposi's sarcoma (KS) is a rare angioproliferative tumor classified in four different clinical–epidemiological forms. The diagnosis is based on histopathological and immunohistochemical analyses. The treatment is heterogeneous and includes several local and systemic therapeutic strategies. Methods: This is a retrospective cohort study including 86 KS patients treated between 1993 and 2022 at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV). The data were extracted from an electronic database. Survival curves were generated using the Kaplan–Meier method, and Cox regression models were employed to explore associations with overall and disease-free survival. The male sex (89.53%), classical variant (43.02%), and cutaneous involvement (77.9%) were predominant. More than 61.6% of patients received a single treatment. Surgery, antiretroviral therapy, and chemotherapy were the mostly adopted approaches. A persistent response was observed in approximately 65% of patients, with a 22% relapse rate (at least 2 years). The overall survival ranges from 90 to 70% at 2 to 10 years after the diagnosis. Iatrogenic KS demonstrated a higher mortality (52.9%). This study reflects our experience in the management of KS. Comorbidities are very frequent, and treatments are heterogeneous. A multidisciplinary approach involving multiple referral specialists is essential for the appropriate management of this disease during diagnosis, treatment, and follow-up. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals which could be associated with cancer development, such as kidney and testicular cancers, pancreatic and hepatocellular carcinoma and thyroid tumor. Available scientific literature offers no information on the role of PFAS in melanoma development/progression. Since 1965, a massive environmental contamination by PFAS has occurred in northeastern Italy. This study compared histopathology and prognosis between melanoma patients exposed (n = 194) and unexposed (n = 488) to PFAS. All patients were diagnosed and/or treated for melanoma at the Veneto Oncological Institute and the University Hospital of Padua (Italy) in 1998–2014. Patients were categorized in exposed or unexposed groups according to their home address and the geographical classification of municipalities affected by PFAS contamination as provided by Veneto Government in 2018. Presence of mitoses was found in 70.5% of exposed patients and 58.7% of unexposed patients (p = 0.005). Median follow-up was 90 months (IQR 59–136). 5-year overall survival was 83.7% in exposed patients and 88.0% in unexposed patients (p = 0.20); 5-year disease-specific survival was 88.0% in exposed patients and 90.9% in unexposed patients (p = 0.50); 5-year disease-free survival was 83.8% in exposed patients and 87.3% in unexposed patients (p = 0.20). Adjusting for imbalanced characteristics at baseline (presence of mitoses), survival was not statistically different between exposed and unexposed patients (overall survival: HR 1.10, 95% CI 0.77 to 1.58, p = 0.57; disease-specific survival: HR 0.99, 95% CI 0.62 to 1.59, p = 0.99; disease-free survival: HR 1.10, 95% CI 0.74 to 1.64, p = 0.62). Although the magnitude of PFAS exposure was not quantifiable, our findings suggested that exposure to PFAS was associated with higher level of mitosis in melanoma patients, but this did not translate into a survival difference. Further studies are required to investigate this relationship and all effects of PFAS on prognosis. [ABSTRACT FROM AUTHOR]

Background: This study aims to provide a comprehensive overview of sex-related characteristics of cutaneous malignant melanoma (CMM), with special reference to its incidence, clinicopathological profile, overall survival, and treatment-related costs. Methods: This retrospective cohort study included all 1,279 CMM patients who were registered in 2015 in the Veneto Cancer Registry (a population-based registry including all 4,900,000 regional residents). The by-sex comparisons included tumor stage and site, histological subtype, and other clinical–pathological variables. A Cox regression analysis was used to test the association between sex and survival, adjusting for the main covariates. Treatment costs were calculated by linking patients with several administrative regional databases. Results: Age-specific incidence rates were significantly higher for men among people >50 years old. For men, the trunk was the most common primary site (59.3%), whereas for women the lower limbs (32.1%) were the most common primary site, followed by the trunk (31.8%), which was lower than for men (p < 0.001). At presentation, the frequency of early stage CMM was higher among women, who also featured a significantly lower risk of death (p = 0.016), after adjusting for covariates. Men also incurred higher costs for melanoma treatment in the first year after their diagnosis. Conclusions: Among younger adults, CMM was more common in women, whereas among older adults, it was more common in men. Sex also influences patients' histopathological characteristics at diagnosis. Women had better overall survival after adjusting for demographic, pathological, and clinical profiles. The costs of treatment were also lower for women with CMM. [ABSTRACT FROM AUTHOR]

Introduction: A number of studies have examined the impact of tumor stage on direct health care costs of patients with melanoma. This study aimed to investigate the association between the direct costs for melanoma and the patients' clinical and histological characteristics. Methods: The present analysis included 1368 patients diagnosed with melanoma in 2017 in the Veneto Region (northeast Italy) and recorded in a regional population-based melanoma registry. The costs were assessed taking monthly and total direct costs into account. Log-linear multivariable analysis was used to identify the clinical and histological cost drivers, focusing on monthly and total direct costs per patient incurred during the first 2 years after a patient's diagnosis. Results: On multivariable analysis, besides the stage of melanoma, also the presence of mitoses (> 2) was associated with higher monthly direct costs [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.15–2.08, p = 0.004] in respect to cases with 0–2 mitoses. Vertical growth was associated with higher costs compared with radial growth (OR 1.28, 95% CI 1.00–1.64, p = 0.055). Moreover, the association between the absence of tumor-infiltrating lymphocytes (TILs) and higher monthly direct costs reached statistical significance (OR 1.31, 95% CI 1.05–1.64, p = 0.017). There were no differences in monthly direct costs by patients' sex or age, ulceration, or tumor site. Conclusion: This study showed that not only tumor stage but also other clinical and histopathologic characteristics have an impact on the direct monthly and total costs of treating melanoma. Further studies on the cost-effectiveness of the various options for managing this disease should take these variables into account, as well as tumor stage, as cost drivers. [ABSTRACT FROM AUTHOR]

Previous studies associated high-level exposure to ultraviolet radiation with a greater risk of cutaneous malignant melanoma (CMM). This study focuses on the changing incidence of CMM over time (from 1990 to 2017) in the Veneto region of Northeast Italy, and its Alpine area (the province of Belluno). The clinicopathological profile of CMM by residence is also considered. A joinpoint regression analysis was performed to identify significant changes in the yearly incidence of CMM by sex and age. For each trend, the average annual percent change (AAPC) was also calculated. In the 2017 CMM cohort, the study includes a descriptive analysis of the disease's categorical clinicopathological variables. In the population investigated, the incidence of CMM has increased significantly over the last 30 years. The AAPC in the incidence of CMM was significantly higher among Alpine residents aged 0–49 than for the rest of the region's population (males: 6.9 versus 2.4; females 7.7 versus 2.7, respectively). Among the Alpine residents, the AAPC was 3.35 times greater for females aged 0–49 than for people aged 50+. The clinicopathological profile of CMM was significantly associated with the place of residence. Over three decades, the Veneto population has observed a significant increase in the incidence of CMM, and its AAPC. Both trends have been markedly more pronounced among Alpine residents, particularly younger females. While epidemiology and clinicopathological profiles support the role of UV radiation in CMM, the young age of this CMM-affected female population points to other possible host-related etiological factors. These findings also confirm the importance of primary and secondary prevention strategies. [ABSTRACT FROM AUTHOR]

Clinical factors, such as tumor thickness, ulceration and growth phase have a role as prognostic factors for stage I melanoma. However, it is still under debate whether these variables influence the related direct costs. We aimed to investigate which clinical factors represent direct health care "cost drivers" for stage I melanoma. Analyses were conducted on a cohort of patients diagnosed with stage I melanoma. Differences in the costs incurred by different groups of patients were examined using Mann-Whitney or Kruskal-Wallis non-parametric tests. Log linear multivariate analysis was used to identify the clinical drivers of the total direct costs one and two years after diagnosis. The study was conducted from the perspective of Italy's National Health care System. One year after diagnosis, patients whose melanomas had a Breslow thickness ≥0.8 mmin (compared with those with lower thickness) and a vertical growth phase (compared with those with radial growth) incurred higher costs for hospitalization, as well as higher overall costs. One year after their diagnosis, treatment of patients with stage I melanoma in the vertical growth phase costs 50% more (95% CI: 22–85%) than their counterparts with a radial growth pattern, resulting in an estimated absolute increase of € 256.23. Having a tumor thicker than 0.8 mm prompted an increase of 91% (95% CI: 43–155%) in the costs (€955.24 in absolute terms). Our data indicate a heterogeneity in the direct costs of stage I melanoma patients during the first year after diagnosis, which can be partly explained by clinical prognostic factors, like tumor thickness and growth pattern. [ABSTRACT FROM AUTHOR]

Background: Cutaneous malignant melanoma (CMM) ranks among the five most common cancers in young people in high-income countries and it features peculiar clinicopathological traits. Very few studies have addressed the quality of care and the costs for adolescents and young adults (AYA) population., Objective: To provide a comprehensive epidemiological and clinicopathological profile of CMM in AYA. The study also addresses the cost-of-illness and the diagnostic-therapeutic performance indicators by patient age category., Methods: This population-based cohort study included 2435 incident CMM (age range 15-65 years; age 15-39 = 394; age 40-65 = 2041), as recorded in 2015, 2017 and 2019 by the Regional Veneto Cancer Registry (Italy). Cramer's-V tested the strength of association between pairs of variables. The Kaplan-Meier method was used to test the association between age and survival rate. The clinical performance indicators were computed using the Clopper-Pearson exact method., Results: In AYA patients (16.2%), CMM incidence rates increased significantly from 1990 to 2019. Low-stage CMM (p = 0.007), radial growth pattern (p = 0.026) and lower Clark levels (p = 0.007) prevailed; males had less advanced malignancies (p = 0.003), with the trunk as the most common primary site (67.5%); the lower limbs (32.6%) were the most common primary site for females (p < 0.001). Overall survival was better in AYA than adults. No significant difference was detected in the clinical management of the two age groups, with the only exception of the margin in wide local excision. The care costs were lower in AYA (€195.99 vs. €258.94, p = 0.004)., Conclusions: In AYA patients, the CMM clinicopathological presentation shows a distinctive profile. The present results provide critical information for optimizing primary and secondary prevention strategies and for tailoring diagnostic therapeutic procedures to the peculiar profile of AYA CMM patients., (© 2024 European Academy of Dermatology and Venereology.)

Promoting standardization and quality assurance (QA) may guarantee better outcomes for patients and ensure a better allocation of healthcare system resources. The present study tested the association between process quality indicators of the clinical pathway for melanoma and both patient short-term mortality and budget utilization. Specific indicators were selected to assess quality of processes in different phases of the pathway as well as the pathway as a whole. Cox regression models were run for each phase to test the association between adherence to the quality indicator and overall mortality. A Tobit regression analysis was used to identify any association between adherence to the quality indicators and total costs over the two years after melanoma was diagnosed. This retrospective cohort study concerned 1,222 incident cases of melanoma in the Veneto Region (north-east of Italy). Adherence to the clinical pathway as a whole was associated with a significant decrease in risk of death (HR= 0.40; 95% CI: 0,19 -0,77). Adherence to quality processes in the diagnostic phase (HR= 0.55 95% CI: 0.31- 0.95) and surgical phase (HR= 0.33 95% CI: 0.16- 0.61) significantly reduced the hazard risk. Tobit regression revealed a significant increase in overall costs for patients who adhered to the whole pathway in comparison with those who did not (β= 2,393.24; p= 0.013). This study suggests that adherence to the quality of management of clinical pathways modifies short-term survival as well as mean cost of care for patients with cutaneous melanoma. Physicians should be encouraged to improve their compliance with clinical care pathways for their melanoma patients, and steadily growing associated costs emphasize the need for policy makers to invest exclusively in treatments of proven efficacy.

Due to the COVID-19 crisis, many scheduled medical and surgical activities have been suspended. This interruption to the healthcare system can negatively affect the diagnosis and management of melanoma. Neglecting melanoma throughout the outbreak may be associated with increased rates of mortality, morbidity, and healthcare expenses. We performed a retrospective review of all dermatological and surgical activity performed in our Melanoma Skin Unit between 23 February 2020 and 21 May 2020 and compared these data with those from the same period in 2019. During the lockdown period, we observed a decrease in dermatologic follow-up (DFU) (-30.2%) and in surgical follow-up (SFU) (-37%), and no modification of melanoma diagnosis (-3%). Finally, surgical excisions (SE) (+ 31.7%) increased, but sentinel lymph node biopsy (SLNB) (-29%) and lymph node dissections(LND) (-64%) decreased compared to the same period in 2019. Our experience supports the continuation of surgical and diagnostic procedures in patients with melanoma during the COVID-19 pandemic. Surgical and follow-up procedures for the diagnosis and treatment of melanoma should not be postponed considering that the pandemic is lasting for an extended period., (© 2021 Wiley Periodicals LLC.)

Acral melanoma (AM) is a rare and aggressive subtype of melanoma affecting the palms, soles, and nail apparatus with similar incidence among different ethnicities. AM is unrelated to ultraviolet radiation and has a low mutation burden but frequent chromosomal rearrangements and gene amplifications. Next generation sequencing of 33 genes and somatic copy number variation (CNV) analysis with genome-wide single nucleotide polymorphism arrays were performed in order to molecularly characterize 48 primary AMs of Italian patients in association with clinicopathological and prognostic features. BRAF was the most commonly mutated gene, followed by NRAS and TP53 , whereas TERT promoter, KIT , and ARID1A were less frequently mutated. Gains and losses were recurrently found in the 1q, 6p, 7, 8q, 20 and 22 chromosomes involving PREX2 , RAC1 , KMT2C , BRAF , CCND1 , TERT , and AKT3 genes, and in the 6q, 9, 10, 11q and 16q chromosomes including CDKN2A , PTEN , and ADAMTS18 genes, respectively. This study confirmed the variety of gene mutations and the high load of CNV in primary AM. Some genomic alterations were associated with histologic prognostic features. BRAF mutations, found with a higher rate than previously reported, correlated with a low Breslow thickness, low mitotic count, low CNV of the AMs, and with early-stage of disease.

Background: Reproducible, high-quality surgery is a key point in the management of cancer patients. Quality indicators for surgical treatment of melanoma has been presented with benchmarks but data on morbidity are still limited. This study presents the quality indicators on morbidity after surgical treatment for non-metastatic skin melanoma in an Italian registry., Methods: Data were extracted from the Central National Melanoma Registry (CNMR) promoted by the Italian Melanoma Intergroup (IMI). All surgical procedures (WE, SNLB or LFND) for non-metastatic skin melanoma between January 2011 and February 2017 were evaluated for inclusion in the study. Only centers with adequate completeness of information (> 80%) were included in the study. Short-term complications (wound infection, dehiscence, skin graft failure and seroma) were investigated., Results: Wound infection rate was 1.1% (0.4 to 2.7%) in WE, 1.3% (0.7 to 2.5%) in SLNB and 4.1% (2.1 to 8.0%) in LFND. Wound dehiscence rate was 2.0% (0.8 to 5.1%) in WE, 0.9% (0.2 to 3.0%) in SLNB and 2.8% (0.9 to 8.6%) in LFND. Seroma rate was 4.2% (1.5 to 11.1%) in SLNB and 15.1% (4.6 to 39.9%) in LFND. Unreliable information was found on skin graft failure., Conclusions: Our findings contribute to available literature in setting up the recommended standards for melanoma centers, thus improving the quality of surgery offered to patients. A consensus on the core issues around surgical morbidity is needed to provide practical guidance on morbidity prevention and management.

Background: While many evidence-based pathways have been introduced to drive quality improvements in cancer care, most of these do not include evidence about their affordability. The main aim of this study was to provide an estimation of the overall budget to cover all the needs of melanoma patients in Veneto Region, managed according to the clinical pathway defined by the Rete Oncologica Veneta. A second objective is to conduct a cost-consequence analysis, comparing two different treatments., Methods: A very detailed whole-disease model was developed describing the patient's pathway from diagnosis through the first year of follow-up. Each procedure involved in the model was associated with a likelihood measure and a cost. The model can be used to estimate the expected direct costs associated with melanoma., Results: We can observe that 0 and I stage, despite accounting for a huge percentage of new melanoma cases are characterized by a small percentage of the total costs. Stage III can be considered as the most expensive stage accounting for 54% of the total costs with a 12% of patients. Finally, the stage IV patients, although very few accounts for almost the 7% of the total costs. Regarding the cost-consequence analysis, it was estimated that the therapies introduced in 2016 led to an approximately 14% increase in the total costs., Conclusions: Modeling a clinical pathway with a high level of detail enables to identify the main sources of spending. The consequent analysis can thus help policymakers to plan the future resources allocation.

Buckwheat (Fagopyrum spp.) is a "pseudo-cereal" of great interest in the production of healthy foods since its flour, derived from achenes, is enriched with bioactive compounds and, due to the absence of gluten, may be used in composition of celiac diets. Amongst buckwheat species, F. tataricum achenes possess a larger amount of the antioxidant flavenol rutin than the common buckwheat F. esculentum. Ongoing climate change may favor plant susceptibility to the attack by pathogenic, often mycotoxigenic, fungi with consequent increase of mycotoxins in previously unexploited feeds and foodstuffs. In particular, Aspergillus flavus, under suitable environmental conditions such as those currently occurring in Italy, may produce aflatoxin B1 (AFB1), the most carcinogenic compound of fungal origin which is classified by IARC as Category 1. In this study, the viable achenes of two buckwheat species, F. tataricum (var. Golden) and F. esculentum (var. Aelita) were inoculated with an AFB1-producing A. flavus NRRL 3357 to analyze their relative performances against fungal invasion and toxin contamination. Notably, we sought the existence of a correlation between the amount of tocols/flavonols in the achenes of buckwheat, infected and non-infected with A. flavus, and to analyze the ability of the pathogen to grow and produce toxin during achene infection. Results suggest that achenes of F. tataricum, the best producer of antioxidant compounds in this study, are less susceptible to A. flavus infection and consequently, but not proportionally, to mycotoxin contamination compared with F. esculentum. Moreover, rutin-derived quercetin appears to be more efficient in inhibiting aflatoxin biosynthesis than the parent compound., (Copyright © 2014 Elsevier B.V. All rights reserved.)