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Epithelioid fibrous histiocytoma (EFH) is a distinctive cutaneous neoplasm with a relatively variable morphological appearance. Recently, it has been shown that this tumor is molecularly characterized by ALK gene fusions. We report three EFHs with unusual histological presentation represented by a prominent/predominant spindle cell proliferation arranged in a variably storiform/whirling architectural pattern with or without stromal sclerosis. One of the cases closely resembled cellular fibrous histiocytoma. All three cases were immunohistochemically ALK-positive and were analyzed for ALK gene rearrangements using a next-generation sequencing-based assay (FusionPlex Sarcoma Kit, ArcherDx). Three novel fusions, namely AP3D1::ALK, COL1A::ALK, and LRRFIP2::ALK, were detected and further confirmed by FISH in all 3 cases and RT-PCR in 1 case. All patients were elderly (62-63 years) and presented with a solitary polypoid lesion on the extremities. The awareness of these morphological variants is important since it entertains a wide and slightly different differential diagnosis than conventional EFH. We also presented evidence that a clear separation of EFH from BFH in all cases may not be as straightforward as previously thought. The consistent ALK immunoexpression and the continually expanding scale of ALK gene rearrangements provide a useful tool to distinguish EFH from its histologic mimics.

Main subtypes of cutaneous lupus erythematosus are represented by acute, subacute cutaneous, intermittent and chronic cutaneous lupus erythematosus. Discoid lupus erythematosus represents the most common phenotype of chronic cutaneous lupus erythematosus. The spectrum of clinical manifestations mirrors that of several and distinct histopathological features. Such variability among different CLE subtypes is also observed at dermoscopy. Dermoscopy is nowadays considered an additional valuable method for skin lesions assessment in general dermatology, following and completing the well-known clinical diagnostic steps, such as medical history and clinical examination. In vivo reflectance confocal microscopy (RCM) is a non-invasive imaging tool able to assess the epidermis and upper dermis producing high resolution (horizontal ∼1.25 μm, vertical ∼5 μm), en face tissue sections used for melanocytic and inflammatory evaluation. In this study, we reported dermoscopic and RCM features about 9 patients affected by subacute and chronic lupus erythematosus retrospectively analyzed.

BRCA1-associated protein (BAP1)-inactivated melanocytic tumor (BIMT) is a group of epithelioid melanocytic neoplasms characterized by the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21. They occur sporadically or in the setting of an autosomal-dominant cancer susceptibility syndrome that predisposes to the development of different internal malignancies. Most of these cutaneous lesions are associated with a BRAF-mutated melanocytic nevus and therefore are included in the group of combined nevi in the last WHO classification of skin tumors. Apart from a BRAF mutation, an NRAS mutation has been reported in rare cases, whereas in some lesions no driver mutation has been detected. Here, we report 2 cases of BIMTs with a BAP1 mutation and a RAF1 fusion. Both lesions proved to be BRAF and NRAS wild type and were associated with a conventional melanocytic nevus with dysplastic junctional features. We suggest that RAF1 fusions can represent an underlying driver genetic event in these cases. Our study extends the morphological and molecular spectrum in BIMTs.

International audience; To identify whether EU certified food – here organic and geographical indications – is more sustainable than a conventional reference, we developed 25 indicators covering the three sustainability pillars. Original data was collected on 52 products at farm, processing and retail levels, allowing the estimation of circa 2000 indicator values. Most strikingly, we show that, in our sample, certified food outperforms its non-certified reference on most economic and social indicators. On major environmental indicators – carbon and water footprint – their performance is similar. Although certified food is 61% more expensive, the extra-performance per euro is similar to classical policy interventions to improve diet sustainability such as subsidies or taxes. Cumulatively, our findings legitimate the recent initiatives by standards to cover broader sustainability aspects.

BAP1-inactivated melanocytic tumor (BIMT) is a group of melanocytic neoplasms with epithelioid cell morphology molecularly characterized by the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21, and a mutually exclusive mitogenic driver mutation, more commonly BRAF. BIMTs can occur as a sporadic lesion or, less commonly, in the setting of an autosomal dominant cancer susceptibility syndrome caused by a BAP1 germline inactivating mutation. Owing to the frequent identification of remnants of a conventional nevus, BIMTs are currently classified within the group of combined melanocytic nevi. "Pure" lesions can also be observed. We studied 50 BIMTs from 36 patients. Most lesions were composed of epithelioid melanocytes of varying size and shapes, resulting extreme cytomorphological heterogeneity. Several distinctive morphological variants of multinucleated/giant cells were identified. Some hitherto underrecognized microscopic features, especially regarding nuclear characteristics included nuclear blebbing, nuclear budding, micronuclei, shadow nuclei, peculiar cytoplasmic projections (ant-bear cells) often containing micronuclei and cell-in-cell structures (entosis). In addition, there were mixed nests of conventional and BAP1-inactivated melanocytes and squeezed remnants of the original nevus. Of the 26 lesions studied, 24 yielded a BRAF mutation, while in the remaining two cases there was a RAF1 fusion. BAP1 biallelic and singe allele mutations were found in 4/22 and 16/24 neoplasms, respectively. In five patients, there was a BAP1 germline mutation. Six novel, previously unreported BAP1 mutations have been identified. BAP1 heterozygous loss was detected in 11/22 lesions. Fluorescence in situ hybridization for copy number changes revealed a related amplification of both RREB1 and MYC genes in one tumor, whereas the remaining 20 lesions studied were negative; no TERT-p mutation was found in 14 studied neoplasms. Tetraploidy was identified in 5/21 BIMTs. Of the 21 patients with available follow-up, only one child had a locoregional lymph node metastasis. Our results support a progression of BIMTs from a conventional BRAF mutated in which the original nevus is gradually replaced by epithelioid BAP1-inactivated melanocytes. Some features suggest more complex underlying pathophysiological events that need to be elucidated.

Basal cell carcinoma (BCC) is the most common skin cancer, and it can be easily treated by surgery or by various other physical modalities and topical chemotherapy. For metastatic, locally advanced BCC and for cancers that cannot be removed by surgery, systemic drugs known as hedgehog pathway blocker are used. High-frequency ultrasound (HFUS) is a non- invasive technique used in diagnosis of some skin cancers. It has proven potentially useful for BCC management. In this study we used high frequency ultrasounds to evaluate BCCs' thickness and the correlation with dermoscopic features.We examined 86 basal cell carcinomas with dermoscopy and with high-frequency ultrasound. The main patterns identified by ultrasound were linear, ellipsoid and non-specific or undefined. Patients were divided by sex and age. The BCCs were grouped by anatomic location. Finally, we recorded specific dermoscopic features of BCCs noting their presence/absence in lesions overall and in each of four quadrants. Then the lesions were excised, and histological examination was made with definition of tumor thickness (in mm).In our study, two main echographic patterns were described: linear, associated with superficial BCC, and ellipsoid, found primarily in nodular variants. However, a small percentage of lesions have otherwise non-specific patterns. We observed a significant correlation between echographic tumor thickness and histotype. We observed high concordance between histological tumor thickness and ultrasounds. Also, dermoscopic criteria as large branching and blue ovoid nests were significantly associated with heightened histologic and echographic assessments of tumor thickness.Our study confirmed the utility of ultrasound in the diagnosis of BCCs and for the first time we have correlated ultrasounds' patterns with dermoscopy and tumor thickness.

Spitz tumors represent a heterogeneous group of melanocytic neoplasms with a spectrum of biological behavior ranging from benign (Spitz nevus) to malignant (spitzoid melanoma). Prediction of the behavior of these lesions based on their histological presentation is not always possible. Recently, mutually exclusive activating kinase fusions, involving ALK, NTRK1, NTRK3, RET, MET, ROS1, and BRAF, have been found in a subset of spitzoid lesions. Some of these genetic alterations were associated with specific morphological features. Here, we report the histological presentation of 6 Spitz tumors with ROS1 fusion. The age of the patients ranged from 6 to 34 years, with strong female prevalence (5:1). All neoplasms were compound melanocytic proliferations with a predominant dermal growth but a conspicuous junctional component displaying atypical microscopic features qualifying them as atypical Spitz tumor. FIP1L1 and CAPRIN1 were identified as 2 novel 5'-fusion partners of ROS1 along with the known PWWP2A-ROS1 fusion. FISH for copy number changes of 9p21, 6p25, and 11q13 was negative in all but 1 neoplasm harboring isolated gain of 8q24. TERT-promoter hotspot mutation analysis was negative in all tumors. All patients are disease-free after a mean follow-up period of 30 months. It is concluded that ROS1-fused spitzoid neoplasms seem to have no distinctive histopathological features although consistent findings were spindled melanocytes arranged in confluent whorling nests, prominent transepidermal elimination of melanocytic nests, and myxoid/mucinous changes.

Food quality schemes (FQS: organic and geographical indication products) are often supposed to be more sustainable by their political advocates. We explore the social sustainability advantage of FQS through the lens of supply chains’ bargaining power (BP) distribution. We propose an indicator synthesizing different sources underlying BP (competition-based, transactional, institutional) and counting two dimensions (fair BP distribution and adaptation capacity), that we apply to 18 FQS supply chains and corresponding reference. FQS perform better than their reference products on both dimensions. This better performance is due to a combination of sources. Objectius de Desenvolupament Sostenible::12 - Producció i Consum Responsables

The carbon and land footprint of 26 certified food products – geographical indications and organic products and their conventional references are assessed. This assessment goes beyond existing literature by (1) designing a calculation method fit for the comparison between certified food and conventional production, (2) using the same calculation method and parameters for 52 products – 26 Food Quality Schemes and their reference products – to allow for a meaningful comparison, (3) transparently documenting this calculation method and opening access to the detailed results and the underlying data, and (4) providing the first assessment of the carbon and land footprint of geographical indications. The method used is Life Cycle Assessment, largely relying on the Cool Farm Tool for the impact assessment. The most common indicator of climate impact, the carbon footprint expressed per ton of product, is not significantly different between certified foods and their reference products. The only exception to this pattern are vegetal organic products, whose carbon footprint is 16% lower. This is because the decrease in greenhouse gas emissions from the absence of mineral fertilizers is never fully offset by the associated lower yield. The climate impact of certified food per hectare is however 26% than their reference and their land footprint is logically 24% higher. Technical specifications directly or indirectly inducing a lower use of mineral fertilizers are a key driver of this pattern. So is yield, which depends both on terroir and farming practices. Overall, this assessment reinforces the quality policy of the European Union: promoting certified food is not inconsistent with mitigating climate change.

Lentigo maligna (LM) is usually diagnosed in sun-damaged skin of elderly patients and a correct excision of the lesion determines a complete healing from the disease. LM is very rare in young patients and, for this reason, it can be commonly misdiagnosed. We describe the case of a locally recurrent LM in a 19-year-old male patient, which initially arose at the age of 17 years. In order to avoid diagnostic pitfalls, clinicians have to put more emphasis on diseases which previously were prerogative only of elderly patients and that now could begin to engage a younger age, according to climate and behavior changes.

The dataset Sustainability performance of certified and non-certified food (https://www.doi.org/10.15454/OP51SJ) contains 25 indicators of economic, environmental, and social performance, estimated for 27 certified food value chains and their 27 conventional reference products. The indicators are estimated at different levels of the value chain: farm level, processing level, and retail level. It also contains the raw data based on which the indicators are estimated, its source, and the completed spreadsheet calculators for the following indicators: carbon footprint and food miles. This article describes the common method and indicators used to collect data for the twenty-seven certified products and their conventional counterparts. It presents the assumptions and choices, the process of data collection, and the indicator estimation methods designed to assess the three sustainability dimensions within a reasonable time constraint. That is: three person-months for each food quality scheme and its non-certified reference product. Several prioritisations were set regarding data collection (indicator, variable, value chain level) together with a level of representativeness specific to each variable and product type (country and sector). Technical details on how relatively common variables (e.g., number of animals per hectare) are combined into indicators (e.g., carbon footprint) are provided in the full documentation of the dataset.

Water Footprint (WF, henceforth) is an indicator of water consumption and has taken ground to assess the impact of agricultural production processes over freshwater. The focus of this study was contrasting non-conventional, certified products with identical products obtained through conventional production schemes (REF, henceforth) using WF as a measure of their pressure on water resources. The aim was to the show whether products that are certified as Food Quality Schemes (FQS, henceforth) could also incorporate the lower impact on water among their quality features. To perform this comparison, we analysed 23 products selected among Organic, PDO and PGI as FQS, and their conventional counterparts. By restricting the domain of analysis to the on-farm phase of the production chain, we obtained that that no significant differences emerged between the FQS and REF products. However, if the impact is measured per unit area rather than per unit product, FQS showed a significant reduction in water demand. Objectius de Desenvolupament Sostenible::12 - Producció i Consum Responsables

This article addresses the issue of the profitability of Food Quality Scheme (FQS) products as compared to reference products, which are defined as analogous products without quality label. We approach this question by taking into account the level of the value chain (upstream, processing, and downstream), the sector (vegetal, animal, seafood) and the type of FQS (PGI, PDO, Organic). We collected original data for several products produced in selected European countries, as well as in Thailand and Vietnam. Comparisons depending on value chain level, sector and FQS are possible by using two comparable indicators: price premium and net price premium (including cost differential). The following principal conclusions were reached: 1) Price is higher for FQS products than for the reference products, regardless of the production level, the type of FQS or the sector; 2) Price premiums generated by FQS do not differ along the value chain, nor between sectors (vegetal, animal or seafood/fish); 3) Price premium for organic products is significantly higher than for PGI products, and this conclusion holds at upstream and processing levels, taking into account the costs directly related to production; 4) All organic products and almost all PDO and PGI products analysed benefit from a positive quality rent; 5) At upstream level and processing level, the relative weight of intermediate consumption in the cost structure is lower for organic products than for reference products. Objectius de Desenvolupament Sostenible::12 - Producció i Consum Responsables

In this paper, we test to what extent Food Quality Schemes (FQS, including Geographical Indications and organic products) contribute to the social and economic sustainability of farmers and regions through employment and education. Through employment, FQS may counter the urban migration trend affecting rural regions, and help retain economic and social capital in the local region. Indeed, as FQS are often small and specialised sectors, the economic inefficiency of such businesses may translated into greater employment and social sustainability. Separately , by requiring a higher-level of quality and hence skills, FQS may encourage greater local educational attainment or skilled immigration. To test these propositions , we analyse the employment and educational outcomes of 25 FQS. Our results show that the FQS products examined have a 13% higher labour usage (labour-to-production ratio) compared to reference products, indicating that they provide greater employment. Additionally, wage levels are 32% higher in FQS compared to references. Despite providing greater employment and higher wages, profitability of FQS (i.e. how much turnover/profit is generated per employee) is nevertheless 32% higher for FQS compared to reference products, due to the ability to attract higher product prices. Finally, there is no clear link between FQS and greater (or lower) education attainment in the supply chain. Overall, our results suggest that FQS can provide a strong contribution to local employment, employee income and business profits, strengthening the social and economic sustainability of producers and regions.; Dans cet article, nous testons dans quelle mesure les systèmes de qualité alimentaire (FQS, y compris les indications géographiques et les produits biologiques) contribuent à la durabilité sociale et économique des agriculteurs et des régions grâce à l'emploi et à l'éducation. Grâce à l'emploi, le FQS peut contrer la tendance à la migration urbaine qui affecte les régions rurales et aider à conserver le capital économique et social dans la région locale. En effet, comme les FQS sont souvent des secteurs restreints et spécialisés, l'inefficacité économique de ces entreprises peut se traduire par un meilleur emploi et une plus grande durabilité sociale. Par ailleurs, en exigeant un niveau plus élevé de qualité et donc de compétences, le FQS peut encourager un meilleur niveau de scolarité local ou une immigration qualifiée. Pour tester ces propositions, nous analysons les résultats en matière d'emploi et d'éducation de 25 FQS. Nos résultats montrent que les produits FQS examinés ont une utilisation de la main-d'œuvre (rapport travail-production) de 13% plus élevée que les produits de référence, ce qui indique qu'ils fournissent un plus grand emploi. De plus, les niveaux de salaire sont 32% plus élevés dans FQS que dans les références. Malgré un meilleur emploi et des salaires plus élevés, la rentabilité du FQS (c'est-à-dire le chiffre d'affaires / bénéfice généré par employé) est néanmoins 32% plus élevée pour FQS que pour les produits de référence, en raison de la capacité d'attirer des prix de produits plus élevés. Enfin, il n'y a pas de lien clair entre le FQS et un niveau d'éducation supérieur (ou inférieur) dans la chaîne d'approvisionnement. Dans l'ensemble, nos résultats suggèrent que FQS peut apporter une forte contribution à l'emploi local, aux revenus des employés et aux bénéfices des entreprises, renforçant ainsi la durabilité sociale et économique des producteurs et des régions.

Improving the eco-efficiency of food systems is one of the major global challenges faced by the modern world. Short food supply chains (SFSCs) are commonly regarded to be less harmful to the environment, among various reasons, due to their organizational distribution and thus the shortened physical distance between primary producers and final consumers. In this paper, we empirically test this hypothesis, by assessing and comparing the environmental impacts of short and long food supply chains. Based on the Life Cycle Assessment (LCA) approach, we calculate eco-efficiency indicators for nine types of food distribution chains. The analysis is performed on a sample of 428 short and long food supply chains from six European countries. Our results indicate that, on average, long food supply chains may generate less negative environmental impacts than short chains (in terms of fossil fuel energy consumption, pollution, and GHG emissions) per kg of a given product. The values of eco-efficiency indicators display a large variability across analyzed chains, and especially across different types of SFSCs. The analysis shows that the environmental impacts of the food distribution process are not only determined by the geographical distance between producer and consumer, but depend on numerous factors, including the supply chain infrastructure. This research received funding from the European Union’s Horizon 2020 research and innovation program STRENGTH2FOOD under grant agreement no. 678024 and title: “Strengthening European Food Chain Sustainability by Quality and Procurement Policy”.

En coup de sabre morphea is a clinical variant of morphea, presenting as a linear depressed, atrophic area in the paramedian forehead or the frontoparietal scalp, resembling a stroke from a sword. It affects the skin and subcutaneous connective tissues, with possible extension to the underlying musculature, cartilage, and bone and variable association with neurologic symptoms. A 50-year-old woman presented to our clinic for evaluation of an atrophic lesion on her forehead and scalp appearing 1 year before, progressively extending over time. An alopecic atrophic area involving the skin and subcutaneous tissues of her right forehead and scalp arranged in a linear fashion with an “en coup de sabre” appearance was observed in relation with hair loss in the affected area. Reflectance confocal microscopy showed marked hyperreflective areas with severe eccrine gland atrophy. All sebaceous glands had disappeared, with sporadic follicular persistence reduction. Histopathological examination of a punch biopsy specimen taken from a central parietal alopecic area was consistent with a diagnosis of morphea. To our knowledge, this is the first report regarding the use of reflectance confocal microscopy as an ancillary diagnostic technique in linear localized morphea of the scalp and face. This noninvasive technique may represent a useful tool in distinguishing between early stages of the disease, with prevalence of inflammatory lymphocytic infiltrate, and late stages characterized by more prominent sclerosis with mild or absent signs of inflammation.

Increasingly, policymakers are setting ambitious goals for sustainability in public procurement, integrated across different pillars. Such ambitions are apparent in public catering services, where procurement models have been shifting towards greater localisation of supply chains and purchasing of more organically grown food. To date however, few studies have examined empirically what the impacts of different procurement models are across these multiple pillars of sustainability. This research aimed to fill the gap, by measuring and comparing the environmental, economic and nutritional outcomes of different models of school meals procurement. Case studies were undertaken of ten primary school meals services in five European countries, capturing different procurement model types. Results showed carbon emissions ranged from 0.95 kgs CO2e per meal in the lowest case to 2.41 kgs CO2e in the highest case, with adoption of low carbon food waste disposal methods and reduction of the amount of ruminant meat in the menus being the most important actions for lowering emissions. In terms of economic impact, local economic multiplier ratios ranged from 1.59 to 2.46, and although the level of local food sourcing contributed to these ratios, the effect was eclipsed, in some cases, by investment in local catering staff. Meanwhile, implementation of a robust standards regime and improving canteen environment and supervision were the most important actions for nutritional quality and intake. The paper discusses the implications of the findings for integrated, sustainable models of food procurement.

Pigmented epithelioid melanocytoma is a highly pigmented, predominantly dermal melanocytic neoplasm composed by epithelioid and spindled melanocytes. It is characterized by a limited number of specific genomic alterations principally involving protein kinase A regulatory subunit alpha (PRKAR1A) and fusion of protein kinase C alpha isoform (PRKCA). However, in some of these neoplasms, no genetic aberrations have been detected. We performed genomic analysis of a nodular heavily pigmented intradermal proliferation composed of monomorphic epithelioid melanocytes with slight cytologic atypia consisting with pigmented epithelioid melanocytoma occurring on the vulva of a 24-year-old woman. A novel fusion transcript HTT-PKN1 and an ATM (Val410Ala) missense mutation were found. No other mutations including TERT-promoter hotspot mutation analysis were detected. The data expand the spectrum of molecular alterations in pigmented epithelioid melanocytoma.

The key role of diet in both human health and environmental sustainability is well known. However, there is a lack of studies investigating the environmental impact of children&rsquo, s dietary behavior. The aim of this observational study was to investigate the dietary environmental impact in a sample of primary school children living in Parma (Italy, n = 172, 8&ndash, 10 years), in relation to their adherence to the Mediterranean diet (MD). Children completed a 3-day food record in both winter and spring. Dietary records were processed to obtain: (i) adherence to the MD and (ii) mean daily carbon and ecological footprints. Adherence to the MD was similar in winter and spring, with almost half of the participants showing a medium MD score. Carbon and ecological footprints were higher during winter, and the main dietary contributors were red and processed meat for both indexes. A small positive correlation was observed between adherence to the MD and total carbon and ecological footprints. This study provided the first analysis of the relationship between adherence to the MD and environmental impact of primary school children. Further research is needed to better investigate the environmental impact of primary school children&rsquo, s diet and the possible relationship between the MD and environmental sustainability.

The ultraviolet (UV) component of solar radiation is the major driving force of skin carcinogenesis. Most of studies on UV carcinogenesis actually focus on DNA damage while their proteome-damaging ability and its contribution to skin carcinogenesis have remained largely underexplored. A redox proteomic analysis of oxidized proteins in solar-induced neoplastic skin lesion and perilesional areas has been conducted showing that the protein oxidative burden mostly concerns a selected number of proteins participating to a defined set of functions, namely: chaperoning and stress response, protein folding/refolding and protein quality control, proteasomal function, DNA damage repair, protein- and vesicle-trafficking, cell architecture, adhesion/extra-cellular matrix (ECM) interaction, proliferation/oncosuppression, apoptosis/survival, all of them ultimately concurring either to structural damage repair or to damage detoxication and stress response. In peri-neoplastic areas the oxidative alterations are conducive to the persistence of genetic alterations, dysfunctional apoptosis surveillance, and a disrupted extracellular environment, thus creating the condition for transformant clones to establish, expand and progress. A comparatively lower burden of oxidative damage is observed in neoplastic areas. Such a finding can reflect an adaptive selection of best fitting clones to the sharply pro-oxidant neoplastic environment. In this context the DNA damage response appears severely perturbed, thus sustaining an increased genomic instability and an accelerated rate of neoplastic evolution. In conclusion UV radiation, in addition to being a cancer-initiating agent, can act, through protein oxidation, as a cancer-promoting agent and as an inducer of genomic instability concurring with the neoplastic progression of established lesions.

BACKGROUND Second primary melanomas (SPMs) are new developed primary melanomas occurring in a subset of patients affected by BRAF-mutated metastatic melanoma during treatment with BRAF-inhibitors. A drug-induced paradoxical activation of mitogen-activated protein kinase (MAPK) signaling pathway in BRAF-wild type/RAS-mutated cells have been proposed as a possible molecular mechanism but data on the mutational status of SPMs are lacking. In order to better understand genetic alterations affecting the biological mechanism of SPMs, we performed a personalized and targeted next-generation sequencing analysis of a patient affected by metastatic melanoma who developed multiple SPMs during treatment with encorafenib (LGX818). METHODS Using a cancer panel of 50 genes for solid tumors enriched with a custom panel of 10 genes specifically involved in melanoma pathogenesis, we analyzed the primary melanoma, two SPMs, one benign compound nevus and the normal DNA extracted from blood lymphocytes of the patient. RESULTS We identified HRAS Q61 somatic mutation in one SPM developed in a pre-existing nevus. In the primary melanoma, besides the BRAF mutation, we identified the clinically actionable IDH1 R132C somatic mutation. Both SPMs were BRAF wild type. The patient harbors the recently recognized pathogenetic germline variant KDR Q472. We observed that mutations detected in tumor samples involving genes related to melanoma pathogenesis (TP53, PIK3CA, FGFR3, ATF1, KIT, HRAS and MAP2K2) were present in heterozygosis in the germline status of the patient. CONCLUSIONS Our results support the paradoxical mechanism of MAPK pathway for SPMs under BRAF inhibitors. Moreover, they suggest that targeted mutational assessment based on matching somatic and germline analysis represent a promising approach to detect the neoplastic landscape of the tumor and to identify most accurate treatment in metastatic melanoma patient.

We report a case of a polypoid atypical Spitz tumor with a prominent fibrosclerotic stromal component, harboring a CLIP2-BRAF fusion, which has hitherto been not reported in melanocytic lesions. The neoplasm occurred in a 78-year-old male patient and appeared microscopically as a predominantly dermal, barely symmetrical, polypoid lesion composed mainly of epithelioid cells showing moderate degree of nuclear pleomorphism with ample amphophilic cytoplasm arranged in nests, fascicles, or single units. The mitotic rate was 2/mm, and the mitoses were confined to the upper portion of the lesion. The Breslow thickness was 2.3 mm. The stroma contained conspicuous plumped fibroblasts and thickened collagen bundles associated with dilated medium-sized vessels. Focally, sclerotic areas were found. A moderately dense, lymphocyte-predominant inflammatory infiltrate scattered through the whole lesion was seen. Despite strong nuclear and cytoplasmic positivity of p16, FISH revealed homozygous loss in locus 9p21. A CLIP2-BRAF fusion was found by next-generation sequencing. No other genetic alterations including a TERT-promoter mutation was found. The patient is disease-free without recurrence or evidence of metastatic disease after 5 years and 2 months of follow-up.

Agriculture contributes significantly to greenhouse gas (GHG) emissions, accounting for more than 10% of total CO 2 emissions in the EU-28 area. The Common Agricultural Policy (CAP) plays an important role in promoting environmentally and climate friendly practices and needs to respond to the new environmental challenges by better integrating its objectives with other EU policies. In this respect, the recent CAP reform 2014–2020 made a further step, making a large part of direct payments conditional on new agricultural practices beneficial for the climate and the environment, i.e. “greening”. In this study we estimate the potential environmental benefits from greening in terms of GHG emissions in four regions of Northern Italy, one of the major European agricultural areas in terms of emissions. The emissions were quantified and broken down into the three main GHGs (carbon dioxide, methane and nitrous oxide) per production process. This information was subsequently used in a Positive Mathematical Programming (PMP) farm-based model on more than 3,000 farms, to estimate the effects of greening on regional land use and its contribution in reducing the total emissions. The new agri-environmental constraints produce a modest abatement of total emissions of greenhouse gases (− 1.5%) in the analyzed area. The model estimates a reduction in CO 2 emissions of about 2%. Emissions from nitrous oxide show a decrease of 2.1% and the reduction in the methane is about 0.4% compared to the observed scenario. The process of “lightening” that affected the greening during the CAP negotiation has inevitably resulted in missing an opportunity to introduce a significant positive change of behaviour into agriculture, in line with the expectations and needs of society for EU agriculture as a provider of public goods.

Foods consumed and dietary patterns are strong determinants of health status. Diet and nutrition have a key role in health promotion and maintenance during the entire lifetime, but what we choose to eat and drink greatly affects the environmental impact on ecosystems as well as monetary resources. Some studies suggest that a healthy diet with a low environmental impact is not necessarily more expensive. This paper aims to identify a healthy, greener and cheaper diet based on current consumption patterns. Dietary information was collected from 104 young adults in the last year of high school in Parma (Italy). Diet was monitored with 7-day dietary records. Subsequently, food items were decoded to obtain nutritional, economic and environmental impact data. An optimization tool based on mathematical programming (Multi-Objective Linear Programming) was used to identify sustainable diet. Three different 7-day diets were identified, based on nutrition recommendations for the healthy Italian adult population, characterized by different targets and optimizing different impacts: first the diet at the lowest cost (Minimum Cost Diet - MCD), then the Environmentally Sustainable Diet (ESD) obtained by minimizing the three environmental indicators (CO2e emissions, H2O consumption and amount of land to regenerate the resources - m(2)). Finally, the Sustainable Diet (SD) was identified by integrating environmental and economic sustainability objectives. Lastly, suggestions and recommendations for communication campaigns and other interventions to achieve sustainable diet are suggested.

Multiple myeloma patients may develop extraosseous involvement in the course of the disease making prognosis very poor and new drugs clearly needed. The PD-1/PD-L1 axis has emerged as a master immune checkpoint in antitumor responses and recent studies investigated the role of PD-L1 in multiple myeloma cells; no data however are still available about PD-L1 expression in extramedullary localizations. We demonstrate PD-L1 expression in 4/12 cases of extraosseous myeloma suggesting that these lesions represent a specialized microenvironment. We found presence of PD-1+ infiltrating lymphocytes in all observed cases supporting the relevance of PD-1/PD-L1 checkpoint in extramedullary myeloma. We also investigated the correlation in PD1/PD-L1 staining between marrow staining and EMP lesions.

The objective of this paper was to test whether investing activity in the futures markets of different commodities (grains, sugar, coffee, cotton, cocoa, livestock) could be identified as a source of the increasing level and volatility of agricultural commodity prices. The causal link between trading activity and market factors (returns, volatility) can be investigated using weekly data, usually derived from the Commitment of Traders Reports released by the US Commodity Futures Trading Commission (CFTC), or daily data expressed as the ratio of volume to open interest (VOIR). To increase the power of the estimation process and investigate the role of causal variables to determine the trends of all the market factors, the authors tested the estimates obtained by seemingly unrelated regression (SUR). One innovation is represented by the evaluation of the inverse relationships between market factors and causal variables. The market factors were also tested as causal variables, avoiding giving priority to only one part of the relationship according to Granger's causality. The lack of significance revealed by the Granger causality test on weekly models could be due to the inappropriate frequency of the information. The ratio of volume to open interest in futures contracts performs better than other parameters extensively adopted in the literature. The likely reason is that it depends on the daily frequency of this parameter, which provides statistical evidence of phenomena that include their effect in weekly intervals. The estimations for the daily model provide statistical evidence of a mutual relationship only between trading activity and realized volatility. No causal relationships were found for returns. The behaviour of all 12 futures markets examined is quite similar and uniform with respect to the scale of the coefficients and their temporal profile.