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Desmoplastic melanoma accounts for 5% of all cases of melanoma, but its diagnosis can be difficult due to its frequent clinical presentation with amelanotic lesions. Histologically, spindled melanocytes surrounded by a collagenous stroma are observed. Compared with other types of melanoma, the desmoplastic types presents greater local aggression, and is more prone to local recurrence, but has a lower risk of lymph node metastasis. Early detection, accurate staging, and proper surgical management are the main factors associated with higher survival rates in melanoma patients. Reflectance confocal microscopy (RCM) has proven to be a valuable imaging tool in the diagnosis of skin neoplasms, being useful for orientating practitioners towards the diagnosis of melanoma and indicating the necessity of performing a diagnostic biopsy. We present the case of 52-year-old woman, who presented to the dermatology department with an irregular, dark-colored plaque in the right deltoid region. Dermoscopy showed asymmetry with an atypical network and some areas of regression. RCM revealed pagetoid cells in the upper epidermis, cell atypia, non-edged papillae, dermal inflammation, and nucleated cells in the dermis, which are highly suggestive of melanoma. A biopsy was also performed. A histopathology exam confirmed the diagnosis of superficially spreading melanoma with a desmoplastic component, and revealed a Breslow index of 0.9 mm, Clark level IV, an absence of mitoses, angiolymphatic invasion and regression, and complete excision. The CT and PET-CT scans were negative. A biopsy of the axillary sentinel lymph node was conducted, with a negative result obtained, establishing the IB stage of the disease. The patient will remain under follow-up to look for a recurrence or a new primary melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Actinic keratoses are lesions with a variable potential for malignant transformation, but with a difficult predictability of evolution towards this type of lesions. Non-invasive skin imaging methods represent diagnostic tools that allow a better evaluation of actinic keratoses lesions, as well as the establishment of a diagnosis with greater specificity and sensitivity. This review aims to identify all skin imaging methods that are useful in the diagnosis and monitoring of the treatment of actinic keratoses, as well as to identify those lesions at risk of transforming into squamous cell carcinoma. Non-melanocytic skin cancers represent an important public health problem due to the increasing incidence and the important local destructive potential. Thus, the early diagnosis and treatment of precancerous lesions (actinic keratoses) is a priority for the dermatologist. In recent years, non-invasive skin imaging methods have seen an important development, moving from simple observational methods used in clinical research, to true diagnostic and treatment methods that make the dermatologist's life easier. Given the frequency of these precancerous lesions, their location on photo-exposed areas, as well as the long treatment periods, with variable, imprecise end-points, the need to use non-invasive imaging devices is increasingly evident to complete the clinical observations in the diagnosis and treatment of these lesions, with the aim of increasing accuracy and decreasing the adverse effects due to long treatment duration. This is the first review that brings together all skin imaging methods (dermoscopy, reflectance confocal microscopy, ultrasonography, dermoscopy-guided high frequency ultrasonography, and optical coherence tomography) used in the evaluation of actinic keratoses and their response to different treatment regimens. [ABSTRACT FROM AUTHOR]

The debate regarding the willingness of enterprises to use transfer pricing for tax optimization is one with significant history (the first OECD report on transfer pricing dates from 1979). In the last fifteen years, this topic gained great traction as globalization became a key word in all economic undertakings. In 2013 the OECD/G20 officially launched the BEPS project, aimed at identifying and closing any loopholes present in the taxation system used by companies to optimize their tax burden. The work was finalized in 2015 by issuing the BEPS Package. However, the fight against base erosion and profit shifting did not end, as the OECD/G20 periodically monitors how the measures are implemented. Considering the importance of the IT sector in Romania, it is significant to investigate if the BEPS Package is an efficient tool in helping Romanian tax authorities prevent aggressive tax optimization in this industry. To provide a tentative answer, a statistical analysis was performed, aimed at comparing the profitability of related and non-related Romanian IT companies. Although the BEPS Package is not the only factor influencing the behavior of taxpayers, the work of OECD/G20 is one of the main forces shaping the Romanian taxation environment. Following the analysis, no significant differences were identified between the profitability of related and non-related companies, leading to the conclusion that local taxpayers are not inclined to engage in aggressive tax optimization, which is also a consequence of the way in which the legislation was drafted, influenced by the BEPS Package. [ABSTRACT FROM AUTHOR]

Iron dysmetabolism affects a great proportion of heart failure patients, while chronic hypertension is one of the most common risk factors for heart failure and death in industrialized countries. Serum data from reduced ejection fraction heart failure patients show a relative or absolute iron deficiency, whereas cellular myocardial analyses field equivocal data. An observed increase in organellar iron deposits was incriminated to cause reactive oxygen species formation, lipid peroxidation, and cell death. Therefore, we studied the effects of iron chelation on a rat model of cardiac hypertrophy. Suprarenal abdominal aortic constriction was achieved surgically, with a period of nine weeks to accommodate the development of chronic pressure overload. Next, deferiprone (100 mg/kg/day), a lipid-permeable iron chelator, was administered for two weeks. Pressure overload resulted in increased inflammation, fibrotic remodeling, lipid peroxidation, left ventricular hypertrophy and mitochondrial iron derangements. Deferiprone reduced cardiac inflammation, lipid peroxidation, mitochondrial iron levels, and hypertrophy, without affecting circulating iron levels or ejection fraction. In conclusion, metallic molecules may pose ambivalent effects within the cardiovascular system, with beneficial effects of iron redistribution, chiefly in the mitochondria. Created using www.biorender.com. [Display omitted] • Iron metabolism is an essential yet potentially dangerous micronutrient that appears to be implicated in cardiovascular diseases. • Chronic cardiac stress induced by hypertension leads to inflammation, oxidative stress, fibrosis, and iron derangements. • Iron chelation can reduce oxidative stress, inflammation, and fibrosis in chronic heart failure. [ABSTRACT FROM AUTHOR]

Bowenoid papulosis is a cutaneous disease that is part of the spectrum of genital in situ carcinomas, caused primarily by infection with oncogenic strains of the HPV virus. The potential to transform into squamous cell carcinoma requires the diagnosis and treatment of the lesions. We present the case of a 34-year-old non-smoker without medical history who presented to our clinic for the appearance of multiple, asymptomatic, well-defined, flat, pigmented violaceous papules at the root of the penis in evolution for a year. Reflectance confocal microscopy (RCM) suggested the diagnosis of bowenoid papulosis, which was confirmed by histopathological examination. The treatment with Imiquimod 5% (3 times/week) and Isoprinosine (4 g/day) was initiated, followed by monitoring of the lesions by repeated RCM examination. The evolution of the patient at 6 weeks of therapy was favourable, with clinical remission of lesions and improvement in RCM aspects of the evaluated skin. In conclusion, RCM represents a useful noninvasive examination method that allows not only the diagnosis but also the follow-up of the treatment response in order to decide the appropriate length of therapy. [ABSTRACT FROM AUTHOR]

Nevus sebaceous of Jadassohn (NSJ) is a rare congenital lesion that affects the adnexal structures of the skin. It is typically located on the scalp and face of females and presents as a well-defined, slightly elevated, yellow lesion. It is also linked to a high risk of secondary tumors, which are more frequently benign than malignant. In vivo reflectance confocal microscopy (RCM) is a non-invasive imaging technique that provides a horizontal image of the skin with a resolution similar to histology. We report a case of basal cell carcinoma (BCC) developed in an NSJ with its dermoscopic, confocal, and histopathological features. A 49-year-old female presented with a well-circumscribed, 1 cm-diameter verrucous, yellowish lesion surrounded by a poorly defined, slightly erythematous, translucent plaque, located on the scalp in the temporoparietal region, which had been present since birth, grew at puberty, and changed its appearance in the last three years. Dermoscopy of the central lesion revealed yellow globules grouped into clusters, with peripheral linear and arborescent thin vessels, surrounded by several translucent nodular lesions with fine, arborizing vessels. RCM examination showed large, monomorphic cells with a hyperreflective periphery and a hyperreflective center located on the central lesion, corresponding to sebocytes, surrounded by multiple dark silhouettes lined with hyperreflective bands of thickened collagen, corresponding to tumor islands. The histopathological findings confirmed the diagnosis of BCC developed on an NJS. RCM can be a useful technique for the non-invasive examination and monitoring of these lesions, taking into account their transformation risk and preventing unnecessary excisions that might have a detrimental aesthetic impact on patients. [ABSTRACT FROM AUTHOR]

High-frequency ultrasonography (HF-USG) is a relatively new imaging method that allows the evaluation in a non-invasive manner of the skin layers and skin appendages. It is a diagnostic tool with increasing usefulness in numerous dermatological pathologies. High reproducibility, non-invasiveness and short diagnostic time make this method an increasingly used tool in dermatological practice. The subepidermal low-echogenic band is a relatively newly described parameter that seems to be a marker not only of intrinsic and extrinsic skin aging, but also of inflammatory processes taking place at the skin level. This systematic review aims to evaluate the role that SLEB has in the diagnosis and monitoring of the treatment of some inflammatory and non-inflammatory dermatological conditions, as well as its utility as a disease marker. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most common keratinocyte carcinoma and the most prevalent skin cancer in humans, worldwide. BCC is histologically characterized by the proliferation of basaloid cells, arranged in globular masses of varying size, often separated from the surrounding stroma by optically empty spaces. Although attributed to tumor retraction during tissue processing for the preparation of pathology slides, these spaces are also seen on cryostat sections. The aim of this study is to in vivo characterize amyloid and mucin deposits in primary BCC lesions through RCM, followed by histopathological correlation. We included twenty-two consecutive subjects totaling thirty-one primary BCCs. Each lesion underwent the same evaluation protocol which included: clinical and dermoscopic images, RCM imaging, excisional biopsy under local anesthesia, and histopathological examination (colloidal iron and cytokeratin 34betaE12 stains). Hypo-reflective peritumoral clefts and hyper-reflective globules were measured on RCM images and compared to mucin and amyloid deposits seen on histology slides. The mean differences between RCM and histology measurements in both mucin and amyloid were not statistically significant. There were medium and strong correlations between RCM and histology regarding mucin and amyloid deposits, respectively. [ABSTRACT FROM AUTHOR]

The mutual agreement procedure is the main instrument available to both taxpayers and tax administrations for mitigating international double taxation arising from transfer pricing adjustments. Although it may apply to cases generated by other tax topics, this article refers strictly to its application in the context of transfer pricing. Ensuring this mechanism operates as smooth as possible is one of the factors contributing to efficient cross-border economic flows of goods and services and their fair taxation, eliminating the risk for multinational groups of paying more taxes than necessary (as a result of transfer pricing adjustments performed by tax authorities). As one of the organisms promoting international cooperation and economic wellbeing, the OECD tracks the performance of member and non-member states in relation to the effective implementation of mutual agreement procedures. The process is not aimed at evaluating the results of one specific country, but rather to offer a global perspective. Through literature review as well as secondary data analysis derived from the annual reports prepared by the National Agency for Fiscal Administration in Romania and the OECD, this article aims at presenting how the Romanian tax authorities are handling mutual agreement procedure cases, as a base for future improvements. Although the Romanian tax authorities have been constantly involved during the last 7 years in solving double taxation cases through mutual agreement procedures, work is still needed in order to make the process more efficient, considering that their results are still significantly below the high-achieving countries, as presented in the OECD reports. [ABSTRACT FROM AUTHOR]

Oily, acne-prone skin is a common skin type which may be monitored in vivo using reflectance confocal microscopy (RCM). The aim of the study was to assess the feasibility of RCM in evaluating the effectiveness of a topical combination of alpha- and beta-hydroxy acids, anti-inflammatory and antibacterial molecules, and Herculane thermal water on acne-prone skin. Thirty-five subjects with oily, acne-prone skin were prescribed topical combination products and were evaluated by clinical, Wood's lamp, and RCM imaging at baseline and after 28 days. At 28 days, the RCM-evaluated number of dilated infundibula, infundibula filled with keratotic material, and infundibula with thickened bright borders, as well as the density of the inflammatory infiltrate, were significantly decreased. Wood's light images at 28 days showed a significantly reduced number of C. acnes-colonized infundibula, and both the median area and the intensity of the red-orange fluorescence were decreased. The reduction in the clinical score was concurrent with the improvement in the RCM parameters, suggesting that this non-invasive imaging technique is appropriate for efficiency evaluations of topical acne treatments. [ABSTRACT FROM AUTHOR]

Skin aging is an intricate physiological process governed by intrinsic and extrinsic factors. Increasing life expectancy has turned skin aging into a growing concern for the general population. Clinical examination of the skin does not fully describe the skin aging process. This study aims to evaluate the healthy skin of five different age groups in order to develop an easy-to-use confocal score for quantifying signs of skin aging and test the correlation between this new score and the already described clinical score, SCINEXA (score of intrinsic and extrinsic skin aging). Thirty-five subjects split into five age groups: <35; 36–45; 46–55; 56–65, and >65 years old were enrolled. Clinical signs were quantified using the SCINEXA score, and known confocal variables of skin aging were evaluated. Three different semi-quantitative scores were calculated: epidermal disarrangement score (EDS), epidermal hyperplasia score (EHS), and dermal score (DS). The EDS showed a stable trend up to the age of 65 and a dramatic increase in older subjects. EHS was characterized by an ascending trend from younger subjects to middle-aged ones. The DS was progressive with age, with a different proportion of distinct collagen types. The confocal CSIESA (confocal score for the assessment of intrinsic and extrinsic skin aging) score correlated well with the SCINEXA score. Reflectance confocal microscopy is a powerful, non-invasive technique for microscopically quantifying aging signs. [ABSTRACT FROM AUTHOR]

The active role of the judge, a fundamental principle of procedural law, is applied as varied as the personalities of the judges who administer justice are different. In relatively simple lawsuits, with a well-defined object and placed in a single demand end, the active role is limited to following a natural, predictable path. However, there are also situations in which the lawsuits have a complex object, with several claims, an object that does not, in fact, resolve the dispute, but will probably lead to another lawsuit. The tendency to emphasize formalism raises the issue of the everincreasing limitation of the judge's role. In this paper I propose to outline some of these boundaries and possible situations in which the judge, exercising his active role by possibly expanding the procedural framework, resolves the dispute and prevents a new trial. [ABSTRACT FROM AUTHOR]

Machine learning research, particularly in genomics, is often based on wide shaped datasets, i.e. datasets having a large number of features, but a small number of samples. Such configurations raise the possibility of chance influence (the increase of measured accuracy due to chance correlations) on the learning process and the evaluation results. Prior research underlined the problem of generalization of models obtained based on such data. In this paper, we investigate the influence of chance on prediction and show its significant effects on wide shaped datasets. First, we empirically demonstrate how significant the influence of chance in such datasets is by showing that prediction models trained on thousands of randomly generated datasets can achieve high accuracy. This is the case even when using cross-validation. We then provide a formal analysis of chance influence and design formal chance influence estimators based on the dataset parameters, namely its sample size, the number of features, the number of classes and the class distribution. Finally, we provide an in-depth discussion of the formal analysis including applications of the findings and recommendations on chance influence mitigation. [ABSTRACT FROM AUTHOR]

Multinucleate cell angiohistiocytoma (MCAH) is a rare, benign, vascular or fibrohistiocytic tumor usually presenting as single or multiple, reddish-brown papules mostly affecting the limbs and dorsum of the hands of middle-aged females. Since 1985, relatively few MCAH cases have been reported. In vivo reflectance confocal microscopy (RCM) findings of MCAH have never been described. We report a case of MCAH with new non-invasive imaging findings through RCM in correlation with dermoscopy and histopathology. A 66-year-old woman with an unremarkable family and personal history of an atypical nevus presented with a lesion on her right breast. It had appeared 12 months earlier and progressively enlarged. Physical examination revealed a 20 × 11.6 mm, non-tender, reddish-brown maculo-papular lesion with blurred margins. Dermoscopy showed diffusely arranged reddish areas, coalescing whitish patches, truncated and dotted vessels, and a peripheral brown reticulated pattern. RCM revealed a poorly outlined lesion with a normal honeycomb pattern, numerous vessels at the dermal–epidermal junction, and isolated, large, mildly reflective, bizarre structures with angulated edges. These findings correlated well with histological features, which established the diagnosis of MCAH. Even though histopathology remains the gold standard in the diagnosis of MCAH, non-invasive tools such as RCM can help rule out other entities, therefore reducing surgery-associated morbidity. [ABSTRACT FROM AUTHOR]

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The empirical nature of Information Retrieval (IR) mandates strong experimental practices. A keystone of such experimental practices is the Cranfield evaluation paradigm. Within this paradigm, the collection of relevance judgments has been the subject of intense scientific investigation. This is because, on one hand, consistent, precise, and numerous judgements are keys to reducing evaluation uncertainty and test collection bias; on the other hand, however, relevance judgements are costly to collect. The selection of which documents to judge for relevance, known as pooling method, has therefore a great impact on IR evaluation. In this paper we focus on the bias introduced by the pooling method, known as pool bias, which affects the reusability of test collections, in particular when building test collections with a limited budget. In this paper we formalize and evaluate a set of 22 pooling strategies based on: traditional strategies, voting systems, retrieval fusion methods, evaluation measures, and multi-armed bandit models. To do this we run a large-scale evaluation by considering a set of 9 standard TREC test collections, in which we show that the choice of the pooling strategy has significant effects on the cost needed to obtain an unbiased test collection. We also identify the least biased pooling strategy in terms of pool bias according to three IR evaluation measures: AP, NDCG, and P@10. [ABSTRACT FROM AUTHOR]

Image retrieval has been an active research domain for over 30 years and historically it has focused primarily on precision as an evaluation criterion. Similar to text retrieval, where the number of indexed documents became large and many relevant documents exist, it is of high importance to highlight diversity in the search results to provide better results for the user. The Retrieving Diverse Social Images Task of the MediaEval benchmarking campaign has addressed exactly this challenge of retrieving diverse and relevant results for the past years, specifically in the social media context. Multimodal data (e.g., images, text) was made available to the participants including metadata assigned to the images, user IDs, and precomputed visual and text descriptors. Many teams have participated in the task over the years. The large number of publications employing the data and also citations of the overview articles underline the importance of this topic. In this paper, we introduce these publicly available data resources as well as the evaluation framework, and provide an in-depth analysis of the crucial aspects of social image search diversification, such as the capabilities and the evolution of existing systems. These evaluation resources will help researchers for the coming years in analyzing aspects of multimodal image retrieval and diversity of the search results. [ABSTRACT FROM AUTHOR]

With a constantly increasing incidence, cutaneous melanoma has raised the need for a better understanding of its complex microenvironment that may further guide therapeutic options. Melanoma is a model tumor in immuno-oncology. Inflammation represents an important hallmark of cancer capable of inducing and sustaining tumor development. The inflammatory process also orchestrates the adaptative immunosuppression of tumor cells that helps them to evade immune destruction. Besides its role in proliferation, angiogenesis, and apoptosis, cyclooxygenase-2 (COX-2) is a well-known promoter of immune suppression in melanoma. COX-2 inhibitors are closely involved in this condition. This review attempts to answer two controversial questions: is COX-2 a valuable prognostic factor? Among all COX-2 inhibitors, is celecoxib a suitable adjuvant in melanoma therapy? [ABSTRACT FROM AUTHOR]

As the diagnosis determines therapy, it is important that the tumor is identified correctly. Dear Editor, Fibroepithelioma of Pinkus (FeP) is an uncommon subtype of basal cell carcinoma (BCC) with a particular growth pattern, first described by Hermann Pinkus in 1953.1 This tumor is slow growing and commonly found on the trunk or extremities of persons in the fifth and sixth decades of life.2 Although its etiopathogenesis is not fully understood, chronic ultraviolet damage seems to be a lesser factor than it is in BCC.3,4 Mutations in the PTCH gene of the Hedgehog signaling pathway could be involved in its development.5 FeP arising after radiation therapy has been reported, although a direct link is yet to be defined.6 FeP is a rare neoplasm that is often difficult to diagnose, as it simulates other skin tumors. The differential diagnosis was modified to include FeP, BCC, and seborrheic keratosis. [Extracted from the article]

Basal cell carcinoma (BCC) is the most prevalent skin cancer in the Caucasian population. A variety of different phenotypic presentations of BCC are possible. Although BCCs rarely metastasize, these tumors commonly destroy underlying tissues and should therefore be treated promptly. As vascular formation and angiogenesis are indicators of tumor development and progression, the presence of blood vessels, their morphology and architecture are important markers in skin lesions, providing critical information towards pathogenesis and diagnosis. BCC commonly lacks pigmentation, therefore it is important to emphasize the usefulness of vascular feature detection, recognition, quantification and interpretation. To answer the question of whether vascular patterns observed on dermoscopy, reflectance confocal microscopy (RCM) and histopathology might reflect the biologic behavior of BCCs, we undertook this review article. Several studies have sought, by various means, to identify vascular features associated with the more aggressive BCC phenotypes. Dermoscopic vascular pattern assessment can facilitate diagnostic discrimination between BCC subtypes, more aggressive BCCs displaying less or no pink coloration and a relative absence of central tumor vessels. RCM, a novel, non-invasive imaging technique, allows for the quantification of blood vessel size, density, and flow intensity in BCCs. BCCs are distinguished on RCM chiefly by vessels that branch and intertwine between neoplastic aggregates, a pattern strongly reflecting tumor neo-angiogenesis. The analysis of these vascular morphological and distribution patterns can provide further support in the diagnosis, assessment, or monitoring of BCCs. Histopathology shows significantly higher microvessel densities in the peritumoral stroma of BCCs, when compared to normal skin or benign tumors. This angiogenic response in the stroma is associated with local aggressiveness, therefore the quantification of peritumoralmicrovessels may further assist with tumor evaluation. How dermoscopy and RCM vascular patterns in BCC correlate with histopathological subtype and thus help in discriminating aggressive subtypes definitely deserves further investigation. [ABSTRACT FROM AUTHOR]

Confocal laser scanning microscopy (CLSM) is a modern imaging technique that enables the in vivo or ex vivo characterization of skin lesions located in the epidermis and superficial dermis with a high quasi-microscopic resolution. Currently, it is considered to be the most promising imaging tool for the evaluation of superficial skin tumors. The in vivo mode adds the advantage of noninvasive, dynamic, in real-time assessment of the tumor associated vasculature and inflammation. It offers the possibility to repeatedly examine the same skin area without causing any damage and to monitor disease progression and treatment outcome. Furthermore, this novel technology allows the evaluation of the entire lesion and can be used to guide biopsies and to define tumor margins before surgical excision or other invasive therapies. CLSM diagnostic features may differentiate between the various histologic subtypes of skin tumors and therefore helps in choosing the best therapeutic approach. In this study, we present the CLSM characteristic features of the most common melanocytic and non-melanocytic skin tumors, as well as future possible CLSM applications in the study of experimental skin tumorigenesis on animal models. [ABSTRACT FROM AUTHOR]

Lichen planus (LP) is a chronic inflammatory skin disease that can sometimes affect mucosal surfaces, with unknown pathogenesis, even though it appears to be an autoimmune disease. The diagnosis of lichen planus is usually based on histopathological examination of the lesions. Nowadays, the classical invasive diagnostic methods are replaced by modern non-invasive techniques. In this review, we present the main non-invasive imaging methods (dermoscopy, reflectance confocal microscopy, optical coherence tomography, ultrasound and diffuse reflection spectrophotometry) used in the diagnosis and therapeutic monitoring of lichen planus. Dermoscopy is a non-invasive method initially used for diagnosis of pigmented tumors but now is used also for inflammatory and infectious skin diseases. In lichen planus, the dermoscopy increases the accuracy of diagnosis, avoids skin biopsies commonly used and can be useful in the therapeutic monitoring by repeated investigation at different stages of treatment. Reflectance confocal microscopy (RCM) is a novel non-invasive imaging technique that is prevalently used for the diagnosis of skin tumors and inflammatory skin diseases. This technology has been mostly employed for bedside, real-time microscopic evaluation of psoriasis, lichen planus, contact dermatitis, revealing specific confocal features to support clinical diagnosis and assist with patient management. Optical coherence tomography (OCT) is an emergent imaging technique, developed over the last decade, based on the interaction of the infrared radiation (900–1,500 nm) and the living tissues. A limited information exists on the benefits of OCT technology for the in vivo diagnosis of LP but could be a useful auxiliary tool in the in vivo differential diagnosis, especially in clinical equivocal settings like mucosal lesions, and in monitoring the response to treatment. Our review shows the possibility of using modern imaging techniques for the in vivo diagnosis and also for evaluation of the treatment response. [ABSTRACT FROM AUTHOR]

Taking into consideration that the immune system plays a very important role in the development of melanoma and non-melanoma skin cancers, which have a high prevalence in immunosuppressed patients and after prolonged ultraviolet radiation, the interest in developing novel therapies, in particular targeting the inflammation in cancer, has increased in the past years. The latest data suggest that therapies such as imiquimod (IMQ), ingenol mebutate (IM), 5-fluorouracil (5-FU), retinoids, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been used with success in the topical treatment of some cancers. Herein, we review the topical treatment targeting the inflammation in skin cancer and the mechanisms involved in these processes. Currently, various associations have shown a superior success rate than monotherapy, such as systemic acitretin and topical IMQ, topical 5-FU with tretinoin cream, or IMQ with checkpoint inhibitor cytotoxic T lymphocyte antigen 4. Novel therapies targeting Toll-like receptor-7 (TLR-7) with higher selectivity than IMQ are also of great interest. [ABSTRACT FROM AUTHOR]

The "Consensus net meeting on dermatoscopy" of 2000 determined a set of significant dermatoscopic features for the diagnosis of pigmented basal cell carcinoma (pBCC). These included small ulcerations, maple leaf-like areas, multiple blue-grey globules, large blue-grey ovoid nests, arborizing telangiectasia, and spoke-wheel structures. The latter have been defined as brown to gray, well circumscribed, radial projections meeting at a darker brown central hub. Spoke-wheel structures have a reported specificity of 100% for pBCC. Because the correlation between dermatoscopy and histology is often difficult owing to the different incidences from which lesions are seen (horizontal in dermatoscopy vs vertical in histology), in this paper we sought to highlight the underpinnings of this particular dermatoscopic feature through in vivo reflectance confocal microscopy (RCM) examination. RCM is a non-invasive imaging technique capable of delivering images of en face optical sections at nearly histological resolution, thus facilitating the correlation with dermatoscopy. RCM examination of a pBCC exhibiting spoke-wheel structures revealed flower-shaped bright tumor islands infiltrated by dendritic cells, surrounded by dark areas of clefting at the level of the dermal-epidermal junction and papillary dermis. These tumor islands were connected to the epidermis through several cord-like projections. [ABSTRACT FROM AUTHOR]

An important function of the immune system is its ability to differentiate between healthy cells in the organism and "foreign" cells, allowing the latest to be attacked and the first ones to be conserved. The most important molecules in this process are considered to be checkpoint inhibitors. This review is focused on the association between cancer and inflammation, underlying the mechanisms of action of monoclonal antibodies that are targeting checkpoint inhibitors: ipilimumab against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and pembrolizumab and nivolumab against programmed cell death protein 1 (PD-1), their indications for treatment, and side effects. Presence of antibodies against checkpoint inhibitors shows promising results in the clinical trials in patients with types of cancer difficult to treat until now such as melanoma, non-small-cell lung cancer (NSCLC), and renal cell carcinoma, offering an increase in the overall survival rate, response rate, and progression-free rate. Resistance is now observed to emerge in patients treated with this therapy, showing the need for more studies in order to design a biomarker that will predict the type of response to immunotherapy. [ABSTRACT FROM AUTHOR]

The authors aim to present the butterfly effect, a concept based on the theory that small changes might have a powerful effect, as an example of the important connection between diet and acne. Western diet is currently a well‐known environmental factor which, mainly via the overstimulation of mTORC1 (mammalian target of rapamycin complex 1), is responsible for the development and aggravation of acne and other age‐related diseases of civilization. From the authors' point of view, "the butterfly effect" extrapolated to acne and diet depicts the importance of dietary interventions in acne so as to prevent more serious mTORC1‐driven diseases of civilization like obesity, diabetes, and cancer. [ABSTRACT FROM AUTHOR]

Background: Primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma is an extremely rare type of cytotoxic lymphoma with increased tendency of spreading to extranodal sites, poor response to conventional therapies for classic CD4+ cutaneous T cell lymphomas, and an unfavorable prognosis. Case report:We present the case of a 40 year old male patient who was referred to our clinic for generalized ulcerated, escharotic, infiltrated papules and plaques and painful ulcerations covered by white deposits on the soft and hard palate of 18 months duration. The unique clinical and histopathological features had posed great diagnostic and therapeutic difficulties. The patient had first been diagnosed with lymphomatoid papulosis, and later with T cell lymphoma and treated with methotrexate, oral retinoids and phototherapy without clinical benefit. During hospitalization in our clinic, the diagnosis of primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma was established and treatment with cyclophosphamide and dexamethasone, associated with local radiation therapy was instituted. Although the cutaneous and oral lesions improved during the first 3 months of treatment, the condition gradually worsened afterwards. Conclusions: Due to the paucity of literature data, frequent atypical presentations, aggressive behavior, and lack of optimal treatment strategies, primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma continues to represent a diagnostic and therapeutic challenge. Further case reports that describe clinical experience and therapeutic outcomes would help clarify its definition, classification and guide the management in this very aggressive cutaneous lymphoma. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies. Therefore, the major goal of cancer treatment is inhibition of tumor cell growth and of metastasis development. In order to choose the best management option for HNSCC patients, we need to identify reliable prognostic factors and to develop new molecular techniques in order to obtain a better understanding of therapy resistance. By acting as neurohormones, neurotransmitters, or neuromodulators, the neuroendocrine factors are able to signal the maintenance of physiological homeostasis or progression to malignant disease. Certain neuropeptides possess strong antitumor properties acting as tumor suppressors and immunomodulators, providing additional benefits for future potential therapeutic strategies. In light of the current understanding, cancer starts as a localized disease that can be effectively treated if discovered on proper time. Unfortunately, more than often cancer cells migrate to the surrounding tissues generating distant metastases, thus making the prognosis and survival in this stage much worse. As cellular migration is mandatory for tumor invasion and metastasis development, searching for alternate controllers of these processes, such as the neuroendocrine factors, it is an active tremendous task. [ABSTRACT FROM AUTHOR]

An early diagnosis is of overwhelming importance for the management and prognosis of mucocutaneous cancer. Actinic cheilitis (AC), defined by the clonal expansion of genomically unstable keratinocytes, is the most common potentially malignant lesion affecting the lips. Squamous cell carcinoma (SCC) is the most frequent oral malignancy, and there is strong evidence that the majority of the SCCs of the lip originate from AC. There is considerable difficulty in discerning between dysplasia and invasive carcinomas solely on a clinical basis. Although dermoscopy has become an essential tool for skin tumor evaluation, reflectance confocal microscopy (RCM) is a non-invasive imaging technology that has proved itself extremely useful in the diagnosis and monitoring of several skin diseases, including AC and SCC. The present study aimed to re-emphasize the usefulness of RCM in the early detection of malignant transformation, using AC and SCC of the lips as working examples. Due to the apparent innocuousness of AC for numerous patients, it is not possible to overstress the importance of a correct and early diagnosis, proper treatment and long-term patient follow-up as being essential for preventing the progression to lip SCC, or for its timely diagnosis. [ABSTRACT FROM AUTHOR]

Varicella-zoster virus (VZV) is a neurotropic virus which causes two distinct syndromes: primary infection presenting as varicella, mainly occurring in children without previous exposure to VZV, and reactivation of the latent VZV in the dorsal root ganglia, causing herpes zoster in adults. Herpes zoster clinically presents as a unilateral, painful, vesicular eruption, usually distributed to one or two adjacent thoracic dermatomes. As it is rarely seen confined to the upper limbs, few reports of herpes zoster involving the ulnar nerve exist in the literature, the majority describing patients who present with segmental zoster paresis of the upper extremity. This paper reports the case of a 73-year-old woman with ulnar and posterior antebrachial cutaneous nerve zoster reactivation and no history of immunosuppressive disorders. Therefore, rare occurrences of herpes zoster, such as the involvement of cervical dermatomes, should also be considered when faced with the differential diagnosis of symptomatic skin rashes of the upper limb, especially in elderly or immunosuppressed patients. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma is a slow growing non-melanoma skin cancer appearing as a non-healing, painless, and sometimes pruriginous sore, usually on sun-exposed areas. Although it rarely metastasizes, BCC diagnosis and treatment should not be delayed due to its local invasive potential. Currently, dermatoscopy is a well propagated and commonly employed tool in clinical practice, providing a fast and handy approach to clinical diagnosis, without the significant financial costs associated with other more sophisticated diagnostic means. Since the very first dermatoscopic descriptions of basal cell carcinoma, the list of dermatoscopic diagnostic criteria has been updated and renewed numerous times. Dermatoscopy significantly augments basal cell carcinoma detection by its capability of discriminating it from other skin lesions and inflammatory skin conditions. Moreover, current evidence suggests that this noninvasive, real-time imaging technique is also valuable in tumor management, seeing that it provides additional information related to histopathological subtype, presence or lack of pigmentation, lateral tumor extension, and tumor response to non-surgical treatments. In this paper, we aim to summarize time-honored as well as current knowledge on the value of dermatoscopy in the diagnosis, classification, and treatment of basal cell carcinoma. [ABSTRACT FROM AUTHOR]

Due to the increasing life expectancy, the geriatric dermatology has become more important and more common in the daily medical practice. A correct diagnosis and a proper management can reduce the morbidity and improve the quality of life. With age, the structure and functions of the skin are continuously changing. The factors which promote the aging of the skin are divided into two categories: intrinsical and extrinsical factors. The intrinsical factors are represented by the physiological processes of the aging of the skin, which are genetically determined, like wrinkles and loss of elasticity. Sun exposure, smoking, stress and other environmental factors are parts of the extrinsical group. The pathology of the elderly can be divided into four large groups: inflammatory dermatoses, skin infections, vascular pathologies and neoplasms. The main inflammatory dermatoses, which are most likely to be found in the elderly, are: asteatotic eczema, contact dermatitis, nummular eczema and drug eruptions. The skin infections which are most commonly found in older patients have various etiologies, for example bacterian (Staphylococcus aureus) fungal (Trichophyton rubrum, Candida albicans etc.) or viral (herpes zoster). These infections need a specific treatment, always taking into consideration the other comorbidities of the patients and the eventual drug interactions. With age, the density of the blood vessels and the cutaneous blood flow are decreasing. Due to the loss of elasticity and the impairment of the immune response, the aged skin is more susceptible to different agressions and has a delayed response to them. As a result, the most common vascular pathologies of the elderly are: senile purpura, stasis dermatitis, ulcers, bedsores and chronic venous insufficiency. Of high importance are also the neoplasms of the elderly. The benign neoplasms are: solar lentigos, actinic keratoses (these two types of lesions suggest an increased sun exposure throughout the entire life and indicate a high risk of developing a malignant neoplasm), seborrheic keratoses, angiomas and fibroepithelial polyps. The most common malignant tumors found at older ages are: basal cell carcinoma, scuamous cell carcinoma and melanoma, all of them being related to increased sun exposure. In conclusion, the spectrum of pathologies of the elderly is very broad, and their treatment requires an important amount of attention, because the patients usualy associate multiple comorbidities and present a high risk of complications. [ABSTRACT FROM AUTHOR]

Non-melanoma skin cancers represent the most common cancer in white-skinned individuals, with a continuous increasing global incidence. The main risk factor for their development is chronic exposure to sunlight. Unlike basal cell carcinoma, squamous cell carcinoma arises from precancerous lesions such as actinic keratoses. The diagnosis of non-melanoma skin cancer is based on clinical examination and dermoscopy, while histopathology certifies the diagnosis. The following article will present the main types of non-melanoma cancers with their respective clinical features, along with diagnostic methods and available therapeutic options. [ABSTRACT FROM AUTHOR]

Rationale. Psoriasis is a prevalent chronic inflammatory disease with worldwide distribution affecting approximately 2% of the Caucasian population. There have been many population- and family-based studies that agree on the strong genetic component of this disease. Several studies have investigated the relationship between cytokine gene polymorphisms, psoriasis, and the occurrence of comorbidities but their data are conflicting. Objective. This study examines cytokine gene single-nucleotide polymorphisms (SNPs) in the context of psoriasis and metabolic syndrome, with a focus on the occurrence of comorbidities in psoriasis patients. The working hypothesis is that particular SNPs may predispose to an accelerated disease course and more comorbidities in psoriasis patients. Methods. This cross-sectional study was carried out in 2016 in the Dermatology Department of "Elias" University Emergency Hospital, Bucharest and included 82 psoriasis patients. Several clinical and laboratory parameters were recorded, and the presence of metabolic syndrome (MetS) was noted. Using real-time PCR, we tested for the following SNPs: rs361525, rs1800629, rs1800896, rs610604, rs17782313. Results. Disease severity was not significantly influenced by any of the five studied SNPs. Gene polymorphism of rs17782313 was found to influence the occurrence of psoriatic arthritis. In these patients, rs610604 and rs17782313 polymorphisms were associated with the presence of diabetes mellitus. Furthermore, rs17782313 influenced the presence of obesity, heterozygotes being more at risk. Our data suggested that MetS occurred independently of the five studied SNPs. Discussion. The influence of certain cytokine gene polymorphisms on multiple organ systems is justification enough for further analysis of the genetic and molecular mechanisms of metabolic syndrome development in psoriasis patients. [ABSTRACT FROM AUTHOR]

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