Search

A subset of Spitz tumors harbor fusions of NTRK3 with ETV6, MYO5A, and MYH9. We evaluated a series of 22 melanocytic tumors in which an NTRK3 fusion was identified as part of the diagnostic workup. Tumors in which NTRK3 was fused to ETV6 occurred in younger patients were predominantly composed of epithelioid melanocytes and were classified by their histopathologic features as Spitz tumors. In contrast, those in which NTRK3 was fused to MYO5A were predominantly composed of spindled melanocytes arrayed in fascicles with neuroid features such as pseudo-Verocay bodies. To further investigate the effects of the fusion kinases ETV6-NTRK3 and MYO5A-NTRK3 in melanocytes, we expressed them in immortalized melanocytes and determined their subcellular localization by immunofluorescence. ETV6-NTRK3 was localized to the nucleus and diffusely within the cytoplasm and caused melanocytes to adopt an epithelioid cytomorphology. In contrast, MYO5A-NTRK3, appeared excluded from the nucleus of melanocytes, was localized to dendrites, and resulted in a highly dendritic cytomorphology. Our findings indicate that ETV6-NTRK3 and MYO5A-NTRK3 have distinct subcellular localizations and effects on cellular morphology.

BackgroundSkin cancer is the most common cancer in the USA. Therefore, it is important to review the contribution of ultraviolet radiation (UVR) exposure to skin cancer in individuals with the highest risk. Documenting the relationship between outdoor sports solar ultraviolet exposure and their risk of skin cancer along with appropriate risk mitigation strategies can help inform clinicians of practical information for counseling sun protective behaviors in this population.MethodsWe conducted a review of the current evidence using PubMed to answer the following research questions: (1) How is ultraviolet radiation measured? (2) What is the modern utility of the ultraviolet index in modifying recreational sun protection behaviors? (3) What is the risk of developing skin cancer for outdoor sport participants? (4) What is the prevalence of skin cancer in sport participants? and (5) Is the number of nevi and solar lentigines elevated in outdoor sport participants?ResultsBased on the literature, individuals who practice outdoor sport-related activities receive high ultraviolet radiation exposure, have a high risk for skin cancer, have a high prevalence for pigmented lesions, and may benefit from electronic sun protection educational interventions.ConclusionsIndividuals who practice outdoor sports experience substantially higher ultraviolet radiation exposure, routinely exceed the recommended exposure limits, and are at a higher risk of developing skin cancer. Therefore, those who are frequently engaged in outdoor leisure activities should be coached about efficient sun protective practices and relevant mobile technologies that may facilitate adherence.

Multiphoton microscopy (MPM) is a promising non-invasive imaging tool for discriminating benign nevi from melanoma. In this study, we establish a MPM morphologic catalogue of common nevi, information that will be critical in devising strategies to distinguish them from nevi that are evolving to melanoma that may present with more subtle signs of malignancy. Thirty common melanocytic nevi were imaged in vivo using MPM. Quantitative parameters that can distinguish between different types of nevi were developed and confirmed by examining the histology of eleven of the imaged nevi. MPM features of nevi examined included cytologic morphology of melanocytes in the epidermis and dermis, the size and distribution of nevomelanocytes both within and around nests, the size of rete ridges, and the presence of immune cells in the dermis. Distinguishing features include cytological morphology, the size of nevomelanocytes, the size of nevomelanocyte nests, and the distribution of nevomelanocytes. Notably, these distinguishing characteristics were not easily appreciated in fixed tissues, highlighting essential differences in the morphology of live skin. Taken together, this work provides a morphologic compendium of normal nevi, information that will be critical in future studies directed at identifying melanocytic nevi that are evolving to melanoma.

BACKGROUND: The need for noninvasive methods in treatment of cutaneous disease has continued to evolve exponentially. Amidst the search for technologies, radiofrequency (RF) has proven efficacious in numerous skin disease processes. Although RF is well known for its cosmetic utility, its mechanism is valued in the treatment of many noncosmetic cutaneous conditions of various etiologies. OBJECTIVE: To identify and describe studies in which RF was used to treat noncosmetic skin conditions and to explore the potential of this modality for further application in dermatologic diseases. MATERIALS AND METHODS: The PubMed database was used to find relevant articles. RESULTS: This search strategy yielded 54 articles that met the eligibility criteria. Noncosmetic indications discussed in these articles include varicose veins (n = 10,550), lymphangioma circumscriptum (n = 72), cutaneous neoplasms (n = 42), cutaneous leishmaniasis (n = 743), acne and acne scarring (n = 158), non-acne scarring (n = 43), primary axillary hyperhidrosis (n = 76), and acute and chronic wounds (n = 94). CONCLUSION: Treatment with RF is an effective, generally noninvasive modality with a relatively short postprocedure recovery time and little potential for severe adverse effects in the treatment of several cutaneous conditions. Further clinical studies would prove useful to assess the efficacy and cost-effectiveness of this treatment.

ObjectivesNon-invasive visualization of hair follicles is important for proper diagnosis and management of alopecia; however, histological assessment remains the gold standard. Laser imaging technologies have made possible noninvasive in vivo evaluation of skin and hair follicle. The aim of this study was to evaluate the ability of multiphoton microscopy (MPM) to non-invasively identify morphological features that can distinguish scarring from non-scarring alopecia.MethodsMPM images were obtained from areas on the scalp affected by alopecia. Investigators blinded to the diagnosis analyzed hair follicle and shaft sizes. Patients were recruited and imaged at the UC Irvine Health Medical Center and the University of California, Irvine Beckman Laser Institute. Patients with androgenetic alopecia (AGA) and alopecia areata (AA), and scarring alopecia, in particular frontal fibrosing alopecia (FFA) were recruited and imaged from July 2016 to July 2017.ResultsWe imaged 5 normal scalp subjects and 12 patients affected by non-scarring (7 subjects) and scarring (5 subjects) alopecia. In normal and non-scarring alopecia patients, MPM identified presence of sebaceous glands associated with hair follicles. MPM images of scarring alopecia were characterized by the presence of inflammatory cells surrounding hair follicles. Measurements of hair follicle diameter sizes were found to be significantly smaller in scarring alopecia patients compared to normal (P

This presentation will discuss recent advances in multiphoton microscopy (MPM) as a tool for in-vivo imaging of human skin to evaluate MPM's potential to enhance the diagnostic accuracy of skin diseases and guide effective treatment.

Metabolic syndrome is a multifactorial process characterized by obesity, hypertension, hyperlipidemia, hyperglycemia, and insulin resistance, significantly increasing the risk of cardiovascular disease (CVD), type 2 diabetes mellitus, and other chronic health conditions. The prevalence of metabolic syndrome is rising globally due to sedentary lifestyles and poor dietary habits. Inflammatory skin diseases, including psoriasis, atopic dermatitis (AD), rosacea, acne vulgaris, lichen planus, acanthosis nigricans, androgenetic alopecia and hidradenitis suppurativa are closely linked to metabolic syndrome and mitochondrial dysfunction. These skin conditions are characterized by dysregulated immune responses and increased activation of inflammatory cytokines and immune cells. Additionally, mechanisms resulting in the induction of mitochondrial apoptosis influence the pathogenesis of these inflammatory skin diseases, while oxidative stress, inflammation and insulin resistance further interlink mitochondrial dysfunction and metabolic syndrome. Understanding the role of mitochondrial dysfunction in the pathogenesis of metabolic syndrome and inflammatory skin diseases is crucial for developing targeted therapies. Further research is needed to explore the contributing pathophysiology and develop strategies for preventing and treating these conditions. Genomic studies have also identified mutations associated with mitochondrial dysfunction and insulin resistance, offering potential targets for personalized therapies. [ABSTRACT FROM AUTHOR]

Dermascopes are commonly utilized for the qualitative visual inspection of skin lesions. While automated image processing techniques and varied illumination strategies have been used to aid in structural analysis of lesions, robust quantification of functional information is largely unknown. To address this knowledge gap, we have developed a compact, handheld dermascope that enables real-time blood flow measurements of skin during conventional visual inspection. In-vitro characterization demonstrated that the dermascope is capable of quantifying changes in flow across a physiologically relevant range even when used in a handheld manner with clinic lighting and dermascope LEDs on. In a small pilot clinical study, we demonstrated the dermascope's ability to detect flow differences between two distinct lesion types.

Dermatoscopes are commonly utilized by medical professionals for the qualitative visual inspection of skin lesions. While automated image processing techniques and varied illumination strategies can aid in structural analysis of lesions, robust quantification of functional information is largely unknown. To address this knowledge gap, we have developed a compact, handheld dermatoscope that enables real-time blood flow measurements of skin using coherent illumination and laser speckle imaging (LSI). A second color camera attached to the dermatoscope helps with the simultaneous real-time observation of the skin lesions and allows the user to acquire and save color images via a custom Graphical User Interface. In-vitro characterization utilizing a blood flow phantom demonstrated that the dermatoscope is capable of quantifying changes in blood flow across a physiologically relevant range even when used in a handheld manner with ambient lighting. We also demonstrated that the dermatoscope can quantify blood flow in skin lesions in human subjects and that significant differences in blood flow are present among lesion types. There was significantly increased blood flow relative to the surrounding skin in cherry angiomas compared to solar lentigos (p

Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune blistering disease. Patients develop non-healing erosions and blisters due to cell-cell detachment of keratinocytes (acantholysis), with subsequent suprabasal intraepidermal splitting. Identified almost 30 years ago, desmoglein-3 (Dsg3), a Ca2+-dependent cell adhesion molecule belonging to the cadherin family, has been considered the "primary" autoantigen in PV. Proteomic studies have identified numerous autoantibodies in patients with PV that have known roles in the physiology and cell adhesion of keratinocytes. Antibodies to these autoantibodies include desmocollins 1 and 3, several muscarinic and nicotinic acetylcholine receptor subtypes, mitochondrial proteins, human leukocyte antigen molecules, thyroid peroxidase, and hSPCA1-the Ca2+/Mn2+-ATPase encoded by ATP2C1, which is mutated in Hailey-Hailey disease. Several studies have identified direct pathogenic roles of these proteins, or synergistic roles when combined with Dsg3. We review the role of these direct and indirect mechanisms of non-desmoglein autoantibodies in the pathogenesis of PV.

Bullous pemphigoid (BP) is an autoimmune blistering disease which carries a significant mortality and morbidity. While historically BP has been characterized as an IgG driven disease mediated by anti-BP180 and BP230 IgG autoantibodies, developments in recent years have further elucidated the role of eosinophils and IgE autoantibodies. In fact, eosinophil infiltration and eosinophilic spongiosis are prominent features in BP. Several observations support a pathogenic role of eosinophils in BP: IL-5, eotaxin, and eosinophil-colony stimulating factor are present in blister fluid; eosinophils line the dermo-epidermal junction (DEJ) in the presence of BP serum, metalloprotease-9 is released by eosinophils at the site of blisters; eosinophil degranulation proteins are found on the affected basement membrane zone as well as in serum corresponding with clinical disease; eosinophil extracellular DNA traps directed against the basement membrane zone are present, IL-5 activated eosinophils cause separation of the DEJ in the presence of BP serum; and eosinophils are the necessary cell required to drive anti-BP180 IgE mediated skin blistering. Still, it is likely that eosinophils contribute to the pathogenesis of BP in numerous other ways that have yet to be explored based on the known biology of eosinophils. We herein will review the role of eosinophils in BP and provide a framework for understanding eosinophil pathogenic mechanisms in mucocutaneous disease.

Notable milestones in the treatment of vascular lesions have been achieved over the past century. Many cutaneous vascular lesions can be successfully treated with lightbased devices. In this review, we will discuss the treatment of port-wine birthmarks, lymphatic malformations, infantile hemangiomas, rosacea, venous lakes, pyogenic granulomas, cherry angiomas, and angiofibromas using lasers, total reflection amplification of spontaneous emission of radiation, intense pulsed light, and photodynamic therapy. In addition, for several of these diagnoses, we will review medical therapies that can be combined with light-based devices to provide enhanced results.

Psoriasis is strongly associated with cardiovascular disease (CVD) and metabolic syndrome, with pediatric and adolescent patients having an increased risk of each compared to the general population. This increased risk is based on shared underlying genetic and cytokine profiles, as well as similar environmental risks. Many screening guidelines do not address the development of CVD and metabolic syndrome in these predisposed patients, particularly in the adolescent population. These deficits are evidenced by the absence of validated 10-year CVD risk calculators for pediatric and adolescent patients with chronic inflammatory diseases, as well as insufficient screening guidelines for insulin resistance in patients with psoriasis. This manuscript aims to contribute literature regarding allopathic and lifestyle recommendations to the most recent 2017 consensus guideline for the pediatric/adolescent population with psoriasis. PubMed, COCHRANE Database of Systematic Reviews and Google Scholar were reviewed by a panel of clinicians with clinical and research expertise in psoriasis and pediatric subspecialties. The patient-centered Strength of Recommendation Taxonomy (SORT) method was utilized to grade the quality of the evidence available. Updates in management surrounding the role of lipoprotein(a) in lipid panels, recommendations for exercise and weight management to decrease insulin resistance, as well as guidance for heart rate and blood pressure management were discussed. Screening and managing pediatric and adolescent patients with psoriasis for the associated comorbidities of CVD and metabolic syndrome is imperative. Future high-quality studies are needed to strengthen the evidence provided throughout this review, which acts as a framework for clinical practice. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia is the most common type of hair loss. Although the exact cause of this condition is not fully understood, it is known to involve excessive amounts of dihydrotestosterone. There are various treatment options available for androgenetic alopecia that aim to target these mechanisms. The FDA-approved therapies for this condition include topical minoxidil, oral finasteride, and low-level light therapy. This review will discuss the potential benefits of using spironolactone, dutasteride, and bicalutamide as alternative treatment options for androgenetic alopecia. [ABSTRACT FROM AUTHOR]

Chronic solar ultraviolet radiation (sUVR) exposure leads to an increased incidence of non‐melanoma skin cancer (NMSC) development, particularly when accumulated over decades. Workers in certain industries, such as construction, agriculture, postal workers, and the military, are at higher risk due to cumulative sUVR exposure in their line of work. By assessing the relationship between sUVR exposure in outdoor workers and their skin cancer risk and defining methods of prevention, clinicians can offer focused sun protection counseling to this unique population. PubMed was used to perform a literature review to address the following research questions: 1. How is ultraviolet radiation measured? 2. What is the modern utility of the ultraviolet index in modifying sun protection behaviors in outdoor industry workers? 3. What is the risk of non‐melanoma skin cancer development in individuals working in outdoor occupations? 4. What is the prevalence of skin cancer among outdoor workers? 5. Is the number of nevi and solar lentigines elevated among individuals employed in outdoor occupations? The literature suggests that individuals in outdoor occupations are exposed to UV levels that often surpass safety limits for occupational UVR exposure, increasing their risk of developing skin cancer and precursor and pigmented lesions. Individuals in high‐risk occupations experience significantly higher levels of sUVR exposure than their indoor worker counterparts, increasing their risk of malignant cutaneous transformation. Accordingly, these individuals must be counseled on effective solar protection methods, and employers should advocate for actionable change. [ABSTRACT FROM AUTHOR]

Nonthermal atmospheric plasma (NTAP)(also known as cold atmospheric plasma [CAP]) is a rapidly emerging technology showing promising treatment results for a wide variety of dermatologic conditions. Research on NTAP for the treatment of pediatric dermatologic conditions is limited. We conducted a systematic review to elucidate reported applications of NTAP for skin conditions in children. Overall, NTAP offers a promising safety profile and painless treatment option that has the potential to deliver similar efficacy to many standard therapies in pediatric dermatology. [ABSTRACT FROM AUTHOR]

Inflammatory skin conditions are significantly impacted by lifestyle habits, particularly those related to diet, exercise, and sleep. Although ancient cultures emphasized the importance of lifestyle behaviors as both etiology and therapy in disease, modern medicine often overlooks nonpharmacological therapy. However, recent studies show that diet can have a significant impact on inflammatory skin diseases such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. Foods high in glycemic index, advanced glycation end-products, and omega-6 polyunsaturated fatty acids are associated with obesity and systemic inflammation, which can exacerbate inflammatory skin diseases. In addition, lifestyle behaviors such as exercise and sleep have been shown to have positive effects on inflammatory skin diseases. This review aims to highlight the importance of lifestyle behaviors in the context of inflammation and inflammatory dermatoses. [ABSTRACT FROM AUTHOR]