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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.

ObjectivesEarly melanoma detection decreases morbidity and mortality. Early detection classically involves dermoscopy to identify suspicious lesions for which biopsy is indicated. Biopsy and histological examination then diagnose benign nevi, atypical nevi, or cancerous growths. With current methods, a considerable number of unnecessary biopsies are performed as only 11% of all biopsied, suspicious lesions are actually melanomas. Thus, there is a need for more advanced noninvasive diagnostics to guide the decision of whether or not to biopsy. Artificial intelligence can generate screening algorithms that transform a set of imaging biomarkers into a risk score that can be used to classify a lesion as a melanoma or a nevus by comparing the score to a classification threshold. Melanoma imaging biomarkers have been shown to be spectrally dependent in Red, Green, Blue (RGB) color channels, and hyperspectral imaging may further enhance diagnostic power. The purpose of this study was to use the same melanoma imaging biomarkers previously described, but over a wider range of wavelengths to determine if, in combination with machine learning algorithms, this could result in enhanced melanoma detection.MethodsWe used the melanoma advanced imaging dermatoscope (mAID) to image pigmented lesions assessed by dermatologists as requiring a biopsy. The mAID is a 21-wavelength imaging device in the 350-950 nm range. We then generated imaging biomarkers from these hyperspectral dermoscopy images, and, with the help of artificial intelligence algorithms, generated a melanoma Q-score for each lesion (0 = nevus, 1 = melanoma). The Q-score was then compared to the histopathologic diagnosis.ResultsThe overall sensitivity and specificity of hyperspectral dermoscopy in detecting melanoma when evaluated in a set of lesions selected by dermatologists as requiring biopsy was 100% and 36%, respectively.ConclusionWith widespread application, and if validated in larger clinical trials, this non-invasive methodology could decrease unnecessary biopsies and potentially increase life-saving early detection events. Lasers Surg. Med. 51:214-222, 2019. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Simple Summary: Early detection of melanoma and differentiation from benign nevi can be challenging even for the most experienced dermatologists. To improve melanoma detection, artificial intelligence algorithms incorporating dermoscopy have been developed, but lack transparency and therefore have limited training value for healthcare providers. To address this, an automated approach utilizing imaging biomarker cues (IBCs), logical features extracted from images that mimic expert dermatologists' dermoscopic pattern recognition skills, was developed. This study excluded deep learning approaches to which IBCs are complementary or alternative. Ten participants assessed 78 dermoscopic images (39 melanomas and 39 nevi) first without IBCs and then with IBCs. Using IBCs significantly improved diagnostic accuracy: sensitivity increased significantly from 73.69% to 81.57% (p = 0.0051) and specificity increased from 60.50% to 67.25% (p = 0.059). These results indicate that incorporating IBCs can significantly enhance melanoma diagnosis, with potential implications for improved screening practices. Further research is needed to confirm these findings across a variety of healthcare providers. Incorporation of dermoscopy and artificial intelligence (AI) is improving healthcare professionals' ability to diagnose melanoma earlier, but these algorithms often suffer from a "black box" issue, where decision-making processes are not transparent, limiting their utility for training healthcare providers. To address this, an automated approach for generating melanoma imaging biomarker cues (IBCs), which mimics the screening cues used by expert dermoscopists, was developed. This study created a one-minute learning environment where dermatologists adopted a sensory cue integration algorithm to combine a single IBC with a risk score built on many IBCs, then immediately tested their performance in differentiating melanoma from benign nevi. Ten participants evaluated 78 dermoscopic images, comprised of 39 melanomas and 39 nevi, first without IBCs and then with IBCs. Participants classified each image as melanoma or nevus in both experimental conditions, enabling direct comparative analysis through paired data. With IBCs, average sensitivity improved significantly from 73.69% to 81.57% (p = 0.0051), and the average specificity improved from 60.50% to 67.25% (p = 0.059) for the diagnosis of melanoma. The index of discriminability (d′) increased significantly by 0.47 (p = 0.002). Therefore, the incorporation of IBCs can significantly improve physicians' sensitivity in melanoma diagnosis. While more research is needed to validate this approach across other healthcare providers, its use may positively impact melanoma screening practices. [ABSTRACT FROM AUTHOR]

On the basis of large cardiovascular clinical trials of lipid-lowering agents that showed a considerable decrease in the incidence of primary melanomas in the active agent arm, we have carried out a randomized, double-blind clinical trial examining the impact of lovastatin on various biomarkers of melanoma pathogenesis. Subjects with at least two clinically atypical nevi were randomized to receive oral lovastatin or placebo for a 6-month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. Eighty subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison with placebo in the primary endpoint of decreasing the level of histopathologic atypia, nor in any of the secondary endpoints of decreasing clinical atypia, impact on nevus number, nor in showing significant changes in any of the molecular biomarkers. There were no significant differences in adverse event profiles for lovastatin compared with placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum low-density lipoprotein (LDL) levels compared with placebo, an expected result. This finding bolsters confidence in subject compliance. Given the results of this trial, it is concluded that if lovastatin were to lower the incidence of melanoma, it would appear not to be doing so by reversing atypia of precursor atypical nevi over the 6-month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed.

Skin cancer is a serious societal problem, and public awareness outreach, including to youth, is crucial. Medical students have joined forces to educate adolescents about skin cancer with significant impacts; even one 50-min interactive outreach session led to sustained changes in knowledge and behavior in a cohort of 1,200 adolescents surveyed. Medical students can act as a tremendous asset to health awareness public outreach efforts: enthusiastic volunteerism keeps education cost-effective, results in exponential spread of information, reinforces knowledge and communication skills of future physicians, and can result in tangible, life-saving benefits such as early detection of melanoma.

Computer-assisted image analysis is useful for quantifying the histologic and molecular changes of sun-induced squamous cell carcinoma progression. We used the CAS 200 image analysis system to measure nuclear morphometric parameters, p53 expression, and proliferation markers in actinic keratosis (AK), sun-exposed, and normal skin in 51 patients. Nuclear morphometry revealed significant increases in nuclear absorbance, irregularity of nuclear shape, and nuclear size in AK compared with normal and sun-damaged skin. These parameters showed significantly greater variability in AK nuclei. Argyrophyllic nucleolar organizer area and number were also significantly greater in AK compared with sun-damaged skin and normal skin. Ki67 and p53 expressions were both increased in sun-damaged skin relative to normal and greater still in AK. These data are evidence that sun damage induces proliferation and p53 abnormalities before the appearance of nuclear abnormalities and their associated DNA instability. Following these changes during a skin cancer chemopreventative trial can then help assess the efficacy of the agent and help determine where in the progression of neoplastic changes it exerts its biological effects.

Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precancerous changes. Epidemiologic evidence in humans, in vitro studies on human cells, and clinical experiments in animals have identified polyphenol compounds found in tea to be possibly useful in reducing the incidence of various cancers, including skin cancer. To examine the potential for a polyphenol from green tea, epigallocatechin gallate, to act as a chemopreventive agent for nonmelanoma skin cancer, a randomized, double-blind, placebo-controlled phase II clinical trial of topical epigallocatechin gallate in the prevention of nonmelanoma skin cancer was performed.

Yellow urticaria, however, presents with a predominant neutrophilic infiltrate and bilirubin deposition that is oxidized and highlighted as olive green by Hall's stain.[3] Nevertheless, yellow urticaria is a clinical diagnosis. Dear Editor, Urticaria, a mast cell-mediated skin reaction, and jaundice, a bilirubin-induced skin change, frequently occur in the clinical setting. However, the simultaneous occurrence of urticaria and jaundice resulting in yellow urticaria is a much rarer phenomenon. [Extracted from the article]

Background: Immunotherapy using programmed cell death 1 protein (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors has been increasingly reported in a variety of nonmelanoma skin cancers (NMSCs).Objective: To analyze the evidence of PD-1 and PD-L1 inhibitors in the treatment of NMSC.Methods: A primary literature search was conducted with the PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases through October 28, 2018, to include studies on the use of PD-1 or PD-L1 inhibitors in patients for NMSC. Two reviewers independently performed study selection, data extraction, and critical appraisal.Results: This systematic review included 51 articles. The most robust evidence was in the treatment of Merkel cell carcinoma and cutaneous squamous cell carcinomas, as supported by phase 1 and 2 clinical trials. Treatment of basal cell carcinoma, cutaneous sarcoma, sebaceous carcinoma, and malignant peripheral nerve sheath tumor also showed benefit with PD-1/PD-L1 inhibitors, but data are limited. There does not appear to be efficacy for PD-1/PD-L1 inhibitors in cutaneous lymphomas.Limitations: More investigation is needed to determine the efficacy, tumor responsiveness, and the safety profile of PD-1 and PD-L1 inhibitors in NMSC.Conclusion: PD-1 and PD-L1 inhibitors exhibit treatment efficacy in a variety of NMSCs. [ABSTRACT FROM AUTHOR]

We describe a case that was initially diagnosed and treated as toxic epidermal necrolysis (TEN) by an outside hospital. After failure to improve on high-dose steroids and intravenous (IV) immunoglobulin, the patient was transferred to our hospital where he was subsequently diagnosed with a disseminated herpes simplex virus (HSV) infection. The patient recovered after 21 days of antiviral therapy. We review key physical examination findings that will help the clinician diagnose a viral etiology in the setting of an acute blistering eruption with mucosal involvement.