Acral melanocytic lesions in the United States: Prevalence, awareness, and dermoscopic patterns in skin-of-color and non-Hispanic white patients.

BACKGROUND: Acral lentiginous melanoma has increased mortality compared with other melanoma subtypes and disproportionately affects ethnic minorities. Acral melanocytic lesions have not been well studied in diverse populations of the United States. OBJECTIVE: We sought to assess the prevalence, awareness, and dermoscopic patterns of acral melanocytic lesions in skin-of-color and non-Hispanic white patients. METHODS: We prospectively examined the palms and soles of 1052 patients presenting to dermatology clinics in New York, NY, and Miami, FL, from October 2013 to April 2015. RESULTS: Acral melanocytic lesions were observed in 36% of our cohort. Skin-of-color patients were more likely to have acral melanocytic lesions than non-Hispanic white patients (P < .01). Acral melanocytic lesions correlated with increased mole counts, particularly on non-Hispanic white patients. The majority of lesions demonstrated benign dermoscopic patterns. We observed 2 lesions with the parallel ridge pattern in our cohort, both found to be atypical nevi on biopsy specimen. Patients often lacked awareness of the presence of their lesions. LIMITATIONS: Interobserver variability in assessing dermoscopic patterns is a limitation. CONCLUSIONS: Melanocytic lesions of the palms and soles are common, particularly in a cohort of multiple ethnicities from the United States. Dermoscopy of acral lesions is an important clinical tool for diagnosis and management of these lesions.

Confocal imaging of carbon dioxide laser-ablated basal cell carcinomas: An ex-vivo study on the uptake of contrast agent and ablation parameters.

BACKGROUND AND OBJECTIVES: Laser ablation can be an effective treatment for the minimally invasive removal of superficial and early nodular basal cell carcinomas (BCCs). However, the lack of histological confirmation after ablation results in high variability of recurrence rates and has been a limitation. Reflectance confocal microscopy (RCM) imaging, combined with a contrast agent, may detect the presence (or absence) of residual BCC tumors directly on the patient and thus provide noninvasive histology-like feedback to guide ablation. The goal of this ex vivo bench-top study was to determine affective ablation parameters (fluence, number of passes) for a CO2 laser that will allow both removal of BCCs and control of the underlying thermal coagulation zone in post-ablated tissue to enable uptake of contrast agent and RCM imaging. MATERIALS AND METHODS: We used 72 discarded fresh normal skin specimens and frozen BCC tumor specimens to characterize the depth of ablation and to evaluate uptake of contrast agent and image quality. Acetic acid was used to enhance nuclear brightness ("acetowhitening") during imaging pre- and post-ablation. Histology sections of the post-ablated imaged surface were visually examined for the appearance of nuclear and dermal morphology and compared to the RCM images. RESULTS: Results for 1-3 passes of 5.5 J/cm(2), 6.5 and 7.5 J/cm(2), and 1-2 passes of 8.5 J/cm(2) showed the uptake of acetic acid for contrast and RCM imaging of the presence and absence of residual BCC tumors in post-ablated tissue. Morphologic details in the images were validated by the histology. CONCLUSION: The use of effective ablation parameters may enable RCM imaging to guide ablation.

Self-acquired patient images: the promises and the pitfalls.

Self-acquired patient images, also known as selfies, are increasingly utilized in the practice of dermatology; however, research on their utility is somewhat limited. While the implementation of selfies has yet to be universally accepted, their role in triage appears to be especially useful. The potential for reducing office wait times, expediting referrals, and providing dermatologic services to patients with limited access to care is promising. In addition, as technology advances, the number of smartphone applications related to dermatology that are available to the general public has risen exponentially. With appropriate standardization, regulation, and confidentiality measures, these tools can be feasible adjuncts in clinical practice, dermatologic surgery, and teledermatology. Selfies likely will have a large role in dermatologic practice and delivery in the future.

Conceptual approach to early melanoma detection: models, tools, issues and challenges.

Identification and removal of melanoma early in its development remains the most effective treatment. However, identification of early melanoma remains challenging and may result in unnecessary morbidity due to the excess excision of benign melanocytic nevi. Herein, we present a conceptual model of benign and malignant melanocytic growths. The potential differences in the location of the cell of origin as well as considerations for neoplasm progression are also reviewed. Several of the clinical tools currently available, the integration of information from those different sources, and approaches to set an optimum biopsy threshold are discussed. While early detection remains a challenge, significant progress has been made. Insight into melanoma growth processes and appropriate use of available tools can result in the detection of thinner melanomas while also decreasing overall biopsy rates.

Loss of Mpzl3 function causes various skin abnormalities and greatly reduced adipose depots.

The rough coat (rc) spontaneous mutation causes sebaceous gland (SG) hypertrophy, hair loss, and extracutaneous abnormalities including growth retardation. The rc mice have a missense mutation in the predicted Ig protein Myelin Protein Zero-Like 3 (Mpzl3). In this study, we generated Mpzl3 knockout mice to determine its functions in the skin. Homozygous Mpzl3 knockout mice showed unkempt and greasy hair coat and hair loss soon after birth. Histological analysis revealed severe SG hypertrophy and increased dermal thickness, but did not detect significant changes in the hair cycle. Mpzl3-null mice frequently developed inflammatory skin lesions; however, the early-onset skin abnormalities were not the result of immune defects. The abnormalities in the Mpzl3 knockout mice closely resemble those observed in rc/rc mice, and in mice heterozygous for both the rc and Mpzl3 knockout alleles, indicating that rc and Mpzl3 are allelic. Using a lacZ reporter gene, we detected Mpzl3 promoter activity in the companion layer and inner root sheath of the hair follicle, SG, and epidermis. Loss of MPZL3 function also caused a striking reduction in cutaneous and overall adipose tissue. These data reveal a complex role for Mpzl3 in the control of skin development, hair growth, and adipose cell functions.

Profiling of Glucose-Sensing Neurons Reveals that GHRH Neurons Are Activated by Hypoglycemia.

Comprehensive transcriptional profiling of glucose-sensing neurons is challenging because of low expression levels of glucokinase (Gck) and other key proteins that transduce a glucose signal. To overcome this, we generated and validated transgenic mice with a neuronal/endocrine-specific Gck promoter driving cre expression and mated them to mice with cre-dependent expression of an EGFP-tagged ribosomal protein construct (EEF1A1-LSL.EGFPL10) that can be used to map and profile cells. We found significant Gck expression in hypothalamic and limbic regions in cells that are activated following administration of glucose or 2-deoxyglucose. Transcriptional profiling from Gck-cre/EEF1A1-LSL.EGFPL10 mice enriched known and previously unknown glucose-sensing populations including neurons expressing growth hormone releasing hormone (GHRH). Electrophysiological recordings show that hypoglycemia activates GHRH neurons, suggesting a mechanistic link between hypoglycemia and growth hormone release. These studies provide a means for mapping glucose-sensitive neurons and for generating transcriptional profiles from other cell types expressing cre in a cell-specific manner.

Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice.

Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca(2+)-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells.

Luteinizing hormone receptor mRNA down-regulation is mediated through ERK-dependent induction of RNA binding protein.

The ligand-induced down-regulation of LH receptor (LHR) expression in the ovaries, at least in part, is regulated by a posttranscriptional process mediated by a specific LH receptor mRNA binding protein (LRBP). The LH-mediated signaling pathways involved in this process were examined in primary cultures of human granulosa cells. Treatment with 10 IU human chorionic gonadotropin (hCG) for 12 h resulted in the down-regulation of LHR mRNA expression while producing an increase in LHR mRNA binding to LRBP as well as a 2-fold increase in LRBP levels. The activation of ERK1/2 pathway in LH-mediated LHR mRNA down-regulation was also established by demonstrating the translocation of ERK1/2 from the cytosol to the nucleus using confocal microcopy. Inhibition of protein kinase A using H-89 or ERK1/2 by U0126 abolished the LH-induced LHR mRNA down-regulation. These treatments also abrogated both the increases in LRBP levels as well as the LHR mRNA binding activity. The abolishment of the hCG-induced increase in LRBP levels and LHR mRNA binding activity was further confirmed by transfecting granulosa cells with ERK1/2 specific small interfering RNA. This treatment also reversed the hCG-induced down-regulation of LHR mRNA. These data show that LH-regulated ERK1/2 signaling is required for the LRBP-mediated down-regulation of LHR mRNA.