大多数人的皮肤上都有几个褐斑,我们称之为黑素细胞痣或痣。痣对人体无害,但偶尔可能转化为潜在致死性肿瘤,也就是恶性黑色素瘤。在放大镜(电子皮镜)下,皮肤科专家通过外观确定了不同类型的痣。广义上:“球状”痣在早年出现,并且可能转化为黑色素瘤;“网状”痣在成年期出现,并且可能与未长痣部位出现的黑色素瘤有关;带“外围球状体”(PG) 的网状痣会生长,但非恶性。良性痣及癌性痣(恶性黑色素瘤)中都可能出现 BRAF 和 NRAS 基因突变(变异)。这些基因是在肿瘤形成中起重要作用的 MAPK 通路的成分。为说明这些基因的作用,这些来自澳大利亚的研究人员探讨了电子皮镜下外观与良性痣中的 NRAS 和 BRAF 突变之间的关系。他们通过电子皮镜检查了 27 人的 40 个后天性(非先天性)痣,然后去痣以进行分析。在显微镜下,研究人员观察到大多数网状痣中的细胞结构无序,但这种情况在球状痣以及 PG 痣中很少见。研究人员使用了一种能够检测单细胞突变的新型高灵敏度方法(“微滴式数字 PCR”),他们发现大多数球状痣以及所有 PG 痣都出现 BRAF 突变,网状痣则出现 BRAF 或 NRAS 突变。研究人员得出结论,所有痣具有 MAPK 基因突变,证明 MAPK 通路在黑素细胞痣及黑色素瘤的形成中起基础性作用。

Research letter Dear Editor, Rarely, melanoma is dominantly inherited, with CDKN2A mutations accounting for > 85% of mutation‐positive families.1 CDKN2A encodes two, nonhomologous proteins, p16 and p14ARF, with individually unique first exons (1α and 1β, respectively) and alternative reading frames. Over 95% of the CDKN2A mutations in familial melanoma occur in the p16 transcript...

Acquired naevi can have unique dermoscopic patterns that correspond to distinct microanatomical growth patterns. Previous studies on acquired naevi stratified according to dermoscopic pattern focused on the frequency of somatic BRAF mutations, whereas NRAS mutations remained to be elucidated. To investigate the BRAF and NRAS mutation prevalence and activation of the mitogen-activated protein kinase (MAPK) pathway in distinct dermoscopic subtypes of acquired naevi. Common mutations present in BRAF and NRAS were assessed in 40 globular, reticular and peripheral rim of globules (PG) subtypes of acquired naevi from 27 participants (19 male, 8 female; mean age 46·7 years) selected from 1261 eligible volunteers. Mutations were determined using the highly sensitive and quantitative QX200 droplet digital™ polymerase chain reaction (ddPCR) system. The BRAF V600E (c.1799T>A or c.1799_1800delTGinsA) and BRAF V600K mutations were detected in 85% ( n = 34/40) of naevi. All BRAF wild-type naevi (15%; n = 6/40) harboured an NRAS codon 12/13 or 61 mutation. BRAF mutations were present in 92% ( n = 12/13) of globular and 100% ( n = 12/12) of PG naevi, whereas reticular naevi were 67% ( n = 10/15) BRAF - and 33% ( n = 5/15) NRAS -mutant ( P = 0·037). We discovered that 100% of the assessed acquired naevi had either a BRAF or NRAS mutation. Using sensitive techniques capable of single-cell mutation detection, it is likely that all acquired naevi will be mutated for BRAF or NRAS . Because both of these mutations are prevalent in distinct dermoscopic naevus subsets, our study supports the role of the MAPK pathway in the development of benign melanocytic proliferations, indicating that additional genomic events besides somatic mutations in BRAF or NRAS are required for melanoma development.

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bjd.15809 This article is protected by copyright. All rights reserved. DR MITCHELL STARK (Orcid ID : 0000-0002-4510-2161)

BACKGROUND:LEO 43204 is a novel ingenol derivative in development for the treatment of actinic keratosis.OBJECTIVES:To compare the safety and preliminary efficacy of three doses of LEO 43204 with ingenol mebutate in actinic keratoses (AKs).METHODS:Patients with at least three visible, discrete, nonkeratotic AKs on four separate selected treatment areas on the forearms received LEO 43204 gel (0·025%, 0·05% and 0·075%) and ingenol mebutate 0·05% gel, by investigator-blinded, randomized allocation, for 2 consecutive days. Patients were assessed at 8 weeks. Primary outcomes included maximum composite local skin response (LSR) score and adverse events (AEs). Secondary outcomes included a reduction in the number of visible AKs.RESULTS:Forty patients completed the trial. For all treatments, mean LSR scores peaked at week 1, and were below baseline by week 8. Mean maximum composite LSR scores for LEO 43204 0·025%, 0·05% and 0·075% were 9·2 (Dunnett adjusted P = 0·02), 10·1 (Dunnett adjusted P = 0·90) and 11·2 (Dunnett adjusted P < 0·01), respectively, vs. ingenol mebutate 0·05% gel (10·0). The most frequent AEs across all treatments were application site pruritus, burning sensation and tenderness. Mean reduction in the number of AKs was comparable for ingenol mebutate and the two lowest doses of LEO 43204 (71·9-73·1%), but LEO 43204 0·075% gave a significantly larger reduction (81·8%; Dunnett adjusted P = 0·04).CONCLUSIONS:LEO 43204 had a similar safety profile to ingenol mebutate and a dose-response relationship for LSRs was demonstrated. The highest LEO 43204 dose (0·075%) significantly reduced the AK count when compared with ingenol mebutate.

Journal of the European Academy of Dermatology and VenereologyVolume 30, Issue 3 p. 473-474 Letter to the Editor The ratio of non-hyperkeratotic and hyperkeratotic actinic keratosis in a high-risk non-melanoma skin cancer cohort in Queensland J. M. Tan, J. M. Tan Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, AustraliaSearch for more papers by this authorS. Sinnya, S. Sinnya Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, AustraliaSearch for more papers by this authorH. Peter Soyer, Corresponding Author H. Peter Soyer Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, AustraliaCorrespondence: H. Peter Soyer. E-mail: p.soyer@uq.edu.auSearch for more papers by this author J. M. Tan, J. M. Tan Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, AustraliaSearch for more papers by this authorS. Sinnya, S. Sinnya Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, AustraliaSearch for more papers by this authorH. Peter Soyer, Corresponding Author H. Peter Soyer Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Queensland, AustraliaCorrespondence: H. Peter Soyer. E-mail: p.soyer@uq.edu.auSearch for more papers by this author First published: 26 November 2014 https://doi.org/10.1111/jdv.12856Citations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume30, Issue3March 2016Pages 473-474 RelatedInformation

BackgroundActinic keratosis (AK) usually co-exists in areas of severe photodamage, but the clinical applicability of reflectance confocal microscopy (RCM) in diagnosing AK currently depends on a set of parameters yet to be defined in comparison to photodamaged skin (PD).ObjectiveTo correlate the RCM features of PD and AK with histopathology.MethodsTwenty participants with a mean age of 64years and skin phototype I and II were studied. RCM was performed on two PD and one AK within a field of 25cm(2) on the left dorsal forearm, followed by shave biopsies. Blinded evaluation of the histopathological and RCM images using established parameters in AK were performed retrospectively in consensus with an expert confocalist, correlated with the histopathological diagnosis by a board-certified dermatopathologist.ResultsA total of 57/60 areas were included. There were 43/57 (75%) and 14/57 (25%) histopathologically confirmed PD and AK respectively. Individual corneocytes, stratum corneum disruption, dermal inflammatory cells, increased vascularity/dilated vessels and solar elastosis were detected in PD and AK upon histopathology and RCM. The features in favour of AK were parakeratosis, hyperkeratosis, more severe keratinocyte pleomorphism and architectural disruption, and the presence of epidermal inflammatory cells. PD also demonstrated keratinocyte pleomorphism and architectural disruption though this was generally less severe than AK. A small subset of PD exhibited a comparable degree of keratinocyte pleomorphism and architectural disruption to the AKs in the cohort.ConclusionsThe viable epidermis demonstrates PD and AK to be part of a disease continuum corresponding to field cancerization. Individual corneocytes, stratum corneum disruption, dermal inflammatory cells, increased vascularity/dilated vessels and solar elastosis may be present in PD; whereas, parakeratosis and hyperkeratosis may represent the key to distinguishing AK from PD using RCM. The significance of epidermal inflammatory cells in the RCM diagnosis of AK remains to be elucidated.