Characteristics of dermal vascularity in melasma and solar lentigo.

BACKGROUND /PURPOSE: Melasma and solar lentigo (SL) are major benign hyperpigmented lesions, and both have been shown to involve the dermal vasculature. This review discusses current knowledge regarding the clinical characteristics of dermal vascularity in melasma and SL, as well as the results of relevant molecular biological investigations. METHODS: PubMed and Google Scholar were searched in December 2023 to identify articles related to melasma, SL, and the dermal vasculature in these lesions. RESULTS: Vascular morphologies in melasma and SL have been detected by histological and non-invasive methods, including modalities such as optical coherence tomography. Biological studies have indicated that factors secreted from vascular endothelial cells, such as stem cell factor and endothelin-1, can promote melanogenesis. With respect to phototherapy, blood vessel-targeting laser treatments are expected to provide long-term suppression of pigmentation, but this regimen is only effective when dilated capillaries are visible. CONCLUSION: In both melasma and SL, clinical and experimental investigations are revealing the contributions of dermal vascularity to hyperpigmentation. More effective treatment may require identification of hyperpigmentation subtypes. In the future, knowledge of treatment (including phototherapy) is expected to accumulate through reliable and validated non-invasive measurements.

Correlation between the efficacy of picosecond-domain laser treatment for solar lentigo and the vascularity in the upper dermis using optical coherence tomography angiography in Asian women.

OBJECTIVES: The purpose of this study was to noninvasively confirm the characteristics of the dermal vasculature in patients with solar lentigo (SL) and determine any association with the efficacy of picosecond-domain laser (PSL) treatment. METHODS: Thirteen facial SL lesions in 11 Asian female patients were included in this study and evaluated over 12 weeks. An Nd:YAG laser was used at 532 nm and 750 ps. Skin color and morphological structure were evaluated by ANTERA-3D® and optical coherence tomography (OCT), respectively. To analyze the vascularity in the upper dermis, an OCT angiography (OCTA) algorithm was applied to the OCT data. RESULTS: After PSL treatment, significant improvement in both hyperpigmentation and abnormally thickened epidermis was observed, but the efficacy varied for each lesion. There was a significant correlation between the change in the melanin index due to PSL treatment and preoperative vascular density in the upper dermis. CONCLUSIONS: To the best of our knowledge, this is the first report to demonstrate a correlation between the efficacy of PSL treatment of SL lesions and the vascularity in the upper dermis. Methods to evaluate the vasculature in the upper dermis may be useful for preoperative prediction of the efficacy of PSL treatment for SL lesions.

Multi-System-Level Analysis Reveals Differential Expression of Stress Response-Associated Genes in Inflammatory Solar Lentigo.

Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein-protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL.

Can we predict postinflammatory hyperpigmentation after laser treatment based on dermoscopic findings of solar lentigo?

Solar lentigo (SL) commonly occurs as hyperpigmented macules in areas exposed to ultraviolet radiation. It typically shows an increased number of melanocytes in the basal cell layer of the skin, with or without elongated rete ridges. This retrospective study aimed to evaluate the characteristic dermoscopic patterns, reflecting different histopathological features, which might be valuable in predicting the possibility of postinflammatory hyperpigmentation (PIH) occurring after laser treatment. In total, 88 Korean patients diagnosed with biopsy-proven SL (a total of 90 lesions were diagnosed) between January, 2016 and December, 2021 were included. Histopathological patterns were classified into six categories. Dermoscopic features were classified into six categories. Pseudonetwork pattern and rete ridge elongation showed a statistically significant negative correlation. This means that a flatter epidermis is likely to manifest as a pseudonetwork pattern. The erythema pattern showed a significant positive correlation with interface changes and inflammatory infiltration. Bluish-gray granules (peppering), a characteristic dermoscopic finding, showed significant positive correlations with interface changes, inflammatory infiltration, and dermal melanophages. Clinicians considering laser treatment for patients with SL should perform dermoscopic tests before treatment. The pseudonetwork relates to flattened epidermis and fewer Langerhans cells; thus, a lower remission of PIH after laser treatment might be expected. If bluish-gray granules or erythema are observed, inflammatory conditions are likely to be involved. In such cases, regression of the inflammatory response through drug therapy, such as topical corticosteroids, should be a priority option before laser treatment.

A mechanism of melanogenesis mediated by E-cadherin downregulation and its involvement in solar lentigines.

OBJECTIVE: Intensive studies have revealed that pleiotropic melanocytic factors are associated with age-spot formation. Dysfunctional keratinocyte differentiation is thought to be an upstream cause of age-spot formation. Although it has been shown that keratinocyte differentiation is mediated by the cell-cell contact factor E-cadherin, its involvement in age-spot formation remains unknown. Thus, to determine the origin of age-spots and an integrated solution for the same, we focused on E-cadherin expression in the present study. METHODS: First, we assessed the solar lentigines in cutaneous and cultured cells by means of immunofluorescence staining. Following that, keratinocytes treated with siRNAs against E-cadherin were co-cultured with melanocytes, and the secreted factors were identified by means of proteomic analysis of the culture supernatants. We also performed quantitative PCR to assess melanogenesis activity and screen ingredients. For behavioural analysis of melanocytes, we performed time-lapse imaging using confocal laser scanning microscopy. RESULTS: E-cadherin expression was downregulated in the epidermis of the solar lentigines, suggesting its involvement in age-spot formation. E-cadherin knocked down keratinocytes not only promoted the secretion of melanocytic/inflammatory factors but also increased melanogenesis by upregulating the expression of melanogenesis factors. Furthermore, live-imaging showed that the downregulation of E-cadherin inhibited melanocyte dynamics and accelerated melanin uptake. Finally, we identified Rosa multiflora fruit extract as a solution that can upregulate E-cadherin expression in keratinocytes. CONCLUSION: Our findings showed that E-cadherin downregulation triggers various downstream melanocytic processes, such as the secretion of melanocytic factors and melanogenesis. Additionally, we showed that the Rosa multiflora fruit extract upregulated E-cadherin expression in keratinocytes.

OBJECTIF: Des études intensives ont révélé que les facteurs mélanocytaires pléiotropiques sont associés à la formation de taches de vieillesse. On pense que la différenciation des kératinocytes dysfonctionnels est une cause en amont de la formation des taches de vieillesse. Bien qu'il ait été démontré que la différenciation des kératinocytes est médiée par le facteur de contact cellule-cellule E-cadhérine, son implication dans la formation des taches de vieillesse reste inconnue. Ainsi, pour déterminer l'origine des taches de vieillesse et une solution intégrée pour celles-ci, nous nous sommes concentrés sur l'expression de la E-cadhérine dans la présente étude. MÉTHODES: Tout d'abord, nous avons évalué les lentigines solaires dans les cellules cutanées et cultivées au moyen d'une coloration par immunofluorescence. Par la suite, les kératinocytes traités avec des siRNA contre l'E-cadhérine ont été co-cultivés avec des mélanocytes, et les facteurs sécrétés ont été identifiés au moyen d'une analyse protéomique des surnageants de culture. Nous avons également effectué une PCR quantitative pour évaluer l'activité de la mélanogénèse et dépister les ingrédients. Pour l'analyse comportementale des mélanocytes, nous avons réalisé une imagerie accélérée à l'aide de la microscopie confocale à balayage laser. RÉSULTATS: L'expression de l'E-cadhérine a été régulée à la baisse dans l'épiderme des lentigines solaires, suggérant son implication dans la formation des taches de vieillesse. Les kératinocytes dans lesquels l'E-cadhérine a été réduite non seulement ont favorisé la sécrétion de facteurs mélanocytaires/inflammatoires, mais ont également accru la mélanogenèse en régulant à la hausse l'expression de facteurs de mélanogenèse. De plus, l'imagerie en direct a montré que la régulation négative de l'E-cadhérine inhibait la dynamique des mélanocytes et accélérait l'absorption de la mélanine. Enfin, nous avons identifié l'extrait de fruit de Rosa multiflora comme une solution capable de réguler positivement l'expression de l'E-cadhérine dans les kératinocytes. CONCLUSION: Nos résultats ont montré que la régulation négative de la E-cadhérine déclenche divers processus mélanocytaires en aval, tels que la sécrétion de facteurs mélanocytaires et la mélanogénèse. De plus, nous avons montré que l'extrait de fruit de Rosa multiflora régulait à la hausse l'expression de l'E-cadhérine dans les kératinocytes.

Melanin accumulation in dermal stem cells deteriorates their exosome-mediated skin basement membrane construction in solar lentigo.

Solar lentigo (SL) is a hyperpigmented macule that occurs in sun-exposed areas and is characterized by the accumulation of melanin pigment in the epidermis. On the contrary, melanin-incorporated macrophages have also been identified in the dermis, which is thought to be caused by melanin transfer due to disruption of the basement membrane, but the detailed mechanism remains unclear. In this study, we analysed SL lesions by pathological methods and examined the mechanism of melanin accumulation in the dermis using cultured skin models in vitro. First, we observed a significant decrease in type IV collagen (COL4), a major component of the basement membrane, in SL lesions. The basement membrane is known to be formed by the interaction of keratinocytes and dermal cells. Therefore, we constructed skin models containing fibroblasts or dermal stem cells and examined their effects on basement membrane formation. The results showed a markedly enhanced production of COL4 mediated by dermal stem cell-derived exosomes. The analysis of melanin localization in the SL dermis revealed that CD163-positive macrophages and CD271-positive dermal stem cells both took up melanin pigment. Exosomes of dermal stem cells incorporating melanosomes were less effective in promoting COL4 expression. These findings suggest that while the promotion of COL4 production in keratinocytes by dermal stem cell-derived exosomes is important for maintaining basement membrane homeostasis, this mechanism is disrupted in SL lesions, leading to chronic melanin accumulation in the dermis.

Use of PRAME immunostaining to distinguish early melanoma in situ from benign pigmented conditions.

BACKGROUND: PRAME (PReferentially expressed Antigen in MElanoma) is an antigen that shows marked overexpression in melanoma compared to normal skin melanocytes. PRAME immunohistochemistry has proven effective in distinguishing melanocytic nevi from melanoma, but it is unclear if it may be used to distinguish melanoma in situ from other benign pigmented lesions. In particular, differentiating from melanocytic hyperplasia in sun-damaged skin is sometimes clinically and histopathologically challenging. We hypothesized that PRAME staining of solar lentigo, sun-damaged skin, and melanoma in situ would aid in setting a threshold of positivity that could be useful in evaluating such conditions. METHODS: We collected and stained typical examples of solar lentigo, melanoma in situ, and non-lesional sun-damaged skin by PRAME immunohistochemistry to assess a potential cutoff of PRAME positivity. RESULTS: Solar lentigo and non-lesional sun-damaged skin had 10 or fewer PRAME-positive cells per millimeter (mean 1.2), on the other hand melanoma in situ had at least 16 (mean 75.1). CONCLUSIONS: PRAME immunostaining appears sensitive and specific in the current series. This could be clinically useful for distinguishing melanoma in situ from benign melanocytic hyperplasia in sun-damaged skin. However, further studies are required to determine if 10 cells per millimeter is an acceptable threshold of positivity.

Treatment of facial and non-facial lentigines with a 730 nm picosecond titanium: Sapphire laser is safe and effective.

OBJECTIVE: A 730 nm picosecond-domain laser was developed to improve the clearance of pigmented lesion and reduce adverse events. This study assessed the safety and efficacy of this system for the clearance of lentigines and explores how the short picosecond pulses interact with tissue via histology. STUDY DESIGN AND METHODS: Twenty subjects with Fitzpatrick skin types II-IV were enrolled in this prospective, IRB-approved study. Four treatments were administered using a 730 nm picosecond-domain laser. Pre- and posttreatment photos were assessed by blinded reviewers at 4- and 12-week follow-up visits, using a 5-point clearance scale. Subject satisfaction was measured using a 5-point scale. Investigator Global Improvement Score (IGIS) was performed at the 4- and 12-week follow-up visits, using an 11-point clearance scale. Subject pain level was measured using an 11-point scale (no pain [0], extreme pain [10]). Histology of 730 and 532 nm picosecond pulses was compared with 755 and 532 nm nanosecond pulses. RESULTS: Sixteen subjects with a total of 118 discontinuous treatment areas, each comprised of 1-20 lesions, completed all study visits. Thirty body regions were studied, including arms (6), hands (16), scalp (1), forehead (2), face (3), and back (2). Spot sizes ranging from 2 to 5 mm diameters were used with fluences ranging from 0.8 to 4.0 J/cm2 . Mean pain score was 3.6 of 10 for all four treatments. Ninety-nine percent of randomly paired 4-week posttreatment images and 100% of 12-week posttreatment images were correctly identified from their respective baseline images by three blinded reviewers. Mean IGIS demonstrated scores of 6.7 and 7.0 at 4- and 12-week follow-up visits, respectively. At the 4- and 12-week follow-up visits, 76% and 73% of subjects, respectively, were satisfied to highly satisfied. The mean clearance score for all 118 treatment areas was 3 of 4 in follow-up visits. At 12-week follow-up, 36% of 118 treatment areas had a clearance score of 4, and 38% had a clearance score of 3. Post treatment, there was typical erythema, edema, dryness, crusting, and itching but negligible purpura, no pinpoint bleeding, blistering or scarring, and no significant hyperpigmentation or hypopigmentation. Histology showed diffuse, focal epidermal vacuolization ~5-10 µm in diameter and mild extravasation of erythrocytes with 730 nm picosecond pulses, while diffuse epidermal vacuolization was observed with coalescence of vacuoles (~20-100 µm), junctional clefting and mild extravasation of erythrocytes with 755 nm nanosecond pulses. Picosecond pulses of the wavelength of 532 nm produced diffuse, focal epidermal vacuolization and larger dermal vacuoles to depths of 500 µm, while 532 nm nanosecond pulses produced diffuse epidermal vacuolization with coalescence of vacuoles and marked dermal hemorrhage. CONCLUSION: This study demonstrated the potential of a new 730 nm picosecond-domain laser for the clearance of lentigines. The results showed good clearance with no adverse events and good subject satisfaction in patients with skin type II-III. Additional studies need to be conducted on darker skin types. The histopathologic findings demonstrate that the picosecond 730 nm laser produces excellent selectivity for pigment with minimal disruption of the dermal-epidermal junction and may therefore reduce healing times and the risk of adverse events.

The dermoscopic inverse approach significantly improves the accuracy of human readers for lentigo maligna diagnosis.

BACKGROUND: A recently introduced dermoscopic method for the diagnosis of early lentigo maligna (LM) is based on the absence of prevalent patterns of pigmented actinic keratosis and solar lentigo/flat seborrheic keratosis. We term this the inverse approach. OBJECTIVE: To determine whether training on the inverse approach increases the diagnostic accuracy of readers compared to classic pattern analysis. METHODS: We used clinical and dermoscopic images of histopathologically diagnosed LMs, pigmented actinic keratoses, and solar lentigo/flat seborrheic keratoses. Participants in a dermoscopy masterclass classified the lesions at baseline and after training on pattern analysis and the inverse approach. We compared their diagnostic performance among the 3 timepoints and to that of a trained convolutional neural network. RESULTS: The mean sensitivity for LM without training was 51.5%; after training on pattern analysis, it increased to 56.7%; and after learning the inverse approach, it increased to 83.6%. The mean proportions of correct answers at the 3 timepoints were 62.1%, 65.5, and 78.5%. The percentages of readers outperforming the convolutional neural network were 6.4%, 15.4%, and 53.9%, respectively. LIMITATIONS: The experimental setting and the inclusion of histopathologically diagnosed lesions only. CONCLUSIONS: The inverse approach, added to the classic pattern analysis, significantly improves the sensitivity of human readers for early LM diagnosis.

Safety and Efficacy of a Novel 730 nm Picosecond Titanium Sapphire Laser for the Treatment of Benign Pigmented Lesions.

BACKGROUND AND OBJECTIVES: Picosecond lasers in dermatology were originally focused on optimizing the removal of unwanted tattoos. Subsequent advances in this technology have expanded its clinical indications to include treatment of benign pigmented lesions, photodamage, melasma, and scar revision. In this retrospective review, we evaluate a novel 730 nm picosecond titanium sapphire laser in treating benign pigmented lesions. STUDY DESIGN/MATERIALS AND METHODS: This is a retrospective review of all patients who presented to our institution between December 2019 and March 2020 for treatment of their benign pigmented lesions with a 730 nm picosecond titanium sapphire laser. All Fitzpatrick skin types (I-VI) were included. Absolute and relative evaluations were conducted by two blinded board-certified dermatologists using high-resolution photographic images. RESULTS: Twenty-two of 64 patients satisfied inclusion and exclusion criteria. Patients received 1.1 ± 0.3 treatment sessions. The absolute average pigmentation score prior to treatment was 2.04 ± 0.7 versus 1.39 ± 0.6 after treatment (P < 0.05). Improvement in pigmentation was observed in 86% of the patients, while 3% had no improvement and 11% had worsening of pigmentation. No other adverse events were observed. Downtime consisted of 1-2 days of mild edema and erythema followed by 3-5 days of mild pigment darkening and superficial crust. CONCLUSION: The novel 730 nm picosecond titanium sapphire laser is a safe and effective treatment for benign pigmented lesions. Future prospective randomized control studies would be beneficial to further clarify its role in the treatment of benign pigmentation. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Melanocyte Activation Mechanisms and Rational Therapeutic Treatments of Solar Lentigos.

To characterize the pathobiology of solar lentigos (SLs), analyses by semiquantitative RT-PCR, Western blotting, and immunohistochemistry revealed the upregulated expression of endothelin (EDN)-1/endothelin B receptors (EDNBRs), stem cell factor (SCF)/c-KIT, and tumor necrosis factor (TNF)α in the lesional epidermis, which contrasted with the downregulated expression of interleukin (IL) 1α. These findings strongly support the hypothesis that previous repeated UVB exposure triggers keratinocytes to continuously produce TNFα. TNFα then stimulates the secretion of EDNs and the production of SCF in an autocrine fashion, leading to the continuous melanogenic activation of neighboring melanocytes, which causes SLs. A clinical study of 36 patients with SLs for six months treated with an M. Chamomilla extract with a potent ability to abrogate the EDN1-induced increase in DNA synthesis and melanization of human melanocytes in culture revealed a significant improvement in pigment scores and color differences expressed as L values. Another clinical study using a tyrosinase inhibitor L-ascorbate-2-phosphate 3 Na (ASP) demonstrated that L values of test lotion (6% APS)-treated skin significantly increased in SLs and in non-lesional skin with a significantly higher ΔL value in SLs when compared with non-lesional skin. The sum of these findings strongly suggests that combined topical treatment with EDN signaling blockers and tyrosinase inhibitors is a desirable therapeutic choice for SLs.

Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy.

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already-described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non-melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus-like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.

Molecular and histological characterization of age spots.

Age spots, also called solar lentigines and lentigo senilis, are light brown to black pigmented lesions of various sizes that typically develop in chronically sun-exposed skin. It is well known that age spots are strongly related to chronic sun exposure and are associated with photodamage and an increased risk for skin cancer; however, the mechanisms underlying their development remain poorly understood. We used immunohistochemical analysis and microarray analysis to investigate the processes involved in their formation, focusing on specific markers associated with the functions and proliferation of melanocytes and keratinocytes. A total of 193 genes were differentially expressed in age spots, but melanocyte pigment genes were not among them. The increased expression of keratins 5 and 10, markers of basal and suprabasal keratinocytes, respectively, in age spots suggests that the increased proliferation of basal keratinocytes combined with the decreased turnover of suprabasal keratinocytes leads to the exaggerated formation of rete ridges in lesional epidermis which in turn disrupts the normal processing of melanin upwards from the basal layer. Based on our results, we propose a model for the development of age spots that explains the accumulation of melanin and the development of extensive rete ridges in those hyperpigmented lesions.

Correlation between digital epiluminescence microscopy parameters and histopathological changes in lentigo maligna and solar lentigo: A dermoscopic index for the diagnosis of lentigo maligna.

BACKGROUND: The clinical and dermoscopic differentiation between lentigo maligna (LM) and solar lentigo (SL)/initial seborrheic keratosis (SK) may be difficult. OBJECTIVE: Our aim was to identify digital epiluminescence microscopy (DELM)-specific criteria that can be helpful in distinguishing LM from SL/SK and to propose a new model of LM dermoscopic progression based on a study of DELM-histopathological correlation. METHODS: A total of 167 consecutive doubtful pigmented lesions of the head (105 LM and 62 SL/SK) were studied. DELM assessment was based on the presence or absence of 15 DELM parameters that were subsequently examined histologically. Statistical analysis was performed to determine which DELM parameters were most strongly associated with LM. RESULTS: The finding of at least 1 of 4 parameters (ie, brown globules, a "necklace" pigment network, an atypical pigment network, and dark-brown/blue-gray ribbonlike structures) showed to be an extremely sensitive (99%) and specific (83.9%) DELM criterion to discriminate between LM and SL/SK. LIMITATIONS: Our findings were obtained by examining medium-high magnification DELM images. CONCLUSIONS: The finding of 1 or more among the 4 above-mentioned DELM parameters allows for the correct identification of 99.0% of the LM lesions, and - when the score is 0 - the correct classification as non-LM, of 83.9% of the SL/SK lesions.

Lentigo maligna melanoma with a history of cosmetic treatment: Prevalence, surgical outcomes and considerations.

INTRODUCTION: Lentigo maligna (LM) is melanoma in situ on sun-damaged skin and presents diagnostic challenges due to overlapping features with benign pigmented lesions. Cosmetic treatments may be inadvertently performed on LM. The aim of this study is to estimate the prevalence of LM with prior cosmetic treatment, and evaluate surgical outcomes. STUDY DESIGN AND METHODS: Retrospective review of biopsy-proven LM presenting over a 10-year-period (2006-2015). Prior cosmetic treatment and biopsies were recorded. Records were reviewed for demographic data, clinical characteristics, and surgical outcomes. RESULTS: 37/503 (7.4%) patients with LM reported prior cosmetic therapy. Most (95%) were on the head and neck; mean size 1.9 cm. Most patients reported cryotherapy (73%), followed by laser (29.7%), topical bleaching agents (18.9%), and electrodessication, and/or curettage (5.3%). Ten patients (27%) received two or more modalities. Eight patients (21.6%) reported prior benign biopsies. Six patients (16%) had invasive disease, two on initial biopsy and 4/34 (11.7%) upstaged upon excision. Average margin for clearance was 9.1 mm. CONCLUSION: Prior cosmetic treatment of LM is not uncommon, and may delay diagnosis and obscure borders, resulting in wider surgical margins. Clinicians should consider a biopsy confirming the benign nature of equivocal lesions prior to cosmetic treatment. Lasers Surg. Med. 49:819-826, 2017. © 2017 Wiley Periodicals, Inc.

Lentigo maligna of the face: A quantitative simple method to identify individual patient risk probability on dermoscopy.

BACKGROUND/OBJECTIVES: The clinical and dermoscopic differential diagnosis of flat pigmented facial lesions represents a great challenge for the clinicians. Our aim was to report a quantitative method based on dermoscopic features to better classify pigmented facial lesions. METHODS: This is a retrospective case-series study that analysed the dermoscopic features of 582 pigmented facial lesions. RESULTS: The individual patient probability of lentigo maligna (LM) was predicted by a multivariate model, with an accuracy of 0.72. According to the odds ratio at the multivariate analysis, an individual scoring index was assigned to each criterion, and a value of 4.56 was identified as optimal cut-off point. Up to a score of 2.5, the probability that a lesion is an LM is 0. The probability increases from 10 to 50% for a score ranging between 4.5 and 6. It is about 90% for a score of 7. CONCLUSION: The optimal cut-off point obtained and the curve that identifies the probability of a patient having a LM could improve the classification and the management strategies of equivocal pigmented facial lesions.

Biological processes in solar lentigo: insights brought by experimental models.

Common in ageing patient, the solar lentigo is a macular hyperpigmented skin lesion that results from chronic exposure to ultraviolet irradiations. Despite sharing numerous features with other pigmented spots, the diagnostic of this benign lesion is well characterized at the tissue level. Recent studies shed lights on several factors and their pathogenic mechanisms involved in the development of the solar lentigo. This review summarizes how diverse experimental approaches allowed the identification of several biomarkers, which contribute to a better understanding on the initiation and the maintenance of this pigmentary disorder.

Inhibitory effect of Phalaenopsis orchid extract on WNT1-induced immature melanocyte precursor differentiation in a novel in vitro solar lentigo model.

Recently, it has been reported that increased expression of WNT1 accelerates the differentiation of melanocyte stem cells (McSCs) in solar lentigines (SLs), hyperpigmented maculae commonly seen on sun-exposed areas of the skin. In this study, to establish an in vitro SL model, human epidermal squamous carcinoma cell line HSC-1, which expresses higher levels of WNT1 than normal human epidermal keratinocytes, was co-cultured with early passage normal human epidermal melanocytes (NHEMs) as an in vitro McSC model. As a result, mRNA expression levels of melanocyte differentiation-related genes MITF and TYR in NHEMs were significantly increased by co-culturing with HSC-1 cells. Furthermore, Phalaenopsis orchid extract (Phex) inhibited McSCs differentiation by suppressing WNT1 expression via down-regulation of DLX2, a transcriptional activator of WNT1, in HSC-1 cells. Therefore, our finding suggested that extracts such as Phex, which suppresses WNT1 expression, may be useful as a novel treatment of SLs.