Solar Elastosis Research Articles

Solar elastosis correlates with high tumor mutation burden and better 5-year disease-specific survival in patients with stage II/III melanoma

ObjectiveTo evaluate the relation between solar elastosis and tumor mutation burden (TMB) in a large clinically annotated cohort of stage II and III melanoma patients. MethodsPrimary cutaneous melanomas from 469 AJCC (8th edition) stage II and III patients with clinical annotation including outcome at 5 years of diagnosis were histopathologically evaluated for solar elastosis. Next-generation sequencing assay MSK-IMPACTTM was employed to determine TMB. Analysis by Fisher’s exact test, chi-square, and Kruskal-Wallis were performed, as well as uni- and multivariate logistic regression. ResultsTumors stratified by low and high TMB showed marked and statistically significant differences in presence and extent of associated solar elastosis. Lower risk patient stage (II versus III by AJCC 8th edition) as well as better 5-year melanomaspecific survival (as binary variable of controls-survivors versus cases-dead of disease at 5 years of diagnosis) were associated with severe solar elastosis. On univariate and multivariate logistic regression models, severe solar elastosis predicted significantly decreased odds of dying of melanoma within 5 years of diagnosis (OR 0.60, 95% CI 0.39-0.89; and OR 0.42, 95% CI 0.20-0.83, respectively; both p<0.05) ConclusionThe association of solar elastosis to TMB and 5-year melanoma specific survival points to its potential as a biomarker of clinical relevance that can be assessed by routine histopathology.

Upper eyelid lymphatic anatomy is associated with blepharoplasty recovery

BackgroundLymphatic vessels support wound recovery and absorb excess fluid. Blepharoplasty involves excess tissue excision, and the present study investigated the relationship between the lymph vessel density of excised tissue and the postoperative course. MethodsForty eyelids from 21 blepharoptosis patients who underwent blepharoplasty were enrolled. Each resected excess tissue sample was divided into four parts by three parasagittal cuts—medial, central, and lateral—and the area percentages occupied by lymphatic vessels and elastic fibers in the cut-exposed inner tissue between skin and muscle were determined by histology. The wound healing process was assessed at 2 weeks and 1, 3, and 6 months postoperatively, by using a visual analogue scale (VAS) for estimating edema and the Vancouver Scar Scale (VSS). ResultsWith increasing age, the area percentage occupied by lymphatic vessels declined significantly (r=-0.581, p<0.001) while an increase in solar elastosis was observed. Percentages of lymphatic vessels were highest at the medial side of the eyelid (p<0.05), and here their relative distribution to the “shallow layer” close to the skin was also highest (p<0.01). Independent of age, the VSS values at 2 weeks and 1 month postoperatively were significantly lower in patients with a higher area percentage of lymphatic vessels (2 weeks: p<0.05; 1 month: p<0.01). ConclusionsIn patients undergoing blepharoplasty, upper eyelid area percentages of lymphatic vessels decreased with advancing age. Higher proportions of lymphatic vessels were associated with improved wound healing outcomes.

What lies behind melasma: a review of the related skin microenvironment.

Melasma is an acquired chronic pigmentary disorder affecting millions of individuals worldwide. However, the pathogenesis of melasma remains unclear. This article provides a comprehensive review of the pathophysiological changes occurring in the skin microenvironment of melasma lesions, which can be summarized as follows: (1) skin barrier dysfunction and abnormal synthesis, transport, and intracellular distribution of melanin in the epidermis; (2) basement membrane damage; (3) solar elastosis, vascular changes, senescent fibroblasts, mast cell infiltration, and sebocyte participation in the dermis; and (4) systemic factors such as sex hormones and oxidative stress. Furthermore, potential therapeutic strategies are introduced to provide novel perspectives for fundamental and clinical research related to melasma.

Cosmetic retinoid use in photoaged skin: A review of the compounds, their use and mechanisms of action.

The inevitable attrition of skin due to ultraviolet radiation, termed photoaging, can be partially restored by treatment with retinoid compounds. Photoaged skin in lightly pigmented individuals, clinically presents with the appearance of wrinkles, increased laxity, and hyper- and hypopigmentation. Underlying these visible signs of ageing are histological features such as epidermal thinning, dermal-epidermal junction flattening, solar elastosis and loss of the dermal fibrillin microfibrillar network, fibrillar collagen and glycosaminoglycans. Retinoid compounds are comprised of three main generations with the first generation (all-trans retinoic acid, retinol, retinaldehyde and retinyl esters) primarily used for the clinical and cosmetic treatment of photoaging, with varying degrees of efficacy, tolerance and stability. All-trans retinoic acid is considered the 'gold standard' for skin rejuvenation; however, it is a prescription-only product largely confined to clinical use. Therefore, retinoid derivatives are readily incorporated into cosmeceutical formulations. The literature reported in this review suggests that retinol, retinyl esters and retinaldehyde that are used in many cosmeceutical products, are efficacious, safe and well-tolerated. Once in the skin, retinoids utilize a complex signalling pathway that promotes remodelling of photoaged epidermis and dermis and leads to the improvement of the cutaneous signs of photoaging.

Basosquamous carcinoma: Comprehensive epidemiological, clinical, dermoscopic, and confocal features from a single center institution.

Basosquamous carcinoma (BSC) is a rare and aggressive nonmelanoma skin cancer (NMSC) that exhibits features of both BCC and squamous cell carcinoma (SCC). The gold standard for diagnosis is histopathological examination. BSC is often challenging to diagnose and manage due to its mixed histological features and potential for aggressive behavior AIM: To identify specific features aiding clinicians in differentiating BSCs using non-invasive diagnostic techniques. We conducted a retrospective descriptive, monocentric study of the epidemiological clinical, dermoscopic, and reflectance confocal microscopy (RCM) features of histopathologically proven BSCs diagnosed between 2010 and 2023. A total of 192 cases were selected. The study population consisted of 17 men (60.9%). Total 95.8% of patients at the time of diagnosis were≥50 years. BSC occurred in the head and neck area in 124 cases (63.1%) of which 65 (33.9%) were in the H-zone. For 47.4% of patients, BSC presented as a macule with undefined clinical margins (43.3%). Dermoscopic images were available for 98 cases: the most common parameter was the presence of whitish structureless areas (59 [60.2%]), keratin masses (58 [59.2%]), superficial scales, and ulceration or blood crusts (49 [50%] both). Vessels pattern analysis revealed hairpin vessels (exclusively) and linear irregular vessels as the most frequent (55 [56.1%] both). RCM examination was performed in 21 cases which revealed specific SCC features such as solar elastosis (19 [90.5%]), atypical honeycomb pattern (17 [89%]), proliferation of atypical keratinocytes (16 [80%]) combined with BCC' ones as bright tumor islands (12 [57.8%]), and cleft-like dark spaces (11 [53.4%]). Our study reflects the largest cohort of BSCs from a single institution. We described an incidence rate of 4.7%, higher than reported in the Literature, with the involvement of patients≥50years in almost 96% of cases and an overall male predominance. At clinical examination, BSC was described as a hyperkeratotic macule with undefined clinical margins with one or more dermoscopic SCC' features, whereas the presence of typical BCC aspects was observed in less than 10% of cases, differently from what was previously reported. At RCM analysis, BSCs presented with an atypical honeycomb pattern with proliferation of atypical keratinocytes, hyperkeratosis, and in nearly 55% of patients, bright tumor islands with cleft-like dark spaces. The distinctive dermoscopic patterns, along with the RCM features aid in the differentiation of BSCs from other NMSCs.

External validation of a predictive model for aged-related skin tears in Fitzpatrick skin types I-IV cohort.

Older Australians are at increased risk of skin tears with the risk not always recognised or the injury able to be prevented. This study externally validated Rayner et al. (2019) Skin Tear Risk Prediction Model in an independent aged cohort with a Fitzpatrick skin types I-IV from across multiple residential-care sites, over a 6-month period. A total of 362 individuals aged between 65 and 102.5 years completed the study. In all, 165-residents sustained one or more skin tears. Logistic regression analysis was conducted of the five variables (gender, previous history of skin tears, previous history of falls, purpura and solar elastosis) identified in the skin tear model. The skin tear model provided 'good' to nearly 'very good discrimination' for correctly classifying residents at-risk or not-at-risk (area under the curve of 0.799 [95% confidence interval, CI: 0.75-0.84]). The skin tear model correctly predicted 75.8% (sensitivity) of participants with skin tears and 71.6% (specificity) of residents without skin tears. The model demonstrated it could work as a screening tool to identify older individuals at risk of skin tears and would benefit clinical practice as it was easy to use, was reproducible, and had good accuracy across aged-care residents with a Fitzpatrick skin type I-IV.

Retrospective Single-Center Case Study of Clinical Variables and the Degree of Actinic Elastosis Associated with Rare Skin Cancers.

(1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches.

Interobserver Variability in the Histopathological Evaluation of Melanoma: Analysis of 60 Cases

IntroductionSince the field of dermatopathology is not an exact science, it is subject to personal subjectivity, which sometimes causes disagreements on the diagnosis and assessment of some histological features. In the case of melanoma, some variables such as regression are associated with low interobserver agreement. On the contrary, other variables such as the measurement of Breslow thickness show high reproducibility. ObjectiveThe main objective of our study was to investigate multiple features of 60 consecutive cases of melanoma to establish interobserver reproducibility. Methods and main resultsWe conducted an observational and descriptive study at Hospital de Manises, Valencia, Spain, IVO Foundation, Valencia, Spain, and Hospital 12 de Octubre, Madrid, Spain. The mean level of agreement of all study variables was moderate (Cohen's kappa coefficient statistic=0.5). The highest agreement corresponded to polypoid morphology, pigmentation, ulceration, and solar elastosis. On the other hand, the lowest level agreement was reached for the presence of cellular pleomorphism and tumor necrosis. ConclusionsOur mean level of agreement was moderate, which reflects that some of the measured characteristics such as cellular pleomorphism or the presence of necrosis cannot be used for future studies or must be redefined and their reproducibility, reestablished. When conducting a research study, it is necessary to analyze the study variables to demonstrate their validity to measure or classify a certain feature. It is also advisable to warrant that that the variables are reproducible to be able to use them for other studies or in the routine clinical practice.

P01 Remodelling of the dermoepidermal junction occurs in intrinsically aged Far East Asian skin without significant epidermal atrophy

Abstract Introduction and aims Ageing is characterized by a gradual decline in physiological function and is influenced by both intrinsic genetic and extrinsic lifestyle and environmental factors. However, much of our knowledge of cutaneous ageing comes from the study of White populations. We have previously shown that the organization of young healthy skin is ethnicity-dependent and that altered epidermal morphology in White volunteers correlates with loss of biomechanical function in the skin. In this study, we used epidermal morphometry to determine whether parameters associated with intrinsic skin ageing in White skin are also observed in Far East Asian skin. Methods Archival skin samples were obtained from the Asian Skin Biobank [young (3–21 years), N = 38, 37 male samples (Chinese, n = 16; Malay, n = 16; other Far East, n = 6); aged (61–86 years), N = 7, one male sample (Chinese, n = 6; Malay, n = 1)] and stained with haematoxylin and eosin prior to image analysis for dermoepidermal junction (DEJ) convolution and measurement of epidermal thickness. Weigert’s resorcin-fuchsin stain was used to ensure samples were photoprotected. Results Weigert’s resorcin-fuchsin stain revealed that all samples were photoprotected, with no evidence of solar elastosis. We next compared whether geographic ancestry of our local Far East Asian population impacted epidermal morphology in young skin; neither DEJ convolution nor epidermal thickness were impacted by geographic ancestry. However, a significant flattening of the DEJ was observed between young and aged samples (P &amp;lt; 0.01). Interestingly, no significant difference in epidermal thickness was observed as a function of age. Conclusions While intrinsically aged Asian skin undergoes the same flattening of the DEJ that is seen in White populations, epidermal thickness does not significantly alter; this is in stark contrast to intrinsically aged White skin, where epidermal atrophy is observed. Hence, the trajectory of intrinsic cutaneous ageing may be ethnicity-dependent, providing further evidence that studies of skin from different ethnicities are necessary.

Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-β, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-β (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Photoprotection and dermatological profile of persons with albinism in Plateau state, Nigeria: findings from a collaborative awareness and screening outreach program

Introduction As a result of genetically being deficient of melanin, albinos are particularly susceptible to skin damage from ultraviolet rays leading to photodermatoses such as sunburns, dermatoheliosis, and cutaneous cancers. These negatively affects quality of life and cause premature death. Little is known of the photoprotective measures available to and dermatological profile of persons with albinism in Plateau state, North Central Nigeria. Objective To describe the dermatological profile of albinos in Plateau state, Nigeria, photo exposure levels, photoprotection strategies, and factors associated with presence of photodermatoses. Patients and methods Consenting individuals with albinism attending the sensitization event hosted by the Centre for Albinism Right and Empowerment Network were recruited. Demographic information, occupational history, solar exposure, photoprotective practices, and perceived sun exposure were all documented using semistructured questionnaires. Physical and dermatological examination, dermoscopy, and laboratory investigations were used to make diagnosis. Statistical package for social sciences, version 26, was used to carry out univariate and bivariate analysis. Results While a wide spectrum of skin diseases was observed among the 59 albinos that participated. Photodermatoses were three times more than nonphotodermatoses. The commonest photodermatoses were solar elastosis (55.9%), solar lentigines (44.1%), actinic keratosis (27.1%), and sunburn (25.4%). Skin cancers affected 10.2% of all patients and 16.6% of persons more than or equal to 20 years. Generally, the presence of photodermatoses was associated with age and occupation while actinic keratotic changes specifically was associated with living in rural areas (P=0.035). Despite this, only seven (11.9%) owned sunscreen at the time of study with more than a third (35.2%) being ignorant of existence of sunscreen lotions. Conclusion Continuous multifaceted programs that involve tracking, education, prevention, early detection, and treatment of photodermatoses will be planned to be targeted towards persons with albinism living in Plateau state.

Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden.

Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies. We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas. Solar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH = 21% and MDA = 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to the MDA cohort (3.34 vs. 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs. Our findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.

Abstract 2501: High mutation burden and ultraviolet light signature in conjunctival squamous cell carcinoma

Abstract Purpose: Conjunctival squamous cell carcinoma (conjSCC) is endemic in sub-Saharan Africa and is a major cause of ocular morbidity and mortality. This study aims to evaluate Tumor Mutation Burden (TMB), genomic signature, and histologic characteristics of conjunctival squamous cell carcinoma (conjSCC) in two cohorts of patients; one from the USA and one from Ethiopia. Methods: Whole exome sequencing data, PD-L1 expression, histologic features, and human papillomavirus (HPV) status were analyzed in conj SCC tumors of 25 patients treated at an Ethiopian (ETH) cancer center and 29 patients treated at a US cancer center. Genomic alterations in conjSCC were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas (TCGA). Results: TMB was found to be relatively high in conjunctival SCC (3.01/Mb, log10), was comparable to TMB values associated with cutaneous SCC, and was higher than most other SCC types available in the TCGA database. ETH samples had higher tumor mutational burden compared to the US cohort (3.34 vs 2.73). Solar elastosis was seen in a higher percentage of tumors from Ethiopia compared with the US cohort (78% vs. 10%). HPV status was similar between the cohorts (ETH: 21%, MDA: 28%). PD-L1 positivity defined as &amp;gt; 1% of tumor cells was seen in 33 of 53 tumors (62%). Mutations associated with ultraviolet light (UV) signature were the most frequently encountered signatures in both cohorts (SBS7b: 74% and SBS7a: 72%). UV signatures were more prevalent in the ETH cohort compared with the US cohort. Conclusions: Conjunctival SCC is associated with a high TMB providing the opportunity for immune checkpoint inhibitor therapy for patients with locally advanced and/or metastatic conjunctival SCC. Clinical trials are needed to assess the efficacy of immune checkpoint inhibitors in patients with conjunctival SCC, particularly in sub-Saharan Africa where this cancer is more frequently seen, and is associated with significant morbidity and mortality. Citation Format: Bita Esmaeli, Frederico O. Gleber-Netto, Oded Sagiv, Curtis R. Pickering, Neil Gross, Jing Ning, Melisachew M. Yeshi, Jonas Mitku, Michael T. Tetzlaff, Priyadharsini Nagarajan. High mutation burden and ultraviolet light signature in conjunctival squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2501.

Amplification of Mutant NRAS in Melanocytic Tumors With Features of Spitz Tumors

NRAS activating mutations are prevalent in melanocytic neoplasia, occurring in a subset of common acquired melanocytic nevi and ∼30% of cutaneous melanomas. In this study, we described a cohort of 7 distinctive melanocytic tumors characterized by activating point mutations in codon 61 of NRAS with amplification of the mutant NRAS allele and shared clinicopathologic features. These tumors occurred predominantly in younger patients, with a median age of 20 years (range, 6-56 years). They presented as papules on the helix of the ear (4 cases) or extremities (3 cases). Microscopically, the tumors were cellular, relatively well-circumscribed, compound, or intradermal proliferations. The tumor cells often extended into the deep reticular dermis and involved the superficial subcutaneous fat in some cases. The melanocytes were epithelioid to spindled with moderate amounts of cytoplasm and conspicuous nucleoli. They were arranged in short plexiform fascicles, nests, and cords. Some cases had occasional pleomorphic and multinucleated melanocytes. Rare dermal mitotic figures were present in all cases. The dermis contained thick collagen bundles and minimal solar elastosis. Follow-up data were available for 5 patients, with a median period of 4.2 years (range, 1-9 years), during which no recurrences or metastases were reported. Our series highlights a clinicopathologically and molecularly distinctive subset of NRAS-mutated tumors with amplification of the mutant NRAS allele.

IMPACT OF ULTRAVIOLET RADIATION ON HUMAN SKIN OWING TO OZONE DEPLETION

&lt;p&gt;Depletion of ozone molecules in the stratospheric layer surges the flow of ultraviolet (UV) rays on the surface of the earth. Generally, UV rays are the hazardous energy waves emitted from the sun that can cause acute and chronic effects on bio species. Exposure to UV rays in humans causes skin problems such as wrinkles, leathery skin, liver spots, actinic keratosis, and solar elastosis. It is also stated to be a basic premise for skin melanoma. Raising environmental pollution and natural disasters triggered the ozone depletion crisis into global criteria. The proposed work is developed with the intent to analyse the harmful effects of UV radiation on human skin. It detects the skin diseases raised due to UV rays and categorizes them based on chronic intensity using the convolution neural network. The deep learning network Multires U-Net is developed to classify acute and chronic UV skin lesions based on intensity. The proposed technique achieved 95% model accuracy in the testing and training process. Hence the proposed model has better efficiency in the detection of UV lesions.&lt;/p&gt;&#x0D;

Tracing human papillomavirus in skin and mucosal squamous cell carcinoma: a histopathological retrospective survey.

Worldwide, squamous cell carcinoma (SCC) incidence is rising. The literature debates the human papillomavirus (HPV)'s role in cutaneous SCC development. We examined HPV histopathology in SCC samples in this study. Retrospective study at tertiary referral skin center in 2020. Histopathological features of HPV, including koilocytosis, hyperkeratosis, acanthosis, hypergranulosis, parakeratosis, solar elastosis, papillomatosis, and tumor grade, were examined in SCC specimens. Two dermatopathologists independently reevaluated all samples. We examined 331 SCC cases (male:female ratio = 3.9:1). The mean age was 68.1, with 15.1 standard deviation. Lesions were most common on the face (40.5%), scalp (22.7%), and extremities (20.8%). Koilocytes were found in 50 (15.1%) lesions. Nail (38.1%, p=0.007), oral cavity (36.8%, p=0.014), and genitalia (60.0%, p=0.026) lesions had higher koilocytosis rates. SCCs were found in 6.6% of specimens, but in situ tumors had the highest koilocytosis (64.7%), significantly higher than other grades (p<0.001). SCC pathology often shows HPV and specific koilocyte histopathology. Well-differentiated SCC has a stronger association with nail, oral, and genital lesions.

MELASMA ETIOLOGY AND TREATMENT: A SYSTEMATIC REVIEW

Introduction: Melasma is a common chronic refractory pigmentation disorder that predominantly affects women and individuals with darker skin types. It significantly alters quality of life and self-esteem because of its disfiguring skin appearance. Objective: to detail current information related to melasma, etiology, epidemiology, pathophysiology, histology, presentation, treatment and prognosis. Methodology: a total of 30 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 19 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: melasma, laser, pigmentation, skin. Results: Females are more affected than males in a 9:1 ratio. Melasma is infrequent prior to puberty and more common in the reproductive years. Melasma is found in 15% and 50% of pregnant women. The prevalence is 1.5% and 33% depending on the population. The most notable factor is exposure to sunlight. Next to pregnancy, direct sun exposure is the most important risk factor for melasma, shown by 27% to 51% of individuals as a trigger and 84% as a clinical deterioration factor. Approximately 83% to 93% of individuals with melasma have modifiable levels of solar elastosis. Conclusions: The treatment of melasma continues to be a challenge, because of the fact that the spots do not disappear completely in most of those affected, in addition to presenting considerable recurrence rates. The first line management is adequate sun protection and the association of sunscreens with color and topical bleaching agents, which may have a different effect on melanogenesis. In case oral medications are needed, tranexamic acid presents the best evidence for treatment. Some procedures support the treatment of melasma, such as microneedling and chemical peels that act through epidermal renewal. Lasers should be used with extreme caution because heat induces post-inflammatory melanogenesis. The combination of topical bleaching agents with medications and oral procedures provides more rapid effects, however more studies are needed regarding the treatment of the condition. KEY WORDS: melasma, laser, pigmentation, skin.

Clinical and histopathological features of lentigo maligna and lentigo maligna melanoma: a retrospective analysis in Korea.

Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are rare in Asian countries. The histopathological diagnosis of LM is often challenging, and misdiagnosis is common. Although histopathologic features of LM/LMM are known, statistical analysis of them were scarcely reported. In this study, we aimed to investigate the histopathological characteristics of LM/LMM in Korean patients and identify key histopathological clues distinguishing LM from benign lentigo. We performed a retrospective study of the clinical and histopathological features of patients diagnosed with LM/LMM at our center between 2011 and 2022. We assessed the histopathological features in each case based on 16 pathological criteria according to previous literature. Pathologically confirmed cases of benign lentigo were analyzed for comparison. Twenty-one patients (10 with LM and 11 with LMM) were analyzed. Several statistically significant difference existed between the features of LM and benign lentigo (N = 10), including asymmetry of overall structure (p < 0.001), cytologic atypia (p < 0.001), predominant single-cell proliferation (p < 0.001), melanocytic nests (p = 0.033), melanocytes forming rows (p = 0.003), pagetoid spread of melanocytes (p < 0.001), and hair follicle invasion by atypical melanocytes (p < 0.001). Degree of solar elastosis was more severe in group "Age ≥ 60" (p = 0.015), and group "Diameter ≥ 20 mm" (p = 0.043). Presence of elongated rete ridges were less common in the older than 60 age group (p = 0.015) and group "Diameter ≥ 20 mm." Invasion was associated with mitosis (p = 0.001, OR 49.285), multinucleated cells (p = 0.035, OR 17.769), and degree of lymphocyte infiltration (p = 0.004). This study investigated the clinical and histopathologic characteristics of LM and LMM in Koreans. Although histopathological diagnosis is challenging, especially in the early stages of LM, our data showed essential histopathological changes in architectural, cytological, and dermal patterns. Considering the potential aggressiveness of LM/LMM, it is essential to recognize its histopathological features and provide timely management.

Update on Melasma Treatments.

Melasma is a prevalent hyperpigmentation condition known for its challenging treatment due to its resemblance to photoaged skin disorders. Numerous studies have shed light on the intricate nature of melasma, which often bears similarity to photoaging disorders. Various therapeutic approaches, encompassing topical and systemic treatments, chemical peeling, and laser therapy, have exhibited efficacy in managing melasma in previous research. However, melasma often reoccurs despite successful treatment, primarily due to its inherent photoaged properties. Given that melasma shares features with photoaging disorders, including disruptions in the basement membrane, solar elastosis, angiogenesis, and mast cell infiltration in the dermal layer, a comprehensive treatment strategy is imperative. Such an approach might involve addressing epidermal hyperpigmentation while concurrently restoring dermal components. In this article, we provide a comprehensive review of conventional treatment methods frequently employed in clinical practice, as well as innovative treatments currently under development for melasma management. Additionally, we offer an extensive overview of the pathogenesis of melasma.

Subtypes of Melanomas Associated with Different Degrees of Actinic Elastosis in Conventional Histology, Irrespective of Age and Body Site, Suggesting Chronic Ultraviolet Light Exposure as Driver for Lentigo Maligna Melanoma and Nodular Melanoma.

(1) Background: Ultraviolet (UV) radiation and sunburns are associated with an increased incidence of acquired nevi and melanomas. However, the data are controversial as to whether chronic UV exposure or high intermittent UV exposure is the major carcinogenic factor in melanocytic tumors. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure in nevi and different clinical melanoma subtypes (i.e., superficial spreading melanoma (SSM), nodular malignant melanoma (NMM), acral lentiginous melanoma (ALM), and lentigo maligna melanoma (LMM)) with respect to clinical variables (age, sex, and body site). (2) Methods: We defined a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 595 melanocytic lesions from 559 patients with their clinical variables. (3) Results: The TEG was correlated with age and UV-exposed body sites. Furthermore, the TEG was significantly higher in LMM than in all other types of melanomas and the TEG in NMM was higher than in SSM, irrespective of patient age and tumor site. (4) Conclusions: High cumulative UV exposure is more strongly associated with LMM and NMM than with other melanoma subtypes.