Solar Elastosis Research Articles

Oculocutaneous Albinism with Squamous Cell Carcinoma, Bowen's Disease and Actinic Keratosis: A Case Report

Oculocutaneous Albinism with Squamous Cell Carcinoma, Bowen's Disease and Actinic Keratosis: A Case Report

Histologic Features Associated With an Invasive Component in Lentigo Maligna Lesions

Lentigo maligna (LM) presents an invasive component in up to 20% of biopsied cases, but to date the histologic features useful in detecting this invasive component have not been described. Some histologic characteristics are hypothesized to contribute to the progression of LM invasion. To identify the histologic characteristics associated with lentigo maligna melanoma (LMM) in patients with LM diagnosed by a partial diagnostic biopsy. A retrospective cross-sectional study of patients treated between January 1, 2000, and December 31, 2017, was conducted in a referral oncology center in València, Spain. Data and specimens of patients (n = 96) with a diagnosis of primary cutaneous melanoma in the form of either LM or LMM who had undergone surgical treatment, a complete histologic examination of the whole tumor, and an initial diagnostic partial biopsy of LM were included in the study. Histologic assessment was blinded to the presence of an invasive component. All biopsy specimens were evaluated for the presence of certain histologic characteristics. Comparisons between invasive samples and samples without an invasive component were performed. The differences in the distribution of variables between the groups were assessed using the χ2 and Fisher exact tests, and the degree of association of the relevant variables was quantified by logistic regression models. A classification and regression tree analysis was performed to rank the variables by importance. In total, 96 patients had sufficient histologic material that could be evaluated. The patients were predominantly male (56 [58.3%]) and had a mean (SD) age at diagnosis of 72 (12) years. Of these patients, 63 (65.6%) had an LM diagnosis and 33 (34.4%) had an LMM diagnosis (an invasive component). The histologic variables associated with the presence of an invasive component were melanocytes forming rows (odds ratio [OR], 11.5; 95% CI, 1.4-94.1; P = .02), subepidermal clefts (OR, 2.8; 95% CI, 1.0-7.9; P = .049), nests (OR, 3.0; 95% CI, 1.1-8.6; P = .04), and a lesser degree of solar elastosis (OR, 0.4; 95% CI, 0.1-1.1; P = .07). A classification and regression tree analysis of the relevant histologic features was able to accurately identify lentigo maligna with an invasive component (LMM) in more than 60% of patients. These findings may be useful in classifying early LM specimens at higher risk of invasion, which may eventually be relevant in identifying the most appropriate management for LM.

Aspect en microscopie confocale par réflectance in vivo des kératoses actiniques: Reflectance confocal microscopy features of actinic keratoses

Though the diagnosis of actinic keratoses is most often clinical, it is sometimes necessary to use non-invasive imaging methods to confirm this diagnosis. Reflectance confocal microscopic examination of actinic keratosis may reveal hyperkeratosis (i.e., detached, isolated or scaly corneocytes), parakeratosis (i.e., nucleated cells in the stratum corneum), dilated vessels and signs of solar elastosis, including clusters of moderately reflecting material and/or undulating shiny elastic fibres that are clearly visible in the superficial dermis. Hopefully, new in vivo microscopic imaging techniques such as line-field confocal optical coherence tomography will make it possible to obtain a three-dimensional examination of the skin and, thus, to further improve diagnostic accuracy of these lesions. © 2019 Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Kératoses actiniques : comprendre et traiter réalisé avec le soutien institutionnel de Galderma International.

COMBINED PHOTOINDUCED PATHOLOGY OF THE SKIN AND EYES IN PATIENTS WITH DERMATOHELIOSIS

Modern information on the mechanisms of the damaging effect of UV radiation on the skin and the eye is presented, constitutional phototype skin (according to the Fitzpatrick scale) and clinical stages of skin photoaging are described (according to R. Glogau). The range of clinical changes arising on the background of solar elastosis can vary depending on the anatomical site of the lesion and include a number of dermatoses included in the concept of solar elastosis syndromes, resulting in the development of malignant dermatoses. Depending on the type of UV exposure - sporadic short-term or systematic long-term, acute and chronic pathological processes caused by the action of UV may develop. The development of eyelid neoplasms (basal cell, metatypical, squamous cell carcinoma, melanoma), solar keratosis of the conjunctiva, pterygium, cataract, and macular retinal degeneration may result from the systematic UV irradiation of the organs of vision.

Histopathologic variables differentially affect melanoma survival by age at diagnosis.

We evaluated clinical, phenotypic, behavioral, and histopathologic variables in relationship to melanoma-specific survival by age at diagnosis among 650 population-based melanoma patients in Connecticut, with 20years of follow-up. Only one variable, skin awareness, was significantly associated with melanoma mortality in both groups. The variables that differed between the age-groups were anatomic site, Breslow thickness, histologic subtype, mitoses, tumor-infiltrating lymphocytes (TILs), and solar elastosis. Head and neck melanoma, Breslow thickness, nodular melanoma, and solar elastosis were all significantly more likely to be associated with mortality among the older subjects; among the younger subjects, the presence of mitoses was associated with an increased probability of dying and TILs were associated with a reduced risk of mortality.

BRAF Mutation Status in Primary, Recurrent, and Metastatic Malignant Melanoma and Its Relation to Histopathological Parameters.

BackgroundBRAF mutations are a common finding in malignant melanoma (MM). Nevertheless, apart from their significance as a therapeutic target in advanced melanoma, their prognostic value is still debated.ObjectiveTo assess BRAF mutation status in primary, recurrent, or metastatic MM and its correlations with histopathological findings.MethodsWe analyzed 203 samples from 178 consecutive patients: 129 primary cutaneous MM, 49 metastatic and recurrent MM of unknown primary site, and 25 cases of recurrences or metastases of primary MM. BRAF mutations in exon 15 were identified with real-time polymerase chain reaction and/or direct sequencing or pyrosequencing. Histopathological examination was performed according to standard procedures.ResultsWe observed a 42.1% prevalence of BRAF mutations at codon 600 among our patients, 84% of whom harbored the V600E mutation. Mutations showed a statistically significant increase in younger patients (P = 0.011), in ulcerated tumors (P = 0.020), and in tumors lacking solar elastosis in adjacent dermis (P = 0.008). Mutations were also more common in male patients, as well as in primary MMs of the torso, and in nonvisceral metastases, however without reaching statistical significance. Logistic regression analysis identified type and ulceration as the only significant predictors of BRAF mutation. The highest frequencies of mutated BRAF were identified in superficial spreading and nodular types, and the lowest in acral lentiginous and lentigo maligna types. In situ MM and primary dermal melanoma displayed intermediate frequencies.ConclusionFrequency of mutated BRAF is type-related and correlated with ulceration, a known adverse prognostic factor.

Cutaneous melanoma: a study on the updated pathologic stage, solar elastosis, and tumor-infiltrating lymphocytes

Background Melanoma ranks as the third most common cutaneous malignancy, but it is the most lethal if early surgical treatment is neglected. Recently, updates were made on the American Joint Committee on Cancer staging system, as well as guidelines for surgical excision. Previously, grading systems were made to measure cumulative damage (solar elastosis) and to evaluate the immune reaction against the tumor [tumor-infiltrating lymphocytes (TIL)]. Aim To apply the fore mentioned advances to a series of 146 Egyptian patients primarily treated by surgery. The histochemical stains used for solar elastosis included Verhoeff stain and Alcian blue stain, pH 2.5. For phenotyping of lymphocytes and natural killer cells, the following immune markers were used: CD3, CD8, CD4, and CD56. Results Most tumors (64.4%) presented with an advanced size (>4 mm), lymph node metastases (66.7%), and inadequate excision margin (66.4%). In association analysis, only age more than 50 years, head and neck location, and the superficial spreading histologic type were significantly associated with solar elastosis. Moreover, only old age (>50 years) and large tumor thickness (>4 mm) are associated with low level of TIL, denoting poor immune reaction. Conclusion The presentation of Egyptian patients with advanced stages of melanoma calls for the implementation of public education program including self-examination of skin to detect melanoma at an early stage. Moreover, prospective follow-up studies are needed to develop guidelines of surgical excision suitable for our advanced cases. The negativity of both solar elastosis and TIL in melanoma of lower extremity supports the trauma of combined immunodeficiency and trauma in oncogenesis at this location.

Histopathological comparison of lesional and perilesional skin in melasma: A cross-sectional analysis

Melasma is a common acquired hyperpigmentary disorder of the sun exposed skin, especially the face. The pathogenesis is unclear but interplay between genetic factors, hormones and ultraviolet radiation is important. We have evaluated the histological characteristics of melasma and compared the findings with adjacent normal skin. Skin biopsies were taken from both melasma and the surrounding perilesional normal skin in 50 Indian women. The sections were stained with hematoxylin and eosin, Fontana-Masson and Verhoeff-Van Gieson stains. Biopsy from melasma showed significant epidermal atrophy, basal cell hyperpigmentation and solar elastosis when compared with the perilesional skin. We found that the proportion of pendulous melanocytes was significantly higher in the lesional biopsy compared with the perilesional biopsy (76% vs 42%, P < 0.001). Similarly, pigmentary incontinence and features of solar elastosis were significantly higher in the lesional skin compared with the perilesional skin. The characteristic histopathological features such as epidermal atrophy, basal cell hyperpigmentation and solar elastosis suggest the role of chronic sun exposure in the pathogenesis of melasma. Presence of pendulous melanocytes is a characteristic feature of melasma. The presence of pendulous melanocytes may have prognostic implications in melasma.

Histološke karakteristike i volumenska gustina elastičnih vlakana u dermu tokom starenja

Introduction: Elastic fibers are constituents of the dermal extracellular matrix, determining the histoarchitecture of the dermal connective tissue. Organization and density of elastic fibers change as skin ages. The aim of this paper was to determine the similarities and differences between the photo-aging and the physiological aging of skin by examining organization and quantifying the elastic fibers in the dermis during aging. The material included samples of photoexposed and photoprotected skin, obtained from 90 cadavers aged 0-82 years. The samples were classified into five age groups: newborns, young age, middle age, mature age and the oldest age. Skin samples were stained using the Halmi modification of Aldehyd fucshin staining method, as well as Alcian blue staining (the Spicer method). Volume density (VD) of the elastic fibers was measured using Image J program. Results: In the skin of newborns and young age group (neck and abdomen) elastic fibers appeared to form a network structure. In the photoexposed skin of the mature age and the oldest group, elastic fibers showed tendency to fragment, while the elastic material exhibited tendency to accumulate. VD of elastic network in the skin of the neck in the middle, mature and the oldest age group was greater than VD of abdominal skin of the respective age groups (3.66±0.28%, 5.61±0.22%, 6.24±0.21% respectively). Age-related statistically significant increase in VD of the elastic network in the skin of the neck, as well as a statistically significant reduction of elastic network VD in the abdominal skin, has been observed (middle age - oldest). Conclusion: Correlation of the organization and quantity of elastic fibers with age exhibits different pattern in photoexposed compared to photoprotected skin. A quantitative evaluation of the volume density of elastic fibers correlates with clinically visible signs of photo-aging, primarily with solar elastosis.

Melasma: Updates and perspectives.

Management of melasma is highly challenging due to inconsistent treatment results and frequent relapses. However, recent studies revealed that melasma may not only be a disease of melanocytes, but also a photoaging skin disorder. Herein, we attempt to validate that melasma is indeed a photoaging disorder by presenting the histopathologic findings of melasma: solar elastosis, altered basement membrane, increased vascularization and increased mast cell count. We also provide some therapeutic implications based on these findings and a discussion on the latest updates and perspectives regarding treatment.

Melanoma coexisting with solar elastosis: a potential pitfall in the differential diagnosis between nevus and melanoma

Melanomas, like nonmelanoma skin cancers, are known to be causally related to sun exposure. It is therefore not surprising to see benign nevi and melanomas in a background of solar damage, which at times may complicate their distinction. Because of their long-standing nature, nevi often occur before the development of solar elastosis and as such are intimately associated with the solar elastosis. In contrast, visible solar elastosis often occurs before the development of melanoma, in which case the band of solar elastosis is displaced downward from the overlying invasive melanoma and/or its host response. We describe 4 cases in which invasive melanoma cells were intimately admixed with actinically damaged elastin fibers in the absence of a prominent host response. In each case, melanoma cells were admixed with prominent solar elastosis and lacked a significant host response, suggesting that they were either histiocytes or an associated melanocytic nevus. Recognition of this potential pitfall may be helpful in the diagnosis of primary/in-transit/satellite/metastatic melanoma as well as when evaluating marginal status and determining Breslow thickness.

Claudin-1 expression decreases with increasing pathological grade in actinic keratosis and may be a marker of high-risk actinic keratosis.

Actinic keratosis (AK) is a common sun-induced skin disorder that can progress to invasive squamous cell carcinoma. However, there is still no reliable method to predict high-risk AK. To identify markers that reflect the biological behaviour of AK and to understand the pathogenesis of AK. In total, 52 patients with AK and 17 site-matched healthy controls (HCs) were enrolled. We evaluated solar elastosis and immunohistochemical features using antibodies to p53, vitamin D receptor (VDR), claudin-1 and Langerin (CD207). Comparisons between AK and HC skin were performed and analyses carried out according to the pathological grade of AK. We found that in both patients and HCs, solar elastosis increased and Langerhans cell (LC) density decreased with ageing. Solar elastosis and p53 expression were higher and VDR expression was lower in patients than in HCs; however, there was no statistical difference between them in relation to the pathological grade of AK. Claudin-1 expression gradually decreased from HC skin to severe AK, and particularly decreased in areas with epidermal atypia. LC density in severe AK was significantly lower than in HC skin and mild AK, while there was no difference in LC density between HC skin, mild AK and moderate AK. Claudin-1 could be a useful marker of the pathological severity of AK. In addition, p53 increases and VDR decreases in AK, not in a gradual manner but in the early steps of carcinogenesis. LC density is relatively maintained in AK until it reaches severe dysplasia.

Telomerase reverse transcriptase promoter mutations and solar elastosis in cutaneous melanoma.

The aims of this study were to assess the prognostic potential of solar elastosis grading and telomerase reverse transcriptase (TERT) promoter mutations (TERTp) in melanoma and to evaluate whether an association between solar elastosis and TERTp exists. Solar elastosis in the dermis was evaluated in hematoxylin and eosin-stained whole slides from 486 malignant melanomas. Pyrosequencing was used to detect TERTp in 189 samples. There was no association between solar elastosis and TERTp (P=0.3). Severe elastosis was associated with older age (P<0.0001), ulceration (P=0.03), and location in the head/neck region (P<0.0001). The absence of elastosis was associated with younger age (P<0.0001), benign nevus remnants (P=0.001), and a positive BRAF V600E expression (P<0.0001). Severe elastosis predicted a worse relapse-free survival (hazard ratio: 2.18; 95% confidence interval: 1.30-3.64; P=0.003). However, it was not independent of age. TERTp was not associated with any adverse prognostic or clinicopathological outcome, nor any mitogen-activated protein kinase-related protein expressions. However, at a cutoff corresponding to the sensitivity of Sanger sequencing, TERTp predicted melanoma-specific death independently of age, and was associated with Breslow thickness, ulceration, tumor stage at diagnosis, BRAF V600E oncoprotein, and absence of p16 expression. In conclusion, TERTp were not related to severe elastosis and may thus be triggered by both chronic and acute intermittent sun exposure, the latter not visible on ordinary hematoxylin and eosin-stained slides. Neither TERTp nor severe elastosis predicted an adverse outcome in melanoma. An absence of elastosis was seen in younger melanoma patients and may be used to select those melanomas originating in a nevus, which often harbors a BRAF mutation.

The role of TERT promoter mutations in differentiating recurrent nevi from recurrent melanomas: A retrospective, case-control study

Repigmentation at previous biopsy sites pose a significant diagnostic dilemma given clinical and histologic similarities between recurrent nevi and locally recurrent melanoma. Though common in melanoma, the role of TERT promoter mutations (TPMs) in recurrent nevi is unknown. We investigated the role of TPMs in recurrent nevi and whether the presence of hotspot TPM distinguishes recurrent nevi from locally recurrent melanoma. We also characterized clinical and histologic features differentiating these lesions. We analyzed 11 locally recurrent melanomas, 17 recurrent nevi, and melanoma and nevus controls to determine TPM status. We also assessed clinical and histologic features of the recurrent groups. Hotspot TPMs were more common in recurrent melanomas than recurrent nevi (P=.008). Recurrent melanomas were more likely to have solar elastosis (P=.0047), multilayering of melanocytes in the epidermis (P=.0221), adnexal involvement (P=.0069), and epidermal consumption (P=.0204). Recurrent nevi had intra-epidermal atypia limited to the area above the scar (P<.0001) and occurred earlier after the original biopsy (P<.0008). Solar elastosis, months to recurrence, and hotspot TPMs were independently associated with recurrent melanoma in multivariate analysis. This was a retrospective study. Hotspot TPMs are significantly more frequent in recurrent melanomas and could serve as a diagnostic clue in histologically ambiguous cases.

Actinic Cheilitis: Report of Three Cases and Review of Literature

Actinic cheilitis (AC) is a potentially malignant lip disorder induced by chronic exposure to ultraviolet light, which mainly affects the vermilion of the lower lip of adults and fair skin. If it is not treated in a timely manner it can become a squamous cell carcinoma of the lip. Histologically, AC presents a series of alterations at the epithelial level ranging from hyperplasia to dysplasia; Connective tissue presents different degrees of actinic elastosis accompanied by inflammatory infiltrate. The objective of this work is to present three cases of patients with AC and analyze their clinical and histopathological characteristics.

Reflectance confocal microscopy features of melanomas on the body and non-glabrous chronically sun-damaged skin.

Melanoma remains a challenge to diagnose, especially when appearing on the background of chronically sun-damaged skin (CSDS). Our goal was to identify and quantify the reflectance confocal microscopy (RCM) features of melanoma on non-facial CSDS. Included lesions were biopsy-proven melanomas, from anatomic sites other than the face, neck, scalp and acral skin, with histopathologic finding of solar elastosis in the underlying dermis. All included lesions underwent clinical, dermoscopic and RCM imaging, obtained in a standardized fashion, prior to biopsy. All images were retrospectively analyzed by four observers. We identified 33 melanomas from 33 patients with 63.6% male patients and overall mean age of 72.8 years. The salient RCM features included an atypical honeycomb or disarranged epidermal pattern (81.8%), pagetoid infiltration of the epidermis by both round and/or dendritic melanocytes (100%), focal proliferation of predominantly dendritic melanocytes as sheets (78.8%), foci with non-edged papillae (84.8%), junctional thickening (60.6%), areas of irregular ring or meshwork pattern (78.8%), and underlying thickened collagen bundles (51.5%). Non-facial CSDS melanomas share features similar to other melanoma types including pagetoid cells and non-edged papillae. The focal proliferation of dendritic pagetoid cells in sheets is similar to that seen in facial CSDS melanomas.

Physical properties of the photodamaged human skin dermis: Rougher collagen surface and stiffer/harder mechanical properties.

Fragmentation of collagen fibrils and aberrant elastic material (solar elastosis) in the dermal extracellular matrix (ECM) is among the most prominent features of photodamaged human skin. These alterations impair the structural integrity and create a dermal microenvironment prone to skin disorders. The objective of this study was to determine the physical properties (surface roughness, stiffness and hardness) of the dermal ECM in photodamaged and subject-matched sun-protected human skin. Skin samples were sectioned and analysed by histology, atomic force microscopy and nanoindentation. Dermal ECM collagen fibrils were more disorganized (ie, rougher surface), and the dermal ECM was stiffer and harder, in photodamaged forearm, compared to sun-protected underarm skin. Cleavage of collagen fibrils in sun-protected underarm dermis by recombinant human matrix metalloproteinase-1 resulted in rougher collagen fibril surface and reduced dermal stiffness and hardness. Degradation of elastotic material in photodamaged skin by treatment with purified neutrophil elastase reduced stiffness and hardness, without altering collagen fibril surface roughness. Additionally, expression of two members of the lysyl oxidase gene family, which insert cross-links that stiffen and harden collagen fibrils, was elevated in photodamaged forearm dermis. These data elucidate the contributions of fragmented collagen fibrils, solar elastosis and elevated collagen cross-linking to the physical properties of the dermal ECM in photodamaged human skin. This new knowledge extends current understanding of the impact of photodamage on the dermal ECM microenvironment.

Platelet-rich Plasma for Skin Rejuvenation and Treatment of Actinic Elastosis in the Lower Eyelid Area.

BackgroundTreatment of the lower eyelid region to rejuvenate the skin or treat actinic elastosis often proves difficult. Established treatment options, such as hyaluronic acid injections, botulinum toxin injections, microneedling, skin resurfacing (microdermabrasion, chemical peel (exfoliation), laser treatment), as well as blepharoplasties and autologous fat transfers, can be associated with significant risks and increased patient burden. Furthermore, they may not be effective for treating the signs of skin aging or actinic elastosis, including dark rings under the eyes, a lack of volume and cutis laxa. A minimally invasive treatment approach which visibly improves the above-mentioned conditions and which involves minimal risk and patient burden would be a desirable alternative.Materials & methodsTwenty patients were treated a total of three times at monthly intervals with PRP (platelet-rich plasma). The patients were examined on the days of treatment and one month after the third injection. The PRP was obtained directly prior to treatment using the Arthrex ACP double syringe at the point of care. The injections (2 ml PRP per side) were administered laterally using 27 G 38 mm cannulas. Accurate photographic documentation and skin elasticity measurements using a cutometer were performed to objectify the subjective assessments from the patient and practitioner questionnaires.ResultsA progressive improvement in the esthetic outcome and a high level of patient satisfaction were determined. The cutometer measurements showed a statistically significant higher level of skin firmness (due to increased collagen production) and a statistically significant increase in skin elasticity (thanks to increased elastin production). Other than the anticipated visible swelling directly after the PRP injection, no other undesirable side effects or complications occurred. The typical burning sensation during the injection had not been reported.ConclusionThe results indicate that a series of PRP injections in the lower eyelid region is a safe, efficient, virtually pain-free, simple and rapid treatment option for an area with otherwise limited treatment alternatives.

Daily oral supplementation with collagen peptides combined with vitamins and other bioactive compounds improves skin elasticity and has a beneficial effect on joint and general wellbeing

Aging is a multifactorial and natural process that causes physiological changes in organs, tissues and cells over time. In the skin and cartilage, aging leads to a decrease in the synthesis and changes in the arrangement of proteoglycans and collagen, in addition to the loss of glycosaminoglycans, which are responsible for the integrity and health of these tissues. We hypothesized that daily oral supplementation with a liquid nutraceutical containing hydrolyzed fish collagen, vitamins, antioxidants and other active ingredients could improve skin texture and elasticity, and in addition have a protective effect on joint health. A double-blind, randomized, placebo-controlled clinical trial was conducted on 120 subjects who consumed either the test product or placebo on a daily basis for 90 days. Subjects consuming the test product had an overall significant increase in skin elasticity (+40%; P < .0001) when compared to placebo. Histological analysis of skin biopsies revealed positive changes in the skin architecture, with a reduction in solar elastosis and improvement in collagen fiber organization in the test product group. As reported in the self-perception questionnaires, these results were confirmed by the subjects' own perceptions in that participants agreed their skin was more hydrated and more elastic. In addition, the consumption of the test product reduced joint pain by −43% and improved joint mobility by +39%. Oral supplementation with collagen bioactive peptides combined with chondroitin sulphate, glucosamine, L-carnitine, vitamins, and minerals significantly improved the clinical parameters related to skin aging and joint health, and therefore, might be an effective solution to slow down the hallmarks of aging.

Elastosis in Actinic Cheilitis. Literature Review

The extracellular matrix (ECM) plays an important role in the regulation of biological events, such as cell migration, proliferation and differentiation. Chronic exposure to ultraviolet (UV) light causes elastosis (to varying degrees), which corresponds to a basophilic degeneration of the ECM. Actinic cheilitis (AC) is a potentially malignant lip lesion induced by regular and prolonged exposure to UV light, which mainly affects the vermilion. AC lesions have a complex stroma characterized by the presence of elastosis, chronic inflammatory infiltrate of different intensity and the appearance of telangiectatic blood vessels. Within this inflammatory infiltrate a significant increase of mast cells (MCs) has been described, located especially around areas of elastosis and at the subepithelial zone. It has been proposed that actinic elastosis is produced both, by degenerative processes and by abnormal synthesis of elastic fibers by photodamaged fibroblasts, which is accompanied by morphological changes in collagen. Although the fibroblast would play a major role in actinic elastosis formation, several studies suggest that other cell types such as MCs also contribute significantly to actinic ECM damage. The purpose of this review is to discuss the characteristics of elastosis in AC.