Chronic Sun Damage Research Articles

Scalp Melanoma: A High-Risk Subset of Cutaneous Head and Neck Melanomas with Distinctive Clinicopathological Features.

Scalp melanomas (SM) have been previously associated with poor overall and melanoma-specific survival rates. The aim of this study was to describe and compare the clinicopathological characteristics and survival outcomes of SM and non-scalp cutaneous head and neck melanoma (CHNM). An observational multi-center retrospective study was designed based on patients with CHNM followed in two tertiary care hospitals. A hundred and fifty-two patients had CHNM, of which 35 (23%) had SM. In comparison with non-scalp CHNM, SM were more frequently superficial spreading and nodular subtypes, had a thicker Breslow index median (2.1 mm vs. 0.85 mm), and a higher tumor mitotic rate (3 vs. 1 mitosis/mm2) (p < 0.05). SM had a higher risk of recurrence and a higher risk of melanoma-specific death (p < 0.05). In the multivariate analysis, scalp location was the only prognostic factor for recurrence, and tumor mitotic rate was the only prognostic factor for melanoma-specific survival. We encourage routinely examining the scalp in all patients, especially those with chronic sun damage.

Osteoporosis and dermatoporosis: a review on the role of vitamin D.

Osteoporosis (OP) and Dermatoporosis (DP) are expressions of the aging process at the skin and bone levels, respectively. Both conditions are associated with increased morbidity for elderly people, and this requires necessary interventions. They share many common risk factors; among these, vitamin D (VD) deficiency appears to have a role. VD is involved in either disease with many mechanisms, among which immunomodulation. VD deficiency has been linked to OP because it inhibits the body's capacity to absorb calcium and maintain optimal bone health. Available evidence suggests that proper vitaminosis D also appears to be vital in preventing skin age-related issues. DP is often seen in elderly individuals, particularly those with long-term sun exposure and a history of chronic sun damage. VD deficiency can be linked to DP, since its involvement in collagen production, epidermal barrier function, inflammation regulation, wound healing, and sun protection. Aim of this review is to summarize the most updated existing evidence on the role of VD in the development of fragility syndromes such as DP and OP and the possible benefits of VD supplementation as a simple and harmful weapon against aging.

A cross-sectional study of clinical, dermoscopic, histopathological, and molecular patterns of scalp melanoma in patients with or without androgenetic alopecia

Scalp melanoma (SM) has a worse prognosis than melanoma in other locations likely because of late diagnosis due to hair coverage, difficulties in interpreting dermoscopy findings, and its unique molecular profile. We aimed to describe the clinical, histopathological, molecular, and dermoscopic patterns of SM and its relation to androgenetic alopecia/elastosis at the tumor site. Through a retrospective cross-sectional study, we identified all SM diagnosed at the A.C.Camargo Cancer Center between 2008 and 2018. In all, 48 SM were analyzed: 45.8% of which exhibited moderate/severe androgenetic alopecia and 54.1% exhibited elastosis. Androgenetic alopecia/elastosis at the site of the SM was associated with older age (p < 0.001), chronic sun damage (p < 0.001), lentigo maligna subtype (p = 0.029), and photodamaged dermoscopic pattern (p < 0.001). Additionally, 41 cases were evaluated with a 14-gene panel: 53.7% displayed mutations and 46.3% were wild-type. BRAF mutations were most common (77%), with BRAF V600K being more frequent (50%) than BRAF V600E (31.2%). The NF1 gene was evaluated in 40 samples, of which 20% exhibited mutations. SM presents differently in areas covered by hair compared to in areas with androgenetic alopecia. Patients without alopecia may have higher Breslow thickness due to late diagnosis because of hair concealment. The high frequency of detrimental mutations can also explain the poor prognosis of SM.

35406 Characterization of photodamaged skin using 3D line-field optical coherence tomography and histopathologic correlation

Noninvasive imaging techniques morphologically characterize photoaging and generate qualitative analysis in photodamaged skin. Optical coherence tomography (OCT) allows a deep laser penetration in the surface, reaching a good quality image of dermis visualization. A new 3-dimensional technology, 3D line field confocal OCT (LC-OCT) has been introduced, allowing a vertical and horizontal reconstruction of the complete skin with cellular resolution. The objective of this study was to observe in an in vivo 3-dimensional mode (3D LC-OCT) the morphologic and cytologic changes of photodamaged skin, to better understand the changes of the different skin layers induced by chronic sun exposure and responsible for chronic sun damage. 9 phototype II-III subjects were included. Dermoscopy and LC-OCT were performed on 2 zones: the sun-damaged area on the dorsal forearm and the non-sun-damaged area on the ventral side of the same forearm. Skin biopsies were obtained from both areas. All metrics were compared as paired data. LC OCT analysis showed increased epidermal thickness (mean: 5.39 μm, P = .0078) and higher number of keratinocytes (mean = 0.997; P = .002) in exposed vs nonexposed areas. The volume of the different keratinocyte layers seemed to be larger in the exposed area. Histology comparisons also showed an increased epidermal thickness on exposed areas. Significant differences were observed for the number of keratinocyte layers that was higher in photodamaged skin. This study provides for the first time a 3D quantitative analysis of photodamaged skin. There was a good correlation with histopathologic evaluation.

Determinants of 25-hydroxyvitamin D Status in a Cutaneous Melanoma Population.

Vitamin D status is influenced by well-known determinants, but factors associated with low 25-hydroxyvitamin D levels in the cutaneous melanoma population are not well defined. The aim of this study was to confirm the well-known determinants and to assess new determinants for 25-hydroxyvitamin D levels in a cutaneous melanoma population. In a prospectively included cohort of 387 patients with cutaneous melanoma the association of 25-hydroxyvitamin D levels with sex, age, body mass index, time of blood withdrawal, Fitzpatrick phototype, vitamin D supplementation, score for intensity of lifetime sun exposure, smoking, education level, hair and skin colour, eye colour, total number of benign naevi, freckles and parameters of chronic sun damage was investigated. In addition, 25-hydroxyvitamin D levels were correlated with pathological parameters of the primary tumour and melanoma stage (8th edition of the American Joint Committee on Cancer (AJCC). Univariate and multivariate logistic regressions were performed using R software. The following factors had a significant effect on vitamin D status: body mass index, seasonal time of blood sampling, vitamin D supplementation, and a subtype of skin, and hair colour.

Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma.

About 50% of melanomas harbour a BRAF mutation. Of these 50%, 10% have a V600K mutation. Although it is the second most common driver mutation after V600E, no specific studies have been conducted to identify a clinical and therapeutic gold standard for this patient subgroup. We analysed articles, including registrative clinical trials, to identify common clinical and biological traits of the V600K melanoma population, including different adopted therapeutic strategies. Melanoma V600K seems to be more frequent in Caucasian, male and elderly populations with a history of chronic sun damage and exposure. Prognosis is poor and no specific prognostic factor has been identified. Recent findings have underlined how melanoma V600K seems to be less dependent on the ERK/MAPK pathway, with a higher expression of PI3KB and a strong inhibition of multiple antiapoptotic pathways. Both target therapy with BRAF inhibitors + MEK inhibitors and immunotherapy with anti-checkpoint blockades are effective in melanoma V600K, although no sufficient evidence can currently support a formal recommendation for first line treatment choice in IIIC unresectable/IV stage patients. Still, melanoma V600K represents an unmet medical need and a marker of poor prognosis for cutaneous melanoma.

Pustular Scab on an Elderly Woman's Head

An older adult presented to our clinic with chronic sun damage. She had history of several actinic keratoses, one of which was removed by electrodessication and curettage. This resulted in a plaque with pustular exudate and was diagnosed with erosive pustulosis of the scalp (EPDS).

Perilesional sun damage as a diagnostic clue for pigmented actinic keratosis and Bowen's disease.

BackgroundChronic sun damage in the background is common in pigmented actinic keratoses and Bowen’s disease (pAK/BD). While explainable artificial intelligence (AI) demonstrated increased background attention for pAK/BD, humans frequently miss this clue in dermatoscopic images because they tend to focus on the lesion.AimTo analyse whether perilesional sun damage is a robust diagnostic clue for pAK/BD and if teaching this clue to dermatoscopy users improves their diagnostic accuracy.MethodsWe assessed the interrater agreement and the frequency of perilesional sun damage in 220 dermatoscopic images and conducted a reader study with 124 dermatoscopy users. The readers were randomly assigned to one of two online tutorials; one tutorial pointed to perilesional sun damage as a clue to pAK/BD (group A) the other did not (group B). In both groups, we compared the frequencies of correct diagnoses before and after receiving the tutorial.ResultsThe frequency of perilesional sun damage was higher in pAK/BD than in other types of pigmented skin lesions and interrater agreement was good (kappa = 0.675). The diagnostic accuracy for pAK/BD improved in both groups of readers (group A: +16.1%, 95%‐CI: 9.5–22.7; group B: +13.1%; 95%‐CI: 7.1–19.0; P for both <0.001), but the overall accuracy improved only in group A from (59.1% (95%‐CI: 55.0–63.1) to 63.5% (95%‐CI: 59.5–67.6); P = 0.002).ConclusionPerilesional sun damage is a good clue to differentiate pAK/BD from other pigmented skin lesions in dermatoscopic images, which could be useful for teledermatology. Knowledge of this clue improves the accuracy of dermatoscopy users, which demonstrates that insights from explainable AI can be used to train humans.

UVB mutagenesis differs in Nras- and Braf-mutant mouse models of melanoma.

BRAF-mutant melanomas are more likely than NRAS-mutant melanomas to arise in anatomical locations protected from chronic sun damage. We hypothesized that this discrepancy in tumor location is a consequence of the differential sensitivity of BRAF and NRAS-mutant melanocytes to ultraviolet light (UV)-mediated carcinogenesis. We tested this hypothesis by comparing the mutagenic consequences of a single neonatal, ultraviolet-AI (UVA; 340-400 nm) or ultraviolet-B (UVB; 280-390 nm) exposure in mouse models heterozygous for mutant Braf or homozygous for mutant Nras Tumor onset was accelerated by UVB, but not UVA, and the resulting melanomas contained recurrent mutations affecting the RING domain of MAP3K1 and Actin-binding domain of Filamin A. Melanomas from UVB-irradiated, Braf-mutant mice averaged twice as many single-nucleotide variants and five times as many dipyrimidine variants than tumors from similarly irradiated Nras-mutant mice. A mutational signature discovered in UVB-accelerated tumors mirrored COSMIC signatures associated with human skin cancer and was more prominent in Braf- than Nras-mutant murine melanomas. These data show that a single UVB exposure yields a greater burden of mutations in murine tumors driven by oncogenic Braf.

Surgical procedures in melanoma: recommended deep and lateral margins, indications for sentinel lymph node biopsy, and complete lymph node dissection.

Surgery is the main treatment for cutaneous melanoma including the primary melanoma as well as lymph node metastases. The recommended margins have changed over time. Similarly, indications for sentinel lymph node biopsy and complete lymph node dissection are constantly evolving if knowledge on the biological behavior of melanomas increases. The current guidelines and the most relevant literature were reviewed to provide an update on the existing recommendations for surgical management of melanoma. Wide excision margins are evidenced-based but not for all situations. Melanoma in situ requires 0.5-1 cm with increasing evidence for 1 cm particularly those presenting on the head-and-neck in the setting of chronic sun damage. Invasive melanomas need 1-2 cm margins, 2 cm for tumors thicker than 2 mm and some large tumors with >1-2 mm thickness and with a lentiginous growth pattern. Lentigo maligna, subungual melanoma, and acral lentiginous melanoma require surgical techniques with complete circumferential peripheral margin assessment. Sentinel lymph node biopsy provides relevant information for melanoma staging. Therefore, it is consistently recommended for melanomas >1-4 mm and highly recommended for melanomas >4 mm, >0.8-1.0 mm or ≤0.8 mm with additional risk factors. Complete lymph node dissection has high morbidity and no impact on survival and is restricted to regional control for clinically detected metastasis. Although the trend is to reduce progressively the recommended surgical margins, further evidence is needed to clarify its role in patients' survival. Sentinel lymph node biopsy is important for establishing a prognosis especially upon considering adjuvant therapy; complete lymph node dissection is only relevant for regional disease control.

Evaluation of subclinical chronic sun damage in the skin via the detection of long-lasting ultraweak photon emission.

It is well known that solar radiation accelerates skin photoaging. To evaluate subclinical photodamage in the skin especially from the early phase of ultraviolet (UV)-induced damage, we have focused on ultraweak photon emission (UPE), also called biophotons. Our previous study reported that the amount of long-lasting UPE induced by UV, predominantly from lipid peroxidation, is a valuable indicator to assess cutaneous photodamage even at a suberythemal dose, although it was only applied to evaluate acute UV damage. The aim of this study was to further investigate whether long-lasting UPE could also be a useful marker to assess subclinical chronic sun damage in the course of skin photoaging. Forty-three Japanese females in their 20s were recruited and were divided into two groups according to their history of sun exposure based on a questionnaire (high- and low-sun-exposure groups). Several skin properties on the cheek and outer forearm were measured in addition to UV-induced UPE. Among the skin properties measured, water content, average skin roughness, and the lateral packing of lipids in the stratum corneum were significantly deteriorated in the high-sun-exposure group as were changes in some skin photoaging scores such as pigmented spots and wrinkles. In addition, those skin properties were correlated with the UPE signals, suggesting the possible impact of oxidative stress on chronic skin damage. Subtle oxidative stress detected by long-lasting UPE may contribute to subclinical cutaneous damage at the beginning phase of chronic sun exposure, which potentially enhances skin photoaging over a lifetime.

Distribution and clinical role of KIT gene mutations in melanoma according to subtype: a study of 492 Spanish patients.

KIT mutations are primarily associated with acral and mucosal melanoma, and have been reported to show higher prevalence in chronic sun-damaged (CSD) than non-CSD melanomas. To investigate the prevalence of KIT mutations in melanoma according to subtype, and determine the clinical role of such mutations. We present results from a study of a Spanish population of 492 melanomas, classified according to the latest World Health Organization (WHO) guidelines. We analysed the mutational status of KIT and correlated with different clinical variables related to sun exposure and family history. KIT mutations were significantly more frequent in acral (3/36; 8.3%) and mucosal (4/8; 50%) melanomas than non-acral cutaneous melanomas. No significant difference was observed in KIT mutational status between CSD and non-CSD melanomas. Our results suggest that KIT mutations in melanoma tumours are unrelated to the development of nevi or chronic sun damage, but their presence is associated with aggressive melanomas which show ulceration, vascular invasiveness, and increased Breslow thickness. These findings are consistent with those reported by The Cancer Genome Atlas network.

Surgical procedures in melanoma in 2020: recommended deep and lateral margins, indications for sentinel lymph node biopsy, and complete lymph node dissection.

Introduction Surgery is the main treatment for cutaneous melanoma including the primary melanoma as well as lymph node metastases. The recommended margins have changed over time. Similarly, indications for sentinel lymph node biopsy and complete lymph node dissection are constantly evolving as long as knowledge on the biological behavior of melanomas increases. Evidence acquisition The current guidelines and the most relevant literature was reviewed to provide an update on the existing recommendations for surgical management of melanoma. Evidence synthesis Wide excision margins are evidenced-based but not for all situations. Melanoma in situ requires 0.5-1 cm with increasing evidence for 1 cm particularly those presenting on the head and in the setting of chronic sun damage. Invasive melanomas need 1-2 cm margins, 2 cm for tumors thicker than 2 mm and some large tumors with >1-2 mm thickness and with a lentiginous growth pattern. Lentigo maligna, subungual melanoma, and acral lentiginous melanoma require surgical techniques with complete circumferential peripheral margin assessment. Sentinel lymph node biopsy provides relevant information for melanoma staging. Therefore, it is consistently recommended for melanomas >1-4 mm and highly recommended for melanomas >4 mm, >0.8-1.0 mm or ≤0.8 mm with additional risk factors. Complete lymph node dissection has high morbidity and no impact on survival and is restricted to regional control for clinically detected metastasis. Conclusions Although the trend is to reduce progressively the recommended surgical margins, further evidence is needed to clarify its role in patients' survival. Sentinel lymph node biopsy is important for establishing a prognosis especially upon considering adjuvant therapy; complete lymph node dissection is only relevant for regional disease control.

Prediction of Immunotherapy Response in Melanoma Patients Cased on Easily Accessible Clinical Indicators

Response rates for Immune checkpoint blocker (ICB) monotherapy in melanoma patients with non-chronic sun damage subtype, which is predominant in the Asian population, is relatively modest (Cancer Res Treat. 2020 Feb 13. https://doi.org/10.4143/crt.2019.598). The use of dual ICB in patients with advanced or metastatic melanoma is controversial, mostly due to reported toxicity. Emerging data have suggested that combining ICB with radiotherapy (RT) could be a promising strategy. However, clinicians need better tools to identify which melanoma patients are likely to benefit from either monotherapy or combination-based approach. We retrospectively reviewed the records of 134 patients with metastatic or advanced melanoma who received ICB monotherapy between 2014 and 2018: acral/mucosal 80%, uveal 16.4%, and chronic-sun damage subtype 3.7%. Various clinical and therapeutic features were evaluated, and the multivariable Cox regression model for overall survival (OS) was used to identify potential prognostic factors. Patients were grouped according to the number of factors using the identified prognostic factors. With a median follow-up of 13.7 months (range, 1.6–60.2 months), the median progression-free survival (PFS) was 3.7 months in all patients. In multivariable analysis for OS, more advanced M stage (M1c/d vs. M1a/b; HR, 1.82; p = .022), development of treatment-related lymphopenia (<1000 cells/μL; HR, 1.89, p = .011), and elevated baseline LDH level (HR, 2.61; p<.001) were significantly associated with dismal treatment outcome. In multivariable analysis for PFS, more advanced M stage (M1c/d vs. M1a/b; HR, 1.59; p = .025), development of treatment-related lymphopenia (<1000 cells/μL; HR, 1.69, p = .012), and elevated baseline LDH level (HR, 2.68; p<.001) were significantly associated with dismal treatment outcome. Development of immune-related adverse events (vitiligo or hypothyroidism) within 6 months showed a trend toward better OS (HR, 2.86, p = .080), but not PFS. Using these four clinically practical indicators, we grouped patients into 4 groups according to the number of risk factors. In patients with 0-1, 2, 3, and 4 risk factors, the 2-year OSs were 79.7%, 42.1%, 15.3%, and 5.9%, respectively (p<.001), and the median PFSs were 8.6 months, 4.4 months, 2.8 months, and 2.0 months, respectively (p<.001). Although further validation is needed, the easily accessible early clinical biomarkers for OS were M stage, treatment-related lymphopenia, development of immune-related vitiligo/hypothyroidism, and elevated baseline LDH level. Better risk stratifying melanoma patients is helpful in defining the role of a combination approach, including our phase II study (NCT04017897).

Abstract 1271: UV irradiation and epigenetic change in melanocyte 5-hydroxymethylcytosine

Abstract Background Melanoma is the main cause of death from skin cancer. Excessive sun exposure with resultant UV irradiation, particularly during childhood, is established as its major environmental risk factor. Epigenetics are becoming increasingly recognized as potential reversible regulators of genomic anomalies responsible for cancerous growth. Loss of DNA hydroxymethylation marks 5-hydroxymethylcytosine (5-hmC) a functionally significant epigenetic event in melanomagenesis, but whether decreased 5-hmC is driven by UV irradiation remains unknown. The aim of this study is to characterize 5-hmC levels in potential melanoma precursor lesions and cultured samples by UV irradiation in vitro. Methods 70 human skin excision cases of chronic UV exposed skin and matched controls were evaluated. In addition, discarded human foreskins were exposed to biologically relevant doses of UVB (302 nm) and UVA (365 nm) irradiation. Tissue samples were then incubated in DMEM medium and after 24 hours fixed in 10% formalin overnight and stored in 70% ethanol prior to sectioning and staining. A dual anti-5-hmC and anti-MART-1 immunohistochemical (IHC) staining protocol was performed, and resultant semiquantitative immunoreactivity scores were analyzed statistically by one-way ANOVA analysis and Bonferroni's Multiple comparisons test or unpaired T-test using GraphPad Prism version 7 (GraphPad Software, La Jolla, CA). All p-values were two-tailed, with a p&amp;lt;0.05 considered statistically significant. Results When comparing sun-protected versus chronically sun-exposed sites of the excision specimens, lower levels of 5-hmC immunoreactivity were noted in melanocytes of sun-protected specimens than sun-exposed samples (p = 0.017). Moreover, a more significant difference (p = 0.0053) was detected between 5-hmC staining in normal skin melanocytes versus 5-hmC loss detected in so-called “atypical melanocytic hyperplasia of sun-damaged skin” that surrounds melanomas. Finally, we sought to determine whether we could induce in vitro a UV effect on 5-hmC similar to that seen with chronic sun-damage. Significant decreased immunoreactivity for 5-hmC was observed in foreskin melanocytes after UV irradiation- a finding that replicated what we observed in patient samples containing chronically UV-altered melanocytes. Conclusions Our results suggest that UVB irradiation's effect on the epigenome may play a crucial role in the development of melanoma. Implementation of the dual staining for anti-5-hmC and anti-MART-1 may be helpful in defining melanocytes altered in the direction of melanomagenesis, and thus may serve as a practical assay in determining potential melanoma precursor fields amenable to surveillance and prophylactic therapies. Citation Format: Kevin Y. Wang, Tanja Zdravkovic, Christine Lian. UV irradiation and epigenetic change in melanocyte 5-hydroxymethylcytosine [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1271.

Clinical, environmental and histological distribution ofBRAF,NRASandTERTpromoter mutations among patients with cutaneous melanoma: a retrospective study of 563 patients*

The distinct somatic mutations that define clinical and histopathological heterogeneity in cutaneous melanoma could be dependent on host susceptibility to exogenous factors like ultraviolet radiation. Firstly, to characterize patients with cutaneous melanoma clinically and pathologically based on the mutational status of BRAF, NRAS and TERT promoter. Secondly, to elucidate the modified features due to the presence of TERT promoter mutations over the background of either BRAF or NRAS mutations. We performed a retrospective study on 563 patients with melanoma by investigating somatic mutations in BRAF, NRAS and TERT promoter. We observed co-occurrence of TERT promoter mutations with BRAF and NRAS mutations in 26.3% and 6.9% of melanomas, respectively. Multivariate analysis showed an independent association between BRAF mutations and a decreased presence of cutaneous lentigines at the melanoma site, and an increased association with the presence of any MC1R polymorphism. We also observed an independent association between TERT promoter mutations and increased tumour mitotic rate. Co-occurrence of BRAF and TERT promoter mutations was independently associated with occurrence of primary tumours at usually sun-exposed sites, lack of histological chronic sun damage in surrounding unaffected skin at the melanoma site, and increased tumour mitotic rate. Co-occurrence of NRAS and TERT promoter mutations was independently associated with increased tumour mitotic rate. The presence of TERT promoter together with BRAF or NRAS mutations was associated with statistically significantly worse survival. The presence of TERT promoter mutations discriminates BRAF- and NRAS-mutated tumours and indicates a higher involvement of ultraviolet-induced damage and tumours with worse melanoma-specific survival than those without any mutation. These observations refine classification of patients with melanoma based on mutational status.

TERT and TERT promoter in melanocytic neoplasms: Current concepts in pathogenesis, diagnosis, and prognosis.

Located on chromosome locus 5p15.33, telomerase reverse transcriptase (TERT or hTERT) encodes the catalytic subunit of telomerase which permits lengthening and preservation of telomeres following mitosis. Mutations in TERT promoter (TERT-p) upregulate expression of TERT, allowing survival of malignant cells and tumor progression in wide variety of malignancies including melanoma. The objective of this review is to examine the roles of TERT and TERT-p in the pathogenesis, diagnosis, and prognostication of cutaneous melanoma. All studies of TERT or TERT-p in cutaneous melanocytic neoplasms with the following inclusion criteria were reviewed: publication date between 2010 and 2019, English language, and series of ≥3 cases were reviewed for evidence supporting the role of TERT in pathogenesis, diagnosis, and prognosis. Studies with <3 cases or focused primarily on mucosal or uveal melanocytic tumors were excluded. TERT-p mutations are frequent in chronic and non-chronic sun damage melanoma and correlate with adverse prognosis, inform pathogenesis, and may provide diagnostic support. While TERT-p mutations are uncommon in acral melanoma, TERT copy number gains and gene amplification predict reduced survival. Among atypical spitzoid neoplasms, TERT-p mutations identify biologically aggressive tumors and support the diagnosis of spitzoid melanoma. TERT-p methylation may have prognostic value in pediatric conventional melanoma and drive tumorigenesis in melanoma arising within congenital nevi. Finally, TERT-p mutations may aid in the differentiation of recurrent nevi from recurrent melanoma.

Current therapies for actinic keratosis

Actinic keratosis (AK) is a very common skin disease caused by chronic sun damage, which in 75% of cases arises on chronically sun-exposed areas, such as face, scalp, neck, hands, and forearms. AKs must be considered an early squamous cell carcinoma (SCC) for their probable progression into invasive SCC. For this reason, all AK should be treated, and clinical follow-up is recommended. The aims of treatment are: (i) to clinically eradicate evident and subclinical lesions, (ii) to prevent their evolution into SCC, and (iii) to reduce the number of relapses. Among available treatments, it is possible to distinguish lesion-directed therapies and field-directed therapies. Lesion-directed treatments include: (i) cryotherapy; (ii) laser therapy; (iii) surgery; and (iv) curettage. Whereas, field-directed treatments are: (i) 5-fluorouracil (5-FU); (ii) diclofenac 3% gel; (iii) chemical peeling; (iv) imiquimod; and (v) photodynamic therapy (PDT). Prevention plays an important role in the treatment of AKs, and it is based on the continuous use of sunscreen and protective clothing. This review shows different types of available treatments and describes the characteristics and benefits of each medication, underlining the best choice.

553 Biophoton-revealed ultraweak oxidative stress represents unnoticed chronic sun damage in the human skin

553 Biophoton-revealed ultraweak oxidative stress represents unnoticed chronic sun damage in the human skin

566 Short-term, incidental sun-exposure causes epigenetic drift which is significantly reduced through daily SPF use and can be replicated in an ex-vivo skin model

Introduction: Up to now, UV-induced epigenetic drift has only been shown to occur in skin that has experienced decades of chronic sun exposure and is associated with large regions of hypo-methylation1. Objectives: 1) To determine if sun-induced epigenetic drift occurs after 5 months of incidental sun-exposure, and if a sun-protection factor (SPF) product can protect against such drift. 2) To develop a 1 week ex-vivo model that mirrors 5-month in-vivo UV-induced epigenetic drift. Materials and Methods: A single center, IRB-approved, biopsy study involving 60 females, age 25-45 with Fitz skin types II-III. Subjects applied a SPF product to the face and one arm over the course of five months, tracked with clinical instrumental measurements, and biopsies taken from both arms at baseline and at the end of the study. DNA was isolated from the biopsies and methylation levels interrogated using a pre-selected, UV-sensitive set of probes from Illumina methylation arrays. Anex-vivo, repeat UV, skin model was developed to assess epigenetic drift and protection. Results: Instrumental measurements confirmed that the untreated and treated arms had melanin changes consistent with UV exposure and protection respectively. Incidental, short-term sun-exposure led to a significant epigenetic drift and in the direction expected by chronic sun-damage; SPF product-use significantly reduced the drift. An almost identical epigenetic drift and SPF protection were detected in the ex-vivo model. Conclusions: This the first study to demonstrate that UV-induced epigenetic drift occurs even during incidental, short-term sun-exposure and that a SPF product can significantly reduce the drift, reinforcing the importance of daily sun-protection. References 1 Vandiver AR, Irizarry RA, Hansen KD et al. Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin. Genome Biol 2015; 16: 80.