Chronic Sun Exposure Research Articles

Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: The Current and Future Role of Radiation Therapy in the Era of Immunotherapy.

Simple SummaryNodal and distant metastases of cutaneous squamous cell carcinomas are very rare and lead to dismal prognoses. Immunotherapy is approved only for cutaneous squamous cell carcinoma patients not amenable to surgery or curative radiation therapy. Radiation therapy has a clear role as an adjuvant treatment for locally advanced disease. Radiation therapy may also have an important role in inoperable and metastatic disease. Oligometastatic disease is a condition that needs to be defined for this carcinoma. This review aims to offer to the readers a comprehensive overview of studies about the role of radiotherapy in the management of advanced or metastatic cutaneous squamous cell carcinomas, also assuming possible further developments in the light of the recent discoveries about tumor biology. The present paper has the merit of re-focusing great attention on the efficacy and cost-effectiveness of radiotherapy in these not yet properly explored scenarios.Radiation therapy (RT) is an effective therapeutic option for small localized cutaneous squamous cell carcinoma (cSCC) among patients who are not eligible for or refuse surgery. RT also has a defined role as an adjuvant treatment in cases of adverse features that predispose to tumor recurrence after local excision. Since the development of cSCC is often a late consequence of chronic sun exposure, its occurrence is more common among elderly patients whose comorbidities may contraindicate surgical procedures. These could be impeded not only by frail medical conditions but also by technical issues. Indeed, an aggressive locoregional behavior of cSCC may culminate in unresectability due to widespread invasion of neighboring tissues. Moreover, cSCC could develop distant metastases. Both locally advanced and metastatic cSCCs carry a poor prognosis. In these scenarios, recent discoveries of tumor molecular targets are promoting the use of promising systemic therapies, especially immunotherapy, over RT. However, the results from using immunotherapy and, even more so, of chemotherapy are still not optimal. By contrast, advances in radiation delivery equipment can safely treat even large and complex-shaped cSCC targets in challenging body sites. In addition, RT could also have a role in metastatic cSCC settings by enhancing the effectiveness of concomitant immunotherapy. The aim of this review is to summarize and comment on the body of literature about the use of radiotherapy for operable and inoperable locally advanced cSCCs and for metastatic ones in an attempt to define its current and future role.

Solar keratosis

Solar keratosis is a common skin condition characterised by scaly skin lesions, usually found on sun-exposed areas of the body. It is also known as actinic keratosis, senile keratosis and solar keratosis; the name originates from Latin and means ‘skin thickening due to sun'. It was first described by Dubreuilh in 1826, and for many years was known as ‘keratoma senilis’. In 1958 it was finally named actinic keratosis, by Pinkus. Solar keratotsis represents dysplastic proliferations of keratinocytes, secondary to chronic sun exposure, especially ultra-violet radiation. Solar keratosis is the most common pre-malignant skin condition; however, it is increasingly thought to represent a spectrum of disease in between photo-damaged skin and squamous cell carcinoma (SCC). A small proportion of solar keratosis progresses to become SCC, and the chances of progression increase with the increase in the number of lesions. Incidence of solar keratosis in the UK is increasing due to an ageing population, leading to increased burden on the healthcare system.

Cumulative Sun Exposure and Melanoma in a Population-Based Case-Control Study: Does Sun Sensitivity Matter?

Simple SummaryMelanoma has been clearly shown to be related to sunburns and other types of intermittent sun exposure. It is less clear how cumulative sun exposure is related to melanoma. In this case–control study, the cumulative hours of sun exposure per day were examined between spring and fall each year over periods or decades of life to estimate lifetime hours of sun exposure. No associations were found before the age of 60. However, when stratified by fair skin color, we found little or no association with hours of sun exposure among fair-skinned individuals, but found an increased risk for higher hours of sun exposure among medium- or darker-skinned individuals for lifetime exposure.Cutaneous melanoma (CM) has consistently been associated with intermittent sun exposure, while the association with chronic sun exposure is debated. The goal of this research was to examine the complex relationship between CM, sun sensitivity and sun exposure based on theoretical concepts of how these factors may be associated. Detailed sun exposure histories across life periods and various measures of sun sensitivity were collected in a population-based case–control study of melanoma in Iowa, USA. Participants were asked about their hours of sun exposure per day between March and October each year over periods or decades of life to estimate cumulative lifetime hours of sun exposure. Increased odds ratios (ORs) for CM were seen for most standard measures of sun sensitivity except for the tendency to sunburn. Minimal associations were seen with total hours of sun exposure early in life. However, an interaction was seen between fair skin color and lifetime hours of sun exposure, where the strongest associations with CM were seen among medium-skinned and dark-skinned participants. This suggests that cumulative sun exposure at high levels may increase CM among non-sun-sensitive individuals typically at lower risk of CM. Such a finding has implications for the prevention effort for melanoma regarding time in the sun among darker-skinned individuals.

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.

Eyelid malignancies in young individuals: clinical peculiarities.

The incidence of malignant eyelid tumors is considerably increasing, even in young patients. The purpose of this study was to identify particularities in individuals under 40years of age affected by eyelid malignancies. Clinical charts of patients under 40years of age who underwent eyelid tumor excision from 2014 to 2020 in two reference centers, one in Brazil and one in the USA, were reviewed. Demographic and outcome measures included: age, gender, skin phototype, comorbidities, diagnosis, time until diagnosis, lesion location, recurrence and metastasis. In addition, associated characteristics, including chronic sun exposure, intentional tanning (outdoor or artificial), history of smoking, use of sunscreen, family history of skin cancer and exposure to pesticides or herbicides, were reviewed. A total of 24 malignant eyelid tumors from 17 patients were identified. Twelve (70.6%) patients were female, and the most prevalent tumor was basal cell carcinoma (62.5%). Three (17.6%) patients had xeroderma pigmentosum and presented with multiple lesions. Family history of skin cancer was reported by 47% of patients. Prolonged sun exposure was reported by 41.2%; history of smoking and intentional tanning were reported by 23.5 and 17.6%, respectively, and might have played a role in carcinogenesis. Although uncommon in young subjects, eyelid malignancies present some peculiarities in individuals under 40years of age. Our results suggest that women with family history of skin cancer and history of chronic exposure to ultraviolet radiation are at risk. Association with genetic syndromes is also relevant among younger age groups.

Cutaneous granular cell tumor: A case series, review, and update.

Granular cell tumor (GCT) or Abrikossoff's tumor is an uncommon neuro-derived tumor in which Schwann cells are found and express S-100 protein. Often, it is a benign lesion. Histopathologically, there are granular cell infiltrations through the entire dermis without necrosis which are periodic acid Schiff (PAS) stain positive and reactive with S-100. The aim of this study is the clinicopathological evaluation of GCT. In this paper, we described the experience of 6 patients with a GCT in different locations (4 cases in the skin and 2 cases in the mucosa), for example, a case with a tumor in the abdomen and a keloidal-like presentation with a highly sclerotic pattern (an uncommon pathological feature). Another case developed a lesion secondary to physical trauma. In one case, the presence of a lesion in the lower lip associated with actinic damage secondary to chronic sun exposure resulted in misdiagnosis with actinic cheilitis and squamous cell carcinoma. Histopathologically, there were granular cell infiltrations through the entire dermis without necrosis which are PAS-positive and reactive with S-100.

Risk factors for actinic cheilitis: A meta-analysis.

Background. Actinic cheilitis (AC) is a potentially malignant disorder characterized by chronic lip inflammation, especially the lower lip, associated with accumulative exposure to solar radiation. The present study aimed to assess the possible risk factors related to AC. Methods. A search for studies on AC risk factors was conducted in the following databases: PubMed (MEDLINE, Cochrane Library), Web of Science (WoS), and Google Scholar. For dichotomous outcomes, the estimates of the effects of intervention were expressed as odds ratios (ORs) using Mantel-Haenszel (M-H) method, and for continuous outcomes, the estimates of the effects of intervention were expressed as mean difference (MD) using the inverse variance (IV) method, both with 95% confidence intervals. Results. Twelve studies were considered in this meta-analysis. The factors from the highest to lowest risk of AC were having a low skin phototype (OR: 3.30), age >50 years (OR: 3.01), having high sun exposure, cumulative throughout life (OR: 2.13) as daily (OR: 2.00), being male (OR: 1.78), and being a drinker (OR: 1.56) or smoker (OR: 1.32). However, the use of sunscreen creams and caps/hats to protect against the sun were factors with no significant influence on the AC risk. Conclusion. Chronic sun exposure in subjects with low skin phototypes is the main risk factor for AC.

Does psoriasis need more radiation dose to clear recalcitrant plaques? A case series of lesions from a single subject

Psoriasis vulgaris is a chronic benign disease of the whole thickness of the epidermis with symptomatic plaque formation impacting quality of life. Relatively low doses of fractionated radiotherapy (RT) have been used in the past to a total dose of four to six Gray (Gy). We present the case of an older male with seven recalcitrant plaques each treated with the same prescribed dose of RT. Superficial radiotherapy (SXRT) with a 100kV beam from a Xstrahl 300 machine to a total dose of 20 Gy in 10 fractions (#s) at five #s per week was used for six areas - four on the scalp and one on each elbow. At six months post treatment, four scalp areas had a continuing complete response (CR) whilst the elbows had a continuing partial response (PR). A seventh area, measuring 21 x 16cm on the lower back, was treated with volumetric modulated arc therapy (VMAT) using six megavoltage photons (MV) at the same prescribed dose. At four weeks, an infield CR was observed, but at eight weeks there was some infield recurrence. Pre- and post-RT biopsies from this field were compared. In the VMAT area with clinical recurrence, RT caused a histological PR. In the VMAT area with clinical CR, there was no histological evidence of disease. These findings raise radiobiological questions. Was the difference in clearance due to lower disease burden, kilovoltage backscatter from bone giving a higher relative dose, a difference in oxygenation or chronic sun exposure of tissues, or a difference in the relative biological effectiveness (RBE) between SXRT (1.2) relative to MV photons (1.0)? We recommend that future studies of RT in psoriasis start with 20Gy in 10#s, preferably with a modality that can penetrate the whole plaque epidermis, which can be quite thickened in patients suffering from psoriasis.

28144 Cobblestoned skin on neck: The differential

Pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-like PDE) is a benign cutaneous condition that mimics pseudoxanthoma elasticum (PXE). PXE is a hereditary distortion and calcification of elastic fibers, not only in cutaneous tissue, but in cardiac and ocular tissues. Histopathology is an important diagnostic tool to distinguish between the two and can save the patient from an extensive work-up if misdiagnosed as PXE. We present, herein, a 62-year-old healthy female of with an asymptomatic papular rash on her neck for 8 months. She wears a hijab, and reports frequent heat and sweat. The patient failed topical steroid creams given by her primary care provider. Exam showed multiple skin-colored to yellow smooth papules on the bilateral and posterior neck, and bilateral antecubital fossae. Biopsy from her left neck showed abrupt loss of elastic fibers in the papillary dermis with a Verhoeff-van Gieson stain. A von Kossa stain did not demonstrate calcium deposition, ruling out PXE. PXE-LPDE is likely an underdiagnosed acquired condition that occurs most commonly in women after the sixth decade of life and has overlapping clinical and histopathologic features with white fibrous papulosis, another benign condition that can be argued is the same entity. We favored PXE-LPDE in our patient due to the band-like loss of elastic fibers in the papillary dermis. Although chronic sun exposure has been implicated in its pathogenesis, our patient has been sun protected for most of her life. Unfortunately, no specific therapy has been shown to be successful in the treatment of PXE-like PDE.

25907 Actinic keratosis in Colombia: First approaches

Introduction: Actinic keratoses (AK) are preneoplastic lesions secondary to chronic sun exposure, whose risk of becoming malignancy is greater than 20%. Prevalence studies of AK are uncommon. Here we describe clinical and epidemiologic characteristics of patients with AK assessed in a dermatology center from Bogota, Colombia.

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.

Metástasis agresiva de glándula parótida y cuello causada por carcinoma cutáneo de células escamosas de cuero cabelludo: reporte de un caso

Introduction: The head and neck are frequent sites for the development of cutaneous cancer and squamous cell carcinoma of the skin (SCC), one of the more frequent malignant non-melanoma skin neoplasms in Chile (436 per 100,000 inhabitants). Between 5-10% skin SCC progresses aggressively generating metastasis to parotid and cervical lymph nodes. Case Report: A 82 years old male, presents painful increased volume lesion in the mandibular area. He has a history of chronic arterial hypertension, acute renal failure, SCC of the scalp, extra-pulmonary tuberculosis, chronic sun exposure and smoking. Extraoral examination showed a 4 cm lesion in the posterior third of the mandibular branch, with undefined edges, a firm consistency and painful on palpation. Intraorally, erythematous mucosa is observed, as well as lack of lubrication, tenderness and cortical bone expansion. Incisional biopsy is performed, imaging and histological exams are requested. The results indicate the presence of SCC, and therefore referral to secondary care. Many risk factors are associated with SCC development, with ultraviolet radiation the most relevant in this case, favoring its appearance on the scalp. The probability of metastasis is low, but when it happens, the majority of cases that started in the scalp, disseminate to the parotid and cervical region. Conclusion: The SCC has a good prognosis. However, there are antecedents, such as size and location, that must alert the professional to perform the monitoring, early screening, control of metastatic nodes in maxillofacial area.

ARTICLE: Efficacy of Ceramide-Containing Formulations on UV-Induced Skin Surface Barrier Alterations.

The human skin, particularly the stratum corneum, serves as a protective barrier against exogenous factors, including ultraviolet radiation (UVR) and pathogen invasions. The impact of UVR on skin cancer and photoaging has been extensively studied. However, the direct impact of UVR on skin barrier integrity under clinical settings remains poorly explored. Due to their benefits in reducing inflammation and promoting skin barrier repair, ceramide-containing formulations can provide added photoprotection benefits. In this study, the efficacy of a ceramide-containing sunscreen and moisturizer were evaluated in preventing UV-induced skin surface barrier changes. Expert grading, instrumental, and tape-stripping assessments demonstrated that UVR induced erythema and hyperpigmentation and caused changes in skin cells surface morphological organization and maturation. Treatment with a ceramide-containing sunscreen and moisturizing cream routine reduced erythema and hyperpigmentation, improved skin hydration, and maintained normal superficial skin cells morphology and turnover after UVR. Our results indicate that barrier-enforcing lipids formulations can provide additional benefits in patient’s daily routine by strengthening the barrier and improving skin health overall against chronic sun exposure. J Drugs Dermatol. 20(4 Suppl):s29-35. doi:10.36849/JDD.S589E.

Frequency of procedural and medical treatments of actinic keratosis

Frequency of procedural and medical treatments of actinic keratosis

ARTICLE: Efficacy of Ceramide-Containing Formulations on UV-Induced Skin Surface Barrier Alterations

The human skin, particularly the stratum corneum, serves as a protective barrier against exogenous factors, including ultraviolet radiation (UVR) and pathogen invasions. The impact of UVR on skin cancer and photoaging has been extensively studied. However, the direct impact of UVR on skin barrier integrity under clinical settings remains poorly explored. Due to their benefits in reducing inflammation and promoting skin barrier repair, ceramide-containing formulations can provide added photoprotection benefits. In this study, the efficacy of a ceramide-containing sunscreen and moisturizer were evaluated in preventing UV-induced skin surface barrier changes. Expert grading, instrumental, and tape-stripping assessments demonstrated that UVR induced erythema and hyperpigmentation and caused changes in skin cells surface morphological organization and maturation. Treatment with a ceramide-containing sunscreen and moisturizing cream routine reduced erythema and hyperpigmentation, improved skin hydration, and maintained normal superficial skin cells morphology and turnover after UVR. Our results indicate that barrier-enforcing lipids formulations can provide additional benefits in patient’s daily routine by strengthening the barrier and improving skin health overall against chronic sun exposure. J Drugs Dermatol. 20(4 Suppl):s29-35. doi:10.36849/JDD.S589E

How do some genetic mutations affect the outcome of patients with skin melanoma?

British Journal of DermatologyVolume 184, Issue 3 p. e91-e91 Plain Language SummaryFree Access How do some genetic mutations affect the outcome of patients with skin melanoma? First published: 05 March 2021 https://doi.org/10.1111/bjd.19768AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract The outcome for a type of skin cancer called melanoma can vary between different individuals. Apart from factors such as the depth of the tumour and degree of spread, the presence of markers for certain genetic changes (mutations) can also affect the disease outcome. One form of mutation (BRAF) is often found in younger patients with a history of intermittent exposure to too much ultraviolet light from the sun; and several targeted therapies can be effective in such patients, who have disease that has now spread to other parts of their body. On the other hand, another type of mutation (NRAS) is typically found in older patients with a history of chronic sun exposure; these patients respond less well to targeted therapy. Both of these mutations require an extra trigger, such as ultraviolet light, for the cells to become cancerous. In addition, frequently mutations of the promoter of the TERT gene, which are linked with damage from ultraviolet light, are associated with more aggressive tumours and a poorer outcome. In this paper, the authors from Spain and Germany looked at data from 563 patients with skin melanoma. They found that BRAF and NRAS mutations were common in the tissues they examined from these patients. The additional presence of the TERT promoter mutation worsened the outcome, particularly in patients who had the NRAS mutation. Patients without any of these mutations that they investigaged tended to have a better outcome overall. Classifying patients according to the presence or absence of these three mutations (BRAF, NRAS and TERT) should help in assessing disease outcome. Linked Article: Manrique-Silva et al. Br J Dermatol 2021; 184:504–513. Volume184, Issue3March 2021Pages e91-e91 RelatedInformation

Management of Actinic Keratoses

Chronic sun exposure causes the development and progression of AKs. This is due to the cumulative ultraviolet (UV) radiation from the sun which causes neoplastic effects in keratinocytes. Ultraviolet radiation exists in three wavelengths: UVA at 315-400 nm, UVB at 280-315 nm, and UVC at 100-280 nm. Generally, only UVA and UVB make it through the ozone layer. The long wavelength of UVA allows it to penetrate the skin as deep as the basal layer. This causes melanocytes within the basal layer to react and produce more melanin, indicative of skin damage .

A clinical study of idiopathic guttate hypomelanosis and its association with diabetes mellitus

Objectives: To study the clinical profile of idiopathic guttate hypomelanosis (IGH) and its association with diabetes mellitus (DM). Materials and Methods: A 1-year descriptive study was carried out in clinically diagnosed cases of IGH. A detailed history was taken and a thorough dermatological examination was carried out in each case. Serum fasting blood sugar [FBS] and postprandial blood sugar (PPBS) levels were determined in all cases. FBS and PPBS were assessed in age- and sex-matched individuals without IGH who were included as the comparative group. Results: There were a total of 102 patients (n = 102) with IGH in the designated study period. The male/female ratio was 1:3.08. The mean age was 36.7 years. The most common age group was 61–70 years (29, 28.4%). History of chronic sun exposure was present in 19 (18.6%). Thirty-one patients (30.4%) showed lesions affecting upper limb, lower limb, and trunk. In the present study, 23 patients with IGH had DM. In the age- and sex-matched comparative group, 19 patients had DM (18.6%). The difference was not statistically significant (P = 0.498). In the present study, 17 patients (17/23, 73.9%) with IGH and DM had 20 lesions or more, while 6 patients (6/23, 26.1%) with IGH and DM had < 20 lesions. Among the 79 non-diabetic patients with IGH, 57 (72.2%) had 20 lesions or more and 22 (27.8%) had less than 20 lesions. This was not statistically significant (P = 0.868). Limitations: Small sample size was the major limitation. Conclusion: There was no association between IGH and DM in this study and there was no association between number of lesions of IGH and DM.

Skin cancer and sun protection practices in Fanconi anemia patients: A cross-sectional study

Skin cancer and sun protection practices in Fanconi anemia patients: A cross-sectional study

Disseminated superficial actinic porokeratosis in a patient with generalized vitiligo: A case report

Disseminated superficial actinic porokeratosis (DSAP) is the most common type of porokeratosis, occurring mainly on sun-exposed skin. Chronic sun exposure is one of the main risk factors, in addition to genetic susceptibility. Most published data concerning the relationship between vitiligo and its predisposition to nonmelanoma skin cancer suggests that patients with vitiligo show the same or even a lower incidence than other populations. Herein, we report a case of disseminated superficial actinic porokeratosis occurring in vitiligo in which chronic sun exposure was the main risk factor