Both Basal Cell Carcinoma Research Articles

Childhood sunburn and risk of melanoma and non-melanoma skin cancer: a Mendelian randomization study

Previous evidence has suggested that childhood sunburn could be a risk factor for cutaneous malignant melanoma (MM) and non-melanoma skin cancer (NMSC). However, existing observational studies could not reveal the causal associations genetically. This study aimed to investigate whether there was a genetic causal relationship between childhood sunburn and skin cancers. Univariable Mendelian randomization (MR) and Causal Analysis Using Summary Effect analysis was carried out for causal estimates and evaluation for the horizontal pleiotropy. Multivariable MR and the mediation effects analysis were used to test whether the causal associations were mediated by potential confounders. A suggestively significant causal association between childhood sunburn and MM was indicated (OR = 4.74; 95% CI: 1.31–17.19; p = 1.79E-02). Genetically predicted childhood sunburn was significantly associated with increased risk of overall melanoma in situ (MIS) (OR = 4.02; 95% CI: 2.00–8.08; p = 9.40E-05), MIS of face (OR = 18.28; 95% CI: 5.28–63.35; p = 4.59E-06), and MIS of trunk (OR = 7.05; 95% CI: 2.06–24.13; p = 1.88E-03). Similar trends were found for childhood sunburn and NMSC (OR = 8.16; 95% CI: 6.07–10.99; p = 1.53E-20), including both basal cell carcinoma (BCC) (OR = 3.76; 95% CI:2.96–4.77; p = 2.19E-08) and squamous cell carcinoma (SCC) (OR = 7.44; 95% CI: 5.09–10.87; p = 2.19E-08). After adjustment for hair and skin color, facial ageing, vitamin D levels, body mass index, alcohol consumption, and smoking status, childhood sunburn showed an independent association with MIS, MIS of face, MIS of trunk, as well as NMSC, including both BCC and SCC. Mediation analysis showed no significant mediation effect. This study demonstrated a causal relationship between childhood sunburn and the risk of both MM and NMSC, which suggested that enhanced screening and prevention for childhood sunburn could contribute to the early detection and decreased risk of MM and NMSC.

High-frequency (20 MHz) high-intensity focused ultrasound: New Treatment of actinic keratosis, basal cell carcinoma, and Kaposi sarcoma. An open-label exploratory study.

BackgroundSkin cancer is common, growing, challenging, and in need of progress in early‐stage treatment. 20 MHz high‐intensity focused ultrasound (HIFU) is new and applied to actinic keratosis (AK) and skin cancers for the first time. HIFU of lower frequency is already used in the treatment of internal cancers.Materials and MethodsEight patients with 201 AK lesions, one patient with 7 basal cell carcinomas (reoccurrences after PDT), and one patient with 7 Kaposi sarcoma lesions (4 treated with radiotherapy in the past) were given 1‐3 HIFU treatments. Twenty megahertz HIFU was dosed as 150 ms at 0.6‐1.2 J/shot applied to target lesions. Probes with different target depths were available. The preferred shot energy and focal depth in AK were 0.9 J and 1.3 mm. A “Sandwich” strategy with HIFU applied in two depths were tried in cancers. The follow‐up period was 3‐6 months.ResultsAll AK cleared except 5, giving a cure rate of 97%. Post‐treatment lesion healed in 1‐2 weeks with no scar. VAS pain was from 1 to 8, and in any case less than experienced with previous PDT. In both basal cell carcinoma (BCC) and sarcoma, healing was confirmed by histological verification.Discussion/conclusion20 MHz HIFU was an effective and safe treatment of AK. This new treatment, applicable to any anatomical site, has promising advantages relative to PDT and has the potential to replace or supplement PDT in future. Case‐observations indicated that HIFU can be useful in skin cancers as well.

A fuzzy logic based approach for prediction of basal cell carcinoma and squamous cell carcinoma among the data of skin cancer

INTRODUCTION: Both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) is a type of skin malignancy which are deadly in nature. Although both can cause a serious setback for the human body, SCC is most dangerous as per human life is concerned.OBJECTIVES: It is necessary to spot out the cases of SCC and BCC among various data of skin cancer. In this research, the same is spotted out with the help of the fuzzy logic system.METHODS: At first, the membership function is constructed from the input data provided. Then based on the generated membership function, a set of fuzzy if-then rules are created. The outliers from the source data are also removed before the generation of the fuzzy membership function. Based on the fuzzy if-then rules, the decision, whether the case is of basal cell or squamous cell carcinoma is taken.RESULTS: The output prediction by the system is compared with the actual pathological report of the patients. The comparison provides an accuracy of 94.94 percent.CONCLUSION: This paper introduces a new technique to predict the existence of multiple cancers (either basal cell or squamous cell) from the mixed cancer dataset. The outcomes of the examination on the source dataset show that the proposed system achieved extraordinary desire accuracy for the portrayal of squamous cell carcinoma and basal cell carcinoma.

Genetic Mutations Underlying Phenotypic Plasticity in Basosquamous Carcinoma

Basosquamous carcinoma (BSC) is an aggressive skin neoplasm with the features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). While genetic drivers of BCC and SCC development have been extensively characterized, BSC has not been well studied, and it remains unclear whether these tumors originally derive from BCC or SCC. In addition, it is unknown which molecular pathways mediate the reprogramming of tumor keratinocytes toward basaloid or squamatized phenotypes. We sought to characterize the genomic alterations underlying sporadic BSC to elucidate the derivation of these mixed tumors. We identifed frequent Hedgehog (Hh) pathway mutations in BSCs, implicating Hh deregulation as the primary driving event in BSC. Principal component analysis of BCC and SCC driver genes further demonstrate the genetic similarity between BCC and BSC. In addition, 45% of the BSCs harbor recurrent mutations in the SWI/SNF complex gene, ARID1A, and evolutionary analysis revealed that ARID1A mutations occur after PTCH1 but before SCC driver mutations, indicating that ARID1A mutations may bestow plasticity enabling squamatization. Finally, we demonstrate mitogen-activated protein kinase pathway activation and the loss of Hh signaling associated with the squamatization of BSCs. Overall, these results support the genetic derivation of BSCs from BCCs and highlight potential factors involved in modulating tumor reprogramming between basaloid and squamatized phenotypes.

Abstract LB-170: 9cis-retinoid UAB30 manifests potent chemopreventive effects in a murine model of UVB-induced basal cell and squamous cell carcinoma

Abstract Vitamin A derivatives such as retinoids are known to inhibit cell proliferation and induce cellular differentiation/apoptosis in various tumor cells. Although many retinoids have been limited due to their severe adverse effects, but 9cUAB30, a highly selective novel retinoid X receptors (RXR)-agonist has been shown an effective anti-carcinogenic activity. Here, we demonstrated the chemopreventive and chemotherapeutic efficacy of 9cUAB30 in UVB-induced photocarcinogenesis in Ptch+/-/SKH-1 murine model, which develops both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Both topical and systemic application to 9cUAB30 significantly reduced UVB-induced skin photocarcinogenesis in terms of tumor number and tumor volume. 9cUAB30 reduced UVB-induced skin hyperplasia, proliferation, and enhanced differentiation of suprabasal epidermal keratinocytes. Induction of apoptosis was also noted in these neoplastic lesions treated with this retinoid. 9cUAB30 was almost equally potent in the inhibition of either UVB-induced skin BCCs or SCCs in Ptch+/-/SKH-1 mice. 9cUAB30-treated residual tumors were manifesting reduced epithelial-mesenchymal transition (EMT) progression with a less aggressive tumor phenotype, which was associated with the enhanced expression of E-cadherin and reduced expression of N-cadherin, Fibronectin, Snail and Twist. 9cUAB30-mediated therapeutic intervention against these tumors was also involved induction of extensive DNA double strand breaks (DSBs) characterized by the enhanced phosphorylation of H2AX. This DNA damage response was unique to 9cUAB30 compare to other known RXR inhibitors such as Bexarotene. It was also independent of reactive oxygen species (ROS) production as ROS scavenger namely, N-acetyl cysteine did not effectively block it. However, 9cUAB30 provoked DNA damage response signaling was associated with the enhanced phosphorylation and activation of ATM, Rad50, ATR, Chk1, and Chk2. In summary, these data demonstrate that 9cUAB30 is a novel cancer chemopreventive agent for UVB-induced skin neoplasm and acts by invoking extensive DDSBs similar to those caused by chemotherapeutic drug like cisplatin. Citation Format: Sandeep C. Chaudhary, Mahendra P. Kashyap, Gloria Nguyen, Craig A. Elmets, Mohammad Athar. 9cis-retinoid UAB30 manifests potent chemopreventive effects in a murine model of UVB-induced basal cell and squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-170.

Toll-Like Receptor 7 Staining in Malignant Epithelial Tumors.

As important players of the innate immune system, Toll-like receptors (TLRs) and their role for tumorigenesis have been in the focus of research. In particular TLR7 is an interesting candidate, as TLR7 agonists are broadly used for the treatment of cutaneous tumors. However, data addressing the baseline expression of TLR7 in both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) on the protein level are lacking, while on the genomic level significantly elevated expression of TLR7 in SCC but not in BCC has been demonstrated. Our aim was to characterize the immunohistochemical staining pattern of TLR7 in SCC and BCC. Besides, we aimed to clarify if, in case of different TLR7 expression between SCC and BCC, TLR7 expression would help to define basosquamous carcinoma (BSC), a tumor entity sharing characteristics of both SCC and BCC. We examined histopathological samples from 23 BCC, 4 BSC, and 24 SCC and characterized the expression of TLR7 by immunohistochemistry and immunofluorescence. We found that TLR7 was not expressed by the tumor tissue of SCC, BCC, and BSC, but by inflammatory cells located within the tumoral and/or peritumoral tissue. Whereas the overall expression of TLR7 did not differ between BCC and SCC (30.4% vs. 45.8%, respectively), we found that within the group of SCC, the well-differentiated SCC showed strong tumoral and/or peritumoral immunocellular TLR7 reactivity in contrast to the poorly differentiated SCC (73.33% vs. 11.1%, respectively). Besides, immunofluorescence double staining revealed the expression of TLR7 in immune cells closely interacting with T cells and natural killer cells. In contrast to genomic data, we did not find a general difference between baseline TLR7 expression of SCC and BCC on the protein level. Nevertheless, the expression of TLR7 by the inflammatory infiltrate associated with SCC may correlate with the degree of differentiation of SCC possibly indicating better outcome.

Exclusive Development of a Single Type of Keratinocyte Skin Cancer: Evidence from an Australian Population–Based Cohort Study

Whether susceptible people develop both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) or one type exclusively during life is unknown. We investigated this in an Australian community cohort of 1,191 adults aged 25-75 years by recording all new BCCs and SCCs for 16 years in people with no previous keratinocyte cancer. Among those who developed multiple skin cancers, age- and sex-specific incidence rates per 100,000 were calculated for those who developed BCC exclusively, SCC exclusively, or BCC and SCC. Corresponding relative risks (and 95% confidence intervals) were estimated by Poisson regression. During follow-up, 116 people developed multiple keratinocyte cancers: 65 (56%) developed BCC exclusively (range 2-8 per person); 18 (16%) developed SCC exclusively (2-5 per person); and 28% developed both types. Of the 116, 88 had a BCC first, of whom 74% subsequently developed only BCCs, and 28 had SCC first, of whom 64% subsequently developed only SCCs. Incidence rates did not differ by sex in the BCC-only, SCC-only, or mixed groups, but they increased significantly with age especially in the SCC-only group. These findings suggest that the majority of people are prone to develop one type rather than a mix of keratinocyte cancers.

Dermoscopy of basosquamous carcinoma

Basosquamous carcinoma (BSC) is a rare and potentially aggressive tumour, characterized by clinical and pathological features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). It is reported to have a nonspecific clinical presentation, which makes naked-eye diagnosis a challenge. To describe the dermoscopic patterns of BSC, which may facilitate early diagnosis and accurate management. This was a retrospective evaluation of clinical and dermoscopic images of histopathologically proven BSC, collected from skin cancer centres in Australia (Perth), Greece (Thessaloniki) and Italy (Naples, Reggio Emilia). Twenty-two tumours were included in the study. Our analysis revealed that the dermoscopic pattern of BSC comprises BCC-related criteria, as well as features that are known to characterize invasive SCC. The most frequently detected criteria were: unfocused (peripheral) arborizing vessels (73%), keratin masses (73%), white structureless areas (73%), superficial scale (68%), ulceration or blood crusts (68%), white structures (64%), blue-grey blotches (59%) and blood spots in keratin masses (55%). Notably, all but one of the tumours exhibited at least one BCC-related plus one SCC-related dermoscopic feature. BSC appears to have overlapping dermoscopic features of BCC and invasive SCC, and detection of at least one dermoscopic criterion of both BCC and SCC should raise suspicion for the tumour. Appreciation of the dermoscopic patterns of BSC might assist in the timely and accurate diagnosis and subsequent optimal management of this unusual and potentially metastatic skin tumour.

Genetic Determinants of UV-Susceptibility in Non-Melanoma Skin Cancer

A milieu of cytokines and signaling molecules are involved in the induction of UV-induced immune suppression and thus the etiology of non-melanoma skin cancer (NMSC). Targeting the UV-induced immunosuppression pathway, and using a large population based study of NMSC, we have investigated the risk associated with functional variants in 10 genes (IL10, IL4, IL4R, TNF, TNFR2, HTR2A, HRH2, IL12B, PTGS2, and HAL). The most prominent single genetic effect was observed for IL10. There was increasing risk for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with increasing number of variant IL10 haplotypes (BCC: ptrend = 0.0048; SCC: ptrend = 0.031). Having two IL10 GC haplotypes was associated with increased odds ratios of BCC and SCC (ORBCC = 1.5, 95% CI 1.1–1.9; ORSCC = 1.4, 95% CI 1.0–1.9), and these associations were largely confined to women (ORBCC = 2.2, 95% CI 1.4–3.4; SCC: ORSCC = 1.8, 95% CI 1.1–3.0). To examine how combinations of these variants contribute to risk of BCC and SCC, we used multifactor dimensionality reduction (MDR) and classification and regression trees (CART). Results from both of these methods found that in men, a combination of skin type, burns, IL10, IL4R, and possibly TNFR2 were important in both BCC and SCC. In women, skin type, burns, and IL10 were the most critical risk factors in SCC, with risk of BCC involving these same factors plus genetic variants in HTR2A, IL12B and IL4R. These data suggest differential genetic susceptibility to UV-induced immune suppression and skin cancer risk by gender.

Basosquamous carcinoma: florid lesion in a Nigerian

Basosquamous carcinoma (BSC) is a rare malignancy with features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a potential for infiltration and destruction. This is a report of a florid scalp lesion of BSC with erosion of the skull. A preoperative diagnosis of BCC was made following a biopsy. However, further evaluation of the excised lesion revealed BSC. Timely diagnosis of this potentially aggressive neoplasm, which could be enhanced by multiple biopsies, is essential for proper treatment.

Dietary fat intake and risk of skin cancer: A prospective study in Australian adults

Although intakes of dietary fat have been associated with both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin, the evidence is sparse and inconsistent. This study prospectively investigated the association between total dietary fat; saturated, polyunsaturated and monounsaturated fatty acids; and percent energy from fat in relation to BCC and SCC of the skin. At baseline in 1992, total fat intake and intake of fatty acids were assessed in an Australian community-based longitudinal study, using a validated semi-quantitative food frequency questionnaire in 1,057 adult residents (aged 25-75 years) in Nambour, Queensland. Information on demography, sun-sensitivity history and sun exposure factors were obtained using self-administered questionnaires. Associations with BCC and SCC in terms of persons newly affected and of tumor counts were assessed using Poisson and negative binomial regression models, respectively, based on incident, histologically-confirmed tumors occurring between 1992 and 2002. No significant linear trends were observed in overall risk of BCC or SCC of the skin with increasing total fat intake. However, in participants with a history of skin cancer, total fat intake (multivariable adjusted RR = 2.42, 95% CI = 1.20-4.88; p for trend = 0.01) was associated with increased numbers of SCC tumors comparing the highest to lowest tertile. In conclusion, SCC tumor risk increased as total fat intake increased in people with a history of skin cancer. Dietary fats were not associated with BCC occurrence.

Increase in basal cell carcinoma incidence steepest in individuals with high socioeconomic status: results of a cancer registry study in the Netherlands

Development of both basal cell carcinoma (BCC) and cutaneous malignant melanoma (MM) is associated with acute and intermittent sun exposure. In contrast to MM, the association between socioeconomic status (SES) and BCC is not well documented. To investigate the incidence of BCC according to SES, stratifying by age and tumour localization in a large population-based cohort. To assess changes over time in the distribution of the patients with BCC across the SES categories. All patients with a histologically confirmed first primary BCC (n = 27,027) diagnosed between 1988 and 2005 in the Southeast of The Netherlands were stratified by sex, age (25-44, 45-64 and > or = 65 years), period of diagnosis, SES category (based on income and value of housing) and localization of the BCC. Age-standardized BCC incidence rates were calculated for the year 2004 by SES category and localization. Ordinal regression was used to assess changes over time in the proportion of patients with BCC by sex, age and SES. For men in all age groups higher BCC incidence in the highest SES category was observed, which remained significant after stratification for tumour localization. For women a consistent relationship was found only in younger women (< 65 years) for truncal BCCs, which occurred more frequently in high SES groups. Between 1990 and 2004, the proportion of BCC patients with high SES increased (+6%) and the proportion with low SES decreased (-7%). High SES is associated with increased incidence of BCC among men. Our data suggest that BCC is changing from a disease of the poor to a disease of the rich.

Measurement of Utility in Nonmelanoma Skin Cancer

Quality of life is an important variable in assessing the impact of a condition on patients. The current literature shows a minimal effect of nonmelanoma skin cancer (NMSC) on patients' quality of life. This contrasts with our own experience. Given this disparity, we sought to perform an additional study in this area. Past studies have used multiattribute methods to assess quality of life. In contrast, the present study uses health utility methods, which rate a patient's quality of life from 0 to 1, with 1 representing perfect health. Forty-one patients were guided through two standardized scenarios using a standard gamble process with a trained interviewer. Health utility scores were determined for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) using various NMSC treatment modalities. All patients had health utility scores of 0.99 or higher. The standard gamble method showed no statistically significant differences in health utility scores for any treatment scenario for BCC or SCC using raw data comparisons. However, a modified standard gamble approach showed significantly higher health utility scores for both BCC and SCC treated using surgical modalities. Using the standard gamble health utility method in patients with BCC or SCC, it appears that these tumors have a minimal impact on the quality of life in the present study group. However, the results may simply reflect the poor sensitivity of the standard gamble health utility method to accurately assess quality of life changes in patients with NMSC. A modification of the standard gamble method did show that patients with NMSC associated surgical treatments with a better health outcome. New outcome measures need to be devised to accurately assess the toll of NMSC on patients.

Squamous cell carcinoma of the skin: dual differentiations to rare basosquamous and spindle cell variants

Basosquamous carcinoma (BSC) is defined as a tumor containing the areas of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a transition zone linking the two. Spindle cell squamous carcinoma (SCSC) may have a variable component of conventional SCC and spindle cells. We present a case of an 89-year-old woman with an eruption on the scalp for several decades. Grossly, the lesion measured 8.5 x 6.0 x 1.8 cm and consisted of a gray-white and focally black tumor. Microscopically, a non-ulcerated upper part of the tumor consisted of large polygonal squamoid cells with occasional keratinization (SCC), trabecular growth of basaloid cells with peripheral palisading (BCC), and an area in which both the components were intermingled. The rest of the tumor was a myxoid area with elongated fusiform spindle cells, which appeared to arise from conventional SCC. Immunohistochemically, the tumor cells in the SCSC (both conventional and spindle cell) area co-expressed CAM5.2, and vimentin. Ber-EP4 was positive in the BCC area with the transition zone of SCC and BCC showing diminished staining. Epithelial membrane antigen was focally positive in the conventional SCC area. To our knowledge, this is the first case report of SCC of the skin that has dual differentiations to BSC and SCSC.