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Basal Cell Carcinoma: What’s New Under the Sun
Abstract
Basal cell carcinoma (BCC) is the most common skin cancer in white populations with an increasing incidence worldwide, thereby imposing an important public health problem. Its etiology is still unclear, but existing data indicate that the risk for BCC development is of multifactorial origin and results from the interplay of both constitutional and environmental factors. Yet, UV radiation (UVR) is believed to be the predominant causative risk factor in the pathogenesis of BCC. For years, BCC and squamous cell carcinoma (SCC) have been grouped together as "nonmelanoma skin cancer." However, it seems that there are considerable biologic differences between BCC and SCC, and thus each type of epithelial cancer should be addressed separately. The present review provides an overview of the intriguing etiologic link of BCC with UVR and attempts a comprehensive review of recent epidemiologic and molecular evidence that supports this association.
... Basal cell carcinoma (BCC) accounts for 75% of all skin cancers and is the most common malignant tumor in white populations. BCC and cutaneous squamous cell carcinoma (cSCC) are referred to as keratinocyte carcinomas (formerly known as nonmelanoma skin cancers) [1].The majority of BCCs is characterized by indolent biological behavior and is cured with surgical excision or topical treatments. However, in some cases, BCC can infiltrate locally into adjacent and deeper structures and cause extensive tissue destruction. ...
... Gene alterations playing some role in BCC pathogenesis include mutations in p53 (17p13), human type II oculo-cutaneous albinism-related gene (OCA2), agouti signaling protein (ASIP), tyrosinase (TYR) and melanocortin 1 receptor gene (MC1R, 16q24.3) [1,7,8]. Mutations in the Hedgehog (Hh) signaling pathway have been detected in practically all BCCs. ...
... Translational research has linked the above mentioned genetic and molecular findings in BCC with the development of treatments targeting these underlying dysregulations. As a result, our therapeutic options have been enriched with the Hedgehog pathway inhibitors (HHI) vismodegib and sonidegib, and the anti-PD- 1 (80%) discontinued treatment, including 180/499 (36%) due to adverse events, 14% due to disease progression, and 10% due to patient request [50]. Among the 180 patients who discontinued vismodegib due to adverse events, those were of mild severity (grade 1 or 2) in 106 patients (59%), and most ...
For patients with advanced BCC, including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment. Results from clinical trials highlight that the overall discontinuation rate of HHI treatment varies from 88% to 92% with vismodegib and is approximately 92% with sonidegib, and half of patients will discontinue HHI after approximately 8 to 12 months. The main factors weighing in on the decision to discontinue HHI, include efficacy (tumor response), adverse events and patient decision. In clinical practice, some of the patients that stop HHI may be re-evaluated if the tumor becomes amenable to surgery, or restart HHI at a later time, while others will need to switch to immunotherapy, depending on the reasons for HHI discontinuation. In this review, we revisit the therapeutic decisions considering a switch from HHI to immunotherapy with anti-PD-1 agent cemiplimab and we highlight the place of cemiplimab in the therapeutic ladder for patients with advanced BCC. We discuss the evidence on the efficacy and safety of anti-PD-1 agents as second-line systemic monotherapy, or in combination with other treatments, and the emergence of checkpoint immunotherapy as a neoadjuvant treatment.
... O carcinoma basocelular (CBC) é a neoplasia maligna mais frequente nos indivíduos caucasianos, e, logicamente, a mais representativa de todas as neoplasias malignas cutâneas [1][2][3][4][5] , detendo caracteristicamente um comportamento localmente invasivo. O carcinoma espinhocelular (CEC) é uma neoplasia maligna cutânea menos frequente, mas ainda assim muito comum, com um carácter mais agressivo e potencialmente fatal. ...
... O carcinoma espinhocelular (CEC) é uma neoplasia maligna cutânea menos frequente, mas ainda assim muito comum, com um carácter mais agressivo e potencialmente fatal. Apesar da reconhecida frequência, as suas verdadeiras incidências revelam-se habitualmente de difícil avaliação e interpretação, por um lado devido à importante variabilidade determinada pelo fototipo da população avaliada e pela sua localização geográfica (em relação com a latitude), e por outro devido à frequente desvalorização em termos de registo oncológico, em que são muitas vezes considerados conjuntamente como cancro cutâneo não-melanoma (CCNM) 1,2,4 . ...
... Apesar de serem entidades clínicas distintas, partilham factores de risco comuns, sendo que o mais relevante é a exposição a radiação ultravioleta, particularmente UVB 2,6,7 . As alterações carcinogénicas induzidas pela radiação UV são cumulativas, traduzindo-se clinicamente após um período de latência de anos a várias décadas após a primeira exposição 1,5,7 de baixa latitude e/ou de altitude elevada, que se expõem frequentemente à radiação solar nas suas actividades profissionais ou de lazer desde idades jovens e não fazendo uso de vestuário protector 1 . A exposição terapêutica ou cosmética a radiação ultravioleta artificial, a exposição a radiação ionizante ou a outros carcinogénios ambientais e a imunossupressão são também factores que potenciam o risco de desenvolvimento de CCNM 1,2,[4][5][6][7] . ...
O cancro cutâneo não-melanoma (CCNM), designação conjunta para os carcinomas basocelulares (CBC) e espinhocelulares (CEC), é o tipo de neoplasia cutânea maligna mais frequente. Com vista à caracterização epidemiológica deste grupo de tumores, foi realizada uma análise retrospectiva dos doentes portadores de CCNM identificados por análise histológica de todas as biopsias cutâneas incisionais ou excisionais ao longo de 5 anos (2004-2008) num serviço de Dermatologia. Foram identificados 3075 CCNM, representando 88% do total de neo- plasias malignas diagnosticadas no mesmo período (n=3493). Destes, 68,3% eram CBC. No seu conjunto, a popu- lação de CCNM era predominantemente constituída por indivíduos idosos e do sexo feminino, tendo sido observado um aumento consistente de frequência ao longo do período avaliado (5,25%/ano). A maioria dos CCNM (n=1443, 81,7%) foi identificada nas áreas de pele foto-exposta, representando 95,1% de todas as neoplasias malignas em áreas foto-expostas. O CCNM foi a neoplasia mais representativa na generalidade das áreas topográficas, à excep- ção do abdómen e da pélvis, representando, em particular, mais de 95% das neoplasias malignas da face, da região cervical e do couro cabeludo. O CBC foi o CCNM predominante em todas as localizações, à excepção dos membros inferiores e superiores, lábio inferior e da área genital, onde o CEC representou, respectivamente, 77,7%, 77,4%, 94,7% e 95,3% dos casos.
O CCNM, como neoplasia maligna cutânea mais frequente, deverá ser alvo de uma monitorização regular, com vista à determinação da sua dinâmica epidemiológica, da eficácia das medidas preventivas e adequação dos recursos de saúde.
PALAVRAS-CHAVE – Neoplasias da Pele; Carcinoma Basocelular, Carcinoma Espinhocelular.
... Basal cell carcinoma (BCC) is the most common type of skin cancer, representing about 75% of all cases (1)(2)(3)(4)(5)(6)(7). Basal cell carcinogenesis is a multifactorial process. ...
... Angiotensin II exerts its biological effects by binding to its receptors AGTR1 and AGTR2 (21). (1,2,5,7): Homozygous for the normal allele; (3,4,6,8,9,10,11): Heterozygous. B: Genotyping of BCC patients for the A1166C mutation in the AGTR1 gene; (1,2,3,8,11): Homozygous for the mutant allele; (7): Homozygous for the normal allele (4,5,6,9,10): Heterozygous. ...
... (1,2,5,7): Homozygous for the normal allele; (3,4,6,8,9,10,11): Heterozygous. B: Genotyping of BCC patients for the A1166C mutation in the AGTR1 gene; (1,2,3,8,11): Homozygous for the mutant allele; (7): Homozygous for the normal allele (4,5,6,9,10): Heterozygous. C: Genotyping of female controls for the G1675A mutation in the AGTR2 gene; (2,3,4,5,6,7,9,10,11): Homozygous for the normal allele (1): Homozygous for the mutant allele. ...
Background/aim:
Basal cell carcinoma (BCC) has been genetically associated with an increased expression of angiotensin-converting enzyme (ACE), an important factor of the renin-angiotensin system which produces vasoconstrictor angiotensin II. Other factors of this system include angiotensinogen (AGT) and angiotensin receptors AGTR1, AGTR2. We investigated the possible association of BCC with genetic variability in the AGT, AGTR1 and AGTR2 genes.
Materials and methods:
DNA samples of 190 Greeks were studied, including 91 patients with BCC and 99 matched healthy controls. Molecular genotyping of patients and controls was performed for the polymorphisms AGT M235T, AGTR1 A1166C and AGTR2 G1675A.
Results:
The mutant T allele that increases AGT gene expression was detected in two-fold increased frequency in BCC patients in comparison to healthy controls (p <0.001). On the contrary, no significant difference was observed in AGTR1 and AGTR2 variants between patients and controls.
Conclusion:
Increased expression of AGT may be associated with BCC.
... Basal cell carcinoma (BCC) is the most common malignant tumor and accounts for 75% of all skin cancers [1]. The highest incidence of BCC has been reported in Australia with rates ranging between 1% and 2% per year, followed by the U.S. and Europe [1,2]. ...
... Basal cell carcinoma (BCC) is the most common malignant tumor and accounts for 75% of all skin cancers [1]. The highest incidence of BCC has been reported in Australia with rates ranging between 1% and 2% per year, followed by the U.S. and Europe [1,2]. The rate of BCC has tripled in the past 30 years, thereby posing an important health problem with a considerable cost for its management [3,4]. ...
... The rate of BCC has tripled in the past 30 years, thereby posing an important health problem with a considerable cost for its management [3,4]. Moreover, the management of a patient with skin cancer may demand a multidisciplinary approach including a plastic surgeon, oncologist, radiologist, and dermatologist [1]. ...
The Hedgehog pathway inhibitors (HPIs), vismodegib and sonidegib, are increasingly employed in the treatment of patients with advanced basal cell carcinoma (BCC). The aim of this review is to create a synthesis of available information in the literature regarding the follow-up of patients with advanced BCC treated with HPIs and to provide the treating physician with a structured practical guide to standardize clinical practice. Several challenges during treatment are addressed: to optimally evaluate tumor responses, to differentiate between resistance (HPI rechallenge not possible) and recurrence (HPI rechallenge may be possible) in case of BCC regrowth, to readily assess for toxicity and tolerability issues, to provide patients with practical ways and behaviors to effectively cope with adverse events, and to improve patient adherence and quality of life. Implications for Practice: This is a practical guide for clinical practice regarding the monitoring and follow-up of patients with advanced basal cell carcinoma (BCC) during treatment with the Hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib. This review aims to bridge the gap in knowledge of assessing tumor response for BCC with both an externally visible component and an infiltrating component measurable with imaging. Furthermore, it addresses the follow-up for adverse events as a challenging multistep process involving practices aiming to readily assess new-onset symptoms of HPI toxicity, perform total-body skin examination, and improve patient adherence and quality of life.
... Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with an estimated life risk in fair skinned individuals to be around 30%, and along with squamous cell carcinoma (SCC), they account for the vast majority of non-melanoma skin cancers (NMSCs) [1][2][3]. BCC has been reported to have a rising incidence globally in the last years, while in the US alone more than 2 million people are diagnosed annually, thus increasing healthcare burden and costs [3][4][5][6]. Accordingly, data from Canada, Europe, Australia and Asia exhibit rising incidence rates [6][7][8][9][10][11][12][13]. ...
... Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with an estimated life risk in fair skinned individuals to be around 30%, and along with squamous cell carcinoma (SCC), they account for the vast majority of non-melanoma skin cancers (NMSCs) [1][2][3]. BCC has been reported to have a rising incidence globally in the last years, while in the US alone more than 2 million people are diagnosed annually, thus increasing healthcare burden and costs [3][4][5][6]. Accordingly, data from Canada, Europe, Australia and Asia exhibit rising incidence rates [6][7][8][9][10][11][12][13]. In terms of histopathology and clinical appearance, BCC has a variety of subtypes including nodular, superficial, infundibulocystic, fibroepithelial, morpheaform and infiltrative while basosquamous and micronodular mainly exhibit distinct histopathologic features and their presence can alter the prognosis and treatment plan [14][15][16]. ...
Introduction:
Basal cell carcinoma (BCC) is the most common skin cancer worldwide and has been reported to have a rising incidence in the last years. Multiple therapeutic modalities are approved for the treatment of BCC, making it difficult for physicians to choose the most suitable option for every patient. Photodynamic therapy (PDT) using either 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) as photosensitizing agents is an established treatment option for low-risk BCC.
Objectives:
This review aims to summarize the available evidence from randomized clinical trials (RCTs) that utilize either ALA or MAL PDT and compare it with other treatment modalities. The main outcomes related to the effectiveness, adverse events, cosmetic outcomes and pain sensation, along with data from long-term follow-ups will be presented and discussed.
Methods:
Thorough literature searches were conducted through the electronic databases ClinicalTrials. gov and Pubmed/MEDLINE from inception up to 28 March 2023. Only studies in English were included. All relevant data were extracted accordingly from the eligible studies.
Results:
Eight RCTs included superficial BCC (sBCC) alone, 7 included nodular BCC (nBCC), 2 included both sBCC and nBCC and 1 included BCC of unspecified subtype. Follow-up duration ranged from 3 months to 5 years. Both ALA-PDT and MAL-PDT demonstrated acceptable efficacy, adverse events, cosmetic outcomes and pain sensation while no major differences were observed between them. PDT was less effective than surgery but with better reported cosmetic outcomes.
Conclusions:
PDT is a safe and efficacious treatment option for sBCC and to a lesser extent nBCC.
... The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy. B asal cell carcinoma (BCC) is the most common malignant tumour in fair-skinned populations and accounts for 75% of all skin cancers (1). Ultraviolet radiation is believed to be the predominant causative risk factor and the incidence of BCC is inversely related to a country's geographic latitude combined with the pigment status of its inhabitants (1, 2). ...
... Ultraviolet radiation is believed to be the predominant causative risk factor and the incidence of BCC is inversely related to a country's geographic latitude combined with the pigment status of its inhabitants (1, 2). The incidence rates of BCC are increasing worldwide, and this imposes an important health problem (1). ...
In electrochemotherapy, permeabilization of the cell membrane by electric pulses increases the anti-tumour effect of chemotherapeutics. In calcium electroporation, chemotherapy is replaced by calcium chloride with obvious benefits. This study explores the effect and underlying mechanisms of calcium electroporation on basal cell carcinomas using either high- or low-frequency electroporation. Low-risk primary basal cell carcinomas were treated in local anaesthesia with intratumoral calcium chloride followed by electroporation with high (167 kHz) or low (5 kHz) frequencies. Non-complete responders were retreated after 3 months. The primary endpoint was tumour response 3 months after last calcium electroporation. Plasma membrane calcium ATPase was examined in various cell lines as plasma membrane calcium ATPase levels have been associated with calcium electroporation efficacy. Twenty-two out of 25 included patients complete the study and 7 of these (32%) achieved complete response at 3 months with no difference in efficacy between high- and low-frequency pulses. High-frequency calcium electroporation was significantly less painful (p=0.03). Plasma membrane calcium ATPase was increased 16–32-fold in basal cell carcinoma cell lines compared with 4 other cancer cell lines. Calcium electroporation for low-risk basal cell carcinomas does not fulfil the requirements of a new dermatological basal cell carcinoma treatment but may be useful as adjuvant treatment to surgery in more advanced basal cell carcinomas. The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy.
... The most common malignant tumour in the white population is basal cell carcinoma (BCC) and accounts for 75% of all non-melanoma skin cancers (1). Reports have shown that rates of BCC have increased in many countries around the world (2,3). ...
... Mohs surgery is considered as an effective and tissuesparing therapeutical approach for nonmelanoma skin cancers (1). The technique gained increasingly popular especially due to its minimal-invasiveness, considering that these types of tumors often occur in functional and aesthetic relevant regions exposed to the sun (e.g., head and neck area). ...
Background:
In vivo reflectance confocal microscopy (RCM) is well established in non-melanoma skin cancer detection and screening. However, there is no sufficient validation regarding intraoperatively obtained images of wound margins. A reliable and fast resection margin detection is of high clinical relevance. Hence, we aimed to investigate feasibility and validity of in vivo RCM imaging for wound margins assessment compared with standard skin surface imaging and the gold standard histopathology.
Methods:
A surgical incision through the center of a large basal cell carcinoma (BCC) affected area in the head and face region was performed. After removing half of the tumor, the wound margins of the remaining half as well as the corresponding skin surface were scanned with an in vivo RCM. A total of 50 wound margin images with BCC, 50 images of BCC-free margins and the corresponding skin surface images from 50 patients were compared with each other and with histopathological findings. Presence of confocal diagnostic criteria for BCC in images was analyzed.
Results:
An overall sensitivity and specificity in detection of BCC in wound margins was 88.5%, and 91.7% compared to skin surface imaging and 97.8% and 90.7%, respectively, compared to histopathology. We identified all known confocal patterns of healthy skin and BCC in wound margin scans: damage of the epidermal layer above the lesion and cellular pleomorphism, elongated and monomorphic basaloid nuclei, nuclear polarization, an increased number of dilated blood vessels with high leukocyte traffic, inflammatory cells.
Conclusions:
The accuracy of in vivo RCM imaging of wound margins is comparable with a standard skin surface imaging. The intraoperative detection of BCC areas in wound margins is as precise as the standard skin imaging and may be supportive for surgical interventions.
... The solar UV radiation consists of three spectral areas: UVA (320-400 nm), UVB (280-320 nm), and UVC (180-280 nm). The atmospheric ozone layer effectively blocks UVC, so that the UV radiation reaching the skin surface is a mixture of 5% UVB and 95% of UVA [7]. The depth of penetration of UV radiation into the skin is dependent on the wavelength, and the effects of UV radiation on human skin differ depending on the wavelength (Figure 1). ...
... Longer wavelength UVA penetrates deeply into the basal layer of the epidermis and dermal fibroblasts. In contrast, UVB is largely absorbed by the epidermis, with little reaching the dermis [7][8][9][10]. Figure 1. Spectrum of solar radiation and penetration into the skin. ...
The majority of skin cancers are caused by over exposure to ultraviolet (UV) radiation. The effects of UV radiation on the expression of drug transporters expressed in human skin has never been studied. In this the effects of UVA and UVB irradiation on the expression of ATP-binding cassette (ABC) transporters and Solute carrier (SLC) transporters was evaluated in normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF) in primary culture. First experiments were intended to validate the inflammatory reaction in response to stimulation by lipopolysaccharide (LPS) in NHEK, NHDF and 3D-reconstructed human epidermis (3D-RHE) model. LPS treatment has shown to increase the expression of IL-8 and TNF-alpha in all three in vitro models. Expression of the most expressed ABC and SLC transporters was then measured in NHEK and NHDF after UVA (30 J/m²) and UVB (40 mJ/m²) irradiation. The most striking result was a significant 29-fold increase of the expression of SLCO4A1 in normal human dermal fibroblasts. In summary, this study shows for the first time a significant regulation of the expression of SLCO4A1 in human dermal fibroblasts induced by UVA irradiation. This finding is of particular interest as most of skin cancers are caused by over exposure to ultraviolet radiation and need to be considered in pharmacokinetic evaluation of topical drugs.
... The solar UVR consists of three spectral areas: UVA (320-400 nm), UVB (280-320 nm), and UVC (180-280 nm). More than 95% of the solar UVR that reaches the earth's surface is UVA, 1-5% is UVB, whereas most UVC is absorbed by the O 3 layer and oxygen in the atmosphere and is thus a very small source of adverse human health effects (Dessinioti et al., 2010). Small changes in stratospheric O 3 increase the penetration of shorter ultraviolet wavelengths (UVA, UVB) at the ground level. ...
... As the depth of penetration into the skin is dependent on the wavelength, UVB is largely absorbed by epidermal cellular components (proteins, DNA), while UVA radiation penetrates deeply into the basal layer of the epidermis and dermal fibroblasts. (Fisher et al., 1997;Dessinioti et al., 2010Dessinioti et al., , 2011Valacchi et al., 2012). Increasing evidence demonstrates that UVA in combination with common environmental pollutants, like PAHs significantly increases visible photodamage in skin (Burke and Wei, 2009). ...
... BCC accounts for 75% of all skin cancers and is the most common malignant tumour in white populations. The average lifetime risk for white-skinned individuals to develop BCC is approximately 30% [14]. Rates of BCC have been reported to be increasing in many countries around the world as a result of the increasing longevity of the general population and sun exposure behaviours. ...
... In addition, not all BCC cases are sent for histopathologic diagnosis and there are large regional variations in reported incidence rates of BCC. These differences may be due to geographic location (latitude) of the study populations, study periods and methods for registering BCC [14]. As most cancer registries record only the first histologically confirmed BCC per patient, the true incidence of BCC may be significantly underestimated [15]. ...
Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer collaborated to develop recommendations on diagnosis and treatment of BCC. A new classification into 'easy-to-treat (common) BCC and 'difficult-to-treat' BCC is proposed. Diagnosis is based on clinicodermatoscopic features for 'easy-to-treat' BCCs. Histopathological confirmation is mandatory in ambiguous lesions and in BCCs located in high-risk areas. The first-line treatment of 'easy-to-treat' BCC is complete surgery. Microscopically controlled surgery shall be offered for high-risk BCC, recurrent BCC and BCC in critical anatomical sites. Topical therapies (5% imiquimod, 5% fluorouracil) and destructive approaches (curettage, electrocautery, cryotherapy, laser ablation) should be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial BCC and thin nodular BCC. The therapy for a 'difficult-to-treat' BCC should preferentially be discussed by a multidisciplinary tumour board. Hedgehog inhibitors, vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCCs. Immunotherapy with anti-programmed cell death 1 (PD-1) antibodies is a promising therapeutic option, currently being investigated in clinical trials. Radiotherapy represents a valid alternative to surgery for BCC on the face, especially in elderly patients. In patients with naevoid basal cell carcinoma syndrome (NBCCS), close surveillance and regular skin examinations are required to diagnose and treat BCCs at early stage. Long-term follow-up is recommended in patients with high-risk BCC subtypes, high-risk sites, multiple BCCs and NBCCS.
... It is the most common malignant tumor in Caucasians and accounts for 75% of all skin cancers, with growing incidence rates worldwide due to climate change-related increase in UV exposure as well as population aging (1). Although its metastatic potential and mortality rates are low, its aggressive growth can cause major tissue damage requiring extensive surgical treatment (2). It is known that BCCs arise from epidermal cells. ...
While basal cell carcinoma is the most common type of skin cancer in humans, its subepidermal presentation is extremely rare. The risk factors for basal cell carcinoma development are well-known, but it remains unclear in which setting the tumor restricts itself to the dermal compartment. We present the fifth known case of subepidermal basal cell carcinoma. However, this particular presentation is unique due to its arisal beneath a capillary malformation. The patient had previously undergone multiple laser treatments which yielded no success. Initially, the vascular malformation was removed and sent for histopathological diagnosis. After the discovery of basal cell carcinoma, wide surgical resection was done. The patient had no recurrence up to the last follow-up at 18 months postoperatively. This case reports a new presentation of a very rare condition, but also highlights the importance of histopathological examination and the need for future research of any possible connection between laser therapy and carcinogenesis.
... Specifically, it affects the parts of the face that are always in the sun, which is the top two-thirds. (Dessinioti et al, 2010;Ferreira et al, 2013). Intermittent bouts of solar exposure raise the risk of disease. ...
Background The most prevalent cutaneous cancer worldwide is basal cell carcinoma. Different histopathological growth patterns of basal cell carcinoma exhibit various clinical behaviors, indicating that this tumor is not unique. Objectives The study's goal was to examine the demographic description of basal cell malignancy patients. Materials and Methods From 1983-2021, 85 Formalin-fixed, paraffin-embedded head-and-neck basal cell carcinoma tissue cassettes were retrospectively studied. They were taken from the archives of the Ghazi Al-Harerri Hospital in Medical City and the University of Baghdad's Department of Oral and Maxillofacial Pathology. World Health Organization recommendations and the evaluation of Hematoxylin & Eosin sections by two expert pathologists validated each case's diagnosis. Results For patients with tumors, the age range from 40-90 years with a mean standard deviation of 63.25±10.85. The age group's distribution of the studied patients had a highly significant difference. Regarding gender, there was no significant difference. The site recorded highly significant differences in "Nose, and Cheek. Regarding different histological patterns recorded highly significant differences and the highest recorded cases were in "Metatypical, and Nodular. Conclusion These findings imply that the head and neck region's metatypical form was BCC's most common histological pattern, with the nose and cheek being the most common sites with the most sun-exposed areas and irritated skin.
... Ultraviolet radiation(UVR), ingestion of arsenic acid (medicine, pesticides), ionizing radiation, X-ray and grenz-ray exposure, topical nitrogen mustard administration, and thermal burns are considered as underlying extrinsic factors 1 . The intrinsic factors include gender, age, body mass index (BMI), fair skin, blond or red hair, light eye color, the tendency to sunburn, immunosuppression, and genetic predisposition (such as a family history of BCC) 2 . Therefore, restricting the intensity of UVR has been recommended as an effective way to prevent this cancer 3 . ...
Basal cell carcinoma (BCC) is the most common cancer with a rising incidence among white-skinned individuals. A number of epidemiological studies have suggested that obesity and serum 25-hydroxy-vitamin D (25(OH)D) levels may affect the arising of BCC. To address this, we selected 443 and 96 single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) and serum level of 25(OH)D from large-scale genome-wide association studies (GWAS), respectively. The univariable and multivariable two-sample Mendelian randomization (MR) analyses were conducted with a series of sensitivity analyses to ensure the results were reliable and reproducible. The results of univariable two-sample MR analysis showed that higher BMI was related to lower risk for BCC (Odds ratio(OR) = 0.90; 95% confidence interval (CI),[0.81,0.99]; p = 0.02). In addition, this causal effect of BMI on BCC still remained (OR = 0.88; 95%CI,[− 0.22, − 0.03], p-value = 0.008) after adjusting for 25(OH)D level in the multivariable MR analysis. However, the results suggested that 25(OH)D level was not associated with BCC(OR = 1.02; 95%CI, [0.94,1.09], p-value = 0.67). In conclusion, similar to the conclusions of retrospective observational studies, the MR results indicate that high BMI is an independent protective factor for BCC. Meanwhile, vitamin D levels may not be causally associated with the risk of basal cell carcinoma and increasing vitamin D supplementation is unlikely to reduce the risk.
... UVR, particularly UVB is the most important etiopathogenic factor for BCC as 80% of the tumors are distributed on the head and neck region. [3] Intermittent periods of intense sun exposure instead of cumulative exposure increase the risk of BCC. The other predisposing factors include ionizing radiation, arsenic exposure, [4] inherited syndromes, and immunosuppression, particularly post-organ transplantation. ...
... The solar UVR spectrum consists of three sub-categories: UVA (320-400 nm), UVB (290-320 nm) and UVC (200-290 nm). UVR reaching the earth's surface is composed mainly of UVA (90-95%) and UVB (1-5%), whereas most of UVC is absorbed by the ozone layer [7]. The biological effect of UVR on the skin varies according to the UV wavelength. ...
Effect of Ultraviolet Radiation and Benzo[a]pyrene Co-Exposure on Skin Biology: Autophagy as a Potential Target. Int. Abstract: The skin is the outermost protective barrier of the human body. Its role is to protect against different physical, chemical, biological and environmental stressors. The vast majority of studies have focused on investigating the effects of single environmental stressors on skin homeostasis and the induction of several skin disorders, such as cancer or ageing. On the other hand, much fewer studies have explored the consequences of the co-exposure of skin cells to two or more stres-sors simultaneously, which is much more realistic. In the present study, we investigated, using mass-spectrometry-based proteomic analysis, the dysregulated biological functions in skin explants after their co-exposure to ultraviolet radiation (UV) and benzo[a]pyrene (BaP). We observed that several biological processes were dysregulated, among which autophagy appeared to be significantly downregulated. Furthermore, immunohistochemistry analysis was carried out to validate the down-regulation of the autophagy process further. Altogether, the output of this study provides an insight into the biological responses of skin to combined exposure to UV + BaP and highlights autophagy as a potential target that might be considered in the future as a novel candidate for pharmacological intervention under such stress conditions.
... [7] Ultraviolet (UV) radiation, particularly UV-B, is the most important etiopathological factor for BCC as 80% of the tumors are distributed on the head and neck region. [8] The prognosis of BCC is good with very low metastatic potential, but it can result in significant patient morbidity due its frequent occurrence in sun-exposed regions of head and neck region. BCC can behave aggressively in the presence of deep invasion and show recurrence and resistance to standard treatment. ...
Introduction:
Basal cell carcinoma (BCC) is the most common type of skin cancer worldwide. The pathogenesis of BCC involves interplay between various environmental and genetic factors. It is believed that chemokines play a significant role in the modulation of cancer growth by generating autocrine and paracrine signaling effects. The present study was conducted to elucidate the expression of chemokine, CXCL11, and its receptor CXCR3, and their interaction with tumor cells and peri-tumoral stroma in various subtypes of BCC.
Aim and objectives:
The aim of this study was to evaluate the immunohistochemical expression of chemokine CXCL11 and its receptor CXCR3 in various subtypes of BCC.
Materials and methods:
The study included 40 cases of histopathologically confirmed BCC. Clinical and histopathological features of various tumor subtypes were noted. Immunohistochemistry was performed using antibodies against CXCL11 and CXCR3, and these were assigned scores 0, 1, and 2 on the basis of immunohistochemical expression.
Results:
The median age of study participants was 65.0 ± 12.2 years with a male-to-female ratio of 1.5:1. The most common site was face, followed by neck, scalp, and back. The tumor subtypes included in the study were nodular (n = 20), pigmented (n = 8), infiltrating (n = 5), superficial (n = 4), and adenoid (n = 3). On immunohistochemistry, CXCR3 expression was seen in 34 (85%) cases with stromal inflammatory cells immunopositivity in 29 (72.5%) cases and tumor cells immunopositivity in 5 (12.5%) cases. CXCL11 expression was seen in 36 (90%) cases with weak expression in stroma and tumor in 18 cases and strong expression in the rest 18 cases. In individual subtypes, higher immunopositivity for CXCR3 and CXCL11 in tumor cells and peri-tumoral stroma was seen for nodular, infiltrating, and pigmented subtypes, compared to adenoid and superficial subtypes.
Conclusion:
Our study shows the enhanced expression of chemokine CXCL11 and its receptor CXCR3 in tumor cells and peri-tumoral stroma of BCC. This expression is greater in tumor cells of aggressive subtypes, i.e. nodular, infiltrating, and pigmented types. This suggests that receptor ligand pathway involving CXCR3 and CXCL11 plays a key role in pathogenesis of BCC, and blocking this pathway may result in inhibition of tumor growth. Thus, these chemokines may serve as future potential targets in developing novel therapeutic regimens against BCC.
... BCC arises from the excessive growth of basal cells in the stratified epithelium and is the most common type of skin cancer, representing approximately 75% of all skin cancers. The incidence of BCC is increasing by up to 10% per year, probably due to an increased life expectancy and UV exposure [92][93][94]. BCC mainly affects the head and neck (approximately 70-80%) but can also affect the trunk and extremities [95]. Basal cell nevus syndrome (BCNS, also known as Gorlin syndrome) is an autosomal dominant inherited disorder characterized by multiple BCCs, odontogenic keratocysts, skeletal abnormalities, calcified falx cerebri, plantar or palmar pits, and other clinical manifestations [96,97]. ...
Skin cancer is one of the most prevalent cancers in the Caucasian population. In the United States, it is estimated that at least one in five people will develop skin cancer in their lifetime, leading to significant morbidity and a healthcare burden. Skin cancer mainly arises from cells in the epidermal layer of the skin, where oxygen is scarce. There are three main types of skin cancer: malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. Accumulating evidence has revealed a critical role for hypoxia in the development and progression of these dermatologic malignancies. In this review, we discuss the role of hypoxia in treating and reconstructing skin cancers. We will summarize the molecular basis of hypoxia signaling pathways in relation to the major genetic variations of skin cancer.
... UVB induces direct DNA damage through the creation of photoproducts, such as cyclobutane pyrimidine dimers (CPDs), that are mutagenic if left unrepaired. However, CPDs seem to also play a central role in UVA-induced mutagenesis, as UVA may induce CPDs as a major pro-mutagenic DNA photoproduct [6]. In addition, UVA and UVB, even at suberythematogenic doses, may mediate skin carcinogenesis through immunosuppressive pathways, after cell membrane damage, DNA damage, and trans-urocanic isomerization [1,[7][8][9]. ...
Indoor tanning (sunbeds, solarium) uses artificial ultraviolet radiation (UVR) to stimulate cosmetic tanning of the skin. Indoor tanning has been officially classified as a human carcinogen in 2009 by the International Agency for Research on Cancer of the World Health Organization (WHO). The differences in the prevalence of sunbed use across countries and over the years highlight underlying legislative, climatic, and cultural differences. Indoor tanning-seeking behaviors may be driven by motivations for an appealing appearance, largely influenced by gender and age, and several misconceptions that a prevacation tan safeguards the skin, that sunbeds can be used to treat acne or to increase vitamin D, or that tanning is a healthy habit. This review provides an epidemiological update on the prevalence of sunbed use, who tends to use sunbeds and why, and details the current evidence on the association of sunbeds with skin cancers, including cutaneous melanoma, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC). Α statistically significant higher risk of cutaneous melanoma, BCC and cSCC with the use of sunbeds has been consistently demonstrated. This risk of skin cancer is even higher with the more frequent use of sunbeds, underscoring a dose–response relationship, and in those first exposed to sunbeds at a younger age. Preventive measures against sunbed use include legislation restricting sunbed use, educational campaigns to inform and discourage from indoor tanning, as well as using the internet, online advertising messages and the social media to reach larger audiences and to promote an untanned appearance.
... The two most common types of NMSC are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with BCC (75%) representing majority of NMSC [4][5][6]. For BCC, the main carcinogenic factor is ultraviolet light (UV) exposure, which explains why most tumors are located on sun-exposed sites, and the risk of developing BCC for white-skinned people is about 30% [7]. For SCC, other risk factors are precursor lesions, including actinic keratosis and SCC in situ [6]. ...
Purpose:
The aim of this retrospective study was to analyze tumor control, toxicity, and aesthetic outcome of patients affected by non-melanoma skin cancer (NMSC) and treated with iridium-192 (192Ir) high-dose-rate (HDR) brachytherapy (BT) using Valencia applicators at the Division of Radiotherapy, University of Pisa.
Material and methods:
From June 2015 to December 2020, 95 NMSC patients, including 61.5% basal cell carcinoma and 38.5% squamous cell carcinoma patients, with median age of 83 years (range, 32-96 years) were treated. In total, 182 lesions with a diameter ≤ 25 mm (median, 12 mm) and a depth ≤ 4 mm, located in scalp (19.2%), face (20.9%), chest (8.8%), nose (16.5%), ear (15.4%), and extremities (19.2%) were analyzed. All lesions were treated with 192Ir-based HDR afterloader using Valencia applicators. 105 lesions (57.7%) were treated with applicator of 20 mm and 77 lesions (42.3%) with applicator of 30 mm in diameter, depending on the size of lesions. Prescribed dose was 40 Gy in 8 fractions (5 Gy/fraction) delivered 2-3 times a week. Biological effective dose (BED) was ≈ 60 Gy.
Results:
The median follow-up was 14 months (range, 3-59 months). The 2-year local control rate was 96%. According to common terminology criteria for adverse events (CTCAE v. 5.0), G1-G2 acute toxicities included dermatitis (22.0%) and pain (8.2%). The most common G1 late toxicities were hypopigmentation (27.5%) and fibrosis (8.2%), and G2 late toxicity included ulceration (0.5%). No G3 or higher acute or late toxicities were reported. Excellent cosmetic results were observed in 77.5% of the lesions, with one only (0.5%) reported as a poor cosmetic result (ulceration refractory to therapy).
Conclusions:
HDR-BT using Valencia applicators is a safe, effective, and well-tolerated treatment modality for NMSC, and can be considered a good alternative for treatment, especially in elderly patients who are often unfit for surgery.
... B asal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin malignancies (1,2). The incidence of both tumours is increasing (3)(4)(5). Mohs micrographic surgery (MMS) combines a high cure rate with complete margin examination and healthy tissue conservation (6). MMS is the first-line therapy in high-risk BCC and SCC (such as those which are recurrent or incompletely excised, mid-facial located, or which show aggressive histological features or perineural invasion) (7)(8)(9)(10). ...
Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of prospective cohorts. This study presents the "real-life" results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1-1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3-6.1), being constant over time (0-5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries.
... Dies konnte insbesondere in den USA belegt werden, wo eine deutliche Inzidenzzunahme von Norden nach Süden zu beobachten ist [1,11] und zuletzt in südlichen Bundesstaaten Raten von 770-1070 pro 100 000 Einwohner verzeichnet wurden [15]. Bei hellhäutigen Menschen wird das durchschnittliche Lebenszeitrisiko an einem BZK zu erkranken auf 30 % geschätzt [16]. Das mittlere Erkrankungsalter von Patienten mit BZK betrug in Deutschland 2014 laut Krebsstatistik 72 Jahre, circa 52 % aller Fälle waren männliche Patienten [9]. ...
Zusammenfassung
Das Basalzellkarzinom (BZK) ist der häufigste maligne Tumor bei hellhäutigen Menschen und macht circa 75 % aller Hautkrebsfälle aus. Seit Jahrzehnten werden weltweit steigende Inzidenzraten berichtet. Hauptrisikofaktoren sind UV-Strahlung, männliches Geschlecht, heller Hauttyp, fortgeschrittenes Alter, langandauernde Immunsuppression, eine positive Familien-/Eigenanamnese sowie bestimmte Genodermatosen. Das BZK metastasiert selten und die Mortalität ist gering, allerdings kann es zu einer erheblichen Morbidität führen. In der Pathogenese sind genetische Mutationen, welche insbesondere den Hedgehog-Signalweg betreffen, bedeutsam. In der Diagnostik werden neben der Inspektion mit dem freien Auge und der Dermatoskopie zunehmend auch nichtinvasive Verfahren (optische Kohärenztomographie, konfokale Laserscanmikroskopie) eingesetzt, wobei auf die histologische Diagnosesicherung nur in Ausnahmefällen verzichtet werden kann. Klinisch und histologisch werden zahlreiche Unterformen unterschieden. Die Unterscheidung zwischen BZK mit hohem und niedrigem Rezidivrisiko beeinflusst die Therapieplanung maßgeblich. Die allermeisten BZK können effektiv und sicher mit chirurgischen Standardverfahren beziehungsweise in ausgewählten Fällen mit topischen Therapien behandelt werden. Lokal fortgeschrittene und metastasierte BZK werden einer Radiatio oder Systemtherapie zugeführt. Die Strahlentherapie ist zudem eine Option für ältere Patienten, wenn Kontraindikationen gegen eine Operation bestehen. In der Systemtherapie sind in Europa aktuell die Hedgehog-Inhibitoren Vismodegib und Sonidegib zugelassen. Eine Zulassung für den PD1-Inhibitor Cemiplimab in der Zweitlinientherapie ist zu erwarten.
... Several studies have estimated that non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), affects more than 3 million Americans a year [2,3]. For BCC, the main carcinogenic factor is ultraviolet light, which explains why most tumours are located on sun-exposed sites and the risk of developing BCC for whiteskinned people is about 30% [4]. Surgical excision is the preferred therapy for non-melanoma skin cancer, with a reported < 5% local recurrence rate. ...
Aim of the study:
The aim of this retrospective study was to analyse tumour control, toxicity, and aesthetic outcome of patients affected by non-melanoma skin cancer (NMSC) treated with 192 Ir high-dose-rate (HDR)-brachytherapy (BT) at the Division of Radiotherapy, University of Pisa.
Material and methods:
From January 2014 to December 2019 we treated 37 patients (median age 79 years; range 31-91 years) affected by NMSC, with the following histological subtypes: 62.2% basal cell carcinoma and 37.8% squamous cell carcinoma. We analysed 40 lesions with a depth ≤ 5 mm, located in 40.0% scalp, 17.5% nose, 25.0% face, and 17.5% ear, all treated with 192 Ir-based HDR-BT, using tailored custom moulds, with a median of 5 catheters (range, 1-9) spaced 1 cm apart. The most common fractionation scheme was 40 Gy in 8 daily fractions; the biological effective dose was 60 Gy.
Results:
The median follow-up was 25 months (range, 3-70 months). The 2-year local control rate was 90%. Common terminology criteria for adverse event (CTCAE vs. 5.0) G1 toxicities were dermatitis (52%), pain (25%), and ulceration (22%). The only G2 acute toxicities were dermatitis and ulceration. The most common G1 late toxicities were fibrosis (17%), atrophy (15%), and hypopigmentation (12%). No G3 or higher acute or late toxicity was reported. Excellent cosmetic results were observed in 65.0% of the lesions; only 1 case (2.5%) reported a poor cosmetic result.
Conclusions:
Surface mould HDR-BT is a safe, effective, and well tolerated treatment modality for NMSC and can be considered a good alternative, especially for elderly patients who are often unfit for surgery.
... Basal cell carcinoma is the world's most prevalent human cancer and is accountable for approximately 70-80% of all skin cancers [23,24]. A report by Dessinioti et al. revealed that Australia had the highest incidence of BCC (~1-2%) annually, with approximately 2448 of a 100,000 population diagnosed in 2011, followed by the US (450 per 100,000 in 2010) and Europe (220.1 per 100,000 yearly average) [25,26]. The South African National Cancer Registry reported approximately 14,414 BCC and 6950 SCC cases in 2016 [27]. ...
Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.
... We have used IsomiR Window to investigate the effect of isomiRs in Basal Cell Carcinoma (BCCs) [36], a malignant tumor of follicular germinative cells (trichoblasts) that accounts for 75% of all skin cancers that is the most common malignant tumor in caucasian populations [53] The profile of sncRNAs was obtained for 15 patients in order to characterize the differences between Nodular (the most common and benign subtype) and Infiltrative (the most aggressive subtype) BCC. Data was preprocessed for adapter trimming and quality filtering. ...
Background
IsomiRs are miRNA variants that vary in length and/or sequence when compared to their canonical forms. These variants display differences in length and/or sequence, including additions or deletions of one or more nucleotides (nts) at the 5′ and/or 3′ end, internal editings or untemplated 3′ end additions. Most available tools for small RNA-seq data analysis do not allow the identification of isomiRs and often require advanced knowledge of bioinformatics. To overcome this, we have developed IsomiR Window, a platform that supports the systematic identification, quantification and functional exploration of isomiR expression in small RNA-seq datasets, accessible to users with no computational skills.
Methods
IsomiR Window enables the discovery of isomiRs and identification of all annotated non-coding RNAs in RNA-seq datasets from animals and plants. It comprises two main components: the IsomiR Window pipeline for data processing; and the IsomiR Window Browser interface. It integrates over ten third-party softwares for the analysis of small-RNA-seq data and holds a new algorithm that allows the detection of all possible types of isomiRs. These include 3′ and 5′end isomiRs, 3′ end tailings, isomiRs with single nucleotide polymorphisms (SNPs) or potential RNA editings, as well as all possible fuzzy combinations. IsomiR Window includes all required databases for analysis and annotation, and is freely distributed as a Linux virtual machine, including all required software.
Results
IsomiR Window processes several datasets in an automated manner, without restrictions of input file size. It generates high quality interactive figures and tables which can be exported into different formats. The performance of isomiR detection and quantification was assessed using simulated small-RNA-seq data. For correctly mapped reads, it identified different types of isomiRs with high confidence and 100% accuracy. The analysis of a small RNA-seq data from Basal Cell Carcinomas (BCCs) using isomiR Window confirmed that miR-183-5p is up-regulated in Nodular BCCs, but revealed that this effect was predominantly due to a novel 5′end variant. This variant displays a different seed region motif and 1756 isoform-exclusive mRNA targets that are significantly associated with disease pathways, underscoring the biological relevance of isomiR-focused analysis. IsomiR Window is available at https://isomir.fc.ul.pt/ .
... UV rays in particular UVB is the most important aetiopathogenic factor, as 80% of tumours are distributed in head and neck region. [17] Intermittent periods of intense sun exposure instead of cumulative exposure increase the risk of BCC. Other factors include ionising radiation, arsenic exposure, inherited syndromes and immunosuppression particularly post organ transplantation. ...
... В настоящее время ген MC1R остается наиболее хорошо охарактеризованным генетическим детерминантом кожи и пигментации волос, а также подтвержденным геном предрасположенности к ракам кожи -злокачественная меланома, базально-клеточный и плоскоклеточный рак [19,[30][31][32][33]. На сегодняшний день идентифицировано более 100 аллелей гена MC1R с несинонимичными заменами. ...
The CRH-POMC system in the skin coordinates pigmentation and the immune response. We performed the association study of single-nucleotide polymorphism SNPs of MC1R gene in a cohort ofpsoriasis patients of Tatar ethnic group from the Volga-Ural region of Russia. The results suggest that polymorphisms of the MC1R gene may contribute to the protection or development of psoriasis in Tatar population.
... BCC is the most frequent skin cancer in fair-skinned adult patients (2). The estimated lifetime risk in this population is approximately 30% (3). The worldwide incidence of BCC is increasing continuously, but it cannot be estimated precisely as this tumour is not consistently registered. ...
Basal cell carcinomas are the most frequent skin cancers in the fair-skinned adult population over 50 years of age. Their incidence is increasing throughout the world. Ultraviolet (UV) exposure is the major carcinogenic factor. Some genodermatosis can predispose to formation of basal cell carcinomas at an earlier age. Basal cell carcinomas are heterogeneous, from superficial or nodular lesions of good prognosis to very extensive difficult-to-treat lesions that must be discussed in multidisciplinary committees. Recent guidelines have updated the management of basal cell carcinoma. The prognosis is linked to the risk of recurrence of basal cell carcinoma or its local destructive capacity. Characteristic molecular events in these tumours are: (i) activation of the hedgehog pathway, which has allowed the development of hedgehog inhibitors for difficult-to-treat lesions that are not accessible to surgery or radiotherapy; (ii) high mutational burden, which suggests that hedgehog inhibitor refractory tumours could be offered immunotherapy; some trials are ongoing. The standard treatment for most basal cell carcinomas is surgery, as it allows excision margin control and shows a low risk of recurrence. Superficial lesions can be treated by non-surgical methods with significant efficacy.
... The ozone layer blocks UVC. Although there is around 20 times more UVA than UVB in terrestrial solar light, it is well-known that UVB is the primary factor underlying UV-induced photoaging due to its higher energy [18]. Indeed, UVB and UVA can both interact with endogenous photosensitizers and chromophores, resulting in reactive oxygen species production that causes damage to DNA and proteins; however, only UVB can directly affect DNA, synthesizing photoproducts including pyrimidine-pyrimidine dimers [19,20]. ...
Solar ultraviolet (UV) radiation is the primary factor of cutaneous aging, resulting in coarse wrinkles and dryness. In this study, we aimed to test whether decanal, an aromatic compound found mainly in citrus fruits, inhibits UVB-mediated photoaging in human dermal fibroblasts and to explore whether its anti-photoaging effect occurs via cyclic adenosine monophosphate (cAMP) signaling. We found that decanal promotes collagen production dose-dependently. Meanwhile, it also increased the intracellular cAMP levels and decreased the number of molecules involved in the mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) pathway, downregulating the collagen genes and upregulating the matrix metalloproteinase (MMP) genes in UVB-exposed dermal fibroblasts. Furthermore, it enhanced hyaluronic acid levels and hyaluronic acid synthase mRNA expression. Notably, the beneficial effects of decanal were lost in the presence of a cAMP inhibitor. Our results revealed the potential of decanal for preventing photoaging and suggested that its effects are cAMP-mediated in human dermal fibroblasts.
... Similar to melanoma, UV is a major environmental carcinogen of BCC. UV-mediated C ? T conversions are observed in several tumor suppressor genes in BCC patients, including patched 1 (PTCH1) and p53 (87). Although direct research on mitochondrial sirtuins and their response to UV in this neoplasm are severely lacking, the links between SIRT3 and p53, especially those discussed above in the melanoma section, suggest that further research will uncover a clear relationship in BCC. ...
Mammalian sirtuins (SIRTs 1‐7), are a family of NAD+‐dependent deacetylases with distinct subcellular localization and biological functions that regulate various important cellular processes. Among these, SIRTs ‐3, ‐4, and ‐5 are located in the mitochondria and have been implicated in caloric restriction, oxidative stress, aging, and various human diseases. Emerging evidence has found dysregulation of mitochondrial sirtuins in multiple dermatological conditions, including responses to ultraviolet radiation (UVR), suggesting their importance in maintaining skin health. In this review, we discuss the roles and implications of mitochondrial sirtuins in cutaneous cellular processes, and their emerging potential as a target for the management of skin diseases, including skin cancer. Among mitochondrial sirtuins, SIRT3 is the most studied and linked to multiple skin conditions and diseases (keratinocyte differentiation, wound healing, chronological aging, UVR and ozone response, systemic sclerosis, melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC)). SIRT4 has been connected to keratinocyte differentiation, chronological aging, UVR response, alopecia, BCC and SCC. Further, SIRT5 has been associated with keratinocyte differentiation, melanoma, BCC and SCC. Overall, while there is compelling evidence for the involvement of mitochondrial sirtuins in skin, additional detailed studies are needed to understand their exact roles in skin and skin cancers.
... The risk factors of this type of cancer are the increased rate of solar radiation exposure and the thinning or lack of ozone layer. The main etiological factor responsible for basal cell carcinoma (BCC) is the chronic ultraviolet (UV) radiation exposure at the expense mostly of UVB rays with 290-320 nm wavelengths [4]. This results in activating of proto-oncogenes and inactivation of tumor suppressive genes in the keratinocytes. ...
Basal cell carcinoma (BCC) is a frequent form of skin cancer, which usually affects people that have been exposed to the sunlight for longer periods of time. The cells of the lower part of the epidermis are called the basal cell layer. These cells constantly divide to form new cells to replace the squamous cells that wear off the skin's surface. As these cells move up in the epidermis, they get flatter, eventually becoming squamous cells. Therefore, the BCC develops from these cells. Most BCCs have indolent behavior, with cure rates very high after low-complexity treatment. However, some lesions are very aggressive and there are only a few papers focusing on the subtype of this skin cancer known with the name ulcus rodens or giant BCC. In this study, we evaluate a case of ulcus rodens or giant BCC, subtype of the BCC skin cancer located in the area of the nasal pyramid, stage III, TxNxMx, with lymphatic and vascular invasion present.
... The highest incidence of BCC is reported in Queensland, Australia. 1 Presence of BCC in non-white population has also been well documented. Most of the cases of BCC in colored population (Asians) are reported to clinics as late presentation. ...
Objectives: Basal cell carcinoma (BCC) is the most common cutaneous malignancy in white population. The pattern of exon specific p53 mutations in BCC and its subtypes remain undetected in our population. This study was designed to evaluate the prevalence and mutational spectrum of p53 mutations in basal cell carcinoma (BCC) and its subtypes in people of color in the population of Karachi, Pakistan. Study Design: Retrospective cross sectional study. Setting: Material and Methods: Convenient sampling technique was used. Sample size was calculated using open EPI software. Analysis of 32 BCC cases for p53 gene mutations in exons 5-8 was detected by polymerase chain reaction technique. Sebaceous carcinoma and malignant melanoma were used as positive controls and normal skin was used as negative control. Results: Out of 32 BCC cases, 26 (81.2%) displayed p53 exon mutations. The number of cases with single exon mutation was 17 (65.3%). Exon 5 mutation was most frequently observed in 8 (30.7%) cases. This was followed by 5 (19.2%) cases with exon 6 mutation and 4 (15.3%) cases with exon 8 mutation. None of the cases revealed exon 7 mutation. A considerable number 9 (34.6%) of BCC displayed dual exon mutation. Dual mutations of exon 6 & 8 were seen in 6 (23%) cases. Exon 5 & 7 mutation was noted in 2 (7.6%) cases followed by a single (3.8%) case with exon 6&7 mutation. The highest number 12 (46.1%) of single and dual exon mutations was recorded in nodular subtype of BCC. Conclusion: The current study confirms the expression of p53 gene mutation in BCC in colored population. Majority of the single mutations were observed in exon 5. Dual exon mutation was the most notable finding of this study. The highest number of single and dual exon mutations was recorded in nodular form of BCC.
Introduction: Basal cell carcinoma (BCC) is the most frequent skin cancer with a rising incidence worldwide. Predilection sites are the head and the neck in 80-85% of cases. Leading risk factors are sun exposure and ionizing radiation. In the middle of the 20th century, radiation-induced epilation was used as an efficient treatment method for tinea capitis. Patient review: We report a case of an 80-year-old man with a 16year history of the successive occurrence of multiple BCCs on the scalp, face, and neck. He also had the history of tinea capitis treated with radiotherapy during childhood. At presentation during clinical and dermoscopic examination approximately 25 BCCs were observed, predominantly on the scalp. The most common BCC lesion was the nodular subtype, followed by the pigmented and superficial subtypes. Histopathological examination confirmed the diagnosis of BCC in multiple lesions and one squamous cell carcinoma (SCC). In personal history, the most important comorbidity was hairy cell leukemia. The therapeutic approach included surgery and 5-fluorouracil 5% cream. Conclusion: Radiation-induced epilation was used as an efficient method for treating tinea capitis. One of its side effects was the appearance of BCC in radiation exposed areas. Surgical excision is the gold standard for BCC treatment. Also, 5-fluorouracil 5% cream may be a good option for patients with multiple BCCs. We present satisfactory results after combined treatment in our patient.
Background
The periocular skin is neoplasms-prone to various benign and malignant. Periocular malignancies are more aggressive and challenging to cure and repair than those in other skin areas. In recent decades, immunotherapy has significantly advanced oncology, allowing the autoimmune system to target and destroy malignant cells. Skin malignancies, especially periocular tumors, are particularly sensitive to immunotherapy. This technique has dramatically impacted the successful treatment of challenging tumors.
Main text
Extraocular cancers, including eyelid (basal cell carcinoma, squamous cell carcinoma, melanoma, merkel cell carcinoma), conjunctival tumors (conjunctival melanoma, ocular surface squamous neoplasia) and other rare tumors, are unique and challenging clinical situations. Several genetic alterations associated with the pathogenesis of these diseases have been identified, and molecular mechanism are essential for the development of the immunotherapy agents, such as Hedgehog pathway inhibitors (vismodegib and sonidegib) for basal cell carcinoma, BRAF/MEK inhibitors (vemurafenib, dabrafenib, and encorafenib) for melanoma, and immune checkpoint inhibitors (Avelumab, pembrolizumab) for Merkel cell carcinoma.
Conclusions
The optimal treatment for periocular skin cancer depends on the type and size of the tumor and whether it involves orbital and adnexal structures. Adjuvant and neoadjuvant therapy with chemotherapy-targeted therapies and immune checkpoint inhibitors should be considered based on tumor type, tumor molecular profile, expected response rate, and candidacy for systemic treatment.
Basal cell carcinoma is most common type of non-melanotic skin cancer. Causative agents are UV and ionizing radiation and chemicals. Nodular, pigmented, superficial, cystic and infiltrative are major subtypes. It is mainly treated by excision surgery in the form of wide local excision and reconstruction is done by various flaps. In our study 10 patients were included and found that carcinoma is commoner in old age female patients and mainly near right canthus of eyeball; treated with surgery which is well tolerated by all the patients.
Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from European Association of Dermato-Oncology (EADO), European Dermatology Forum, European Society for Radiotherapy and Oncology (ESTRO), Union Européenne des Médecins Spécialistes, and the European Academy of Dermatology and Venereology developed updated recommendations on diagnosis and treatment of BCC. BCCs were categorised into 'easy-to-treat' (common) and 'difficult-to-treat' according to the new EADO clinical classification. Diagnosis is based on clinico-dermatoscopic features, although histopathological confirmation is mandatory in equivocal lesions. The first-line treatment of BCC is complete surgery. Micrographically controlled surgery shall be offered in high-risk and recurrent BCC, and BCC located on critical anatomical sites. Topical therapies and destructive approaches can be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial and low-risk nodular BCCs. Management of 'difficult-to-treat' BCCs should be discussed by a multidisciplinary tumour board. Hedgehog inhibitors (HHIs), vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCC. Immunotherapy with anti-PD1 antibodies (cemiplimab) is a second-line treatment in patients with a progression of disease, contraindication, or intolerance to HHI therapy. Radiotherapy represents a valid alternative in patients who are not candidates for or decline surgery, especially elderly patients. Electrochemotherapy may be offered when surgery or radiotherapy is contraindicated. In Gorlin patients, regular skin examinations are required to diagnose and treat BCCs at an early stage. Long-term follow-up is recommended in patients with high-risk BCC, multiple BCCs, and Gorlin syndrome.
Objectives
To assess the independent causal effect of body mass index (BMI) and 25-hydroxy-vitamin D (25(OH)D) level on basal cell carcinoma(BCC), we performed univariable and multivariable two-sample Mendelian randomization (MR) analysis.
Methods
We used overlapping genome-wide significant single nucleotide polymorphisms(SNPs) for BMI and 25(OH)D as instrumental variables and selected effective SNPs to applied a series of MR methods including inverse variance weighted (IVW),MR Egger,and Weighted median. After that, we employed sensitivity analysis to make sure the results were reliable and robust.
Results
In the univariable two-sample MR analysis, higher BMI was related to lower risk for BCC (Odds ratio(OR)=0.90; 95%confidence interval (CI),[0.81,0.99]; p = 0.02). In the multivariable MR, the causal effect of BMI on BCC after adjusting for 25(OH)D level still remained(OR=0.88; 95% CI,[−0.22; −0.03], p-value=0.008).However,our results suggest that 25(OH)D level was not associated with BCC(OR=1.02; 95%CI,[0.94,1.09],p-value=0.67).
Conclusion
Similar to the conclusions of previous observational studies, the MR results suggest that BMI is an independent protective factor for BCC. While, vitamin D levels may not be causally associated with the risk of basal cell carcinoma and increasing vitamin D supplementation is unlikely to reduce the risk.
Hintergrund und zielsetzung:
Die chirurgische Exzision ist die bedeutendste Therapiemodalität zur Versorgung von Basalzellkarzinomen (BCC). Oft kommt es zu einer unvollständigen Exzision, die eine Reexzision nach sich zieht. Allerdings enthalten Reexzisionspräparate häufig keine Tumorreste, weswegen die Reexzision im Nachhinein überflüssig ist. Ziel unserer Studie ist die Identifikation von klinisch-pathologischen Merkmalen, die mit dem Vorhandensein von histologischen Tumorresten in Reexzisionspräparaten assoziiert sind.
Patienten und methoden:
255 unvollständig resezierte BCC von 222 Patienten wurden in diese Fall-Kontroll-Beobachtungsstudie eingeschlossen. Acht klinisch-pathologische Merkmale wurden in einer binären logistischen Regressionsanalyse mit dem Vorhandensein oder Nichtvorhandensein von histologischen Tumorresten in Reexzisionspräparaten korreliert.
Ergebnisse:
Ein höheres Alter bei der ersten Exzision und ein BCC in der Rezidiv-Hochrisikozone erwiesen sich als unabhängige Risikofaktoren für das Vorhandensein von histologischen Tumorresten in Reexzisionspräparaten.
Schlussfolgerungen:
Die Ergebnisse unserer Studie zeigen, dass eine Reexzision von unvollständig resezierten BCC in der oben genannten Subpopulation definitiv notwendig ist. Für die Nachbehandlung unvollständig resezierter BCC, die sich in der Rezidiv-Niedrigrisikozone jüngerer Patienten befinden, können jedoch auch weniger invasive Therapien wie Imiquimod in Betracht gezogen werden.
Background and objective:
Surgical excision is the primary mode of treating basal cell carcinoma (BCC). Incomplete excision is a common phenomenon usually dealt with by re-excision. However, re-excision specimens often do not contain any tumor residues, rendering the procedure superfluous in hindsight. Our study objective is the identification of clinicopathological features associated with the presence of histological tumor residues in re-excision specimens.
Patients and methods:
222 patients with a total of 255 incompletely resected BCCs were enrolled in this observational case-control study. Eight clinicopathological features were correlated in a binary logistic regression analysis to the presence or absence of histological tumor residues in re-excision specimens.
Results:
Advanced age at first excision and a BCC in the high-risk zone for recurrence were found to be independent risk factors for the presence of histological tumor residues in re-excision specimens.
Conclusions:
Our study results indicate a clear need for re-excision of incompletely resected BCCs in the aforementioned subpopulation. However, less invasive therapies such as imiquimod may be considered for the follow-up treatment of incompletely resected BCCs located in the low-risk zone for recurrence in younger patients.
Basal cell carcinoma is the most frequent malignant neoplasm in white-skinned individuals. It develops in different body areas, including in the scalp, which is a unique anatomical region due to the high number of pilosebaceous follicles; the scalp is protected from UV exposure, a main risk factor for basal cell carcinoma development. Moreover, scalp basal cell carcinoma has been described as more aggressive and difficult to treat than other forms of basal cell carcinoma. Even though it is not yet clear whether scalp basal cell carcinomas represent a different entity, it seems important to give them special attention due to their potential aggressiveness, invasion capacities, tendency to relapse, and treatment difficulties.KeywordsPigmented scalp lesionsBasal cell carcinomaUV exposureDermoscopeTumorsScalp
Basal cell carcinoma (BCC) is the most frequent histological type of cancer in the world and accounts for approximately 80% of all skin cancers. In the majority of cases, they are slow-growing, low metastatic potential tumors, easy to cure by surgical or nonsurgical procedures. Giant BCC (GBCC) is a rare variant of BCC and according to the American Joint Committee on Cancer, this includes lesions with a diameter larger than 5 cm. GBCC's incidence has been reported to be less than 1%, and it displays a more aggressive behavior with both local invasion and higher metastatic potential. Archodaki et al. specifically reported that metastasis was present in 17.6% of GBCC patients during the primary examination. Patients with GBCC who are not suitable for either surgery or radiotherapy since 2012 seem to have another therapeutic option. Vismodegib is an oral small-molecule inhibitor of the Hedgehog pathway (HPI) that was approved for treating metastatic or locally advanced BCC in patients who are poor candidates for surgery or radiotherapy. In this case, we present a woman with two simultaneous facial GBCCs who was treated successfully using vismodegib as a monotherapy.
Basal cell carcinoma (BCC) is the most common malignant tumor in light‐skinned people and amounts to about 75 % of all cases of skin cancer. Increasing incidence rates have been reported for decades all over the world. The main risk factors include UV radiation, male sex, light skin type, advanced age, long‐term immunosuppression, a positive individual or family history, and certain genodermatoses. BCC metastasizes only rarely, and its mortality is low, but it is associated with significant morbidity. Genetic mutations especially in the hedgehog pathway play an important role in BCC pathogenesis. Non‐invasive procedures such as optical coherence tomography or confocal laser scan microscopy are increasingly utilized for diagnostics in addition to visual inspection and dermatoscopy, but only in exceptional cases can histological confirmation of the diagnosis be dispensed with. Various clinical and histological subtypes have been defined. Differentiating between BCC with high and low risk of recurrence has a significant influence on the choice of treatment. Most BCC can be treated effectively and safely with standard surgery, or in selected cases with topical treatment. Locally advanced and metastasized BCC must be treated with radiation or systemic therapy. Radiation is also an option for older patients with contraindications for surgery. The hedgehog inhibitors vismodegib and sonidegib are currently approved for systemic therapy of BCC in Europe. Approval for the PD1 inhibitor cemiplimab as second‐line therapy is expected in the near future.
Objectives
The objective of the study was to analyze the demographic profile, histopathological features, risk factors, and recurrence rates in patients with basal cell carcinoma.
Materials and Methods
A retrospective study was conducted from 2012 to October 2018 in 29 patients with histopathologically confirmed basal cell carcinoma. All the patients had undergone either excision or cryotherapy as per the institution protocol. Information on the history of the disease, occupation, history of sun exposure and clinical and histopathological features were collected and analyzed.
Results
A female preponderance was found ( n = 18, 62.1%), majority of the patients were unemployed (44.8%), 19 patients (65.5%) gave a history of sun exposure, and the nose was the most common site of disease. Ten females (34.5%) did not have any excessive exposure to the sun, but gave a history of exposure to heat and fumes in the kitchen. Six patients (20.7%) had a preexisting nevus at the same site and superficial spreading type was the most common histopathological type ( n = 24, 82.8%). Excision gave the best result. Four patients (13.8%) had recurrence of the disease.
Limitations
Small sample size was the major limitation. The risk factors and occupation could not be analyzed objectively.
Conclusion
This is a pioneer study from Kerala. A female preponderance (62.1%) was observed. The role of heat, fumes, type of oven, and use of reheated oil in cooking as risk factors for the development of BCC needs analysis in future studies. Superficial spreading type was the most common pattern observed in histopathology slides (82.8%). Excision gives near-complete clearance and a good cosmetic result with less risk of recurrence.
Background
Basal cell carcinoma (BCC) is the commonest cancer affecting white‐skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. First‐line treatment is usually surgical excision, but alternatives are available. New published studies and the development of non‐surgical treatments meant an update of our Cochrane Review (first published in 2003, and previously updated in 2007) was timely.
Objectives
To assess the effects of interventions for BCC in immunocompetent adults.
Search methods
We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS.
Selection criteria
Randomised controlled trials (RCTs) of interventions for BCC in immunocompetent adults with histologically‐proven, primary BCC. Eligible comparators were placebo, active treatment, other treatments, or no treatment.
Data collection and analysis
We used standard methodological procedures expected by Cochrane. Primary outcome measures were recurrence at three years and five years (measured clinically) (we included recurrence data outside of these time points if there was no measurement at three or five years) and participant‐ and observer‐rated good/excellent cosmetic outcome. Secondary outcomes included pain during and after treatment, early treatment failure within six months, and adverse effects (AEs). We used GRADE to assess evidence certainty for each outcome.
Main results
We included 52 RCTs (26 new) involving 6690 participants (median 89) in this update. All studies recruited from secondary care outpatient clinics. More males than females were included. Study duration ranged from six weeks to 10 years (average 13 months). Most studies (48/52) included only low‐risk BCC (superficial (sBCC) and nodular (nBCC) histological subtypes). The majority of studies were at low or unclear risk of bias for most domains. Twenty‐two studies were industry‐funded: commercial sponsors conducted most of the studies assessing imiquimod, and just under half of the photodynamic therapy (PDT) studies.
Overall, surgical interventions have the lowest recurrence rates. For high‐risk facial BCC (high‐risk histological subtype or located in the facial 'H‐zone' or both), there may be slightly fewer recurrences with Mohs micrographic surgery (MMS) compared to surgical excision (SE) at three years (1.9% versus 2.9%, respectively) (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.16 to 2.64; 1 study, 331 participants; low‐certainty evidence) and at five years (3.2% versus 5.2%, respectively) (RR 0.61, 95% CI 0.18 to 2.04; 1 study, 259 participants; low‐certainty evidence). However, the 95% CI also includes the possibility of increased risk of recurrence and no difference between treatments. There may be little to no difference regarding improvement of cosmetic outcomes between MMS and SE, judged by participants and observers 18 months post‐operatively (one study; low‐certainty evidence); however, no raw data were available for this outcome.
When comparing imiquimod and SE for nBCC or sBCC at low‐risk sites, imiquimod probably results in more recurrences than SE at three years (16.4% versus 1.6%, respectively) (RR 10.30, 95% CI 3.22 to 32.94; 1 study, 401 participants; moderate‐certainty evidence) and five years (17.5% versus 2.3%, respectively) (RR 7.73, 95% CI 2.81 to 21.3; 1 study, 383 participants; moderate‐certainty evidence). There may be little to no difference in the number of participant‐rated good/excellent cosmetic outcomes (RR 1.00, 95% CI 0.94 to 1.06; 1 study, 326 participants; low‐certainty evidence). However, imiquimod may result in greater numbers of good/excellent cosmetic outcomes compared to SE when observer‐rated (60.6% versus 35.6%, respectively) (RR 1.70, 95% CI 1.35 to 2.15; 1 study, 344 participants; low‐certainty evidence). Both cosmetic outcomes were measured at three years.
Based on one study of 347 participants with high‐ and low‐risk primary BCC of the face, radiotherapy may result in more recurrences compared to SE under frozen section margin control at three years (5.2% versus 0%, respectively) (RR 19.11, 95% CI 1.12 to 325.78; low‐certainty evidence) and at four years (6.4% versus 0.6%, respectively) (RR 11.06, 95% CI 1.44 to 84.77; low‐certainty evidence). Radiotherapy probably results in a smaller number of good participant‐ (RR 0.76, 95% CI 0.63 to 0.91; 50.3% versus 66.1%, respectively) or observer‐rated (RR 0.48, 95% CI 0.37 to 0.62; 28.9% versus 60.3%, respectively) good/excellent cosmetic outcomes compared to SE, when measured at four years, where dyspigmentation and telangiectasia can occur (both moderate‐certainty evidence).
Methyl‐aminolevulinate (MAL)‐PDT may result in more recurrences compared to SE at three years (36.4% versus 0%, respectively) (RR 26.47, 95% CI 1.63 to 429.92; 1 study; 68 participants with low‐risk nBCC in the head and neck area; low‐certainty evidence). There were no useable data for measurement at five years. MAL‐PDT probably results in greater numbers of participant‐ (RR 1.18, 95% CI 1.09 to 1.27; 97.3% versus 82.5%) or observer‐rated (RR 1.87, 95% CI 1.54 to 2.26; 87.1% versus 46.6%) good/excellent cosmetic outcomes at one year compared to SE (2 studies, 309 participants with low‐risk nBCC and sBCC; moderate‐certainty evidence).
Based on moderate‐certainty evidence (single low‐risk sBCC), imiquimod probably results in fewer recurrences at three years compared to MAL‐PDT (22.8% versus 51.6%, respectively) (RR 0.44, 95% CI 0.32 to 0.62; 277 participants) and five years (28.6% versus 68.6%, respectively) (RR 0.42, 95% CI 0.31 to 0.57; 228 participants). There is probably little to no difference in numbers of observer‐rated good/excellent cosmetic outcomes at one year (RR 0.98, 95% CI 0.84 to 1.16; 370 participants). Participant‐rated cosmetic outcomes were not measured for this comparison.
AEs with surgical interventions include wound infections, graft necrosis and post‐operative bleeding. Local AEs such as itching, weeping, pain and redness occur frequently with non‐surgical interventions. Treatment‐related AEs resulting in study modification or withdrawal occurred with imiquimod and MAL‐PDT.
Authors' conclusions
Surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with MMS over SE for high‐risk facial primary BCC (low‐certainty evidence). Non‐surgical treatments, when used for low‐risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. Of the non‐surgical treatments, imiquimod has the best evidence to support its efficacy.
Overall, evidence certainty was low to moderate. Priorities for future research include core outcome measures and studies with longer‐term follow‐up.
Background: Non-melanoma skin cancer (NMSC) represents the most frequently diagnosed cancer in humans. Occupational solar UV radiation exposure is associated with a higher-risk of developing NMSC, but still Romania does not acknowledge this affliction as an occupational disease. The study aims to determine if occupationally-induced NMSC is associated with more aggressive clinical and histopathological features compared to sporadic NMSC. Material and methods: A retrospective, analytical, comparative study was conducted during 2017-2019 in a University Department of Dermato-venereology in Bucharest, Romania, with focus on patients presenting with NMSC who underwent surgical excision of lesions followed by histopathological examination, classified as outdoor or indoor workers. High-risk clinical and histopathological characteristics were analysed and correlated with outdoor UV exposure. Outcomes: The study included 51 consecutive patients diagnosed with NMSC, of which 25 outdoor workers (OW) and 26 controls as indoor workers with no occupational UV exposure background. OW presented with 21 BCC and four SCC, while controls with 22 BCC and four SCC. Males were predominant in both groups and most patients came from urban environment. The mean age value was lower for the OW group compared to controls. OW had a 4.66 times higher risk of developing NMSC with aggressive location and size χ² (1, N=51) = 6.246, p=0.013, OR=4.66 (95% CI: 1.34, 16.23) and a 24-fold risk of developing NMSC with clinically poorly defined margins χ² (1, N=51) = 21.697, p<0.001, OR=24.44 (95% CI: 5.38,110.92). The risk of developing a high-risk histopathological subtype was 15 times greater for OW χ² (1, N=51) = 13.814, p<0.001, OR=15.27 (95% CI: 2.94,79.08). Moderate to severe desmoplastic reaction was 8.57 more frequent in controls χ² (1, N=51) = 12.244, p=0.001, OR=8.57 (95% CI: 2.42, 30.30). Grades 2 and 3 of actinic elastosis were significantly associated with outdoor work (χ² (1, N=51) = 33.382, p<0.001, OR=131.25 (95% CI: 13.60, 1266.37). The presence of ulceration and pigment association of tumors on the histopathological report were not significantly associated with outdoor working. Conclusion: 1. Occupational NMSC in Romania is associated with high-risk clinical features; 2. Poorly defined borders is a significant clinical high-risk factor associated with occupational UV exposure in NMSC; 3. High-risk histopathological subtypes are more frequently encountered in outdoor workers diagnosed with NMSC compared to indoor workers with no occupational UV exposure background; 4. Occupational NMSC is associated with significantly higher grades of desmoplastic reaction and of actinic elastosis compared to indoor workers.
Basal cell carcinoma is the most common type of cancer in Central Europe and has a high medical relevance. Due to its high tendency of recurrence, an important parameter in the planning of therapy is the risk of recurrence. After clinical and histological diagnosis, the majority of tumors are treated surgically, although radiation and topical procedures are also possible therapeutic alternatives in certain constellations. Hedgehog inhibitors, a completely new class of substances, have recently been approved for rare metastatic and locally advanced diseases, thus significantly expanding the range of treatments. This article provides an overview of the current guideline-based diagnosis and therapy of basal cell carcinomas in Germany.
Purpose:
Basal cell carcinoma (BCC) is the most commonly diagnosed skin cancer and is treated by surgical resection. Incomplete tumor removal requires surgical revision, leading to significant healthcare costs and impaired cosmesis. We investigated the clinical feasibility of a surgical navigation system for BCC surgery, based on molecular tissue characterization using rapid evaporative ionization mass spectrometry (REIMS).
Methods:
REIMS enables direct tissue characterization by analysis of cell-specific molecules present within surgical smoke, produced during electrocautery tissue resection. A tissue characterization model was built by acquiring REIMS spectra of BCC, healthy skin and fat from ex vivo skin cancer specimens. This model was used for tissue characterization during navigated skin cancer surgery. Navigation was enabled by optical tracking and real-time visualization of the cautery relative to a contoured resection volume. The surgical smoke was aspirated into a mass spectrometer and directly analyzed with REIMS. Classified BCC was annotated at the real-time position of the cautery. Feasibility of the navigation system, and tissue classification accuracy for ex vivo and intraoperative surgery were evaluated.
Results:
Fifty-four fresh excision specimens were used to build the ex vivo model of BCC, normal skin and fat, with 92% accuracy. While 3 surgeries were successfully navigated without breach of sterility, the intraoperative performance of the ex vivo model was low (< 50%). Hypotheses are: (1) the model was trained on heterogeneous mass spectra that did not originate from a single tissue type, (2) during surgery mixed tissue types were resected and thus presented to the model, and (3) the mass spectra were not validated by pathology.
Conclusion:
REIMS-navigated skin cancer surgery has the potential to detect and localize remaining tumor intraoperatively. Future work will be focused on improving our model by using a precise pencil cautery tip for burning localized tissue types, and having pathology-validated mass spectra.
Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States, with an estimated 4.3 million cases diagnosed each year. The major risk for BCC is primarily related to sun exposure; however, multiple modifiable and nonmodifiable risk factors contribute to the development of this condition. Although it rarely metastasizes, BCC can cause significant morbidity through local tissue destruction and infiltration into vital underlying organs. There are multiple treatment options for BCC, but Mohs micrographic surgery is considered to be the gold standard of therapy. For individuals with unresectable or metastatic BCC, new and emerging therapies involving inhibition of the Hedgehog signaling pathway have shown promising results. This article discusses the most current literature for dermatology nurses on the epidemiology, assessment, and treatment of BCC with the focus on early detection and management to lower morbidity and offer better patient outcomes.
Basal cell carcinoma is the commonest malignancy in Caucasians with incidence rates of 300 per 100,000 reported in the USA. Rates are increasing at over 10% per year leading to a lifetime risk of 30%. Although mortality is low, the disease is responsible for considerable morbidity and places a substantial burden on health service provision in the UK. Furthermore, lesions may recur and patients often develop multiple tumours giving major implications for treatment and follow-up. Four main types of basal cell carcinoma are seen: nodulo-ulcerative; pigmented; morpheaform and superficial. Diagnosis is by histological evaluation although many tumours have a characteristic clinical appearance. The differential diagnosis is large. Identified risk factors include male gender, skin type 1, red/blonde hair and increasing age. Patients with basal cell carcinoma are more likely to develop malignant melanoma and squamous cell carcinoma but it is still unclear whether there is a link with internal malignancy. The main treatment modalities are surgery and radiotherapy. Each has advantages and disadvantages. The choice of treatment depends on many factors. Principles of treatment include identification of high-risk patients to enable early detection, complete removal of the lesion, and careful follow-up to detect recurrence or new lesions. Approximately 10% of tumours recur, depending on site, size and treatment modality. Metastatic basal cell carcinoma and the association of ultraviolet radiation to basal cell carcinoma risk are reviewed.
Epidemiology shows a relationship between solar exposure and all types of skin cancer. Understanding the mechanisms of skin cancer requires knowledge of the photomolecular events that occur within the relevant epidermal cell types in vivo. Studies to date have focused on UVR-induced DNA lesions in keratinocytes, the majority epidermal cell population which gives rise to most skin cancers. Malignant melanoma, arising from melanocytes (5%–10% of epidermal cells), accounts for most skin cancer deaths. We report on new techniques to detect DNA photolesions in human epidermal melanocytes in situ. Previously nonexposed buttock skin of volunteers of skin types I/II was exposed to clinically relevant doses of narrow bandwidth UVB (300 nm) and UVA (320 nm, 340 nm, 360 nm) radiation. Biopsies were taken immediately afterwards and processed for routine histology. Microscope sections were prepared and double-stained with fluorescent-tagged monoclonal antibodies for thymine dimers and melanocytes. UVR dose–response curves for dimer levels within melanocyte nuclei were determined by image analysis and compared with dimer levels in adjacent basal cell keratinocytes. Our data show that UVB and UVA readily induce thymine dimers in melanocytes at levels that are comparable with those found in adjacent keratinocytes. This new technique will enable melanocyte specific studies, such as DNA repair kinetics, to be done in vivo.Keywords: image analysis
To establish the relationship between ultraviolet-B radiation and squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and actinic keratosis (AK), a cross-sectional prevalence survey was performed in a sample of 808 white, male watermen 30 years of age and older residing in the Eastern Shore of Maryland. A measure of personal cumulative ultraviolet-B exposure was determined for each subject from data collected through interviews and field and laboratory measurements. A personal interview elicited skin type, medication history, and other factors. Clinical diagnoses and histologic confirmation were done for current and previously removed skin tumors. The ratio of subjects with SCC to subjects with BCC was approximately 1:1; however, the ratio of BCC to SCC was 1.25:1 because BCC cases were more prone to multiple lesions. Watermen with SCC or AK but not BCC had higher average annual ultraviolet-B doses than age-matched controls. This was particularly marked in watermen younger than 60 years of age. Logistic regression showed that an older age, childhood freckling, and blue eyes significantly increased the risk of the development of all three types of skin tumor. Ease of sunburning was associated with BCC and AK, but not with SCC. Watermen in the upper quartile of cumulative ultraviolet-B exposure had a 2.5 times higher risk for the development of SCC when compared with the lower 3 quartiles. This suggests that high levels of ultraviolet-B exposure are important in SCC occurrence. The risk of AK developing was 1.5 times higher for those whose cumulative ultraviolet-B exposure exceeded the median. The relationship of BCC to cumulative ultraviolet-B exposure was not clear and this suggests that different etiologic mechanisms operate for SCC and BCC.
Data for the incidence of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin, registered for six regions of Norway during 10 years (1976-1985), were used to evaluate the biological amplification factor Ab for induction of these cancers by sunlight. Ab is the ratio of the increment in skin cancer production to the increment in causative sunlight exposure. Two different approximations were used for the action spectrum for carcinogenesis: an erythema action spectrum; and an action spectrum for mutagenesis of cells in the basal layer of the skin. These two fundamentally different approaches yielded Ab values that were similar to within about 10%: 2.1-2.3 for BCCs; and 1.6-1.8 for SCCs. Using a radiation amplification factor for ozone depletion of 0.8-1.1, we find that the total amplification factor for BCCs is within the range 1.6-2.1 and that that for SCCs is within the range 1.3-1.7 at northern latitudes of 60-70 degrees. Thus, an ozone depletion of 1% will result in an increase in the incidence of BCCs by 1.6-2.1% and of SCCs by 1.3-1.7%. There were no significant differences between the values for men and women. Neither was there any significant difference between Ab values found for skin commonly exposed to sunlight (face) and for skin sites normally covered by clothes and therefore receiving much lower exposures, in spite of the fact that the tumor density per unit skin area was a factor of 20 or more larger at the former sites. This observation, as well as the curves relating cancer incidence with annual exposure to carcinogenic sunlight, supports a power law relationship between cancer incidence and annual sun exposure. Sunlight appears to be the main cause of BCCs and SCCs even at the high latitudes of Northern Norway. All over, BCCs were found to be about 6 times more frequent than SCCs. The ratio of the incidence of BCCs to that of SCCs seemed to be independent of the latitude. Finally, BCCs were found to be equally frequent among men and women, while SCCs were found to be about twice as frequent among men as among women.
Objective:
To assess if there are any significant differences in the sex, anatomical site, and age distribution of patients with different histological subtypes of basal cell carcinoma (BCC).Design:
Histopathology reports were analyzed with respect to the subtype of BCC, site of a tumor, and age and sex of a patient.Setting:
Histopathology reports were reviewed from 1 private laboratory that derived its cases from general practitioners, surgeons, and dermatologists.Patients:
Patients with BCC (N=3885) for whom case data were received by the pathology laboratory from January 2, 1991, to June 12, 1991, were included in the study.Interventions:
None.Main Outcome Measures:
Superficial BCCs differed from other subtypes of BCC by occurring more commonly on the trunk and in younger patients.Results:
The mean age (56.8 years) of the patients with superficial BCCs was significantly lower than that of the patients with other subtypes of BCC who were examined (P<.001); the mean ages of the patients with these other subtypes were as follows: nodulosuperficial BCC, 62.9 years; nodular BCC, 63.9 years; nodulomorpheic BCC, 66.1 years; and morpheic BCC, 66.0 years. The majority of superficial BCCs occurred on the trunk and limbs (73.3%), while the majority of all other subtypes occurred on the head and neck.Conclusions:
Superficial BCC differs from the other subtypes of BCC in terms of patient age and tumor site, and these findings may reflect differences in the etiology.Arch Dermatol. 1997;133:593-596
Objective
To investigate the role of pigmentary traits, different patterns of sun exposure, artificial sources of UV radiation, and lifestyle-related factors on the risk of basal cell carcinoma (BCC) in a Mediterranean population from central-southern Italy.Design
Hospital-based case-control study.Setting
A referral dermatological hospital in Rome, Italy.Patients
A convenience sample of 166 case patients with histologically confirmed BCC and 158 cancer-free control subjects with minor dermatological conditions observed between March 1995 and June 1997.Results
In the multivariate analysis, the mean number of weeks per year spent at the beach before the age of 20 years was significantly associated with BCC. A dose-response trend was found for subjects who had spent 3 to 4 (odds ratio, 1.8; 95% confidence interval, 0.8-4.4), 5 to 8 (odds ratio, 3.7; 95% confidence interval, 1.5-9.0), or more than 8 (odds ratio, 4.5; 95% confidence interval, 1.9-10.5) weeks per year at the beach (P = .01 for trend). There was a significant association with the presence of actinic keratoses or solar lentigines, whereas no effect was found for skin type, history of sunburns, exposure to nonsolar UV radiation, and lifestyle-related habits such as cigarette smoking, alcohol consumption, and coffee drinking. Subjects reporting a family history of skin cancer had an extremely increased risk of BCC.Conclusion
The definite association with recreational sun exposure during childhood and adolescence and the strong relation with family history of skin cancer suggest that genetic predisposition and peculiar exposure patterns to UV radiation are key independent risk factors for the development of BCC in a southern European population.
To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell carcinoma and 174 matched controls, and 168 cases with cutaneous malignant melanoma and 176 matched controls. Controls were matched on age, gender and place of residence. Subjects indicated their hair colour before 7 years of age, and at 25 years of age and their skin phototype. Interviewers assessed the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases were of skin type II than skin type IV; skin type II was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR > 9.7, blond hair vs. brown/black: OR = 2.4, and skin type II vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous malignant melanoma.
DNA damage induced by UV radiation and visible light (290-500 nm) in AS52 Chinese hamster cells was analysed by an alkaline elution assay with specific repair endonucleases. Cells were exposed to extensively filtered monochrome or broad-band radiation. Between 290 and 315 nm, the ratio of base modifications sensitive to Fpg protein (i.e. 8-hydroxyguanine and formamidopyrimidines) and T4 endonuclease V (i.e. cyclobutane pyrimidine dimers) was constant (approximately 1:200), indicating that the direct excitation of DNA is responsible for both types of damage in this range of the spectrum. While the yield of pyrimidine dimers per unit dose continued to decrease exponentially beyond 315 nm, the yield of Fpg-sensitive modifications increased to a second maximum between 400 and 450 nm. The damage spectrum in this wavelength range consisted of only a few other modifications (strand breaks, abasic sites and pyrimidine modifications sensitive to endonuclease III) and is attributed to endogenous photosensitizers that give rise to oxidative DNA damage via singlet oxygen and/or type I reactions. The generation of Fpg-sensitive modifications by visible light was not linear with dose but followed a saturation curve. It is calculated that the exposure of the cells to low doses of solar radiation results in the formation of cyclobutane pyrimidine dimers and Fpg-sensitive modifications in a ratio of 10:1.
• Exposure to ultraviolet radiation is the principle cause of basal and squamous cell carcinomas of the skin, which are the most frequent tumors occurring in white residents of the United States. Using a mathematical model based on epidemiologic data, we quantified the potential benefits of using a sunscreen with a sun protective factor of 15 and estimate that regular use of such a sunscreen during the first 18 years of life would reduce the lifetime incidence of these tumors by 78%. Additional benefits of sunscreen use during childhood include reduced risk of sunburn, retarding the pace of skin aging, and possible reduction in melanoma risk. We recommend that pediatricians encourage sunscreen use and sun avoidance as a regular part of pediatric preventive health care.
(Arch Dermatol 1986;122:537-545)
IT IS SOMETIMES a paradox in medicine that rare conditions are intensively studied, while common conditions are often overlooked. Such has been the case with basal cell carcinoma (BCC). The public health burden of BCC is considerable, yet the profile afforded to this cutaneous malignancy is low. This is surprising, as BCC is the most common human cancer.1 It may be a reflection of the fact that BCC has a very low mortality rate. Using mortality rates as a measure of the importance of BCC in a population, however, will grossly underestimate its importance. Morbidity from this skin cancer is considerable in terms of cosmetic and functional outcome. Increasing numbers of younger individuals are being affected, and treatment consumes considerable medical resources. Morbidity is likely to increase, as, in the white population of North America, the incidence rate of BCC has doubled approximately every 14 years.2 Incidence figures for BCC are likely to be underestimates, as many lesions are treated without histological confirmation, but figures quoted for males and females range from 175 and 124 per 100 000 in Minnesota3 to 849 and 605 per 100 000, respectively, in Australia.4
Introduction and Design:
Squamous cell carcinoma of the skin (SCC), a common cancer in white populations, is related to sunshine exposure; however, relatively little information is available on how timing and character of exposure affect the relationship. The purpose of this study was to investigate the nature of the relationship of SCC to individual solar UV exposure after control for phenotype and pigmentary factors. All newly diagnosed cases of SCC were in men aged 25 through 79 years, ascertained in the province of Alberta from January 1, 1983, through December 31, 1984, who were approached for participation; 80% completed a standardized etiologic interview that was conducted in their homes by a trained interviewer. Control subjects were chosen at random from the Alberta Health Care Insurance Plan subscribers list, matched only by sex (male) and age (within a 5-year age group). The response rate among controls was 71%.
Results:
Subjects with pale skin and red hair had an elevated risk of SCC. Subjects whose mother was of southern European ancestry had a reduced risk of SCC. After accounting for pigmentary factors, no association was seen between risk of SCC and cumulative lifetime sun exposure. However, a strong trend toward increasing risk was seen with increasing chronic occupational sun exposure in the 10 years prior to diagnosis.
Conclusion:
The results suggest that recent sun exposure (in the 10 years prior to diagnosis) may be important in accounting for individual risk of SCC.(Arch Dermatol. 1995;131:164-169)
Background
Basal cell carcinoma (BCC) is the most common type of skin cancer in whites. Long-term exposure to UV radiation is considered a major risk factor. We decided to investigate whether maximally exposed areas of the body are also the most frequent sites where BCCs develop.Design
Retrospective analysis of distribution and histopathologic features of 3065 facial BCCs.Setting
University hospital.Patients
Patients with primary or recurrent BCC of the face.Intervention
Exact topographic documentation followed by removal of BCC with Mohs prcedure and analysis of tumor extension.Main Outcome Measure
To test the hypothesis that site-specific UV exposure correlates with site-specific BCC frequency.Results
The most frequent sites of BCC were the nose (n = 1373), orbital area (n = 386), and ears (n = 269). Subdivision of these anatomical units showed that most nasal BCCs are located at the base of the nose (n = 851), while the apex (n = 292) and the dorsum of the nose (n = 230) were less frequent sites despite their prominent sun exposure. The shaded retroauricular fold (n = 99) and the sun-exposed preauricular crest (n = 105) were similar in frequency of BCCs; fewer BCCs were located on the helix of the ears (n = 65). Finally, almost 10 times more BCCs were found in the medial quadrant of the orbit (n = 225) than in the lateral quadrant (n=24). No correlation between prominent UV-exposed facial contours and particular histologic features, such as solid, morpheaform, or adenoid-cystic, could be established.Conclusions
Site-specific cumulative UV exposure alone is a poor predictor of frequency or histologic features of BCC. Additional site-specific textural qualities of facial skin may be considered as potential cofactors for the development of BCC.
Background and Design:
The frequency of melanoma and nonmelanoma skin cancer is increasing rapidly in the United States. However, the linkage of these cancers to sun exposure has been questioned because of differences in anatomic site distribution. To obtain insights into the development of these skin cancers, we examined reports of 132 patients with xeroderma pigmentosum (XP), an inherited cancer-prone, DNA repair—deficient disorder with marked clinical and laboratory UV hypersensitivity.
Results:
Malignant skin neoplasms were present in 70% of the patients with XP at a median age of 8 years, which is 50 years earlier than in the US white population. Fifty-seven percent of the patients had basal cell or squamous cell carcinoma, and 22% had melanoma. The frequency of melanomas, like the frequency of nonmelanoma skin cancers (basal cell and squamous cell carcinomas), anterior eye cancers, and tongue cancers, but unlike that of internal neoplasms, was increased 1000-fold or more in patients with XP who were younger than 20 years. As in the general population, the anatomic distribution of melanomas was different from that of nonmelanomas in the patients with XP.
Conclusions:
These data suggest that (1) DNA repair plays a major role in the prevention of cutaneous cancers in the general population and (2) sunlight exposure is responsible for the induction of melanoma as well as nonmelanoma skin cancer in patients with XP, although acting by different mechanisms for the two types of skin cancer.(Arch Dermatol. 1994;130:1018-1021)
Because it is not possible to monitor skin cancer accurately using routine methods, special surveys have been undertaken in Nambour, a typical subtropical community in Queensland, Australia. Estimates of inci- dence reported here are based on skin cancers medically treated between 1985 and 1992 and new cases diagnosed by dermatologist s in two examination clinics in 1986 and 1992. Among men and women aged 18-69 years in 1986, age-adjusted incidence rates of basal cell carcinoma were 2,074 and 1,579 per 100,000 per year, respectively—the highest incidence rates of a specific cancer ever reported. Squamous cell carcinoma occurred at half the rate of basal cell carcinoma among men and at about one third the rate among women. Although as expected, fair skin, a history of repeated sunburns, and nonmalignant solar skin damage diagnosed by dermatologist s were strongly associated with both types of skin cancer, outdoor occupation was not. Significant self-selection was observed among outdoor workers, whereby people with fair or medium complexions and a tendency to sunburn were systematically underrepresented among those in long-term outdoor occupations although they accounted for more than 80 percent of the community study sample. The mitigating effect of this selection bias may partly explain the paradox of the lack of quantitative evidence of a causal link between sun exposure and skin cancer in humans. Am J Epidemiol 1996;144:1034-40. bias (epidemiology); cohort studies; incidence; risk factors; skin neoplasms
BACKGROUND
Basal cell carcinoma (BCC) is characterized by marked interpatient variation in tumor accrual. The authors previously reported that presentation with a cluster of BCC is associated with an inherited predisposition to develop many additional lesions suggesting clustering is a critical event. A cluster is defined as the presence of two or more new, primary BCCs, at initial or later presentation.METHODS
The authors recruited 927 cases and determined whether 1) clustering was an early or late event and 2) tumor accrual was altered after clustering.RESULTSIn the cases, 669 patients developed only 1 lesion, 112 patients presented more than once but with single lesions (single presentation phenotype[SPP]-more), 94 cases had a cluster at first presentation (multiple presentation phenotype [MPP]-cluster initial), and 52 cases first presented with 1 lesion but later had a cluster (MPP-cluster later). The authors found that 1) clustering occurred relatively late. The mean ages at first presentation with 1 BCC of the SPP-more (61.5 years) and MPP-cluster later patients (60.4 years) were similar although presentations with clusters in the MPP-cluster initial (67.6 years, P = 0.0002) and -cluster later cases (68.1 years, P = 0.002) occurred significantly later. 2) Clustering was associated with increased accrual. Thus, 26 patients (MPP-cluster later/a) in the MPP-cluster later group had a additional BCC postcluster. Mean accrual post-cluster (1.99 BCC/year) in these cases was significantly increased (P = 0.0001) compared with precluster accrual (0.39 BCC/year).CONCLUSIONS
The authors found that the formation of BCC clusters represents a critical event such that after a cluster presentation, tumor accrual is significantly increased. Cluster presentation is a relatively late event suggesting reduced effectiveness in immune surveillance. Cancer 2000;89:1012–8. © 2000 American Cancer Society.
BACKGROUND
Patients with basal cell carcinoma (BCC) demonstrate marked variation in clinical phenotype, suggesting the presence of distinct subgroups. Patients with truncal lesions comprise an interesting subgroup, because, although the pathogenesis of these tumors is unclear, there is evidence to suggest that their development is mediated by different mechanisms than the mechanisms that mediate the development of BCC on other sites. The authors now speculate that some patients inherit a predisposition to truncal BCC and develop disproportionately more BCC on this site than other patients.METHODS
The authors studied 100 patients who, at the time of initial presentation, had a truncal BCC lesion and 493 patients who had a lesion on the head and neck. The 493 patients with head and neck lesions included 36 patients who subsequently developed a truncal BCC and 457 patients who do not.RESULTSInitial presentation with a truncal tumor was associated with significantly more subsequent BCC lesions on this site compared with patients who presented initially with a head and neck lesion. The mean truncal tumor accrual after initial presentation in patients who presented with an initial truncal BCC lesion was 0.13 BCC lesions per year compared with 0.03 BCC lesions per year in patients who presented with an initial head and neck lesion (P < 0.001). Patients with truncal lesions were significantly younger at the time of initial presentation and developed more clusters of BCC lesions (2–10 new tumors at any presentation) compared with patients who did not develop tumors on the trunk.CONCLUSIONS
These data suggest that the development of a truncal BCC is not random but, rather, is associated with a predisposition. In contrast, the accrual of nontruncal BCC lesions was similar in patients with and without initial truncal lesions, suggesting that different mechanisms determine the development of truncal BCC and nontruncal BCC. Cancer 2001;92:354–8. © 2001 American Cancer Society.
The melanocortin 1 receptor, a seven pass transmembrane G protein coupled receptor, is a key control point in melanogenesis. Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to phaeomelanin production, resulting in a red or yellow coat colour. Activating mutations, in animals at least, lead to enhanced eumelanin synthesis. In man, a number of loss-of-function mutations in the MC1R have been described. The majority of red-heads (red-haired persons) are compound heterozygotes or homozygotes for up to five frequent loss-of-function mutations. A minority of red-heads are, however, only heterozygote. The MC1R is, therefore, a major determinant of sun sensitivity and a genetic risk factor for melanoma and non-melanoma skin cancer. Recent work suggests that the MC1R also shows a clear heterozygote effect on skin type, with up to 30% of the population harbouring loss-of-function mutations. Activating mutations of the MC1R in man have not been described. The MC1R is particularly informative and a tractable gene for studies of human evolution and migration. In particular, study of the MC1R may provide insights into the lightening of skin colour observed in most European populations. The world wide pattern of MC1R diversity is compatible with functional constraint operating in Africa, whereas the greater allelic diversity seen in non-African populations is consistent with neutral predictions rather than selection. Whether this conclusion is as a result of weakness in the statistical testing procedures applied, or whether it will be seen in other pigment genes will be of great interest for studies of human skin colour evolution.
We have previously shown that high DNA repair capacity protects psoriasis patients against chemically induced basal cell carcinoma [Dybdahl et al. Mutat. Res. 433 (1999) 15–22]. We have used the same study persons to investigate the correlation between expression of eight genes involved in nucleotide excision repair and DNA repair capacity. mRNA levels of XPA, XPB, XPC, XPD, XPF, XPG, CSB and ERCC1 in primary lymphocytes from 33 individuals were quantified by dot-blots and normalized to β-actin. ERCC1 and XPD mRNA quantities were highly correlated (r=0.89; P<10−11) while XPA, XPB, XPC, XPG, XPFand CSB mRNAs were moderately correlated (r=0.2–0.7). Thus, the mRNA expressions seem to fall in at least two groups. There was a three to sevenfold variation in the expression levels of the mRNAs. This is in contrast to the more than a hundredfold variation in mRNA levels reported in cancer patients.DNA repair capacity was measured in a host cell reactivation assay, where primary lymphocytes were transfected with an UV-irradiated plasmid encoding firefly-luciferase. Only ERCC1 and XPD mRNA levels correlated with the DNA repair capacity (P<0.03). In order to see if ERCC1 or XPD activity was limiting for DNA repair, we cotransfected with plasmids encoding NER genes, thus over-expressing either XPB, XPC, XPD, CSB or ERCC1 in the host cell reactivation assay. Only XPB over-expression increased DNA repair capacity. Thus, there is no indication that neither XPD nor ERCC1 limits the DNA repair capacity. However, our results indicate that ERCC1 and XPD mRNA levels may be used as a proxy for DNA repair capacity in lymphocytes.
Background:
Skin cancers represent a major challenge within the ever growing group of long time surviving organ transplant recipients (OTR) world wide. Especially UV-induced non-melanoma skin cancers (NMSC) like invasive squamous cell carcinomas (SCC) and actinic keratoses (AK), and basal cell carcinoma (BCC), outnumber every other form of cancer in organ transplant recipients. Despite encouraging reports of protective effects of broad-spectrum sunscreens in immunocompetent patients, evidence for the prevention of NMSC in immunocompromised patients is still missing.
Objectives:
To assess preventive effects of regular sun-screen use on AK, SCC and BCC in chronically immunocompromised organ transplant recipients.
Methods:
Hundred and twenty matched (age, sex, skin type, graft, transplant duration, previous post-transplant skin malignancies) organ transplant recipients (40 heart, 40 kidney, 40 liver grafted) were recruited for this prospective, single-center study. Both groups received equally written and oral information on sun protection measures. Sixty patients were provided with a free broad spectrum study-sunscreen (SPF>50, high-UVA absorption) for daily application of 2 mg cm(-2) to the head, neck, forearms, and hands.
Results:
All 120 patients completed the 24 months study. Within this 24 month study interval 42 of the 120 patients developed 82 new AK (-102 sunscreen group vs. +82 control; P<0.01), 8 new invasive SCC (0 vs. 8; P<0.01) and 11 BCC (2 vs. 9; ns). In spite of equal numbers of AK at baseline, a marked difference in favor of the intent-to-treat sunscreen group was recorded after 24 months (89 vs. 273; P<0.01, mean difference 3.07 [1.76-4.36]) and the lesion count was significantly lower as compared to the initial visit (89 vs. 191; P<0.01, mean difference 1.7 [0.68-2.72]). With an average of 5.6 applications per week throughout the 24 months the study sunscreen was generally well tolerated. Serum 25-hydroxy vitamin D levels as marker for vitamin D status were decreased in all patients without adequate substitution and 25(OH)D was found to be lower in the sunscreen-group as compared to the control group (mean value 53 ng mL(-1) vs. 60 ng mL(-1)).
Interpretation:
Regular use of sunscreens, as part of a consequent UV-protection strategy, may prevent the development of further AK and invasive SCC and, to a lesser degree, BCC in immune-compromised organ transplant recipients.
A strong association has been found between skin cancer and exposure to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is frequently mutated in human cancers, is believed to be an early target in UV radiation-associated skin carcinogenesis. We have previously developed a sensitive, polymerase chain reaction-based method capable of detecting and quantifying a UV radiation-specific mutation in the p53 gene (codons 247 and 248: AAC CGG --> AAT TGG) in normal skin. We have used this method to examine whether UV radiation-specific mutation frequency is associated with risk of basal cell carcinoma (BCC) and with sun exposure.
This case-control study in Australia involved 53 case subjects with BCC and 75 control subjects. DNA was isolated from normal skin (mirror-image anatomic site to the cancer site for case subjects and a randomly selected site for control subjects) and assayed for p53 mutation. Relationships between p53 mutation frequency and risk of BCC, sun sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95% confidence intervals (95% CIs).
Case subjects were more likely to have a p53 mutation than control subjects (OR = 3.1; 95% CI = 1.3-7.1). In addition, the odds of BCC increased monotonically with increasing frequency of p53 mutation. No statistically significant associations could be demonstrated between p53 mutation frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total lifetime sun exposure, or sun exposure to the biopsy site.
Our results indicate that tandem CC --> TT mutations involving codons 247 and 248 of the p53 gene are associated with an increased risk of BCC but cannot be used as an accurate measure of total UV-radiation exposure.
The ability of cells to respond to and to mitigate environmental stress is crucial for their survival. Constitutive and facultative pigmentation have evolved in order for human skin to contend with high levels of terrestrial ultraviolet radiation (UVR). When this melanin 'shield' is compromised, individuals are exposed to increased skin cancer risk. The purpose of this review is to discuss new insights into the genetic basis of phenotypic risk factors for skin cancer, their connection to pigmentation and tanning, the precise molecular connections linking UVR to the tanning response, and potential methods of modulating pigmentation that avoid genotoxic damage. Highly translational implications of this research include a scientific basis on which to counsel patients regarding the carcinogenicity of UVR exposure related to tanning and potential new tanning agents that may actually protect against skin cancer by circumventing the need for UVR exposure.
SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449). Amide 31 produced complete tumor regression at doses as low as 12.5mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC.
Inherited diseases of pigmentation were among the first traits studied in humans because of their easy recognition. The discovery of genes that regulate melanocytic development and function and the identification of disease-causative mutations have greatly improved our understanding of the molecular basis of pigmentary genodermatoses and their underlying pathogenetic mechanisms. Pigmentation mutants can account for hypo-/amelanosis, with or without altered melanocyte number, resulting in different phenotypes, such as Waardenburg syndrome, piebaldism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, oculocutaneous albinism and Griscelli syndrome. In this review, we summarize the basic concepts of melanocyte biology and discuss how molecular defects in melanocyte development and function can result in the development of hypopigmentary hereditary skin diseases.
Susceptibility to environmental carcinogenesis is the consequence of a complex interplay between intrinsic hereditary factors and actual exposure to potential carcinogenic agents. Exposure to sunlight is the primary etiological agent for basal cell carcinoma (BCC).
The aim of this study was to determine the effects of different ultraviolet (UV) doses on DNA damage in epidermal keratinocytes in vivo and to elucidate if patients with BCC are more susceptible to UV-induced DNA damage in comparison with normal healthy volunteers in response to solar simulator radiation (SSR).
Skin biopsies obtained post-UV irradiation from both normal healthy volunteers and BCC patients were analyzed for DNA damage, using immunohistochemical approach with TDM-2 antibody, which binds specifically to cyclobutane pyrimidine dimmers (CPDs).
In both normal volunteers and BCC patients, the peak of CPD-positive cells occurred at 4.5 h post-SSR. There was a statistically significant difference in CPD positivity between BCC patients and normal volunteers, at time points (from 4.5 h to 48 h post-SSR). For a given dose of SSR based on each individual minimal erythema dose (MED), a greater number of CPD-positive cells could be shown.
This study has shown for the first time and in vivo in human volunteers that BCC patients are more susceptible to UV-induced DNA damage in comparison with normal healthy volunteers.
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.
Human pigmentation is a polygenic quantitative trait with high heritability. Although a large number of single nucleotide polymorphisms (SNPs) have been identified in pigmentation genes, very few SNPs have been examined in relation to human pigmentary phenotypes and skin cancer risk. We evaluated the associations between 15 SNPs in 8 candidate pigmentation genes (TYR, TYRP1, OCA2, SLC24A5, SLC45A2, POMC, ASIP and ATRN) and both pigmentary phenotypes (hair color, skin color and tanning ability) and skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases and 870 common controls. We found that the TYR Arg402Gln variant was significantly associated with skin color (p-value = 7.7 x 10(-4)) and tanning ability (p-value = 7.3 x 10(-4)); the SLC45A2 Phe374Leu variant was significantly associated with hair color (black to blonde) (p-value = 2.4 x 10(-7)), skin color (p-value = 1.1 x 10(-7)) and tanning ability (p-value = 2.5 x 10(-4)). These associations remained significant after controlling for MC1R variants. No significant associations were found between these polymorphisms and the risk of skin cancer. We observed that the TYRP1 rs1408799 and SLC45A2 1721 C>G were associated with melanoma risk (OR, 0.77; 95% CI, 0.60-0.98 and OR, 0.75; 95% CI, 0.60-0.95, respectively). The TYR Ser192Tyr was associated with SCC risk (OR, 1.23; 95% CI, 1.00-1.50). The TYR haplotype carrying only the Arg402Gln variant allele was significantly associated with SCC risk (OR, 1.35; 95% CI, 1.04-1.74). The OCA2 Arg419Gln and ASIP g.8818 A>G were associated with BCC risk (OR, 1.50; 95% CI, 1.06-2.13 and OR, 0.73; 95% CI, 0.53-1.00, respectively). The haplotype near ASIP (rs4911414[T] and rs1015362[G]) was significantly associated with fair skin color (OR, 2.28; 95% CI, 1.46-3.57) as well as the risks of melanoma (OR, 1.68; 95% CI, 1.18-2.39) and SCC (OR, 1.54; 95% CI, 1.08-2.19). These associations remained similar after adjusting for pigmentary phenotypes and MC1R variants. The statistical power of our study was modest and additional studies are warranted to confirm the associations observed in the present study. Our study provides evidence for the contribution of pigmentation genetic variants, in addition to the MC1R variants, to variation in human pigmentary phenotypes and possibly the development of skin cancer.
The ultraviolet B (UVB) waveband within sunlight is an important carcinogen; however, UVA is also likely to be involved. By ascribing mutations to being either UVB or UVA induced, we have previously shown that human skin cancers contain similar numbers of UVB- and UVA-induced mutations, and, importantly, the UVA mutations were at the base of the epidermis of the tumors. To determine whether these mutations occurred in response to UV, we exposed engineered human skin (EHS) to UVA, UVB, or a mixture that resembled sunlight, and then detected mutations by both denaturing high-performance liquid chromatography and DNA sequencing. EHS resembles human skin, modeling differential waveband penetration to the basal, dividing keratinocytes. We administered only four low doses of UV exposure. Both UVA and UVB induced p53 mutations in irradiated EHS, suggesting that sunlight doses that are achievable during normal daily activities are mutagenic. UVA- but not UVB-induced mutations predominated in the basal epidermis that contains dividing keratinocytes and are thought to give rise to skin tumors. These studies indicate that both UVA and UVB at physiological doses are mutagenic to keratinocytes in EHS.
A comprehensive bibliographic search of the literature was conducted to identify studies on Cutaneous Malignant Melanoma (CMM) and non-melanoma skin cancer (NMSC), Vitamin D receptor (VDR) polymorphisms, Vitamin D intake and 25(OH)D serum levels. Fully adjusted risk estimates were found and extracted for the two polymorphisms FokI and BsmI and Vitamin D intake. Ten studies were included in the meta-analysis, with a total of 6805 skin cancer cases. We found an association with CMM for both polymorphisms. The summary relative risks (SRR) for the studies on CMM were: 1.21 (1.03-1.42) and 1.21 (0.95-1.54) for the Ff and ff versus wild-type of FokI, respectively. The SRR for ff versus wild-type became significant with the inclusion of NMSC. The SRR for the studies on CMM were: 0.78 (0.65-0.92) and 0.75 (0.59-0.95) for the Bb and BB versus wild-type of BsmI, respectively. There is also a slight indication of a role of dietary Vitamin D in CMM development. In conclusion, this meta-analysis suggests a possible significant role of VDR FokI and BsmI polymorphism in CMM and NMSC risk. The association with Vitamin D intake is less clear and further studies could be useful to clarify the role of diet.
Ultraviolet radiation (UVR) is an essential risk factor for the development of premalignant skin lesions as well as of melanoma and non-melanoma skin cancer. UVR exerts many effects on the skin, including tanning, carcinogenesis, immunomodulation, and production of vitamin D. Vitamin D (vit D) is important in the maintenance of healthy bones as well as other purported beneficial effects, amongst which is the potential for reducing risk of malignancy--though oral supplementation is fully capable of maintaining systemic levels. The known medical harm from UV exposure relates primarily to cancer of the skin--the most common organ in man to be affected by cancer. In this review, we summarize the knowledge about the ultraviolet (UV) response in regards to inflammation, immunosuppression, carcinogenesis and the tanning response. We also discuss vit D and UV, as well as public health implications of tanning behavior and commercial interests related to the promotion of UV exposure. As the most ubiquitous human carcinogen, UVR exposure represents both a challenge and enormous opportunity in the realm of skin cancer prevention.
Basal cell carcinomas (BCCs) were essentially a molecular 'black box' until some 12 years ago, when identification of a genetic flaw in a rare subset of patients who have a great propensity to develop BCCs pointed to aberrant Hedgehog signalling as the pivotal defect leading to formation of these tumours. This discovery has facilitated a remarkable increase in our understanding of BCC carcinogenesis and has highlighted the carcinogenic role of this developmental pathway when aberrantly activated in adulthood. Importantly, a phase 1 first-in-human trial of a Hedgehog inhibitor has shown real progress in halting and even reversing the growth of these tumours.
Measurements have been made of the distribution of natural ultraviolet radiation (UVR) at 41 sites on the face of a large fibreglass model of a head. The dosemeter used was the polymer film polysulphone. The results have been correlated with published values of the distribution of basal cell carcinomas on the face. Although the comparison has highlighted the problems of trying to relate frequency of skin tumour occurrence to sunlight exposure, the present results are compatible with the hypotheses that human skin cancer incidence increases with environmental UVR exposure, and that sunlight is not the only factor in the aetiology of basal cell carcinomas of the face.
This 36-month prospective study of a group of 61 people at high risk to develop multiple basal cell carcinomas (BCC) examined the circulating lymphocyte subsets of the population, patterns of sun exposure, and the longitudinal development of basal cell carcinoma. Sun exposure status was highly correlated with immune status defined by the CD4/CD8 T-lymphocyte ratio. There were significantly more BCC at 18 and 36 months in the 35 patients with high sun exposure and low CD4/CD8 ratio than in the 20 patients with low sun exposure and high CD4/CD8 ratio. A multivariate analysis assessed the relative importance of prior basal cell carcinoma, sun exposure, and immune status on the development of the skin cancer. Basal cell carcinoma developing in the previous 18 months and sun exposure during those 18 months were the first and second most important variables in determining development of basal cell carcinoma during the next 18 months. CD4/CD8 ratio had no additional predictive ability once prior skin cancers and sun exposure were accounted for. A low ratio of CD4/CD8 cells correlated with high sun exposure during the preceding 18 months.
In a prospective study of self-reported demographic, constitutional, and life-style factors in relation to basal cell carcinoma of the skin, we followed a cohort of 73,366 nurses in the United States who were 34 to 59 years of age in 1980 and who had no previous skin or other cancer. In 4 years of follow-up, compared with women living in the Northeast, women residing in California (age-adjusted relative risk [RR] = 1.57; 95% confidence interval [CI] = 1.30 to 1.89) and Florida (RR = 2.12; 95% CI = 1.54 to 2.92) were more likely to develop basal cell carcinoma. Compared with women having naturally dark brown hair, the age-adjusted relative risk of basal cell carcinoma was increased among women with red (RR = 2.45; 95% CI = 1.89 to 3.19), blonde (RR = 1.37; 95% CI = 1.09 to 1.71), or light brown hair (RR = 1.27; 95% CI = 1.08 to 1.49) and was decreased among women with black hair (RR = 0.66; 95% CI = 0.41 to 1.06). Risk was positively associated in a dose-response manner both with tendency to sunburn as a child or adolescent and with lifetime number of severe and painful sunburns on the face or arms. These risk factors remained significant predictors of disease when included simultaneously in multivariate analyses. Tendency to tan was associated with decreased risk, although this risk was not significant after controlling for the other constitutional determinants and region. Cigarette smoking did not alter the risk of basal cell carcinoma. These prospective data emphasize the importance of sunlight, and skin response to sunlight, as determinants of basal cell carcinoma among women.
Metastatic basal cell carcinoma was found in 12 patients at the University of Wisconsin Mohs Surgery Clinic during the period 1936 to 1989. All patients were white men. The time of onset of the primary tumor ranged from childhood to 71 years. Eleven patients had previous treatment for basal cell carcinoma; two patients had received x-ray radiation to the face for teenage acne. The locations of the primary basal cell carcinomas were the face (n = 10), back (n = 1), and arm (n = 1). The primary tumors ranged from 3.6 x 3.0 to 20.0 x 7.0 cm. The interval from onset to the first sign of metastases ranged from 7 to 34 years. In all cases, the primary tumor was histologically identical to the metastatic lesion. Perineural extension of the basal cell carcinoma in the primary lesion was found in five cases. Regional lymph nodes were the most frequent site of metastasis. Treatment consisted of a combination of surgery, radiation, and chemotherapy. Only two patients survived more than 5 years after surgical treatment. One patient has survived 25 years and is still alive.
Basal cell carcinoma is the most common malignancy in humans. Although rarely metastatic, it is capable of significant local destruction and disfigurement. This two-part article reviews the current understanding of basal cell carcinoma biology. Part I examines significant clinical, histologic, and ultrastructural features that relate to invasive potential. Genetic characteristics, including tumor growth rate, chromosomal abnormalities, and oncogene presence, are discussed, and expression of important cell and matrix proteins, including keratin, fibronectin, and HLA antigens, are reviewed. Further topics to be explored in Part II include host immunologic responses, theories of pathogenesis, and valuable second-line therapeutic regimens for treatment of multiple cancers.
Host-tumor relationships involve several factors that can enhance or suppress neoplastic growth. This second part of a review of basal cell carcinoma biology examines the role that hormones, cytokines, local and systemic immunity, congenital and genetic syndromes, and environmental factors play in the development of this neoplasm. Theories of etiology and pathogenesis are discussed, and transplantation and cell culture techniques used to study this cancer are explored. Valuable second-line therapies for treatment of multiple tumors are reviewed, and important areas of present and future research are emphasized.
The roles of ethnic origin, pigmentary traits, sun sensitivity and other cutaneous characteristics as risk factors for basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) were examined in a case-control study of prevalent and incident cases of histopathologically confirmed skin cancers. Two hundred and twenty six confirmed cases of BCC, 45 of SCC and 1,015 controls with no lesions were identified in a population-based survey of skin cancer in 1987 in Geraldton, Western Australia. The risk of both cancers was higher in native-born Australians than in migrants. The risk of BCC decreased with increasing age at arrival in Australia. Southern European ancestry was strongly protective against BCC (for any southern European grandparents) and SCC (no case of SCC had any grandparents of southern European origin). Inability to tan was the strongest pigmentary risk factor for both BCC and SCC. Among factors that incorporated a measure of sun exposure as well as sun sensitivity, freckling on the arm in childhood was important for both cancers, the number of moles on the back was important for BCC, and forearm skin colour and having a permanent colour difference between the neck and adjacent protected areas were important for SCC. Among measures of sun damage to the skin, solar elastosis of the neck was a strong risk factor for both BCC and SCC, loss of fine texture of the skin of the back of the hands (as measured by cutaneous microtopography) was important for BCC and telangiectasia of the face for SCC. When all important variables for each cancer were examined together in a single model with age, sex, migrant status or age at arrival in Australia, and ethnicity, in ability to tan, solar elastosis of the neck, and the number of moles on the back were independently significant risk factors for BCC and solar elastosis of the neck and having a permanent colour difference between the neck and adjacent protected areas were independently significant risk factors for SCC. The effects of age at arrival or migrant status and ethnic origin remained important in the models incorporating these factors. A history of ever having acne and a history of warts were protective for BCC and a history of acne was protective for SCC.
Major increases have occurred in the incidence of basal cell carcinoma and squamous cell carcinoma of the skin, as well as in cutaneous malignant melanoma during the period 1973 through 1987 in British Columbia. The greatest increases in basal and squamous cell carcinomas are on the head and neck. This indicates that exposure to sunlight is the major causative factor. The greatest increase in melanoma is on the trunk in men and on the lower limbs in women. The dramatic increases in nonmelanoma skin cancers in British Columbia, a relatively low sunlight area, suggest that major prevention programs are needed in areas that are not considered "sunspots."