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Basal Cell Carcinoma

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Non Melanoma Skin Cancer
Skin Cancer
Prevention of Skin Cancer

Information Patients and the Public (9 links)


Information for Health Professionals / Researchers (4 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Nguyen AH, Detty SQ, Agrawal DK
Clinical Implications of High-mobility Group Box-1 (HMGB1) and the Receptor for Advanced Glycation End-products (RAGE) in Cutaneous Malignancy: A Systematic Review.
Anticancer Res. 2017; 37(1):1-7 [PubMed] Related Publications
Inflammation and the immune system play a role in the development and progression of melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). The pro-inflammatory and tumor-promoting effects of the high-mobility group box-1 (HMGB1) protein and the receptor for advanced glycation end products (RAGE) have been investigated in these cutaneous malignancies. The clinical implication of these molecules is not fully described. The National Library of Medicine database was searched for articles addressing the clinical relevance of HMGB1 and RAGE in melanoma, BCC, and SCC. This systematic review includes nine articles, with six summarizing RAGE in cutaneous malignancies and three involving HMGB1. RAGE has been found to be up-regulated in SCC lesions, as well as melanoma. Levels of RAGE were highest in stage IV melanomas. Lower levels of soluble RAGE have been associated with poor overall survival in melanoma. Sporadic extracellular expression of HMGB1 was evident in BCC and SCC lesions, which could be released by necrotic tumor cells. HMGB1 was found to be a prognostic marker in melanoma, and HMGB1 levels were elevated in patients who were non-responders to ipilimumab treatment. HMGB1 and RAGE could serve as potential prognostic markers or therapeutic targets in treating melanoma, BCC, and SCC, but further research regarding the clinical utility of the HMGB1-RAGE axis in cutaneous malignancies is warranted.

Newlands C, Currie R, Memon A, et al.
Non-melanoma skin cancer: United Kingdom National Multidisciplinary Guidelines.
J Laryngol Otol. 2016; 130(S2):S125-S132 [PubMed] Free Access to Full Article Related Publications
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides consensus recommendations on the management of cutaneous basal cell carcinoma and squamous cell carcinoma in the head and neck region on the basis of current evidence. Recommendations • Royal College of Pathologists minimum datasets for NMSC should be adhered to in order to improve patient care and help work-force planning in pathology departments. (G) • Tumour depth is of critical importance in identifying high-risk cutaneous squamous cell carcinoma (cSCC), and should be reported in all cases. (R) • Appropriate imaging to determine the extent of primary NMSC is indicated when peri-neural involvement or bony invasion is suspected. (R) • In the clinically N0 neck, radiological imaging is not beneficial, and a policy of watchful waiting and patient education can be adopted. (R) • Patients with high-risk NMSC should be treated by members of a skin cancer multidisciplinary team (MDT) in secondary care. (G) • Non-infiltrative basal cell carcinoma (BCC) <2 cm in size should be excised with a margin of 4-5 mm. Smaller margins (2-3 mm) may be taken in sites where reconstructive options are limited, when reconstruction should be delayed. (R) • Where there is a high risk of recurrence, delayed reconstruction or Mohs micrographic surgery should be used. (R) • Surgical excision of low-risk cSCC with a margin of 4 mm or greater is the treatment of choice. (R) • High-risk cSCC should be excised with a margin of 6 mm or greater. (R). • Mohs micrographic surgery has a role in some high-risk cSCC cases following MDT discussion. (R) • Delayed reconstruction should be used in high-risk cSCC. (G) • Intra-operative conventional frozen section in cSCC is not recommended. (G) • Radiotherapy (RT) is an effective therapy for primary BCC and cSCC. (R) • Re-excision should be carried out for incompletely excised high-risk BCC or where there is deep margin involvement. (R) • Incompletely excised high-risk cSCC should be re-excised. (R) • Further surgery should involve confirmed marginal clearance before reconstruction. (R) • P+ N0 disease: Resection should include involved parotid tissue, combined with levels I-III neck dissection, to include the external jugular node. (R) • P+ N+ disease: Resection should include level V if that level is clinically or radiologically involved. (R) • Adjuvant RT should include level V if not dissected. (R) • P0 N+ disease: Anterior neck disease should be managed with levels I-IV neck dissection to include the external jugular node. (R) • P0 N+ posterior echelon nodal disease (i.e. occipital or post-auricular) should undergo dissection of levels II-V, with sparing of level I. (R) • Consider treatment of the ipsilateral parotid if the primary site is the anterior scalp, temple or forehead. (R) • All patients should receive education in self-examination and skin cancer prevention measures. (G) • Patients who have had a single completely excised BCC or low-risk cSCC can be discharged after a single post-operative visit. (G) • Patients with an excised high-risk cSCC should be reviewed three to six monthly for two years, with further annual review depending upon clinical risk. (G) • Those with recurrent or multiple BCCs should be offered annual review. (G).

Naik MP, Mehta A, Abrol S, et al.
Topical 5% 5-fluorouracil in the treatment of multifocal basal cell carcinoma of the face: A novel chemotherapeutic approach.
Orbit. 2016; 35(6):352-354 [PubMed] Related Publications
To determine the safety and efficacy of topical 5-fluorouracil (5-FU) 5% ointment in treatment of non-syndromic multifocal basal cell carcinoma. A 55-year-old male patient, with 8 hours of daily sun exposure, having histologically proven and radiologically non-syndromic, multifocal basal cell carcinoma with involvement of 6 sites on the face, was treated with topical 5-FU 5% ointment twice daily over all sites except the site involving lid margin to prevent corneal toxicity. Left lid lesion underwent wide surgical excision with 5-mm clear margins and reconstruction with nasal septal mucoperichondrium and local skin mobilization. Pharmacologic effects first appeared at 4 weeks and by 8 weeks, the lesions had scabbed and had fallen off with no induration but residual mild perilesional erythema. Patient had post-op histopathological clear margins and recovered uneventfully. No recurrence in 6 months. A topical 5-FU 5% ointment represents a paradigm shift in the treatment of BCC from invasive and disfiguring options (surgery and chemoradiotherapy) to cheap, convenient, effective, non-invasive, non-disfiguring topical chemotherapy. Topical 5% 5-FU is a safe and effective modality of treatment of superficial spreading multifocal basal carcinoma, especially lesions larger than 10 mm, where margins cannot be identified clearly and recurrent lesions.

Lin SH, Cheng YW, Yang YC, et al.
Treatment of Pigmented Basal Cell Carcinoma with 3 mm Surgical Margin in Asians.
Biomed Res Int. 2016; 2016:7682917 [PubMed] Free Access to Full Article Related Publications
Background. In Asians, most basal cell carcinomas (BCCs) are pigmented with clear borders. The consensus of 4 mm surgical margin for BCC largely depends on studies in nonpigmented BCCs in Caucasians. However, little is known about recurrences of pigmented BCCs with a narrower surgical margin. We aimed to investigate 5-year recurrence of BCCs, either pigmented or nonpigmented, in Taiwanese with 3 mm surgical margin. Materials and Methods. 143 patients with BCC (M/F = 66/77, average 64 years) were confirmed pathologically from 2002 to 2013. Based on the pathological margin (>1 mm, ≤1 mm, and involved), patients were categorized into the complete excision group (n = 77), histology with close proximity group (n = 43), and unclear surgical margin group (n = 23). Results. Among 143 cases, 105 were pigmented. With standard 3 mm excision, there were 7 recurrences, with 6 of them from nonpigmented BCC group. Logistic regression showed that pigmentation was associated with lower recurrence. Interestingly, 5-year recurrence of completely excised and histology with close proximity BCC (0/77 versus 1/43) was not different statistically. Conclusions. A 3 mm surgical margin is adequate for pigmented BCC. A "wait and see" approach rather than further wide excision is appropriate for BCC with <1 mm free margin.

Fife K, Herd R, Lalondrelle S, et al.
Managing adverse events associated with vismodegib in the treatment of basal cell carcinoma.
Future Oncol. 2017; 13(2):175-184 [PubMed] Related Publications
Basal cell carcinomas are the most common form of skin cancer. Some develop into advanced cases not suitable for standard therapy. Vismodegib is the first-in-class oral hedgehog pathway inhibitor (which is dysregulated in 90% of basal cell carcinomas), and has demonstrated efficacy for advanced disease in clinical trials. An UK expert panel met to discuss management strategies for adverse events associated with vismodegib (most commonly taste disturbances, muscle cramps and alopecia). Managing patient expectations and implementing treatment breaks were considered important strategies. Quinine was useful to alleviate muscle cramps. For taste disturbances, food swaps alongside dietician referral were suggested. The experts concluded that these common adverse events can be successfully managed to allow optimum treatment duration of vismodegib.

DO Carmo NG, Sakamoto LH, Pogue R, et al.
Altered Expression of PRKX, WNT3 and WNT16 in Human Nodular Basal Cell Carcinoma.
Anticancer Res. 2016; 36(9):4545-51 [PubMed] Related Publications
BACKGROUND/AIM: Nodular and superficial are the most common subtypes of basal cell carcinoma (BCC). Signaling pathways such as Hedgehog (HH) and Wingless (WNT) signaling are associated with BCC phenotypic variation. The aim of the study was to evaluate of the expression profiles of 84 genes related to the WNT and HH signaling pathways in patients with nodular and superficial BCC.
MATERIALS AND METHODS: A total of 58 BCCs and 13 samples of normal skin were evaluated by quantitative real-time polymerase chain reaction (qPCR) to detect the gene-expression profile.
RESULTS: qPCR array showed segregation in BCC subtypes compared to healthy skin. PRKX, WNT3 and WNT16 were significantly (p<0.05) altered: PRKX was up-regulated, and WNT3 and WNT16 were down-regulated in nodular BCC.
CONCLUSION: PRKX, WNT3 and WNT16 genes, belonging to the WNT signaling pathway, are involved in the tumorigenic process of nodular BCC.

Sobhani M, Taheri AR, Jafarian AH, Hashemy SI
The activity and tissue distribution of thioredoxin reductase in basal cell carcinoma.
J Cancer Res Clin Oncol. 2016; 142(11):2303-7 [PubMed] Related Publications
PURPOSE: Basal cell carcinoma (BCC) is the most prevalent cancer worldwide. Different mechanisms are proposed to be involved in its pathogenesis such as oxidative stress. Oxidative stress, which is the consequence of the disruption of redox balance in favor of oxidants, is involved in the initiation or progression of many tumors. Thioredoxin reductase (TrxR) is a key enzyme of the thioredoxin (Trx) system, containing Trx and TrxR and NADPH, which is one of the main cellular oxidoreductases with an essential role in cellular health and survival through providing and maintaining redox balance. Therefore, we aimed to study and compare the activity and tissue distribution of TrxR in tumoral tissue and its healthy margin in patients with BCC.
METHODS: After biopsy and taking samples from 18 patients, TrxR activity was measured using a commercial kit and its tissue distribution was assessed immunohistochemically.
RESULTS: Both the activity and tissue distribution of TrxR in tumoral tissues were significantly higher compared to their healthy margins. Regarding the tissue distribution, this significant increase in TrxR in tumoral tissues was documented based on both staining intensity and abundance of positive cells in immunohistochemistry.
CONCLUSIONS: Based on these results, it is concluded that TrxR is involved in the pathogenesis of BCC; however, more investigations are required to clarify whether this increase is a consequence of BCC or it is an initiating mechanism.

von Schuckmann LA, Hughes MC, Green AC, van der Pols JC
Forearm hair density and risk of keratinocyte cancers in Australian adults.
Arch Dermatol Res. 2016; 308(9):617-624 [PubMed] Related Publications
Evidence suggests that progenitor cells of keratinocyte cancers (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) may originate from epidermal stem cells including hair follicle stem cells. We hypothesised that, therefore, a relatively higher density of hair follicles on human skin may increase keratinocyte cancer risk. To evaluate this, we assessed density of mid-forearm hair in Australian adults who were randomly selected participants in a community-based cohort study of skin cancer. Hair density was assessed clinically against a set of four standard photographs showing grades of hair density, and incidence data on histologically confirmed BCC and SCC across a 20-year period were collected. Incidence rate ratios were calculated for categories of forearm hair density using multivariable regression analysis with adjustment for age, sex, phenotypic characteristics and markers of chronic sun exposure. Among the 715 participants (43 % male, average age 61 years), 237 developed at least one BCC and 115 persons developed at least one SCC. Participants with dense forearm hair (n = 169, all male) had a higher incidence of BCC (IRR = 2.24, 95 % CI 1.20, 4.18, P = 0.01) and SCC (IRR = 2.80, 95 % CI 1.20, 6.57, P = 0.02) compared to individuals with sparse forearm hair after multivariable adjustment. Stratified analyses showed that among men, those with dense versus sparse hair developed SCC more commonly (IRR = 3.01, 95 % CI 1.03, 8.78, P = 0.04). Women with moderate versus sparse hair density were more likely affected by BCC (IRR = 2.29, 95 % CI 1.05, 5.00, P = 0.038). Thus, our study suggests that in both men and women, a higher density of body hair may be associated with increased BCC and SCC risk.

Lupu M, Caruntu C, Ghita MA, et al.
Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma.
Dis Markers. 2016; 2016:9831237 [PubMed] Free Access to Full Article Related Publications
Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC.

Zhang Z, Behshad S, Sethi-Patel P, Valenzuela AA
Glasses: Hiding or causing skin cancer?
Orbit. 2016; 35(5):262-6 [PubMed] Related Publications
This article evaluates malignant transformation of lesions presenting in the periocular skin under the eye spectacle nose pad. A non-comparative retrospective chart review of clinical features and pathological findings of patients presenting with periocular malignancies in the exact vicinity where the nose pads of their eye spectacles rested was completed. The study took place in one tertiary oculoplastic referral center between 2007-2013. Ten patients were included, six of whom were male. All subjects wore eye spectacles while awake for at least 15 years, and had an evident suspicious lesion in the exact area that coincided with the resting place of the nose pad. The mean age was 73.5 years (range 65-85 years) and all patients had the lesion present for at least one year. Most cases were squamous skin malignancies (five squamous cell carcinomas [SCC], 2 intra-epidermal carcinomas [IEC], while 3 basal cell carcinomas [BCC]). Treatment involved surgical excision of the lesion with frozen section for margin control and reconstruction with a myocutaneous flap. Periocular malignancies of the inferior medial canthal area, where the nose pad of eye spectacle places pressure, can be easily missed or misdiagnosed. Marjolin ulcers (MU) classically present as an aggressive SCC in area of chronic inflammation, which has been previously correlated to constant pressure, repetitive trauma, or non-healing wounds in other areas of the body. We propose that the traumatic chronic pressure in the infero-medial canthal region from long-term eye spectacle nose pad use, may induce poor lymphatic regeneration leading to an immune system deficiency that predisposes this skin to a malignant transformation. The presence of chronic eye spectacle nose pads also prevents proper and timely detection of such malignancies. Complete excision of these lesions with margin control, adequate follow-up for possible recurrence, and surveillance for new lesions on the patient's contralateral side, is crucial for adequate management.

AlZou AB, Thabit MA, AlSakkaf KA, Basaleem HO
Skin Cancer: ClinicoPathological Study of 204 Patients in Southern Governorates of Yemen.
Asian Pac J Cancer Prev. 2016; 17(7):3195-9 [PubMed] Related Publications
BACKGROUND: Skin cancer is a group of heterogeneous malignancies, in general classified into nonmelanoma skin cancer (NMSC) and melanoma skin cancer (MSC). Incidences are high in many parts in the world with considerable geographical and racial variation. In the Yemen, there has been scarce information about skin cancer. The aim of this study was to evaluate the demographic characteristics and histological trend of skin cancer in Southern Governorates of Yemen.
MATERIALS AND METHODS: This retrospective study covered 204 cases of skin cancer at the Modern Histopathology Laboratory and Aden Cancer Registry and Research Center, Faculty of Medicine and Health Sciences, University of Aden, for the period 20062013. Data were classified regarding different demographic and tumor related variables and analyzed using CanReg4 for cancer registry and SPSS (version 21).
RESULTS: The commonest encountered skin cancer was NMSC (93.1%). Generally, skin cancer appears slightly more frequently in females than males with a 1:1.06 male: female ratio, with a mean age of 62.9 years. Slightly higher than onethird (36.3%) were from Aden governorate. The head and neck proved to be the most common site in both males and females (58%). Basal cell carcinoma (BCC) is the most common histological type of skin cancer (50.5%).
CONCLUSIONS: Skin cancer is a common cancer in patients living in southern governorates of Yemen. The pattern appears nearly similar to the international figures with a low incidence of MSC.

Yu KK, Dasanu CA
Rapidly Fatal Dissemination of Merkel Cell Carcinoma in a Patient Treated with Alemtuzumab for Chronic Lymphocytic Leukemia.
Conn Med. 2016 Jun-Jul; 80(6):353-8 [PubMed] Related Publications
Alemtuzumab is FDA-approved for the treatment of chronic lymphocytic leukemia (CLL). Nonetheless, its use for this indication has fallen out of favor due to serious concerns for infectious complications and increased risks of second malignancies from the profound and lasting immunosuppression. We report here in a patient with a rapidly progressive metastatic Merkel cell carcinoma (MCC) who was previously treated with alemtuzumab and fludarabine for CLL. He developed profound lymphopenia and hypogammaglobulinemia. While the risk of MCC is increased in CLL, its rapid dissemination has not been previously reported with fludarabine alone. In light of the rapidly fatal outcome in our patient due to MCC, we advise caution with the use of alemtuzumab. In patients treated with alemtuzumab for nononcologic indications, aggressive surveillance for cutaneous malignancies should be implemented until its safety profile can be further characterized.

Ruini C, Hartmann D, Saral S, et al.
The invisible basal cell carcinoma: how reflectance confocal microscopy improves the diagnostic accuracy of clinically unclear facial macules and papules.
Lasers Med Sci. 2016; 31(8):1727-1732 [PubMed] Related Publications
Difficult to diagnose and early non-melanoma skin cancer lesions are frequently seen in daily clinical practice. Besides precancerous lesions such as actinic keratosis, basal cell carcinomas (BCCs) score the highest frequency in skin tumors. While infiltrative and nodular BCCs require a surgical treatment with a significant impact on the patients' quality of life, early and superficial BCCs might benefit from numerous conservative treatments, such as topical immune-modulators or photodynamic therapy. Dermoscopy has shown a high sensitivity and specificity in the diagnosis of early BCCs, and non-invasive imaging techniques like reflectance confocal microscopy (RCM) have proven to be helpful. The aim of our study was to investigate the importance of RCM in the diagnosis of BCCs with indistinct clinical and dermoscopic features. We retrospectively examined 27 histologically proven BCCs in which diagnosis was not possible based on naked eye examination; we separately reviewed clinical, dermoscopic, and confocal microscopy features and evaluated the lesions meeting the common diagnostic criteria for BCCs, and our diagnostic confidence. All lesions were clinically unclear, with no characteristic features suggestive for BCC; dermoscopy showed in most cases unspecific teleangiectasias (74 %) and micro-erosions (52 %). Confocal microscopy revealed in most of the cases the presence of specific criteria: peripheral palisading of the nuclei (89 %), clefting (70 %), stromal reaction (70 %), dark silhouettes (70 %), inflammatory particles (70 %), and tumor islands (67 %). In the absence of significant diagnostic clinical signs and with unclear dermoscopic features, specific confocal patterns were present in most of the lesions and enabled a correct diagnosis. In the absence of significant clinical features of BCC and in the case of uncertain dermoscopy, striking confocal features are detectable and easy to recognize in most cases. Confocal microscopy can therefore be instrumentful in the diagnosis of the so-called invisible BCCs.

Wilson ME, Pointdujour-Lim R, Lally S, et al.
Acute Charles Bonnet Syndrome following Hughes procedure.
Orbit. 2016; 35(5):292-4 [PubMed] Related Publications
A 69-year-old male experienced monocular formed visual hallucinations after occlusion of the right eye following resection of eyelid basal cell carcinoma and reconstruction with a Hughes procedure (tarsoconjunctival flap). His symptoms included recurrent, well-defined, organized, complex, formed images of small children playing in the snow. These visual phenomena occurred only in the occluded eye, began several hours after surgery, and recurred intermittently several times daily for 4 days, lasting several minutes with each occurrence. The patient retained insight into the false nature of the images throughout the duration of his symptoms, and the hallucinations resolved spontaneously while the flap was still in place. To our knowledge, this is the first reported case of Charles Bonnet Syndrome (CBS) following a Hughes procedure in a patient with normal visual acuity in the non-occluded fellow eye. Unlike other reported cases of acute onset CBS following transient monocular occlusion, hallucinations in the occluded eye remitted prior to restoration of vision in the occluded eye. Ophthalmologists should be aware of the potential for CBS following even transient monocular occlusion and should consider warning patients about its potential to occur.

Wernli KJ, Henrikson NB, Morrison CC, et al.
Screening for Skin Cancer in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
JAMA. 2016; 316(4):436-47 [PubMed] Related Publications
IMPORTANCE: Skin cancer, primarily melanoma, is a leading cause of morbidity and mortality in the United States.
OBJECTIVE: To provide an updated systematic review for the US Preventive Services Task Force regarding clinical skin cancer screening among adults.
DATA SOURCES: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies published from January 1, 1995, through June 1, 2015, with surveillance through February 16, 2016.
STUDY SELECTION: English-language studies conducted in asymptomatic populations 15 years and older at general risk for skin cancer.
DATA EXTRACTION AND SYNTHESIS: Relevant data were abstracted, and study quality was rated.
MAIN OUTCOMES AND MEASURES: Melanoma incidence and mortality, harms from cancer screening, diagnostic accuracy, and stage distribution.
RESULTS: No randomized clinical trials were identified. There was limited evidence on the association between skin cancer screening and mortality. A German ecologic study (n = 360,288) found a decrease of 0.8 per 100,000 melanoma deaths in a region with population-based skin cancer screening compared with no change or slight increases in comparison regions. The number of excisions needed to detect 1 skin cancer from clinical visual skin examinations varied by age and sex; for example, 22 for women 65 years or older compared with 41 for women aged 20 to 34 years. In 2 studies of performing visual skin examination, sensitivity to detect melanoma was 40.2% and specificity was 86.1% when conducted by primary care physicians (n = 16,383). Sensitivity was 49.0% and specificity was 97.6% when skin examinations were performed by dermatologists (n = 7436). In a case-control study of melanoma (n = 7586), cases diagnosed with thicker lesions (>0.75 mm) had an odds ratio of 0.86 (95% CI, 0.75-0.98) for receipt of a physician skin examination in the prior 3 years compared with controls. Eight cohort studies (n = 236,485) demonstrated a statistically significant relationship between the degree of disease involvement at diagnosis and melanoma mortality, regardless of the characterization of the stage or lesion thickness. Tumor thickness greater than 4.0 mm was associated with increased melanoma mortality compared with thinner lesions, and late stage at diagnosis was associated with increased all-cause mortality.
CONCLUSIONS AND RELEVANCE: Only limited evidence was identified for skin cancer screening, particularly regarding potential benefit of skin cancer screening on melanoma mortality. Future research on skin cancer screening should focus on evaluating the effectiveness of targeted screening in those considered to be at higher risk for skin cancer.


Screening for Skin Cancer: US Preventive Services Task Force Recommendation Statement.
JAMA. 2016; 316(4):429-35 [PubMed] Related Publications
IMPORTANCE: Basal and squamous cell carcinoma are the most common types of cancer in the United States and represent the vast majority of all cases of skin cancer; however, they rarely result in death or substantial morbidity, whereas melanoma skin cancer has notably higher mortality rates. In 2016, an estimated 76,400 US men and women will develop melanoma and 10,100 will die from the disease.
OBJECTIVE: To update the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for skin cancer.
EVIDENCE REVIEW: The USPSTF reviewed the evidence on the effectiveness of screening for skin cancer with a clinical visual skin examination in reducing skin cancer morbidity and mortality and death from any cause; its potential harms, including any harms resulting from associated diagnostic follow-up; its test characteristics when performed by a primary care clinician vs a dermatologist; and whether its use leads to earlier detection of skin cancer compared with usual care.
FINDINGS: Evidence to assess the net benefit of screening for skin cancer with a clinical visual skin examination is limited. Direct evidence on the effectiveness of screening in reducing melanoma morbidity and mortality is limited to a single fair-quality ecologic study with important methodological limitations. Information on harms is similarly sparse. The potential for harm clearly exists, including a high rate of unnecessary biopsies, possibly resulting in cosmetic or, more rarely, functional adverse effects, and the risk of overdiagnosis and overtreatment.
CONCLUSIONS AND RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults (I statement).

Sánchez G, Nova J, Rodriguez-Hernandez AE, et al.
Sun protection for preventing basal cell and squamous cell skin cancers.
Cochrane Database Syst Rev. 2016; 7:CD011161 [PubMed] Related Publications
BACKGROUND: 'Keratinocyte cancer' is now the preferred term for the most commonly identified skin cancers basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), which were previously commonly categorised as non-melanoma skin cancers (NMSC). Keratinocyte cancer (KC) represents about 95% of malignant skin tumours. Lifestyle changes have led to increased exposure to the sun, which has, in turn, led to a significant increase of new cases of KC, with a worldwide annual incidence of between 3% and 8%. The successful use of preventive measures could mean a significant reduction in the resources used by health systems, compared with the high cost of the treatment of these conditions. At present, there is no information about the quality of the evidence for the use of these sun protection strategies with an assessment of their benefits and risks.
OBJECTIVES: To assess the effects of sun protection strategies (i.e. sunscreen and barrier methods) for preventing keratinocyte cancer (that is, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) of the skin) in the general population.
SEARCH METHODS: We searched the following databases up to May 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registries and the bibliographies of included studies for further references to relevant trials.
SELECTION CRITERIA: We included randomised controlled clinical trials (RCTs) of preventive strategies for keratinocyte cancer, such as physical barriers and sunscreens, in the general population (children and adults), which may provide information about benefits and adverse events related to the use of solar protection measures. We did not include trials focused on educational strategies to prevent KC or preventive strategies in high-risk groups. Our prespecified primary outcomes were BCC or cSCC confirmed clinically or by histopathology at any follow-up and adverse events.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for eligibility using Early Review Organizing Software (EROS). Similarly, two review authors independently used predesigned data collection forms to extract information from the original study reports about the participants, methods of randomisation, blinding, comparisons of interest, number of participants originally randomised by arm, follow-up losses, and outcomes, and they assessed the risk of bias. We resolved any disagreement by consulting a third author and contacted trial investigators of identified trials to obtain additional information. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS: We included one RCT (factorial design) that randomised 1621 participants.This study compared the daily application of sunscreen compared with discretionary use of sunscreen, with or without beta-carotene administration, in the general population. The study was undertaken in Australia; 55.2% of participants had fair skin, and they were monitored for 4.5 years for new cases of BCC or cSCC assessed by histopathology. We found this study to be at low risk of bias for domains such as allocation, blinding, and incomplete outcome data. However, we found multiple unclear risks related to other biases, including an unclear assessment of possible interactions between the effects of the different interventions evaluated (that is, sunscreen and beta-carotene). We found no difference in terms of the number of participants developing BCC (n = 1621; risk ratio (RR) 1.03, 95% confidence interval (CI) 0.74 to 1.43) or cSCC (n = 1621; RR 0.88, 95% CI 0.50 to 1.54) when comparing daily application of sunscreen with discretionary use, even when analyses were restricted to groups without beta-carotene supplementation. This evidence was of low quality, which means that there is some certainty that future studies may alter our confidence in this evidence.We reported adverse events in a narrative way and included skin irritation or contact allergy.We identified no studies that evaluated other sun protection measures, such as the use of sun-protective clothing, sunglasses, or hats, or seeking the shade when outdoors.
AUTHORS' CONCLUSIONS: In this review, we assessed the effect of solar protection in preventing the occurrence of new cases of keratinocyte cancer. We only found one study that was suitable for inclusion. This was a study of sunscreens, so we were unable to assess any other forms of sun protection. The study addressed our prespecified primary outcomes, but not most of our secondary outcomes. We were unable to demonstrate from the available evidence whether sunscreen was effective for the prevention of basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC).Our certainty in the evidence was low because there was a lack of histopathological confirmation of BCC or cSCC in a significant percentage of cases. Amongst other sources of bias, it was not clear whether the study authors had assessed any interaction effects between the sunscreen and beta-carotene interventions. We think that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Dessy LA, Marcasciano M, Fanelli B, et al.
Surgical treatment of nasal non-melanoma skin cancer in elderly patients using dermal substitute.
Acta Otolaryngol. 2016; 136(12):1299-1303 [PubMed] Related Publications
CONCLUSIONS: The nose is often involved by non-melanoma skin cancer (NMSC) and the increase in the incidence of such tumors, the morbidity and treatment-related costs represent a significant burden to healthcare systems. A bioresorbable dermal substitute (Hyalomatrix(®)) has been used for immediate dermal coverage and nose restoration after excision of infiltrating nasal NMSCs in elderly ASA III patients. Further studies on dermal substitutes are needed to improve benefit to patients.
OBJECTIVE: Surgical treatment of nasal non-melanoma skin cancer (NMSC) in elderly patients.
MATERIALS AND METHODS: Ten elderly ASA III patients with nasal defects after resection of infiltrating NMSC were reconstructed in a two-stage strategy. The surgical protocol targeted an initial wide tumor excision and apposition of a dermal induction template (Hyalomatrix(®)) and successive full thickness skin autograft. Results were documented by photography, visual analog scale for patient satisfaction, and Vancouver scar scale for evaluation of final graft characteristics.
RESULTS: All patients were tumor-free during the 2 years follow-up. The procedure achieved acceptable nose reshaping and graft scarring evolution. Patient satisfaction was good-to-high.

Zlatarova ZI, Nenkova BN, Softova EB
Eyelid Reconstruction with Full Thickness Skin Grafts After Carcinoma Excision.
Folia Med (Plovdiv). 2016; 58(1):42-7 [PubMed] Related Publications
BACKGROUND: Various techniques have been proposed for reconstruction of the eyelid anterior lamella after carcinoma excision: among these are the transposition of skin flaps, and full-thickness skin grafts or combination of these two.
AIM: To present our experience in eyelid reconstruction with full-thickness skin grafts and to assess the aesthetic and functional outcomes.
PATIENTS AND METHODS: The present retrospective study included 39 patients (20 males, 19 females, mean age 71 yrs) with surgically excised eyelid carcinoma, followed by reconstruction using full-thickness skin grafts. The patients were treated between 2005 and 2014. Parameters recorded were patient demographics, histological classification of malignancy, tumor localization and size, postoperative defect size. In cases of large full-thickness lower lid defect Hughes tarsoconjunctival flap was used for reconstruction of posterior lamella. Full-thickness skin grafts donor sites included upper eyelid, preauricular area and inner brachial area. We appraised the grafts viability one week after surgery and the aesthetic results - 6 months after surgery by the graft colour and lid position.
RESULTS: In 95% of the cases the skin grafts were viable. The full-thickness skin graft (FTSG) failed in two patients because of subcutaneous haematoma. There were a few early postoperative complications including graft hypertrophy, graft contraction, and partial graft failure, which were managed without additional surgery. All 39 patients had normal postoperative lid function. All 39 had either good (14) or excellent (25) cosmetic results.
CONCLUSIONS: Our findings suggest that full-thickness skin graft is a good choice in periocular reconstructive surgery after carcinoma excision. The surgical technique is easy to perform producing proper functional and aesthetic results.

Tibes R
Sonidegib phosphate: new approval for basal cell carcinoma.
Drugs Today (Barc). 2016; 52(5):295-303 [PubMed] Related Publications
Basal cell carcinoma (BCC), although mostly locally confined, is the most common cancer. Most BCCs harbor inactivating mutations in the membrane receptor/gene Ptch, thereby activating the Hedgehog signaling pathway (Hh) via the essential signaling molecule Smoothened (SMO). Novel small-molecule inhibitors or antagonists of SMO have shown excellent response rates in patients with locally advanced, unresectable and metastatic BCC in roughly 35-60% of patients, with disease control rates and clinical benefit being even higher. Sonidegib is the second-in-class SMO inhibitor approved for locally advanced, unresectable and metastatic BCC. Sonidegib is given once daily continuously, with specific side effects as listed in the label indication. Resistance develops over time and knowledge gleaned from other SMO inhibitors indicates that SMO mutations preventing drug binding as well as mechanisms activating the Hh pathway downstream of SMO are responsible, ultimately reactivating Hh pathway signaling. The next challenge will be to define novel salvage and SMO combination strategies for BCC and other tumors.

Erfan G, Puig S, Carrera C, et al.
Development of Cutaneous Toxicities During Selective Anti-BRAF Therapies: Preventive Role of Combination with MEK Inhibitors.
Acta Derm Venereol. 2017; 97(2):258-260 [PubMed] Related Publications
is missing (Short communication).

Czapiewski P, Majewska H, Kutzner H, et al.
TTF-1 and PAX5 Are Frequently Expressed in Combined Merkel Cell Carcinoma.
Am J Dermatopathol. 2016; 38(7):513-6 [PubMed] Related Publications
Thyroid transcription factor-1 (TTF-1) is a marker of tumors of pulmonary and thyroid origin, and its expression practically excludes diagnosis of Merkel cell carcinoma (MCC). However, TTF-1 expression in combined MCC was recently reported. PAX5 is a marker of B-cell origin that is also expressed in most classical MCC cases; however, its expression was not described in combined MCC. The authors decided to evaluate the expression of both these markers in a group of 5 combined MCCs (2 with invasive squamous cell carcinoma, 2 with squamous cell carcinoma in situ, and 1 with basal cell carcinoma). Expression of TTF-1 was found in 4 of 5 cases; in 3 cases, the marker was shown in the MCC component (weakly in 2 cases and strongly in 1 case), whereas the non-MCC component presented TTF-1 expression in 2 cases. A weak-to-moderate immunoreactivity for PAX5 was identified in all cases of the MCC component but in none of the non-MCC component. The results show that the expression of TTF-1 is a frequent finding in combined MCC and can be present in the neuroendocrine component, which differs from the conventional MCC. In contrast, PAX5 expression pattern is similar to that of the classical MCC.

Urech M, Kyrgidis A, Argenziano G, et al.
Dermoscopic Ulceration is a Predictor of Basal Cell Carcinoma Response to Imiquimod: A Retrospective Study.
Acta Derm Venereol. 2017; 96(7):117-119 [PubMed] Related Publications
is missing (Short communication).

Chen L, Silapunt S, Migden MR
Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update.
Future Oncol. 2016; 12(18):2095-105 [PubMed] Related Publications
The Hedgehog inhibitors are promising alternative for patients with advanced basal cell carcinoma that are not amenable to radiotherapy or surgery. Sonidegib, also known as LDE225, is an orally available SMO antagonist that was recently approved by the US FDA for the treatment of patients with locally advanced basal cell carcinoma. This article will provide an overview of the pharmacology and pharmacokinetics of sonidegib and in-depth analysis of the BOLT trial with additional data from the 12-month update. The present challenges associated with Hedgehog inhibitors will also be discussed.

Ransohoff KJ, Ally MS, Stefanick ML, et al.
Impact of residential UV exposure in childhood versus adulthood on skin cancer risk in Caucasian, postmenopausal women in the Women's Health Initiative.
Cancer Causes Control. 2016; 27(6):817-23 [PubMed] Related Publications
BACKGROUND: Sun exposure is a major risk factor for skin cancer; however, the relative contribution of ultraviolet (UV) exposure during childhood versus adulthood on skin cancer risk remains unclear.
OBJECTIVE: Our goal was to determine the impact of residential UV, measured by AVerage daily total GLObal solar radiation (AVGLO), exposure during childhood (birth, 15 years) versus adulthood (35, 50 years, and present) on incident non-melanoma skin cancer (NMSC) and malignant melanoma (MM) in postmenopausal women.
METHODS: Women were followed with yearly surveys throughout the duration of their participation in the Women's Health Initiative Observational study, a multicenter study from 1993 to 2005. A total of 56,557 women had data on all observations and were included in the baseline characteristics. The main exposure, residential UV (as measured by AVGLO), was measured by geographic residence during childhood and adulthood. Outcome was risk of incident NMSC and MM.
RESULTS: Over 11.9 years (median follow-up), there were 9,195 (16.3 %) cases of NMSC and 518 (0.92 %) cases of MM. Compared with the reference group (women with low childhood and low adulthood UV), women with low childhood and high adulthood UV had a 21 % increased risk of NMSC (odds ratio 1.21, 95 % confidence interval 1.12, 1.31). Women with high childhood and high adulthood UV had a 19 % increased risk of NMSC (odds ratio 1.19, 95 % confidence interval 1.11, 1.27). Surprisingly, women with high childhood UV and low adulthood UV did not have a significant increase in NMSC risk compared with the reference group (odds ratio 1.08, 95 % confidence interval 0.91, 1.28) in multivariable models. Residential UV exposure in childhood or adulthood was not associated with increased melanoma risk.
CONCLUSION: This study reveals an increase in NMSC risk associated with adulthood residential UV exposure, with no effect for childhood UV exposure.

Li H, Pedersen L, Nørgaard M, et al.
The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.
BMC Cancer. 2016; 16:295 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking.
METHODS: We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first.
RESULTS: The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung.
CONCLUSION: CuSCC and non-cuSCC were rare events among metastatic melanoma patients.

Christensen E, Mjønes P, Grimstad Ø, et al.
Diagnostic Accuracy in Subtyping Basal Cell Carcinoma by Clinical Diagnosis Compared with Punch Biopsy.
Acta Derm Venereol. 2016; 96(6):862-3 [PubMed] Related Publications
is missing (Correspondence).

Ornat M, Kobierzycki C, Grzegrzolka J, et al.
SOX18 Expression in Non-melanoma Skin Cancer.
Anticancer Res. 2016; 36(5):2379-83 [PubMed] Related Publications
BACKGROUND/AIM: SRY-related HMG box protein 18 (SOX18) is a transcription factor involved in a range of physiological processes, including differentiation of endothelial cells during new vessel formation. Numerous studies are being conducted to determine its role in carcinogenesis.
MATERIALS AND METHODS: Thirty-five cases of squamous cell carcinoma (SCC), 61 cases of basal cell carcinoma (BCC), 15 cases of actinic keratosis (AK) and 15 normal skin (NS) cases were examined in the study. Expression of SOX18 was investigated with immunohistochemistry and light optic microscopy. The obtained results were subjected to statistical analysis including available clinicopathological data.
RESULTS: Nuclear expression of SOX18 was shown in vascular endothelial cells, basal layer cells of NS epidermis, as well as in AK, BCC and SCC cancer cells. Expression of SOX18 in SCC, BCC and AK cells was significantly higher than in NS (p<0.01, p<0.001 and p<0.01, respectively). Additionally, higher expression of SOX18 in BCC than in SCC cells (p<0.001) was observed.
CONCLUSION: SOX18 may play a role in the development of BCC and SCC. Further studies with the use of additional markers tested at the mRNA and protein level are necessary for better explanation of SOX18 function in cancer transformation.

Espeli V, Ruegg E, Hottinger AF, et al.
Weekly Multi-agent Chemotherapy (CMF-b) for Advanced Non-melanoma Skin Cancer.
Anticancer Res. 2016; 36(5):2359-64 [PubMed] Related Publications
BACKGROUND/AIM: Advanced unresectable and metastatic non-melanoma skin cancers (NMSC) are rare, but often arise in elderly patients. When surgery or irradiation are no longer feasible, chemotherapy is often precluded by the patient's age and comorbidities. Whether low-dose multi-agent chemotherapy could be an alternative for this vulnerable population in an outpatient setting was the issue examined in this retrospective analysis.
PATIENTS AND METHODS: Twenty-six patients with advanced unresectable or metastatic NMSC received weekly multi-agent chemotherapy with carboplatin at an area under the curve of 2 or 40 mg total dose of cisplatin, with 15 IU total dose of bleomycin, 40 mg total dose of methotrexate, and 500 mg total dose of 5-fluorouracil (CMF-b) until best response, toxicity, or progression of their disease.
RESULTS: Twenty-four patients were treated as outpatients; two were hospitalized. Twenty-three patients were previously treated with surgery or radiotherapy. The median age was 68 years (range=44-100 years). The median number of cycles was 6 (range=1 to 17). The overall response rate was 61.5% (seven complete remissions, nine partial remissions) for the entire cohort and 63.6% (two complete remissions and five partial remissions) for patients >80 years. The median duration of response was 6.1 months (range=1.6-63 months). Responses longer than 6 months were obtained in 11/26 (42.3%) of the entire cohort and in 4/11 (36.3%) patients >80 years. Symptom improvement was observed in 17 patients (65.3%). Toxicity was acceptable, with grade 3 renal failure (n=1) and grade 3 or 4 myelotoxicity (n=2).
CONCLUSION: CMF-b is a safe, weekly low-dose multi-agent regimen that offers palliation for vulnerable patients with NMSC.

Omland SH, Nielsen PS, Gjerdrum LM, Gniadecki R
Immunosuppressive Environment in Basal Cell Carcinoma: The Role of Regulatory T Cells.
Acta Derm Venereol. 2016; 96(7):917-921 [PubMed] Related Publications
Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed by immunohistochemistry followed by automated image analysis in facial BCC, peritumoural skin and normal, buttock skin. Quantitative real-time PCR (qRT-PCR) was performed for FOXP3 and cytokines involved in T-reg attraction and T-cell activation. T-regs comprised 45% of CD4-cells surrounding BCC. FOXP3 was highly expressed in BCC, but absent in buttock skin. Unexpectedly, expression of FOXP3 was increased in peritumoural skin, with the FOXP3/CD3 fractions exceeding those of BCC (p?=?0.0065). Transforming growth factor (TGF)-? and T-reg chemokine expression was increased in BCC and peritumoural skin, but not in buttock skin, with expression levels correlating with FOXP3. T-regs are abundantly present both in BCC and in peritumoural skin, mediating an immunosuppressed microenvironment permissive for skin cancer.

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