World Congress on Cancers of the Skin Abstracts 001 (PP03) Immunocytochemical expression of IMP-3 by cutaneous in situ and invasive squamous carcinomas: a novel biomarker to predict progression of in situ cutaneous lesions to invasive cancers? K. Aljefri,1 M. Ally,2 H. Fassihi,3 F. Lewis,3 N. Attard,3 J. Mellerio,3 C. D’Arrigo,4 L. Igali5 and A. Robson3 1

Dermatology Department, Royal Victoria Infirmary, Newcastle upon Tyne, U.K., 2Dermatology, Stanford School of Medicine, CA, U.S.A., 3St John’s Institute of Dermatology, London, U.K., 4Pathology Department, Dorset County Hospital, Dorset, U.K. and 5Pathology Department, Norfolk and Norwich University Hospital, Norwich, U.K. Insulin-like growth factor II mRNA-binding protein 3 (IMP-3) is an oncoprotein important in cell growth and migration in fetal development. Many studies have found IMP-3 expression in malignant tumours but not in adjacent benign tissues. Lu et al. reported that IMP-3 expression in dysplastic cervical lesions is closely associated with their invasive potential, and with more aggressive clinical behaviour of cervical squamous carcinoma (Lu D, Yang X, Jiang NY et al. IMP-3, a new biomarker to predict progression of cervical intraepithelial neoplasia into invasive cancer. Am J Surg Pathol 2011; 35: 1638–45). To date, reports have been limited to cervical, renal and urothelial carcinomas and malignant melanoma. We studied the expression of IMP-3 in a series of 62 dysplastic and/or invasive squamous lesions of the skin. These included 25 dysplastic or squamous cell carcinomas (SCCs) in situ (SCCIS) of various types and 37 SCCs, 11 of which have a coexisting in situ component. Paraffin-embedded blocks were retrieved from the departmental archives, processed and stained with IMP-3 (Dako, IgG monoclonal 691, dilution 1 : 100, ethylenediaminetetraacetic acid antigen retrieval pretreatment). The stained slides were then reviewed for strength and location of immunostaining. Four of 25 SCCISs had diffuse strong IMP-3 expression, and two of these had adjacent normal epidermis that was immunonegative. Four vulval lesions were negative. The five examples of psoralen–ultraviolet A-induced dysplasia were negative. Sixteen of 37 SCCs had expression of IMP-3, usually strongly and diffusely, including two of six tumours arising following renal transplantation. Five of 10 SCCs arising in epidermolysis bullosa (EB) were positive; three of the patients with EB with positive tumours have died of widespread malignancy. These findings suggest that expression of the oncoprotein IMP-3 is associated with invasive but not in situ SCCs, and therefore might play an important role in the development of invasion in some tumours.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

002 (PP05) Comparison of the American Joint Committee on Cancer and Brigham and Women’s Hospital staging systems for cutaneous squamous cell carcinoma of the head and neck: a retrospective review M. Bajwa, J.Y. Rhee and S. Walsh Maxillofacial Unit, Western Sussex Hospitals NHS Foundation Trust, Chichester, U.K. Recent evidence suggests that the American Joint Committee on Cancer (AJCC) staging for cutaneous squamous cell carcinoma (cSCC) is of limited prognostic value as there is a tendency for most tumours to be classified as T2. The Brigham and Women’s Hospital (BWH) staging system has been shown to have improved prognostic value; however, this evidence is based on tumours from all body sites (Karia PS, JambusariaPahlajani A, Harrington DP et al. Evaluation of American Joint Committee on Cancer, International Union Against Cancer, and Brigham and Women’s Hospital tumor staging for cutaneous squamous cell carcinoma. J Clin Oncol 2013; 32: 327–34; Jambusaria-Pahlajani A, Kanetsky PA, Karia PS et al. Evaluation of AJCC tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system. JAMA Dermatol 2013; 149: 402–10). The purpose of this study was to assess the BWH staging system for cSCC of the head and neck region only. All cSCCs treated in a single institution during 2007 and 2008 were reviewed. Follow-up was for 5 years. Patients who died within the 5 years from noncancer-related reasons were excluded. Cases with incomplete datasets were also excluded. The outcomes of interest were local recurrence (LR) and regional metastases (RM). In total 106 patients met the inclusion criteria; 84 were male and 22 female. The mean age of patients was 793 years. A total of nine patients (85%) had LR and eight (75%) had RM. The ear was the most high-risk site and the parotid was the most common site for RM. No tumours included in the study were staged as AJCC T3/T4 or BWH T3. The AJCC staging classified 63 tumours as T1 and 43 as T2. AJCC T1 tumours showed LR in 15% of cases and RM in 47%; AJCC T2 tumours showed LR in 186% and RM in 116%. The BWH staging classified 63 as T1, 24 as T2a and 19 as T2b. BWH T1 tumours showed LR in 15% of cases and RM in 47%; T2a tumours showed LR in 125% and RM in 41%; T2b tumours showed LR in 263% and RM in 211%. BWH stage T2b lesions were identified as high risk especially for RM. The BWH staging demonstrated better prognostic value than the AJCC staging for cSCC of the head and neck. Further larger studies are required to validate these findings.

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2 WCCS Abstracts

003 (PP11) Solar elastosis and cutaneous melanomas: further evidence of multiple causal pathways M. Kvaskoff,1 N. Pandeya,2 A. Green,3 C. Baxter,3 M. Davis,3 R. Mortimore,4 L. Westacott,4 D. Wood,5 J. Triscott,5 R. Williamson6 and D. Whiteman1 1

Harvard Medical School, Boston, MA, U.S.A., 2University of Queensland, Brisbane, Queensland, Australia, 3QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia, 4Queensland Medical Laboratory, Brisbane, Queensland, Australia, 5IQ Pathology, Brisbane, Queensland, Australia and 6 Sullivan Nicolaides Pathology, Brisbane, Queensland, Australia Cutaneous melanomas are postulated to arise through at least two causal pathways, summarized as the ‘chronic sun exposure’ and ‘naevus’ pathways (Whiteman DC, Stickley M, Watt P et al. Anatomic site, sun exposure, and risk of cutaneous melanoma. J Clin Oncol 2006; 24: 3172–7; Whiteman DC, Watt P, Purdie DM et al. Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous melanoma. J Natl Cancer Inst 2003; 95: 806–12). While chronic sun exposure is thought to underlie the majority of melanomas arising on the head or neck, the role of chronic sun exposure for melanomas arising at other anatomical sites is less clear. In a case–case study, we sought to determine the prevalence and epidemiological correlates of melanomas exhibiting solar elastosis among patients with tumours on the trunk (n = 418) or head/neck (n = 92) who were ascertained from pathology laboratories servicing a populous region of Australia between 2007 and 2010. Patients self-reported information about their past sun exposure (including weekday and weekend exposures and sunburns at different periods of life) and their phenotype (including skin type, naevus and freckling densities). A dermatologist counted naevi and solar keratoses. Sections of each patient’s melanoma were examined by dermatopathologists and scored for dermal elastosis in adjacent skin using a three-point scale (nil/mild, moderate, marked). We measured associations between putative risk factors and degree of dermal elastosis at each site using polytomous logistic regression. Marked dermal elastosis was observed in 10% and 59% of trunk and head/neck melanomas, respectively; a further 27% and 17%, respectively, exhibited moderate elastosis. At both sites, marked elastosis was positively associated with age (Ptrend < 00001) and inversely associated with naeval remnants (Ptrend < 0001). For trunk melanomas, marked dermal elastosis was positively associated with the highest quartiles of total sun exposure [odds ratio (OR) 547, 95% confidence interval (CI) 108–2760] and facial freckling (OR 298, 95% CI 117–756), and inversely associated with deeply tanning skin (OR 029, 95% CI 008–111) and high naevus counts (OR 008, 95% CI 001– 066). Mostly similar patterns were observed for melanomas arising on the head or neck. These findings confirm that a proportion of melanomas arising on the trunk exhibit marked solar elastosis, and that such melanomas occur in people with low naevus counts, high freckle counts and high levels of chronic sun exposure. Taken together, these data are consistent with a pathway of melanoma development characterized

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by chronic sun exposure that can occur even at sites considered intermittently exposed to the sun.

004 Lymphatics and blood vessels in irradiated skin tissue R. Shayan,1 P. Gill,1 P. Mahar,1 T. Karnezis,2 M. Ashton,2 D. Grisnell,2 I. Taylor2 and D. HunterSmith3 1

The Alfred Hospital, Melbourne, Victoria, Australia, 2Royal Melbourne Hospital, Melbourne, Victoria, Australia and 3Frankston Hospital, Melbourne, Victoria, Australia The lymphatic vasculature facilitates tumour metastasis to locoregional lymph nodes, the most important prognostic indicator in many solid tumours including melanoma. Aside from surgical removal of the primary tumour and lymph nodes thought to be involved, additional treatment modalities such as chemo- or radiotherapy (XRT) are also beneficial to certain patients. XRT is known to be effective in controlling tumour recurrence at the primary site or nodal basin; however, a major side-effect is impaired tissue healing in surrounding normal tissues. We sought to study the response of lymphatics to determine whether their effect may be implicated in the clinical effects of tumour recurrence. Recently identified lymphatic markers have enabled the study of lymphatics in normal tissue and in the generation of pathological ‘neolymphatics’. Tumours studied in animals and humans that exhibit greater lymphatic densities are more likely to undergo nodal spread. We studied samples of irradiated human breast skin (n = 11) compared with normal control skin (n = 22) to understand better the effect of radiotherapy on blood vessels and lymphatics. Tissues were stained using validated lymphatic vessel immunohistochemical markers and quantified by two independent, blinded observers microscopically. A validated quantification software package was employed and both internal and external quantification controls were utilized. Immunohistochemical staining using the lymphatic larker M2-40, a monoclonal antibody to the molecule podoplanin, and the blood vessel (BV) marker CD31 showed positive staining for lymphatics (LVs) and BVs in normal control and XRT skin (n = 11). Quantification showed that the number of BVs in the control tissues (4227  623) and the number of BVs in the skin specimens (389  61) were not statistically different (P < 007). In contrast, the LV density seen in XRT tissue samples (301  0034) was significantly lower than the LB density seen in control tissues (48  0023, P < 005). While beneficial in terms of tumour recurrence, immunohistochemical analysis of XRT vs. normal tissues from the same patients demonstrated that while BV density is unaltered, LV density is reduced by XRT. The difference in the LV density may play a significant role in long-term tissue changes in XRT tissue, and may account for poor wound healing. Conversely, the reduction in LV density may also mean that in a potential local tumour recurrence, tumour cells may be loculated or confined to the local area, reducing the change of nodal spread. © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 3

005 Validation of self-reported information regarding skin cancer (nonmelanoma skin cancer and cutaneous malignant melanoma) A.-S. Sonne Holm and H.C. Wulf Dermatological Research Department D92, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark Having access to reliable medical data is essential from both a clinical and epidemiological perspective. Self-reported information is used extensively and is in many cases the only available source of information. Hence, the objective of this study was to evaluate the validity of a self-reported history of skin cancer or precursors thereof. In the summer of 2011, a walkin bus, located at strategic places around Denmark, provided the setting for a nationwide individualized skin cancer prevention campaign aimed to attract participants most at risk of developing skin cancer. The participants completed a questionnaire in which they stated whether they at some point had had skin cancer or precursors thereof. To verify the selfreported information, all the patients’ pathology results were obtained through the nationwide pathology database. The campaign was funded by the LEO foundation. In total 4042 participants had answered the question regarding skin cancer or precursors thereof, of whom 28% had not written their social security number, were dead or had emigrated since the campaign was conducted, and thus were excluded due to lack of access to their pathology tests. Thus, the dataset consisted of 2898 individuals available for verification, of whom 235 had stated that they had either skin cancer or precursors thereof. For individuals who had stated that they did not have skin cancer or precursors, there was an incorrect classification rate of14%. For the individuals who stated that they had had cutaneous malignant melanoma, there was an incorrect classification rate of 30%, while it was 26% and 62% for individuals who stated that they had had nonmelanoma skin cancer or precursors of skin cancer, respectively. Overall, there was an incorrect classification rate of 26%. Analysis revealed no discrepancies between the study population and the excluded participants. Self-reported information regarding not having had skin cancer or precursors thereof appears to be credible information. While another study (Renzi C, Mastroeni S, Mannooranparampil T et al. Reliability of self-reported information on skin cancer among elderly patients with squamous cell carcinoma. Ann Epidemiol 2011; 21: 551–4), examining patients at a dermatology referral centre, showed accurate reporting regarding having had skin cancer, the present study, of the general population, showed that the validity of selfreported information is quite poor. This raises the question of whether self-reported information regarding skin cancer should be applied in research.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

006 Clinicopathological features and prognosis in BRAF mutated metastatic melanoma: a single-centre analysis L. Kandolf-Sekulovic, T. Vukanovic, S. Jovandic, Z. Mijuskovic, L. Zolotarevski, M. Rajovic, M. Novakovic and Z. Magic Military Medical Academy, Belgrade, Serbia There are a few reports revealing that BRAF mutational status is associated with certain risk factors, specific clinicopathological characteristics, and differences in overall survival. In this study, clinicopathological and prognostic association of BRAF status in metastatic melanomas treated at our centre were assessed. This retrospective pilot study involved 47 patients (28 male and 19 female, median age 63 years, range 23–84 years) with stage IV melanoma treated from 2009 to 2014. Samples were assessed by allele-specific real-time polymerase chain reaction assay for detection of BRAF V600 mutations. BRAF mutations were found in 20/47 patients (43%). The median age of patients with BRAF mutations was 565 years (range 33–79), and it was 67 years (range 23–84) in BRAF wild-type patients. Overall 7% of patients were younger than 40 years in the BRAF wild-type group, and 25% in the BRAF mutated melanoma group. Also, there was a trend towards a higher proportion of patients with a history of outdoor work (42% vs. 9%) and presence of solar lentigo (36% vs. 17%) in patients with BRAF wild-type tumours vs. BRAF mutated melanoma, respectively. No correlation was found for the primary melanoma location, clinicopathological subtype or ulceration status. The median Breslow thickness in the BRAF mutated group was 48 mm (range 08–22), while in the BRAF wild-type group it was 52 mm (range 25–18) (P > 005). In the mutated group four of 20 melanomas (7%) were in stage I, and none in the BRAF wild-type group. There were no differences found in progression-free survival, distant-metastasis-free survival, distant-metastasis survival and overall survival between the BRAF mutated and BRAF wildtype groups. In conclusion, despite the small number of patients, previously reported clinicopathological and prognostic associations of BRAF mutated melanoma were partially confirmed in our study.

007 Epidemiological study and survival analysis of head and neck melanoma , E. Herrera-Acosta, M. MendiolaJ.-L. Bernabo ndez, N. Lo pez-Navarro and E. Herrera-Ceballos Ferna Virgen de la Victoria University Hospital, Malaga, Spain Head and neck melanoma (HNM) accounts for nearly 20% of all melanomas. Head hair cover, which widely differs between sexes, provides a photoprotective shield and thus influences the ultraviolet radiation reaching the skin (Lesage C, Barbe C, Le Clainche A et al. Sex-related location of head and neck melanoma strongly argues for a major role of sun exposure in cars and photoprotection by hair. J Invest Dermatol 2013; 133: 1205–11; Tejera-Vaquerizo A, Mendiola-Fernandez M, FernanBritish Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

4 WCCS Abstracts

dez-Orland A, Herrera-Ceballos E. Thick melanoma: the problem continues. J Eur Acad Dermatol Venereol 2008; 22: 575–9). Increasing incidence of melanoma and persistence of thick tumours has been recently recognized. Sentinel node biopsy in HNM remains controversial. Therefore, our objectives were (i) to study the location of HNM in both sexes; (ii) to study the historical trend of incidence and tumour thickness of HNM; and (iii) to analyse survival in our patients with HNM, in whom sentinel node biopsy (SNB) was not performed, and to compare it with published studies where SNB and selective lymphadenectomy were performed. This was a longitudinal retrospective study of patients diagnosed with HNM between January 1996 and August 2013. Overall, 115 patients were included (51% women, mean age 64 years). A clear-cut, sexrelated distribution was found between a ‘peripheral’ area (scalp, forehead, temples, ears and neck) and a ‘central’ area (other parts of the face), with 78% of HNMs being located in the peripheral area in men and 65% in the central area in women (P < 0001). Tumours were thinner in women, with 67% of HNMs having Breslow thickness < 1 mm, vs. 43% in men (P < 001). During the 17-year study period, an increase in total HNMs diagnosed was found, as well as a nonstatistically significant increase in HNMs with Breslow thickness > 4 mm (25% vs. 13%). The 5-year disease-free survival was 98% for Breslow thickness < 1 mm and 33% for Breslow thickness >4 mm. There was no statistically significant difference compared with the results of a recent study where SNB was performed. In conclusions, a clear-cut, sex-related distribution of HNMs was found: men tend to have HNMs in regions that usually have less hair density than in women. This supports the hypothesis that hair cover can protect against melanoma. Regarding historical trends, an alarming persistence of thick HNMs was observed. Early melanoma diagnosis and surveillance remains a challenge. Finally, our analysis suggests that performing SNB brings no improvement in survival in patients with HNM. More larger studies are necessary to confirm these data.

008 Clinical and epidemiological profile of malignant melanomas: correlation between prognosis and the expression of fatty acid synthase and proteins involved in the cell cycle and angiogenesis on,2 M.L. Cintra,3 C. Gomes,1 M. Martinez,1 J. Le 3 1 R. Stelini, O. Almeida, E. Graner1 and K. Zechinn1 1

Oral Pathology Service, Piracicaba Dental School, Department of Pathology University of Campinas, Piracicaba, S~ao Paulo, Brazil, 2Oral Pathology Service, Public Oral Health and Forensic Dentistry, University of S~ao Paulo, Ribeir~ao Preto, S~ao Paulo, Brazil and 3Pathology Dermatology Service, Faculty of Medical Sciences, Department of Anatomical Pathology University of Campinas, Campinas, S~ao Paulo, Brazil The present study aimed to identify the clinical and histopathological characteristics of malignant melanoma. Also, the expression of fatty acid synthase and proteins involved in cell cycle and angiogenesis was examined. This study comprises 638 patients with a histopathological diagnosis of primary cutaneous, ocular and metastatic melanomas, from our pathoBritish Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

logical department between 1993 and 2012. Only patients with a micrometric Breslow thickness ≥ 20 mm were included, and specimens from melanomas in situ or without the inclusion measures for the preparation of tissue microarrays were excluded. The first objective was to evaluate characteristics of patients (age, sex) and tumours (Breslow index, Clark level, ulceration, location, histological type). The array included the tumours’ most representative areas from primary cutaneous melanomas (n = 80), ocular melanomas (n = 26) and metastatic melanomas (n = 28). Among the cutaneous melanomas, 41 cases were female (51%) and 39 male (49%). The mean age of patients at diagnosis was 63  14 years. According to the clinical and histopathological characteristics of the patients, melanomas were classified as extensive superficial melanomas (26%), nodular melanomas (23%), acral lentiginous melanomas (10%), lentigo maligna melanomas (6%), mucosal lentiginous melanomas (5%) and without further specification (WFS; 30%), which includes desmoplastic (14%), intradermal (4%), pigmented (9%), amelanotic (5%), extensive radial (4%) and melatonin (14%). The average Breslow index was 49  27 mm. Regarding the Clark levels, the samples showed the following profile: 11% stage III, 54% stage IV and 24% stage V. Ulcerations were present in 60% of cases. The lesions were located in the head and neck area (20%), trunk (24%), upper limbs (34%), lower limbs (12%) and skin WFS (10%). Considering that in several malignancies, including melanomas, there is high expression and activity of the fatty acid synthase gene (FASN), alterations in the cell cycle and angiogenesis are associated with a higher recurrence rate, metastasis spread and poor prognosis. The discovery of potential prognostic markers is proposed in this study. In addition, our results will be important to better understand the biological behaviour of malignant melanoma and might contribute to improving the prognosis and survival of patients.

009 Folliculotropic mycosis fungoides: report of 18 cases in a single centre in Argentina A. Abeldan˜o, M. Arias, A. Benedetti, M. Maskin, A. Rothlin, C. Lamas and C. Trila Hospital Argerich, Ciudad Autonoma de Buenos Aires, Argentina Folliculotropic mycosis fungoides (FMF) is a rare variant of mycosis fungoides (MF) with distinct clinicopathological features (Muniesa C, Estrach T, Pujol RM et al. Folliculotropic mycosis fungoides: clinicopathological features and outcome in a series of 20 cases. J Am Acad Dermatol 2010; 62: 418–26; Benner MF, Jansen PM, Vermeer MH, Willemze R. Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood 2012; 119: 1643–9). It is characterized by the presence of an infiltration of the follicular epithelium by atypical lymphocytes associated or not with the presence of mucin. We analysed the clinical, histological and immunophenotypical features of FMF in our patient population. We performed a retrospective analysis of the database of our department of dermatology. All patients meeting the clinicopathological criteria of FMF were included. A review of the © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 5

clinical data assessed the following parameters: diagnosis, sex, age at diagnosis, response to treatment and survival rate. Between November 1995 and December 2013 we diagnosed 158 cutaneous T-cell lymphomas; 118 were MF. Among these patients we found 18 cases of FMF (15%). Thirteen were male and five female. The mean age at diagnosis of FMF was 501 years (range 32–79). The mean follow-up time was 666 months. Regarding the stage of MF at the initial diagnosis of FMF: 12 were IIB, four IB, one IIIA and one IVA. Patients were treated with radiotherapy, psoralen–ultraviolet A (PUVA), methotrexate, interferon (IFN), IFN + PUVA, bexarotene, vorinostat and chemotherapy. Regarding evolution and response to treatment, only two patients had complete response; one was lost to follow-up and another one was recently diagnosed. Eleven patients had partial response despite treatment. The remaining three patients did not respond to treatment, and presented progressive disease since diagnosis. About 16% of our patients presented a transformation to a large T-cell lymphoma (three of 18). Six patients died (33%), and the deaths were directly related to the lymphoma in five cases. In conclusion, the relative frequency of FMF among patients with MF was 15%. Most patients were diagnosed at an advanced stage of the disease. Response to therapy was poor in most of the patients, with initial partial response in 61% of cases and progressive disease in 33%. Five of the six deaths were related to lymphoma. As has been published previously, FMF behaves more aggressively than conventional epidermotropic MF and has a poor prognosis, showing a trend towards more rapid disease progression and resistance to conventional therapy.

010 Treatment of actinic keratosis and other skin tumours with ingenol mebutate gel R. Ortega Facultad de Medicina, Granada, Spain The objective of this study was to assess the effectiveness and safety of ingenol mebutate gel (IMG) as a topical treatment for actinic keratoses (AKs) and other skin tumours. This was a retrospective study of patients with AK and basal cell carcinoma (BCC). Data extracted from clinical records included information from baseline and follow-up visits at 3–4 days, 15, 30 and 60 days after treatment with IMG. Patients received IMG 150 lg for 3 days for lesions located on the face and/or scalp, while other locations were treated with 500 lg for 2 days. During all follow-up visits, local skin reactions such as erythema, oedema, flaking/scaling, crusting and presence of vesicles or erosion were assess and scored on a scale of 0 (no signs) to 4 (maximum severity). A descriptive analysis of the characteristics of the sample was performed. Clinical evolution of the lesions was analysed with Friedman and Wilcoxon tests. In total 109 treatments with IMG in 105 patients with an overall mean age of 688  102 were reviewed. The sample compromised a majority of men (688%) with Fitzpatrick phenotypes I and III. Overall 725% of patients had a family or personal history of skin cancer. Treated lesions were located mainly on the face (AK 67%, © 2014 The Authors BJD © 2014 British Association of Dermatologists

BCC 69%) and scalp (AK 33%, BCC 25%). At the final visit after treatment, 76% of treatments were associated with a complete remission of the lesion, while 24% were reported as partial. The presence of some degree of local reaction was observed in 99% of cases, with a significant reduction of their intensity at day 15 after treatment (P < 005). Cosmetic results were considered either good or very good in 86 patients, with improvement in skin appearance for 87 patients (84%). Dropouts associated with local skin reactions were reported for six patients. In conclusion, in two-thirds of patients treated with IMG, complete removal of the lesion was achieved in the treated area. Local skin reactions in most patients after 3–4 days significantly decreased after 2 weeks. A good or very good cosmetic result was seen in most cases and 84% of patients had an improvement in skin appearance.

011 Clinical and histopathological features of aggressive basal cell carcinoma ¨ . Gu ¨l,1 S. Soylu,2 E. Benzer3 and I. Pak3 U 1

Department of Dermatology, Medical School, Akdeniz University, Antalya, Turkey, 2Dermatology Department, Ministry of Health, Numune Education and Investigation Hospital, Ankara, Turkey and 3Pathology Department, Ministry of Health, Oncology Education and Investigation Hospital, Ankara, Turkey Basal cell carcinoma (BCC) is the most frequent type of skin cancer in humans. Most BCCs are slow-growing, relatively nonaggressive tumours. However, a minority of BCCs have an aggressive biological behaviour, causing extensive deep-tissue invasion, metastasis and recurrence. The object of this study was to evaluate clinical and histopathological features of aggressive BCC. Our study group consisted of 19 recurrent and/or invasive BCCs, and the control group consisted of 19 patients with nonaggressive BCC. For all of the patients, age, sex and localization of the lesions were recorded. For recurrent and/or invasive BCCs, the number of recurrences, the time interval between the first and recurrent lesion occurrence, and the tissues that were invaded were also noted. In both groups, histopathologically squamous differentiation, the number of mitoses, the loss of regularity in palisading, cystic changes, morpheaform or sclerosing stroma, increase in tumour cells, nuclear pleomorphism, the cell group type, growth pattern and existence of ulceration were examined. The aggressive group consisted of 19 patients, seven female and 12 male. The mean age was 587 years (range 41–73). Three had only recurrent tumour, six were both recurrent and invasive, and 10 had only invasive tumour. The localization of the lesions was most frequently periorbital. The interval between recurrence ranged from 6 months to 8 years. The mean age of the nonaggressive group was 638 years (range 50–87), with 11 male and eight female patients. The most frequent localization of the lesions was the nose. Histopathologically, in the aggressive BCC group, a loss of regularity in palisading was revealed in 16 cases, morpheaform or sclerosing stroma in 14 cases, infiltrative tumour in 15 cases, squamous differentiation in 15 patients and an increase in tumour cell nuclear pleomorphism in 14 cases. In the control group, a loss of regularity in palisading was revealed in six cases, British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

6 WCCS Abstracts

morpheaform or sclerosing stroma in three cases, infiltrative tumour in six patients, squamous differentiation in 13 patients, and increase of tumour cell nuclear pleomorphism in six cases.

012 Advanced basal cell carcinomas: possible candidates for vismodegib therapy C.O. Andreia,1 C. Monica,1 A. Mihail,2 U. Ana2 and G.S. Roxana1 1

University of Medicine and Pharmacy Carol Davila, Bucharest, Romania and Clinical Hospital DR. Victor Babes, Bucharest, Romania Basal cell carcinoma (BCC) is the most common human cancer. Variants of BCC include nodular, superficial, morpheaform, cystic, basosquamous and micronodular types. BCC is highly treatable by surgical excision, electrodesiccation, curettage, Mohs surgery, irradiation and anticancer drugs (vismodegib). Oral vismodegib is effective in the treatment of patients with locally advanced or metastatic BCC, who are not candidates for other treatments [Weinstock MA, Still JM. Assessing current treatment options for patients with severe/ advanced basal cell carcinoma. Semin Cutan Med Surg 2011; 30 (Suppl. 4): S10–3]. Vismodegib is a small-molecule, systemic inhibitor of the hedgehog (Hh) intracellular signalling pathway [Sekulic A, Migden MR, Oro AE et al. Efficacy and safety of the Hedgehog pathway inhibitor vismodegib in patients with advanced basal cell carcinoma (BCC): ERIVANCE BCC study update. Presented at the 48th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, 1–5 June 2012; abstr. 8579]. We present six cases of various forms of histologically confirmed advanced BCCs. One of them had multiple BCCs localized on the face and two of them had recurrent BCCs following radiotherapy. Patients were men aged 55–76 years, with Fitzpatrick phototypes II and III, with chronic long-term ultraviolet radiation exposure. Some had a medical history of heart diseases, hypertension and liver pathology. The lesions were nodular and nodular–ulcerative, with pearly, telangiectatic border and central ulceration, occurring on sun-exposed areas, ranging in size from 6 to 105 cm, evolving over 3– 6 years. Because the BCCs were locally advanced and some of them had recurred following radiotherapy, the appropriate treatment for these patients was considered to be oral vismodegib. Lab tests performed included complete blood count, showing no major changes (mild leucocytosis, lymphocytopenia, eosinophilia), serum aminotransferases (mildly increased) and serum cholesterol. Histopathological examination of the lesional skin biopsy detected the main features of BCC: normal epidermis with dermal tumour masses, malignant basal cells with large nuclei and relatively little cytoplasm, and peritumoral lacunae. Our patients had giant BCCs situated on the face, trunk and retroauricular area, some of them recurrent following radiotherapy, so they were suitable candidates for oral treatment with vismodegib 150 mg once daily. This medication has been recently approved for the treatment of locally advanced or metastatic BCC refractory to standard treatments, or for patients who are not viable candidates for surgery or radiation therapy, as in our cases. 2

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013 Clinical, dermoscopic and histopathological features of basal cell carcinoma in young adults O.A. Orzan, I. Popescu, A. Pehoiu, I. Tudose, L.G. Popa, M. Nichita and C. Giurcaneanu Elias University Emergency Hospital, Bucharest, Romania The incidence of basal cell carcinoma (BCC) has increased within the last few years, not only among elderly persons, but also in the population younger than 40 years. There are still controversies in the literature about the aggressive potential of BCC in young patients compared with the BCC in the elderly. Therefore it would be of great interest to analyse further the clinical, dermoscopic and histopathological features of these tumours in young adults. We performed a retrospective case analysis of 10 patients under the age of 40 years (age 24– 40 years) with a previous diagnosis of BCC, describing the clinical, dermoscopic and histological characteristics of these tumours. The data were determined using records of all patients registered over 4 years in our dermatology department. The results showed an almost equal male-to-female ratio, and a mean age at diagnosis of 35 years. It was difficult to estimate the median duration of BCC prediagnosis as most of the tumours were interpreted as common naevi by the patients, with a declared evolution of > 1 year. Most of the tumours were located in the face and neck region, on sun-exposed areas (seven of 10 cases); three lesions were located on the trunk and none on the extremities. There were six nodular BCCs, and two superficial and two pigmented tumours, with a size variation of 05–2 cm. The dermoscopic features were arborizing vessels, blue ovoid nests, spoke-wheel and leaf-like structures and ulceration, with no doubtful characteristics. The main histological subtype was solid (six cases), with deep dermal infiltration in six cases. Complete excision was performed in nine of 10 cases. BCC in young patients may not be suspected because it is infrequent. However, the tumours included in our analysis showed typical clinical and dermoscopic features of BCC, allowing precise diagnosis of all lesions before surgical excision. Delay of diagnosis and treatment was due to patient misinterpretation of lesions as naevi, in the context of young age and poor patient awareness, which emphasizes the need to focus on educational programmes for skin cancer prevention. This paper was cofinanced from the European Social Fund, through the Sectoral Operational Programme Human Resources Development 2007– 2013, project number POSDRU/159/1.5/S/138907 “Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields – EXCELIS”, coordinator The Bucharest University of Economic Studies.

014 The evaluation of 534 cases of basal cell carcinoma with respect to age, sex, anatomical region and histopathological types ¨ . Gu ¨l U Akdeniz University, Antalya, Turkey Basal cell carcinoma (BCC) is a frequently seen skin cancer. Although the mortality rate is low, BCCs cause important © 2014 The Authors BJD © 2014 British Association of Dermatologists

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health problems. I aimed to investigate 485 cases of BCC retrospectively and to evaluate statistically these cases with respect to age, sex, anatomical region and histopathological type. In total 534 cases of BCC were investigated retrospectively. They were examined at the Onkoloji Education and Research Hospital and Numune Education and Research Hospital. BCC diseases seen early in life, such as Kaposi sarcoma and borderline hepatocellular nodules, were not included in the study in order not to effect the evaluation. Age, sex, the localization of the lesion and histopathological types were recorded. The study group consisted of 312 men (mean age 629 years, range 31–91) and 222 women (mean age 644 years, range 22–91). Evaluation according to BCC histopathological types was nodular type (943%), superficial (55%) or morpheaform (02%). Evaluation according to anatomical region was head and neck (935%), trunk (52%), upper extremities 01%) or perianal region (02%). The superficial type was observed statistically significantly earlier than the nodular type. They were nodular BCCs mostly in the head and neck region, and more frequently superficial BCCs on the trunk. There were no statistically significance differences between age and sex, age and anatomical region, sex and anatomical region or sex and histopathological type.

no hyperkeratotic AKs (grade III). In addition to the most frequently encountered dermoscopic findings such as red pseudonetwork, strawberry pattern and surface scale, we also observed erosions or crusts (four cases) and white pseudocysts (two cases). For pigmented AK the most common dermoscopic findings were brown pseudonetwork and brown globules, but one case showed brown blotches over a red background. Most lesions showed moderate dysplasia (62%), while < 20% corresponded to mild or severe dysplasia. Erosions or crusts and pigmented structures were found alongside any degree of dysplasia. Additionally, AKs categorized as macules showed the full spectrum of dysplasia, from mild to severe. We did not observe any correlation between the clinical and dermoscopic assessment and the histological degree of dysplasia. Clinicohistological correlation of AK might not be as strong as previously thought. AKs are clinically heterogeneous lesions that can range from red or pigmented macules with slight or no scale to hyperkeratotic papules or plaques. AKs are not routinely biopsied, and only lesions that pose diagnostic difficulties are sampled. This explains the high proportion of pigmented AKs in our study. A higher degree of hyperkeratosis does not necessarily translate to a more severe degree of dysplasia.

015 Correlation between clinical and dermoscopic evaluation of actinic keratosis and the degree of dysplasia I. Longo,1 S. Arias-Santiago,2 E. de las Heras,3 ndez-Guarino,4 J.L.L. Estebaranz,5 A. Toll,6 M. Ferna  n7 S. Vidal-Asensi1 and C. Serra-Guille

016 The role of dermoscopy in diagnosis of various basal cell carcinoma clinical subtypes: the results of a multicentre study D.T. Zivkovic,1 T. Ros,2 L.K. Sekulovic3 and Z. Mijuskovic3



Hospital Central de la Defensa Gomez Ulla, Madrid, Spain, Hospital Virgen de las Nieves, Granada, Spain, 3Hospital Ramon y Cajal, Madrid, Spain, 4 Hospital Central de la Cruz Roja, Madrid, Spain, 5Fundacion Hospital Alcorcon, Madrid, Spain, 6Hospital de Mar, Barcelona, Spain and 7Instituto Valenciano de Oncologıa, Valencia, Spain Actinic keratoses (AKs) are classically described as red scaly macules, papules or plaques that can also present with thick hyperkeratosis. A gradient of more severe dysplasia with increasing hyperkeratosis that is also correlated with dermoscopic examination has been described. The aim of this study was to test the capability to predict the degree of dysplasia based on clinical and dermoscopic images of patients with histologically confirmed AKs. A group of seven dermatologists experienced in the assessment of patients with skin cancer participated in an online survey where clinical and dermoscopic images were presented. There were 12 patients and 16 AKs. The 32 images were randomly presented for evaluation of clinical features (macule, papule or plaque), grade classification (I, II or III) and suspected degree of dysplasia (mild, moderate or severe). Then, the 16 pairs of clinical and dermoscopic images were shown as correlative cases. Roughly 70% of lesions were macules, 25% of which lacked surface scale. More than one-third of lesions were pigmented AKs, and the majority were macules without surface scale. Clinically most lesions were flat (75% were graded as type I) and there were © 2014 The Authors BJD © 2014 British Association of Dermatologists


Clinic of Dermatovenereology, Clinical Center of Nis, Faculty of Medicine, Nis, Serbia, 2Clinic of Dermatovenereology, Clinical Center of Vojvodina, Novi Sad, Serbia and 3Clinic of Dermatovenereology, Faculty of Medicine, Military Medical Academy, Belgrade, Serbia It has been confirmed in previous studies that dermoscopy increases diagnostic accuracy and is necessary for early detection of basal cell carcinoma (BCC), which is essential for effective treatment. However, the dermoscopic criteria of different BCC subtypes are still not fully established, and the treatment approach may vary according to clinical subtype. The objective of our study was to assess the frequency of BCC dermoscopic criteria in different BCC clinical subtypes. Digital dermoscopic images of histopathologically confirmed BCCs were evaluated for the presence of predefined standard BCC criteria. The results were correlated with tumour clinical characteristics. In total, 221 tumours from 190 patients (120 in male patients, 101 in female patients; median age 67 years, range 15–94) were evaluated. The most common clinical subtypes were superficial BCC (sBCC) and nodular BCC (nBCC) (87, 394% each) followed by 42 (190%) pigmented BCCs (pBCC) and five (23%) morphoeic BCCs. Superficial BCC was more common on the trunk (60% vs. 22%, P < 0001) and nodular BCC was predominant on the head and neck (70% vs. 31%, P < 0001), while pigmented BCC was equally distributed between head and neck, and trunk (P < 0001 vs. nBCC). The most differing features in favour of nBCC were arborizing British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

8 WCCS Abstracts

telangiectasia (present in 41% of sBCC vs. 90% of nBCC vs. 60% of pBCC, P < 0001) and ulceration (24% vs. 63% vs. 36%, respectively, P < 0001). Short fine superficial telangiectasia (51% vs. 9% vs. 24%), multiple small erosions (32% vs. 2% vs. 14%, P < 0001) and shiny white-red structureless areas (88% vs. 15% vs. 17%, P < 0001) were found to be most common in sBCC. As expected, large blue-grey ovoid nests were most commonly found in pBCC, but were also occasionally seen in sBCC and nBCC (9% vs. 10% vs. 67%, P < 0001), as were maple-leaf structures (8% vs. 1% vs. 50%, P < 0001) and multiple in-focus grey dots (7% vs. 10% vs. 19%, P = 006). Interestingly, large blue-grey ovoid nests were more commonly found in pBCC on the head and neck than in pBCC on the trunk (90% vs. 45%, respectively, P < 0001). In contrast, maple-leaf structures were more commonly found in pBCC on the trunk (65% vs. 40%, P = 011). Overall, slightly pigmented tumours were found under dermoscopy in 39% of sBCCs and 23% of nBCCs, pointing to the more difficult-to-treat tumours. In conclusion, dermoscopy can accurately distinguish the clinical subtypes of BCC. Also, the detection of pigmented structures in clinically nonpigmented sBCC and nBCC could provide additional information that together can possibly guide treatment decisions as described recently.

017 Multicentre study evaluating the sensitivity and specificity of optical coherence tomography for the diagnosis of basal cell carcinoma M. Ulrich,1 T. Maier,2 H. Kurzen,3 T. Dirschka,4 C. Kellner,5 E. Sattler,2 C. Berking,2 J. Welzel6 and Uwe Reinhold5 1

Dermatologie am Regierungsviertel/CMB Collegium Medicum Berlin, Berlin, Germany, 2Ludwig-Maximilians-University, Munich, Germany, 3 Hautarztpraxis, Freising, Germany, 4Praxis Prof Thomas Dirschka, Wuppertal, Germany, 5Dermatology Center Bonn Friedensplatz, Bonn, Germany and 6Department for Dermatology and Allergology, General Hospital Augsburg, Augsburg, Germany Basal cell carcinoma (BCC) represents the most common cutaneous neoplasm, and in early stages a diagnosis may be difficult to obtain (Flohil SC, Seubring I, van Rossum MM et al. Trends in basal cell carcinoma incidence rates: a 37-year Dutch observational study. J Invest Dermatol 2013; 133: 913– 18). As noninvasive therapies become more common for superficial lesions, noninvasive diagnostic techniques are increasingly required (Lallas A, Tzellos T, Kyrgidis A et al. Accuracy of dermoscopic criteria for discriminating superficial from other subtypes of basal cell carcinoma. J Am Acad Dermatol 2014; 70: 303–11). The aim of this study was to investigate the diagnostic value of optical coherence tomography (OCT) for BCC in a typical clinical setting (Banzhaf CA, Themstrup L, Ring HC et al. Optical coherence tomography imaging of nonmelanoma skin cancer undergoing imiquimod therapy. Skin Res Technol 2014; 20: 170–6; Mogensen M, Joergensen TM, Nuernberg BM et al. Assessment of optical coherence tomography imaging in the diagnosis of non-melanoma skin cancer and British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

benign lesions vs. normal skin: observer-blinded evaluation by dermatologists and pathologists. Dermatol Surg 2009; 35: 965– 72; Olmedo JM, Warschaw KE, Schmitt JM, Swanson DL. Optical coherence tomography for the characterization of basal cell carcinoma in vivo: a pilot study. J Am Acad Dermatol 2006; 55: 408–12). In this prospective study, consecutive patients with suspicious erythematous plaques or lesions underwent clinical assessment, dermoscopy and OCT with the diagnosis recorded at each stage. Once all diagnoses had been recorded, the results of the histological diagnosis were made known. The primary efficacy end point was a diagnosis of BCC for each lesion. Secondary end points were the diagnosis of other possible conditions. In total 164 patients with 256 lesions were recruited. Histology was missing for 21 lesions, leaving 235 lesions for analysis. Overall 60% of lesions (141/235) were identified through histology as BCC. The sensitivity increased from 900% as a result of clinical assessment alone, through 906% in combination with dermoscopy to 957% following OCT assessment. The specificity increased significantly from 286% for clinical assessment, through 543% after dermoscopy to 753% following OCT. The positive predictive value for diagnosis of BCC using OCT was 852%; the negative predictive value was 921%. The diagnostic accuracy for all lesions increased from 658% with clinical evaluation through 762% with dermoscopy to 874% with the addition of OCT.

018 Subtyping basal cell carcinoma by clinical diagnosis vs. punch biopsy M. Roozeboom,1 H. Kreukels,2 P. Nelemans,3 K. Mosterd,1 V. Winnepenninckx,4 M.A. Hamid,4 E. de Haas2 and N. Kelleners-Smeets1 1

Department of Dermatology, Maastricht University Medical Center, Maastricht, the Netherlands, 2Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands, 3Department of Epidemiology and 4 Department of Pathology, Maastricht University Medical Center, Maastricht, the Netherlands International guidelines on diagnosis and treatment of basal cell carcinoma (BCC) stipulate that biopsy of clinically suspected BCC prior to treatment is necessary to confirm diagnosis and identify the most aggressive histological subtype. Depending on BCC subtype (superficial, nodular or aggressive), physicians can choose a noninvasive treatment, standard surgical excision or Mohs’ micrographic surgery. However, the difference in diagnostic accuracy for BCC subtyping between punch biopsy and clinical diagnosis has never been evaluated. Previous studies showed that the most aggressive subtype is detected in 84–92% of cases by punch biopsy. Disadvantages of performing a punch biopsy are discomfort for the patient and the associated time and costs. In contrast, clinical diagnosis is a painless and time- and money-saving procedure. Previous studies demonstrated that physicians can differentiate a BCC from other skin diseases with a sensitivity of 64–89%. As treatment options are expanding and several treatments are suitable only for certain subtypes, knowing the © 2014 The Authors BJD © 2014 British Association of Dermatologists

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subtype of BCC is important. The aim of this study was to compare the diagnostic accuracy of subtyping BCC clinically and histologically. The gold standard was the most aggressive histological subtype on the subsequent surgical excision. In addition, we investigated the impact of omitting a punch biopsy on treatment recommendations. In total 152 histologically confirmed primary BCCs in 116 patients were included. BCCs were clinically and histologically divided into three subtypes: superficial, nodular and aggressive. The prevalences of superficial, nodular and aggressive BCC on surgical excision were 16.4% (25/152), 52.0% (79/152) and 31.6% (48/ 152), respectively. The negative predictive value (NPV) to discriminate between nodular/aggressive and superficial BCC was 69% for punch biopsy [95% confidence interval (CI) 56–76] compared with 53% for the clinical diagnosis (95% CI 38– 66). Discrimination between aggressive and nodular BCC showed an NPV of 91% for punch biopsy (95% CI 84–95) compared with 74% for the clinical diagnosis (95% CI 68– 81). The impact of omitting a punch biopsy was calculated by the difference in proportions of over- and understaging between clinical diagnosis and punch biopsy. Clinical diagnosis without subsequent punch biopsy tends to overstage about one in four superficial BCCs as nodular or aggressive and to understage about one in four aggressive BCCs as nodular BCC. In summary, accurate BCC subtyping can help to select an optimal treatment in consultation with the patient. Punch biopsy is more accurate in BCC subtyping than clinical diagnosis. The impact of over- or understaging must be weighed against the extra burden of a punch biopsy.

019 Is clinical examination of basal cell carcinoma a useful method for assessing tumour thickness? E. Christensen1 and O.A. Foss2 1

St. Olav’s University Hospital and Norwegian University of Science and Technology (NTNU), Trondheim, Norway and 2St. Olav’s University Hospital, Trondheim, Norway Tumour thickness can affect the outcome of topical treatments for basal cell carcinoma (BCC) [McKay KM, Sambrano BL, Fox PS et al. Thickness of superficial basal cell carcinoma (sBCC) predicts imiquimod efficacy: a proposal for a thickness-based definition of sBCC. Br J Dermatol 2013; 169: 549–54]. Predicting tumour thickness can be a challenge and may even, with the use of a single punch biopsy, be inaccurate (Christensen E, Mjønes P, Foss OA et al. Pre-treatment evaluation of basal cell carcinoma for photodynamic therapy: comparative measurements of tumour thickness in punch biopsy and excision specimens. Acta Derm Venereol 2011; 91: 651–4). The objective of this study was thus to evaluate whether clinical examination of BCC is a useful method for assessing tumour thickness compared with histology. Prospective evaluation of BCC thickness using clinical and histopathological investigations of individual tumours was performed. From each BCC a clinical estimate of the thickness (in millimetres) was carried out before a punch biopsy and then an elliptical surgical excision were used to provide tissue for histopathological investigation. © 2014 The Authors BJD © 2014 British Association of Dermatologists

The agreements between the corresponding tumour thickness measurements by the clinical and two histopathological methods were analysed using Bland–Altman plots. In total 159 thickness measurements from 53 BCCs were included in the analyses. Tumours were of superficial (n = 14), nodular (n = 24) and aggressive (n = 15) histopathological growth types. The difference between the BCC thickness measurements from the clinical and histopathological examinations was significant, although with an evident relationship between the results of the two methods. Clinical examination overestimated the thickness of thin tumours, mainly of the superficial subtype, and underestimated the thickness of thick tumours of the nodular and aggressive subtypes. In conclusion, there was poor agreement between clinical and histopathological measurements of BCC thickness. The results suggest that biopsy and histopathological measurement of BCC thickness should precede the use of topical therapy.

020 What’s in a name: should keratoacanthomas be treated as squamous cell carcinomas? A long-term follow-up study of 62 patients with keratoacanthoma A. Molina,1 Z. Jiyad,2 V. Akhras2 and B. Powell1 1

Department of Plastic Surgery and 2Department of Dermatology, St George’s Hospital, London, U.K. The most recent standards published by the Royal College of Pathologists suggest that keratoacanthomas should be reported not as a distinct entity but as keratoacanthoma-type squamous cell carcinomas [Slater D, Walsh M. Standards and datasets for reporting cancers. Available at: Resources/RCPath/Migrated%20Resources/Documents/G/G124 _DatasetSquamous_Dec12.pdf (last accessed 15 May 2014)]. This has significant implications for patient follow-up and counselling. As there are few long-term studies of keratoacanthoma outcomes in existence, we decided to carry out a retrospective audit of patients who were diagnosed with keratoacanthoma between 2006 and 2012 to evaluate whether there is in fact a risk of recurrence. In total 62 patients were surveyed by telephone and their electronic medical records and histopathology reports were consulted. There were 29 male and 33 female patients, with a mean age at diagnosis of 705 years. Most patients were treated by excision, but eight had curettage and cautery. All had high scar satisfaction (mean 9/10 on a Likert scale). Classic signs of regression and/or involution were seen in 19 cases histologically. Importantly, with a follow-up time of at least 2 years, but up to 7 years, there were no recurrences or need for further treatment within our cohort. We question the need to manage keratoacanthomas as squamous cell carcinomas. Typically, a 2-year follow-up period, discussion in a skin cancer multidisciplinary team and the involvement of a specialist nurse or key worker would be required – all of which have significant cost implications in the current financial climate. With no evidence of a significant recurrence rate following a diagnosis of keratoacanthoma, can this be justified? British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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021 Pharmacodynamics of ingenol mebutate 005% gel assessed by histology show an immediate immune reaction in actinic fields S. Emmert,1 H.A. Haenssle,1 J.R. Zibert,2 M. Schon,1 T. Litman,2 A. Hald,2 M.H. Hansen,2 M.L. Oesterdal2 and M.P. Schon1 1

Department of Dermatology, Venereology and Allergology, Georg August University, Goettingen, Germany and 2LEO Pharma A/S, Ballerup, Denmark Ingenol mebutate (IMB) is a protein kinase C (PKC) activator inducing immune modulatory actions. In studies with tumour-bearing mice, topical application of IMB resulted in an immune response characterized by infiltration of mainly neutrophils and induction of cell death (necrosis). The aim of this study was to investigate the pharmacodynamics of IMB gel in paired 25-cm2 areas with actinic keratosis (AK)-containing or referenced sun-protected normal skin (RS). In total 27 patients with two to five typical AK lesions within a 25-cm2 area on the forearm, and a 25-cm2 area of RS on the inner upper arm suitable for biopsy were included. IMB 005% gel was applied to the treatment areas once daily on two consecutive days. A total of five biopsies per patient were obtained from one AK lesion outside the forearm treatment area at day 0 (baseline), two AK lesions within this area at days 2 (during) and 3 (after treatment), and from RS outside the upper-arm treatment area at day 0 (baseline) and day 3 (after treatment). The primary outcome measures were degree of leucocyte infiltration and necrosis in the biopsies. The secondary outcome measures included markers for inflammation, apoptosis and endothelium activation, and mRNA and microRNA expression profiles. Data on the patients (all white, mainly Fitzpatrick skin type II, mean age 738 years, mean duration of AK 50 years) showed surprisingly, after just 2 days of treatment, a strong inflammatory response in AK lesions and less in RS. This included substantial infiltration of T cells (in particular CD4+ T cells in the papillary dermis and CD8+ T cells in the epidermis), neutrophils (abundant in intraepidermal pustules) and macrophages, and intracellular adhesion molecule-1 expression on the vascular endothelium. IMB gel induced epidermal cell death (necrosis and apoptosis) in AK lesions and less in RS. In addition, IMB gel had an effect on the expression of numerous genes, both in RS and in AK lesions. The functional annotation of the common differentially expressed genes revealed inflammatory responses, and response to wounding and wound healing. In treated AK lesions compared with AKs at baseline, genes involved in epidermal development and proliferation were downregulated. In conclusion, 2 days of IMB 005% gel treatment induced an immediate immune reaction, characterized with among other cells CD4/8+ T cells, indicating PKC-activation dependent, immune-mediated effects and cell death in actinic fields harbouring tumour and aberrant cells.

British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

022 Ingenol mebutate gel 005% is efficacious in treating subclinical actinic keratoses in a field with cancerization: assessment by reflectance confocal microscopy €wert-Huber,1 M. Ulrich,1 S. Lange-Asschenfeldt,1 J. Ro 1 2 €lker-Call, M.L. Oesterdal, K. Skak,2 M. Vo J.R. Zibert2 and E. Stockfleth1 1

Klinik f€ur Dermatologie, Venerologie und Allergologie, Charite Universit€atsmedizin, Berlin, Germany and 2LEO Pharma A/S, Ballerup, Denmark Reflectance confocal microscopy (RCM) allows noninvasive imaging and monitoring of skin lesions at near histological resolution. Ingenol mebutate gel is a 2–3-day topical treatment for actinic keratosis (AK) in a field. RCM was used to assess the effects of ingenol mebutate gel and vehicle gel in AK and subclinical AK (SC-AK) (clinical trial ID NCT01449513). In total, 24 patients with actinic field cancerization on the hands and forearms were included. To avoid unforeseen issues with the feasibility of the RCM assessments, two stages of the study were implemented: a first stage of patients (n = 8) received treatment with ingenol mebutate gel 005% alone, and a second stage of patients (n = 16) was randomized (1 : 1) to either ingenol mebutate gel 005% or vehicle gel. Treatment was applied on two consecutive days on a 25-cm2 area located on field-cancerized skin. RCM was used to identify three AK and three SC-AK lesions, of which one AK and one SC-AK lesion were selected for biopsy after treatment (day 3); thus two of each lesion type remained for follow-up to day 57. Two assessors independently evaluated the RCM results. All patients treated with ingenol mebutate gel 005% (n = 16) showed a local skin reaction with a mean composite score of 61 out of a maximum of 24, including erythema (100%), flaking/scaling (100%), crusting (88%), vesiculation/pustulation (88%), swelling (62%) and erosion/ ulceration (44%), all of which resolved by the end of the trial. Based on a clinical assessment, the local complete clearance of AKs in the field was 14 of 32 AK lesions with ingenol mebutate gel, and one of 16 with vehicle gel. Based on RCM-visualized honeycomb grading, assessed by the two assessors [primary (secondary) assessor], ingenol mebutate gel completely cleared 11 (nine) of 32 AK lesions and 23 (18) of 32 SC-AK lesions on day 57. This is the first study that has assessed the ability of ingenol mebutate gel to clear subclinical lesions in the treatment field. Ingenol mebutate gel represents a novel effective treatment for actinic field cancerization, showing pronounced effect in AK and SC-AKs.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

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023 Assessment of the in vivo effects of ingenol mebutate 005% gel for the treatment of actinic field cancerization by reflectance confocal microscopy €wert-Huber,1 M. Ulrich,1 S. Lange-Asschenfeldt,1 J. Ro 1 1 €lker-Call, M.L. Oesterdal, K. Skak,2 M. Vo J.R. Zibert2 and E. Stockfleth1 1

Klinik f€ur Dermatologie, Venerologie und Allergologie, Charite Universit€atsmedizin, Berlin, Germany and 2LEO Pharma A/S, Ballerup, Denmark In this study we aimed to use reflectance confocal microscopy (RCM), a novel, noninvasive imaging technique, to assess the in vivo biological effects of ingenol mebutate gel in actinic keratosis (AK) and subclinical AK (SC-AK) and to compare the results with the response in normal aged reference skin and with treatment with placebo. In total 24 patients with actinic field cancerization and a minimum of three AKs on the hands and forearms were included in the study. The first group of eight patients received treatment with ingenol mebutate gel, whereas the second group of 16 patients was randomized (1 : 1) to either ingenol mebutate gel or placebo. Patients receive treatment on two consecutive days (day 1 and 2) on two 25-cm2 areas, the first located on the dorsum manus or forearms and the second on nonsun-exposed skin on the volar upper arm. Within the 25-cm2 field, RCM was used to identify three SC-AKs showing cellular atypia but lacking clinical signs of AK. RCM evaluation was carried out on all seven sites (three AKs, three SC-AKs and one reference skin site) on days 1, 2, 3, 8 and 57. Clinical photographs were taken at each visit, and a biopsy for histological evaluation was obtained from one AK and one SC-AK at day 3. Local skin reactions (LSRs) to ingenol mebutate occurred in all patients, and were milder and resolved faster in reference skin than in actinic fields. The LSRs varied clinically from erythema, vesicle formation and pustules to erosion and crusting. On RCM, keratinocytic cell death with acantholysis and microvesicle formation could be visualized along with infiltration with inflammatory cells. RCM was applicable for monitoring the in vivo changes occurring after application of ingenol mebutate, although severe inflammation and oedema in combination with technically limited penetration depth interfered with the evaluation of dermal layers. The reaction to ingenol mebutate was more pronounced in AK and SC-AK than in reference skin, both clinically and on RCM. In reference skin, necrosis and microvesicle formation were localized mainly around hair follicles, suggesting follicular penetration of ingenol mebutate. These findings relate well to the clinical observation of small vesicles in a follicular distribution. In AK, RCM showed widespread necrosis with microvesicles and inflammatory cells, corresponding clinically to confluent pustules. Ingenol mebutate represents a novel, effective treatment for actinic field cancerization, showing pronounced response in AKs and SC-AKs compared with reference skin.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

024 Stage I mycosis fungoides: frequent association with a favourable prognosis but disease progression and disease-specific mortality may occur A. Wernham, F. Shah, R. Amel-Kashipaz, M. Cobbold and J. Scarisbrick University Hospitals Birmingham NHS Foundation Trust, Birmingham, U.K. Mycosis fungoides (MF) is the most prevalent form of primary cutaneous T-cell lymphoma, characterized by a monoclonal proliferation of CD4+ neoplastic T cells infiltrating the skin. The majority of patients with early-stage disease (IA–IIA) have an excellent outcome. Stage IA patients (< 10% body surface area involved) have a near-normal life expectancy. However, 25% of patients with stage I disease will progress to advanced stages (IIB, tumours; III, erythroderma; IV, nodal disease). Specific features previously shown to be associated with stage I progression include increasing age, male sex, plaques and enlarged lymph nodes [Benton EC, Crichton S, Talpur R et al. A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sezary syndrome. Eur J Cancer 2013; 49: 2859–68]. Patients with early-stage MF at diagnosis were identified from our cutaneous lymphoma database. Data collected included patient demographics, stage at diagnosis, stage progression, and clinical, haematological, immunohistochemical and genotypic features. In total 84 patients were identified, including 46 men and 38 women (ratio 12 : 1); the mean length of follow-up was 87 months (range 5–424, median 59). Overall 36 patients had stage IA disease, 48 stage IB (> 10% patches/plaques) and none IIA (patches/plaques plus dermopathic lymphadenopathy). The mean age at diagnosis was 58 years. Twenty-eight patients had stage progression (33%). Patients with stage progression were older at diagnosis (54 vs. 49 years), and 16 of 46 (35%) men and 12 of 38 (32%) women progressed. Plaques were more frequent at presentation in the progressed group, while features of poikiloderma and hypopigmentation featured less frequently. There were five deaths, three from MF and two from other causes. The overall survival was 94%, 5-year survival 96% and disease-specific survival 96%. In total 14 of 36 (39%) stage IA patients progressed (seven to IB, two to IIA, four to IIB and one to IVA). The mean time to progression was 85 months. There were two lymphoma deaths, both with progression from stage IA to IIB: one at just 26 months and one at 390 months after diagnosis. Overall 14 of 46 (30%) stage IB patients had stage progression (one to IIA, nine to IIB, two to III and two to IVA). The mean time to progression was 52 months. There was one lymphoma death in this group at 21 months after diagnosis. One-third of patients with earlystage MF had stage progression. This is higher than expected but may reflect referral patterns to a supraregional centre with more patients with progressive than early stable disease. Increasing age at diagnosis and male sex were both associated with stage progression. These data highlight the need for follow-up in early-stage disease and confirm that a small number of patients with stage I disease have poor survival (< 5 years). British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

12 WCCS Abstracts

025 Unique presentation of refractory leukaemic cutaneous CD3/T-cell receptor-negative phenotype T-cell lymphoma with complete remission after allogeneic stem cell transplantation H. Sanli,1 B.N. Akay,1 S. Saral,1 P. Topcuoglu2 and A.O. Heper3 1

Department of Dermatology, 2Department of Hematology and 3Department of Pathology, Ankara University Medical Faculty, Ankara, Turkey Sezary syndrome (SS) is the leukaemic form of mycosis fungoides (MF), manifesting usually with erythroderma. SS presenting with distinct skin lesions may be related to aberrant surface phenotypes. We herein report a case of SS presenting with ichthyosiform skin lesions histopathologically showing leukaemic cutaneous CD3/T-cell receptor (TCR) phenotype T-cell lymphoma with CD30+ large-cell transformation from MF with a unique presentation. A 49-year-old man was admitted to our department with a 3-year history of xerosis, crusting and ichthyosiform lesions involving his extremities and trunk. Histopathology of skin biopsy specimens with haematoxylin and eosin stains showed superficial and deep dermal nodular and dense lymphoidal cellular infiltration. All of the lymphoidal cells were CD3+CD20 CD7 . CD4 expression was observed in most of the cells. There were also numerous large, anaplastic cells, positive with CD30+ among the lymphoid infiltrate. Complete blood count work-out revealed 61 500 leucocytes (lymphocytes 37%, neutrophils 6%, eosinophils 37%, monocytes 6%, Sezary cells 15%). Flow cytometric analysis of the peripheral blood revealed T cells lacking CD3 and TCR expression, and 90% of T helper lymphocytes were CD4+CD7 without loss of CD26 expression. The beta2 microglobulin level was 98 mg dL 1 (normal range 109– 253 mg dL 1). The serum lactate dehydrogenase level was elevated at 453 U L 1 (normal range 125–220 U L 1). On the basis of these findings, a diagnosis of CD3/TCR MF with large-cell transformation and SS with ichthyosiform lesions was made. The disease was resistant to combination therapies with extracorporeal photopheresis, interferon-a and psoralen– ultraviolet A. The patient had undergone allogeneic haematopoietic stem cell transplantation that resulted complete response, and he is still under remission 2 years after transplantation.

026 Folliculotropic mycosis fungoides: a distinct clinicopathological variant frequently showing resistance to skin-directed therapy necessitating consecutive systemic treatments R. Bhutani, F. Shah, B. Vydianath, R. AmezKashipaz, M. Cobbold, S. Chaganti, R. Grieve, A. Stevens and J. Scarisbrick Queen Elizabeth Hospital, University Hospitals Birmingham NHS Trust, Birmingham, U.K. Folliculotropic mycosis fungoides (FMF) is a rare, distinct variant of cutaneous T-cell lymphoma identified in the European Organisation for Research and Treatment of Cancer/World

British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

Health Organization classification. FMF has characteristic clinical features such as milia, comedones and alopecia and histological features of folliculotropism, but neither has a universal definition. FMF may have an aggressive course, with patients with widespread plaques (stage IB) having a similar outcome to patients with tumour-stage mycosis fungoides (MF) (stage IIB), and a median survival of 3–5 years. All patients with histological evidence of folliculotropism and mycosis fungoides were identified from the Cutaneous Lymphoma Database (Gerami P, Guitart J. Spectrum of histopathologic and immunohistochemical findings in folliculotropic mycosis fungoides. Am J Surg Pathol 2007; 31: 1430–8). The age and stage at diagnosis were recorded along with clinical features of FMF, distribution of lesions, symptoms such as pruritus, treatments and outcome. Twenty-one patients (15 male, six female) were identified with a mean age at diagnosis of 52 years. Fourteen patients (67%) presented with early (stage I) disease consisting of patches and/or plaques (stage IA, n = 8; IB, n = 6) and seven presented with advanced disease: four tumour stage (IIB), two erythrodermic (III) and one with lymph node involvement (stage IVA). Ten of 14 patients (71%) with early-stage disease had plaques, and six of seven (86%) with advanced stages of disease had tumours at presentation. Pruritus was the prominent symptom at presentation (76%, n = 16). Alopecia was noted in 24% (n = 5) and comedones/ milia in only two patients (10%). Most patients (90%) had involvement of the trunk and 66% had lesions on the head or neck. Patient selection included all those with a histological diagnosis of FMF (Gerami and Guitart). Additional histological features included mucinous degeneration (33%, n = 7), epidermotropism (52%, n = 11) and syringotropism (24%, n = 5); 14% (n = 3) had large-cell transformation. The firstline treatment was topical steroids/expectant in 24% (n = 5), phototherapy in 48% (n = 10), radiotherapy in 24% (n = 5) and systemic therapy in one (stage IVA). Subsequently 67% (n = 14) had phototherapy, 52% (n = 11) had localized radiotherapy, 14% (n = 3) had total-skin electron beam therapy and 67% (n = 14) received systemic therapies (mean 26 therapies, range 1–5). Two patients have been successfully treated with bone marrow transplantation. The mean followup time was 46 months, and five of 14 patients (36%) with early-stage disease progressed during follow-up, including 29% to advanced disease. Two patients died from their disease. The age, sex ratio and stage at diagnosis were similar in this FMF cohort to patients with classical MF. Overall 36% progressed during a mean follow-up of < 4 years. Two-thirds required systemic therapies including 40% with stage I disease. Multiple systemic therapies were often required and 10% had bone marrow transplantation. This study shows a high rate of resistance to skin-directed therapy and the need for multiple consecutive systemic therapies. Successful management of FMF may require more aggressive therapy than for classical MF.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 13

027 (PL02) Turning the tide? Declining rates for keratinocyte cancers among people aged < 45 years in Australia, 2000–11 C. Olsen,1 P. Williams2 and D. Whiteman1 1

QIMR Berghofer Medical Research Institute, Brisbane, Australia and Virginia Commonwealth University, Richmond, VA, U.S.A. Keratinocyte cancers [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] are by far the most common cancers in humans, and their diagnosis and management imposes substantial costs on health systems (Fransen M, Karahalios A, Sharma N et al. Non-melanoma skin cancer in Australia. Med J Aust 2012; 197: 565–8). Population data on incidence trends are scant because few jurisdictions reliably record diagnoses or treatments (Jensen AØ, Olesen AB, Dethlefsen C, Sørensen HT. Do incident and new subsequent cases of non-melanoma skin cancer registered in a Danish prospective cohort study have different 10-year mortality? Cancer Detect Prev 2007; 31: 352–8; Stefoski Mikeljevic J, Johnston C, Adamson PJ et al. How complete has skin cancer registration been in the U.K.? A study from Yorkshire. Eur J Cancer Prev 2003; 12: 125–33). We derived recent trends for keratinocyte cancer for the Australian population from 2000 to 2011 using billing data from Medicare Australia. Medicare Australia is the universal health insurance scheme, which is estimated to capture 98% of clinical interactions relating to the diagnosis and management of skin cancer in Australia. Specifically, we captured data for the eight billing codes relating to first surgical excisions of histologically confirmed BCC or SCC, the 24 codes for treatment of residual/recurrent SCC/BCC and the five codes used for other treatments for BCC/SCC (including cryotherapy, curettage etc.). For each procedure, we examined counts, rates and the average annual percentage rate of change over the study interval. Overall, there were sizeable and statistically significant increases in excision rates for keratinocyte cancers [33% per annum (p.a.) for men and 22% p.a. for women]; however, temporal trends differed significantly by age group. For men and women aged < 45 years, we observed significant declines in diagnostic and treatment procedures for keratinocyte cancers. Rates of first-time surgical excision declined from 1040 per 100 000 persons in the year 2000 to 953 per 100 000 persons in 2011, an average decrease of 13% p.a. (P = 0004). In contrast, there were substantial increases in rates of keratinocyte cancer treatments in all older age groups. Rates of increase were highest for men aged 75–84 years (86% p.a.). Of note, biopsy rates for nonmalignant lesions increased substantially in all age groups over the study period (80% p.a. for men and 73% p.a. for women), suggesting no lessening in surveillance for suspicious skin lesions in any age group. In summary, while overall treatment rates for keratinocyte cancers have increased substantially during the past decade, excision rates for keratinocyte cancers are falling in younger Australians. Taken together, these data strongly suggest that primary prevention campaigns initiated in Australia in the 1990s are now beginning to show their effects within the subgroups of the population most likely to benefit. Con2

© 2014 The Authors BJD © 2014 British Association of Dermatologists

tinued monitoring of keratinocyte cancer rates will determine whether these declines are sustained into the future.

028 (PL04) MC1R gene variants and nonmelanoma skin cancer: a pooled analysis from the M-SKIP project E. Tagliabue,1 M.C. Fargnoli,2 S. Gandini,1 P. Maisonneuve,1 M. Kayser,3 J. Han,4 R. Kumar,5 N. Gruis,6 W. Branicki,7 T. Dwyer,8 L. Blizzard,9 n,12 P. Helsing,10 P. Autier,11 J. Garcıa-Borro 13 14 15 P. Kanetsky, M.T. Landi, J. Little, J. NewtonBishop,16 F. Sera17 and S. Raimondi1 1

European Institute of Oncology, Milan, Italy, 2University of L’Aquila, L’Aquila, Italy, 3Erasmus MC University Medical Center, Rotterdam, the Netherlands, 4Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, U.S.A., 5German Cancer Research Center, Heidelberg, Germany, 6 Leiden University Medical Center, Leiden, the Netherlands, 7Institute of Forensic Research, Krakow, Poland, 8Murdoch Children’s Research Institute, Royal Children’s Hospital, Victoria, Australia, 9Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia, 10Oslo University Hospital, Oslo, Norway, 11International Prevention Research Institute, Lyon, France, 12University of Murcia, Murcia, Spain, 13Moffitt Cancer Center, Tampa, FL, U.S.A., 14National Cancer Institute, NIH, Bethesda, MD, U.S.A., 15University of Ottawa, Ottawa, Canada, 16Institute of Cancer and Pathology, University of Leeds, Leeds, U.K. and 17UCL Institute of Child Health, London, U.K. The melanocortin 1 receptor gene (MC1R) is involved in the genetics of human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between specific and combined MC1R variants and the risk of nonmelanoma skin cancer (NMSC), and to evaluate whether risk estimates differ by phenotypic characteristics. Data were gathered through the M-SKIP project, an international pooled analysis on MC1R variants, skin cancer and phenotypic characteristics. For the present study, we included data on 2211 cases of basal cell carcinoma (BCC), 788 cases of squamous cell carcinoma (SCC), 152 cases of both BCC and SCC and 9008 controls. We performed a two-stage analysis with random effect models, and stratified analyses to evaluate the association of single and combined MC1R variants with NMSC development. All the analyses are adjusted, if available, for age, sex, intermittent and chronic sun exposure, lifetime and childhood sunburns, and smoking status. We observed a significant association with BCC for five MC1R variants: V60L, D84E, R151C, R160W and D294H, and with SCC for six MC1R variants: V60L, V92M, R151C, I155T, R160W and D294H. Considering NMSC overall, we observed a significant association for all variants except R142H and I155T. When we analysed MC1R variants combined, we found that subjects carrying at least one MC1R variant had an increased risk of BCC, SCC and NMSC overall. The summary odds ratios (SORs) with 95% confidence intervals (CIs) were, respectively, 131 (110–196), 161 (135–191) and 141 (120–167). When we assigned a score to each subject according to the number of R and r alleles, we observed a significant linear trend for each point increase in MC1R score British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

14 WCCS Abstracts

for BCC, SCC and NMSC overall: the per-point SORs (95% CIs) were 118 (108–129), 128 (117–141) and 122 (112–133), respectively. In the stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair or without freckles. The difference between the SORs for subjects with or without red hair was statistically significant for both SCC and NMSC overall (P = 001 and 005, respectively). In conclusion, our pooled analysis provided evidence for a role of MC1R variants in both BCC and SCC development. We also suggest that the role of MC1R variants in NMSC may be modified by the red hair colour phenotype.

029 (PL07) Risk of melanoma is increased in people with HIV/ AIDS in the posthighly active antiretroviral therapy era C. Olsen, L. Knight and A. Green QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia Following the introduction of highly active antiretroviral therapy (HAART) the risk of AIDS-defining cancers has decreased, but the incidence of many non-AIDS-defining cancers has reportedly increased in those with HIV/AIDS (Long JL, Engels EA, Moore RD, Gebo KA. Incidence and outcomes of malignancy in the HAART era in an urban cohort of HIV-infected individuals. AIDS 2008; 22: 489–96). Whether melanoma risk has also changed in patients with HIV/AIDS post-HAART is unknown. It is important to quantify this risk given the increased longevity of patients treated with HAART (Palella FJ Jr, Delaney KN, Moorman AC et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338: 853–60) and the consequent increased period at risk of melanoma against a background of rising rates in most white populations (Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013; 49: 1374–403). It is also important to understand better the association between HIV and melanoma, as laboratory studies have indicated a role for immune surveillance in melanoma genesis, and increasingly immunotherapeutic approaches for the treatment of metastatic disease are being developed (Cebon J, Gedye C, John T, Davis ID. Immunotherapy of advanced or metastatic melanoma. Clin Adv Hematol Oncol 2007; 5: 994–1006). We conducted a systematic review and meta-analysis to evaluate melanoma risk in patients with HIV/ AIDS compared with the general population in the pre-HAART and post-HAART eras. We searched the Medline, Embase and Web of Science citation index databases to April 2013. All cohort studies of patients diagnosed with HIV/AIDS that permitted quantitative assessment of the association with melanoma were eligible. Detailed quality assessment of eligible studies was conducted, focusing particularly on adjustment for ethnicity, a priori considered essential for an unbiased assessment of melanoma risk. Data were pooled using a random British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

effects model. From 288 articles, we identified 21 that met the inclusion criteria, 13 presenting data for the post-HAART era and eight for the pre-HAART era. Post-HAART, the pooled relative risk (pRR) for the association between HIV/AIDS and melanoma was 126 [95% confidence interval (CI) 097– 164] and 146 (95% CI 123–172) among studies that accounted for ethnicity, with evidence of significant heterogeneity (P = 0004, I2 = 555). Pre-HAART pRRs were 126 (95% CI 111–143; Phet = 082) and 128 (95% CI 110– 149) among studies adjusted for ethnicity. People with HIV/ AIDS remain at a significantly increased risk of developing melanoma in the post-HAART era. White-skinned people with HIV/AIDS would benefit from regular screening of the skin for suspicious pigmented lesions and they should be counselled to avoid excessive sun exposure.

030 (PP06) Quality of life and knowledge about sun exposure of patients with actinic keratosis: PIQA study preliminary results n,1 S. Arias-Santiago,2 J.L. Artola,3 C. Serra-Guille ndez -Guarino,5 J.L. Lo pezE. de las Heras,4 M. Ferna nchez-Aguilar,8 Estebaranz,6 L. Martınez,7 D. Sa A. Toll9 and I. Longo10 1

Instituto Valenciano de Oncologıa, Valencia, Spain, 2Hospital Virgen de las Nieves, Granada, Spain, 3Hospital Galdakao, Bilbao, Spain, 4Hospital Ramon y Cajal, Madrid, Spain, 5Hospital Central de la Cruz Roja, Madrid, Spain, 6 Fundacion Hospital Alcorcon, Madrid, Spain, 7Hospital Carlos Haya, Malaga, Spain, 8Hospital Clınico, Santiago de Compostela, Spain, 9Hospital del Mar, Barcelona, Spain and 10Hospital Central de la Defensa Gomez Ulla, Madrid, Spain Actinic keratosis (AK) is a highly prevalent condition with frequent recurrences. Therefore, it is important to assess its impact on the quality of life (QoL) in order to evaluate the outcome of available interventions, among other purposes. We conducted a prospective observational study of patients with AK treated and followed up by 200 Spanish dermatologists (PIQA study). Data from patients’ knowledge and beliefs were assessed through a generic seven-item questionnaire; QoL was evaluated with the Actinic Keratosis Quality of Life Scale (AKQoL). This is a translated and under-validation version of the Danish questionnaire for AK evaluation that has three main domains: function (attitude towards sun exposure), emotions and control of life. Comparisons of AKQoL total score and domain scores, related to patients’ knowledge on sun protection, were performed with a one-way ANOVA test. In total 128 patients with AK with a median age of 76 years were included in the analysis (683% male, 317% female); roughly 40% reported elementary-school education. More than 75% were receiving treatment for a chronic condition. The most frequently described phototypes were II (488%) and III (341%). The mean AKQoL total score was 61  47, while the domain scores were 20  15 for function, 24  21 for emotions and 13  13 for control of life. Overall, patients who had been previously treated for AK (488%) reported a higher total QoL score (worse quality of © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 15

life) (75  49 vs. 48  42, P = 0004), likewise for function (24  15 vs. 17  15, P = 0014) and emotions (29  21 vs. 19  20, P = 0009). Those who perform skin ‘self-examination’ obtained higher total (76  43 vs. 53  48, P = 0019) and control of life scores (17  14 vs. 10  12, P = 0005). Patients who considered AK as a reason for consultation ‘because it is a disease’ obtained significantly higher total scores (79  48 vs. 51  45, P = 0005) and also higher scores for function (24  15 vs. 18  15, P = 0031) and emotions (31  22 vs. 19  20, P = 0003). Categorizing the item ‘creams and lotions can prevent skin ageing’ as false was associated with lower scores (total: 32  32 vs. 65  48, P = 0021; function: 12  10 vs. 21  16, P = 0038 and control: 04  08 vs. 14  13, P = 0006). In conclusion, the presence of AK along with patients’ knowledge and beliefs regarding sun exposure can significantly impact patients’ QoL. An increased concern about the disease as reflected by reason for consultation and performing self-skin examination negatively impairs QoL. Therefore, educational strategies are necessary to decrease the negative impact of disease concern.

031 (PP12) More people die from thin melanomas than thick melanomas in Queensland, Australia: implications for screening? D. Whiteman and C. Olsen QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia Melanoma incidence has been rising steadily in fair-skinned populations around the world, with most of the increase due to greater numbers of thin lesions being diagnosed (Coory M, Baade P, Aitken J et al. Trends for in situ and invasive melanoma in Queensland, Australia, 1982–2002. Cancer Causes Control 2006; 17: 21–7; Welch HG, Woloshin S, Schwartz LM. Skin biopsy rates and incidence of melanoma: population based ecological study. BMJ 2005; 331: 481). Melanoma mortality has also been rising, albeit much less quickly than incidence (Welch et al.). There is a perception that most people who die from cutaneous melanoma present initially with thick melanomas. However, the veracity of this proposition has never been tested, as population-based data describing total mortality by the thickness of the primary tumour are scarce. We therefore analysed the characteristics of all 4218 persons who died in the state of Queensland, Australia between 1990 and 2009 inclusive for whom the cause of death was ‘melanoma’. We requested linked histology and death data from the state cancer registry (notification of melanoma has been compulsory since 1982) to examine mortality rates according to the thickness of the primary lesion. We also calculated the annual percentage change (APC) in mortality rates. Overall, melanoma mortality was stable for men [APC 04%, 95% confidence interval (CI) 06 to 14%) and women (APC 00%, 95% CI 10 to 09%) over the 20-year interval; however, there were marked changes in mortality rates by thickness category. During the period 1990–2009, mortality from thin melanomas (< 1 mm) increased rapidly in men (APC 30%) and women (APC 25%). In contrast, mortality from thick © 2014 The Authors BJD © 2014 British Association of Dermatologists

melanomas (≥ 4 mm) increased only modestly, and mortality rates from patients presenting initially with metastatic disease declined significantly in men and women (APC 27% and APC 20%, respectively). In the most recent period (2005–09), more Queensland residents died from thin melanomas (268 deaths, 205% of all melanoma deaths) than from thick melanomas (216 deaths, 165%). The numbers of deaths attributable to melanoma in the intermediate thickness categories were higher for lesions of thickness 1–19 mm (n = 300, 230%) than 20–29 mm (n = 237, 182%). Approximately 10% of patients who died from melanoma had multiple primary lesions (76%, two primaries; 26%, more than two). The patterns of mortality were unchanged when we restricted the analyses to those with only one primary melanoma. The proportion of deaths attributable to thin melanomas has been increasing steadily in Queensland, in conjunction with a rising incidence of thin melanomas. These long-term data suggest that primary prevention should remain the principal strategy for melanoma control, as thin lesions still confer substantial mortality in populations where the incidence is high.

032 (PP14) Individualized skin cancer prevention campaigns can attract individuals at high risk A.-S. Sonne Holm, N.K. Curth, P. A. Philipsen and H.C. Wulf Dermatological Research Department D92, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark Regarding risk-related sun behaviour and skin cancer, it is clear that knowledge is not sufficient to generate a behavioural change. It has become a health educational challenge to create prevention campaigns that have a tangible effect on individuals at risk, as they often fail to relate to those intended. Therefore, the objectives of this study were to estimate whether an individualized campaign approach can attract participants most at risk of developing skin cancer, and to use cross-sectional data to examine the association between skin cancer and sun sensitivity, ultraviolet (UV) exposure and intermittent UV exposure. During the summer of 2011, a walk-in bus, located at strategic places, provided the setting for a nationwide individualized skin cancer prevention campaign aimed to attract participants most at risk of developing skin cancer. Participants completed a questionnaire, had a photo of their sunspots on the face taken in black-light and had the sun sensitivity of their skin measured. Staff were available for guidance and interpretation of tests and photos. All analyses were adjusted for age and sex. The campaign was funded by the LEO Foundation. In total 4177 participants completed the questionnaire. Compared with other studies, the present study found a higher prevalence of skin cancer diagnosis, sunburns, sun vacations and solarium use. There was a significant difference in age between individuals with a diagnosis of skin cancer and individuals with no diagnose of skin cancer (P ≤ 0001), but no sex difference (P = 0103). Having high sun sensitivity was a predictor for a history of skin cancer (P = 0022). No British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

16 WCCS Abstracts

significant association between sunburns, use of a solarium or having been on a sun vacation all within the last 12 months, and the probability of skin cancer were found. It is likely that individuals who have been diagnosed with skin cancer change their sun-related behaviour after the diagnosis, but given that the data are cross-sectional they might not be able to show an association. In conclusion, a relatively high proportion of individuals who are at high risk of developing skin cancer visited the bus, including individuals with prior and current skin cancer and high risk sun-behaviour such as using solarium, holidaying at sunny locations and getting sunburns. Thus, the campaign succeeded in attracting participants at elevated risk of developing nonmelanoma skin cancer and cutaneous malignant melanoma, who are otherwise considered difficult to reach.

033 (PP19) Drug reaction with eosinophilia and systemic symptoms with vemurafenib use A. Cardenas, M.L. Munson, W. Aldairy and L.M. Shih Genentech, Inc., a Member of the Roche Group, South San Francisco, CA, U.S.A. Vemurafenib (Zelborafâ) is an orally available selective inhibitor of oncogenic V600-mutant BRAF kinase, and is currently approved for the treatment of adult patients with unresectable or metastatic BRAFV600 mutation-positive melanoma. Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity syndrome characterized by a potentially lifethreatening, multiorgan reaction that can result in a fatal outcome in 10–40% of patients. In most patients, symptoms resolve without sequelae when the drug is discontinued. A wide range of medications, including anticonvulsants, have been associated with DRESS syndrome, and there have been reports of DRESS syndrome in patients using vemurafenib. The incidence rate of DRESS syndrome in vemurafenib-treated patients with malignant melanoma is 2 per 3034 exposures (006%) (Larkin J, Del Vecchio M, Ascierto PA et al. Vemurafenib in BRAFV600 mutant metastatic melanoma: an open-label, multicenter safety study of 3222 patients. Lancet Oncol 2014; 15: 436–44), which is comparable with that of anticonvulsants known to be associated with DRESS syndrome (001– 004%). F. Hoffmann-La Roche, Ltd, sponsored a retrospective review of the Roche global safety database to 12 March 2013, from which 13 cases were identified. Nine patients had DRESS syndrome as the reported event term; four were classified as probable DRESS syndrome. The most frequent clinical manifestations were eosinophilia (100%), rash (92%), hepatic involvement (69%) and fever (62%). Vemurafenib was discontinued or interrupted in 10 of 13 cases; 10 patients had a reported outcome of ‘improved’ or ‘resolved’. Steroid therapy was initiated in eight cases; no treatment details were available for the remaining five cases. We will present three descriptive case reports of patients with melanoma receiving vemurafenib who developed DRESS syndrome, two of whom were able to continue receiving vemurafenib after discontinuation and drug rechallenge at a lower dose. In conclusion, there appears to be British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

a causal association between vemurafenib and DRESS syndrome. As a result of this analysis, DRESS syndrome has been added as an adverse drug reaction in the vemurafenib reference safety information.

034 (PP21) Risk of cutaneous T-cell lymphoma among patients with chronic lymphocytic leukaemia and other subtypes of non-Hodgkin lymphoma T. Chang, A. Weaver, T. Shanafelt, T. Habermann, C. Wriston, J. Cerhan, T. Call and J. Brewer Mayo Clinic, Rochester, MN, U.S.A. Development of second haematological malignancies in patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL) is well documented in diseases including Hodgkin lymphoma, therapy-related acute myeloid leukaemia/myelodysplastic syndromes, and transformation to diffuse large B-cell lymphoma. While rare reports of cutaneous T-cell lymphoma (CTCL) in patients with CLL exist, the prevalence and significance of this association is unknown. We sought to evaluate the incidence of secondary CTCL among CLL and other subtypes of non-Hodgkin lymphoma (NHL) using the Surveillance, Epidemiology, and End Results (SEER) programme. Included in this analysis were patients with CLL and NHL diagnosed between 1992 and 2008 who were reported to 13 SEER registries. Patients with CTCL diagnosed prior to NHL diagnosis or with a concurrent diagnosis of CTCL and NHL within 1 month were excluded. Incidence density estimates for CTCL were subsequently determined in the remaining patients with CLL and NHL. Standardized incidence ratios (SIRs) were constructed by comparing the observed number of cases of CTCL with the expected number in the general U.S. population. Our results included 31 286 patients (243%) with CLL and 97 691 (757%) with other subtypes of NHL. Among patients with CLL, 12 developed CTCL over a median follow-up of 43 years [interquartile range (IQR) 21–77 years]. In other subtypes of NHL, 43 patients developed CTCL over a median follow-up of 32 years (IQR 10–72 years). Among women with CLL, the incidence of CTCL was 281 per 1 million person-years (95% CI 34– 1013), a risk not significantly higher than in the general population (SIR 15, 95% CI 02–55). Among men with CLL, the incidence of CTCL was 1042 per 1 million person-years (95% CI 500–1918) and the risk was significantly higher than expected in the general population (SIR 30, 95% CI 14–55). Among patients with other subtypes of NHL, the incidence of CTCL in female patients was 920 per 1 million person-years (95% CI 562–1421), and 979 per 1 million person-years (95% CI 620–1469) in male patients, both being significantly higher than expected in the general population (SIR women 59, 95% CI 36–91; SIR men 37, 95% CI 23–55). We conclude that the risk of CTCL in men with CLL is significantly greater than in the general population. Men and women with other subtypes of NHL are also at greater risk than in the general population. Future studies will determine whether this increased risk is related to side-effects of © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 17

therapy (e.g. immunosuppression) or shared risk factors (e.g. genetic, environmental, behavioural etc.).

035 (PP22) Cutaneous metastases of leiomyosarcoma D. Winchester, T. Hocker and R. Roenigk Mayo Clinic, Rochester, MN, U.S.A. Leiomyosarcoma is a rare smooth-muscle sarcoma with potential to metastasize, often fatally, to the lungs, liver or brain. However, little is reported of cutaneous metastases of this tumour. Only 15 cases exist in the dermatology literature, all through individual case reports (Vandergriff BA, Krathen RA, Orengo I. Cutaneous metastasis of leiomyosarcoma. Dermatol Surg 2007; 33: 634–7). As a result, important prognostic factors of cutaneous leiomyosarcoma metastases are poorly defined. Our study reports our institution’s experience of 21 cases of cutaneous leiomyosarcoma metastases and compares them with the literature to date. After institutional review board approval, skin biopsies read out by our dermatopathologists as leiomyosarcoma were reviewed, dating from 1965 to 2013. Only leiomyosarcoma skin biopsies with a confirmed primary site other than the metastasis site, confirmed via previous biopsy, were included. The median age for patients with a first leiomyosarcoma skin metastasis was 665 years, and 13 of the 21 patients were female. The median interval between diagnosis of the primary tumour and the development of cutaneous metastasis was 39 months. The median time of survival after diagnosis of cutaneous metastasis was 16 months. Sites on the skin were the location of the primary tumour in 14 of the 21 cases (67%); seven cases originated in other sites of the body, the uterus comprising four of these. The most common location for a first cutaneous metastasis was the scalp, (15of 21, 71%), followed by sites on the trunk, (four of 21, 19%). In 12 cases where internal metastases (lungs, gastrointestinal tract etc.) were confirmed as well, seven cases (58%) had skin metastases diagnosed before the internal metastases were found. Defining a cutaneous leiomyosarcoma as a primary site or a metastasis is a crucial point, as each has drastically different outcomes (Wang WL, Bones-Valentin BS, Prieto VG et al. Sarcoma metastases to the skin. Cancer 2012; 118: 2900–4). In this study, the 16-month median survival time after diagnosis of cutaneous metastasis indicates it as a poor prognostic indicator. While primary leiomyosarcoma of the skin can metastasize, it does not seem to bear the same poor prognosis. This study also shows that the scalp is the most common site of cutaneous metastasis for leiomyosarcoma; the combination of all case reports of cutaneous leiomyosarcoma metastasis shows a similar trend (Vandergriff et al.). We provide new data showing that in cases with internal metastases nearly 60% have a skin metastasis before the internal metastasis is diagnosed.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

036 Melanoma epidemiology in Argentina: incidence in the population aged below 20 years M.C. Latorre,1 F. Moreno,2 M. Larralde,3 F. Stengel,4 A. Pierini,5 A. Cervini5 and D. Loria1 1

RAMC Collaborative Group, Buenos Aires, Argentina, 2ROHA Network, Buenos Aires, Argentina, 3Hospital Aleman, Buenos Aires, Argentina, 4Buenos Aires Skin, Buenos Aires, Argentina and 5Hospital Garraham, Buenos Aires, Argentina According to the last census in Argentina (2010) the population is nearing 40 million, with 35% below 20 years of age (27% aged 0–14 years). Knowledge on the epidemiology of childhood cancer in Latin America is limited. A nationwide childhood cancer registry in Argentina, implemented in the late nineties, is also collecting cancer cases for patients aged 15–19 years. A cutaneous melanoma population-based registry initiated in 2003 is characterizing melanomas, quantifying their incidence and identifying risk populations. Little is known about cutaneous malignant melanoma epidemiology in Argentina. Since 1985, melanoma age-adjusted mortality rates, for all ages, have increased annually by almost 28% in both sexes (2007 rates were male, 13 per 100 000 and female, 09 per 100 000). Cutaneous melanoma in childhood is a rare event. The aim of this study is to describe melanoma incidence and characteristics in children and adolescents in Argentina. Data were obtained from two registries. Breslow thickness was divided into ≤ 100, 101–200, 201–400 and > 400 mm. Incidence rates for patients aged 0–14 years were calculated for 2002–05 and 2006–10, and in 2002 for those aged 15–19 years. Rates are expressed as new cases per million youths and were standardized. Population data were provided by INDEC (National Statistics Institute). We collected 49 melanoma cases in children under15 years and 40 cases in adolescents aged 15–19 years (73% in the 10–19-year age group). In situ lesions formed 12% of cases. Excluding in situ lesions, the Breslow thickness range was 04–100 mm. Both in children and adolescents, localizations differed between sexes. The age-standardized incidence rates for children under 15 years were 054 for 2002–10, 041 for 2002–05 and 063 for 2006–10. The rate ratio for 2006–10 vs. 2002–05 was 15. The age-standardized incidence rate for those aged 15– 19 years in 2002–10 was 13 per 100 000. The distinct localization according to sex matches with the total age distribution. The presence of lesions up to 7 mm points to the reluctance to accept melanoma diagnosis in children. With the collaborative work of two registries, we achieved high completeness of registration in the 0–14-year age group. Completeness for those aged 15–19 years may be less. The increased incidence in 2006–10 suggests a better diagnosis in recent years.

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18 WCCS Abstracts

037 A comparison of six melanoma risk prediction models: assessment of performance using independent datasets C. Olsen and D. Whiteman QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia Identifying people at high risk of melanoma is important for both targeted prevention activities and surveillance. A number of clinical tools have been developed to classify people according to their level of risk. A recent review of these risk prediction tools reported that only one of them had been assessed in terms of its external validity, a test of a model’s generalizability (Vuong K, McGeechan K, Armstrong BK, Cust AE. Risk prediction models for incident primary cutaneous melanoma: a systematic review. JAMA Dermatol 2014; 150: 434–44). This is concerning, as the performance of a risk prediction tool can be overestimated when it is developed and assessed in the same dataset (Royston P, Moons KG, Altman DG, Vergouwe Y. BMJ 2009; 338: b604). A true evaluation of external validity requires evaluation in an independent population. We assessed the external validity of six melanoma risk prediction tools (Mar V, Wolfe R, Kelly JW. Predicting melanoma risk for the Australian population. Australas J Dermatol 2011; 52: 109–16; Fortes C, Mastroeni S, Bakos L et al. Identifying individuals at high risk of melanoma: a simple tool. Eur J Cancer Prev 2010; 19: 393–400; Cho E, Rosner BA, Feskanich D, Colditz GA. Risk factors and individual probabilities of melanoma for whites. J Clin Oncol 2005; 23: 2669–75; Fears TR, Guerry D 4th, Pfeiffer RM et al. Identifying individuals at high risk of melanoma: a practical predictor of absolute risk. J Clin Oncol 2006; 24: 3590–6; Quereux G, Moyse D, Lequeux Y et al. Development of an individual score for melanoma risk. Eur J Cancer Prev 2011; 20: 217–24; MacKie RM, Freudenberger T, Aitchinson TC. Personal risk-factor chart for cutaneous melanoma. Lancet 1989; 2: 487–90). We used two independent datasets, one consisting exclusively of melanoma cases (n = 762) and the second a large population-based sample of people without melanoma (controls, n = 43 794). For each risk prediction tool tested we applied the fully specified model and calculated a risk score for each person in the two new populations, applying the risk metrics (as defined by the model developers) to classify people into risk categories. We then compared these predictions with actual outcomes, examining sensitivity in the melanoma cases and specificity in the disease-free controls. The best-performing risk prediction model was the one described by MacKie et al., with a sensitivity of 089 for men and 079 for women, and a specificity of 088 for men and 072 for women. The tool developed by Cho et al. was highly specific (092 for men and 099 for women) but less sensitive (064 for men and 037 for women). Other models were either highly specific (Mar et al.) or had low (Quereux et al.) or very low specificity (Fortes et al.; Fears et al.) and higher sensitivity. These findings indicate that the generalizability of existing risk prediction tools for melanoma is problematic. In part, the widespread adoption of such prediction models is hindered by use of nonstandardized British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

assessment items, inconsistency in data presentation, and various interpretations of what constitutes ‘high risk’.

038 Referral of invasive melanoma to a melanoma multidisciplinary team meeting, 2012 C.M.R. Fahy,1 C. Quinlan,1 H.P. Redmond,2 C. Gleeson,1 J.F. Bourke,1 J. Fitzgibbon2 and M. Murphy1 1

South Infirmary, Victoria University Hospital, Cork, Ireland and 2Cork University Hospital, Cork, Ireland In this review we examined how many invasive primary melanomas diagnosed at a hospital in 2012 were discussed at the melanoma multidisciplinary team (MDT) meeting. Melanoma MDT meetings are usually attended by histopathologists, plastic and general surgeons, dermatologists, medical and radiation oncologists, radiation and cancer nurse specialists and nonconsultant hospital doctors. National guidelines suggest that all melanomas are referred for discussion to a melanoma MDT. At present, the responsibility for ensuring that melanomas are discussed at MDT meetings lies with the referring clinician. Histopathology reports from all cases of primary melanoma diagnosed between January and December 2012 were obtained. These cases were compared with those referred for discussion at the melanoma MDT from January 2012 to March 2013 by examining records of melanoma MDT minutes. These data was then compared with national registration of diagnosed melanoma. The GraphPad InStat statistical program was used for statistical analysis. There were 611 case discussions at the melanoma MDT from January to December 2012. Some patients were discussed on multiple occasions as clinical situations evolved. In 2012 there were 116 cases of primary invasive melanoma (IM) diagnosed; 101 (87%) of these cases were discussed at an MDT meeting. In total, 78 cases of primary melanoma discussed were referred from external institutions. Dermatology had 55 cases of IM; 98% (54/55) of which were referred to the MDT. Plastic surgery referred 72% (28/39) of cases of IMs for MDT review. The numbers of IMs diagnosed from other specialities included general surgery (12 of 13, 92% referred); general practitioner (two of five, 40% referred); maxillofacial surgery (four of four, 100% referred) and ear–nose–throat (one of one, 100% referred). The Breslow depths of IM cases not referred to MDT were 035–12 mm. Two of 116 cases of IM (17%) were not nationally registered. Among 176 cases of melanoma in situ (MIS) diagnosed, 30 of 125 cases of lentigo maligna were discussed at the MDT meeting and 29 of 51 cases of nonlentigo maligna melanoma were referred. Five of 176 cases (28%) of MIS diagnosed were not registered with the national register of cancer. Although this is a very active melanoma MDT, not all invasive melanomas diagnosed at this institution are being referred to this forum. In 2012 only 86% of invasive melanomas were discussed. It is likely that the percentage of melanomas referred to MDTs from institutions without an in-house MDT is even lower. The mechanism for referring melanomas to MDTs nationally needs to be evaluated and streamlined. © 2014 The Authors BJD © 2014 British Association of Dermatologists

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039 Risk of subsequent malignant melanoma in patients with melanocytic naevus in England: a national record-linkage study E. Ong,1 R. Goldacre,1 R. Sinclair2 and M. Goldacre1 1

Nuffield Department of Population Health, University of Oxford, Oxford, U.K. and 2Department of Dermatology, Epworth Hospital, Melbourne, Australia High numbers of melanocytic naevi (MNs) or dysplastic (atypical) MNs have consistently been shown to be important and strong risk factors for the development of melanoma. We aimed to characterize further the risk of melanoma in those with a melanocytic naevus, using linked hospital and mortality records covering the whole population of England from 1999 to 2011. We constructed two cohorts: one that comprised people with a hospital or day-case record of MN (271 656 people) and a control cohort comprising people without (10 130 417 people). Anyone with a melanoma on the same record as MN, or one prior to it, was not admitted to either cohort. We followed up these two cohorts to determine the observed and expected numbers of people in each cohort diagnosed with subsequent melanoma and calculated rate ratios (RRs), based on person-years at risk, standardized by age, sex, year of first admission, region and quintile of socioeconomic deprivation score. We excluded people diagnosed with melanoma within 1 year of cohort entry to reduce any biasing effects of misdiagnosis. Comparing the MN cohort relative to the non-MN cohort, the overall RR was 468 [95% confidence interval (CI) 439–498]. RRs were significantly high across all age groups: < 25 years, RR 379 (95% CI 282–503); 25–59 years, RR 502 (95% CI 462–545); ≥ 60 years, RR 468 (95% CI 419–521). Significantly increased RRs were found for both male (RR 592, 95% CI 536–653) and female patients (RR 413, 95% CI 381– 448). We found RRs to be increased across all anatomical sites. Significant increases were present when MNs and subsequent melanoma occurred at the same site, as well as when they occurred at different sites. RRs were consistently higher when considering same-site associations. For example, MNs on the trunk were associated with an increased risk of both melanoma on the trunk (RR 899, 95% CI 769–1046) and melanoma elsewhere (RR 566, 95% CI 497–642). We were unable to distinguish between different types of MN or to ascertain the number of MNs in each patient. Our patients were in hospital or in day-case care when MNs were recorded, and so the patients in our cohort are likely to have presented with atypical MN appearances. MNs were the ‘principal’ reason for hospital contact for 91% of patients in the MN cohort. Our results show that patients with a hospital diagnosis of MN have a high risk of developing melanoma both around the MN site and elsewhere in the body, and might, therefore, benefit from increased surveillance.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

040 Solar lentigines are associated with measured ultraviolet radiation exposure during holidays and are increased in patients with cutaneous malignant melanoma L.W. Idorn, P. Datta, J. Heydenreich, P.A. Philipsen and H.C. Wulf Department of Dermatological Research, Bispebjerg University Hospital, Copenhagen NV, Denmark Solar lentigines are benign pigmented lesions of the skin. Previous research on the association of solar lentigines with ultraviolet radiation (UVR) exposure has been based on retrospective questionnaires about UVR exposure. In the present study we aimed to investigate the following: (i) the association of solar lentigines with current UVR exposure assessed by objective measurements of UVR exposure in a prospective observational study of healthy individuals without skin cancer; and (ii) the number of solar lentigines in patients with cutaneous malignant melanoma (CMM) compared with matched controls. Forty-eight healthy individuals without skin cancer and 48 patients with CMM completed the investigation. Healthy individuals and patients with CMM were matched individually by sex, age, occupation and constitutive skin type. The main outcome measures were (i) number of solar lentigines on the shoulders and upper back counted on UV photographs; (ii) current UVR exposure assessed by personal electronic UVR dosimeters that measures time-related UVR, and corresponding sun diaries during a summer season (median 107 days of observation per participant); and (iii) past UVR exposure assessed by interviews. Regarding current UVR exposure in healthy individuals, the number of solar lentigines increased with the daily number of hours spent outdoors between noon and 1500 h on holidays [P = 0027; mean 15 lentigines per hour, 95% confidence interval (CI) 2–29 lentigines] and with the number of days spent at the beach during the observation period (P = 0048; mean 04 lentigines for each day spent at the beach, 95% CI 0005–08 lentigines). Regarding past UVR exposure in healthy individuals, the number of solar lentigines increased with the reported number of lifetime sunburns (P < 0001; mean 03 lentigines for each sunburn, 95% CI 01–04 lentigines). Patients with CMM had a higher number of solar lentigines on the shoulders and upper back compared with matched controls (median 125 vs. 65, P = 0044). In healthy individuals without skin cancer, solar lentigines are associated with current UVR exposure in terms of exposure hours around noon on holidays, and the number of days at the beach. Additionally, solar lentigines are associated with the reported number of lifetime sunburns. Patients with CMM have a higher number of solar lentigines compared with matched controls, which suggests a high level of past UVR exposure.

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041 Glasgow U.K. Melanoma Affluence Observational Study G. Parkins and G. Wylie Alan Lyle Centre for Dermatology, Glasgow, U.K. Previous studies have suggested a link between incidence of skin cancer and higher socioeconomic class. This is thought to be related to expendable income and ultraviolet leisure exposure through variables such as travel abroad. Up to 2011, data showed that this could be applied to Scotland as a whole, with most new cases of malignant melanoma being found in the most affluent quintile [Information Services Division Scotland. Cancer statistics, skin cancer. Available at: (last accessed 19 February 2014)]. Glasgow particularly has stark contrasts in affluence and deprivation. According to the Scottish Government, Glasgow has 42% of Scotland’s most deprived postcode areas, yet almost 60% of all package holidays abroad originate from Glasgow [The Scottish Government. Scottish Transport Statistics, no. 28, 2009. Available at: (last accessed 19 May 2014)]. The use and number of tanning salons is also higher. Against this backdrop an observational study was carried out to determine whether this relationship between skin cancer and higher socioeconomic status exists in Glasgow. In total 52 new cases of melanoma were selected at random from four different geographical sites across Glasgow, which has a catchment population of approximately 700 000. The biopsies were collected between 2012 and 2013. Variable such as patient age, melanoma subtype and Breslow thickness were taken from clinical records and histological reports. For each patient an ACORN Affluence postcode rating score was documented. ACORN is a respected commercial provider of widely used demographic data including income levels, property ownership and social class. It uses a 1–5 rating, with 1 classed as most affluent. Statistical comparisons were analysed between sex, age, Breslow thickness and affluence score. Overall 58% of the cohort was female. Average values were Breslow thickness 30 mm (range 03– 20 mm), age 65 years (range 28–90) and affluence score 28 (mode = 1). The largest proportion (38%) were found to have postcodes corresponding to group 1. Direct comparison of Breslow thickness against affluence score was calculated using a paired t-test. Out of interest, age and Breslow thickness were also directly compared. No statistical significance could be generated for any of these variables. Therefore, despite Glasgow’s relative high deprivation, a preponderance to package holidays abroad and higher sunbed use in lower social classes, it would appear there is no overt skew away from previously documented high affluence factor in new cases of melanoma.

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042 Epidemiological trends in malignant melanoma in a large urban population in England from 1999 to 2012 W. Alwan,1 P. Karagiannis,2 G. Poulos2 and K. Lacy2 1

Lewisham and Greenwich NHS Trust, University Hospital Lewisham, London, U.K. and 2St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospitals NHS Foundation Trust, London, U.K. This study analysed trends in stage, site, 5-year survival and mortality from malignant melanoma in a patient population referred to a tertiary referral centre based in a centralized urban location. We carried out a retrospective study of 1769 cases (913 male, 856 female) referred to our unit from 1999 to 2012 through analysis of our local melanoma database, electronic patient records and case note review. Cases of cutaneous malignant melanoma of histopathological stage IB and above according to the American Joint Committee on Cancer criteria were included (Balch CM, Gershenwald JE, Soong SJ et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27: 6199–206), with a smaller local cohort of 235 patients for whom all stages of melanoma were recorded. Data on incidence, mortality, Breslow thickness, body site and disease stage were analysed. The mean age at diagnosis was 58 years for all patients during the study interval (men 60 years, women 56 years). The incidence of melanoma (stage IB and above) increased 17-fold from 328 to 577 per 100 000 of the population from 1999 to 2012, in line with national trends. Breslow thickness increased over the study period for the entire database population from a mean of 225 mm in 1999–2000 to 243 mm in 2011–12. The trunk was the most common body site affected in men (36%) and the lower limbs in women (36%). No significant differences were observed in stage of disease at presentation for different body sites. The mortality rate (melanoma-specific deaths) also increased, with a rate of 196 per 100 000 in 2011–12, compared with 010 per 100 000 at the outset of the study, with men having the poorest outcomes (224 per 100 000 vs. 170 per 100 000 for women). The 5-year melanoma-specific survival figures were 96%, 85%, 78% and 32% for stage I, II, III and IV disease, respectively, consistent with published data (Balch et al.). Malignant melanoma continues to rise in incidence and is associated with significant mortality. Primary prevention strategies to reduce disease incidence and delayed presentation are crucial. The rising mortality rate highlights the necessity of early detection of tumours given the poor outcomes associated with advanced disease. No improvement in survival was seen during our study; however, we hope that the new targeted and immunomodulatory therapies will result in improved future survival rates in our patient population.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

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043 Thick melanomas: a persistent problem A. Lock, N. Wijesuriya and R. Cerio Barts Health NHS Trust, London, U.K. The occurrence of cutaneous melanoma remains on the increase in Europe, but recently has stabilized. Many recent studies have shown an increase in detection of melanomas < 1 mm in thickness, probably due to earlier diagnosis. However, the incidence of thick malignant melanomas (TMMs) seems to have remained at least constant (Tejera-Vaquerizo A, Mendiola-Fernandez M, Fernandez-Orland A, Herrera-Ceballos E. Thick melanoma: the problem continues. J Eur Acad Dermatol Venereol 2008; 22: 575–9; Murray CS, Stockton DL, Doherty VR. Thick melanoma: the challenge persists. Br J Dermatol 2005; 152: 104–9). Our skin cancer multidisciplinary team meeting serves a region with a population of approximately 17 million. We manage over 200 new cutaneous melanomas per year. We reviewed our primary cutaneous melanomas over a 12-month period, specifically those with a Breslow thickness ≥ 35 mm, aiming to identify important associations or demographic factors associated with TMM. Fifteen cases of TMM were identified. Of these, nine were female and six male. Thirteen of the 15 (87%) were aged over 60 years, and most patients were of white ethnicity. Eleven of the 15 melanomas (73%) were of nodular subtype, and the Breslow thickness ranged from 35 mm to 15 mm (mean 64). Seven of the cases were ulcerated (47%), with a mean dermal mitotic count of 9 per mm2 (range 1–27). Pre-existing naevus was seen in none and lymphovascular spread was present in two of 15 (13%). Despite the size of the lesions, six of the 15 patients (40%) had noticed a change in the lesion for at least 4 months before seeking advice. Most cases (67%) of TMM identified were in white patients aged ≥ 60 years, and were of nodular subtype. Body site was variable and included most sites, including the ankle. It may be that nodular melanomas behave biologically differently from other subtypes, and the ABCD (asymmetry, border, colour, diameter) criteria to aid diagnosis may indeed lead to late presentation. Perhaps the latter is applicable mainly to the superficial spreading subtype. Our study reinforces the observation that the incidence of TMM is not decreasing. In this group sex difference was minimal. The reason for our findings remains unclear and is multifactorial. However, new strategies and education programmes are, therefore, required for the earlier detection of such tumours to reduce their incidence in these patients.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

044 Incidence of skin cancer risk factors experienced by U.S. military personnel during recent overseas deployments J. Powers,1 N. Patel,2 E. Powers,2 G. Stricklin3 and A. Geller4 1

Vanderbilt University School of Medicine, Division of Dermatology, Nashville, TN, U.S.A., 2Vanderbilt University School of Medicine, Nashville, TN, U.S.A., 3Tennessee Valley Healthcare System, Nashville, TN, U.S.A. and 4Harvard School of Public Health, Boston, MA, U.S.A. A retrospective study of veterans showed that those with melanoma had high rates of deployment in tropical climates (34%) vs. age-matched controls (6%; P = 00002) (Brown J, Kopf AW, Rigel DS, Friedman RJ. Malignant melanoma in World War II veterans. Int J Dermatol 1984; 23: 661–3]. A retrospective review of tumour registries showed melanoma incidence to be higher in military personnel aged 45 years or older (P < 005) (Zhou J, Enewold L, Zahm SH et al. Melanoma incidence rates among whites in the U.S. military. Cancer Epidemiol Biomarkers Prev 2011; 20: 318–23). The past decade of U.S. combat missions, Operation Enduring Freedom (OEF)/ Operation Iraqi Freedom (OIF)/Operation New Dawn (OND), have occurred at a more equatorial latitude (33°N) than the mean centre of the U.S. population (38°N) [United States Census Bureau. Available at: (last accessed 19 May 2014)], increasing the potential for ultraviolet irradiance and the development of skin cancer. We hypothesized that U.S. military workers engaged in recent OEF/OIF/OND deployments have skin cancer risk factors. A 30-question survey was offered to recent OEF/OIF/OND veterans presenting to the Nashville Post-Deployment Clinic at the Tennessee Valley Healthcare System. Data from 197 surveys were analysed using Microsoft Excel and GraphPad statistical software. Overall 64% of respondents were identified as white, 22% as African American and 8% as Hispanic. Almost half (48%) were fair skinned and 50% were not fair skinned. In total 22% reported being made very aware of the risks of skin cancer vs. 42% who reported not being made aware at all. Some 77% had ≥ 4 h of bright sun exposure during a typical day and 52% reported ≥ 7 h. Only 27% noted ready access to sunscreen while working vs. 32% with no access and 40% with limited access. In total 62% of respondents had at least one sunburn during deployment, with 42% noting two or more sunburns and 16% reporting four or more sunburns; 15% had at least one blistering sunburn. Overall 29% of veterans observed changes in size, shape or colour of moles since deployment; however, only 4% had a skin exam performed by a physician since deployment. This study demonstrates room for improvement for skin cancer prevention in the veterans’ population.

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045 Epidemiological profile of cutaneous melanoma in midwest Brazil: a population-based study of 21 years F. Cavarsan,1 M.P. Curado,2 J. Oliveira3 and D. Silva2 1

Brazilian Melanoma Group, Goiania, Goias, Brazil, 2Goiania Based Cancer Registry, Goiania, Goias, Brazil and 3Association Against Cancer of Goias State, Goiania, Goias, Brazil We set out to analyse the evolution of the incidence and trends of cutaneous melanoma in a city in midwest Brazil over 21 years. We utilized the reported cases of cutaneous melanoma among patients living in an area of the Brazilian midwest, in the period 1988–2008, identified by the city’s population-based cancer registry. The cases were stratified by sex, age group and anatomical site. We performed calculations of the proportions, and crude and standardized incidence ratios using SPSS software, and for trend analyses we used the Poisson regression model of the Joinpoint program. In total 871 cases were observed, 445 women and 426 men. In women the standardized incidence rates ranged from 112 per 100 000 in 1988 to 628 per 100 000 in 2008. In men this changed from 017 per 100 000 in 1988 to 672 per 100 000 in 2008. A statistically significant increase was observed in both men [annual percentage change (APC) 97%] and women (APC 79%). The sites of greatest impact were the trunk and limbs. The incidence rates increased in both sexes, especially after the age of 50 years. We conclude that the incidence rates of cutaneous melanoma increased significantly in both sexes in the midwest of Brazil, by about 10% in men and 8% in women. Therefore the risk of cutaneous melanoma in the midwest was higher in men than in women. More studies are needed to examine the reasons for these differences.

046 Cutaneous squamous cell carcinoma: a retrospective study H. Hami,1 A. Ayoujil,1 F. Habib,2 A. Soulaymani,1 A. Mokhtari1 and A. Quyou1 1

Laboratory of Genetics and Biometry, Faculty of Science, Ibn Tofail University, Kenitra, Morocco and 2Al Azhar Oncology Center, Rabat, Morocco Squamous cell carcinoma (SCC) is the second most common nonmelanoma skin cancer worldwide, after basal cell carcinoma. The aim of this study was to determine the frequency and epidemiological characteristics of cutaneous SCC. This was a retrospective study of all patients treated for cutaneous SCC between 1994 and 2004. During this period there were 34 new cases diagnosed with SCC, accounting for 312% of all skin cancers reported during the study period. More than twothirds of the patients (67%) were men, with a male-to-female ratio of 2 : 1. The average age at diagnosis was 67  175 years (range 16–95). The risk of developing SCC was associated with age; 85% of cases were diagnosed in patients aged 55 years and older and 79% in those aged 55–89 years. More than a quarter of the patients (26%) were diagnosed with metastatic disease. Among the cases for whom the British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

outcome was known, three (9%) died during the study period. The most recent estimates of nonmelanoma skin cancer incidence and mortality in the world reveal sharp differences between developed and developing countries, possibly related to missed opportunities for early diagnosis and incomplete reporting of nonmelanoma skin cancer in Africa.

047 Estimating risks of basal cell carcinoma and squamous cell carcinoma: a risk prediction tool developed from a large prospective cohort study D. Whiteman, B. Thompson, A. Thrift and C. Olsen QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia The principal risk factors for keratinocyte cancers (basal cell carcinoma and squamous cell carcinoma) have long been known; however, clinicians and patients have few tools to integrate these factors into a score to help manage future risks. We used data from a large, prospective cohort study to derive and validate a risk stratification tool. The participants were 43 794 adults aged 40–69 years selected at random from a population register in 2011. Participants self-completed a baseline survey that collected information on places of residence; past history of sunburn, solar keratoses and skin cancer; and family history of skin cancer. Validated items elicited information on phenotypic factors including hair and eye colour, tanning and burning tendency, and freckling and naevus burden. Information was captured about sun exposure received on work and nonwork days at baseline, and in 10year age groups from childhood. We identified subsequent diagnoses of keratinocyte cancers occurring during the first 2 years of follow-up through record linkage to a universal health insurance register. (We included all keratinocyte cancers, as the tool is intended to triage patients for prevention or surveillance activities, irrespective of skin cancer type.) We used two-thirds of the dataset to derive the risk prediction model. We included terms for potential predictors that were significantly associated with keratinocyte cancer in univariate analyses. We then performed backwards stepwise logistic regression to arrive at a final model, checking for multicollinearity and interaction. We validated the model independently in the remaining one-third of the dataset using tests for discrimination and calibration. We did this for all participants in our primary analysis, irrespective of prior skin cancer history. In secondary analyses, we repeated the process separately for those with and without prior skin cancer. In the primary analysis, the model retained terms for age (P < 001), sex (P = 001), ethnicity (P = 004), skin colour (P < 001), freckling tendency (P < 001) and prior skin excisions (P < 001) or ablations (P < 001). In the validation dataset, the model showed high discriminatory accuracy [area under the receiver operating curve (AUC) 080, 95% confidence interval (CI) 079–081] with excellent calibration (Hosmer– Lemeshow goodness of fit P-value < 001). When we derived models separately for those with and without a prior history of skin cancer, essentially the same items were retained, with some loss of discriminatory accuracy (no prior skin cancer © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 23

AUC 071; prior skin cancer AUC 068). These data demonstrate that patients at high risk for skin cancer can be identified accurately using an empirical risk stratification tool comprising seven items.

048 Detecting and quantifying ultraviolet-induced skin damage: an evaluation of new instruments L. Ruppert,1 J. Schmitt,2 P. Elsner,3 A. Bauer,4 M. Fartasch,5 S. John,6 R. Scheidt,1 K. Bachmann1 and T. Diepgen1

of our a priori hypotheses. Interobserver and test–retest reliability were excellent for UV-exposed locations (j = 075– 099) and fair to excellent for non-UV-exposed body sites (j = 050–074). Internal consistency was moderate to excellent (Cronbach’s a 067–094). A four-factor model for UVdamage can be extracted over all locations according to the scree plot. Our study shows that the newly introduced instruments are adequate tools for a standardized, reproducible, quantitative evaluation of UV-induced skin damage performed by a dermatologist.


Clinical Social Medicine, University Hospital Heidelberg, Heidelberg, Germany, 2Center for Evidence-Based Healthcare, University Hospital TU Dresden, Dresden, Germany, 3Department of Dermatology and Dermatological Allergology, Friedrich-Schiller-University Jena, Jena, Germany, 4Department of Dermatology, University Hospital TU Dresden, Dresden, Germany, 5 Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute, Ruhr-University Bochum, Bochum, Germany and 6Department of Dermatology, University Osnabr€uck, Osnabr€uck, Germany Ultraviolet (UV) exposure is the most relevant risk factor for nonmelanoma skin cancer. Epidemiological evidence indicates that outdoor workers have a twofold increased risk for cutaneous squamous cell carcinoma (SCC). Therefore, SCC including actinic keratosis due to occupational exposure to solar UV radiation is currently recommended as a new occupational disease in Germany. Adequate instruments to measure the extent of UV-induced skin damage are needed to evaluate the occupational risk of skin cancer. In light of the absence of validated tools we aimed to develop standardized, reproducible measurement instruments to quantify UV-induced skin damage at different body sites. Three different scales were created: photographic guide, light damage scale) and light damage total score (LDTS). The instruments were tested for validity and reliability in five different study centres across Germany. Light damage was assessed by a dermatologist at 12 different body sites (capillitium, face, neck, back of hands, forearms, extension side of upper arm, inside of upper arm, cleavage, abdomen, back, bottom and lower extremities) in persons affected and not affected by skin cancer (n = 216). Of these, a subsample of 83 participants was examined separately by two physicians (for interobserver reliability) and 55 participants were evaluated twice by the same physician (for test–retest reliability). To test the validity of the instruments, a priori hypotheses were defined: (i) different localizations show identical ordering according to light damage throughout all instruments; (ii) all three instruments show a strong correlation with each other (q > 06); and (iii) patients with skin cancer show higher UV damage of the skin compared with persons not affected by skin cancer. To evaluate the relationship between the instruments, Spearman’s correlation coefficients were calculated. Interobserver and test–retest reliability were tested by Cohen’s j. Cronbach’s a was used to assess the internal consistency of the developed scales. An exploratory factor analysis was performed for the most extensive score (LDTS). Good construct validity was shown by strong correlations of the instruments (q = 062–089) and the verification © 2014 The Authors BJD © 2014 British Association of Dermatologists

049 Phenotypic and environmental risk factors for basal cell carcinoma at sun-protected and sunexposed body sites M. Khalesi,1,2 D. Whiteman,1 C. Rosendahl,3,4 R. Johns,3 T. Hackett,3,4 A. Cameron,3,4 M. Kimlin2 and R. Neale1 1

QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia, Queensland University of Technology, Brisbane, Queensland, Australia, 3Skin Cancer College Australasia, Brisbane, Queensland, Australia and 4University of Queensland, Brisbane, Queensland, Australia The association between ultraviolet radiation and basal cell carcinoma (BCC) is complex, and there are indications that it may differ according to the anatomical site of the tumour. A relatively high proportion of BCCs occur on body sites that are infrequently exposed to the sun, and BCCs occurring on different sites tend to be of different histological subtypes. While much is known about the complex constitutional and environmental risk factors for general BCC occurrence, little is known about their relative importance in BCC occurring at different body sites. We conducted a case–case study to compare the phenotypic and environmental characteristics of people diagnosed with incident BCC on body sites that are generally sun protected (trunk, buttocks and thighs; n = 108) vs. those with incident BCC on sun-exposed sites (head, neck, forearms and lower legs; n = 94). BCCs on the sun-protected sites were more likely to occur in men than in women, and also in those who had a more ultraviolet-sensitive phenotype, such as fair skin and hair, blue eyes, tendency to burn and inability to tan. The number of melanocytic naevi was strongly associated with BCC site, with those who had a higher number of naevi on their body being less likely to develop BCC on the sun-protected sites than on sun-exposed sites, after adjustment for other phenotypic factors and time outdoors, with odds ratios (ORs) between 03 and 05. There was a suggestion that history of severe acne increased the likelihood of BCC occurring on sun-protected body sites [OR 208; 95% confidence interval (CI) 066–651]. Of the photodamage markers examined, the presence of actinic keratoses was the most strongly associated with having a BCC on a sunprotected site. There was evidence of a dose response, with ORs increasing from 364 (95% CI 086–1538) in those with one to five actinic keratoses to 1402 (95% CI 270–7263) in those with > 30 actinic keratoses. Other markers, including solar elastosis, solar lentigines and telangiectasia, showed 2

British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

24 WCCS Abstracts

weaker associations, but were still more strongly associated with BCC on a sun-protected site (ORs between 13 and 15). We also found that people with more than five seborrhoeic keratoses were four times more likely to develop BCC on sunprotected sites. Our findings suggest that BCCs on sunprotected sites are due to excessive sun exposure. The strong association with naevi suggests that there are constitutional factors, possibly genetic, that also underlie the propensity for BCCs to arise on these sites.

050 Actinic keratoses and field change and their associations with squamous cell carcinoma in renal transplant recipients in Manchester, U.K. J. Lear,1 S. Wallingford,1 C. Proby2 and A. Green1 1

Manchester Academic Health Sciences Centre, Manchester, U.K. and 2 Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, U.K. The precise relationship of actinic field change to discrete actinic and verrucous keratoses (AKs) and to squamous cell carcinoma (SCC) is unknown. We investigated the prevalence of actinic field change in addition to discrete AK and estimated the risk of SCC related to field change among renal transplant recipients (RTRs). We analysed cross-sectional data from 452 white RTRs attending dermatological follow-up at two hospitals in Manchester, U.K. (May 2010 to October 2011). Discrete AKs and actinic field changes were identified by a dermatologist. All new SCCs were histologically confirmed. In total 130 RTRs (29%) had AKs (count range 1–69), of whom 70 (54%) also had field change. Four RTRs (7%) with discrete AK [odds ratio (OR) 20] and 15 (21%) with AK and field change (OR 93) developed SCC, compared with 1 (03%) RTR with SCC but no AK. Of 20 RTRs with SCC diagnosed in the study period, 11 (55%) had them present within areas of field change. The study had limitations. Patients’ previous histories of AK and field change were lacking, and the number of new SCCs observed during the study period was small. In conclusion, RTRs with confluent actinic skin damage are at exceptionally high risk of SCC and should receive close dermatological surveillance.

051 Trends in the incidence of nonmelanoma skin ^nia, cancer in a population aged < 40 years in Goia Brazil S. Pereira,1 M.P. Curado2 and A.M.Q. Ribeiro3 1

Federal University of Goias, Goi^ania, Goias, Brazil, 2Population-Based Cancer Registry of Goi^ania, Goi^ania, Goias, Brazil and 3International Prevention Research Institute, Lyon, France We set out to verify trends in the incidence of nonmelanoma skin cancer (NMSC) in the young population of Goiania, Brazil from 1988 to 2009. The data were obtained from the population-based cancer registry of Goiania in central-west Brazil. In that period, 1836 cases of NMSC were registered in 1536 people, of which 1614 were basal cell carcinoma (BCC) and 222 squamous cell carcinoma (SCC). The incidence of BCC British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

increased from 170 to 369 per 100 000 population in men, and from 238 to 614 per 100 000 in women. Significant increasing trends were verified in men, with an annual percentage change of 28%, while in women it was 39%. Regarding SCC, nonsignificant decreasing trends were identified for both sexes. BCC trends per age group showed increases in men starting from age 30 years, and in women from 25 years of age. There was a trend for more BCCs in men on the head and neck, and limbs; while for women this was seen for all anatomical regions. Therefore NMSC is not rare in young populations. BCC incidence is increasing in the population under 40 years of age in central-west Brazil, especially in women.

052 Multiple skin neoplasms in individuals aged < 40 years in central-west Brazil S. Pereira,1 M.P. Curado2 and A.M.Q. Ribeiro3 1

Federal University of Goias, Goi^ania, Goias, Brazil, 2Population Based Cancer Registry of Goi^ania, Goi^ania, Goias, Brazil and 3International Prevention Research Institute, Lyon, France The aim of this study was to investigate the occurrence of multiple skin malignancies in a population aged < 40 years in Goiania, Brazil in the period 1988–2009. Data were obtained from the population-based cancer registry of Goi^ania in central-west Brazil. All cases of skin cancer (basal cell carcinoma, squamous cell carcinoma and skin melanoma) were analysed to indentify multiple lesions. We investigated the existence of genetic syndromes or transplants present in patients with multiple lesions. In the 22-year period there were 1995 registered cases of skin cancer in 1688 individuals. Of these, 164 individuals had multiple lesions, of whom 555% were women and 445% men. Of the 471 multiple lesions, basal cell carcinoma was the most frequent (853%), followed by squamous cell carcinoma (119%) and skin melanoma (28%). The presence of a genetic syndrome was seen in 16 patients (98%) with multiple lesions. Of these, eight were cases of albinism, five xeroderma pigmentosum, two naevoid basal cell, one epidermodysplasia verruciformis, and one case of a kidney transplant. The average number of lesions was 5 per patient. Patients with multiple lesions without genetic syndromes accounted for nearly 90% of cases, with an average of 25 lesions per patient; > 15% of patients had three lesions. The diagnosis of the second primary tumour was made in 650% of cases within 6 months and 894% within 5 years after the first diagnosis. The incidence of multiple neoplasms increased in men from 030 to 098 per 100 000, and in women from 043 to 116 per 100 000 in the study period. There was a significant trend for increased incidence in women, with an annual percentage change of 86% (95% confidence interval 32–143; P = 0003). Multiple skin tumours in patients aged under 40 years are not uncommon in Brazil. The incidence is increasing, particularly in women. The diagnosis of multiple lesions can be made from 6 months to 5 years after the first lesion. Therefore the prevention of skin cancer should be recommended from childhood. © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 25

053 Evaluation of sun exposure behaviour and use of sun protection among medical professionals J. Xu1 and K. Varma2 1

Sandwell and West Midlands Hospitals NHS Trust, Birmingham, U.K. and North Cumbria University Hospitals NHS Trust, Carlisle, U.K. Excess exposure to ultraviolet radiation has been identified as the most important modifiable risk factor for skin cancer. Physicians’ individual attitudes and behaviour will not only impact personal well-being but also influence promotion of sun protection to others. This study aimed to look at behaviours concerning sun exposure and its prevention among doctors across various specialties in the U.K. No previous studies have been identified in the literature regarding sun exposure behaviours among secondary care medical professionals. Doctors were invited to participate in an anonymous questionnaire, which was available both in written and online format. In total 163 medical professionals completed the questionnaire. One-third of doctors demonstrated sun-seeking behaviours and > 10% of medical professionals use tanning beds. Incidence of sunburn (more than one episode per year) was rated highest among women, but interestingly female doctors also reported more frequent sun-protective behaviours than their male colleagues. More than 65% of medical professionals have never performed skin self-examination or had their skin examined by another healthcare professional. Our findings illustrate that doctors engage in multiple skin cancer risk behaviours. A comprehensive approach to change behaviour requires exploration of attitudes, and sun education should be highlighted among medical professionals and promoted within the healthcare system. 2

054 Developing the ideal sunscreen for persons with albinism in Tanzania U. Osterwalder,1 S. Acker,2 C. Hanay3 and s4 M.S. Valde 1


BASF PCN GmbH, Monheim am Rhein, Germany, BASF Grenzach GmbH, Grenzach-Whylen, Germany, 3Similasan AG, Jonen, Switzerland and 4 RDTC at KCMC, Moshi, Tanzania Persons with albinism require reliable sun protection, especially in geographical regions near the equator such as Tanzania. The Regional Dermatology Training Center in Moshi, Tanzania is establishing a sustainable sunscreen programme for persons with albinism. This paper discusses how the ‘Kilimanjaro Suncare’ sunscreen is being further developed. Ideally, a sunscreen provides uniform protection across the entire range of ultraviolet radiation (UVR), similar to shade and clothing. A convenient approach for the estimation of the UV screening performance of sunscreens is computational simulations. Calculation of the in silico sun protection factor (SPF) models the principle of the in vivo SPF and employs the same algorithm as used with in vitro SPF measurements, but replaces the transmission measurement by the calculation of the combined extinction of the UV filters in an irregular sunscreen film. With the help of the freely accessible BASF Sunscreen © 2014 The Authors BJD © 2014 British Association of Dermatologists

Simulator (, it can be determined how far away from the ideal sunscreen a certain UV filter combination performs. The closer the normalized transmitted UV dose at 1 minimal erythemal dose comes to 1, the more ideal is the spectral profile of the respective sunscreen. Some of the currently available (UVB-biased) sunscreens transmit up to seven times the amount of UVR than the ideal sunscreen. However, even the best sunscreen with an ideal protection profile cannot guarantee sustainable sun protection if it is not used properly. It is essential that the sunscreen is accepted as a means of avoiding photoageing and skin cancer and its application becomes a pleasant daily ritual. A turnaround in incidences of skin cancer seems likely only if sunscreen is used daily, in the same way that people clean their teeth or as they use a three-point safety belt in cars. For further development of the ‘Kilimanjaro Suncare’ sunscreen, the following ‘must’ criteria for performance have been defined: minimum SPF 50, minimum UVA protection factor less than one-third of SPF, and appropriate rheology for good spreading properties and such that recyclable jars can be used. Furthermore, over a dozen ‘want’ criteria have been discussed and evaluated. A comparison of criteria yielded the following top three ‘want’ criteria: (i) cosmetic elegance and acceptability, (ii) sweat resistance and (iii) minimal penetration of the UV filters into the skin. Before any change of the ‘Kilimanjaro Suncare’ sunscreen is implemented in the sustainable sunscreen programme, a pilot study will be conducted with a selection of persons with albinism.

055 Expert opinion survey on actinic keratosis I. Longo,1 S. Arias-Santiago,2 J.L. Artola,3 E. de las ndez-Guarino,5 J.L. Lo pezHeras,4 M. Ferna 6 nchez-Aguilar,8 Estebaranz, L. Martınez,7 D. Sa  Rodrıguez-Prieto11 and A. Toll,9 P. Redondo,10 M.-A. 12 n C. Serra-Guille 1

Hospital Central de la Defensa Gomez Ulla, Madrid, Spain, 2Hospital Virgen de las Nieves, Granada, Spain, 3Hospital Galdakao, Bilbao, Spain, 4Hospital Ramon y Cajal, Madrid, Spain, 5Hospital Central de la Cruz Roja, Madrid, Spain, 6Fundacion Hospital Alcorcon, Madrid, Spain, 7Hospital Carlos Haya, Madrid, Spain, 8Hospital Clınico, Santiago de Compostela, Spain, 9Hospital del Mar, Barcelona, Spain, 10Clınica Universitaria de Navarra, Navarra, Spain, 11Complejo Asistencial de Leon, Leon, Spain and 12Instituto Valenciano de Oncologıa, Valencia, Spain There is increasing controversy concerning the most convenient terminology to define actinic keratosis (AK). Some argue that the concept of premalignant lesion should prevail, while others, in the light of molecular studies, prefer to include AK as part of the spectrum of cutaneous squamous cell carcinoma. With the objective to explore the opinion of clinicians mainly involved in the management of patients with skin cancer, we elaborated a 15-item questionnaire that was sent to members of our Cutaneous Oncology and Surgery Task Group. A total of 48 dermatologists with a median of 17 years of experience answered the survey, most of them currently working at secondary and tertiary hospitals (n = 23 and n = 15, British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

26 WCCS Abstracts

respectively) and private practices (n = 22). Roughly 50% invest at least half of their daily practice in the care of patients with skin cancer. Regarding the concept of AK, it was considered an intraepidermal carcinoma by 42%, a precancerous lesion by 40% and a keratinocytic dysplasia by 19%. Most of the experts (60%) do not employ the clinical grading (I–III) in daily practice, but most (88%) usually describe its clinical features (pigmented, atrophic, hypertrophic etc.). Also, more than 85% consider an AK with severe dysplasia equivalent to an intraepidermal carcinoma in terms of management. More than 40% of the experts consider that there is a good correlation between clinical grading and histological findings, although 47% state that the degree of histological dysplasia is lacking in pathology reports. An AK is not usually biopsied, and when this histological diagnosis is found the most common reasons for performing a biopsy are to exclude an invasive squamous cell carcinoma (48%) or because of suspicion of another neoplasia (21%). Dermoscopy was evaluated as not useful in distinguishing between a noninvasive keratinocytic lesion and a microinvasive squamous cell carcinoma by 60% of respondents. The vast majority of dermatologists (90%) commonly employ the term ‘field cancerization’ with their patients. Development of AK within a field cancerization is reported to occur in 51–75% of patients and in > 75% of patients by 52% and 30% of the respondents, respectively. The preferred terms to describe AK vary between two extremes: intraepidermal carcinoma or precancerous lesion. A greater degree of consensus is needed to define guidelines and recommendations for the appropriate management of AKs, which in > 51% of patients are estimated to develop within a field cancerization.

056 Series of 21 years of nonmelanoma skin cancer in a city of the Brazilian midwest: a population-based study F. Cavarsan,1 M.P. Curado,2 J.C. Oliveira2 and D.R. Silva3 1

Brazilian Dermatology Society, Goiania, Goias, Brazil, 2Goiania Based Cancer Registry, Goiania, Goias, Brazil and 3Association Against Cancer of Goias State, Goiania, Goias, Brazil The aim of this study was to analyse the evolution of the incidence and trends of nonmelanoma skin cancer (NMSC) in a city of midwest Brazil over 21 years. We utilized the reported cases of NMSC in people living in the capital city of a midwest Brazilian state, in the period 1988–2008, identified by the city population-based cancer registry. The cases were stratified by sex, age group, morphology [basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)] and anatomical site. We performed calculations of the proportions, and crude and standardized incidence ratios using SPSS-18 software, and for trend analyses we used the Poisson regression model of the Joinpoint program. In total there were 14 218 women and 11 899 men, with 19 961 BCCs and 6156 SCCs. In about 99% of cases there was histological confirmation. We observed increasing incidence in both sexes for both BCC and SCC British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

[annual percentage change (APC) for BCC, 68% for both sexes; APC for SCC, 66% in men and 54% in women). There was an increase in incidence with age. The face was the most common site. The incidence of BCC is increasing in both men and women, while for SCC the increase was greater among men. Age is a risk factor as there was an increase in incidence after age 50 years. The face and trunk are the sites of highest incidences for BCC and SCC. Prevention with clinical examination of all of the skin is the best recommendation for the early diagnosis of NMSC.

057 Neglected cutaneous carcinomas E.-H. Kristian, M.-G.M. Elena, G.-R. Vero´nica and O.-C. Jorge Dermatology Department. University Hospital Dr Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon, Mexico Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two most frequent nonmelanoma skin cancers that affect humans. Multiple treatment options are now available, and precise guidelines give patients better outcomes. In developing countries like Mexico, sanitary systems are not always well employed and patients can fall into a gap between misdiagnosis, wrong treatments and poorly conducted followups. We present five cases of highly invasive, neglected cutaneous carcinomas. Giant BCC is defined as a tumour of ≥ 5 cm maximum diameter that is locally aggressive, has a greater risk of metastasis and is associated with a poor prognosis. SCCs classified as high-risk types are tumours characterized by thickness > 4 mm, perineural invasion and poor differentiation. The highest cure rates are achieved by complete excisional surgery, but can result in disfigurement and poor acceptance from the patient. Alternative therapeutic measures, such as electrosurgery, chemotherapy and radiotherapy, as well as newer agents that inhibit the hedgehog pathways, are being used as neoadjuvant treatments to reduce tumour size. Patients presenting with horrifying/giant BCC and SCC pose a therapeutic challenge requiring multidisciplinary team efforts. The described cases are a few of the neglected skin carcinomas that we still receive annually at our outpatient clinic. Although BCCs rarely metastasize, they can be very locally aggressive, causing tissue destruction and alteration of normal facial anatomy and significant morbidity when left untreated. These patients share the same history of long periods of time between the appearance of the initial lesion and the time of diagnosis. Interestingly, most had seen multiple physicians and received a long list of topical medications before reaching the right diagnosis. These unfortunate cases of neglected skin carcinomas could easily have been treated at earlier stages with curative excisional surgery or other available means, avoiding their otherwise devastating outcome. The main reasons that led to a delay in consultation and treatment were fear of the diagnosis and an obvious lack of wellprepared first-contact medical attention. Dermatologists in developing countries like ours need to have closer contact with general practitioners, medical oncologists and surgical © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 27

oncologists in order to optimize patient follow-up and early diagnoses, so prompt referrals can be made. In this era, where novel treatments for locally advanced and metastatic BCCs are emerging, patients such as those presented here can now have more treatment options and aspire to better outcomes.

058 The process of introducing a new technique for treatment of superficial skin cancer into an established radiation therapy department E. Sinclair,1 K. Osmar,2 A. Wighton2 and J. Harriman3 1

University of Toronto, Toronto, Canada, 2Sunnybrook Health Sciences Centre, Toronto, Canada and 3London Cancer Centre, London, Canada This study describes the introduction of photodynamic therapy (PDT) to a radiation therapy department and the process involved in being ready to treat our first patient. Thousands of years ago the Egyptian, Chinese and Indian civilizations knew that sunlight, alone or in combination with salves, could be used to treat various diseases such as psoriases and skin cancer. We began by completing a thorough literature search. PDT is a noninvasive procedure that involves a photosensitizing drug and its subsequent activation by light to destroy target cells. This has proven to be very successful in the treatment of superficial skin lesions. Actinic keratoses (AKs) are very common, with around 2 million cases diagnosed yearly. Of these, 5–20% will transform into squamous cell carcinoma within 10–25 years. This estimate may be very low, as AKs are not usually registered anywhere as a cancer and many are never seen by a dermatologist. R€ owert-Huber et al. state that based on their clinical behaviour, AKs are a malignant neoplasm; they do not progress to SCCs because they are already SCCs, they are not a precancer or a precursor to cancer as they are a cancer in their own right [R€owert-Huber J, Patel MJ, Forschner T et al. Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification. Br J Dermatol 2007; 156 (Suppl. 3) 8–12]. They are backed by several other authors. Cryosurgery and electrodesiccation and curettage are the mainstay treatments; however, the cosmetic outcome from PDT for AK treatment is superior. We concluded that PDT is an excellent treatment option for our skin cancer population. We began by purchasing and installing the lamps and cream for the treatment of patients with AK, superficial basal cell carcinomas and Bowen disease. We designed suitable patient education materials describing the treatment and the subsequent side-effects. We devised several protocols covering eye shielding, application of cream, anaphylaxis, questions and answers, morning warm-up and education materials for the staff who would deliver the treatment. Accommodation proved to be our main obstacle, as space in a cancer centre is at a premium. However, this was resolved when we could prove how much income we hoped to generate. We designed a set of clear metrics for the delivery of PDT as there was none available in the literature, for distance, break times, size of areas etc. We treated the project as we would a clinical mark-up for treatment to be given by radiation, therefore standardizing the whole process. © 2014 The Authors BJD © 2014 British Association of Dermatologists

059 Malignant melanoma: first results from a population-based cancer registry S.M. Garba,1 H. Hami,1 H.M. Zaki,2 A. Soulaymani,1 H. Nouhou2 and A. Quyou1 1

Laboratory of Genetics and Biometry, Faculty of Science, Ibn Tofa€ıl University, Kenitra, Morocco and 2Laboratory of Pathological Anatomy and Cytology, Faculty of Health Sciences, Abdou Moumouni University, Niamey, Niger Malignant melanoma is a rare but dangerous type of skin cancer worldwide, accounting for 16% of all cancers. It is the nineteenth most commonly diagnosed cancer in both men and women and the twenty-second leading cause of cancer death, with an estimated 232 130 new cancer cases and 55 489 cancer deaths in 2012. The aim of this study was to estimate the incidence of malignant melanoma and determine its epidemiological characteristics. This was a retrospective study of melanoma cases reported between 1992 and 2009 to the National Cancer Registry, which was established in 1992. During the period of study, 33 patients were diagnosed with melanoma, accounting for 07% of all cancers reported during this period. In 2009, the incidence of malignant melanoma was 29 new cases per 100 000 people. In total 61% of the patients were female, with a female-to-male ratio of 15. The average age at diagnosis was 53  146 years for all patients (range 26–78), 607  154 years for men and 48  12 years for women. Two-thirds (67%) of people diagnosed with the disease were aged ≥ 50 years at the time of diagnosis, with 64% of new cancer cases occurring among those aged 50–74 years. The most prevalent ethnic groups were the Djerma-Sonrai (52%) and Haoussa (36%). The most common sites for melanoma were the skin (88%) and eye (12%) (International Classification of Diseases version 10 codes C44 and C699, respectively). In 91% of cases, the initial diagnosis of melanoma was established by pathological examination. The exact incidence of malignant melanoma is difficult to estimate, as the patients often refuse consultations and are reluctant to undergo histopathological examination. They prefer to consult traditional healers.

060 Statistical survey of extramammary Paget disease based on proposed clinicopathological tumour– nodes–metastasis classification and staging, and examination of treatments for advanced cases H. Kamiya and Y. Kitajima Xxxxxxxxxxx We conducted a statistical survey of extramammary Paget disease (EMPD) in coordination with the Japanese Association of Dermatologic Surgery. We investigated 3095 cases of EMPD (2034 male and 996 female, where data available) from 79 institutions from 1999 to 2013. The aims of this survey were as follows: (i) statistical analysis based on proposed clinicopathological tumour–nodes–metastasis (TNM) classification and staging in Japan {Ohara K, Onishi Y, Kawabata Y. [Diagnosis and treatment of extramammary Paget’s disease]. Skin British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

28 WCCS Abstracts

Cancer 1993; 8: 187–208 (in Japanese)}; (ii) examination of the margin of the surgical excision and indication of lymph node dissection; and (iii) evaluation of treatment outcomes for advanced cases including local recurrence and distant metastasis. We evaluated the results of the epidemiological survey and prognosis assessment in detail, and calculated the cumulative survival rate by proposed clinicopathological TNM classification and staging. There were significant differences among the five groups (stages 1A, 1B, 2, 3, 4) by proposed TNM staging. However, we were unable to conclude whether this classification reflects the true prognosis. Additionally, we evaluated the prognosis of the patients based on the presence or absence of sentinel lymph node metastasis and of lymph node dissection. Further studies are necessary to determine whether this surgical procedure results in a survival benefit in patients with EMPD. There were no significant differences in survival when chemotherapy and surgery were used together for stage 3 and 4 patients. The optimal therapeutic strategy for advanced cases requires further investigation.

061 Incidence of skin cancer within the Scottish population G. Parkins, A. Matthews and G. Wylie Alan Lyle Centre for Dermatology, Glasgow, U.K. Skin type, ultraviolet radiation and genetics all play a role in the development of melanoma and nonmelanoma skin cancers. With a large number of the population in Scotland having Fitzpatrick skin types I and II, their risk of developing skin cancer is higher. Our aim was to assess the general trends in skin cancer incidence within Scotland. We sourced data on melanoma and nonmelanoma skin cancers from the Information Services Division Scotland, which has figures for skin cancer incidence and survival [Information Services Division Scotland. Cancer statistics, skin cancer. Available at: http:// Skin/ (last accessed 19 February 2014)]. We specifically looked at trends in the incidence of melanoma, basal cell carcinoma and squamous cell carcinoma. The incidence of melanoma and nonmelanoma skin cancer has increased. The number of cases of basal cell carcinoma rose from 2910 across all age groups in 1990 to 7553 in 2011, equal to a rise in incidence of 160%. A similar picture was seen with squamous cell carcinoma, with 892 cases in 1990, rising to 2982 cases in 2011, equating to rise in incidence of 234%. The number of cases of cutaneous melanoma increased from 495 cases in 1990 to 1202 cases in 2011, a rise of 143%. It was noted between 2009 and 2010 that the rates of melanoma and nonmelanoma skin cancer fell by 1%, but subsequently increased in 2011 to above the previous highest recording. The relative survival at 5 years after diagnosis between 1983 and 1987 was 64% and 819% for male and female patients, respectively. This had increased to 854% and 917%, respectively, for the period 2003–2007. The incidence of melanoma and nonmelanoma skin cancer has risen exponentially. Increasing age and exposure to ultraviolet radiation through holidays British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

abroad and sunbeds play a role in the trends seen. The levelling off of incidence in recent years may reflect a plateau in skin cancer rates. However, it is encouraging that the rise in incidence has been met with improvement in survival from melanoma, especially among men, who have shown an absolute increase in survival of 21% over 20 years. Given that the management of melanoma has not really changed in this time, the improved survival may be a result of public health messages specifically on sun protection and the importance of early detection of skin cancer.

062 Employing mobile units in the prevention of skin cancer in Brazil C. Silveira, T. Buosi and E. Mauad Barretos Cancer Hospital, Barretos, S~ao Paulo, Brazil Brazil is the fifth largest country by area in the world, and has a great social inequality and serious difficulties in securing physicians in areas with little infrastructure, located far from major centres. For 2014, it is estimated that 576 000 new cases of cancer will be diagnosed in Brazil, out of which 188 000 will be skin cancer [Gomes da Silva JA, Ministerio da Sa ude, Instituto Nacional de C^ancer. Estimativa 2014: Incid^encia de C^ancer no Brasil. Available at: estimativa/2014/estimativa-24042014.pdf (last accessed 20 May 2014)]. In 2004, a tertiary hospital located in the state of S~ao Paulo started a skin cancer screening programme by way of prevention mobile units (PMUs) in remote regions of the country (Mauad EC, Silva TB, Latorre MR et al. Opportunistic Screening for skin cancer using a mobile unit in Brazil. BMC Dermatol 2011; 11: 12). The goal of this study was to demonstrate the preliminary results of using a mobile unit as a tool for the screening, diagnosis and treatment of skin cancer in several poor regions of Brazil. These mobile units travelled through some Brazilian states providing specialized medical care for a population who had great difficulty in gaining access to this type of care. The PMU, built on the platform of a 10-m-long articulated van truck, is equipped with an outpatient room and small surgical centre, having a daily operating capacity of 40 patients affected by skin cancer, including minor surgeries and cryotherapy. Every city visited by the PMU had a local nurse, who was responsible for performing a triage of the patients to be seen. These nurses undergo annual training with the PMU staff. The results showed that in the last 5 years (2009–2013) 23 220 patients were seen, of whom 5222 underwent surgical procedures and 4500 (862%) had positive anatomopathological results for pathological skin cancer. Out of all positive cases, 985% were nonmelanoma skin cancer and 15% were melanomas. Most lesions (937%) were diagnosed at clinical stage 0 and 1 (Union for International Cancer Control). Thus, the work performed in the PMU has proved to be effective for screening, early diagnosis and treatment of malignant skin tumours in remote regions of Brazil.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 29

063 Skin cancer prevention, tanning and vitamin D: a content analysis of print media in Germany and Switzerland D. Reinau,1 R. Blumenthal2 and C. Surber1 1

University Hospital Basel, Basel, Switzerland and 2Berufsverband der Deutschen Dermatologen, Berlin, Germany To gain insight into the content and quality of press coverage pertaining to skin cancer prevention and related topics (solaria, vitamin D), we conducted a comprehensive analysis of print media articles published in Germany and Switzerland over a 1-year period between 2012 and 2013. In each country, a professional media monitoring agency prospectively identified relevant articles printed in a wide range of popular newspapers and magazines. Using a standardized coding sheet, we assessed descriptive characteristics (e.g. primary topic, publication source), content (presence or absence of prespecified information) and quality (correctness) of the articles. Overall, we included 2103 articles for analysis. Articles reporting on sun protection (n = 1287) most commonly recommended applying sunscreen (952%), followed by wearing appropriate clothing (604%), seeking shade (593%) and wearing protective headgear (446%). Of the articles reporting on skin cancer detection (n = 267), 599% recommended regular dermatological screening by a health professional, and 648% fostered skin self-examinations. Articles focusing on solaria (n = 315) preponderantly mentioned potential adverse health effects. Yet 51% and 70% advocated indoor tanning to enhance physical appearance and cutaneous vitamin D photosynthesis, respectively. For the latter purpose, exposure to solar or artificial ultraviolet radiation was also promoted in 831% of the articles focusing on vitamin D (n = 320), with 12% of these not mentioning any precaution measures. In total, 268% of all analysed articles contained misleading or erroneous statements. By far the most were related to sunscreen use and vitamin D issues. Print media can serve as powerful education tools to foster skin cancer prevention. However, misleading or erroneous reports hold the danger to create confusion and may even negatively impact sun-safe behaviour. In this context, the media coverage of vitamin D gives special cause for concern.

064 Are patients’ clinical data important for skin cancer population screening via teledermatology? C. Silveira,1 T. Buosi,1 L. Barros,2 R. Vieira,1 R. Haikel1 and E. Mauad1 1

Barretos Cancer Hospital, Barretos, S~ao Paulo, Brazil and 2Integrated Health Center, Barretos, S~ao Paulo, Brazil Skin cancer is the most common cancer affecting the world population, with 2–3 million new nonmelanoma skin cancer cases and 132 000 new cases of melanoma diagnosed each year (American Cancer Society. Cancer Facts & Figures 2012. Atlanta: American Cancer Society, 2012). Teledermatology, a technique in which dermatological medical information (digital photography and a clinical questionnaire) is sent by means © 2014 The Authors BJD © 2014 British Association of Dermatologists

of electronic communication, is an activity that has been applied as a screening method in some countries, showing quite expressive results (Miot HA, Paix~ao, MP, Wen, CL. Teledermatology – past, present and future. An Bras Dermatol 2005; 80: 523–32). The goal of this study was to evaluate the need for the patient’s clinical questionnaire, in addition to digital photography for population and opportunistic screening for skin cancer via teledermatology. The study population comprised 1204 people served by a prevention mobile unit between February 2010 and July 2012. All participants were seen by a doctor and had images of the lesions captured. In the first stage of the study only pictures were sent to two doctors, who had at least 10 years of experience in the diagnosis and treatment of skin cancer to give their diagnoses. In the second stage, in addition to the photographs, a questionnaire containing patients’ clinical data was also sent, addressing their personal and family medical history, history and physical characteristics of the lesion and skin cancer risk factors. The two observers used the images and gave their diagnosis, classifying them as lesions suspicious for malignancy, lesions with benign features or nonassessable lesions. The results were compared and subjected to descriptive statistical and accuracy analyses. The anatomopathological result was compared with the diagnosis of the observers. The accuracy of observer one was 819% without the help of the questionnaire (first stage) and 809% with the aid of the questionnaire (second stage). The accuracy of observer two was 873 and 858, respectively. Thus, in the present study, the questionnaire containing the patients’ clinical data did not improve the results of the observers. Therefore, one could use only digital photography for population and opportunistic screening for skin cancer via teledermatology.

065 Malignant skin neoplasms as a manifestation of primary multiple cancer N. Malishevskaya,1 A. Sokolova1 and S. Berzin2 1

Federal State Budgetary Institution ‘Ural Research Institute of Dermatology, Venereology and Immunopathology,’ the Ministry of Health of the Russian Federation, Ekaterinburg, Russia and 2Sverdlovsk Regional Oncology Center, Ekaterinburg, Russia The problem of multiple primary malignant tumours is becoming more important due to the increasing incidence of cancer. Multiple primary malignancies have several clinical forms: primary multiple skin cancer, skin cancers combined with extracutaneous localizations, and cancer induced by radiotherapy and chemotherapy. A retrospective analysis of the registration cards of newly diagnosed patients with malignancies, subjected to check-ups from 2000 to 2010, was held in the Sverdlovsk Regional Oncology Center. To study the frequency of detection of extracutaneous malignancies in patients with skin cancer (n = 579) we analysed data from their case histories, showing that 272 patients had basal cell skin carcinoma (BCC), 202 patients had squamous cell carcinoma (SCC) and 105 patients had skin melanoma (SM). In total 134 cases of primary multiple skin cancer were identified, of British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

30 WCCS Abstracts

which five cases (37%) were primary multiple melanomas and nine (67%) were a combination of melanoma with BCC. The proportion of patients with primary multiple melanoma among all newly registered patients with melanoma was only 11%. We diagnosed one case of melanoma developing on the cheek in the atrophic scar formed after radiotherapy for BCC. Among all the patients with skin cancer, primary multiple extracutaneous malignant neoplasms were detected in 62 people (107%). Among 474 patients with BCC and SCC, malignant neoplasms of extracutaneous localization were recorded in 125% of patients, more often in women (144%) than in men (105%). Among 105 patients with SM, tumours of extracutaneous localization occurred 43 times less than for BCC and SCC, in 29% of cases (19% for women, 37% for men). This difference may be due to the median age of the analysed group of patients with SM, which was 476  29 years – significantly below the average age of patients with SCC (601  32 years) and BCC (673  39 years). Most often the second malignant tumour was localized in the colon (212%), lung and bronchus (200%), urinary tract organs (143%), rectum (114%) and lower lip (114%). Skin cancer in women is most frequently (657%) combined with reproductive system tumours. A combination of BCC and thyroid gland cancers was diagnosed in 86% of women. In men, skin cancers were accompanied by malignancies of the gastrointestinal tract (370%), lung and bronchus (259%) and lips (111%). The results provide a basis for considering all patients with primary multiple cancers as a risk group for extracutaneous localizations, and support performing follow-up monitoring.

two private sector organizations. Only one surveyed industry (U.K. armed forces) had a formal and enforced occupational sun protection policy. However, four of the six employers did give advice on sun protection, with two of these institutions supplying workers with the Health and Safety Executive guidance on sun protection. One employer gave out no advice as such but supplied their workers with sunscreen if requested. All but one employer supplied sunscreen if it was requested. One city council response stated they were sued several years ago for an adverse medical reaction to sunscreen and no longer provided it to their workers. It is disappointing that only one employer with significant outdoor exposure had an enforced occupational sun protection policy. However, it is encouraging that both public and private sector companies appear to offer good, and often official, sun protection advice that is structured and written. Some groups repeat this advice after a time interval, in one example this was every 2 years. Although it is encouraging to see some employers taking an interest in occupational sun exposure and the danger it poses, it is not clear whether the risk of potential future legal claims is the only motive for these policies. Ideally there should be increasing adoption of occupational sun-safety education programmes involving employers, dermatologists and cancer foundations.

067 (PL01) Unravelling transforming growth factor-b signalling in human cutaneous squamous cell carcinoma A. Rose,1 C. Pourreyron,1 K. Purdie,2 C. Harwood,2 I. Leigh,1 C. Proby,1 A. South1 and G. Inman1 1

066 Occupational sun protection: fully protected? G. Parkins and G. Wylie Alan Lyle Centre for Dermatology Glasgow, Glasgow, U.K. Solar ultraviolet radiation is a well-known risk factor in the development of skin cancer. This is of particular concern among outdoor workers, with studies showing that they have a significantly greater risk of developing nonmelanoma skin cancers compared with indoor workers (Reinau D, Weiss M, Meier CR et al. Outdoor workers’ sun-related knowledge, attitudes and protective behaviours: a systematic review of crosssectional and interventional studies. Br J Dermatol 2013; 168: 928–40). Against this backdrop, our aim was to determine whether employers of large groups of outdoor workers adopted any specific sun protection policy. We contacted various large public and private sector companies that employ outdoor workers, including four city council departments, the Forestry Commission, Amey, the Lawn Tennis Association, Network Rail, two large Scottish footballs clubs, the U.K. armed forces, British Airways and the roads network company BEAR Scotland. We categorized responses regarding employee sun protection advice or policy into (i) no policy, (ii) advice only or (iii) formal and enforced occupational sun protection policy. Responses were received from four public sector and

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University of Dundee, Dundee, U.K. and 2Barts and London School of Medicine and Dentistry, London, U.K. The incidence of cutaneous squamous cell carcinoma (cSCC) continues to rise. A small subset become metastatic, which is associated with poor survival. Transforming growth factor (TGF)-b has emerged as a key orchestrator of skin tumorigenesis. The extent of its role in cSCC remains poorly defined. We aimed to assess the frequency of mutation of the TGF-b type 1 and 2 receptors (TbRI and TbRII) in cSCC, and the structural/functional impact on TGF-b signalling both in vitro using human primary cSCC cell lines and in primary human cSCC tissue. We carried out targeted Roche-454 sequencing of TbRI and TbRII using 82 microdissected human cSCC tumour samples and 21 human cSCC cell lines. PolyPhen-2 algorithms and 3D-modelling (PyMolTM) examined the functional and structural impact of sequence variants. Whole cell lysates of cSCC cell lines were assessed for altered TGF-b signalling and correlated to mutational status. Incucyte ZoomTM live cell imaging was utilized to examine TGF-b growth arrest in vitro. TbRI and TbRII mutants were generated using site-directed mutagenesis. The Dual-Luciferaseâ Reporter Assay was used to assess loss of function, utilizing a (CAGA)12-luciferase reporter plasmid cotransfected with mutant receptors into TbRI and TbRII null cell lines. Sequenced TbR wild-type and mutant tumours were examined by immunohistochemistry for immunoreactivity to key mediators of the TGF-b signalling pathway. © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 31

Overall 44% of tumour samples (n = 82) and 29% of cell lines (n = 21) harboured mutations of TbRI and TbRII, many arising at key residues for both receptor contact and kinase function. No mutations were seen in normal skin (n = 7). Both TbR wild-type metastatic cell lines and mutant TbR cell lines evade TGF-b-induced growth arrest. One-third of all cell lines tested showed loss of active TGF-b signalling, also correlating with TbR mutation status. TGF-b lost the ability to induce (CAGA)12-luciferase in a number of both TbRI and TbRII extracellular and kinase domain mutations. TGF-binduced growth arrest was restored in a TbRII mutant primary cSCC cell line following transfection of wild-type TbRII plasmid. Presence of TbR mutation correlated with loss of active TGF-b signalling in immunohistochemistry, as indicated by loss of immunoreactivity to phospho-Smad3 (P = 0001). In conclusion, mutations of TbRs are a relatively common event in sporadic cSCC and may be a key driving event in cSCC tumorigenesis. Analysis of TbR status could be utilized as a prognostic tool and patient stratification for therapeutic interventions seeking to target the TGF-b pathway.

068 (PL06) Human leucocyte antigen and human papillomavirus in male genital lichen sclerosus, penile precancer and penile cancer T.N. Shim,1 R. Meys,1 S.I. Goolamali,2 F. Tavarozzi,3 N. Francis,4 M. Dinneen,2 A. Freeman,1 C. Jameson,1 A. Muneer,1 S. Minhas,1 M.N. De Koning,5 K.J. Purdie,6 F.M. Gotch,2 S.G.E. Marsh,3 C.A. Harwood6 and C.B. Bunker1 1

University College Hospital, London, U.K., 2Chelsea and Westminster Hospital, London, U.K., 3Anthony Nolan Research Institute, London, U.K., 4 Imperial Healthcare NHS Trust, London, U.K., 5DDL, Rijswijk, the Netherlands and 6Queen Mary University, London, U.K. Male genital lichen sclerosus (MGLSc) is an acquired cutaneous disease that results in sexual and urological dysfunction and penile squamous cell carcinoma (PSCC). Factors such as human papillomavirus (HPV) and immunogenotype may contribute to the pathogenesis of MGLSc. HPV is involved in the pathogenesis of penile carcinoma in situ (PCIS) and PSCC, but the part played by immunophenotype is unknown. This study has addressed the roles of human leucocyte antigen (HLA) and HPV and their interaction in MGLSc, PCIS and PSCC. In total 197 cases (88 MGLSc, 72 PCIS and 37 PSCC) were studied. DNA was extracted from both paraffin-embedded sections (for HPV) and blood (for HLA). Broad-spectrum polymerase chain reaction combined with a reverse hybridization assay was used to identify all HPV types. The previously published HLA results from healthy blood donors were used as control subjects. For categorical data, the v2-test was utilized together with Yates correction for continuity and Bonferroni corrections for multiple statistical testing. The initial results suggested that B*35, B*51, C*15, DRB1*04 and DRB1*10 were associated with susceptibility to MGLSc, and DQA1*01 with protection against MGLSc, but statistical significance was lost with Bonferroni correction. C*15 (corrected P = 0.049) con© 2014 The Authors BJD © 2014 British Association of Dermatologists

fers susceptibility to PCIS, whereas DQA1*01 (corrected P = 0.02) protects from PCIS. B*07 and DQA1*01 initially appeared to protect against PSCC, but statistical significance was not achieved with Bonferroni correction. HPV DNA was identified in 33 of 88 (38%) MGLSc, 65 of 72 (90%) PCIS and 20 of 37 (54%) PSCC. HPV-16 was the most prevalent type found in this study: 11 of 88 (12%) MGLSc, 35 of 72 (49%) PCIS and 10 of 37 (27%) PSCC. Subgroup analyses were performed according to HPV-16 status. HPV-16-associated MGLSc cases showed no statistically significant association with HLA. C*15, DQA1*02 and DQA1*03 appeared associated with HPV-16-infected PCIS cases, and B*57 seemed to predispose to HPV-16-infected PSCC, but Bonferroni statistical significance was not obtained. This is the first study to explore HLA and HPV and their interaction in MGLSc, PCIS and PSCC. Although larger sample sizes are needed to tease out the relationships, these results imply that immunogenotype may play a role in the pathogenesis of PCIS but not of MGLSc.

069 (PL08) TERT promoter mutation characterization in acral lentiginous melanomas V. Vazquez,1,2 A.L. Vicente,2 A. Carloni,2 G. Berardinelli,2 C. Scapulatempo,2,3 O. Martinho2,4 and R. Reis2,4 Melanoma and Sarcoma Department, 2CPOM – Molecular Oncology Center, Pathology Department, Barretos Cancer Hospital, Barretos, Brazil and 4 Instituto de Investigacß~ao em Ci^encias da Vida e Saude (ICVS) da Universidade do Minho, Minho, Portugal Acral lentiginous melanoma (ALM) is a less common and aggressive melanoma subtype with a singular clinical and molecular characterization. TERT (telomerase reverse transcriptase gene) promoter mutations have being described as frequent in melanomas and infrequent in ALM, but their real incidence and clinical relevance are unclear. The objectives of the study was to describe the prevalence of TERT promoter mutation in ALM, the correlation to other usual mutations and clinical aspects. In total 55 samples from 43 patients with ALM were analysed. Primary tumour samples were obtained from all cases. Ten lymph nodes and two cutaneous metastases were also studied. DNA was extracted from formalin-fixed paraffin-embedded tissue of all cases, and the mutation profile of BRAF, NRAS, KIT, PDGFRA and the TERT promoter were determined by polymerase chain reaction (PCR) amplification followed by direct Sanger sequencing. KIT and PDGFRA gene amplification was determined by quantitative PCR. Clinical information for survival, clinical stage and Breslow tumour classification were obtained from medical records. TERT promoter mutations were found in seven of 43 samples (16%): six of 43 (14%) primary tumours and one of eight (12%) lymph nodes. In eight cases where both primary and lymph node TERT promoter mutation status was seen, two presented mutations in the primary sample and not in the lymph node, one in the lymph node and not in the primary, and five were wild-type in both. Three cases presented BRAF V600E mutations, with no TERT promoter mutations. From six cases 1 3

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32 WCCS Abstracts

(14%) with KIT mutations, two (5%) presented simultaneous TERT promoter mutations. There was one case with TERT promoter mutation and PDGFRA mutation. There was no NRAS mutation or KIT/PDGFRA amplification. The survival curves did not show a difference according to TERT promoter mutation status. The mutation status was not associated with the Breslow classification or tumour–nodes–metastasis clinical stage. We showed that TERT promoter mutation is present in one of six ALMs. No significant association was observed between the TERT mutation status and the clinical and molecular features of ALM. Future studies are needed to evaluate the biological and clinical impact of TERT in a larger series of ALMs.

070 (PL09) Decreased major histocompatibility complex I expression and deranged antigen presentation in Merkel cell carcinoma correlates with a poorer prognosis V. Huang,1 J. DeCaprio,1 C. Elco,1 A. Dorosario,1 L. Wang2 and R. Clark1 1

Brigham and Women’s Hospital, Boston, MA, U.S.A. and 2The Institute for Cancer Care at Mercy Medical Center, Baltimore, MD, U.S.A. Merkel cell carcinoma (MCC) is a polyomavirus-associated cancer that actively expresses viral antigens but is nonetheless highly aggressive. We previously attempted to study MCC viral antigens by mass spectrometry. However, neither viral antigens nor ubiquitously expressed housekeeping genes were expressed on the cell surface, likely because major histocompatibility complex (MHC) I was strongly downregulated. We previously found that transcription of MHC I and III critical components of the peptide-loading complex (TAP-1, TAP-2 and tapasin) was decreased in MCC cell lines but was normalized by type II but not type I interferons. To evaluate the clinical significance of MHC I downregulation, immunohistochemistry of primary MCC was performed and correlated with patient outcomes. MHC I was downregulated in 44 of 73 tumours evaluated. Preliminary analyses suggest a trend for longer survival in patients with high-intensity MHC I vs. patients with low expression (hazard ratio 325, 95% confidence interval 117–898; P = 0023). In immunodeficient NSG mice, MCC cell lines formed solid tumours that recapitulated the downregulation of MHC I observed in primary tumours and in cultured cell lines. Intratumoral injection of type I interferon-c led to upregulation of MHC I expression by immunohistochemistry and increased transcription of MHC I, TAP-1, TAP-2 and tapasin as assayed by reverse-transcription polymerase chain reaction. In summary, we found that MHC I downregulation is a feature of primary MCC, may correlate with poorer outcomes and can be reversed by pretreatment with type II but not type I interferons. Interferon-c is clinically approved and we would recommend its use in combination with immunomodulatory therapies (cytotoxic T-lymphocyte antigen 4/programmed death-1 blockade) in the adjuvant therapy of MCC.

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071 (PP01) The actinic keratosis microRNAome: microRNA expression in actinic keratosis and matched healthy-appearing skin T. Litman,1 M.H. Hansen,1 S. Emmert,2 H.A. Haenssle,2 M.P. Schon2 and J.R. Zibert1 1

LEO Pharma A/S, Ballerup, Denmark and 2Department of Dermatology, Venereology and Allergology, Georg August University, Gottingen, Germany MicroRNAs (miRNAs) constitute a group of short noncoding RNAs that regulate gene expression at the post-transcriptional level. They play a key role in many physiological and pathological processes, including development and differentiation of cells, inflammation and cancer. Actinic keratoses (AKs) are precursor lesions to squamous cell carcinoma (SCC) and may even represent an early stage of SCC. However, only limited data exist of the underlying molecular signature of AK and SCC, and hitherto no data have been reported on miRNA expression profiles of AK. Therefore, we here aimed to provide a comprehensive map of the miRNA expression pattern of AK. Twenty-five typical clinical AKs and matched healthyappearing skin (HAS) biopsies were prospectively collected and preserved as formalin-fixed paraffin-embedded samples and total RNA was extracted. From seven patients miRNA expression profiles were generated by applying a quantitative polymerase chain reaction (qPCR) panel covering 742 human miRNAs. From the profiles 14 selected miRNAs were validated in all 25 patients by reverse-transcription qPCR. Thirty-three miRNAs were differentially expressed (log2 difference > 05, P < 005) between AK and HAS, including miR-21, miR-22, miR-31, miR-93, miR-211 and miR-409–3p (all upregulated in AK), and miR-10a, miR-19b, miR-30e, miR-101, miR-141 and miR-200a (downregulated in AK). Based on target prediction and gene enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathways were identified that could potentially be affected by these miRNAs, including glycosaminoglycan biosynthesis, focal adhesion and ErbB signalling. A comparison of our data with published miRNA expression studies on SCC showed some overlap between AK and SCC. In particular, miR-21 and miR-31 were upregulated and miR30e and miR-101 were downregulated in AK and SCC compared with HAS. Our analysis of the AK microRNAome has uncovered novel miRNAs and potential pathways associated with AK and SCC ( number NCT01387711).

072 (PP04) Induction of complete regression of cutaneous squamous cell carcinomas by topical application of dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors in K14-Fyn Y528F mice X. Yang,1 C. Marshall,1 T. Dentchev,1 T. Salah,1 F. Stauffer,2 A. Lerchner,2 F. Seiler,2 F. Kalthoff2 and J. Seykora1 1

University of Pennsylvania, Philadelphia, PA, U.S.A. and 2Novartis Institutes for Biomedical Research, Basel, Switzerland Cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer. Human cSCCs demonstrate activation

© 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 33

of canonical oncogenic signalling pathways that include extracellular signal-related kinase (ERK)1/2, phosphoinositide 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR), and Src tyrosine kinases and phosphosignal transducer and activator of transcription (p-STAT)3. The K14-Fyn Y528F transgenic mouse is a model of cSCC that develops pr-cancerous lesions and cSCCs resembling human lesions with activation of the Erk1/2, phosphoinositide-dependent kinase (PDK)1/mTOR, pSTAT-3 and Src tyrosine kinase pathways. We wondered whether topically applied inhibitors specifically targeting the PI3K/mTOR pathway would induce regression of cSCCs in K14-Fyn Y528F mice. To test this hypothesis, 6-week-old cohorts of K14-Fyn Y528F mice were treated with small-molecule catalytic kinase inhibitors with low nanomolar potency in vitro against mTOR and class I PI3K kinases. A 06% gel containing DPT-NX7 or a 12% gel containing NIBR1112 were compared with control gel. The DPT-NX7-treated cohort contained seven mice with 25 cSCCs and the NIBR1112-treated cohort 10 mice with 38 cSCCs, while the control cohort contained seven mice with 28 cSCCs. The size range of cSCCs was similar in each cohort (8–166 mm2) and was measured using callipers before treatment and weekly thereafter. The gels were applied directly to lesions daily. After 2 weeks, NIBR1112 treatment decreased tumour size on average by 77%, while DPT-NX7 reduced tumour size by 63%. In the same period, the average tumour size increased by 9% in controls (P < 0001). After 5 weeks, the average tumour size decreased by about 96% in both the NIBR1112 and the DPTNX7 cohorts, with complete tumour regression rates of 79% and 76% in the NIBR1112 and the DPT-NX7 cohorts, respectively. In contrast, no significant regression was observed in the control cohort. Clinical and histological evaluation of regressing cSCCs in both the DPT-NX7 and NIBR1112 cohorts demonstrated residual epidermal hyperplasia, minimal inflammation and no ulceration. Immunohistochemical analysis of regressing cSCCs demonstrated normalization of phosphorylation levels of key pathway molecules such as S6 kinase, p-STAT-3 and PDK-1. In summary, topical application of DPT-NX7 or NIBR1112 gel induced almost complete cSCC regression in the K14-Fyn Y528F model without prominent inflammation or ulceration. These data suggest that topical application of potent dual PI3K/mTOR inhibitors may be useful for treating cSCCs.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

073 (PP07) The development of cutaneous squamous lesions in patients treated with vemurafenib: investigation of a possible role for human papillomavirus in addition to activated RAS K. Purdie,1 A. South,2 M. Sommerlad,3 H. Rizvi,4 I. Leigh,2 C. Proby2 and C. Harwood1 1

Centre for Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, U.K., 2Division of Cancer Research, Jacqui Wood Cancer Centre, Ninewells Hospital and Medical School, Dundee, U.K., 3Department of Dermatology and 4 Department of Pathology, Barts Health NHS Trust, London, U.K. Approximately half of metastatic melanomas have an activating mutation in the BRAF oncogene. The development of vemurafenib, a specific inhibitor for mutant BRAF, has been associated with tumour regression and improved overall survival in patients with BRAF-positive melanoma. However, one sideeffect is the de novo development of benign and malignant squamoproliferative lesions in up to 25% of individuals. The putative mechanism involves paradoxical increased mitogenactivated protein kinase (MAPK) signalling by BRAF inhibitors in the context of mutated or activated RAS. However, cutaneous squamous cell carcinomas (SCCs) have been reported to develop in association with wart-like lesions, and upregulation of the MAPK pathway is known to facilitate human papillomavirus (HPV) replication, suggesting a possible role for HPV in the pathogenesis of these lesions. We have examined RAS mutational status and the presence of HPV DNA in 45 skin biopsies from seven patients receiving vemurafenib (26 benign squamoproliferative lesions, 13 SCCs, six normal skin samples). A majority (80%, 36 of 45) of the samples were positive for beta- (epidermodysplasia verruciformis-associated) HPV, with a lower proportion (9%, four of 45) positive for cutaneous alpha-HPV. However, only a minority (9%, one of 11 SCCs; 33%, six of 18 benign squamoproliferative lesions; overall 24%, seven of 29) of lesions with apparent viral features at the clinicopathological level contained high levels of HPV DNA indicative of active infection. Activating RAS mutations were detected in 15of 45 (33%) samples (nine of 27 benign squamoproliferative lesions and six of 12 cSCCs). The majority (93%, 14 of 15) of mutations occurred in HRAS, with one mutation identified in KRAS and none in the NRAS gene. Nine of 15 (60%) activating RAS mutations occurred in codon 61, while three of 15 mutations (20%) were identified in each of codons 12 and 13; all three codons have been previously reported as mutational hotspots characteristic of vemurafenib-associated cSCC. The high frequency of RAS mutations in our sample series, together with the rapid time frame of their development, supports the hypothesis that these mutations are pre-existing and confer a selective advantage in the context of vemurafenib therapy. Our data suggest that HPV is unlikely to play a major aetiological role in these lesions.

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34 WCCS Abstracts

074 (PP08) Preclinical evidence that gamma-tocotrienol, a natural vitamin E constituent, ameliorates ultraviolet B-mediated DNA damage and impedes skin inflammatory and photoageing processes W.N. Yap,1 C.W. Fong,2 G. Sethi1 and A.P. Kumar1,3 1

National University of Singapore, Singapore, Singapore, 2Davos Life Science Pte Ltd, Singapore, Singapore and 3University of North Texas, TX, U.S.A. Tocotrienol (T3) is a less abundant and poorly studied form of vitamin E and has, for decades, been overshadowed by the more common form tocopherol (TP), in particular alphatocopherol (aTP). However, recent in vitro and in vivo evidence clearly shows that T3 possesses stronger anticancer and antiinflammatory properties than aTP due to its three double bonds on its farnesyl side chain. In this study, we elucidated the apparent disparity of photoprotection between cT3 and aTP by different administration routes (oral and topical) in a chronic model, which is physiologically and pathologically relevant. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell viability assay and flow cytometry were carried out to study ultraviolet (UV)B-induced cell cytotoxicity and apoptosis. Single-strand breaks (SSBs) and double-strand breaks (DSBs) of DNA were investigated using immunofluorescence and western blotting. Oxidative stress and inflammatory markers were detected by enzyme-linked immunosorbent assay. High-performance liquid chromatography was used to quantify vitamin E uptake. SKH-1 hairless mice were UVB irradiated for 30 weeks in this skin cancer prevention study. Two different delivery systems were applied to compare the disparity of the photoprotective effect of cT3 and aTP. Among eight isomers of vitamin E, cT3 exerted the most potent effect in protecting UVB-induced cytotoxicity and apoptosis in HaCaT and CCD1106 epidermal keratinocyte cells. cT3 repaired SSBs and DSBs more efficiently than aTP by suppressing UVB-stimulated DNA lesions (cyclobutane pyrimidine dimers and 6,4-photoproducts) and dephosphorylated histone H2AX at a lower dose and in a shorter time. Elevated levels of oxidative stress markers (8-hydroxy-2ʹ-deoxyguanosine, malondialdehyde and protein carbonyl), as well as inflammatory markers (interleukin-6, interleukin-8 and cyclooxygenase-2), on UVB radiation showed attenuation by cT3 treatment. cT3 2% formulated cream was capable of reversing UVB-exposed epidermal hyperplasia at 24 weeks. It is noteworthy that the cT3-treated cohort for both administration routes demonstrated splenomegaly protection, with statistically significant lower granulocyte infiltration in the spleen. This may be ascribed to high intracellular uptake of cT3 by skin cells. This study unravels a new role of cT3 in dermatology, therefore presenting a potentially superior vitamin E analogue for the prevention of UVB-induced skin inflammation and photocarcinogenesis.

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075 (PP15) Prevalence of human papillomavirus in male genital lichen sclerosus, penile carcinoma in situ and penile carcinoma: correlation with p16INK4a expression and immune status T.N. Shim,1 M.N. de Koning,2 S.I. Goolamali,3 R. Meys,3 N. Francis,4 C. Jameson,1 A. Freeman,1 M. Dinneen,3 S. Minhas,1 A. Muneer,1 K.J. Purdie,5 C.A. Harwood5 and C.B. Bunker1 1

University College Hospital, London, U.K., 2DDL, Rijswijk, the Netherlands, Chelsea and Westminster Hospital, London, U.K., 4Imperial Healthcare NHS Trust, London, U.K. and 5Queen Mary University, London, U.K. Penile squamous cell carcinoma (PSCC) is associated with significant morbidity and mortality. It appears to have two aetiopathogenic pathways: (i) human papillomavirus (HPV) dependent and (ii) HPV-independent, male genital lichen sclerosus (MGLSc) related. Clinically penile carcinoma in situ (PCIS) is recognized to precede PSCC in many cases. p16INK4a has been suggested as a surrogate biomarker of HPV infection. Here, we have determined the prevalence of HPV in MGLSc, PCIS and PSCC, and correlated the results with p16INK4a immunostaining and immune status. In total 186 cases (87 MGLSc, 62 PCIS and 37 PSCC) were studied. Of these, 25 were immunosuppressed: 13 with HIV, four transplant recipients (two renal, one bone marrow and one lung) and eight on immunosuppressants. DNA was extracted from paraffinembedded sections and typed for beta, genital and wart HPV by using broad-spectrum polymerase chain reaction combined with a reverse hybridization assay. p16INK4a antibody (JC8; Santa Cruz, sc-56330) at dilution 1 : 200 was used to stain paraffin-embedded tissue sections using conventional immunohistochemical techniques. The c2-test was used to evaluate the relationship between categorical variables. HPV DNA was identified in 33 of 87 (38%) cases of MGLSc, 57 of 62 (92%) PCIS and 20 of 37 (54%) PSCC. High-risk HPV was detected in 24 of 87 (28%) cases of MGLSc, 51 of 62 (82%) PCIS and 15 of 37 (41%) PSCC. HPV-16 was the most prevalent HPV subtype detected, in 10 of 87 (11%) MGLSc, 28 of 62 (45%) PCIS and 10 of 37 (27%) PSCC. Strong p16INK4a immunostaining correlated with high-risk HPV in PCIS (P < 0001) and PSCC (P = 00016) but not MGLSc (P = 053). Subgroup analyses were performed according to the immunosuppression status. Strong p16INK4a immunostaining correlated with highrisk HPV in transplant recipients (P = 0046) but not in those who received immunosuppressants (P = 0064) or had HIV (P = 0071). HPV was detected in 54% of cases of PSCC, supporting the bimodal aetiopathogenesis of PSCC. HPV was detected in 92% of cases of PCIS, in keeping with a similar prevalence rate in the literature using similar technical approaches. Positive p16INK4a staining showed strong correlations with the detection of high-risk HPV in PCIS and PSCC. A previous study has shown that p16INK4a expression is independent of immune status. While our study showed a correlation of p16INK4a with high-risk HPV in transplant recipients, the interpretation is limited by the small cohort size. In this study, HPV was present in 38% of cases of MGLSc. This does not 3

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correlate with p16INK4a immunostaining, suggesting detection of skin surface ‘passenger HPV’, and it is unlikely that HPV plays a role in the aetiopathogenesis of MGLSc.

076 (PP18) Vemurafenib induces proliferation, differentiation, invasion and stromal activation in a threedimensional human skin carcinoma model M. Tham,1 M. Berning,1 A. Jauch2 and P. Boukamp1 1

Division of Genetics of Skin Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany and 2Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany Adverse effects of melanoma therapy by the BRAF V600E-targeting small-molecule inhibitor vemurafenib lead to the development of skin keratoacanthomas (KAs) and squamous cell carcinomas (SCCs) in a significant number of patients. As KAs and SCCs are observed within a few weeks of therapy, we hypothesize that vemurafenib treatment is directly involved in the progression of pre-existing oncogenic keratinocyte lesions. Using monolayer cultures of cutaneous cells and three-dimensional organotypic cocultures of the skin, we investigated the direct and indirect effects of vemurafenib. By treating BRAF V600E-mutant A375 melanoma cells, we confirmed that vemurafenib blocks Raf/mitogen-activated protein kinase (MAPK) kinase (MEK)/extracellular-signal related kinase (ERK)/MAPK signalling. In contrast, treatment of all BRAF wild-type cells, including dermal fibroblasts, normal human epidermal keratinocytes (NHEKs) and premalignant HaCaT and benign tumorigenic HRAS G12V-transfected HaCaT-RAS A-5 cells, resulted in MEK/ERK pathway hyperactivation, while the Akt and p38 pathways were not affected. Despite MAPK activation, neither proliferation nor apoptosis was altered in HaCaT keratinocyte monocultures. Genetic analyses of HaCaT cells treated for 5 weeks with vemurafenib did not show genomic instability, but rather showed a selective growth advantage of genetic subpopulations. To investigate long-term effects of increased BRAF signalling, NHEK, HaCaT and HaCaT-RAS A-5 cells were treated with vemurafenib in organotypic cocultures. After 1 week of treatment, all analysed keratinocytes showed a dose-dependent increase in differentiation as detected by filaggrin immunofluorescence. This represents a direct effect of vemurafenib on keratinocytes and resembles the frequent hyperkeratosis in patients with vemurafenib-treated melanoma. Remarkably, while NHEK and HaCaT cells stayed highly differentiated in the epithelia, HaCaT-RAS A-5 cells showed increased proliferation and invasion into the underlying dermal equivalent after 3–5 weeks of treatment in a dose-dependent manner. Thus, our findings strongly correlate with the in vivo data of rapidly developing hyperkeratosis and KAs/SCCs in patients with vemurafenibtreated melanoma. It yet has to be determined whether the increased proliferation and invasive growth of HaCaT-RAS A-5 cells are direct effects of vemurafenib or are mediated indirectly through an altered microenvironment induced by MAPK-activated fibroblasts. In conclusion, we demonstrated that the selective BRAF V600E inhibitor vemurafenib directly © 2014 The Authors BJD © 2014 British Association of Dermatologists

triggers MAPK pathway hyperactivation in cutaneous BRAF wild-type cells. Moreover, we observed increased differentiation of all analysed keratinocytes as well as increased proliferation and invasive growth of benign HaCaT-RAS A-5 cells in organotypic cocultures. This reflects the clinical observation of rapidly evolving and well-differentiated KAs/ SCCs after vemurafenib treatment, providing evidence for the hypothesis of a selective pressure on premalignant cells.

077 (PP20) Immunosuppression, human papillomavirus and Merkel cell polyomavirus in male genital lichen sclerosus, penile precancer and penile cancer T.N. Shim,1 S.I. Goolamali,2 N. Francis,3 M. Dinneen,2 A. Muneer,1 S. Minhas,1 A. Freeman,1 C. Jameson,1 K.J. Purdie,4 C.A. Harwood4 and C.B. Bunker1 1

University College Hospital, London, U.K., 2Chelsea and Westminster Hospital, London, U.K., 3Imperial Healthcare NHS Trust, London, U.K. and 4 Queen Mary University, London, U.K. Immunosuppression and viruses such as human papillomavirus (HPV), and more recently Merkel cell polyomavirus (MCPyV), have been reported as potential causative or associated agents in many cutaneous skin cancers. We have investigated the roles of HPV, MCPyV and immunosuppression in male genital lichen sclerosus (MGLSc), penile carcinoma in situ (PCIS) and penile squamous cell carcinoma (PSCC). DNA was extracted from microdissected, formalin-fixed, paraffin-embedded (FFPE) tissue of 164 cases (77 MGLSc, 52 PCIS and 35 PSCC). Both 120-b.p. and 268-b.p. b-globin products indicative of the presence of intact amplifiable DNA could be amplified in 143 cases (68 MGLSC, 41 PCIS and 34 PSCC). Broad-spectrum polymerase chain reaction (PCR) combined with a reverse hybridization assay was used to type beta, genital and wart HPV. PCR was performed to identify the presence of MCPyV using two previously described sets of primers: MCVPS1 (small tumour antigen) and MCPyV (large tumour antigen), both of which yield short PCR products (109 and 195 b.p., respectively), which are well suited for testing poor-quality DNA derived from FFPE tissue. Visible PCR products obtained by PCR amplification were classified as polyomavirus-positive samples. MCVPS1 DNA was not detected in any of the cases. However, 11 cases (five MGLSc, three PCIS and three PSCC) were positive for MCPyV. Two of five cases of MGLSC were positive to HPV-16. All three cases of PCIS were positive to HPV, of which two cases were HIV positive. One HIV-positive case was positive for HPV-6 and the other had multiple infections: HPV-11, 33, 39 and 92. Twenty of the total 143 cases were immunosuppressed: nine with HIV, five transplant recipients (two bone marrow, two renal and one lung) and six on immunosuppressant medication (two sarcoidosis, one myasthenia gravis, one ulcerative colitis, one pemphigus vulgaris and one psoriasis). Only two of nine cases of HIV were positive for both MCPyV and HPV (P = 009). To our knowledge, this is the first study of MCPyV in MGLSc, PCIS and PSCC. There is compelling evidence to support the role of MCPyV in British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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the tumorigenesis of Merkel cell carcinoma. More recently, the presence of MCPyV has been reported in nonmelanoma skin cancer (squamous cell carcinoma, Bowen disease and basal cell carcinoma) affecting immunosuppressed and immunocompetent patients. Our results do not support a role for MCPyV in the pathogenesis of MGLSc or in squamous carcinogenesis of the penis.

078 Heat-shock protein (Hsp)70 inhibition enhances the effect of the Hsp90 inhibitor NVP-AUY922 on melanoma cells A. Yeramian,1 A. Vea`,2 M. Santacana,1 X. MatiasGuiu1 and R.M. Marti2 1

Department of Pathology and Molecular Genetics and 2Department of Dermatology, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, Lleida, Spain In the last 10 years, heat-shock proteins (Hsps) have emerged as potential targets for cancer therapy. Hsp90 inhibitors target multiple survival pathways, a number of which are highly mutated in malignant melanoma (MM) (Grbovic OM, Basso AD, Sawai A et al. V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors. Proc Natl Acad Sci U S A 2006; 103: 57–62). However, Hsp90 inhibition turns on an increased compensatory expression of Hsp70, reducing thus the antitumoral effect of the Hsp90 inhibitor NVP-AUY922. In this study, we tested the effects of NVP-AUY922 on five metastatic melanoma cell lines. We also evaluated the antitumour efficacy of NVP-AUY922 when combined with an Hsp70 inhibitor in the A375M cell line. MM cell survival was assessed by MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] and clonogenic assays. We measured the expression of key survival proteins by western blot, and assessed nuclear factor(NF)-jB transcriptional activation by in vitro luminescent assay. Cell cycle analysis and annexin /immunoperoxidase staining was performed using a flow cytometer. Our results show that NVP-AUY922 decreased the growth of MMs in vitro, and their clonogenic survival. NVP-AUY922 reduced the expression of client proteins involved in cell survival, and inhibited basal NF-jB activity in melanoma cells by increasing the levels of IjB-alpha. The combination of both Hsp90 and Hsp70 inhibitors (pifithrinl) induces a synergistic reduction of cell survival, suggesting that Hsp70-induced levels by Hsp90 inhibition are involved in a cytoprotective effect. Pifithrin-l induces a synergistic increase of both early and late apoptotic cell death when combined with an Hsp90 inhibitor in A375M cells, suggesting a protective role of Hsp90 in NVP-AUY922-induced antitumour effects. Furthermore, pifithrin-l induces a synergistic increase in sub-G1 when combined with an Hsp90 inhibitor in A375M cells. In conclusion, targeting both Hsp90 and Hsp70 seems to be of therapeutic benefit in MM in an in vitro model. This combination has to be tested in vivo models of MM. This study was supported by the Lliga Contra el Cancer de les Comarques de Lleida.

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079 Expression of cancer testis antigens NY-ESO-1, MAGE-A1 and MAGE-A4 as a prognostic factor in patients with primary cutaneous melanoma D. Katalinic University Hospital Centre Zagreb, Zagreb, Croatia Cancer testis antigens (CTAs) form a group of proteins that are expressed predominantly in gametes and trophoblasts, but are absent in most adult tissues. During malignant transformation CTA genes are often activated (Hodi FS. Well-defined melanoma antigens as progression markers for melanoma: insights into differential expression and host response based on stage. Clin Cancer Res 2006; 12: 673–8). This paper deals with the clinical significance of the immunohistochemical expression of NY-ESO-1, MAGE-A1 and MAGE-A4 antigens in patients with cutaneous naevi and melanoma. All patients were white and of European origin, and prior to enrolment in the study an informed consent form was signed by all subjects. The study was approved by the local ethics committee. The study included 93 patients: 49 with primary cutaneous melanoma (mean age 466  3 years, range 28–64) and 44 with naevi (mean age 382  2 years, range 25–60) who had undergone surgery. NY-ESO-1, MAGE-A1 and MAGE-A4 antigen expression was determined by an immunohistochemical method using the following monoclonal antibodies (mAbs) to the following antigens (mAb/antigen): ES121/NY-ESO-1, MA454/MAGE-A1 and 57B/MAGE-A4. Additionally, the expression of these antigens was compared with the clinicopathological features of the patients. All 44 naevi were negative for the mAbs ES121, MA454 and 57B. In melanoma, the immunoreactivity was as follows: ES121, 12 of 49 (24%); MA454, 14 of 49 (29%) and 57B, 17 of 49 (35%). However, 34 of 49 (69%) were positive for at least one CTA. No statistically significant difference in patient survival was found with regard to CTA expression. This study demonstrates that the expression of different CTAs might be a valuable prognostic factor regarding distinction between cutaneous naevi and melanoma.

080 Oxidative stress, normal melanocytes and melanoma L. Denat,1 M. Dutordoir,1 F. Laugier,2 Y. Phalente,1 C. Jones,1 N. Dumaz2 and L. Marrot1 1

L’Oreal Research and Innovation, Aulnay-sous-Bois, France and 2INSERM Unite 976, Institut de Recherche sur la Peau, H^opital Saint-Louis, Paris, France Epidermal melanocytes are particularly exposed to oxidative stress. On the one hand, even if reports are conflicting, melanin may have pro-oxidant properties in some conditions. On the other hand, sun exposure is a major inducer of reactive oxygen species. Oxidative stress can disrupt melanocyte homeostasis, leading to cell death or malignant transformation. There is increasing evidence for the significance of oxidative stress in melanoma initiation and progression. Moreover, intrinsic antioxidant defences are compromised in © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 37

melanoma. We compared basal expression of about 200 genes encoding phase I or phase II metabolism enzymes in cocultured normal human melanocytes and keratinocytes from the same donors. Some significant differences were observed, in particular melanocytes were well equipped for protection against pro-oxidant species compared with keratinocytes. The impact of various stressors such as solar ultraviolet radiation, hydrogen peroxide and hydroquinone was also assessed. Melanocytes were less sensitive to the various evaluated stresses, and gene expression modulations were observed mostly in keratinocytes compared with melanocytes. These results suggest that epidermal cells sharing the same genetic background and growing in the same culture medium displayed specificities in basal and stress-induced expression of genes controlling metabolism and that normal melanocytes were equipped to cope with oxidative stress. To understand the role of oxidative stress in melanoma development, premelanoma models expressing BRAF or cKIT mutations have been generated and the impact of various stressors on melanocyte transformation will be studied.

081 A role for vitamin D in melanoma prevention, growth and metastasis K.M. Dixon,1 N. Painter,1 A. Shariev,1 S.S. Deo,1 S.J. Assinder,1 A.W. Norman2 and R.S. Mason1 1

Disciplines of Anatomy & Histology and Physiology, Bosch Institute, The University of Sydney, Sydney, NSW, Australia and 2Department of Biochemistry, University of California, Riverside, CA, U.S.A. Australia has the highest incidence of melanoma in the world, where it is responsible for 75% of all skin cancer deaths. The relationship between melanoma and sunlight is interesting in that sunburn is causal while occupational sun exposure is not, and it has been suggested that patient outcome may be linked to vitamin D levels at diagnosis. The biologically active compound, 1,25-dihydroxyvitamin D3 (1,25D), which is produced in skin, can mediate its effects through either a wellestablished genomic pathway or a nongenomic pathway. We previously showed that 1,25D and a low calcaemic nongenomic analogue reduced ultraviolet (UV)-induced melanocyte cell death and DNA damage (thymine dimers), and that these effects were reversed by a nongenomic antagonist but not affected by a genomic antagonist. Moreover, we demonstrated that the UV-induced increase in tumour suppressor p53 was further enhanced when melanocytes were incubated with 1,25D immediately after UV. Thus, we have clear evidence that targeting of the nongenomic pathway in melanocytes prevents potentially mutagenic DNA damage that may lead to melanoma. Incubation of human melanoma cell lines with 1,25D significantly (P < 0001) reduced cell growth and migration. We speculate that the ability of 1,25D to inhibit growth and metastasis of melanoma cells may be associated with our finding in these melanoma cells of a 1,25D-induced increase (P < 005) in PTEN, a known tumour suppressor and

© 2014 The Authors BJD © 2014 British Association of Dermatologists

target of the metastasis suppressor, NDRG1. Nongenomic vitamin D analogues, which have no demonstrated toxicity in normal cells, may prove useful in preventing and inhibiting the growth and metastasis of melanoma cells.

082 Induction of both extrinsic and intrinsic apoptotic cell death mechanisms in human metastatic melanoma cells through hypericin-based photodynamic therapy B. Kleemann,1 B. Loos,2 D. Lang,1 T. Scriba1 and L.M. Davids1 1

University of Cape Town, Cape Town, South Africa and 2University of Stellenbosch, Cape Town, South Africa Cutaneous metastatic melanoma remains the most lethal form of skin cancer representing > 75% of skin cancer-related deaths. Resistance to chemotherapy is a primary cause of treatment failure and it remains pertinent to introduce improved or adjunctive forms of therapy. Photodynamic therapy (PDT) is a photomedicine for cancer that uses the synergistic cytotoxic action of a photosensitizer, light and oxygen. Together and upon activation, it causes the production of reactive oxygen species, which in turn destroys the tumour. A potent photosensitizer used in this treatment is hypericin (HYP), an extract from St John’s wort (Hypericum perforatum). However, its efficacy in treating melanoma has not been established. South Africa has the second highest incidence of malignant melanoma skin cancer in the world, second only to Australia. The importance of this therapy lies in the tumour specificity of the photosensitizer, leaving the healthy body intact, a clear advantage over conventional chemo- and radiation therapy. This in vitro study set out to determine the efficacy of HYP-PDT in inducing melanoma cell death. Cell viability studies revealed effective killing of melanoma cells at a dose of 3 lmol L 1 HYP-PDT. Cell death protein expression analyses showed an extrinsic caspase-dependent mode of cell death in unpigmented A375 melanoma cells (CASP3 and CASP8 cleavage at 24 h). Pigmented UCT Mel-1 melanoma cells exhibited an intrinsic caspase-dependent mode of cell death (CASP3 and PARP cleavage at 4 h and 7 h). Moderately pigmented 501mel melanoma cells showed PARP cleavage at 7 h, independent of CASP3. Furthermore, fluorescenceactivated cell sorting analyses revealed late-stage apoptosis/ necrosis in A375 (4 h, 7 h) and UCT Mel-1 (30 min, 7 h, 24 h) and necrosis in 501mel (1 h) melanoma cells. Confocal microscopy of transiently expressed, organelle-specific GFP-fusion proteins showed HYP only colocalizing with melanosomes and lysosomes. The colocalization of HYP with these organelles may circumvent melanoma cell death resistance mechanisms such as increased export of melanosomes and induction of autophagy. These novel findings point to a more tailored approach to treating pigmented and unpigmented melanoma using HYP-PDT as a potential adjunctive therapy.

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083 Investigating the in vitro effect of hypericininduced photodynamic therapy on the cells of the tumour microenvironment A. Popovic, F. Biteghe and L.M. Davids University of Cape Town, Cape Town, South Africa Bidirectional communication between cells and their microenvironment is critical for both normal tissue homeostasis and tumour development. As such, interactions between the cells of the tumour microenvironment (TME) and the associated malignant tumoral cells represent a powerful relationship that influences the initiation and progression of cancer. A prerequisite for effective cancer treatments is therefore the efficient and selective targeting of the tumoral cells with minimal collateral damage to the surrounding normal cells. We have shown hypericin-induced photodynamic therapy (HYP-PDT) to be effective in reducing melanoma cells (Davids LM, Kleemann B, Kacerovska D et al. Hypericin phototoxicity induces different modes of cell death in melanoma and human skin cells. J Photochem Photobiol B 2008; 91: 67–76). However, PDT’s effect on peritumoral cells, the normal cells surrounding the tumour, remains intriguing. The aim of this study was to investigate the cellular and molecular effects of HYP-PDT on normal human skin cells, of which cultured primary human keratinocytes, melanocytes and fibroblasts were chosen for this study. Cell viability analysis revealed a differential response to a range of HYP-PDT doses, in all the human skin cell types, with fibroblasts being the most susceptible, showing a significant difference in cell viability at 1 lmol L 1 (5640%  356), 2 lmol L 1 (4769%  389), 3 lmol L 1 (3294%  564) and 4 lmol L 1 (3357%  472) HYP-PDT. Melanocytes were less susceptible with a significant difference in cell viability at 2 lmol L 1 (6040%  714), 3 lmol L 1 (6083%  804) and lmol L 1 (3827%  427) HYP-PDT. Furthermore, keratinocytes were the least susceptible with an initial significant difference in viability at 4 lmol L 1 (7895%  6563) HYP-PDT. HYP-PDT susceptibility correlated with intracellular reactive oxygen species (ROS) production post-treatment: a significant 3814  1095-fold increase in ROS in fibroblasts, but no significant change in ROS in melanocytes and keratinocytes was observed. Moreover, cellular morphological changes, 24 h post-treatment suggested that these cells are undergoing cell death. Currently, we are investigating different induced modes of cell death, using fluorescence-activated cell sorting and our results thus far show a variation in response to HYPPDT by different human skin cells. Future directions include investigating whether the TME affects skin cancer cell response to HYP-PDT and chemotherapy. This therefore contributes to improved targeting of tumour cells and sparing peritumoral normal cells.

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084 Skin carcinogenesis in Ras/Fos/PTENnull transgenic mice reveals activated p-mammalian target of rapamycin not AKT cooperation with MDM2mediated p53 loss in papillomatogenesis and malignant conversion, yet p-AKT drives malignant progression D. Greenhalgh, F. Macdonald, D. Yao, C. Gilbert, N. Sinclair and J. Quinn Dermatology Section, School of Medicine, MVLS Glasgow University, Glasgow, Scotland, U.K. Papillomatogenesis and malignant conversion have been investigated in a transgenic mouse model driven by RasHa/fos activation (HK1.ras, HK1.fos) and RU486-induced PTEN loss (K14.creP-D5PTENflx). HK1.ras/fos-D5PTEN mice exhibited rapid papillomatogenesis but delayed malignant conversion and progression was restricted to well-differentiated squamous cell carcinomas (wdSCC). Here elevated p53/p21 expression in papillomas helped inhibit conversion until p53 became lost, whereas p21 persisted to limit early-stage progression. Given PTEN-mediated regulation of AKT signalling and targets such as mammalian target of rapamycin (mTOR), their expression profiles were determined. Despite PTEN loss, activated AKT (p-AKT) expression was unexpectedly low/absent in HK1.ras/ fos-D5PTEN hyperplasia/papillomas and sporadic in wdSCCs. In being a major target of AKT, a similar profile was envisaged for mTOR. However, unlike p-AKT, p-mTOR was strongly expressed in basal layers of HK1.ras/fos-D5PTEN hyperplasia and throughout papillomatogenesis. In late-stage papillomas, basal layer p-mTOR expression was joined by elevated p-MDM2166 expression, previously sequestered in suprabasal layers of p53/p21-positive hyperplasia/papillomas. This combination helped overcome the compensatory p53/p21 expression response leading to malignant conversion, as wdSCCs expressed high levels of p-mTOR and p-MDM2166. However, on progression to more aggressive SCCs, both p-mTOR and p-MDM2166 expression faded and SCCs also became devoid of total MDM2. Furthermore, these p53-negative wdSCCs not only retained p21 expression in wdSCC basal layer keratinocytes, but p21 expression increased and this coincided with both reduction in p-mTOR and p-MDM2166, and another intriguing anomaly of early progression in this model where wdSCCs displayed reduced cyclin E2/D1 expression and reduced proliferation. Hence, p21 may inhibit early-stage malignant progression via downregulation of p-mTOR/pMDM2, possibly as a feedback to p53 loss. If so, such p21-mediated attempts to restore p53 failed, and p-MDM2 expression appears unnecessary for sustained p53 downregulation, which has implications for the efficacy of MDM2 inhibitors/p53 restoration. Collectively, these data suggest that in this carcinogenesis context, elevated p53/p21 compensate for PTEN loss via inhibition of p-AKT expression in papillomatogenesis, yet this sentinel pathway became circumvented/countered by elevated p-mTOR expression in the proliferative basal layers. Once additional p-MDM2166 became basal, the subsequent loss of p53 facilitated Ras/fos-mTOR cooperation and © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 39

conversion to wdSCC. However, persistent p21 expression limited early-stage progression by targeting this cooperation route, either via downregulation of p-mTOR/p-MDM2 or reduced proliferation via cyclin E2/D1 regulation, an effective response until p-AKT expression exerts major effects to circumvent this p21 response resulting in progression to aggressive SCCs.

085 Activated AKT/MAPK cooperation interdicts compensatory p21 expression in Ras/Fos-PTENnull skin carcinogenesis to accelerate malignant progression via restoration of elevated cyclin D1/ E2 following MDM2-mediated p53 loss J. Quinn, D. Yao, C. Gilbert, F. Macdonald and D. Greenhalgh Department of Dermatology, School of Medicine, MVLS, Glasgow University, Glasgow, Scotland, U.K. To investigate progression mechanisms in skin carcinogenesis driven by inducible PTEN ablation and rasHa/fos oncogene activation (HK1.ras/fos-PTENflx), stage-specific tumours were analysed for p-AKT, p-ERK1/2 and p-MDM2 expression in conjunction with p53/p21 status. Previously, malignant conversion in HK1.ras/fos-D5PTEN carcinogenesis was inhibited by p53/p21 coexpression but following p53 loss, persistent p21 expression limited early-stage malignant progression to a welldifferentiated squamous cell carcinoma (wdSCC) histotype in part via cyclin D1/E2 inhibition and a reduced BrdU/mitotic index. This study now reports that HK1.ras/fos-PTENflx papillomas exhibited a surprisingly low level of p-AKT given loss of the PTEN phosphatase activity. This appeared alongside strong p53/p21 expression in the proliferative basal layers, despite elevated p-ERK1/2. Following conversion and p53 loss, p-AKT levels increased in wdSCCs (keratin K1+/p53–) but expression remained confined to suprabasal cells as persistent p21 expression actually increased in the basal layers, consistent with reduced cyclin activity and a transient decrease in proliferation rates. In more aggressive SCCs (keratin K1 ) this elevated p21 response was circumvented/nullified by increasing basal layer coexpression of p-AKT/p-ERK1/2 resulting in the restoration of elevated cyclin D1/E2 expression, increased mitotic index and eventual p21 loss. An identical progression scenario was observed following TPA-promotion of bigenic HK1.ras-PTENflx mice where p53/p21 loss occurred early in papillomatogenesis and facilitated rapid malignant conversion and a similar context where elevated p-AKT/p-ERK/cyclin D1/E2 mediated the progression to poorly differentiated SCCs (pdSCC). Given p53 loss occurred prior to malignant conversion, MDM2 status was assessed in its elimination and the maintenance of p53– tumours. Initial HK1.ras/fos-D5PTEN hyperplasia displayed elevated p-MDM2166/MDM2 levels in suprabasal compartments (p53+/p21+/p-ERK+); whereas papillomas exhibited p-MDM2166/MDM2 in basal layer cytoplasm/nuclei, alongside strands of p53– keratinocytes. Following conversion to wdSCC (p53–/p21+) and progression to (p21–/p-AKT+/p-ERK+) SCCs or TPA-promoted pdSCCs, © 2014 The Authors BJD © 2014 British Association of Dermatologists

firstly p-MDM2166 expression then total MDM2 became reduced, suprabasal and lost. Hence, p-MDM2-mediated p53 ubiquitination may drive papilloma conversion but appears unnecessary for sustained p53 downregulation during progression despite, its reduction being a possible p21 target of a feedback loop in the inhibition of wdSCC progression to SCC. Collectively, these data identify malignant progression mechanisms based on ras/ERK/fos-D5PTEN/AKT cooperation and cell cycle deregulation within each tumour context created by temporal PTEN, (p-MDM2-associated) p53 and/or p21 loss.

086 Three-dimensional organotypic skin cultures to study direct effects of ciclosporin on human keratinocytes L. Schardt, M. Berning and P. Boukamp Division of Genetics of Skin Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany Rising incidences of cutaneous squamous cell carcinomas (SCCs) in solid organ transplant recipients (OTRs) are a huge challenge in immunosuppression therapy. Besides therapeutic effects on the immune surveillance, increasing evidence for an immunity-independent mechanism of certain immunosuppressive drugs in SCC development is published. Particularly high incidences of SCCs in OTRs are associated with the immunosuppressive drug ciclosporin. Yet, the mechanism remains elusive. We utilized a three-dimensional organotypic skin culture system, built of human skin keratinocytes and human dermal fibroblasts (cdm-OTCs) to mimic SCC development in OTRs. The basis of these cdm-OTCs is a modified cell-derived dermal equivalent, recently established in our group, which allows studies of human SCC cell characteristics and especially invasion processes in vitro over an extended period of time. As a prerequisite this system enabled us to study ciclosporin effects on human keratinocytes in a physiological environment excluding immune responses. It is unclear which stage of keratinocyte transformation is required for ciclosporin to promote tumorigenicity. To clarify this question, normal human epidermal keratinocytes (NHEK), premalignant human keratinocytes (HaCaT cells), and two human SCC cell lines (SCL-I and SCC-12) were propagated in cdm-OTCs treated with ciclosporin for 6 weeks. Based on haematoxylin–eosin stains ciclosporin treatment did not affect NHEK. In contrast, HaCaT cells showed more vital basal cells, compared with the mocktreated cdm-OTCs, and first sites of invasion. The expected significant invasion of SCL-I and SCC-12 in cdm-OTCs was not further intensified by ciclosporin. As only nontumorigenic HaCaT cells, which exhibit several genetic aberrations characteristic for SCCs, showed a significant phenotype shift, we hypothesize that premalignant cells are the target of ciclosporin leading to SCC progression. SCCs in OTRs develop mainly in sun-exposed skin. Therefore, we applied ultraviolet (UV) A/B irradiation to ciclosporin-treated cdm-OTCs. Preliminary experiments suggest that a combination of UV irradiation and ciclosporin for 6 weeks does not cause tumorigenic converBritish Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

40 WCCS Abstracts

sion of NHEK. Corresponding experiments with premalignant HaCaT cells are ongoing. Concluding, our model will allow us to explore the direct effects of ciclosporin on keratinocytes, as well as indirect effects through fibroblast dependent modulation. It will further allow us to identify pathways involved in an immunity-independent effect of ciclosporin on SCC progression in OTRs.

087 ROCK-2 activation alters keratinocyte differentiation and initiates malignant conversion in ras/fos/PTENnull transgenic mouse skin carcinogenesis S. Masre,1 N. Rath,2 M. Olson2 and D. Greenhalgh1 1

Department of Dermatology, School of Medicine, MVLS Glasgow University, Glasgow, Scotland, U.K. and 2Tumour Microenvironment Laboratory, Beatson Institute for Cancer Research, Glasgow, Scotland, U.K. To study mechanisms of tumour progression in mouse skin cancer, ROCK-2 signalling deregulation and cooperation with activated rasHa and fos oncogenes together with PTEN tumour suppressor gene loss was investigated in transgenic mouse skin carcinogenesis. Transgenic mice that expressed a 4-hydroxytamoxifen (4HT)-activated human ROCK-2/ oestrogen receptor fusion transgene from a keratin 14 promoter (K14.Rocker) were crossed to mice expressing activated rasHa or fos exclusively in the epidermis (HK1.ras, HK1.fos) and/or RU486-inducible PTEN ablation (K14.creP.D5PTEN). Initial 4HT treatments of HK1.ras or HK1.ras-Rocker produced similar papillomas (8–10 weeks) but with HK1.ras-Rocker tumours (16 weeks) converted to malignancy and exhibited a mix of well-differentiated squamous cell carcinoma (wdSCC) and SCC. In addition, continued promotion from wounding appeared to be critical to this event, suggesting the appropriate (late-stage) papilloma context had to be achieved prior to ROCK 2-mediated events becoming causal. Furthermore cessation of 4HT treatment demonstrated an apoptotic response in p21+ wdSCC histotypes, suggesting an oncogenic dependence upon continued K14.Rocker activities. However, on cessation of 4HT in aggressive (p21 ) SCCs, K14.Rocker activities appeared to be dispensable, suggesting that in this context, ROCK-2 helps initiate the malignant conversion process but its activities are not required to maintain the malignant phenotype at later stages. Previously, bigenic rasHa/PTENnull or fos/PTENnull mice also exhibited tumours that required acquisition of either additional oncogenes to induce conversion or chemical promotion with TPA (i.e. AP-1 c-fos/jun). K14.Rocker mice were crossed with HK1.fos and/or K14.creP.D5PTEN mice and treated with Ru486 (3 weeks) and 4HT (up to 26 weeks). Bigenic HK1.fos-Rocker also exhibited increased hyperplasia and a significantly altered keratinocyte differentiation consistent with major disruption of epidermal physiology, culminating in highly keratotic papillomas. Early indications from preliminary trigenic K14.fos.D5PTEN-Rocker cohorts suggest that subsequent loss of PTEN may elicit a rapid conversion to malignancy unlike previous models, and support a strong cooperative link between ROCK-2 signalling, FOS activation and PTEN loss. Collectively British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

these data suggest that ROCK-2 deregulation plays major roles in malignant conversion rather than malignant progression, and in cooperation with rasHa or fos activation and PTEN loss, creates a valuable mouse skin model to study stage-specific ROCK-2 activities in carcinogenesis.

088 Expression of matrix metalloproteinases in basal cell carcinoma I. Tudose,1 M. Alecu,2 F. Staniceanu3 and O.A. Orzan1 1

Elias University Emergency Hospital, Bucharest, Romania, 2Victor Babes Hospital, Bucharest, Romania and 3Colentina Hospital, Bucharest, Romania Basal cell carcinoma (BCC) is the most common malignant tumour seen in humans. It is a slow growing tumour that only rarely metastasizes, but which can cause significant local destruction and cosmetic disfigurement. One of the factors contributing to the tumour progression is the excessive degradation of the matrix components, a process that is mainly controlled by matrix metalloproteinases (MMPs) (Kerkela E, Saarialho-Kerke U. Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer. Exp Dermatol 2003; 12: 109–25). The aim of our study was to analyse the expression of stromal and tumoral MMPs in BCC. Among 759 cases of BCC that were surgically excised during a 4-year period, we have selected 130 cases having similar clinical and histological features; 78 cases were primary tumours and 52 were recurrent tumours. We performed immunohistochemical tests for MMP 1, 2, 3, 11, 13. Our results showed that there are no significant differences regarding expression of MMP 1, 2, 3 and 13 in the group of primary vs. recurrent tumours in contrast to expression of MMP 11. Although all of the analysed cases were positive for MMP 11, this marker had a significant higher positivity in recurrent tumours, both in stromal and tumour cells, compared with primary tumours. We conclude that the expression of MMP 11 may serve as a marker for the invasion capacity of BCC cells and as well as for the prognosis of this skin cancer.

089 CYP11A1 in skin: an alternative route to photoprotection by vitamin D compounds W. Tongkao-On,1 S. Carter,1 K.M. Dixon,1 K. Lee,1 C. Gordon-Thomson,1 G.M. Halliday,1 V.E. Reeve,1 R.C. Tuckey2 and R.S. Mason1 1

University of Sydney, Sydney, New South Wales, Australia and 2University of Western Australia, Perth, Western Australia, Australia Topical vitamin D compounds have been shown to protect skin from damage by ultraviolet radiation (UVR) (Dixon KM, Norman AW, Sequeira VB et al. 1a,25(OH)₂-vitamin D and a nongenomic vitamin D analogue inhibit ultraviolet radiationinduced skin carcinogenesis. Cancer Prev Res 2011; 4: 1485–94). 20-Hydroxyvitamin D3 (20OHD) is produced in skin from UVR-induced vitamin D3, through the actions of the enzyme CYP11A1. To test whether 20OHD is photoprotective and compare with topical calcitriol, we examined its effects on © 2014 The Authors BJD © 2014 British Association of Dermatologists

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DNA damage in UVR-exposed human keratinocytes in vitro, and in Skh:hr1 mice exposed to solar-simulated UVR radiation, followed by topical application of vehicle, calcitriol or 20OHD. Post-UVR DNA damage in the form of thymine dimers and 8-oxoguanine in human keratinocytes was significantly reduced by 72  06% and 97  05%, respectively (P < 0001, both, similar to calcitriol) in the 20OHD-treated cells, compared with the vehicle-treated cells. This reduction in thymine dimers in keratinocytes by 20OHD was abolished in the presence of the chloride channel blocker, DIDS, which inhibits nongenomic actions of calcitriol in osteoblasts and keratinocytes (Sequiera VB, Rybchyn MS, Gordon-Thomson C et al. Opening of chloride channels by 1a,25-dihydroxyvitamin D3 contributes to photoprotection against UVR-induced thymine dimers in keratinocytes. J Invest Dermatol 2013; 133: 776– 82). Photoprotection by 20OHD against thymine dimers after UVR in mice was highly effective (reduced by 98  08%, P < 0001). In studies of contact hypersensitivity, which is suppressed by UVR in mice and humans, topical application of 20OHD to mice protected against UVR-induced immunosuppression, similar to calcitriol (46  06% protection with 20OHD, 44  05% with calcitriol). Both UVR-induced DNA damage and immunosuppression contribute to increased susceptibility to UVR-induced skin tumours. This study indicates a potentially antiphotocarcinogenic role of the naturally occurring vitamin D metabolite, 20OHD, which does not depend on 1a-hydroxylation for generation, and may explain why vitamin D receptor knockout mice show increased susceptibility to photocarcinogenesis, while 1a-hydroxylase (CYP27B1) knockout mice show no increased susceptibility.

090 Prevention and treatment of cutaneous squamous cell carcinomas by targeting aryl hydrocarbon receptor (AHR) signalling T. Haarmann-Stemmann, K. Frauenstein, J. Tigges, K. Fischer, C. Esser and J. Krutmann Leibniz-Research Institute for Environmental Medicine, D€usseldorf, Germany The aryl hydrocarbon receptor (AHR) is a ligand-activated and ultraviolet (UV) B-sensitive transcription factor controlling major parts of the DNA-damage-independent UVB response. In its inactive form, the AHR rests in a cytosolic multiprotein complex. Upon binding of a ligand, such as the tryptophan photoproduct FICZ, this complex dissociates and the AHR shuttles in the nucleus to alter the expression of its target genes. Beside various drug-metabolizing enzymes, AHR target genes encode for proteins involved in cell division and apoptosis. As apoptosis is probably the most important mechanism in the epidermis restraining photocarcinogenesis, we have previously investigated the role of AHR in regulating apoptosis in human keratinocytes (KC) and mouse skin. We found that an inhibition of AHR in vitro as well as in vivo resulted in a significant elevation of UVB-induced apoptosis, which was due to a reduced expression of the cell-cycle regulators E2F1 and checkpoint kinase-1. In the present study, we investigated if targeting of this antiapoptotic pathway © 2014 The Authors BJD © 2014 British Association of Dermatologists

affects UVB-induced skin carcinogenesis. Therefore, we performed a photocarcinogenesis study in AHR-proficient and AHR-null SKH-1 hairless mice. We observed ~50% fewer skin tumours in AHR-null mice compared with control mice, indicating that the AHR damps KC apoptosis in vivo and thereby contributes to skin carcinogenesis. Our results demonstrate for the first time that the AHR is a promising target for chemoprevention of cutaneous squamous cell carcinomas (cSCC). We next asked if the inhibitory effect of AHR on UVBinduced apoptosis is also retrievable in human A431 cSCC cells. UVB exposure of A431 cells resulted in an increase of apoptosis, which was further elevated by a 3’-methoxy-4’ -nitroflavone (MNF)-mediated inhibition of AHR, indicating that AHR’s antiapoptotic function is not restricted to normal KC but also present in KC-derived cSCC cells. Hence, an enhancement of genotoxicant-induced apoptosis through AHR antagonism might be of therapeutic relevance. Therefore, we coexposed A431 cells to MNF and three genotoxic drugs differing in their mode of action: etoposide (topoisomerase inhibitor), cisplatin (intercalating agent) and 5-fluorouracil (antimetabolite). After different times of exposure, we investigated cell viability and apoptosis. In contrast to cells treated solely with the genotoxic drugs, cells coexposed to MNF showed a markedly increase in apoptosis. Thus, a combined treatment with an AHR antagonist and a cytostatic drug may allow reduction of the dose and duration of chemotherapy of cSCC. We conclude that the AHR is probably a suitable molecular target for both chemoprevention and treatment of cSCC.

091 Mutation screening and mRNA expression levels of the PTCH1 gene in naevoid basal cell carcinoma syndrome lez,3 L.D. Mazzuoccolo,1 F. Martinez,2 A. Gonza C. Muchnik,2 P. Azurmendi2 and F. Stengel4 1

C.E.M.I.C, Buenos Aires, Argentina, 2Laboratorio de Biologıa Molecular, IDIM Alfredo Lanari, UBA, Buenos Aires, Argentina, 3Instituto de Oncologıa Angel Roffo, UBA, Buenos Aires, Argentina and 4Hospital Eva Peron, Gral San Martın, Argentina Naevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder characterized by developmental abnormalities and tumorigenesis, mainly basal cell carcinoma (BCC), largely due to PTCH1 mutations. As PTCH1 acts as a tumoral suppressor gene and the proposed two-hit tumorigenesis model has not been fully demonstrated in NBCCS, the aims of this work were to find germinal and somatic mutations in BCCs and to determine their mRNA levels in BCC and normal skin samples. Mutational analysis of the entire PTCH1 coding region was performed using polymerase chain reaction (PCR) amplification and bidirectionally sequenced from blood and BCC samples of 20 unrelated patients with NBCCS. Additionally, multiplex ligation probe amplification (MLPA) was done to look for large gene rearrangements. We assigned the germline origin to a mutation found in both sample sources and the somatic origin to a mutation found in BCC only. The British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

42 WCCS Abstracts

PTCH1 mRNA levels were evaluated in BCCs and normal surrounding tissue (NST) samples from 19 patients with NBCCS and control skin samples from four healthy subjects using relative quantitative real-time PCR with GAPDH as the reference gene. We identified 11 germline and five somatic mutations that comprised seven deletions, two insertions, one duplication and six substitutions. According to this, the two-hit model was evident in five of 16 patients fully studied (complete sequenced and accurate MLPA). The PTCH1 mRNA levels showed the highest values in BCCs [ratio 1506  312 (P < 00001) vs. NST and control skin samples]; increased levels in NST compared with controls (95  15 vs. 10  01, P < 0001) were found. Moreover, expression levels in BCC with both germline and somatic mutations were increased with respect to BCCs with a germinal mutation only (2306  497 vs. 675  418, P < 005). No differences were found between BCCs from patients either carrying germinal mutations or not. Here we provide the first evidence in South America that PTCH1 mutations were responsible in 55% of patients with NBCCS and that the two-hit hypothesis was the tumorigenesis model in five BCCs. The increased PTCH1 expression in both BCCs and NST established the overall Hedgehog pathway activation in this syndrome. An additive effect by the number of mutations in PTCH1 gene was found, suggesting that the two-hit model could regulate the gene expression. Finally, these results encourage the use of early genetic diagnosis as a valuable tool in NBCCS and future studies in other genes involved in the pathway are needed to improve their overall performance. The combined mutation screening and gene expression pattern analysis would provide new insights for future therapeutics targets.

092 Aquaporin 3 as a hyperproliferative marker in psoriasis, basal cell carcinoma and squamous cell carcinoma: an immunohistochemical study A. Tawdy, M. Fawzi, M. Amer and Z. Madawy Cairo University, Cairo, Egypt Nonmelanoma skin cancers (NMSCs) and psoriasis represent common hyperproliferative skin disorders. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the two most common NMSCs, and can result from dysregulation of the homeostasis of keratinocyte proliferation and differentiation. We studied cases presenting with BCC, SCC and psoriasis histopathologically and immunohistochemically using aquaporin (AQP)3 and Ki-67. This was to assess the possibility of using AQP3 as a marker of hyperproliferation. Forty-five patients with BCC, SCC and psoriasis, and 15 healthy participants were included. Each was subjected to short medical history and cutaneous examination. A skin biopsy from each case and healthy control was examined and immunohistochemistry was done for all participants using anti-AQP3 and anti-Ki-67 antibodies, in order to assess the degree and pattern of expression of their immunohistochemical profile. AQP3 expression was mainly membranous in all groups and a few cases also showed a cytoplasmic pattern. AQP3 expression was signifiBritish Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

cantly higher in the disease group (BCC 3681  5592, SCC 3679  4903, psoriasis 3750  606) compared with the control (1349  3785) (P < 001). The areas showing strong positivity for Ki-67 were also positive for AQP3 and they were positively correlated. On comparing Ki-67 and AQP3 between the different groups, both were significantly highest in the psoriasis group (P = 0001 and P < 001, respectively). We conclude that AQP3 can possibly serve as a proliferation marker and could be added to the list of diagnostic and prognostic tools for hyperproliferative disorders.

093 Topical application of PLK1 inhibitors as neoadjuvant therapy for human cutaneous squamous cell carcinoma C. Pourreyron, S. Wright, S. Watt, I. Leigh and A. South Division of Cancer Research, University of Dundee, Dundee, U.K. The incidence of cutaneous squamous cell carcinoma (cSCC) is fast increasing worldwide. In the U.K., 35% of treated cSCC require complex repair ( that could be reduced by topical application of neoadjuvant therapies. We have previously identified polo-like kinase 1 (PLK1) as being important for cSCC keratinocytes. PLK1 is a master regulator of cell division; overexpression in cancer has been correlated with poor prognosis and survival. Intratumoral injection of the PLK1 inhibitor BI2536 greatly reduced the growth of cSCC subcutaneous xenograft. Intravenous injection of BI2536 showed a similar effect but was associated with high toxicity, which was in line with two neutropenia-related deaths in a phase II trial. We are investigating further PLK1 inhibitors that are at various stages of clinical development, in order to identify the most specific and the least toxic candidates for topical treatment of cSCC. Using MTS and cell toxicity assays we have determined the EC50 in seven cSCC and five normal keratinocyte populations (NHK) for six different PLK1 inhibitors. Two of them, ON-01910 and HMN 214, specifically reduced cell viability and induced cell death in tumour cells with an EC50 of 006–03 mmol L 1 and 03–07 mmol L 1 for cSCC keratinocytes compared with 3106 and 95 mmol L 1 for NHK, respectively. Intratumoral injection of ON-01910 dramatically reduced cSCC xenograft volume in vivo (mean of ON-01910treated tumour volume 294  185 mm3 vs. vehicle-treated tumour volume 776  194 mm3, n = 5 for each group). Topical application of ON-01910 onto organotypic cultures only partially decreased PLK1 activation and did not affect tumour cell viability. Although intratumoral injection of HMN-214 did not alter cSCC xenograft growth, topical application of HMN-214 disrupted the proliferative compartment in organotypic cultures set up with cSCC keratinocytes but not in those set up with NHK. Similar results were obtained with BI2536 application on organotypic cultures suggesting that topical administration of BI2536 could also be considered for cSCC treatment. To further test topical application of PLK1 inhibitors, we have developed a xenotransplantation model of human cSCC in mice. In this model, a full-thickness portion © 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 43

of skin is removed from the dorsal area of a SCID mouse to engraft a skin equivalent set up with tumour or normal keratinocytes. To date, we have obtained fast-growing and massively invasive tumours with one cSCC keratinocyte population. We are currently using this model to test whether the specific PLK1 inhibitors identified in vitro are efficacious with topical application in vivo.

094 Ultraviolet B-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes nka,2 A. Bebes,1 G. Tax,1 B. Fazekas,1 H. Polya 2  Kinyo , K. Farkas,2 A. ,1 F. Nagy,3 K. Szabo  Ad  a ny,1 M. Sze ll2 and E.  m3 L. Keme 1

Department of Dermatology and Allergology, Faculty of Medicine, University of Szeged, Szeged, Hungary, 2MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary and 3Institute of Plant Biology, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary Ultraviolet (UV) B is the most prominent physical carcinogen in the environment leading to the development of various skin cancers. We have previously demonstrated that the human orthologue of the Arabidopsis thaliana constitutive photomorphogenesis (COP)1 protein, huCOP1, is expressed in keratinocytes in a UVB-regulated manner and is a negative regulator of p53 as a post-translational modifier. However, it was not known whether huCOP1 plays a role in mediating the UVB-induced early transcriptional responses of human keratinocytes. In this study we found that stable small-interfering (si) RNA-mediated silencing of huCOP1 affects the UVB response of several genes within 2 h of irradiation indicating that altered huCOP1 expression sensitizes the cells toward UVB. Pathway analysis identified a molecular network in which 13 out of the 30 examined UVB-regulated genes were organized around three central proteins. As the expression of the investigated genes was upregulated by UVB in the siCOP1 cell line, we hypothesize that huCOP1 is a repressor of the identified pathway. Several members of the network have been implicated previously in the pathogenesis of nonmelanoma skin cancers; therefore, clarifying the role of huCOP1 in these skin diseases may have clinical relevance in the future.

095 Contribution of collagen XIII and XXIII to squamous cell carcinoma development S. Santoleri,1 G.M. Nieto,1 A. Heikkinen,1 R. Heljasvaara,1 A.-M. Auvinen,1 T. Pihlajaniemi1 and M. Koch2 1

Oulu Center for Cell-Matrix Research, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland and 2 University of Cologne, Cologne, Germany Collagens are important not only as structural components but also by regulating cell behaviour. Our work addresses the roles of the structurally homologous collagens XIII and XXIII in skin tumour formation. Both collagens are transmembrane pro© 2014 The Authors BJD © 2014 British Association of Dermatologists

teins, which may also occur as shed protein at cell–extracellular matrix interphases (Heikkinen A, Tu H, Pihlajaniemi T. Collagen XIII: a type II transmembrane protein with relevance to musculoskeletal tissues, microvessels and inflammation. Int J Biochem Cell Biol 2012; 44: 714–17). Their expression is induced in malignant transformations and they have been suggested to play a role in tumour progression and metastasis (V€ais€anen T, V€ais€anen M-R, Autio-Harmainen H, Pihlajaniemi T. Type XIII collagen expression is induced during malignant transformation in various epithelial and mesenchymal tumours. J Pathol 2005; 207: 324–35; Banyard J, Bao L, Hofer MD, Zurakowski D et al. Collagen XXIII expression is associated with prostate cancer recurrence and distant metastases. Clin Cancer Res 2007; 13: 2634–42; Spivey KA, Banyard J, Solis LM et al. Collagen XXIII: a potential biomarker for the detection of primary and recurrent non-small cell lung cancer. Cancer Epidemiol Biomarkers Prev 2010; 19: 1362–72; Spivey KA, Chung I, Banyard J et al. A role for collagen XXIII in cancer cell adhesion, anchorage-independence and metastasis. Oncogene 2012; 31: 2362–72). We have recently generated collagen XIII knockout mice (Latvanlehto A, Fox MA, Sormunen R et al. Muscle-derived collagen XIII regulates maturation of the skeletal neuromuscular junction. J Neurosci 2010; 30: 12230–41) and a collagen XXIII knock-in mouse line with markedly reduced expression (unpublished). Both collagens are expressed in normal skin, and to study their roles during malignant processes we have used a classical, chemically induced cutaneous squamous cell carcinoma (SCC) model of mouse skin carcinogenesis in single mutant mice as well as double mutants for these alleles. All mice developed tumours but the number of tumours was significantly reduced in collagen XXIII deficiency, while lack of collagen XIII resulted in more aggressive malignant conversion in short term. This project will lead to the identification of pathways in skin carcinogenesis regulated by collagens XIII and XXIII together and separately, and the findings may lead to the development of novel diagnostic tools and therapeutic targets.

096 Preliminary results of the examination of gene abnormal methylation in T-cell cutaneous lymphoma and parapsoriasis N. Potekaev,1 D. Zaletaev,2 I. Khamaganova,3 V. Lysenko1 and O. Shvec1 1

Moscow Scientific and Practical Centre for Dermatology and Cosmetology, Moscow, Russia, 2Research Centre of Medical Genetics, Moscow, Russia and 3 Department of Skin Diseases and Cosmetology, Russian National Research Medical University named after N.I. Pirogov, Moscow, Russia The epigenetic regulation of gene activity, which is based on abnormal methylation/demethylation, may be essential in cancerogenesis. The imbalance of methylation was shown in neoplastic cells. Abnormal methylation of the promoter CpG islands takes place simultaneously with genome hypomethylation. The result is inactivation of the gene. The same type of methylation is described in genes that take part in apoptosis, angiogenesis, signal transmission, DNA reparation, metastatic British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

44 WCCS Abstracts

process, detoxification and drug resistance. Genes can be totally inactivated without any structural changes of nucleotide sequence. The objective of the study was to examine abnormal methylation of gene regulatory loci in cutaneous T-cell lymphomas (CTCL) and parapsoriasis (PP) as a possible precursor of CTCL. Methylation in genes involved in cancerogenesis (RASSF, MLH1, P16, GSTP1, RARB, N33, CDH1, ESR, P21, CAV, CD44, MGMT, GPX3RB1, P14) was examined in 26 patients including 12 patients with CTCL (mycosis fungoides) and in 14 patients with PP (nine with large-plaque form, five with small-plaque PP); the method of examination of abnormal methylation in gene regulatory loci was methylation-sensitive arbitrarily primed polymerase chain reaction (PCR). In three patients with mycosis fungoides abnormal methylation was detected, including methylation of p21 in three cases, methylation of RASSF in two cases, and in one case methylation of p16, CDH1, CD44 was detected besides methylation of p21 and RASSF. The clinical picture in these three patients was presented by growth of multiple tumours on the skin. The search of abnormal methylation was negative in patients with earlier stages of CTCL or PP. In conclusion, the abnormal methylation was detected in patients with IIb stage of mycosis fungoides. Further investigations are necessary for obtaining reliable statistical data in order to decide whether methylation-sensitive arbitrarily primed PCR can be used for diagnostics and prognosis in patients with CTCL and PP.

097 (PL05) Randomized comparison of two doses of the antiprogrammed death-1 monoclonal antibody MK-3475 for ipilimumab (IPI)-refractory and IPI-naive melanoma R. Kefford,1 O. Hamid,2 C. Robert,3 A. Ribas,4 J.D. Wolchock,5 F.S. Hodi,6 A.M. Joshua,7 W.-J. Hwu,8 T.C. Gangadhar,9 A. Patnaik,10 P. Hersey,11 J. Weber,12 R. Joseph,13 K. Gergich,14 X. Li,14 P. Chun,14 S. Ebbinghaus,14 S.P. Kang14 and A. Daud15 1

Westmead Hospital and Melanoma Institute, Sydney, New South Wales Australia, Australia, 2The Angeles Clinic and Research Institute, Los Angeles, CA, U.S.A., 3Institut Gustave Roussy, Villejuif, Paris, France, 4David Geffen UCLA School of Medicine, Los Angeles, CA, U.S.A., 5Memorial SloanKettering Cancer Center, New York, NY, U.S.A., 6Dana-Farber Cancer Institute, Boston, MA, U.S.A., 7University of Toronto, Princess Margaret Hospital, Toronto, Ontario, Canada, 8University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A., 9Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, U.S.A., 10South Texas Accelerated Research Therapeutics (START), San Antonio, TX, U.S.A., 11 University of Sydney, Sydney, New South Wales, Australia, 12Moffitt Cancer Center, Tampa, FL, U.S.A., 13Mayo Clinic Cancer Center, Jacksonville, FL, U.S.A., 14Merck Sharp & Dohme Corp., Whitehouse Station, NJ, U.S.A. and 15University of California San Francisco, San Francisco, CA, U.S.A. MK-3475 has shown durable antitumor activity in melanoma across multiple doses and schedules. We compared the efficacy and safety of two MK-3475 doses in patients with melanoma (study sponsored by Merck Sharp & Dohme Corp.). In sepaBritish Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

rate cohorts, ipilimumab-naive (IPI-N) and ipilimumab-refractory (IPI-R) patients were randomized 1: 1 to MK-3475 2 or 10 mg kg 1 every 3 weeks (2 Q3W or 10 Q3W). IPI-N patients received ≤ 2 prior systemic therapies. IPI-R patients had any number of prior therapies and unequivocal or confirmed progressive disease per immune-related response criteria (irRC) after ≥ 2 IPI doses; all BRAF-mutant patients were previously treated with BRAF inhibitors. The primary endpoint was overall response rate (ORR) assessed by RECIST 11 every 12 weeks by independent central review. Investigator-assessed response by irRC was also obtained. A total of 103 IPI-N (2 Q3W, n = 51; 10 Q3W, n = 52) and 173 IPI-R (2 Q3W, n = 89; 10 Q3W, n = 84) patients were randomized. In both cohorts, treatment arms were well balanced for known prognostic factors. As of the 18 October 2013 cut-off, all IPI-N and 47% of IPI-R patients had ≥ 9 months of follow-up. Among evaluable IPI-N patients, no significant between-dose differences were observed for ORR by RECIST (33% with 2 Q3W vs. 40% with 10 Q3W; P = 04835) or irRC (39% vs. 40%; P = 09040). There were also no between-dose differences in IPI-R patients (RECIST 26% vs. 26%; P = 09558; irRC 27% vs. 32%; P = 04568). Response duration ranged from 6+ to 39+ weeks by RECIST (4+ to 42+ weeks by irRC) in both cohorts (median not reached), with ~90% of responses ongoing. Median progression-free survival (PFS) was similar between doses in IPI-N (27 vs. 23 weeks by RECIST; 36 vs. 26 weeks by irRC) and IPI-R (22 vs. 14 weeks by RECIST; 31 vs. 25 weeks by irRC) patients. In IPI-N patients, 24-week PFS rates were 51% vs. 48% by RECIST and 60% vs. 50% by irRC. In IPI-R patients, 24-week PFS rates were 45% vs. 37% by RECIST and 57% vs. 57% by irRC. The safety profile was generally similar between patients treated with 2 Q3W and 10 Q3W. There were no drug-related deaths. In summary, MK-3475 2 mg kg 1 Q3W and 10 mg kg 1 Q3W provided similar efficacy and safety in both IPI-N and IPI-R patients. Treatment was well tolerated with an acceptable toxicity profile. The high ORR provided by MK-3475 comes with long durability in both IPI-N and IPI-R melanoma.

098 Abstract withdrawn

099 Neck dissection for node-positive head and neck cutaneous malignant melanoma K.Y. Wong, C. Deutsch, R.D. Price and A.J. Durrani Cambridge University Hospitals NHS Foundation Trust, Cambridge, U.K. There are no specific guidelines regarding level of neck dissection (ND) and structure preservation in the management of cutaneous head and neck malignant melanomas. The reported risk of locoregional recurrence is 16–32% despite comprehensive neck surgery. We present the outcomes of ND for nodepositive cutaneous head and neck melanoma at a single tertiary hospital. All patients (2007–2012) who had an ND for

© 2014 The Authors BJD © 2014 British Association of Dermatologists

WCCS Abstracts 45

cutaneous head and neck malignant melanoma were identified for analysis. Outcomes including disease-free and overall survival were retrospectively correlated with patient demographics, level of ND, histology and use of adjuvant therapy. Sentinel lymph node biopsy for head and neck melanoma staging has been available at our hospital since 2011. A total of 22 NDs were evaluated (14 modified radical NDs, seven selective NDs, one radical ND) in 20 patients with a mean age of 66 years (range 45–82; 85% male). Breslow thickness was < 1 mm in two patients, 1–4 mm in 10 patients and > 4 mm in eight patients. Locoregional recurrence occurred in eight patients (40%) on average 8 months after ND. In 55% of patients, a higher number of positive metastatic lymph nodes was detected than preoperatively. Radiotherapy was given as adjuvant treatment in eight patients (40%) but was not associated with improved regional control. Patients with node-positive cutaneous head and neck malignant melanoma often have a higher burden of involved lymph nodes histologically than can be detected preoperatively. Novel adjuvant therapies may affect the number of patients who proceed to lymph node dissection in the future.

100 Management of vulval melanoma: a need for U.K. consensus guidelines? R.N. Matin, R. Turner, A. Gittins, S.M. Cooper, O. Cassell and M.J. Payne Oxford University Hospitals NHS Trust, Oxford, U.K. Vulval melanomas comprise 1% of all gynaecological malignancies. Despite its poor prognosis, minimal data exist reporting optimal management of this rare malignancy. Staging investigations and treatments have historically been extrapolated from those used for vulval squamous cell carcinoma. However, evidence suggests that the biological behaviour of vulval melanoma is similar to cutaneous melanoma and management strategies should thus be similar. To date, there are no U.K. consensus guidelines for management. We report our experience of vulval melanoma over a 10-year period (2003– 2013) in a U.K. tertiary referral centre. A retrospective casenotes review identified 10 women with vulval melanoma. Mean age at presentation was 69 years (range 39–88). Mean Breslow thickness was 53 mm (range 0–18 mm). Seven cases were American Joint Committee on Cancer (AJCC) stage IIA or above at diagnosis. Wide local excision (margins 1–4 cm) was undertaken in all cases. Resection margins applied were independent of Breslow thickness or AJCC stage. At least two surgical procedures were undertaken in 50% of cases, to achieve histological clearance of at least 1 cm. Seven out of 10 cases were discussed at the Specialist Skin Cancer Multidisciplinary Team (SSMDT) meetings between 1–28 months after primary pathological diagnosis. No patient underwent sentinel lymph node biopsy (SNB). Five patients underwent groin dissection following primary excision (between four and 16 lymph nodes excised). One of these patients had clinically apparent nodal disease at presentation. Overall, three patients had negative groin dissection and one patient underwent groin © 2014 The Authors BJD © 2014 British Association of Dermatologists

dissection following subsequent disease relapse. Mean followup was 33 years (range 07–114 years). Melanoma-specific mortality was 33% (n = 3). Our data demonstrate the inconsistency in management of vulval melanoma. Evidence suggests that staging and resection principles used to manage cutaneous melanoma should be applied when managing vulval melanoma. For cutaneous melanoma, SNB provides accurate staging information, enhances regional disease control and improves melanoma-specific survival for intermediate-thickness tumours. In light of recent evidence validating its use, we propose SNB should be offered to selected patients with vulval melanoma in experienced centres. In doing so, data can be collected to evaluate its benefit in vulval melanoma and help guide prospective adjuvant clinical trial enrolment for a targeted treatment approach. We would support the development of U.K. consensus guidelines in the management of vulval melanoma. In the meantime, we recommend collaborative decision-making between gynaecological oncologists and SSMDTs to guide optimal management of this rare cancer.

101 Training decreases gender differences in melanoma recognition T.M. Tian and A. Oakley Waikato Hospital, Hamilton, New Zealand Early recognition of melanoma by patients and healthcare professionals improves prognosis. An online quiz was devised to ascertain how gender, age and profession affect differentiation of melanomas from benign lesions. During a 6-week period, unselected visitors to a dermatology website were invited to participate anonymously in an online quiz. Anatomical views and close-up images of pigmented skin lesions included five melanomas and five benign lesions. Dermatoscopic views were not included. For each lesion, participants were asked to choose between ‘melanoma’ or ‘benign lesion’. Demographic data collected were gender, age group and profession. There were 1670 participants, and 1504 completed the quiz (90%). There was a female majority of 59% (885/1504). Most participants were in the 25–49 age group (62%), with 12%, 25% and 1% aged < 25, 50–75 and > 75 years, respectively. Around 26% (396/1504) did not work in health care, 60% (905/1504) were healthcare professionals and 14% (203/ 1504) were dermatology specialists. Healthcare professionals achieved significantly higher scores (mean of 687) than nonhealthcare professionals (584), and dermatologists achieved significantly higher scores than the other two groups (733, P < 0001). Participants aged 25–49 years were significantly better at recognizing melanomas than those in other age groups (P = 0002). The majority of healthcare professionals (70%) and dermatologists (74%) were in this age group, which may explain the higher scores achieved. Subanalysis within each profession group showed no significant differences in scores between the different age groups. Men achieved higher scores (mean of 686) than women (652) (P < 0001). Analysing score differences between men and women showed the biggest difference in those not working British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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in health care (mean of 619 vs. 563, P = 0003), and to a lesser extent also in those working in health care (699 vs. 678, P = 0027). There was no difference in mean scores between male and female dermatologists (733). In this online quiz on melanoma recognition, dermatologists were better at recognizing melanomas than other health professionals, who were in turn better than those that did not work in health care. Overall, men were better than women at recognizing melanomas, but specialist training in dermatology eliminated gender differences.

102 Patient compliance with self-performed full-body skin photography recommendations J. Kantor1,2 1

University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A. and Florida Center for Dermatology, P.A., St Augustine, FL, U.S.A. Patients with dysplastic naevi, floridly expressed banal naevi, and those with a history of melanoma or family history of melanoma have an increased risk of developing malignant melanoma over the general population. As part of a multipronged approach both to detect early evolving melanoma and minimize the number of unnecessary biopsies performed on such patients, full-body skin photography has been advocated and adopted broadly in the U.S.A. and elsewhere. As professionally performed full-body photography may be costly and may not be covered by medical insurance, we sought to explore whether patients would comply with physician recommendations for self-performed photography. This prospective analytical study included data on 55 consecutive patients with a history of melanoma or dysplastic naevi. All patients were advised using a standardized script that the physician recommends full-body photography, and were instructed on a standardized quadrant-based approach to taking these photographs at home with the assistance of a family member or friend. The average age of patients in this study was 449 years [95% confidence interval (CI) 416– 483] and 40% (266–534%) of the subjects were male. Twenty-nine per cent (CI 167–415%) of subjects had a history of melanoma, and 218% (106–331) had a family history of melanoma. Subjects had a history of an average of 31 (23–40) excisions for dysplastic naevi or melanoma in the past; 345% (216–475) of subjects complied with physician recommendations for skin photography at the time of the follow-up visit. As a secondary analysis, logistic regression was used to assess for a significant relationship between compliance with photography recommendations and a personal or family history of melanoma, sex, history of nonmelanoma skin cancer, and other baseline variables. None of the baseline variables reached the level of statistical significance, although this study was not powered to detect significant differences in these secondary endpoints. Physician-recommended and patient self-performed skin photography represents a viable approach to following dysplastic naevi and detecting early incipient melanomas. Slightly over one-third of patients complied with the physician’s recommendation 2

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and performed self-photography. Given that professionally performed photographs are not associated with a high level of compliance, self-performed skin photography may represent a valuable addition to the armamentarium of those of us dedicated to treating patients with melanoma and dysplastic naevi.

103 The many faces of acral melanoma zquez A.S. Ayala Corte´s, V. Garza Rodrıguez, O.T. Va Martınez and J. Ocampo Candiani Hospital Universitario ‘Dr Jose Eleuterio Gonzalez’ de la Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico Malignant melanoma is an important health problem, with rising global incidence; and in spite of increasing efforts dedicated to treatment and prevention, mortality remains high. Acral lentiginous melanoma (ALM) is the least frequent subtype representing 4% of the cases. Additionally, it is commonly diagnosed in later stages than other melanomas due to more aggressive behaviour, involvement of difficult inspection areas and atypical clinical presentations (Pereda C, Traves V, Requena C et al. Clinical presentation of acral lentiginous melanoma: a descriptive study. Actas Dermosifiliogr 2013; 104: 220– 6; Piliang MP. Acral lentiginous melanoma. Clin Lab Med 2011; 31: 281–8). Focusing on the last point, our aim was to describe the multiple clinical presentations of ALM at first consult. We reviewed our medical records retrospectively, from October 2010 to October 2013, for ALM cases. We recorded clinical diagnosis, extent of the disease (histopathology reports and metastasis evidence) at the moment of the first dermatology consult; also we recorded previous visual diagnoses from nondermatology consults. We present eight case reports picturing the wide clinical manifestations of ALM, which can mimic onychomycosis, warts, haematomas, chronic ulcers, naevus and pyogenic granuloma. They were five women and three men, the mean age was 63 years (30–80 years). Three patients had incisional biopsies not representatives of the entire lesion. One patient presented node involvement and another presented metastasis to brain, lung and hip. Most of the remaining patients had Clark level ≥ III (one of V, three of III, one of I). Three patients received previous treatment for nonmalignant diseases: onychomycosis, haematoma and warts, from nondermatology consults; these unfortunate misdiagnoses allowed the lesions to proliferate, causing Clark V, node involvement and Clark III, respectively, at the time of the diagnosis. The clinical spectrum of our patients ranged from longitudinal melanonychia to deforming and metastatic tumours. Early diagnosis is essential to improve the prognosis; however, we present further observations suggesting diagnosis delay attributed at least in part to its multiple clinical presentations. In conclusion, we underscore the importance of raising awareness over this complicated and multiform disease, in order to improve its clinical outcome.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

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104 Skin cancer in albinos: our experience G. Ozoh,1 C. Onyekonwu,1 U. Ojinmah,1 P. Ozoh1 and A. Okoro2 1

University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu, Nigeria and Ebony State University, Abakaliki, Nigeria The deleterious effects of ultraviolet rays and nonmelanoma skin cancer are extremely burdensome to numerous albinos in our country, due to closeness to the Equator with the residents’ excessive sun exposure almost all-year round. Albinos are ignorant of photoinduced skin damage, lack sun-protection habits and have a poor health-seeking attitude, compounded by poverty, which results in outdoor jobs (Okoro AN. Albinism in Nigeria: a clinical and sociological study. Br J Dermatol 1975; 92: 485–92; Udem N, Ozoh GA, Udem S et al. Preformulation studies and evaluation of 5-fluorouracil cream from 5-fluorouracil injection. Niger J Dermatol 2011; 1: 7–9). A free monthly outpatient albino clinic was established in a dermatology department of a tertiary institution in 2009 (Ozoh GA. Sun-protection (photoprotection). Niger J Dermatol 2011; 1: 43). The aim of this project was to offer albinos free medical services and photoeducation. Preliminary results are hereby presented. A multidisciplinary approach was initiated, involving dermatologists, oncologists, plastic surgeons, ophthalmologists and pharmacists. Regular meetings and workshops were organized. Albinos were given instructions about sun protection, regular self-examination and regular skin clinic visits (3– 6 monthly). In clinics they were physically examined and investigated. All skin lesions detected were documented and suspicious lesions biopsied. Confirmed malignant lesions were treated by plastic surgeons. Dermatologists sometimes provided free sunscreen and 5-fluorouracil creams. Ophthalmologists treated eye problems. A total of 754 albinos were seen in 5 years (2009–2013); the male to female ratio was 1: 12; the average age was 287 years. Photoinduced lesions were seen in 691%, including lentigines 457%, keratosis 401%, elastosis 332%, squamous cell carcinoma (SCC) 81%, basal cell carcinoma (BCC) 4%, and combined SCC/BCC 2%. Twelve (15%) patients died from complications of extensive SCC or BCC and late presentation. In conclusion, the burden of sun-damaged skin among albinos is enormous as shown in the results. Although the mortality rate in nonmelanoma skin cancer generally is low if patients present early, our main problem is late presentation of patients compounded by poverty and ignorance of the deleterious effect of excessive and chronic sun exposure on albino skin. A multidisciplinary approach has improved the outcome of patients’ management. Many albinos now know about sun protection, and when and where to seek medical intervention. This multidisciplinary approach is recommended for areas where the burden of albinism is high. Further initiatives will include advocacy and funding for life-long skin care. 2

© 2014 The Authors BJD © 2014 British Association of Dermatologists

105 Vismodegib for periocular and orbital basal cell carcinoma K.Y. Wong,1 K. Fife,1 J.T. Lear,2 F.R. Ali,2 R.D. Price1 and A.J. Durrani1 1

Cambridge University Hospitals NHS Foundation Trust, Cambridge, U.K. and 2Salford Royal NHS Foundation Trust, Manchester, U.K. Basal cell carcinoma (BCC) is the most common periocular skin cancer and can lead to significant morbidity. The aim of this study was to assess the effectiveness of vismodegib, a first-in-class Hedgehog signalling pathway inhibitor, for periocular and orbital BCCs based on clinical response and tolerability. Vismodegib is approved for use in the U.S.A. and U.K. based on the pivotal study Erivance BCC (Sekulic A, Migden MR, Oro AE et al. Efficacy and safety of vismodegib in advanced basal cell carcinoma. N Engl J Med 2012; 366: 2171–9). All patients with periocular or orbital BCCs who met the criteria for vismodegib treatment were recruited prospectively between May 2012 and 2013 from two hospitals. Eleven patients received oral vismodegib (150 mg daily) until disease progression, unacceptable toxicity or withdrawal. All patients were followed up monthly. Patient demographics, tumour size, comorbidities, treatment duration including dosing regimen, adverse events, response rate, duration of response, progression-free survival and disease-free survival were retrospectively analysed. All 11 patients had biopsy-proven BCCs with no metastatic disease at presentation. Indications for vismodegib treatment included inoperable disease (n = 2); significant morbidity associated with orbital exenteration and/or radiotherapy (n = 8); or low chance of surgical cure due to multiple recurrences (n = 1). The mean age was 74 years (range 45–90) and six patients (55%) had orbital involvement. The mean lesion longest dimension was 47 mm (range 10– 115) and five cases (45%) represented recurrence following previous surgery and/or radiotherapy. As of 8 March 2014, the mean treatment duration was 11 months (range 2–16) and mean follow-up duration 15 months. The most common adverse events (91% of patients) included dysgeusia (82%), muscle spasms (73%), alopecia (73%) and asthenia (55%). All of these were mild or moderate in severity. Treatment was discontinued in eight patients (73%) because of adverse events (n = 4), patient request (n = 1), investigator request (n = 1), death not considered related to the study drug by the investigator (n = 1; lung cancer) or surgical clearance (n = 1). Seven patients (64%) had a complete response and four (36%) had a partial response. The partial response of 75% in one patient allowed subsequent surgical resection with clear margins. Vismodegib appears to be effective for treating periocular and orbital BCCs with orbital salvage of patients who otherwise would have required exenteration.

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106 Long-term efficacy and clearance of actinic keratosis using sequential treatment with ingenol mebutate 0015% gel after cryosurgery B. Berman,1 G. Goldenberg,2 C.W. Hanke,3 S. Tyring,4 W.P. Werschler,5 K.M. Knudsen,6 J. Goncalves,7 T. Larsson6 and N. Swanson8 1

University of Miami Miller School of Medicine, Miami, FL, U.S.A., Mount Sinai School of Medicine, New York, NY, U.S.A., 3St Vincent Hospital, Indianapolis, IN, U.S.A., 4University of Texas Health Science Center, Houston, TX, U.S.A., 5University of Washington School of Medicine, Seattle, WA, U.S.A., 6LEO Pharma A/S, Ballerup, Denmark, 7LEO Pharma Inc., Parsippany, NJ, U.S.A. and 8Oregon Health and Science University, Portland, OR, U.S.A. Recurrence rates of actinic keratoses (AK) after cryosurgery alone are high. Ingenol mebutate (IngMeb) gel field treatment following cryosurgery may be more effective than cryosurgery alone. We present long-term efficacy results evaluating sequential AK treatment with cryosurgery followed by oncedaily IngMeb 0015% gel (NCT01541553). In this multicentre, phase 3, randomized, two-arm, parallel-group, doubleblind, vehicle-controlled, 12-month study, patients with four to eight clinically typical, discrete AKs within a contiguous 25-cm2 treatment area on the face or scalp were enrolled. On day 1, all visible lesions were marked on a transparency and frozen using cryosurgery. After 3 weeks of healing, patients were randomized to field treatment with once-daily IngMeb 0015% gel or vehicle for three consecutive days, applied at home. Baseline and new lesions were followed throughout the study. Primary efficacy endpoint was complete clearance rate of AKs at week 11. Duration of complete clearance was assessed at months 6, 9 and 12. Secondary endpoints included percentage reduction in total number of AKs from week 11 to month 12. A total of 329 patients (805% with face and 195% with scalp lesions) were randomized to IngMeb (n = 167) or vehicle (n = 162); 158 and 150 patients, respectively, received treatment at week 3. Patients were well matched demographically. Patients were white, predominantly male (824%), with a median age of 67 years (range 34–89); most were Fitzpatrick skin type I (152%) or II (480%). IngMeb significantly improved complete clearance rates vs. vehicle at week 11 (605% vs. 494%; P = 004, ratio 122) and month 12 (305% vs. 185%; P = 001, ratio 167). Across 12 months, mean reduction in AKs from baseline was 682% for IngMeb vs. 541% for vehicle (P = 0002). Probability of sustained AK clearance was greater in the IngMeb group compared with the vehicle group: 78% vs. 68% at 6 months; 64% vs. 57% at 9 months; 55% vs. 40% at 12 months. Sustained clearance was derived from added benefit of IngMeb on frozen lesions, 431% vs. 309% for cryosurgery alone (P = 002), and prevention of development of new lesions, with 611% of IngMeb-treated patients not developing new lesions in the treated field vs. 481% of vehicle-treated patients (P = 002). Sequential treatment with cryosurgery followed by IngMeb 0015% gel provided significant clinical benefit at month 12 beyond cryosurgery alone. This sequential treatment 2

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approach of lesion-specific and field therapy effectively cleared baseline lesions and reduced both recurrence of existing lesions and development of new lesions in the treated field over 12 months. Funding source: LEO Pharma.

107 Nonmelanoma skin cancer in Canada C.W. Lynde,1 D. Zloty,2 G. Searles,3 J. Claveau,4 K. Barber,5 L. Guenther,6 M. Bourcier,7 M. Sapijaszko,8 R. Vender9 and Y. Poulin10 1

Lynde Centre for Dermatology, Toronto, Ontario, Canada, 2The Skin Care Centre, Vancouver, British Columbia, Canada, 3Searles Dermatology and Aesthetics, Edmonton, Alberta, Canada, 4Clinique Dermatologique Joel Claveau, Ste-Foy, Quebec, Canada, 5Dr Kirk Barber, Calgary, Alberta, Canada, 6Guenther Medicine Professional Corporation, London, Ontario, Canada, 7Marc Bourcier, Moncton, Ontario, Canada, 8Mariusz Sapijaszko, Edmonton, Alberta, Canada, 9Dermatology Centre, Hamilton, Ontario, Canada and 10Yves Poulin, Ste-Foy, Quebec, Canada Nonmelanoma skin cancer (NMSC) is the most commonly diagnosed cancer among Canadians (Canadian Cancer Society’s Steering Committee on Cancer Statistics. Canadian Cancer Statistics. Toronto, ON: Canadian Cancer Society, 2013). Basal and squamous cell carcinomas (BCC and SCC, respectively) are the predominant forms of NMSC, accounting for approximately 95% of all cases in Canada (Demers AA, Nugent Z, Mihalcioiu C et al. Trends of nonmelanoma skin cancer from 1960 through 2000 in a Canadian population. J Am Acad Dermatol 2005; 53: 320–28). The yearly incidence of NMSC in Canada has been steadily increasing (Demers et al.; Canadian Partnership Against Cancer. The Economic Burden of Skin Cancer in Canada: Current and Projected, 2010. Available at: The economic burden associated with NMSC is expected to rise proportionally; annual direct and indirect costs associated with BCC and SCC currently stand in excess of $90 million (Hayes RC, Leonfellner S, Pilgrim W et al. Incidence of nonmelanoma skin cancer in New Brunswick, Canada, 1992 to 2001. J Cutan Med Surg 2007; 11: 45– 52). BCCs and SCCs are the most common forms of NMSC, accounting for approximately 736% and 219% of all cases in Canada, respectively (Demers et al.). Despite SCC/BCC being the most common skin cancers in Canada, there have never been official NMSC guidelines. We undertook to produce guidelines for our Canadian population. Ten Canadian dermatologists and dermatological surgeons all specializing in skin cancer were tasked with the development of evidence-based guidelines on the prevention and management of actinic keratoses (AKs), SCCs and BCCs. A PubMed search of English-language clinical trials was conducted using the following search terms: ‘squamous cell carcinoma’, ‘basal cell carcinoma’, ‘actinic or solar’, ‘keratosis or keratoses’, ‘skin’ and ‘cutaneous’. Of the initial ~800 ‘clinical trial’-type reports identified, 296 publications were relevant to the treatment of NMSC. The relevant publications were categorized according to type of lesion and treatment modality. Each study was formally © 2014 The Authors BJD © 2014 British Association of Dermatologists

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evaluated by three members of the Committee, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system (Atkins D, Best D, Briss PA et al. Grading quality of evidence and strength of recommendations. Br Med J 2004; 328: 1490). Panel members subsequently met as a group and agreed on the treatment recommendations for the Guidelines as a whole. Our group of Canadian dermatologists has developed evidence-based Guidelines on the prevention and management of AKs, SCCs and BCCs, which can be useful for our population and have applicability to other world populations.

108 Education and awareness of skin cancer risk in liver transplant recipients and patients with inflammatory bowel disease: a comparison V. Campbell, N. McDougall and G. Turner Royal Victoria Hospital, Belfast, U.K. The risk of nonmelanoma skin cancer (NMSC) is increased with immunosuppression therapy. Our aim was to compare how aware liver transplant recipients and patients with inflammatory bowel disease (IBD), attending two separate services, were of this increased risk. Liver transplant recipients received extensive formal education regarding skin care and the risks of immunosuppression therapy at the time of transplantation. The IBD group received informal education on commencement of therapy and on an opportunistic basis. This was a prospective audit in a tertiary referral centre. Data were collected from consecutive liver transplant recipients and patients with IBD attending outpatient clinics between October 2013 and January 2014. Patients on immunosuppression therapy were asked to complete a questionnaire regarding awareness of NMSC risk and any previous episodes of suspected or documented skin cancer. Thirty-four patients with liver transplants (15 male, 19 female) and thirty-four patients with IBD (19 male, 15 female) completed the questionnaire. Mean ages were 52 and 36 years, respectively. Of the transplant patients, 23 were on tacrolimus, two on azathioprine, two on ciclosporin, and seven on combination therapy. Thirty-eight per cent of transplant patients had been on immunosuppression therapy < 2 years, with 29% on therapy > 10 years. In the IBD group, 29 took azathioprine and five mercaptopurine. Fifty per cent of patients with IBD had been on immunosuppression therapy < 2 years, with 9% on therapy > 10 years. Twenty-three (68%) transplant patients recalled being informed of the increased NMSC risk but two (6%) could not remember and nine (26%) denied being informed. Eighteen (53%) patients with IBD recalled being informed of the NMSC risk; three (9%) could not remember and 13 (38%) denied being informed. For patients on therapy < 2 years, 92% of transplant recipients and 705% of patients with IBD recalled being informed of the NMSC risk. Recall diminished to similar levels in both groups as treatment duration increased. Only 10 (29%) transplant recipients and 11 (32%) patients with IBD were aware of what skin changes to look out for. Five transplant patients were referred to Dermatology with one subsequent © 2014 The Authors BJD © 2014 British Association of Dermatologists

diagnosis of NMSC. One patient with IBD was referred with a subsequent diagnosis of NMSC. Each was on tacrolimus and azathioprine, respectively. Despite increasing awareness of NMSC risk in physicians, there remains a significant level of ignorance among patients. We suggest implementing a skincare pro forma to document patient education on a more frequent basis, particularly targeting patients on therapy > 10 years. Patients need to receive specific education on what skin changes to look out for.

109 Treatment of actinic keratoses with ingenol mebutate 0015% gel in solid organ transplant recipients ndez-Aragu s2 and S. Vidal€e I. Longo,1 I. Herna 1 Asensi 1

Hospital Central de la Defensa Gomez Ulla, Madrid, Spain and 2Hospital Gregorio Mara~non, Madrid, Spain Solid-organ transplant recipients (OTR) are at increased risk of progression of actinic keratosis to invasive squamous cell carcinoma (SCC). We report the outcome of treatment with ingenol mebutate in solid OTR with multiple or large (> 15 mm) facial actinic keratoses. Five male patients with solid organ transplants (three renal and two hepatic) were included. The mean age was 69 years (54–84) and mean time since transplantation was 124 years (7–25). Previous cutaneous tumours included five SCC (one in two patients and three in another) and eight basal cell carcinomas (one patient had seven). All patients have been previously treated for actinic keratoses, mostly isolated lesions, but two have had received field-directed therapies that included imiquimod and photodynamic therapy. Four patients presented areas of field cancerization with multiple actinic keratoses on the frontal or frontoparietal regions, and one patient had bilateral involvement. Another patient had a large actinic keratosis measuring 15 9 10 mm on the frontal region. On average the treated areas did not exceed a surface area of 20 cm2. Follow-up visits after completing the treatment were scheduled at 1 week, 6 weeks and after 4 months. Four patients reported moderate side-effects and one patient reported severe local side-effects with significant oedema beyond the treated area. The inflammatory response subsided in 1 week except in one patient that was prolonged for > 2 weeks. The patient who had bilateral involvement was instructed to treat the areas sequentially and he noticed less inflammatory response in the area treated in the second place. At 6 weeks, four patients showed a complete response and one patient showed a partial response with > 75% of clearance. After an average of 56 months there has been no recurrence on the treated area. All patients reported being satisfied with the treatment outcome and were eager to repeat it in case of being necessary. As life expectancy of solid OTR increases so does the prevalence of actinic keratoses. These patients have multiple recurrences that need many treatment cycles. Ingenol mebutate offers another alternative for the management of actinic keratoses, either for isolated or for multiple lesions within an area of field cancerization. Given British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

50 WCCS Abstracts

the short duration of therapy there is less worry about graft impairment, which is the main concern in these patients.

110 An audit of the recording of clinical risk factors in immunosuppressed renal transplant recipients with squamous cell carcinoma D. Caruana, I. Ngu, R. Herd, C. Geddes and L. Mackintosh NHS Greater Glasgow and Clyde, Glasgow, U.K. Cutaneous squamous cell carcinoma (SCC) may be classified as high or low risk by clinical and pathological features. SCC is staged according to the American Joint Committee on Cancer 7 (AJCC7) staging system, which takes into account high-risk features. Accurate recording of clinical risk factors on pathology reports is essential for staging of SCC. The Scottish Intercollegiate Guidelines Network (SIGN) draft national clinical guideline on the management of primary cutaneous SCCs states the importance of early identification of high-risk tumours and recommends high-risk SCCs be discussed at a skin cancer multidisciplinary team meeting (MDTM). Immunosuppression is a clinical high-risk factor, SCC is the commonest tumour in renal transplant recipients (RTR) in whom SCCs have higher rates of recurrence. We wished to audit current clinical practice against the SIGN guidelines, the aim being to audit recording of clinical risk factors on the histology request. The secondary aim was to identify pathological risk factors and the number of high-risk SCCs currently discussed at the local skin cancer MDTM. A retrospective audit of SCCs diagnosed in RTR was carried out. Each skin biopsy report from all pathology laboratories in the West of Scotland (WoS) between 1 January 2012 and 31 December 2013 from all RTR patients was extracted from the WoS electronic renal patient record (SERPR). Each report was read to detect SCCs, recording of high-risk features and discussion at MDTM. There were 81 newly diagnosed SCCs in 48 patients. Nine lesions were treated by curettage and electrodessication. Nine lesions had a diagnostic biopsy, of which seven were re-excised revealing no residual tumour and one re-excision fell outwith the audit period. Data were collected on the remaining 64 SCC. Immunosuppression was recorded in 39 (61%), anatomical site in 64 (100%) and clinical size in five (8%) of cases. Pathological tumour diameter was recorded in 61 (95%) and tumour depth in 59 (92%) cases. Tumour differentiation was recorded in 64 (100%); no tumour subtypes were recorded. Presence/ absence of lymphovascular/perineural invasion was recorded in 59 (92%)/53 (83%) cases. Completeness of excision was recorded in 64 (100%); for incomplete excisions, deep/ peripheral margin involvement was recorded in 100%. Where data were available, seven (11%) cases were discussed in a MDTM. This audit highlights deficiencies in the recording of clinical risk factors in particular immunosuppression and clinical size. Sixty-four high-risk SCCs were excised over the 2-year audit period. These data may assist in future planning of the MDT workload. British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

111 Ingenol mebutate 005% gel reduces cancer cells in squamous cell carcinoma in situ and shows marginal effect in seborrhoeic keratosis R. Rosen,1 M. Freeman,2 J.R. Zibert,3 J. Katsamas,3 K.M. Knudsen3 and L. Spelman4 1

Southderm Proprietary Ltd, Kogarah, Queensland, Australia, 2The Skin Centre, Benowa, Queensland, Australia, 3LEO Pharma, Ballerup, Denmark and 4Specialist Connect, Woolloongabba, Brisbane, Queensland, Australia Safety and efficacy was investigated following lesion-specific topical application of ingenol mebutate (IngMeb) 005% gel in treating squamous cell carcinoma (SCC) in situ (SCCIS) or seborrhoeic keratosis (SK) on nonhead locations in separate clinical trials. Two multicentre, open-label trials in patients with either SCCIS or SK were conducted. Patients were allocated to receive IngMeb 005% gel, applied to either one histologically confirmed SCCIS once daily on two consecutive days (n = 25 lesions), or two to four SK lesions once daily on three consecutive days (n = 80 lesions). SK lesions were occluded (n = 40) or alcohol swabbed prior to treatment (n = 40); only the latter will be reported herein. For both studies, the clinical clearance rate (CCR) was assessed on day 57 or 85 in the SCCIS trial, and on day 43 for the SK trial. At the end of the SCCIS trial the treatment area was excised and the histological clearance rate (HCR) was evaluated. Additionally safety, including local skin response (LSR), was assessed. In the SCCIS trial, patients achieved a combined (days 57 and 85) 36% HCR or 64% CCR. In the SK trial, patients achieved 15% CCR. In both trials, the LSRs were dominated by (SCCIS/ SK) erythema (100%/93%), flaking/scaling (80%/46%), swelling (56%/60%) and vesiculation/pustulation (32%/ 30%). The severities of the LSRs were mostly mild (grade 2 out of 5) in SCCIS, and reached a mean composite score of 45 out of 24 in SK. Adverse events were generally mild to moderate in intensity. All parameters resolved without sequelae by the end of the trials. Neither scarring nor abnormal proliferation was reported. Ingenol mebutate 005% gel, when treating SCCIS for two and SK for three consecutive days, induced a LSR in both SCCIS and SK lesions, with more flaking/scaling in SCCIS. The CCR tended to be high in SCCIS, but marginal in SK. This may indicate different penetration of ingenol mebutate in SCCIS and SK, or selectivity of ingenol mebutate for cancer cells over benign cells. Funding source: LEO Pharma A/S ( numbers, NCT00329121 and NCT01214564).

112 A comprehensive literature review of skin cancer prevention and surveillance in renal transplant recipients M.F. Chin,1 A.V. Anstey1 and P. Gill2 1

Welsh Institute of Dermatology, Cardiff, U.K. and 2University of South Wales, Pontypridd, U.K. Skin cancer in renal transplant recipients (RTRs) is a leading cause of mortality post-transplantation. A literature review was carried out to determine how clinical practice in skin cancer © 2014 The Authors BJD © 2014 British Association of Dermatologists

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prevention and surveillance for RTRs has evolved in the past three decades. The literature search was undertaken between September 2013 and February 2014 using MEDLINE and CINHAL databases. The following key search terms were used: skin cancer(s), renal, kidney, transplant(s), transplantation, patient experience(s). Only English language papers were included. Literature reviews, systematic reviews and original research papers were included. Relevant articles were reviewed using standard appraisal techniques. The articles identified revealed a cumulative incidence for nonmelanoma skin cancer (NMSC) in RTRs in the U.K. and Australia after 10 years of 30% and 70%, respectively. Furthermore, the articles showed that NMSCs in RTRs are more likely to advance locally or metastasise compared with in the nonimmunosuppressed. In 2000, skin cancer surveillance was routinely available in just 20% of RTRs in the U.K. This survey was repeated in 2006 in the U.K. and Australia. This showed that 66% of U.K. centres were providing skin cancer surveillance, compared with 97% of Australian centres. Dermatologists were more likely to be involved in this service in Australia than in the U.K. The literature review revealed moderate evidence for the benefit of follow-up by dermatologists post-transplant. One U.K. study found high rates of patient compliance with sun protection and awareness of skin cancer in RTRs routinely referred within 6–12 months of transplant to dermatology. Another study reported on RTRs followed up by dermatology; patients who developed malignant melanoma were diagnosed sooner and had a better outcome. However, the evidence from these studies suggested that dermatology follow-up of RTRs remains patchy at best in the U.K. Workload data from the British Association of Dermatologists suggests that routine dermatology follow-up for all RTRs is currently not possible for overstretched dermatology services. Our literature review found no evidence of patient inclusion in a team-based approach to educating patients about risk and promoting photoprotection in this vulnerable group. In conclusion, this review revealed strong evidence for increased risk of skin cancer in RTRs. However, dermatology resources in the U.K. are limited, and skin cancer prevention and routine surveillance is patchy at best. Novel approaches to raising patient awareness of this issue are now needed. We found no evidence of the RTRs themselves being involved in addressing this problem.

113 Establishing a place for advanced practice in skin cancer radiation therapy: experiences of two urban cancer centres E. Sinclair1 and J. Harriman2,3 1

Sunnybrook Health Science Centre, Toronto, Ontario, Canada, 2Department of Oncology, University of Toronto, Toronto, Ontario, Canada and 3London Victoria Hospital, London, Ontario, Canada According to the U.S. Census Bureau by 2030 the population will increase to approximately 365 million. The number of new cancer cases in Ontario is projected to increase by more than 60% by 2020, and double by 2028. Skin cancer is the most common form of cancer in North America. With over © 2014 The Authors BJD © 2014 British Association of Dermatologists

13 million new cases each year, it constitutes nearly 40% of all diagnosed cancers and the incidence is steadily increasing. One in every five North Americans will develop skin cancer in their lifetime. Quality patient care from referral to treatment and follow-up, calls for dedicated interdisciplinary expertise. Radiation therapists (RTs) are already fully integrated members of the oncology healthcare team. Treatments are typically planned and administered by RTs. The opportunity arose to develop advanced practice RT (APRT) roles by harnessing the RTs’ unique skill set, adding positive clinical impact. A series of projects was funded to investigate the feasibility of this new healthcare provider role in radiation: APRT Development (2004–2006); Clinical Specialist Radiation Therapist (CSRT) (APRT) Demonstration (2007–2010); CSRT (APRT) Sustainability (2010–2014). This study shows some of the positive impacts that the RT’s evolution into the APRT had on two successful multidisciplinary skin cancer clinics. Evaluations were completed in: wait times; access to care; delegation of activities; service enhancement; patient satisfaction; team acceptance; competence; patient safety; and education and training. The APRT took on many projects, e.g. would the development of clearly defined booking guidelines combined with the triaging of all new referrals to the skin clinic by the APRT reduce the wait time from referral to consult? This resulted in an improvement, with 87% of patients now meeting their consult target compared with 21% previously. Concordance data were collected using the radiation oncologist as the gold standard: concordance of 96% dose prescription, 94% field placement and 98% establishment of treatment plan were found. The results showed that an APRT role produced several benefits: decreased workload of physicians; increased patient throughput; improved resource utilization; and improved wait times. An APRT, fully trained in basic skin radiation therapy can free up oncologists’ time to pursue more complicated cases and time for more new patients, reducing wait times for services and increased access for patients.

114 Ablative fractional laser-assisted methyl aminolaevulinate photodynamic therapy (MAL-PDT) vs. conventional MAL-PDT for the treatment of actinic cheilitis: a randomized, comparative study D.-Y. Ko, S.-H. Choi, K.-H. Kim and K.-H. Song Skin Cancer Center, Department of Dermatology, College of Medicine, Dong-A University, Busan, Republic of Korea Actinic cheilitis (AC) is a preinvasive malignant lesion that has potential to progress into squamous cell carcinoma (SCC). SCC of the lip metastasizes much more frequently than analogous lesions, so, early and effective treatment is important. Conventional modalities of AC treatment may very often have low efficacy and disabling side-effects. Photodynamic therapy (PDT) on actinic keratoses (AK) showed high response rates and superior cosmetic outcomes compared with conventional therapies. However, PDT for AC is not very common. We compared the clinical and histological long-term outcome, British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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recurrence rate, cosmetic outcomes and safety between erbium-doped yttrium aluminium garnet (Er:YAG) ablative fractional laser (AFL)-assisted PDT (Er:YAG AFL-PDT) and conventional methyl aminolaevulinate PDT (MAL-PDT) in AC. We included 49 patients with histologically proven AC that did not respond after various previous therapies. Twelve patients were treated with one or two sessions of Er:YAG AFL-PDT, while others were treated with MAL-PDT. Er:YAG AFL therapy was performed using 550–600 lm ablation depth, level 1 coagulation, 22% treatment density and a single pulse. MAL cream was then applied under occlusion for 3 h and illuminated with a red light-emitting diode lamp at 37 J cm 2. Overall response rate, recurrence rate, cosmetic outcomes and safety were assessed clinically and histologically at 3, 6 and 12 months after treatment. After 3 months, Er:YAG AFL-PDT was more effective (917%) than MAL-PDT (784%), and the recurrence rate was lower for Er:YAG AFL-PDT (91%) than for MAL-PDT (256%) at 12 months. After 12 months, overall efficacy of Er:YAG AFL-PDT was significantly higher than that of MAL-PDT (833% vs. 514%, P = 005). No significant difference was found between Er:YAG AFL-PDT and MAL-PDT in terms of cosmetic outcomes or safety. Er:YAG AFL-PDT showed significantly higher efficacy and lower recurrence rate than conventional MAL-PDT for treating intractable AC.

115 Ingenol mebutate gel in actinic keratosis: fast and furious. . .but worth it S. Vidal-Asensi, I. Longo, D. Estrella-Aquino and J. Garcia-Funes Central Defense Hospital, Madrid, Spain Ingenol mebutate (IM) is a novel treatment, recently introduced for the treatment of actinic keratosis (AK) and field of cancerization. In 2013 we began to prescribe IM for head or face AK in a 3-day application, giving the normal explanations about field treatment, and an appointment for 3 months. Soon after, many patients came back on the following days complaining because of their ‘unexpected’ local skin reactions (LSR). It disturbed our work, made patients lose the confidence in doctor and drugs, and decreased the adherence. Then, we decided to standardize: (i) the information to the patients; (ii) the adding of an appointment at 1 week after the beginning of the treatment; (iii) the prescription of a topical treatment for the LSR; and (iv) to include the quantification of the LSR and the results of the treatment on the medical history. As done classically, events were categorized using a three-grade scale: 0 = none, 1 = mild, 2 = moderate and 3 = severe. However LSR items, were taken from the new scoring: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. The doctor’s leaflet of IM gel includes a three-point photographic scale applicable to lesions sited on the trunk or extremities that uses the same three-point scoring, so it was easy to perform. To establish its usefulness we recorded 34 clinical cases, 20 male and 14 female subjects, with a mean age of 78 years. All were white, British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

most with skin phototype II and some III. The majority had undergone previous treatment for AK. Only eight patients applied the treatment on the scalp, and the remaining on their face. The mean score of the LSR was 24 (0–3), with no general reactions, and three patients stopped the treatment because of a very fast severe reaction (erosion or blistering). In conclusion, we think that the skin’s changes must be considered in a semiquantitative three-point scale, but maximum scores in only one item such as crusting, vesicles or erosions should always be considered as severe reactions. Taking into account the high mean age of our patients, it is better to warn of this LSR with the aid of the leaflet, and give a 1-week appointment. Topical treatments like chlorhexidine solution and fusidic acid cream should be added to treat the foreseeable LSR. With no doubt, IM is convenient and highly efficacious in the elderly; adverse effects are easily managed, if anticipated.

116 For skin cancer prevention practices and the impact on the experiences € ¨ kten and Z. Ozer C. O Department of Internal Medicine Nursing, Akdeniz University Nursing Faculty, Antalya, Turkey The aim of this review, was to determine the impact of the applications used for protection from skin cancer on the experiences. We conducted a systematic literature review to evaluate the study results within applications for protection from skin cancer on the experiences. Akdeniz University Center electronic databases including MEDLINE, CINAHL, Science Direct and the Cochrane library were searched for studies published in English with ‘skin cancer and preventive procedures’, ‘skin cancer and preventive practices’ and ‘applications for protection from skin cancer’ key words. Search results reached 60 788 articles; also references of the determined studies were reviewed. After investigation of the articles published between 2002 and 2008, which can be accessed in full text, the original three articles have been sampled. In the recent literature review, there are three studies about the applications used for protection from skin cancer on the experiences. A descriptive study was conducted by Alberg and colleagues in 2002 (Alberg AJ, Herbest RM, Genkinger JM, Duszynski KR. Knowledge, attitudes, and behaviors toward skin cancer in Maryland youths. J Adolesc Health 2002; 31: 372–7). In this study, the most frequent applications the participants utilized to protect from skin cancer were ‘wearing a hat while in the sun’ and ‘using sunscreen’. Also, the results showed the likelihood of being sunburned during the past summer decreased with favourable attitudes toward skin protection. Another study was conducted by Woolley and colleagues in 2004 (Woolley T, Buettner PG, Lowe J. Predictors of sun protection in northern Australian men with a history of nonmelanoma skin cancer. Prev Med 2004; 39: 300–7). In this study, the most frequent applications the participants utilized to protect from skin cancer were ‘wearing a long-sleeved shirt and wide-brimmed hat’, ‘trying to avoid going out in the sun around midday’ © 2014 The Authors BJD © 2014 British Association of Dermatologists

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and ‘using sunscreen’. Participants who typically wore a longsleeved shirt and wide-brimmed hat reported greater numbers of previously excised skin cancers or suspicious skin lesions. Participants who wore a long-sleeved shirt and wide-brimmed hat were more likely to state that they had not experienced recent sunburn. Another study was conducted by Dobbinson and colleagues (Dobbinson S, Wakefield M, Hill D et al. Prevalence and determinants of Australian adolescents’ and adults’ weekend sun protection and sunburn, summer 2003–2004. J Am Acad Dermatol 2008; 59: 602–14). In this study, for adults, wearing longer styles of clothing on the arms and legs was also protective and associated with a 39% reduced odds of sunburn. The protective applications for skin cancer can reduce the negative experiences. Nurturing positive attitudes toward sun-protective behaviours should assume a prominent role in education.

117 Daylight photodynamic therapy of actinic keratoses: a randomized double-blinded prospective study to compare BF-200 ALA with methyl-5-aminolaevulinate N. Neittaanma¨ki-Perttu,1 T. Karppinen,2 €nroos,2 T. Tani2 and E. Snellman3 M. Gro 1

Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland, 2P€aij€at-H€ame Social and Health Care Group, Lahti, Finland and 3 Tampere University and Tampere University Hospital, Tampere, Finland Daylight-mediated photodynamic therapy (DL-PDT) using methyl-5-aminolaevulinate (MAL) is effective for thin, grade I, actinic keratoses (AK). There are no published studies of other photosensitizers used in DL-PDT. The aim of the study was to compare the efficacy and adverse effects of BF-200 ALA (5-aminolaevulinic acid nanoemulsion) with MAL in DL-PDT of grade I–III AKs. A total of 177 AKs symmetrically in 13 patients randomized for a split-face, prospective, observer-blinded study received BF-200 ALA or MAL DL-PDT. Grade I AKs were treated once and grade II–III AKs twice with a 025-mm layer of photosensitizers. Pain was assessed during and after the daylight exposure. Efficacy at 3 months was assessed clinically, histologically and in hyperspectral images. BF-200 ALA cleared 71/84 (84%) and MAL 69/93 (74%) of the AKs (P = 0099), all grades responding equally, but with new AKs appearing during follow-up (n = 4, BF-200 ALA; n = 8, MAL). BF-200 ALA and MAL treatments resulted in 62% and 38% complete histological clearance (P = 0375); p53 expression decreased 544% and 337%, respectively (P = 0552). The clearance of field cancerization was detectable in the hyperspectral images. Both treatments were nearly painless with similar adverse reactions and no difference in patient preference. In conclusion, a minor but nonsignificant difference appeared between BF200 ALA and MAL effectiveness in DL-PDT. Thicker lesions in both groups responded when treated repeatedly. Importantly, a thin 025-mm layer of the photosensitizer was sufficient, which may lead to lower expense.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

118 FIELD study 1: safety of ingenol mebutate 0015% gel field treatment after cryosurgery of actinic keratosis at 12 months B. Berman,1 G. Goldenberg,2 W. Hanke,3 S.K. Tyring,4 W.P. Werschler,5 K.M. Knudsen,6 T. Larsson,6 J. Goncalves7 and N. Swanson8 1

University of Miami Miller School of Medicine, Miami, FL, U.S.A., Mount Sinai School of Medicine, New York, NY, U.S.A., 3St Vincent Hospital, Carmel, IN, U.S.A., 4University of Texas Health Science Center, Houston, TX, U.S.A., 5Department of Medicine/Dermatology, University of Washington School of Medicine, Seattle, WA, U.S.A., 6LEO Pharma A/S, Ballerup, Denmark , 7LEO Pharma Inc., Parsippany, NJ, U.S.A. and 8 Oregon Health and Science University, Portland, OR, U.S.A. FIELD study 1 was a phase 3, multicentre, randomized, twoarm, parallel-group, double-blind, 12-month study evaluating efficacy and safety of sequential field treatment with ingenol mebutate (IngMeb) 0015% gel or vehicle gel following cryosurgery, for actinic keratosis (AK) on the face or scalp (NCT01541553). Patients aged ≥ 18 years with four to eight clinically typical, visible, discrete AKs within a 25-cm2 area on the face or scalp were enrolled. At baseline, cryosurgery was administered to all AKs in the treatment field. Patients were randomized to receive IngMeb 0015% or vehicle gel to the selected field once daily for three consecutive days, after 3 weeks of healing. Safety was assessed 3 weeks after cryosurgery, and days 3, 7, 14, 28 and 56 after field therapy, and at 6, 9 and 12 months after cryosurgery. Safety endpoints included incidence and severity of local skin reactions (LSRs) and adverse events (AEs). A total of 329 patients (805% face and 195% scalp lesions) were randomized to IngMeb (n = 167) or vehicle (n = 162) following cryosurgery; 158 and 150 patients received the respective field treatment. All AEs relating to application of the study medication were transient, resolving by week 11. Over 12 months, 19 AEs occurred in 16 patients for IngMeb and seven AEs occurred in six patients for vehicle. Of these, 15 AEs in the IngMeb group and one in the vehicle group were related to study medication. At month 12, there were no AEs related to IngMeb and one case of hypopigmentation in the vehicle group considered related to cryosurgery by the investigator. There were no treatment-related serious AEs. All LSRs resolved rapidly in the IngMeb group, returning to baseline levels 2 weeks post-treatment application. Discontinuations in either group were not related to AEs or LSRs. Most common AEs for IngMeb were application-site pain (42%) and itch (24%). There were three cases of squamous cell carcinoma within the treatment field in the vehicle group, and two cases of basal cell carcinoma, one in each treatment group. None of these was related to treatment. IngMeb 0015% gel field therapy after cryosurgery was well tolerated. All LSR scores in the IngMeb group returned to baseline values within 2 weeks of treatment. At 12 months, there were few treatment-related AEs and no treatment-related serious AEs. 2

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119 Long-term efficacy and clearance of actinic keratosis using sequential treatment with ingenol mebutate 0015% gel after cryosurgery B. Berman,1 G. Goldenberg,2 W. Hanke,3 S.K. Tyring,4 W.P. Werschler,5 K.M. Knudsen,6 T. Larsson,6 J. Goncalves7 and N. Swanson8 1

University of Miami Miller School of Medicine, Miami, FL, U.S.A., Mount Sinai School of Medicine, New York, NY, U.S.A., 3St Vincent Hospital, Indianapolis, IN, U.S.A., 4University of Texas Health Science Center, Houston, TX, U.S.A., 5Department of Medicine/Dermatology, University of Washington School of Medicine, Seattle, WA, U.S.A., 6LEO Pharma A/S, Ballerup, Denmark, 7LEO Pharma Inc., Parsippany, NJ, U.S.A. and 8Oregon Health and Science University, Portland, OR, U.S.A. Cryosurgery effectively treats individual lesions of actinic keratosis (AK), but does not address subclinical AKs in actinically damaged skin, and recurrence rates are high. Combined use of ingenol mebutate (IngMeb) gel following cryosurgery may be more effective than cryosurgery alone. We present long-term efficacy results evaluating sequential treatment of AKs with cryosurgery followed by once-daily IngMeb 0015% gel (NCT01541553). In this multicentre, phase 3, randomized, two-arm, parallel-group, double-blind, vehicle-controlled, 12month study, patients with four to eight clinically typical, discrete AKs within a contiguous 25-cm2 treatment area on the face or scalp were enrolled. On day 1, all visible lesions were frozen using cryosurgery and patients were randomized to field treatment with once-daily IngMeb 0015% gel or vehicle gel for three consecutive days, applied at home after 3 weeks of healing. The primary efficacy endpoint was complete clearance rate of AKs at 11 weeks. The duration of complete clearance was assessed at months 6, 9 and 12. Secondary endpoints included percentage reduction in the total number of AKs from week 11 to 12 months. A total of 329 patients (805% with face and 195% with scalp lesions) were randomized to IngMeb (n = 167) or vehicle gel (n = 162) following cryosurgery; 158 and 150 patients received treatment with IngMeb or vehicle at week 3. Patients were well matched demographically and most were skin type I (15%) or II (48%). IngMeb significantly improved complete clearance rates vs. vehicle at 11 weeks (605% vs. 494%, ratio 122, P = 004). At 12 months, the complete clearance rate was 305% for IngMeb vs. 185% for vehicle, ratio 167 (P = 001); mean reduction in AKs was 595% vs. 444% (P = 0004). The probability of sustained clearance was greater with IngMeb. Sustained clearance was derived from added benefit of IngMeb on frozen lesions 431% vs. 309% for cryosurgery alone, ratio 141 (105–189), P = 002, and prevention of emerging subclinical lesions, with 611% of IngMeb-treated patients not developing new lesions in the treated field vs. 481% with vehicle (P = 001). Sequential treatment with cryosurgery followed by IngMeb provided significant clinical benefit over cryosurgery alone for 12 months. This combined treatment approach of lesion-specific and field therapy effectively cleared visible and subclinical lesions, thus reducing the risk of recurrence of existing lesions and new lesions. 2

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120 Continued neglect of skin exam by generalists D. Chandler Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, U.K. Skin cancer is the most common cancer in the U.K. and rates are rising fast. Previous studies have highlighted the importance of a complete skin examination in reducing the morbidity and mortality associated with cutaneous malignancy. Nonspecialist doctors working in hospitals are exposed to a wide variety of dermatological conditions, and are well placed to identify suspicious skin lesions; however this does require that the skin be examined. We aimed to determine how frequently doctors performed skin examination in medical patients on admission to hospital. The admission records of 250 adult patients admitted to the medical wards of a district general hospital in the U.K. were reviewed for evidence of skin examination having been performed. Skin examination was performed in 96% of patients (n = 24) on admission. In 46% of cases (n = 11) this was a targeted examination to assess for specific skin signs associated with an underlying medical condition, for example determining if excoriations or spider naevi were present in a patient with chronic liver disease. In 17% of cases (n = 4) skin examination was performed to confirm a skin condition described by the patient during the history taking. In the remaining 38% of cases (n = 9) there was no indication for skin examination. Skin lesions were detected in four of these patients, including two cases of basal cell carcinoma. Of particular importance is the finding that in 88% of patients (n = 22) skin examination was not performed despite it being of direct relevance to the presenting complaint. There was an associated morbidity in 36% of these cases (n = 8). Cutaneous malignancies and other important skin lesions may not be detected unless a complete skin examination is performed, yet the fact remains that this rarely occurs in hospital even when there is a specific indication to do so. Skin examination should be part of the routine assessment of all patients on admission to hospital. Medical students and doctors should receive better training in skin examination with emphasis on early detection of skin cancer.

121 (PP13) Pain and quality-of-life outcomes following wide local excision and sentinel lymph node biopsy for melanoma: a multicentre U.K. study C.H. Thomson,1 O. Cassel,2 H. Peach,3 J. Garioch1 and M. Moncrieff1 1

Norfolk and Norwich University Hospitals NHS Trust, Norwich, U.K., Oxford University Hospitals NHS Trust, Oxford, U.K. and 3Leeds Teaching Hospitals NHS Trust, Leeds, U.K. Standard care for invasive melanoma is surgical and postoperative pain can transform into the debilitating complex regional pain syndrome (CRPS). The aims of this study were to assess pain and quality of life in patients with melanoma across three U.K. treatment centres. In this prospective, cross-sectional 2

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study, 221 patients from three U.K. centres completed questionnaires comprising a neuropathic pain assessment tool (painDETECT) and a melanoma quality-of-life tool (FACT-M). All patients had undergone a wide local excision of a primary cutaneous melanoma and had a negative sentinel lymph node biopsy (American Joint Committee on Cancer stage I and II). The mean age was 586 years (range 20–85) and median time from surgery to questionnaire was 19 months (range 08–96). A total of 357% of patients reported pain at their surgical site and the mean rating for average pain over the last 4 weeks was 095/10. Seventeen patients (77%) rated their average pain as ≥ 5/10. Four patients (18%) scored in the high risk of neuropathic pain category as well as describing symptoms in keeping with CRPS. The age of patients experiencing pain was significantly lower than those who did not have pain (median 550 vs. 635 years, P < 0001). Pain scores showed a negative correlation with quality-of-life scores (P < 0001) but were not related to time since surgery. These results suggest the cohort experiencing pain is more likely to consist of independent, working age patients and the adverse socioeconomic impact of chronic pain could be devastating. This evidence has direct implications for current, international melanoma practice and highlights the need to assess postoperative pain and refer early to appropriate pain services. A trial investigating potential perioperative intervention to prevent postoperative neuropathic pain is merited.

122 Delineating margins of lentigo maligna using a hyperspectral imaging system €ki-Perttu,1 M. Gro €nroos,2 L. Jeskanen,1 N. Neittaanma 3 1 €lo €nen, A. Ranki, O. Saksela1 and E. Snellman4 I. Po 1

Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland, 2P€aij€at-H€ame Social and Health Care Group, Lahti, Finland, 3 University of Jyv€askyl€a, Jyv€askyl€a, Finland and 4Tampere University and Tampere University Hospital, Tampere, Finland Lentigo maligna (LM) represents the most prevalent in situ form of melanoma. Assessment of the LM borders is challenging because of the unpredictable subclinical extension, which often leads to repeated excisions. There is a need for a noninvasive method for presurgical margin control. This pilot study aimed to test the capability of a novel hyperspectral imaging system (HIS) in delineation of LM margins preoperatively in order to avoid the need for re-excisions. Eleven patients with 11 LM lesions on the facial area were included in the study. The lesion borders were assessed clinically by eye and Wood’s light examination. Hyperspectral images of each LM lesion were taken in vivo before surgical procedures. Borders given by HIS were compared with those estimated clinically. Results were confirmed by histopathology. In six out of 11 cases lesion borders were delineated more accurately (wider or smaller) with HIS than clinically, compared with histological analysis. In four of 11 cases HIS showed the subclinical extension of the lesion borders as confirmed by histology. In two of 11 cases LM was smaller than those clinically suspected in

© 2014 The Authors BJD © 2014 British Association of Dermatologists

both HIS and histological analysis. In four of 11 cases HIS delineated the lesion borders identically with clinical and Wood’s light assessment. In these cases there was no subclinical extension histologically either. In one of 11 cases HIS showed lesion extension but histological examination showed subclinical extension only on one side of the lesion, this was regarded as a false positive. No false negatives were found. In four cases there were subclinical actinic keratoses on the skin surrounding the LM and the lesions were detected by HIS and separated from LM borders. In conclusion, the results of this pilot study indicate that the HIS is capable of detecting the subclinical borders of LM. By detecting accurate margins for the lesions, re-excisions could be avoided. In addition, HIS could also be used to spare facial tissue in cases where lesion borders are smaller than with clinical assessments.

123 Setting up an isolated limb infusion service: a single centre’s learning curve and outcomes J. Maraka, E. Dickinson and M. Moncrieff Norfolk and Norwich Hospital, Norwich, U.K. Isolated limb infusion (ILI) is an established procedure for treating unresectable in-transit melanoma metastasis as a limb salvage procedure. Regional chemotherapy (melphalan and actinomycin-D) is infused into the limb in a hypoxic circuit via percutaneous catheters at low pressure. The technique was first used in the Sydney melanoma unit as an alternative to isolated limb perfusion, as ILI is less invasive and resource intensive. A new ILI service was established in 2010 in a large U.K. teaching hospital; to date, 23 patients have been treated with 25 procedures. We aim to review the outcomes and describe the extent of the learning curve encountered while establishing the service. The response rate was reported in accordance with the World Health Organization guidelines for reporting cancer treatment results. Limb toxicity was graded according to the Wieberdink toxicity grading. Complications were graded as described by the classification of Dindo et al. (Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205–13). Indications for ILI included unresectable in-transit melanoma metastasis (21 patients), locally advanced squamous cell carcinoma (one patient), and unresectable recurrent Merkel cell (one patient). The national ILI protocol was adopted and implemented as the treatment pathway for all patients. The median age was 72 years. Seven patients (30%) experienced grade I–II toxicity, 10 patients (43%) had grade III toxicity and there was grade IV toxicity (tissue damage/ epidermolysis, threatened or actual compartment syndrome) in six patients (26%). The median hospital stay was 14 days. Median follow-up was 9 months with an overall response rate of 64%. Complete response (CR) was achieved in 44% of cases (11/25), a partial response (PR) rate in 20% (five of 25), and 24% (six of 25) had progressive disease. Patients who had a PR subsequently underwent resection or CO2 laser ablation of the residual, chemoresistant deposits. Median disBritish Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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ease-free survival for patients with a response (CR or PR) was 10 months. Seven patients had grade III complications requiring surgical intervention, including one thermal burn and one fasciotomy. ILI is an effective strategy for managing unresectable locoregional cutaneous melanoma metastases and other extremity tumours, even in newly established centres. However, it is a high-risk procedure with a prolonged recovery time and a significant major morbidity rate. Patients need to be extensively counselled preoperatively. The significant learning curve associated with the ILI technique is not to be underestimated, although adoption of established protocols with external mentorship and practising in a major treatment centre could obviate some of the risk.

124 Magnetic resonance imaging after intradermal injection of magnetic tracer for lymphatic mapping and sentinel lymph node identification in patients with cutaneous melanoma: proof of concept S. White,1 P. Malcolm,1,2 B. Anninga,3 J. Klasse,4 B. ten Haken,5 S. Vreemann,4 R. Bezooijen,4 M. Hall-Craggs,6,7 M. Moncrieff1 and M. Douek3 1

Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, U.K., 2University of East Anglia, Norwich, U.K., 3Kings College London, London, U.K., 4Medisch Spectrum Twente, Enschede, the Netherlands, 5 Universiteit Twente, Enschede, the Netherlands, 6University College London Hospitals, London, U.K. and 7SentiMAG, Endomagnetics Ltd, Cambridge, U.K. Sentinel lymph node (SLN) status is the most important prognostic indicator for patients with primary cutaneous melanoma. Detection and treatment of micrometastases in the SLN is associated with improved survival and regional disease control. The lymphatic drainage of primary cutaneous melanoma is notoriously unpredictable. Therefore the international gold standard for performing SLN biopsy (SLNB) employs radioactive colloid and preoperative lymphoscintigraphy, to map the lymphatic drainage of the melanoma, identifying all regional lymph node basins and SLNs. A hand-held gamma probe and blue dye are used intraoperatively to locate and excise the SLNs, guided by the preoperative lymphoscintigraphy. However, the use of radioactive colloid is not without problems, particularly limited global availability. We aimed to assess a magnetic resonance imaging (MRI) protocol to evaluate the use of a superparamagnetic iron oxide (SPIO) magnetic tracer (Sienna+; Endomagnetics Ltd), for identifying the lymphatic drainage and locating SLNs in patients with primary cutaneous melanoma. Patients with primary cutaneous extremity melanomas (American Joint Committee on Cancer stage IB–IIC) scheduled for SLNB, who were eligible for enrolment within the MELAMAG trial, were recruited into the MRI substudy. All patients underwent standard preoperative SLN localization with radioactive colloid and lymphoscintigraphy. Patients subsequently underwent preoperative MRI localization. Preinjection T1-weighted and T2-weighted scanning was followed by intradermal injection of Sienna+ and local massage at the primary melanoma site. T2-weighted scans were repeated British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

15 min postinjection. Intraoperatively the SLNs were located using a combination of a hand-held magnetometer (SentiMag; Endomagnetics Ltd), the hand-held gamma probe and blue dye. Five patients with extremity melanoma (four lower, one upper) were recruited to the MRI substudy. Preoperative lymphoscintigrams were directly compared with the preoperative MRI scans pre- and postintradermal injection of Sienna+. In all five cases the MRI scanning technique identified the same number and location of lymphatic drainage basins as lymphoscintigraphy. In four cases the MRI technique demonstrated the same number of lymphatic channels as lymphoscintigraphy. In three cases the number of SLNs identified was the same for both techniques. The imaging findings for both preoperative imaging modalities correlated closely to intraoperative findings. This phase I feasibility study demonstrates for the first time that MRI in combination with SPIO magnetic tracer is a potential alternative to lymphoscintigraphy for preoperative lymphatic mapping in patients with cutaneous melanoma. Larger phase II trials including more challenging patients with head, neck and truncal primary melanomas are warranted.

125 Sentinel node biopsy in cutaneous melanoma: prognostic factors and survival of patients with false negatives lez, D. Etchichury, G. Urrutia, M. Pistone A. Gonza Creydt and C. Spinelli Arizmendi Instituto Alexander Fleming, Buenos Aires, Argentina Sentinel node biopsy (SNB) is the standard treatment in stage Ib–II cutaneous melanoma (CM). A false negative (FN) is one that relapses in the nodal area after a negative SNB. As a result, the patient is understaged and the prognosis is worse. The aim of the study was to analyse prognostic factors (PF) and the outcome of patients with FN-SN. Between March 1995 and December 2012, 310 consecutive SNBs were performed. There were 174 male patients (561%) with a median age of 50 years (3–79). The primary site was the chest 137 (442%), lower limb 84 (271%), upper limb 57 (184%) and head/neck 32 (103%). The mean Breslow thickness was 18  12 mm (03–9). There was ulceration in 67/288 (233%). The SNB location was the axilla 169 (545%), groin 99 (319%) and neck 42 (135%). The number of nodal areas investigated were one in 268/310 cases (865%), two in 39 (126%) and three in three (1%); SN in transit (IT): nine (29%); mean SN 2  1 (1–7); learning curve (LC): 50 cases. A patent blue and probe combination was employed, but in the first 52 cases (168%) just blue. Local anaesthesia was used in 161 (519%). Follow-up (FU) was 58  39 months (5–147). Univariate analysis: age, sex, site of CM, Breslow, ulceration, anaesthesia, nodal site, number of nodal areas dissected, SN number, LC and patent blue vs. blue+probe. SN not found: six (19%); SN+: 41 (132%); FN-SN: 16/310 (52%). Considering all positive nodes, i.e. 57 (41 SN+ plus 16 FN-SN), the real FN rate was 16/57 (28%). The mean nodal relapse interval was 40  30 months (5–102). In univariate analysis, independent PF (IPF): Breslow > 2 mm and © 2014 The Authors BJD © 2014 British Association of Dermatologists

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axilla SN location (the latter decreased FN risk). Lower limbs (P = 008) and IT-SN location (P = 006) increased FN risk, without statistical significance. In multivariate analysis: Breslow > 2 mm (P = 004/confidence interval 10378–74759), the only IPF. Axilla (P = 0057), marginal significance. For recurrence-survival analysis 13 patients were excluded (42%) with a < 12-month FU. Relapses occurred in 51/297 (172%). Disease-free survival (DFS) of 3 years: 94%, 783% and 375% in SN , SN+ and SN-FN, respectively; 5-year rates: 892%, 74% and 125% (P < 00001). Thirty-two patients out of 297 (108%) died of CM; CM-specific survival (CM-SS) at 3 years: 978%, 811% and 871% for SN , SN+ and FN–SN, respectively; 5-year rates: 951%, 766% and 662% (P < 00001). In conclusion, the FN rate is 52% (FU: 58  39 months). The only IPF was Breslow thickness > 2 mm. The 5-year DFS (SN : 892%, SN+ 74% and FNSN: 125%, P < 00001) and CM-SS (SN : 951%, SN+: 766 and FN–SN: 662%, P < 00001) is significantly worse in FN-SN patients. Our results can be seen as unfavourable when compared with MSLT- I. An explanation for this is that in our series patients treated during LC were also included. The experience and quality of a multidisciplinary team (nuclear medicine, surgery and pathology) is essential to reduce FN rates. We consider that SNB should be focused in high-volume centres where it is feasible to acquire and maintain the accuracy of the method.

126 Is it so easy to treat facial basal cell carcinoma? A. Derjabo,1 I. Cema1 and L. Derjabo2 1

Riga Stradins University, Riga, Latvia and 2University of Latvia, Riga, Latvia Basal cell carcinoma (BCC) is the most common skin cancer worldwide (Sartore L, Lancerotto L, Salmaso M et al. Facial basal cell carcinoma: analysis of recurrence and follow-up strategies. Oncol Rep 2011; 26: 1423–9; Tinelli M, Ozolins M, Bath-Hextall F et al. What determines patient preferences for treating low risk basal cell carcinoma when comparing surgery vs. imiquimod? A discrete choice experiment survey from the SINS trial. BMC Dermatol 2012; 12: 19). The long-term efficiency (recurrence rate) for different treatment modalities with respect to the histological type, precise anatomical localization and size is not clear yet. Our long-term follow-up results and limitations for treatment modalities are being demonstrated. The aim of the study was to evaluate the long-term efficiency and limitations of surgery, radiotherapy, laser and cryosurgery for the treatment of facial BCC. A retrospective, cohort, single-institution study was performed. Data of treated patients were collected using the National Health Service. Patients were treated in the oncology centre from January 2000 until December 2005. Four treatment modalities (surgery, radiotherapy, laser and cryosurgery) were used for primary T1-T2N0M0 facial BCC. All tumours were morphologically confirmed. Only patients observed > 5 years were included in the study. Patients were followed up for a mean © 2014 The Authors BJD © 2014 British Association of Dermatologists

duration of 98 months (range 84–120). A group of 968 patients were affected by BCC on facial regions within this study. The sample consisted of 634 female and 334 male patients, with a mean age of 65 years (range 18–93, median 65 years). The recurrence rate > 5 years for surgery was 92%, for radiotherapy 85%, for laser 138% and for cryosurgery 267%. Multivariate logistic regression was used to analyse the recurrence probability on BCC characteristics – the histological type, size, precise anatomical localization, and patient age and sex. The main limitations revealed for surgery were elderly age and associated illness; for radiotherapy – age from 60 years and infiltrative histological type; for laser – infiltrative histological type, size > 20 mm, localization on the lip and ear; and for cryosurgery – infiltrative histological type, size > 6 mm, localization on the lip, eyelid, ear, nose and forehead. It was concluded that facial BCC must be treated in consideration of patient preferences, treatment limitations, the histological type, size, precise anatomical localization, and patient age and sex.

127 Incomplete excision of nonmelanoma skin cancers: patients’ characteristics and recurrence rates after a long-term follow-up P. Kocyigit, S. Bostanci, H.K. Gungor, P. Korkmaz, M. Gundogdu, A. Maden and Y. Houshyar Ankara University Medical School, Ankara, Turkey In 07–50% of patients with nonmelanoma skin cancer (NMSC), who undergo conventional surgical excision, postoperative dermatopathological examination reveals that the tumour extends into the margins of the excised specimen. Due to the risk of tumour recurrence, many authors suggest re-excision. However, some reports show evidence about spontaneous regression of NMSCs, particularly basal cell carcinomas (BCCs), after incomplete excision. In addition, tumour location, morphology and patients’ intolerance for further procedures make it difficult to perform additional surgical treatment in some cases. There have been only a few reports about long-term follow-up of patients with incomplete excision of NMSC. Herein, we investigated 40 patients who had 48 NMSCs that were excised in our dermatological surgery department between January 1999 and August 2008, and had postoperative tissue specimens revealing that the tumour extended into the margins of the excised specimen. The patients were followed up for at least 5 years (5–13 years). The mean age of the patients was 61 years ( 12 SD). Twenty-nine patients were male and 11 were female. The median duration of the tumours was 12 months (min. 1 month, max. 960 months) and their median size was 10 mm (min. 3 mm, max. 45 mm). The median surgical excision margin was 5 mm (min. 1 mm, max. 10 mm). Forty-one of the cases with incomplete excision were BCC, six were squamous cell carcinoma (SCC) and one was Bowen disease. During the follow-up period 22% of the cases recurred. The median time for recurrence was 2 years (min. 1 year, max. 13 years). Nine recurrent cases were derived from BCCs British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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and two from SCCs. Six of the recurrent BCC subtype were nodular, two were infiltrative and one was metatypical. Two were already recurrent cases after a previous surgical excision. All were located on high-risk facial areas. On account of the relatively high risk for lesion recurrence, surgical or other therapeutic options should be considered, particularly in patients with incompletely excised high-risk tumours. Close follow-up even longer than 5 years is recommended for those in whom additional therapeutic approaches could not be performed.

128 Prognostic prediction by sentinel lymph node biopsy for extramammary Paget disease D. Ogata,1 Y. Kiyohara,2 S. Yoshikawa2 and T. Tsuchida1 1

Saitama Medical University, Saitama, Japan and 2Shizuoka Cancer Center Hospital, Shizuoka, Japan Extramammary Paget disease (EMPD) is characterized by the intraepidermal spread and usually presents as carcinoma in situ (CIS). However, once it has invaded the dermis, invasive EMPD is sometimes associated with lymph node (LN) metastasis and may develop distant metastases. Sentinel LN biopsy (SLNB) is now accepted in the management of melanoma and breast cancer. SLNB provides prognostic information and identifies patients with LN micrometastases. In this study, we retrospectively evaluated the usefulness of SLNB for EMPD. We evaluated outcomes in 50 patients with primary extramammary Paget disease assigned to undergo wide excision and SLNB, with immediate lymphadenectomy for nodal metastases detected on biopsy. The median follow-up period was 51 months. The diagnosis was confirmed by incisional biopsy. SLN detection was performed by preoperative lymphoscintigraphy, intraoperative blue-dye injection and a hand-held gamma-detecting probe. By using triple methods, the detection rate of the SLNs was 100%. The patients comprised 34 men and 16 women. A total of 112 SLNs were excised. The average number of the SLNs found was 21. SLNs were detected in the unilateral inguinal region in 23 patients and the bilateral in 27 patients; in the latter patients the primary lesion was located medially in the genital region. The incidence of SLN metastases was 18%. The rate of SLN positivity for each invasion level was 0% (none of 10) for CIS, 0% (none of 19) for microinvasion and 38% (eight of 21 patients) for dermal invasion. There were no complications after SLNB. Eight patients with positive SLNs underwent lymphadenectomy. Five of the eight patients who underwent lymphadenectomy are free of the disease (follow-up period: 25–89 months) and had fewer than three positive LNs. In contrast, three patients who died of the disease had more than three positive LNs. A nodal recurrence was detected in one of the 17 patients (6%) with negative SLNs. In conclusion, biopsy-based staging of primary EMPD provides important prognostic information. SLNB can detect occult lymph node metastasis and possibly contribute to improve the prognosis. However, the therapeutic value of SLNB remained uncertain in British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

this study, and we intend to conduct a prospective study in the immediate future.

129 Squamous cell carcinoma of the pinna: can histological features predict risk of metastases? E. Mayo,1 A. Lee,2 J. Horne,2 A. Gulati,2 H.M. Yuen2 and S. Sharma2 1

University of Southampton, Southampton, U.K. and 2University Hospital Southampton NHS Foundation Trust, Southampton, U.K. Squamous cell carcinoma (SCC) of pinna origin is considered to have a high risk of metastases of up to 16% compared with < 5% for SCCs of any origin. Previous work has suggested that histological features of the primary tumour may be used to provide evidence for further surveillance or therapeutic management. The aim was to identify any association between histological features and risk of metastasis. Having obtained ethical approval, an electronic search was performed in the University Hospital Southampton NHS Foundation Trust histopathology records for all patients with auricular SCC from the last 5 years. Inclusion criteria included pinna origin, completed 2-year follow-up and absence of immunosuppressive history. The specimens were analysed with regard to several histopathological features that were thought to be relevant to metastasis. Statistically significant associations between histological features and risk of metastases were described using standard analytical methods. A total of 192 patients were included; four (21%) patients developed metastases, each with lymph node involvement. Perineural invasion was the only histological feature to be significantly associated with increased risk of metastases (P < 0001). In conclusion, the overall metastatic rate in our group of patients was found to be much lower than in other studies. Factors other than histological features alone may explain the nature of the results. Our work suggests that although some histological features were statistically associated, they do not predict a high enough risk of metastatic disease to provide evidence for further surveillance or elective lymphadenopathy.

130 Ingenol mebutate 005% gel under occlusion is efficacious in treating superficial basal cell carcinoma L. Spelman,1 R. Rosen,2 K.M. Knudsen,3 J.R. Zibert3 and M. Freeman4 1

Specialist Connect, Woolloongabba, Queensland, Australia, 2Southderm Proprietary Ltd, Kogarah, Queensland, Australia, 3LEO Pharma A/S, Ballerup, Denmark and 4The Skin Centre, Benowa, Queensland, Australia Ingenol mebutate (IngMeb) applied for 2 days has shown efficacy in treating superficial basal cell carcinoma (sBCC). The objective of this study was to evaluate the safety and efficacy of IngMeb 005% gel with and without occlusion in sBCC lesions (NCT01325688). IngMeb 005% gel was applied for three consecutive days in patients aged ≥ 18 years with a histologically confirmed sBCC (4–15 mm in © 2014 The Authors BJD © 2014 British Association of Dermatologists

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diameter and < 1 mm thick) on the trunk/extremities. Patients (n = 75) were randomized to occlusion with: a fullocclusive aluminium disk (ALU, n = 25), a semiocclusive dressing with OpsiteTM (OP, n = 26), or no occlusion (NO, n = 24). Safety outcomes included treatment-related adverse events (AE) and local skin responses (LSR) (maximum score 24). Efficacy was evaluated at day 120 by both complete clinical clearance rates (CCCR) and complete histological clearance rates (CHCR) of lesions. Two patients were incorrectly assigned following randomization, therefore, the actual assignment numbers were 27 for ALU, 24 for OP, and 24 for NO. Overall, 40% of patients received treatment for < 3 days. The percentage of patients with AEs was similar in all three treatment groups. The majority of AEs were not considered treatment related. In total, 15 treatment-related AEs were reported, of which 11 were in the ALU group, and the most common AE was application-site pain. A total of 15 serious AEs were reported, and by the end of the trial, all were either recovered or recovering. Mean composite LSR scores were: 113 ALU, 75 OP and 89 NO. Worsening was observed in the following numbers of patients: scarring, three of 27 (ALU) and one of 24 (OP); hypopigmentation, eight of 27 (ALU), three of 24 (OP) and five of 24 (NO); hyperpigmentation, three of 27 (ALU). With all dressings, an improvement was observed, throughout the follow-up period of 120 days, in one patient per treatment group for scarring and hypopigmentation, respectively. However, for hyperpigmentation, improvement was only evident for the NO group. In the ALU group, 22/27 patients only tolerated one treatment due to the severity of the LSR. The effect evaluated as CHCR/CCCR of lesions was: 704%/741% (ALU), 375%/750% (OP), and 542%/750% (NO). Treatment of sBCC lesions with IngMeb 005% gel under occlusion with an aluminium disk is highly efficacious even with only one in-office treatment with one unit dose. Despite only a single application in multiple patients, IngMeb 005% resulted in high histologically and clinically confirmed clearance rates. This modality will possibly only be limited by the occurrence of hypopigmentation in 30% of cases.

131 Plastic and reconstructive Mohs surgery enhances outcomes compared with conventional excision and reconstruction R. Wain and H. Tehrani Mersey Regional Centre for Mohs Surgery, Department of Plastic & Reconstructive Surgery, St Helen’s and Knowsley Teaching Hospitals NHS Trust, St Helens, Merseyside WA9 3DA, U.K. Comparisons between Mohs micrographic surgery (MMS) and conventional excision (CE) have been made in the past, in particular relating to tumour recurrence rates; however, there are no comparative studies of reconstructive outcomes between these two methods in the current literature. We compared the reconstructive techniques and histological findings of our patient group to evaluate the effectiveness of plastic and reconstructive MMS vs. CE and reconstruction. All patients listed for © 2014 The Authors BJD © 2014 British Association of Dermatologists

MMS in our service between January 2013 and January 2014 were included. Preoperative patients were prospectively assessed for the margins and type of reconstruction that would be necessary if CE were utilized. Post-MMS, the extent of complete excision and reconstructive method used were recorded and compared with the preoperative non-MMS plan. In total 157 patients were analysed over 13 months, with a mean age of 634 years and a male-to-female ratio of 1 : 15. The anatomical distribution of the lesions was consistent with the current literature and included 93% basal cell carcinoma, 6% squamous cell carcinoma and 1% microcystic adnexal carcinoma (MAC). Had CE and reconstruction been used, 47% of patients would have received a more invasive or cosmetically less desirable reconstruction, and 24% of margins would remain incomplete. The outcome was unchanged in 20% of patients. A small but significant proportion (9%) of patients would have lost fundamental structures, for example orbital exenteration, or undergone reconstructions unnecessarily crossing aesthetic subunits. This supports existing evidence that MMS permits optimum tissue preservation while virtually guaranteeing complete excision. While in its infancy, plastic and reconstructive MMS offers a valuable service with a demonstrable benefit seen in 80% of patients undergoing MMS in our unit. Additionally, comparison of MMS and CE provides a method for evaluating the efficiency and effectiveness of the service. A high percentage of patients demonstrating no gain in outcomes over CE may indicate inefficient usage of the MMS service and may be a useful method for other MMS centres to ensure they provide a cost-effective service in a constrained financial climate.

132 Prognostic factors for local recurrence and lymph node metastasis in cutaneous squamous cell carcinoma of the head and neck treated with Mohs surgery A. Gonza´lez,1 D. Etchichury,2 M.P. Creydt,1 M. Rivero1 and C.S. Arizmendi2 1

Instituto de Oncologıa Angel H. Roffo, Buenos Aires, Argentina and Instituto Alexander Fleming, Buenos Aires, Argentina Most cutaneous squamous cell carcinomas (SCCs) arise on the head and neck. Local control after surgery or Mohs surgery(MS) is as high as 90–95%. However, local recurrence (LR) or nodal metastasis (NM) may occur. High-risk cutaneous SCCs may be identified based on primary tumour and/or patient factors. The aim of this study was to analyse prognostic factors for LR and NM in a consecutive series of patients. Between June 1990 and June 2012, 4732 nonmelanoma head and neck skin cancers were treated with MS. Cutaneous SCC made up 137% of cases (n = 649). Excluded from analysis were 110 SCC in situ, SCC on the fingers (seven) or lip (33), patients with genetic syndromes (four) or on immunosuppression (four) and 57 lost to followup. The remaining 434 patients were followed up for a mean 569 months (range 10–251). We recorded sex, age, tumour size, site, grade differentiation, perineural involvement and previous treatment. Men formed 703% of the group (n = 305) and the overall median age was 72 years (range 28–97). 2

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Regarding grade differentiation, where data were available, 291/415 (701%) were well differentiated, 95/415 (229%) moderately and 29/415 (7%) poorly (no data for 19). The median tumour size was 2 cm (range 02–12). The sites were ear/periauricular (108, 249%), forehead/temple (92, 212%), nose (77, 177%), cheek or chin (69, 159%), scalp (56, 129%), orbit (23, 53%) and neck (nine, 21%). Six patients (14%) had perineural involvement and 61 (141%) had undergone previous treatment. Next, logistic regression was used to identify factors associated with LR and NM. Fifteen patients (35%) developed LR. The median interval to LR was 143 months (range 6–51), with 14 of 15 (93%) occurring in the first 24 months. Of the patients with LR, 11/15 (73%) were men, and the median age was 647 years (range 45–92). The median tumour size was 25 cm (range 1–4). LRs comprised six of 69 (9%) tumours on the cheek or chin, five of 92 (5%) on the forehead/temple, one of 23(4%) on the orbit, two of 77 (3%) on the nose and one of 56 (2%) on the scalp. Ten were well differentiated, three moderately and two poorly. Seven of these 15 patients (47%) had undergone previous treatment. Univariate analysis showed that previous treatment (P < 0001) and cheek and chin location (P = 002) were significantly associated with LR. Marginal statistic significance was seen for tumour size (P = 0056) and perineural involvement (P = 052). In multivariate analysis previous treatment [P < 001, hazard ration (HR) 557, 95% confidence interval (CI) 202–1533) and cheek or chin location (P = 0446, HR 304, 95% CI 103–894) were independent factors. Nineteen patients (44%) developed NM. The median interval to NM was 124 months (range 1–32), with 16 of 19 (84%) during the first 24 months. Men formed 89% of this group (17 of 19) and the median age was 77 years (range 50–86). The median tumour thickness was 28 cm (range 18–6). The sites of NM were cheek or chin (four of 69, 6%), ear/periauricular (six of 108, 56%), forehead/temple (five of 192, 54%), scalp (two of 56, 36%) and nose (two of 77, 26%). Four of the 19 patients (21%) had undergone previous treatment. Of the NMs nine were well differentiated, five moderately and five poorly. Seven of the patients had undergone previous treatment. In the univariate analysis for NM, poor differentiation (P = 0002) and tumour thickness ≥ 2 cm (P < 0001) were significant. Male sex (P = 008) and local recurrence (P = 0059) reached marginal significance. Poor differentiation (P = 00041, HR 459, 95% CI 163–1292) and tumour thickness ≥ 2 cm (P < 001 HR 925, 95% CI 266–3212) were independent factors in multivariate analysis. In conclusion, LR was seen in 35% of cases and NM in 44%. Independent predictive factors for LR were previous treatment and cheek and chin location. Independent predictive factors for NM were poor differentiation and tumour size. Except for cheek and chin location, all predictive factors identified are in agreement with the new staging system (American Joint Committee on Cancer 2010). High-risk tumours are more likely to present LR or NM. Adjuvant radiotherapy, close follow-up or sentinel node biopsy should be considered to detect LR/NM early, allowing life-saving intentions.

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133 Squamous cell carcinoma in the albino African: therapeutic and preventive aspects K. Kanga,1 K. Alexandre,2 K. Komenan,2 G.I. Patrice,2 K. Jean-Marie2 and N.-A.B. Solange2 1

Felix-Houphouet Boigny University, Abidjan, Cocody, Cote D’Ivoire and University Trainy Center of Treichville, Abidjan, Treichville, Cote D’Ivoire The African albino is constantly exposed to the sun throughout the year. From an early age the child albino receives no preventive measures against the carcinogenic effects of the sun on their skin. Many albinos die anonymously before reaching the age of 30 years. We wanted to show our experience in the management of cutaneous squamous cell carcinoma in individuals living with albinism. Our results led us to take preventive action towards this neglected population. We conducted a retrospective study from 2008 to 2013. We used Epi info 6 for treatment of our statements. Thirty albino African patients with histologically confirmed cutaneous squamous cell carcinoma were operated on and followed for a period of 5 years. In total 88 surgeries were performed. All patients benefited from oncological resection of their tumour with a margin of safety of at least 1 cm. Loss of skin substance was covered by direct suture (51%), thin skin graft (32%), wound healing (12%) or local skin flap (5%). We had an 80% cure rate without recurrence after at least 6 months. The deaths that occurred in six patents (20%) were due to lymph node metastases at admission (George A, Alexander MD, Ulrich KH, Advanced skin cancer in Tanzanian albinos: preliminary observations. J Natl Med Assoc 1981; 73: 1047–54). For economic reasons and lack of technical facilities no other therapeutic means were used, including radiotherapy or chemotherapy. The patients underwent follow-up after surgery every 3 months. During consultations, examination of new suspicious lesions was performed, awareness about the harmful effects of the sun was promoted and clothing advice was provided. In conclusion, if skin cancers are deemed rare in the black population in general, they remain one of the main causes of death at a young age in the population of people living with albinism [Dieng MT, Diop NN, Deme A et al. Squamous cell carcinoma in black patients: 80 cases. Ann Dermatol Venereol 2004; 131: 1055–7 (in French)]. For better protection of these albino children, we initiated in 2013 a project to create the first local centre for prevention of skin cancer. 2

134 Peer review of Mohs slides to optimize Mohs micrographic surgery C. Van Lee,1 B. Graafland,1 S. Koljenovic,1 M. Neumann,1 T. Nijsten,1 K. Munte2 and R. Van den Bos1 1

Erasmus MC, Rotterdam, the Netherlands and 2Maasstad Ziekenhuis, Rotterdam, the Netherlands Mohs micrographic surgery (MMS) achieves a low skin cancer recurrence rate (1–2%). At least 30% of skin cancer recurrences after MMS are due to misinterpretation of slides by the surgeon (Hruza JG. Mohs micrographic surgery local recur© 2014 The Authors BJD © 2014 British Association of Dermatologists

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rences. J Dermatol Surg Oncol 1994; 20: 573–7; Campbell T, Armstrong AW, Schupp CW et al. Surgeon error and slide quality during Mohs micrographic surgery: is there a relationship with tumor recurrence? J Am Acad Dermatol 2013; 69: 105–11). The primary purpose of this study was to determine the rate of misinterpretation after an added peer review. The secondary purpose was to determine risk factors for misinterpretation. This retrospective study included 1655 basal cell carcinomas (BCCs) treated with MMS performed at a single University Hospital (eight surgeons) between 2007 and 2011. All slides were routinely reviewed by a pathologist. In 108 cases the pathologist disagreed with the interpretation of the surgeon (65%). For this study purpose, these 108 cases were re-evaluated by an experienced Mohs surgeon and a pathologist. In 76 of these 108 cases, disagreement did not lead to an incomplete MMS procedure (e.g. benign structures were misinterpreted as tumour cells). In 32 cases, missed BCC cells implied an incomplete MMS procedure. Compared with the 1623 complete MMS procedures, the 32 incomplete MMS cases were significantly more likely to be previously incompletely excised or recurrent BCCs, and more often had a defect size > 20 mm in diameter (P < 005). However, the complete and incomplete excised BCCs did not differ in terms of BCC subtype, tumour location, number of Mohs stages and acting Mohs surgeon (P > 005). After adjusting for pathological growth type and surgical pretreatment, a defect size > 20 mm in diameter remained a significant risk factor for missed BCC cells (P < 005, odds ratio 31, 95% confidence interval 15– 64). In conclusion, an additional peer review may increase the effectiveness of MMS, especially in large tumours.

135 Confocal microscopy to guide laser ablation of cutaneous basal cell carcinoma A. Rossi, H. Sierra, K. Nehal and M. Rajadhyaksha Memorial Sloan Kettering Cancer Center, New York, NY, U.S.A. Basal cell carcinoma (BCC) is the most common skin cancer and is proposed to be the most common malignancy worldwide. About 35 million new cases of nonmelanoma skin cancers are diagnosed in the U.S.A. every year, and the incidence rate is increasing worldwide. Of these, about 70% are BCCs. Treatment ranges from traditional surgery to topical therapies. For high-risk areas with minimal tissue reservoir, such as the face, Mohs micrographic surgery is the treatment of choice, in order to spare normal tissue. Laser ablation of malignancies, including BCC, has been reported in multiple studies; however, BCC can often have subclinical extension so exact borders may be hard to delineate. We explored the utility of reflectance confocal microscopy in aiding the laser ablation of BCC tumours both ex vivo and in vivo. After institutional review board approval, discarded tissue from Mohs surgery was imaged using a Vivascope 1500 confocal microscope with 830-nm illumination to identify the basal cell tumour and guide ablation. The tissue was then ablated using an ultrapulsed CO2 laser and imaged again to check for remaining tumour. For imaging of residual BCC in ablated tissue, acetic © 2014 The Authors BJD © 2014 British Association of Dermatologists

acid was used for contrast, which condenses chromatin and causes the nuclear morphology to appear bright (known as acetowhitening). Acquisition of images and mosaics was performed pre- and postablation. Seventeen Mohs tissue samples containing BCC were imaged and ablated. The preimaging was able to identify tumour islands and postimaging showed areas of ablated tissue that corresponded to successful destruction with the laser. The ultrapulse CO2 laser operating at 106 lm was used with the computer pattern generator mode and a size pattern of 3 mm. Fluence ranged from 5 to 1250 J cm 2 and the number of passes ranged from one to four. One patient underwent ablation for superficial BCC. Preablation reflectance confocal microscopy confirmed the presence of tumour. Five passes were used with the ultrapulsed CO2 laser at 75 J cm 2 with a 3-mm pattern. Postablation confocal microscopy confirmed tumour destruction. Postablation histology also confirmed tumour clearance. Tumour ablation was indentified with confocal images showing cellular structural changes and loss of tumour islands, and was confirmed on frozen sections. These features showed good correlation with permanent haematoxylin and eosin histology. An ablation depth of 100 lm (confirmed with frozen sections) was achieved.

136 Our experience in Mohs surgery compared with classical excision in basal cell carcinomas of the face R. Cosgarea,1 O. Harceaga,1 S. Senila,1 C. Baican1 and L. Rogojan2 1

Department of Dermatology, University of Medicine and Pharmacy ‘Iuliu Hatieganu’, Cluj-Napoca, Romania and 2Department of Pathology, County Clinical Emergency Hospital, Cluj-Napoca, Romania Among basal cell carcinomas (BCCs), the aggressive pathological subtypes have a higher risk of recurrence. Micrographic surgery represents the surgical technique with the highest rate of complete excision for skin tumours. The aim of our study was to compare the rate of recurrence of micrographic surgery vs. classical surgery for BCC on the face. This was a prospective clinical study developed from May 2010 to January 2014 with a median follow-up of 23 months, on two groups of patients: 52 patients with 53 BCCs treated by classical surgery and 73 with 79 BCCs excised by Mohs surgery. We compared the recurrence rates for the two methods. A clinical free margin of 4 mm was excised for the tumours by classical surgery, and for the Mohs surgery group, 2 mm around the tumour. Horizontal sections were taken from the deepest part upwards. There were 42 female and 31 male with 79 BCCs treated by micrographic surgery, with six patients each having two tumours. Thirteen tumours were recurrent after a previous surgery. The localization of the tumour was evaluated, with 47% being located on the nose, and the rest on the infraorbital area, medial canthus and nasolabial fold. The nodular and infiltrative types were dominant. Between one and three steps were performed for excision and pathological evaluations. Overall 35% of BCCs were free after the first excision and five tumours needed three excisions due to incomplete resection. British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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The tumours that needed three steps of excision were evaluated in terms of histological type, tumour location, size, and location of the tumour infiltrate on the excised specimens. Local flaps represented the most common method of reconstruction of the defects. Three tumours recurred in the control group (6%) and one tumour recurred in the group treated by Mohs surgery (1%). The recurrent tumour from the Mohs surgery group was a tumour that recurred after a previous treatment done by electrocauterization leaving a fibrotic scar. We tried to establish the benefits and disadvantages of micrographic surgery in the treatment of facial carcinomas. The recurrence rate was smaller after micrographic surgery than classical surgery. However, the time for excision in micrographic surgery is double and the costs are higher too. But the lower rate of recurrence after Mohs surgery and the maximum spared free tissue are very important arguments to consider this as an appropriate technique for BCCs of the face.

137 A trial of skin graft for various cutaneous tumours: combination with surface electrocoagulation after split-thickness skin graft without adipectomy M. Maeda Department of Dermatology, Gifu Prefectural General Medical Center, Gifu, Japan For various cutaneous tumours including malignant tumours such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), dermatoplasty with a split- or full-thickness skin graft, or sometimes a Thiersch skin graft, is usually of use after total resection. Because adipectomy (resection of fatty tissue) is required after a free-handed skin graft, which needs extra work and preparation time before the graft operation, we proposed a newly devised method as follows. Measuring of length and breadth of the resectioned tumours, same-sized skin grafts were prepared from the clavicle or inguinal regions without any adipectomy, which were similar to the split level of the graft. In total, 34 cases were involved in this trial, consisting of 13 SCCs, eight Bowen disease, five BCCs, two keratoacanthomas, two malignant melanomas and four other cases. The size of the ulcer after the skin graft was taken by surface electrocoagulation was about 40% smaller in both the clavicle and inguinal regions, which means omitting extra suture work. This method may be useful for daily common operations, because it was shown to have the merit of shortening operation times due to omission of extra adipose tissue removal. Subsequently, suturing the ulceration resulting from the graft is reduced to a minimum.

138 Large (near total) defects of the lower lip after Mohs surgery: better cosmetic results are obtained  flaps by combining Karapandzic and Abbe A. Gonza´lez, M.P. Creydt, D. Etchichury, C. Spinelli and C. Ferrua Instituto Angel H. Roffo, Buenos Aires, Argentina Mohs surgery (MS) is the best option for lower-lip tumours because of its high rate of tumour clearance and sparing of norBritish Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

mal tissue. The Karapandzic flap (KF) can successfully replace up to 80% of the total lip length, while preserving function. One of the limitations of the KF is the blunting or rounding of the commissures. By combining a KF with a cross lip flap (CLF) (Abbe flap) the length of both lips should be evenly distributed, and the commissures restored to normal. We evaluated a series of patients undergoing reconstruction treatment with a combination of KF and CLF for large defects of the lower lip. Between June 1990 and June 2013, 5123 nonmelanoma skin cancers of the head and neck were treated with MS at our institution. Only 44 (08%) were located on the lower lip. Four cases were reconstructed with a combination of KF and CLF. All of these patients were men, with a median age of 67 years (range 59–80). The median tumour size was 2 cm (range 15–25). Histology corresponded to squamous cell carcinoma, either well differentiated (two) or semidifferentiated (two). The final defect involved 60–80% of the total length of the lower lip. In one case the commissure was involved. Two cases had been treated previously with surgery, and one had been reconstructed with a KF. In one case (commissure involvement) a third flap was needed (V–Y island flap). In this patient a commissuroplasty was done 4 months later. The flap survival was 100% in all cases. We observed no complications. One patient needed tube feeding until division of the CLF. Lip function was restored: eating, speech and dental hygiene were considered normal in all patients. The aesthetic results were considered very good to excellent in all cases, and the commissures looked normal in all patients. The major advantage of the KF for lower-lip reconstruction is that the oral sphincter is recreated with the innervated, well-vascularized remaining lip tissue. When applied to near-total lower-lip defects, the KF may result in blunting or rounding of the commissures and also in some degree of microstomia. When combining a CLF interposed to the shortened lip segment, the balance between the upper and lower lip is restored, and the commissures preserve a normal aspect. In this short series, the functional and cosmetic results were considered very good to excellent in all patients.

139 Basal cell carcinoma at craniofacial embryological fusion planes: propensity for greater depth of invasion and recurrence revisited L. Armstrong,1 M. Magnusson2 and M. Guppy1 1

The University of New England, Armidale, New South Wales, Australia and Toowoomba Cosmetic Plastic Surgery, Toowoomba, Queensland, Australia Several factors implicated in the pathogenesis of basal cell carcinoma are not completely understood. Facial embryological fusion planes, the zones of mesenchymal migration, and fusion of the primordial facial processes in the early stages of embryogenesis have been suggested to influence the spread, pathogenesis and recurrence of cutaneous carcinoma. The aim of this study was to establish whether basal cell carcinoma originating in embryological fusion planes has a greater propensity for earlier depth of invasion, leading to an increased rate of lesion recurrence in these areas. This study was retrospective in nature, with the participant cohort formed from 2

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operating theatre logs of a plastic surgery practice in 2006– 2007. Using hand-drawn diagrams in participants’ consultation notes, lesions were allocated to a specific zone of an anatomical diagram of the face and aggregated into two anatomical domains according to their correlation with embryological fusion planes. Pathology records were assessed to determine the lesion depth of invasion and surface area, and a search of lesion recurrence was performed through relevant pathology laboratories. The excision margins of clearance were assessed in conjunction with lesion recurrence. Of 331 cases of facial basal cell carcinoma included in the study, 70 lesions were located in embryological fusion planes. No significant difference was found in the mean surface area or depth of invasion for lesions located in embryological fusion planes or other facial areas (P > 005). Ten lesion recurrences were identified within the participant cohort, none of which were located in zones correlated to embryological fusion planes. Recurrent lesions were excised with a significantly greater percentage of close and incomplete excision margins than nonrecurrent lesions (P < 005). These findings suggest that basal cell carcinomas arising in embryological fusion planes are not at greater risk of recurrence due to an embryological phenomenon, but rather, lesion recurrence is primarily influenced by adequacy of excision margins. Previous research assessing rates of recurrence in embryological fusion planes has not concurrently assessed the margins of excision in these zones. It is believed that the greater rate of lesion recurrence reported in embryological fusion planes is due to the inadequacy of excision margins, as these planes are located in highly cosmetically sensitive areas of the face. It is recommended that physicians treating basal cell carcinomas in these planes should ensure that adequate excision margins are achieved in conjunction with an acceptable cosmetic outcome. This may result in increased pressure to refer these lesions for specialized treatment.

Comas has previously not been investigated. We present an additional case and review the literature from a surgical perspective. A 40-year-old woman presented with a painful 3-cm nodule overlying her posterior calf that had been increasing in size over the last 2 years. Clinical examination revealed a wellcircumscribed lesion that appeared fixed to the underlying tissue. There was no history of preceding trauma. Her past medical history was unremarkable with no personal history of tuberous sclerosis. She underwent an excisional biopsy taken to fascia that showed a close peripheral margin (1 mm) and a positive deep margin. Subsequently a 1-cm peripheral re-excision including fascia was performed to ensure clearance. The defect was temporized with a split-skin graft reconstruction. Histology showed features consistent with a PEComa with positive immunohistochemistry for HMB-45, CD10, smooth muscle actin and desmin. There was no significant mitotic activity or necrosis present. The wider re-excision provided a peripheral clearance of 7 mm and deep clearance of 5 mm. Follow-up at 6 months showed no local recurrence or evidence of metastatic spread. Primary cutaneous PEComas most commonly occur in middle-aged patients, with a median age of 46 years and a 3 : 1 female-to-male predominance. The majority of tumours are located at acral regions. There was no evidence of local recurrence or metastases at 6 months’ follow-up of all 37 known cases, but 16 cases required a wider excision for positive margins. The margin of the wide excision was documented only in a single case. A single case of a PEComa behaving in a malignant fashion has been reported but metastases have not been described. As a rare entity, PEComas have a malignant potential and prognostic implications that are not well defined. However, it would seem that provided clear histological resection margins are achieved, there is a low rate of recurrence.

140 Primary cutaneous PEComa: a case report and review of surgical excision margins I. Ling, B. Aldridge, A. Gilmour and I. Mackay

141 Topical diphencyprone immunotherapy as a treatment for metastatic malignant melanoma, squamous cell carcinoma and eccrine porocarcinoma: a report of 15 cases F. Harper, F. Worsnop, B. Powel and V. Akhras

Canniesburn Plastic Surgery Unit, Glasgow, U.K. PEComas are rare distinct mesenchymal tumours derived from perivascular epithelioid cells (PECs) [Calder KB, Schlauder S, Morgan MB. Malignant perivascular epithelioid cell tumor(‘PEComa’): a case report and literature review of cutaneous/subcutaneous presentations. J Cutan Pathol 2008; 35: 499–503]. Pea et al. first described them, noting the presence of unusual PECs with clear cytoplasm showing immunophenotypic features of both smooth muscle and melanocytic differentiation (Pea M, Martignoni G, Zamboni G, Bonetti F. Perivascular epithelioid cell. Am J Surg Pathol 1996; 20: 1149–53). Primary cutaneous PEComas are rare and make up approximately 8% of all PEComa cases. Thus far only 37 cases have been reported in the literature. While most can be considered benign, some have malignant potential, so clear resection margins are advisable. The surgical management of cutaneous PE-

St George’s Hospital, London, U.K. Diphencyprone (DCP) is a potent contact sensitizer, well established in treating alopecia areata and cutaneous warts. Successful use of DCP in metastatic malignant melanoma (MM) was first described in combination with cimetidine in 1989 (Harland CC, Sailian EM. Regression of cutaneous metastatic malignant melanoma with topical diphencyprone and oral cimetidine. Lancet 1989; 2: 445) and as a single agent in 2007 (Damian DL, Thomson JF. Treatment of extensive cutaneous metastatic melanoma with topical diphencyprone. J Am Acad Dermatol 2007; 56: 869–71). Its mechanism of action will be discussed. We report DCP treatment in 12 patients with metastatic MM, two patients with multiple squamous cell carcinomas (SCCs) with DCP, who were otherwise deemed unsuitable for surgical intervention, and one patient with eccrine porocarcinomas (ECPs) who had declined surgery. All

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patients were sensitized with DCP 2% in acetone on the inner forearm occluded for 48 h. DCP was then applied weekly if appropriate, with titration to produce tolerable contact hypersensitivity. Of the 12 patients with metastatic MM who were treated, nine had already failed previous treatment, including surgery, radiotherapy, localized chemotherapy and topical imiquimod. Two patients (17%) had complete clearance of their metastases, while five (42%) had a partial response. We felt that while five patients developed disease progression, they had appreciable slowing of their disease while using DCP. In addition, we have three cases of nonpigmented skin cancer that have been treated with DCP. As such, this marks the first report of successful treatment of a skin malignancy other than metastatic MM with DCP. An 83-year-old patient with six histologically proven ECPs showed complete clearance of all lesions by week 6 following treatment, and this effect has been maintained for 18 months to date. We have also treated two patients with multiple SCCs. One patient had previously undergone electrochemotherapy, which was unsuccessful, but has to date had a partial response to DCP, while the other has had subjective slowing of her disease, although she continues to develop new lesions. DCP treatment was well tolerated, with only one patient experiencing systemic symptoms limiting use. It is easy to administer and inexpensive, and treatment can be performed in an outpatient setting or at home. Our experience treating ECPs is extremely encouraging and we conclude that DCP should be considered for all cutaneous malignancies where other treatments have failed or are inappropriate.

142 An algorithm for reconstruction of the nose after skin cancer excision L. Nae-Ho and L. Jin-Won Department of Plastic and Reconstructive Surgery, Medical School, Chonbuk National University, Jeonju, Korea Reconstruction of nasal defects can be quite challenging. The location, size, shape and orientation of defects are important factors in nasal reconstruction. The purpose of this study was to establish a nasal reconstruction algorithm for nasal defects, based on our experience with 118 patients who were operated on for skin malignancy at our institute. Medical records and photographs of 118 patients were retrospectively reviewed between January of 2009 and July of 2013 at our hospital. The following criteria were evaluated: age, sex, type of surgical excision, defect location, defect size and type of nasal reconstruction. We developed an algorithm for operation based on defect size, location and complexity. We divided the nose into three zones. Defects that covered more than one zone were categorized as complex defects. We classified the nose into the following five units: the glabella, nasal dorsum, nasal tip and the two alae. Although various methods of local flap were used for treatment, certain flaps were used predominantly in nasal reconstruction of certain defects. The paramedian forehead flap, glabellar flap, Miter flap, bilobed flap, V–Y advancement flap and full-thickness skin graft were British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

used in each region. Nasal skin cancer is an increasing problem and the nose is the most prominent feature of the central face. Even small defects pose a significant challenge to plastic surgeons. In this study, we were able to develop a simple algorithm on flap choice based on location, size and complexity for treatment of nasal defects.

143 Reconstructive options for the lower eyelid after Mohs surgery A. Gonza´lez,1 M. Devoto,1 M.P. Creydt,1 D. Etchichury,2 C.S. Arizmendi2 and G. Ruaux1 1

Instituto de Oncologıa Angel H. Roffo, Buenos Aires, Argentina and Instituto Alexander Fleming, Buenos Aires, Argentina Mohs surgery (MS) is preferred in lower eyelid surgery for its high cure rates and sparing of healthy tissue. Lower-eyelid reconstruction represents a challenge because function and aesthetics should be restored. We set out to analyse reconstructive options after MS of the lower eyelid. Between June 1990 and June 2013, 8598 cases of nonmelanoma head and neck skin cancers were treated with MS. The periocular location was represented in 151% of cases (1294 of 8598), and the lower eyelid in 460% of these (595 of 1294). Women represented 622% of the cohort and the mean age was 59 years (range 19–97). The mean defect size was 09 cm (range 02–7).We divided the series in those without free margin involvement (766%, 456 of 595) and with free margin involvement (234%, 139 of 595). In defects without free margin involvement we did not record the reconstructive options in 16 cases. In the remaining 440 cases, the first reconstructive options were flaps in 623% (274 of 440). These were advancement (442%, 121), transposition (208%, 57), advancement rotation (135%, 37), keynote (91%, 25) and other (124%, 34). For simple defects we used direct closure (161%, 71 of 440), or secondary intention healing or partial closure (136%, 60 of 440). Grafts were selected for different indications in 8% of cases (35 of 440). As a rule, for defects with free margin involvement > 50%, reconstructive options were direct closure (108%, 15 of 139) or canthotomy plus canthoplasty (259%, 36 of 139). When the defect was 50–75% we preferred the Tenzel flap (101%, 14 of 139). For larger defects we used either the Hughes flap (230%, 32 of 139) or Mustarde flap (194%, 27 of 139). In 15 cases (108%), due to complex defects it was necessary to combine more than one reconstructive option. In these patients a tarsal conjunctival graft was frequently used. Different reconstructive options are useful in rebuilding the lower eyelid to preserve function and aesthetics. Selection depends on the size, depth and location of the defect, but fundamentally whether the free margin is involved or not. For defects without free margin involvement we prefer advancement or rotation advancement flaps. We consider the keynote flap to be an excellent alternative. In defects with free margin involvement we prefer canthotomy plus canthoplasty, Tenzel flap or Hughes flap according to the extent of the defect. 2

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144 The Burrow’s flap W. Bakkour and V. Ghura Manchester Mohs Unit, Salford Royal NHS Foundation Trust, Manchester, U.K. Burrow’s grafts are full-thickness skin grafts that utilize the dog ear resulting from partial primary closure to close part or all of the residual defect. Like any full-thickness skin graft, the Burrow’s graft is limited in terms of the cosmetic result achievable and in its applicability for deeper defects, as it cannot replace volume beyond full-thickness skin. We describe a new modification to the Burrow’s graft whereby primary closure is performed at one end of the defect to create the dog ear. This is then moved while still attached by a pedicle of skin and/or subcutaneous tissue to fill the remainder of the defect. This provides vascular support for the Burrow’s triangle, increasing its viability and allowing subcutaneous tissue if needed to be included with skin for deeper defects. We describe our results and findings in the use of this new flap in over 10 patients over the past 12 months. We have found it both a useful and flexible technique applicable to multiple sites. We have used the Patient and Observer Scar Assessment Scale as an objective method to assess resulting scars in the Burrow’s flap group and those having traditional Burrow’s grafts. We have found that wound healing is enhanced both in the short and long term compared with what might be expected with a standard Burrow’s graft. Our experience finds that the Burrow’s flap modification improves the viability and applicability of the Burrow’s triangle making it a more versatile repair option.

145 (PL03) Skin cancer care in England V. Poirier, T. Jones, A. Ives, J. Newton-Bishop and J. Verne Public Health England, London, U.K. Skin cancers, namely nonmelanoma skin cancer (NMSC) and malignant melanoma (MM), are the most common cancers in England. The treatment and consequent cost related to NMSC is often considered insignificant compared with MM. We considered the trends in the numbers of day case and inpatient treatments for skin cancer during a 5-year period in England, including procedures used, specialties involved and costs. Details of admissions between 2007 and 2011 for a diagnosis of skin cancer (International Classification of Diseases version 10 code C43 or C44) were extracted from the inpatient hospital episode statistics. We identified the procedures used and the specialties involved. Healthcare Resources Group codes were used to estimate the costs involved. NMSC admissions were matched to the National Cancer Data Repository to determine their morphology: squamous cell carcinoma (SCC) or basal cell carcinoma (BCC). There has been a significant increase in hospital admissions between 2007 and 2011 for NMSC (76 528 vs. 109 333) and MM (11 157 vs. 14 475). The main procedures recorded in 2011 were surgical excisions both for NMSC (78%) and MM (715%). Mohs surgery was © 2014 The Authors BJD © 2014 British Association of Dermatologists

undertaken mainly for BCC. Over 16 000 flaps and grafts were undertaken for NMSC in 2011 compared with 1766 for MM. There was some use of amputation for MM and SCC. Most day cases were managed by dermatologists and plastic surgeons, and the latter represented the main specialty involved with inpatient care. Dermatologists’ involvement with day cases increased between 2007 and 2011 (+39% for NMSC and +53% for MM) but decreased for plastic surgeons ( 33% and 59%). The overall cost of inpatient treatment in England in 2011, based on our data, was £811 million for NMSC and £144 million for MM. In conclusion, we have provided some evidence for the amount of surgery and consequent costs involved in the treatment of NMSC compared with MM. This is an underestimate, as treatment also takes place on an outpatient basis. Given the predicted increase in the incidence of NMSC over the coming years in an ageing population, it is essential to improve assessment of the level of care and costs involved, as well as to increase public awareness of the disease.

146 (PP02) Lgr5+ and Lgr6+ stem cell progeny in the skin after ultraviolet exposure G. van de Glind, H. Rebel, K. Tensen and F. de Gruijl Leiden University Medical Centre, Leiden, the Netherlands Recently, Lgr5+ and Lgr6+ stem cells were discovered in (mouse) skin. During homeostasis Lgr5+ stem cells are found deep in the hair follicle (bulb or lower bulge), and they renew the hair follicle. Lgr6+ stem cells are found higher up in the isthmus and in the interfollicular epidermis (IFE). These cells regenerate the upper part of the hair follicle, sebaceous glands and IFE. Stem cells are prime targets for accumulating mutations, due to their cycling and their long residency. The aim of this study was to investigate Lgr5+ and Lgr6+ cells and their progeny in ultraviolet (UV)-induced hyperplasia and repopulation of the basal layer of the IFE after ablation by a UV overdose. We hypothesize that Lgr6+ stem cells are prime targets in UV carcinogenesis, and that Lgr5+ cells may become targets if they move upward into the IFE in hyperplasia or after an ablative overexposure. We used transgenic mice containing a LacZ reporter gene switched on in either Lgr5+ or Lgr6+ cells (enhanced green fluorescent protein+) upon administering tamoxifen (both in haired and hairless background) for lineage tracing (beta-galactosidase staining then marks these cells and their progeny). Hyperplasia was induced by 4–8 weeks of daily UV exposure just below the threshold dose for a sunburn. Alternatively, the basal layer of the IFE was ablated with a single, just tolerable, overdose of UVB. After induction of hyperplasia we found Lgr5 progeny only in the hair follicles of haired mice and in deep-seated cysts in hairless mice. No progeny was found in the IFE. However, at 1 week after ablation we found Lgr5 progeny in the IFE of haired mice, but not any Lgr5+ stem cells. Progeny of Lgr6+ stem cells was found in the isthmus and in the IFE of haired mice after induction of hyperplasia and ablation. In hairless British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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mice the progeny was also found in the hair follicle remnants and IFE. Hence, progeny of Lgr5+ stem cells does not appear to play a role in UV-induced hyperplasia of the IFE, in either haired or hairless mice. However, these cells do contribute transiently to the repopulation of the IFE after an ablative severe sunburn in haired mice. Progeny of Lgr6+ stem cells contributes more permanently to both hyperplasia and repopulation of the IFE after ablation. Lgr6+ stem cells are therefore more likely targets in UV(B) carcinogenesis than Lgr5+ stem cells, also after episodes of severe sunburn.

147 (PP09) Nicotinamide for skin cancer chemoprevention: enhancement of DNA repair after ultraviolet and arsenic exposure by replenishing cellular energy D. Damian, B. Thompson, B. Kim and G. Halliday Dermatology, University of Sydney, Sydney, NSW, Australia While ultraviolet (UV) radiation is the prime cause of skin cancer, chemical carcinogens such as arsenic play an important role in skin cancer development in Bangladesh, West Bengal and other areas with arsenical groundwater contamination. The risk of arsenic-induced skin cancers remains elevated many years after cessation of arsenic exposure, and hence there is a great need for affordable chemoprevention. Arsenic and UV act as skin cancer cocarcinogens in mouse models and have been shown to cause oxidative DNA damage synergistically. Nicotinamide has been shown to reduce actinic keratoses and possibly nonmelanoma skin cancer incidence in phase 2 clinical trials. To determine the effects on DNA repair, human HaCaT keratinocytes were incubated with or without nicotinamide and arsenic and then exposed to solar-simulated UV radiation. Cells were then allowed to undergo DNA repair for 15–75 min before being fixed and stained for oxidative DNA damage (8-oxo-2ʹ-deoxyguanosine; 8oxoG). Sodium arsenite significantly increased 8oxoG levels in irradiated keratinocytes (P < 001; n = 3, repeated measures ANOVA), and nicotinamide significantly increased repair of 8oxoG in irradiated cells treated with and without arsenic (both P < 005). Nicotinamide also enhanced repair of both 8oxoG and cyclobutane pyrimidine dimers (CPDs) in arsenic-treated, irradiated ex vivo human skin (P < 005, n = 3). We also investigated the effects of nicotinamide on DNA repair in primary human melanocytes. Nicotinamide reduced levels of 8oxoG and CPDs in irradiated cells (P < 005 and P < 001, respectively, n = 3). This enhanced DNA repair in the presence of nicotinamide was confirmed with an unscheduled DNA synthesis (UDS) assay (P < 005, n = 3, one-way ANOVA). As the primary precursor of nicotinamide adenine dinucleotide (NAD)+, an essential coenzyme in ATP production, nicotinamide is thought to exert its UV-protective effects via its role in replenishing cellular energy stores. We next assessed the effect of nicotinamide and a highly selective inhibitor of NAD+ production, FK866, on UDS in keratinocytes and primary human melanocytes. FK866 significantly reduced the ability of nicotinamide to enhance DNA repair in each cell type (both P = 002, n = 6, one-way ANOVA), indicating that its protective effects may occur by British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

preventing UV-induced cellular ATP loss. Nicotinamide is nontoxic and inexpensive and shows promise for chemoprevention of melanoma and nonmelanoma skin cancer.

148 (PP10) Phase 2 randomized, double-blind study of sonidegib (LDE225) in patients with locally advanced basal cell carcinoma and metastatic basal cell carcinoma M. Migden,1 A. Guminski,2 R. Gutzmer,3 L. Dirix,4 K. Lewis,5 P. Combemale,6 R. Herd,7 S. Gogov,8 T. Yi,9 M. Mone,9 R. Kudchadkar,10 U. Trefzer,11 J. Lear,12 D. Sellami9 and R. Dummer13 1

The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A., Royal North Shore Hospital, St. Leonards, Australia, 3Medizinische Hochschule Hannover, Hannover, Germany, 4Sint-Augustinus Ziekenhuis, Antwerp, Belgium, 5University of Colorado Cancer Center, Aurora, CO, U.S.A., 6Centre Leon Berard, Lyon, France, 7Glasgow Royal Infirmary, Glasgow, U.K., 8Novartis Pharma AG, Basel, Switzerland, 9Novartis Pharmaceuticals Corporation, East Hanover, NJ, U.S.A., 10H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, U.S.A., 11Dermatologikum Berlin, Berlin, Germany, 12Manchester Royal Infirmary, Manchester, U.K. and 13Universit€atsSpital Z€urich, Skin Cancer Center University Hospital, Z€urich, Switzerland Sonidegib blocks hedgehog signalling [aberrantly activated in ≥ 95% of basal cell carcinomas (BCCs)] through selective inhibition of smoothened. Patients with locally advanced BCC (LaBCC), not amenable to curative surgery or radiotherapy, or with metastatic BCC (mBCC), were randomized 1 : 2 to receive sonidegib 200 or 800 mg daily (BOLT study; NCT01327053). The primary end point of the study was the objective response rate (ORR), either complete response (CR; with histopathological confirmation) or partial response [(PR); achieved with point estimate ≥ 30% and 95% confidence interval (CI) lower bound > 20% in either arm]. The secondary end points were duration of response (DoR), CR rate, time-to-tumour response (TTR) and progression-free survival (PFS); these were assessed by central review according to modified Response Evaluation Criteria In Solid Tumors (mRECIST; LaBCC) or RECIST 11 (mBCC) criteria. Statistical comparison between arms was not planned. Safety was assessed until around 30 days after the last dose. Patients (194 with LaBCC, 36 with mBCC) were enrolled from July 2011 to January 2013. The primary end point was met for both arms (139-month median follow-up) in the full analysis set (FAS, the intent-to-treat population) and the primary efficacy analysis set (pEAS: LaBCC with tumour fully assessable per mRECIST; mBCC assessable per RECIST 11). For the LaBCC 200-mg vs. 800-mg arms, the respective ORRs (95% CI) were 470% (346–597; n = 66; FAS) and 429% (277–590; n = 42; pEAS) vs. 352% (269–441; n = 128; FAS) and 376% (278– 483; n = 93; pEAS). For the mBCC 200-mg vs. 800-mg arms, the respective ORRs (95% CI) were 154% (19–454; n = 13; FAS/pEAS) vs. 174% (50–388; n = 23; FAS/pEAS). The remaining data are reported for the FAS. By investigator, the ORRs (95% CI) for the LaBCC 200-mg vs. 800-mg arms were 652% (524–765) vs. 570% (480–657); the ORRs (by 2

© 2014 The Authors BJD © 2014 British Association of Dermatologists

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investigator) for the mBCC 200-mg vs. 800-mg arms were 231% (50–538) vs. 348% (164–573). Disease control (CR+PR+disease stabilization) rates were 909% vs. 782% (LaBCC) and 923% vs. 826% (mBCC) for the 200-mg vs. 800-mg arms, respectively. The median DoR was not estimable for LaBCC or mBCC (200 mg), and it was 83 months (95% CI not estimable) for mBCC (800 mg). Median PFS was not estimable for LaBCC, but was 131 months (95% CI 56–131; 200 mg) and 76 months (95% CI 62–111; 800 mg) for mBCC. The median TTRs (95% CI) for the 200-mg vs. 800-mg arms were 39 months (36–42) vs. 37 months (26–38) for LaBCC and 46 months (18–74) vs. 10 months (10–21) for mBCC. The median exposures were 89 months (200 mg) and 65 months (800 mg). Adverse events leading to discontinuation (200 mg/ 800 mg) included muscle spasms (38%/87%), dysgeusia (25%/47%), decreased weight (25%/47%) and nausea (25%/40%). Sonidegib demonstrated meaningful disease control with sustained responses and prolonged PFS in patients with advanced BCC – a population with limited treatment options – with a better benefit–risk profile for the 200-mg vs. 800-mg dose.

thicker tumours (> 4 mm, 115%) compared with older women (94%) and younger men (63%). Older men had a higher proportion of previous squamous cell carcinomas than older women or younger men (P < 001), and this proportion increased significantly faster for older men than younger men (P = 0046). In conclusion, epidemiological studies have consistently reported evidence that recreational sun exposure rather than chronic sun exposure is associated with melanoma risk. The new data presented here suggest that health promotion campaigns should address the risks associated with recreational sun exposure at all ages, on all body sites including the head and neck, and deliver early detection campaigns to older individuals and especially men.

150 (PP17) The development of the BRAF inhibitor encorafenib (LGX818) and mitogen-activated protein kinase kinase inhibitor binimetinib (MEK162) in patients with metastatic melanoma R. Dummer,1 K. Flaherty,2 R. Kefford,3 P.A. Ascierto,4 L. Moutouh-de Parseval,5 E. Wasserman6 and D. Schadendorf7 1

149 (PP16) Cutaneous melanoma in older persons V. Poirier, T. Jones, A. Ives, J. Newton-Bishop and J. Verne Public Health England, London, U.K. Previous reports from the U.K. have highlighted a higher incidence of melanoma in women. However, we recently reported a considerable and remarkable change in melanoma incidence, with the most rapid increases occurring in older people and especially men. We consider here whether this reflects an emerging pattern indicative of a proportion of tumours with a different aetiological route to melanoma. We examined melanoma (International Classification of Diseases version 10 code C43) incidence trends (1990–2010) in England using the National Cancer Data Repository. Three cohorts were compared: men aged ≥ 60 years (older men), women aged ≥ 60 years (older women) and men under 60 years (younger men). They were broken down by the following variables: anatomical site, socioeconomic deprivation, tumour morphology, Breslow thickness and previous occurrence of skin cancer. Directly standardized incidence rates were calculated and Poisson regression was used to model the changes in these rates over time. Between 1990 and 2010 the melanoma incidence rate for older men varied by anatomical site (P < 001), with the fastest rise on the trunk and upper limbs. There was no significant variation for older women (P = 007) or younger men (P = 089). Melanoma incidence rates have increased irrespective of deprivation status, but rates in the least deprived population increased faster for older men than younger men (71% vs. 39%; P = 003). The incidence rate for superficial spreading melanoma in older men increased faster (124%) than in older women (89%) and younger men (79%), although not significantly (P > 005). For older men, melanoma incidence rates increased faster for © 2014 The Authors BJD © 2014 British Association of Dermatologists

University Hospital Zurich, Zurich, Switzerland, 2Massachusetts General Hospital, Boston, MA, U.S.A., 3Melanoma Institute Australia, Westmead Institute for Cancer Research and Westmead Hospital, The University of Sydney, Sydney, New South Wales, Australia, 4National Cancer Institute, Naples, Italy, 5Novartis Pharma AG, Basel, Switzerland, 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, U.S.A. and 7University Hospital Essen, Essen, Germany Activating mutations in BRAF and NRAS account for 40–50% and 15–25% of mutations in cutaneous melanoma, respectively, and treatment is rapidly evolving with the recent approval of immunotherapies and agents targeting the mitogen-activated protein kinase (MAPK) signalling pathway. Here, a summary of the data supporting clinical development of the BRAF inhibitor encorafenib (LGX818) and the MAPK kinase (MEK) inhibitor binimetinib (MEK162) for the treatment of metastatic cutaneous melanoma will be presented. Encorafenib, a potent, highly selective BRAF inhibitor, has demonstrated phase 1 single-agent clinical activity in BRAF inhibitornaive patients with BRAF V600-mutant metastatic melanoma [overall response rate (ORR) 65%, 17 of 26; and BRAF inhibitor-pretreated ORR 11%, three of 28]. Common adverse events associated with encorafenib included cutaneous toxicities (palmoplantar erythrodysesthesia syndrome, hyperkeratosis, keratosis pilaris, alopecia, dry skin), arthralgia and fatigue. Currently, there are no approved specific therapies for patients with NRAS mutant melanoma. In a phase 2 study, the MEK inhibitor binimetinib was the first targeted agent to show clinical activity in the NRAS mutant subset, with 20% of patients with melanoma with NRAS mutations (six of 30) achieving partial response. Adverse events commonly associated with binimetinib included dermatitis acneiform, peripheral oedema, diarrhoea, increased creatine phosphokinase and retinal events. A phase 3 trial evaluating binimetinib vs. dacarbazine in NRAS mutant melanoma (NEMO; NCT01763164) is currently British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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recruiting worldwide. To increase the duration of patient response to encorafenib monotherapy and potentially improve single-agent safety profiles, the combination of encorafenib and binimetinib in BRAF V600 mutant melanoma was investigated in a phase 1b/2 study. Clinical response was achieved with the combination in both BRAF inhibitor-naive (ORR 89%, eight of nine) and BRAF inhibitor-pretreated patients (ORR 21%, three of 14). The combination of encorafenib plus binimetinib was well tolerated with no substantial increase in adverse events for the combination compared with singleagent therapy. The combination also mitigated some on-target BRAF inhibitor-associated adverse events, including cutaneous toxicities (hyperkeratosis, keratoacanthoma, squamous cell carcinoma, palmoplantar erythrodysesthesia syndrome), myalgia and arthralgia. Only low incidences of febrile events, photosensitivity and rash have been reported in this study to date. A phase 3 trial assessing the combination of encorafenib plus binimetinib or encorafenib alone vs. the BRAF inhibitor vemurafenib in BRAF V600 mutant melanoma (COLUMBUS; NCT01909453) is currently enrolling globally.

151 Modelling polarization speckles for skin cancer detection T. Lee,1 L. Tchvialeva,2 G. Dhadwal,2 S. Kalia,2 H. Zeng,1 D. McLean,2 W. Wang3 and H. Lui2 1

BC Cancer Agency, Vancouver, British Columbia, Canada, 2Vancouver Coastal Health Research Institute and University of British Columbia, Vancouver, British Columbia, Canada and 3Heriot-Watt University, Edinburgh, U.K. Recently a noninvasive optical technique that involves the acquisition and analysis of polarization speckles has been proposed for early malignant melanoma (MM) detection. This technique utilizes a polychromatic laser and two cameras equipped with polarizers. When the polarized laser is projected onto a skin surface, a polarization speckle pattern is formed. This pattern is recorded by the two cameras simultaneously in such a way to capture the polarized signals parallel and perpendicular to the incident light. Dividing the difference of the two signals by their sum yields the depolarization ratio, which denotes the amount of depolarization of the light due to the interaction of the skin. A previous study suggested that the fourth-order statistical moment of the depolarization ratio distribution could be predictive. This study attempted to establish and verify models for MM detection based on polarization speckles. In addition, the performance of a blue vs. a red laser was compared. Applying the polarization speckle method, the study measured skin lesions using blue (407-nm) and red (663-nm) lasers sequentially. Six parameters – skin surface roughness, average intensity ratio between the blue and red lasers, red and blue laser speckle contrast (a common property for analysing laser speckle images) and the fourthorder moment of the depolarization ratio for the red and blue light – were obtained and analysed by logistic regressions, which were used to build a classification model. Four separate lesion classification models were created for (i) MM vs. seborrhoeic keratosis (SK), (ii) MM vs. melanocytic naevus, (iii) British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

skin cancer [melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] vs. benign (naevus and SK), and (iv) MM vs. others (SK, naevus, BCC and SCC). An independent test dataset was used to validate these models. The classification performance was denoted by the area under the receiver operating characteristic curves. The study examined a sample of 168 patients from a general dermatology clinic. The training set was formed by 133 lesions (79% of lesions). To distinguish MM from SK, the red depolarization and the intensity ratios were the significant predictors. For the other three models the red depolarization ratio was the only predictor. Validations of the models using the remaining 21% (35) of the lesions showed that the area under the curves were 088, 065, 074 and 070 for the above four tasks, respectively. This study showed that the red depolarization ratio was the strongest predictor for MMs and skin cancers.

152 Cyclooxygenase-2 activity and 8-hydroxy-2deoxyguanosine level in melanocytic skin tumours I. Nicolae,1 C.D. Ene (Nicolae),2 L. Dinu3 and A. Anghel4 1

Clinical Hospital of Infectious and Tropical Diseases ‘Prof. Dr. Victor Babes’, Bucharest, Romania, 2University of Medicine and Pharmacy ‘Carol Davila’, Bucharest, Romania, 3MedLife Clinic, Bucharest, Romania and 4 Academica Clinic, Bucharest, Romania Numerous reports suggest that DNA oxidative damage and modified activity of cyclooxygenase (COX)-2 increase cancer risk. In this study we evaluated the quantitative level of 8hydroxy-2-deoxyguanosine (8-OHdG) and COX-2 activity in melanocytic skin tumours. We determined the COX-2 activity and 8-OHdG levels in normal skin (14 samples), tumour tissue (28 samples of melanoma, 19 samples of dysplastic naevi) and tissue adjoining melanoma (16 samples). The study was approved by the hospital ethics committee. All patients consented for the use of tissue fragments in research and for teaching, without prejudice of the diagnosis or their personal appearance. We obtained low levels of both COX-2 (022  003 U mg 1 protein) and 8-OHdG (156  83 pg lg 1 DNA) in normal skin, compared with melanoma (127  064 U mg 1 protein, P < 00001; 1338  732 pg lg 1 DNA, P < 0001; respectively), dysplastic naevi (056  021 U mg 1 protein, P < 001; 981  293 pg lg 1 DNA, P < 0005; respectively) and melanoma adjoining tissue (038  010 U mg 1 protein, P > 005; 1 358  173 pg lg DNA, P > 01; respectively). We calculated a positive correlation between COX-2 activity and 8OHdG levels in melanoma tissue (r = 0712, P < 00001), dysplastic naevi (r = 0904, P < 00001), melanoma adjoining tissue (r = 0299, P < 005) and normal skin (r = 0173, P > 005). This results show a significant alteration in genome stability and COX activity in cutaneous melanocytic tumours, which sustains the hypothesis that oxidative stress generates toxic substances involved in carcinogenesis and mutagenesis.

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153 What is the value of an annual nurse-led skin cancer surveillance clinic as part of the long-term follow-up of the kidney/pancreas transplant population? S. Russell and J. Lear Central Manchester Foundation Trust, Manchester, U.K. The Transplant/Dermatology clinic was established in 2006, in response to skin malignancy guidance by the National Institute for Health and Care Excellence (2006). This document highlighted that transplant patients were at ‘high risk’ of nonmelanoma skin cancer (NMSC). This unique clinic is a joint collaboration between a regional renal/pancreas transplant unit and local dermatology services. It is a weekly nurse-led clinic run in the dermatology department by a transplant advanced nurse practitioner and supported by a consultant dermatologist. It was developed primarily for the education, early detection and treatment of nonmelanoma skin malignancies in the transplant population. In 2012–2013 a clinic audit collected data on 740 patients. Their age range was 18– 81 years, and they were 1–42 years post-transplant. Their skin types were I (6%), II (20%), III (54%), IV (10%), V (8%) and VI (1%). Nearly half (48%) had taken a holiday in a sunny climate in the past year, and 15% for > 2 weeks. Moderate or large outdoor exposure in U.K. was recorder in 28%. Sunscreen was applied as recommended by 48%, and this was sun protection factor (SPF)30 or above in 95%. The skin cancer history of the 740 patients was also retrieved. They had undergone past treatment for squamous cell carcinoma (12%), basal cell carcinoma (115%), malignant melanoma (05%), actinic keratosis (13%) or Bowen disease (6%). In total 52% of patients ≥ 20 years post-transplant had a history of NMSC. When comparisons were made with 2006–2007 records, the frequency of sunscreen use had not improved since 2006 (42%). However, the use of sunscreen with SPF ≥ 30 had increased dramatically (from 40% to 95%). Holidays abroad remained constant, with 15% having extended periods of time in sunny climates. This clinic generated listings for excision or biopsy in 14% of patients (2012–2013) vs. 22% for 2006. Patients with previous NMSC, with increased risk of reoccurrence, are being followed up in a ‘higher risk’ skin clinic on a regular basis and no longer attend the surveillance clinic. The benefit of this routine skin surveillance clinic is highlighted by the significant levels of early detection of NMSC and premalignancies, with treatment expedited in a timely manner. These patients are then directed to a ‘higher risk’ clinic. Although skin protection advice has been given every year, there has not been any change in sunscreen application during summer months, but there has been an improvement in the use higher SPF sunscreens. Audit data confirm that the risk of NMSC increases the longer a patient is on immunosuppression; over half of the patients ≥ 20 years post-transplant have had an NMSC. The training of transplant nurses in routine skin surveillance and incorporating this skill into long-term transplant care is recommended.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

154 Efficacy and cosmetic results of high-dose-rate brachytherapy with Valencia applicator for the treatment of superficial skin cancer in elderly patients A. Marin,1 E. Vargas-Diez,2 Y. Delgado,2 D. Buchser,1 A. Godoy,2 M.-J. Concha,2 L. Cerezo1 and E. Dauden2 1

Department of Radiation Oncology and 2Department of Dermatology, Hospital Universitario De La Princesa, Madrid, Spain The objective of this study was to determine the outcome (efficacy and cosmetic results) of elderly patients with superficial skin cancer treated with high-dose-rate brachytherapy with the Valencia applicator. This was a prospective study of elderly patients diagnosed with basal cell and squamous cell carcinomas who refused any other treatment except radiotherapy, or in whom surgery was contraindicated due to comorbidities. Patients with T1–2N0M0 disease were included in the study and treated with high-dose-rate brachytherapy using the Valencia contact applicator. In total 38 elderly patients with 48 tumours (40 basal cell carcinomas and eight squamous cell carcinomas) were treated at our institution from 2009 to 2013 with high-dose-rate brachytherapy. The mean patient age was 82 years (range 62–96). All but one of the skin tumours were located on the face. Forty-three tumours were newly diagnosed and five were recurrent tumours. Complete remission was obtained in 100% of patients. The mean clinical follow-up was 28 months (range 4–58). All tumours remained under control (did not recur) during the follow-up period. The minimum tumour dose was 51–57 Gy in 17–19 fractions at 3 Gy per fraction and five fractions per week, in cutaneous lesions up to 3 cm in diameter and 3 mm estimated depth. The cosmetic results were evaluated as ‘excellent’ or ‘good’ in all patients. Our study shows that high-dose-rate brachytherapy with the Valencia contact applicator is an effective alternative treatment for superficial skin cancer in elderly patients, with excellent cosmetic results.

155 Conventional and high-definition optical coherence tomography in the diagnosis of basal cell carcinoma: a systematic review A. Hussain, L. Themstrup and G. Jemec Department of Dermatology, Roskilde Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark Optical coherence tomography (OCT) is a noninvasive imaging tool that was first introduced in dermatology in 1997. Since then OCT has been studied in relation to many different skin diseases, although most research has turned to nonmelanoma skin cancer. Several independent OCT studies of basal cell carcinoma (BCC) have been published, providing both the need and the material for a critical review of the diagnostic OCT criteria for BCC. A systematic review of the published literature on the diagnosis of BCC was performed using Medline, PubMed, Google Scholar and The Royal Danish Library. In total 39 papers were identified. Twenty-two were excluded because they did not meet the inclusion criteBritish Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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ria, leaving 17 papers for analysis. The results suggest that eight tumour characteristics can be recognized in conventional OCT images of BCC, and of these, three OCT characteristics appeared in > 50% of reports. These frequently found characteristics including rounded dark structures in the upper dermis surrounded by a hyper-reflective halo (100% of studies), disruption of epidermal layering (100% of studies) and hyporeflective lateral tumour borders (59% of studies). Histopathologically the rounded dark structures correspond to BCC islands and the hyporeflective lateral tumour borders correspond to cellular palisading at the margins of basal cell nests. Because of the heterogeneity of the studies it was not possible to calculate the sensitivity and specificity of the most common characteristics. High-definition (HD)-OCT has a higher resolution but a lower penetration depth than conventional OCT. Frequently found HDOCT characteristics of BCC were similar to those found in conventional OCT, and one paper described the possibility of differentiating BCC subtypes with HD-OCT. However, the total body of work is significantly smaller in en face OCT than in conventional OCT, making it difficult to compare the results. The reviewed data suggest that OCT is reliably able to identify BCC, but currently not subtypes. To aid future development within this field, improved technology, image analysis for pattern recognition and the inclusion of, for example, tumour vasculature in tumour assessment may further improve the diagnostic capabilities of OCT.

156 Predicted increased risk of squamous cell carcinoma induction associated with sunbed use P. Tierney,1 S. Ibbotson,1 F. de Gruijl2 and H. Moseley1 1

Photobiology Unit, Ninewells Hospital & Medical School, University of Dundee, Dundee, U.K. and 2Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands Solar ultraviolet radiation (UVR) is acknowledged as the principle cause of skin cancer. Furthermore, sunbeds have been classified as carcinogenic by the International Agency for Research on Cancer. Therefore an increased risk of developing nonmelanoma skin cancer is expected when one is exposed to both sources of UVR. This additional risk factor was determined from a squamous cell carcinoma (SCC) tumour induction model based on albino mice (De Gruijl FR, Van der Leun JC. Development of skin tumors in hairless mice after discontinuation of ultraviolet irradiation. Cancer Res 1991; 51: 979– 84). The risk model for SCC induction was adapted to include the use of sunbeds along with the lifetime cumulative dose from day-to-day and holiday exposure (Tierney P, Ferguson J, Ibbotson S et al. Nine out of 10 sunbeds in England emit ultraviolet radiation levels that exceed current safety limits. Br J Dermatol 2013; 168: 602–8). These two factors were established as the ‘baseline’ exposure. Age and environmental UVR exposure are the two most important factors in determining the relative risk. Application of meta-analysis with biological amplification factor 23 and age-dependent factor 38 from British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

epidemiological studies was used to estimate the risk of SCC associated with the extra dose accumulated with sunbeds. The relative risk was defined as the risk of SCC induction from (sunbed + baseline)/baseline. We additionally investigated the various body sites, from those normally exposed such as face and arms to more usually unexposed sites. With these scenarios, the relative risk of SCC induction from median sunbed exposure output in addition to median baseline sun exposure level was 41 at age 35 years and 78 at age 65 years. This is the first time that a risk model for skin carcinomas has been developed that includes real sunbed exposure data. It shows that the additional risk associated with sunbed use may be significant, particularly when high-output, fast-tan sunbeds are used.

157 The use of photodynamic therapy to treat basal cell carcinoma, squamous cell carcinoma in situ and actinic keratosis in Asian patients in Singapore C.C. Oh, C.T.S. Theng, H.Y. Chia, C.S.L. Koh and W.S. Chong National Skin Centre, Singapore, Singapore Topical photodynamic therapy (PDT) is a treatment modality employing light and a topical photosensitizer to treat basal cell carcinomas (BCC), squamous cell carcinoma (SCC) in situ and actinic keratosis (AK). Most published data to date on PDT have been on Fitzpatrick skin types I/II. Our study evaluates the effectiveness of PDT in the treatment of the above skin conditions in skin patients with type IV skin in Singapore. This is a retrospective analysis of Asian patients with histologically confirmed skin tumours (BCC, SCC in situ and AK) who were treated with PDT at the National Skin Centre, Singapore. The overall clearance rate of BCC at 3 months was 88% (seven of eight patients), SCC in situ 73% (41 of 56 patients) and AK 62% (eight of 13 patients). PDT is a useful treatment modality for BCC, SCC in situ and AK in Asian patients with skin type IV. Further prospective studies will be needed to evaluate its overall efficacy in Asian patients.

158 Here comes the sun: results from a national skin cancer campaign evaluation I. Lewis, S. Pearce and M. Matthews Tenovus Cancer Charity, Cardiff, U.K. The aim of this study was to compare levels of public knowledge on sun safety and skin cancer with self-perception of sun safety knowledge and associated behaviour. The research also compares three interlinking modes of campaign delivery through charity shops, community pharmacies and a combination of both over 3 years. The methodology takes an action research approach to implementing quantitative evaluation methods. The key research method is a survey presented as a sun safety quiz. Pharmacy and charity shop customers complete the quiz in the shop during the campaign, guided by trained shop and pharmacy staff. During 2012 and 2013 a Welsh cancer charity carried out an innovative sun safety cam© 2014 The Authors BJD © 2014 British Association of Dermatologists

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paign evaluation through 19 charity shops and 25 pharmacies. The aim was to gauge public awareness of skin cancer signs, symptoms and risky behaviour, and to compare the effectiveness of charity and pharmacy retail outlets as delivery vehicles. The findings revealed positive results for running the campaign through charity shops in terms of uptake, response rates and feedback on the intervention, adding to literature in this area. Findings from 2013 showed a statistically significant link between the frequency of sunburns and knowledge of skin cancer (P < 0001), specifically showing that a good level of knowledge on sun safety does not mean good sun safety behaviour (Miles A, Waller J, Hiom A, Swanston S. SunSmart? Skin cancer knowledge and preventive behaviour in a British population representative sample. Health Educ Res 2005; 20: 579–85). The results from 2012 and 2013 led to sponsorship by Pharmacy Network Wales to run the campaign in over 700 pharmacies in Wales during 2014. The methodology for evaluating the 2014 campaign built on findings from 2012 and 2013 and included self-perception of skin cancer awareness as well as knowledge on sun safety and self-reported behaviour. These findings will be collected during May 2014 and will add to findings from the two previous campaigns, as well as developing new avenues for exploration in the area of public behaviour in relation to skin cancer and campaign methodology.

159 Heat shock protein 72 and cleaved caspase-3 response to ultraviolet and infrared radiation , G. Blaser and P. Boukamp E.P. Lorie DKFZ, Heidelberg, Germany Most skin cancers are caused by long-term exposure to the sun, and ultraviolet (UV)A and UVB play a key role. But the sun is not composed solely of UV radiation, as near-infrared (IRA) represents one-third of the solar energy that reaches our skin. Heat shock protein (Hsp)72 responds rapidly to stress such as UV, and it is believed to inhibit apoptosis and lead the cells into a cell survival state, derailing the cell from apoptosis. Studies have mostly focused on the effects of one UV source (UVA, B or C) in monolayer cultures, simple in vitro skin models or mouse models, which do not resemble the human in vivo situation well. In this study we have used our group’s long-term scaffold based skin organotypic cultures (OTCs) to investigate the effects of UVA (60 J cm 2), UVA+B (60 J cm 2 + 100 mJ cm 2), IRA (860 J cm 2) and UVA followed by IRA, on the stress and apoptotic response depending on the radiation source. We focused on Hsp72 and apoptosis via activated caspase-3. The OTCs that were UVA/UVA+B irradiated had an internal control, which made it possible to see ‘neighbouring’ effects in covered vs. uncovered tissue. For the IRA exposed samples we used the same type of OTCs. We examined the expression of Hsp72 and cleaved caspase-3 by immunofluorescence, 2 h, 3 days and 14 days after exposure. Examination 3 days after UVA exposure showed an induction of Hsp72 in the epidermis. Also a de novo expression of Hsp72 was seen in the dermal compartment. Surprisingly UVA+B did not cause a similar response. Cleaved cas© 2014 The Authors BJD © 2014 British Association of Dermatologists

pase-3 expression had no change 3 days after UV treatment, but had an induction 14 days after in UVA+B-treated samples. IRAtreated samples gave no Hsp72 induction and only a minor caspase-3 activity, while irradiating the cultures with UVA followed by IRA had a minor epidermal Hsp72 induction and again dermal de novo expression, but no activation of caspase-3. In conclusion we can say that UVA indeed causes a strong induction of Hsp72 as described previously, but we do not see the same effects when using a combined UVA+B, IRA or UVA+IRA source. Additionally, cleaved caspase-3 has a different expression with the different radiation regimes, meaning that it might be important to rethink the strategy of basing studies on only one source and focus more on combining them to understand the stress and apoptotic response after sun exposure.

160 Metastatic balloon cell malignant melanoma: case report V. Garza-Rodrıguez,1 A. Villarreal-Martınez,1 C. Mendoza-Rodrıguez,1 I. Miranda-Maldonado,2 mez-Flores1 and O. Welsh-Lozano,1 M. Go 1 J. Ocampo-Candiani 1

Dermatology Department and 2Anatomic Pathology Department, University Hospital Dr. Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon, Mexico Malignant melanoma is a tumour with great metastatic potential. One main problem at the time of diagnosis is the inability to recognize uncommon histological variants. Balloon cell malignant melanoma (BCMM) is the rarest histological type of primary cutaneous melanoma. Its benign morphological appearance presents a challenge for accurate clinicopathological diagnosis. Attention is drawn to the diagnostic difficulties that may be encountered in distinguishing these lesions from other clear cell tumours. An 92-year-old woman who came to our dermatology clinic with multiple erythematous nodules (1–5 cm diameter) on her left lower limb, some of them ulcerated with serohaematic exudate presenting 3 months prior. She had been referred 3 years previous for an excisional biopsy in an unspecified lesion on her left foot, without any specific diagnosis. An incisional biopsy was then realized from one of the lesions with histopathology analysis, and mycological and bacterial cultures. All cultures were negative for any microorganism. The histopathological analysis revealed multiple large, polyhedral, foamy cells with abundant cytoplasmic vacuoles (balloon melanoma cells); immunohistochemical stains were positive for melan-A and vimentin and negative for cytokeratin. These findings were compatible with metastatic BCMM. BCMM represents an unusual histological pattern, with few cases reported in the literature. Its clinical presentations are variable: nodular, ulcerated, polypoid with clinical differential diagnoses of halo naevus, basal cell carcinoma, squamous cell carcinoma and cutaneous adnexal tumours (Lee L, Zhou F, Simms A et al. Metastatic balloon cell malignant melanoma: a case report and literature review. Int J Clin Exp Pathol 2011; 4: 315–21). When BCMM metastasizes, it may present as a tumour consisting predominantly of foamy

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cells, with mild pleomorphism and mitotic figures (balloon melanoma cells). Immunohistochemical studies with antibodies to S100 protein, melan-A and HMB-45 are positive in BCMM and its metastases [Magro C, Crowson N, Mihm M. Unusual variants of malignant melanoma. Mod Pathol 2006; 19 (Suppl. 2): S41–70]. In the absence of prior clinical and pathological history, numerous differential diagnoses must be considered when the tumour is composed exclusively of foamy to clear balloon cells, including renal cell carcinoma, adrenal tumours, clear cell sarcoma or xanthomatous lesions (Lee et al.). The clinical investigation and correlation in reaching a timely diagnosis of BCMM is important to avoid disease progression and metastatic disease.

161 Concurrent melanoma and thyroid cancer E. Cho,1 J.H. Lee,2 J.H. Han,1 G.M. Kim,2 Y.M. Park,1 J.Y. Lee1 and J.H. Lee1 1

Department of Dermatology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea and 2Department of Dermatology, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea Patients with cutaneous malignant melanoma are more susceptible to other primary cancers. Recent studies have identified an association between cutaneous malignant melanoma and thyroid cancer. There may be a genetic link between cutaneous malignant melanoma and thyroid cancer due to the high prevalence of a mutation in the BRAF oncogene. Herein, we report on a case of cutaneous malignant melanoma that developed in a patient who also had papillary thyroid carcinoma. A 67-year-old woman presented with a 2-year history of a solitary, 30 9 10-cm, denuded, reddish to black-coloured plaque on the lateral aspect of her right sole. Histological findings revealed nested atypical melanocytes that formed confluent expansile nodules. Immunohistochemical staining showed positivity for HMB-45 and high expression of Ki-67. After the confirmative diagnosis of cutaneous malignant melanoma, we performed surgical excision and a ray amputation at the fifth metatarsal level of her right foot. The preoperative laboratory evaluation included thyroid functional tests, which were within normal limits. However, in a preoperative positron emission tomography–computed tomography scan, which was performed to evaluate metastasis, a focal hot lesion was checked in the left lobe of the thyroid gland. Papillary thyroid carcinoma was confirmed by fine-needle aspiration. Total thyroidectomy was performed. During the follow-up period of 3 years, no recurrence of cutaneous melanoma or thyroid cancer was detected.

162 Mystery of multiple melanomas in chronic lymphoedema T.M. Tian and G. Duncan Hawke’s Bay Hospital, Hawke’s Bay, New Zealand The development of malignancy in areas of chronic lymphoedema is well recognized. The best documented is Stewart– Treves syndrome, which describes lymphangiosarcoma in British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

chronic lymphoedema. Skin cancers developing in lymphoedema are less common, with 12 cases documented for squamous cell carcinoma and three for malignant melanoma. A white man with no risk factors for melanoma presented with a superficial spreading melanoma of his right lower leg at the age of 53 years. His only medical history was severe idiopathic bilateral leg lymphoedema from the age of 10 years. He underwent an experimental ankle-to-groin lymphadenectomy of his left leg at the age of 34 years, which unfortunately worsened the oedema in his left leg. In the 2 years after development of the first melanoma, he developed a further five primary superficial spreading melanomas in his right leg, both distal and proximal to the first melanoma. He did not develop any melanomas in his left leg, which underwent lymphadenectomy and had more severe oedema, or in the rest of his body. All the lesions were surgically resected with the appropriate margins and histologically confirmed by two pathologists to be primary rather than metastatic melanomas. Development of skin cancers in areas of lymphoedema has been documented; however, this is the first time that multiple primary melanomas on the background of chronic lymphoedema has been described. The pathophysiological process linking chronic lymphoedema and malignancy is poorly understood. It has been postulated that impaired flow of the lymphatic system leads to delayed tumour recognition and destruction. It has also been suggested that lymphatic stasis increases accumulation of carcinogens, or that lymphoedema itself may be an independent carcinogenic factor. Previous reports note the development of cutaneous malignancies after lymphadenectomy, thus it is interesting that in this patient with bilateral lymphoedema, it was the leg that had undergone the lymphadenectomy and had the worse lymphoedema that did not develop any melanomas. It can perhaps be postulated that the presence of an intact, albeit impaired, lymphatic system is necessary for the development of melanomas, and that the impaired lymphatic system rather than the actual lymphoedema itself may predispose to the development of melanomas.

163 Micronodular basal cell carcinoma mimicking naevus comedonicus H. Yesil,1 E. Arca,2 A. Akar,2 G. Acikgoz2 and I. Yavan3 1

Dermatology Department, Etimesgut Military Hospital, Ankara, Turkey, Dermatology Department, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey and 3Pathology Department, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey Basal cell carcinomas (BCCs) are the most common type of malignant skin tumours, which predominantly effect fairskinned individuals. Up to 80% of all lesions are found on the face and neck. Approximately 15% develop on the trunk. Although a universally accepted classification schema is lacking, there are various subtypes reported for BCC. Micronodular BCC is a rare variant known to have a destructive behaviour with subclinical spread and high rates of recurrence. Here we report a 56-year-old white man presenting 2

© 2014 The Authors BJD © 2014 British Association of Dermatologists

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with a nonsymptomatic lesion on his face. The patient stated that a solitary papular lesion first appeared on the skin over the right infraorbital rim. In 5 months, similar papular lesions emerged near the old one. Physical examination revealed comedo-like papular eruptions making a group with an inflammatory rim surrounding it. The clinical appearance resembled a naevus comedonicus lesion, which is a rare epidermal naevus type presenting with grouped or linear comedonal papules developing at any time from birth to middle age. Dermoscopic examination of the lesion was nonspecific. After total excision, histopathology confirmed the diagnosis of micronodular BCC. Many epidemiological studies have shown that micronodular variants of BCC are located prevalently on the head and neck region, like naevus comedonicus lesions. These two entities can both clinically resemble each other, as in our patient. At first sight, the clinical appearance is of a simple comedonal acne lesion. However, further evaluation showed that it was not so simple. As micronodular BCC is a more infiltrative and destructive type, it can require more surgical stages with wider tissue margins if it is not diagnosed in time. On the other hand it should be kept in mind that a naevus comedonicus lesion can be a component of ‘naevus comedonicus syndrome’ presenting with neurological and skeletal abnormalities. We propose that localized comedo-like lesions of the face should make us consider both micronodular BCC and naevus comedonicus in the differential diagnosis.

164 Squamous cell carcinoma and vitiligo: a case report G.K. Bedi and E. Hindle St Helens and Knowsley Teaching Hospitals, Merseyside, U.K. Ultraviolet radiation predisposes to the development of nonmelanoma skin cancer (NMSC). Melanin safeguards the skin against this. This leads one to conjecture that patients with vitiligo are at a higher risk of developing skin malignancies. However, despite the lack of protective melanin and increased oxidative stress due to epidermal hydrogen peroxide in vitiligo, there is no significantly increased risk for chronic actinic damage and NMSC (Schallreuter KU, Tobin DJ, Panske A. Decreased photo damage and low incidence of non-melanoma skin cancer in 136 sun-exposed Caucasian patients with vitiligo. Dermatology 2002; 204: 194–201; Schallreuter KU, Behrens-Williams S, Khaliq TP et al. Exp Dermatol 2003; 12: 268–77). Increased epidermal functioning wild-type p53 expression in vitiligo). Squamous cell carcinoma (SCC) has been reported in vitiligo lesions, following long-term psoralen and ultraviolet-A (PUVA) therapy. However, cases of occurrence of SCC in vitiligo patches in white patients not on PUVA are few and far between. We report a 59-year old white man with vitiligo who developed SCCs localized to the depigmented patches. We discuss the mechanisms involved in preventing the initiation of these cancers, and propose the possible explanation for our patient developing SCC.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

165 Histology-guided radiotherapy: circumferential margin control of curative radiotherapy for ill-defined basal cell carcinoma D. Holyoake, T. Ha, S.-K. Chan and K. Fife Cambridge University Hospitals, Cambridge, U.K. When surgical excision of a carcinoma with reconstruction is not possible, stepwise examination of a circumferential rim of tissue can define the lateral extent of poorly demarcated basal cell carcinoma (BCC) and guide field borders for curative radiotherapy. The recommended treatment for poorly demarcated BCC on or near the face is Mohs micrographic surgery to ensure clear margins prior to reconstruction. If radical surgery is not possible, radiotherapy may achieve disease control, but field borders are hard to plan when the extent of disease is unclear. We describe the previously unreported technique of using slow Mohs mapping – stepwise examination of a continuous circumferential rim of tissue to define the peripheral extent of tumour infiltration before radical radiotherapy. Two male patients were treated, both to a dose of 55 Gy in 20 fractions over 4 weeks. Patient A presented aged 65 years with crusting over the forehead, having undergone excision of a nodular BCC 14 years earlier. Biopsy confirmed recurrent infiltrative BCC over an area larger than 10 9 6 cm. The patient had been treated for multiple other skin tumours, suffered from depression and Parkinson disease and was unwilling to face extensive surgery with reconstruction. His tumour was poorly defined, making radiotherapy planning very difficult. He underwent resection of a continuous rim of tissue outside the clinically apparent edge of the disease, which proved positive in two locations. He then underwent resection of a further circumferential border at a distance of 1 cm, which was free of involvement by BCC. Patient B underwent multiple resections over a 20-year period for recurrent BCC on his left parietal scalp. At age 72 years he suffered multiple biopsy-proven recurrences at the edges of his 12-cm diameter skin graft. He suffered from severe heart failure, had a biventricular pacemaker and mitral valve replacement and was not fit for a general anaesthetic. He underwent staged resection of a continuous rim of tissue outside the clinically apparent disease under local anaesthetic. The first ‘layer’ was involved by micronodular BCC in several locations, but the second layer was clear. Radiotherapy was then planned by the clinical oncologist with the direct guidance of the operating dermatologist, to cover the disease extent with suitable clinical and planning margins. Close collaboration between the dermatology surgeon and oncologist is necessary for the optimal management of these patients.

166 An unusual acanthosis nigricans in a rare lymphoma J. Samson,1 V. Suja,2 A. Samad2 and S. Sankar2 1

Dr. Somervell Memorial CSI Medical College, Karakonam, Trivandrum, Kerala, India and 2Government Medical College, Trivandrum, Kerala, India A 48-year-old man presented with generalized hyperpigmentation and indurated plaques over the elbows and inguinal British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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regions for 7 months. He had low-grade fever, loss of appetite and weight loss. He was ill looking with nontender, hard enlarged lymph nodes of the submental, axillary, epitrochlear and inguinal groups. There was generalized hyperpigmentation of the skin with sparing of the scalp, nasolabial regions, axillae, cubital fossae and popliteal fossae. The dorsa of the hands and feet were hyperpigmented and velvety, with exaggeration of the pigmentation over the knuckles. The palms and soles showed velvety hyperkeratosis. An indurated plaque of about 4 9 3 cm was present on the left elbow. There were multiple discrete hyperpigmented and hyperkeratotic papules 02–05 cm in size on the exposed sites. Investigations included erythrocyte sedimentation rate (105 mm in the first hour) and absolute eosinophil count (4500 cells mm 3). Fine-needle aspiration cytology from the epitrochlear lymph node showed a reactive change. A biopsy from the hyperpigmented velvety skin over the dorsum of the hand was consistent with acanthosis nigricans. The hyperpigmented hyperkeratotic discrete papules showed features suggestive of insect bite reaction. The indurated plaque showed immature lymphocytes with vesicular and convoluted nuclei, interspersed eosinophils and plasma cells in the dermis, and high endothelial venule proliferation with extensive hyalinization of blood vessels. The lymph node showed similar morphology along with total effacement of the lymph node architecture. An immunohistochemical study showed the T-cell marker CD3 to be positive, and the B-cell marker CD20 negative. Scattered cells were CD30 positive, meaning that they were Epstein–Barr virus infected. Correlating the clinical, histopathological and immunohistochemical findings, a final diagnosis of angioimmunoblastic T-cell lymphoma involving the lymph node and skin was made (Frizzera G, Moran EM, Rappaport H. Angioimmunoblastic lymphadenopathy with dysproteinemia. Lancet 1974; 1: 1070–3; Huang CT, Chuang SS. Angioimmunoblastic T-cell lymphoma with cutaneous involvement. Arch Pathol Lab Med 2004; 128: 122–4). The patient was started on the CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisolone) regimen; he showed improvement and remained symptom free for 2 years, but later succumbed to the same disease. This case is reported because of the following facts: (i) the entity angioimmunoblastic T-cell lymphoma is rare, and this lymphoma involving the skin is rarer; (ii) the scattered CD30 positivity shows that the cells were Epstein–Barr virus infected (one of the reported causes of this lymphoma); and (iii) malignant acanthosis nigricans is commonly associated with gastric adenocarcinoma, and its association with a lymphoma is rare.

167 A case of the cutaneous multicentric plasma cell type of Castleman disease J. Lin, L. Chen, Q. Zhang, J. Luan and J. Xu Huashan Hospital Fudan University, Shanghai, China Multicentric Castleman disease (MCD) is a rare polyclonal lymphoproliferative disorder that manifests with lymphadenopathy and inflammatory symptoms (M} uzes G, Sipos F, CsoBritish Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

mor J, Sreter L. Multicentric Castleman’s disease: a challenging diagnosis. Pathol Oncol Res 2013; 19: 345–51; Kawabata H, Kadowaki N, Nishikori M et al. Clinical features and treatment of multicentric Castleman’s disease: a retrospective study of 21 Japanese patients at a single institute. J Clin Exp Hematop 2013; € , G€ 53: 69–77; Karapinar TH, T€ ufekcßi O ozmen S et al. Multicentric plasma cell type of Castleman disease in a child: difficulty in diagnosis and treatment. J Pediatr Hematol Oncol 2013; 35: e306–8; Chen H, Xue Y, Jiang Y et al. Cutaneous and systemic plasmacytosis showing histopathologic features as mixed-type Castleman disease: a case report. Am J Dermatopathol 2012; 34: 553–6; El-Osta HE, Kurzrock R. Castleman’s disease: from basic mechanisms to molecular therapeutics. Oncologist 2011; 16: 497–511). The cutaneous multicentric plasma cell variant of Castleman disease has rarely been reported, and the optimal therapeutic approach is unknown. In this case report, we discuss the case of a 61-year-old Chinese man with the multicentric plasma cell variant of Castleman disease, who developed asymptomatic erythematous nodules and plaques on his face, scalp, neck and axilla. He also presented with cervical and axillary lymphadenopathies, splenomegaly, bone marrow insufficiency and pulmonary and gastrointestinal involvement, emphasizing the difficulty in diagnosis and treatment approach. Skin biopsy revealed nodal infiltration of lymphocytes and plasma cells in the intermediate and deep dermis, and plasma cells were positive for CD38, CD138, kappa and lambda, and negative for human herpesvirus 8. However, laboratory findings of anaemia, hypoalbuminaemia, polyclonal gammaglobulinaemia, high C-reactive protein level, and elevated serum interleukin (IL)-6 level were consistent with hyper-IL-6 syndrome. Hence, the diagnosis of the cutaneous multicentric plasma type of Castleman disease was made. After five courses of cyclophosphamide, vincristine and prednisone therapy, the skin lesions have gradually diminished. This patient is still under follow-up.

168 Primary eccrine carcinoma requiring Mohs micrographic surgery and adjuvant radiotherapy A. Chandrakumar,1 D. Veitch,1 I. Proctor,2 S. Hughes2 and C. Perrett1 1

Department of Dermatology and 2Department of Histopathology, University College London Hospital, London, U.K. We report a challenging case of primary eccrine ductal carcinoma of the right parietal scalp, which was treated with Mohs micrographic surgery (MMS) and adjuvant radiotherapy. A fit and well 84-year-old woman presented to the general surgeons with a 4-year history of three discrete nodules over the right parietal scalp. Two of these nodules were excised as they had become itchy and painful. Two months later, multiple nodules developed around the excision scars. Histology of the two excised nodules showed the dermis to be extensively infiltrated with cribriform nests of cells with central lumina. Elsewhere in the dermis and subcutis were nests and cords of medium-sized polygonal tumour cells with eosinophilic cytoplasm and moderately pleomorphic © 2014 The Authors BJD © 2014 British Association of Dermatologists

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central ovoid nuclei. These cells were strongly positive for cytokeratin 7, oestrogen receptor, progesterone receptor and gross cystic disease fluid protein, and negative for cytokeratin 20 on immunohistochemistry. The histological findings were compatible with either primary eccrine ductal carcinoma or metastatic carcinoma of the breast. Thorough investigation including computed tomography of the chest, abdomen and pelvis, and mammography and ultrasound of the breast did not reveal a primary breast carcinoma or metastases elsewhere. A diagnosis of primary eccrine ductal carcinoma was therefore made. Magnetic resonance imaging demonstrated a 65 9 4-cm tumour extending into subcutaneous fat and deep into the periosteum, although no overt bony cortical erosion was identified. Although the peripheral margins were clear after four levels of MMS, the deep margin remained positive for tumour down to the periosteum. The post-Mohs defect on the right parietal scalp measured 8 9 55 cm and was subsequently closed with a skin graft from the right thigh. Three months after the graft had settled, the area was treated with adjuvant single-phase radiotherapy at a total dose of 55 Gy in 20 fractions. Over 2 years after initial MMS and 20 months postradiotherapy, the patient remained in remission with no evidence of metastasis. Eccrine carcinomas are rare adnexal tumours that account for < 001% of all cutaneous tumours. Characteristically, they are invasive, have high rates of local recurrence, and metastasize in up to 60% of cases. MMS reduces the rate of recurrence of these tumours compared with wide local excision. There are no consensus guidelines regarding the role of adjuvant radiotherapy in primary eccrine carcinoma due to its rarity. This case highlights the difficulties in treatment of locally aggressive eccrine carcinomas that cannot be completely excised by MMS alone.

169 The role of Mohs micrographic surgery in the treatment of microcystic adnexal carcinoma P. Jayasekera,1 G. Sharpe1 and H. Tehrani2 1

Royal Liverpool and Broadgreen NHS Hospitals, Liverpool, U.K. and 2St Helens and Knowsley Hospitals NHS Trust, Liverpool, U.K. Microcystic adnexal carcinoma (MAC) is a locally aggressive tumour with a propensity for perineural and perivascular invasion, resulting in a high recurrence rate even with wide surgical margins (Leibovitch I, Huilgol SC, Selva D et al. Microcystic adnexal carcinoma: treatment with Mohs micrographic surgery. J Am Acad Dermatol 2005; 52: 295–300). We present two patients who had Mohs micrographic surgery (MMS) in order to excise MACs. An 84-year-old man presented with a lesion on the right lower eyelid that had been neglected for a number of years. Initial biopsy indicated morphoeic BCC, and a magnetic resonance imaging scan showed abnormal soft tissue within the right lower eyelid extending to the conjunctiva. Due to orbital involvement an exenteration was carried out; histology was reported as MAC incompletely excised at the medial peripheral margin. The patient was referred for MMS to the involved area, subsequently undergoing two excision © 2014 The Authors BJD © 2014 British Association of Dermatologists

stages and repair with a split-thickness skin graft. At the 1year follow-up there was no evidence of recurrence. A 59year-old woman had a lesion excised from the right eyebrow, which was reported as a possible syringoma. The lesion recurred after 5 years and further excision revealed an incompletely excised MAC. The patient was referred for MMS, and after a detailed history was taken it was noted that the patient had symptoms consistent with perineural invasion. On examination there was a firm subcutaneous lesion present at the scar site. The lesion proved to be extensive, displaying both perineural and perivascular invasion, and required 10 Mohs excision stages to gain tumour clearance. The defect was repaired with a forehead flap and the patient made an uneventful recovery with no recurrence 6 months postoperatively. She retained function in her right eye, which would have undergone exenteration if MMS were unavailable. MMS has been shown, in small series, to provide a lower recurrence rate than formal excision and has been proposed as the mainstay of treatment for MAC. Recurrence rates after MMS have been reported as low as 0–12% (Snow S, Madjar DD, Hardy S et al. Microcystic adnexal carcinoma: report of 13 cases and review of the literature. Dermatol Surg 2001; 27: 401–8). Our cases serve to highlight the role of MMS in the treatment of MAC, and we agree with other authors who suggest that MMS should be employed either as a primary treatment modality, or as an adjunct for cases having undergone incomplete excision.

170 Angioimmunoblastic T-cell lymphoma a diagnostic challenge J.O. Garza, N. Vazquez, J.O. Candiani, V. Garza, L. Barbosa and I. Miranda Hospital Universitario Dr Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon, Mexico Angioimmunoblastic T-cell lymphoma accounts for 18% of all peripheral T-cell lymphomas worldwide and usually affects older individuals in the seventh decade of life, with a slight male predilection. It is a primary CD4, CD8 T-cell disorder with concomitant B-cell and endothelial dysregulation. Clinical features commonly reported include peripheral lymphadenopathy, hepatosplenomegaly and constitutional symptoms, including weight loss, fever and night sweats. Skin involvement occurs in up to 50% of patients with angioimmunoblastic T-cell lymphoma but has not been well characterized. Angioimmunoblastic T-cell lymphoma is typically diagnosed by lymph node biopsy. (Balaraman B, Conley JA, Sheinbein DM. Evaluation of cutaneous angioimmunoblastic T-cell lymphoma. J Am Acad Dermatol 2011; 65: 855–62). We present the case of a 55-year-old woman with a history of hypothyroidism, haemolytic anaemia and a recently diagnosed hypereosinophilic syndrome referred from haematology to dermatology because of a 2-year rash localized in the neck that appeared intermittently. One year earlier this rash had spread to the upper limbs and trunk on both sides, accompanied by itching. The patient was treated with British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

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unspecified topical steroids, with no clinical improvement. At physical examination, multiple erythematous, coalescent, nonevanescent plaques and palpable violaceous nodules were noted in her trunk and all limbs. The histopathology analysis reported T-cell lymphoma. Immunohistochemical staining was performed, which was diffusely positive for CD4, CD3 and CD5, with focal positivity for CD8 and TIA-1. The haematology department considered axillary lymph node biopsy, with a histopathological report of angioimmunoblastic T-cell lymphoma with immunostains CD3+, CD4+, CD5+, CD7+, CD8 , CD10 and Epstein-Barr virus staining positive. Our patient was treated with cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone and thalidomide, with clinical improvement in her symptoms and dermatoses. Clinical remission was achieved after 5 months. Afterwards, she received an autologous stem cell transplantation without relapse so far. The diagnosis of cutaneous angioimmunoblastic T-cell lymphoma is very challenging, given the lack of clinical and histological criteria. There are some reports in the literature with different morphology of the lesions, and histology usually reports a perivascular infiltrate, vascular hyperplasia and vasculitis that are nonspecific. Therefore, one must be more cautious with the clinical history, symptoms and laboratory findings. Our patient had a history of an autoimmune haemolytic anaemia, recently diagnosed as a hypereosinophilic syndrome with arthritis. All these findings plus the cutaneous involvement made us consider the possibility of T-cell lymphoma.

171 Surgery results in complete cure of Lambert–Eaton myasthenic syndrome in a patient with metastatic Merkel cell carcinoma R. Siau,1 A. Morris2 and R. Karoo1 1

Welsh Centre of Burns and Plastic Surgery, Swansea, U.K. and 2University Hospital of Wales, Cardiff, U.K. Lambert–Eaton myasthenic syndrome is a paraneoplastic phenomenon associated with neuroendocrine tumours, most frequently small cell lung carcinoma. Merkel cell carcinoma is a rare cause of Lambert–Eaton myasthenic syndrome. A 70-yearold man was referred with metastatic axillary nodal disease from a previously resected Merkel cell carcinoma of the left arm. Preoperatively, the patient was wheelchair bound from Lambert–Eaton myasthenic syndrome. Level I–III left axillary node clearance was performed, and within 6 months he had experienced full recovery of muscle power and mobility. We describe a case of complete cure of Lambert–Eaton myasthenic syndrome following axillary nodal clearance in a patient with metastatic Merkel cell carcinoma.

British Journal of Dermatology (2014) 171 (Suppl. 4), pp1–76

Abstracts 172–188 are not included here

189 Efficacy and safety of methyl aminolaevulinate cream activated by daylight in actinic keratosis: two randomized, investigator-blinded, controlled, phase 3 studies in Europe and Australia R.-M. Szeimies,1 N. Basset-Seguin,2 D. Rubel,3 S. Shumack,4 S. Leclerc,5 N. Kerrouche5 and J.P. Lacour6 1

Klinikum Vest GmbH, Recklinghausen, Germany, 2Hopital Saint-Louis, Paris, France, 3Woden Dermatology, Phillip, Australia and Probity Medical Research, 4St George Dermatology and Skin Cancer Center, Kogarah, Australia and Probity Medical Research, 5Galderma R&D, Sophia Antipolis, France and 6 H^opital Archet-2, University Hospital of Nice, France Conventional photodynamic therapy (c-PDT) using light-emitting diode lamps and methyl aminolaevulinate cream is approved for the treatment of actinic keratoses (AKs). Although it provides a high rate of AK clearance with a good cosmetic outcome, it is time consuming and usually associated with pain. Clinical studies performed in Scandinavia have shown that daylight photodynamic therapy (DL-PDT) with methyl aminolaevulinate cream provides similar AK clearance rates to c-PDT, is almost painless, and simplifies the procedure. With DL-PDT the photosensitizer is activated immediately upon its formation, whereas with c-PDT the photosensitizer accumulates for 3 h under occlusion and then is activated by the lamp. Two multicentre, randomized, investigator-blinded, controlled, intraindividual noninferiority studies compared DL-PDT and c-PDT with methyl aminolaevinulate cream for the treatment of AK in Australia and Europe in 100 and 108 patients, respectively. At week 12 after a single DL-PDT session, the lesion complete response rate with DL-PDT was noninferior to c-PDT: about 89% vs. 93% in the Australian study and 70% vs. 74% in the European study. The maximal subject-reported pain was significantly lower with DL-PDT compared with c-PDT (mean pain score on a 0 to 10 scale of 0.8 vs. 5.7 in the Australian study and 0.7 vs. 4.4 in the European study, both P < 0.001). There were fewer subjects with related adverse events with DL-PDT compared with c-PDT (about 39% vs. 59% and 50% vs. 61%, respectively). DL-PDT with methyl aminolaevinulate cream in comparison with c-PDT was as effective, well tolerated and almost painless in two phase III studies conducted in different parts of the world.

© 2014 The Authors BJD © 2014 British Association of Dermatologists

Abstracts of the XV World Congress on Cancers of the Skin, 3-6 September 2014. Edinburgh, Scotland.

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