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Összefoglaló. A Gorlin–Goltz-szindróma – más néven naevoid basalsejtes carcinoma szindróma – egy ritka, viszont számos orvosi társszakmát érintő, rendkívül változatos megjelenésű és genetikailag is heterogén betegség. Bár a tudományos kutatások egyik kedvenc területe, az aránylag alacsony betegszám, valamint a genotípus és a fenotípus közötti, igen komplex összefüggések miatt a kórképről meglévő ismereteink még nem teljesek. A témában megjelent nemzetközi és magyar nyelvű publikációk jelentős része esetközlésekre és a szindróma általános ismertetésére szorítkozik. A közlemény célja, hogy áttekintést adjon a szindróma genetikai vonatkozásairól. A nemzetközi és a magyar nyelvű szakirodalom áttanulmányozását végeztük. A naevoid basalsejtes carcinoma szindróma genetikai hátterének, az egyelőre azonosítatlan örökletes tényezőknek pontos megismerése még várat magára. A genetikai vizsgálatok a szindróma pontosabb megértéséhez, könnyebb diagnosztizálásához, a pozitív családtervezéshez és a személyre szabott terápiákhoz is hozzájárulhatnak. Orv Hetil. 2020; 161(49): 2072–2077. Summary. Gorlin–Goltz syndrome, or nevoid basal cell carcinoma syndrome, is a rare disease that requires multidisciplinary approach in patient management. The disease is genetically heterogenous and has an extremely variable expressivity. Although the syndrome is in the focus of scientific research, our knowledge of it is still limited due to the relatively low number of recognised patients and the complexity of genotype-phenotype correlation. Several papers in this field have been published in the international and also in the Hungarian literature but most of these reports are single cases or small case series of families and outline general information about the disease. Authors aimed to review the literature of the syndrome and to report the genetic background and its role in the diagnosis and treatment. A review of the English and Hungarian literature was performed. The full genetic background of the syndrome is not yet discovered. Increasing the awareness of the syndrome, collecting and thoroughly analysing the medical records and performing genetic tests on the patients may lead to the better understanding of the disease; they may also help early diagnosis and treatment, positive family planning and may establish personalized medicine. Orv Hetil. 2020; 161(49): 2072–2077.

Cutaneous T-cell lymphoma is a heterogeneous group of malignancies including both indolent and aggressive forms, with an average 5-year disease-specific survival rate of 11-100%. Prognostic factors in cutaneous T-cell lymphoma according to the different subtypes are not clearly defined, however extracutaneous manifestation seems to predict a poor prognosis. Tonsil involvement was revealed as a cause of oropharyngeal complaints in two of our male patients, treated for histologically confirmed tumour stage of mycosis fungoides. In the first case urgent tracheostomy followed by radiotherapy, while in the other case systemic treatment resulted in complete remission of the tonsil involvement. Both patients were subsequently lost due to the progression of mycosis fungoides. Factors predicting an unfavourable prognosis included extracutaneous manifestation, late stage disease, age over 60 years, elevated lactate-dehydrogenase levels, and large cell transformation. With our cases we would like to shed light to the prognostic markers of mycosis fungoides, and to the rare tonsil involvement, which is potentially life-threatening and requires urgent intervention.

Background Acral lentiginous melanoma (ALM) occurs on the palms, soles and subungual surface and has poor prognosis. It is uncommon in the Caucasian population and has remained unreported in East-Central Europe. Objectives Our aim was to collect data from East-Central Europe by analysing the demographic and clinicopathologic features of patients with ALM and comparing data with the reports in literature. Methods We conducted a single-centre, retrospective review between 1976 and 2016 at one of the largest melanoma referral centres in Hungary. Results We identified 176 patients with ALM (3.83%) from 4593 patients with melanoma (mean age: 66.2 years). The tumours were mainly located on the lower extremities (88.63%). The mean Breslow tumour thickness was 3.861 mm, 37.50% of the tumours were thicker than 4.00 mm, and 71.6% exhibited microscopic ulceration. Nearly one-third of the patients underwent sentinel lymph node (SLN) biopsy, and 60.3% of the biopsies were positive for metastasis. The positive SLN status was associated with significantly thick tumours and reduced survival. Patients with ALM had 5- and 10-year overall survival rates of 60.5% and 41.6%, respectively. The mean delay in diagnosis was 18 months after the discovery of skin tumours. In multivariate analyses, age, tumour thickness and distant metastasis were independent risk factors for poor survival (P Conclusions Our study, which is the first single-centre report in East-Central Europe focusing on ALM, confirms that patient and tumour characteristics and prognostic factors are similar with previous literature data involving Caucasians; however, tumour thickness and survival suggest even worse prognosis.

Objective The prevalence of xeroderma pigmentosum (XP) is quite low in Europe, which may result in a delay in determining the appropriate diagnosis. Furthermore, some subtypes of XP, including XPA, may manifest themselves with quite severe neurological symptoms in addition to the characteristic dermatological lesions. Accordingly, the aim of the current study is to highlight the predominant neurological aspects of XPA, as well as mild-to-moderate dermatological signs in a Hungarian family with 5 affected siblings. Case reports The symptoms of the Caucasian male proband started to develop at 13–14 years of age with predominantly cerebellar, hippocampal, and brainstem alterations. His elder sister and three younger brothers all presented similar, but less expressed neurological signs. The diagnostic work-up, including clinical exome sequencing, revealed 2 novel compound heterozygous mutations (p.Gln146_Tyr148delinsHis, p.Arg258TyrfsTer5) in the XPA gene. Surprisingly, only mild-to-moderate dermatological alterations were observed, and less severe characteristic ophthalmological and auditory signs were detected. Conclusions In summary, we present the first family with genetically confirmed XPA in the Central-Eastern region of Europe, clearly supporting the notion that disturbed function of the C-terminal region of the XPA protein contributes to the development of age-dependent neurologically predominant signs. This case series may help clinicians recognize this rare disorder. Electronic supplementary material The online version of this article (10.1007/s10072-019-04044-6) contains supplementary material, which is available to authorized users.

BACKGROUND The use of UV-emitting tanning devices for cosmetic purposes is associated with an increased risk of melanoma and non-melanoma skin cancer. Young women are the most frequent users, therefore, there is an increasing concern about the regulation of sunbed use. OBJECTIVE The primary objective is to assess the current legislation on sunbed use among European countries. METHODS We developed a 30-item questionnaire to gather the most relevant information about sunbed use legislation. The questionnaire was sent to Euromelanoma coordinators and to designated coordinators out of the Euromelanoma network. RESULTS We obtained a response rate of 64%. More than 25% of the countries did not report any specific legislation. Roughly one-third of the countries does not have a restriction for minors. Even in countries with a specific legislation, a lack or insufficient enforcement of age limit was observed in up to 100% of the inspections based on the PROSAFE report from 2012. Self-tanning devices were reported in 50%, and almost 40% of countries do not require supervision of use. Although a warning display is required in 77% of cases, a signed informed consent is not required in 80%. In the vast majority of cases, the number of licensed or closed tanning centres is unknown. CONCLUSIONS Despite the evidence of its harmful effects, and its frequent use by young people, many of whom are at high risk of skin cancer because of fair skin, a significant number of European countries lack a specific legislation on tanning devices. In order to limit the access of young people to sunbeds, a more strictly enforced regulation is needed, as well as regulation regarding advertisement, and location of tanning centres, in addition to health promotion campaigns that target the vulnerable population of young women seeking its use for improved cosmesis.

BACKGROUND AND OBJECTIVES: The incidence of melanoma is increasing. This places significant burden on societies to provide efficient cancer care. The European Cancer Organisation recently published the essential requirements for quality melanoma care. The present study is aimed for the first time to roughly estimate the extent to which these requirements have been met in Europe. MATERIALS AND METHODS: A web-based survey of experts from melanoma centers in 27 European countries was conducted from 1 February to 1 August, 2019. Data on diagnostic techniques, surgical and medical treatment, organisation of cancer care and education were collected and correlated with national health and economic indicators and mortality-to-incidence ratio (MIR) as a surrogate for survival. Univariate linear regression analysis was performed to evaluate the correlations. SPSS software was used. Statistical significance was set at p < 0.05. RESULTS: The MIR was lower in countries with a high health expenditure per capita and with a higher numbers of general practitioners (GPs) and surgeons per million inhabitants. In these countries, GPs and dermatologists were involved in melanoma detection; high percentage of dermatologists used dermatoscopy and were involved in the follow-up of all melanoma stages; both medical oncologists and dermato-oncologists administered systemic treatments and patients had better access to sentinel lymph node biopsy and were treated within multidisciplinary tumour boards CONCLUSION: Based on these first estimates, the greater involvement of GPs in melanoma detection; the greater involvement of highly trained dermatologists in dermatoscopy, dermatosurgery, follow-up and the systemic treatment of melanoma; and the provision of ongoing dermato-oncology training for pathologists, surgeons, dermatologists and medical oncologists are necessary to provide an optimal melanoma care pathway. A comprehensive analysis of the melanoma care pathway based on clinical melanoma registries, will be needed to more accurately evaluate these first insights.

Neonatal blue-light phototherapy induced a blistering reaction followed by eruption of melanocytic nevi on the exposed skin surface of a child with transient neonatal porphyrinemia. New nevi are still developing 4 years after the triggering event. The role of phototoxicity-induced epidermal injury, that of porphyrins and the influence of neonatal blue-light therapy, in this unique phenomenon are discussed.

Abstract: Introduction and aim: Melanoma is a highly aggressive tumour with often unpredictable outcome. Our aim with this study was to determine factors influencing early detection of melanoma. Method: We analyzed 139 questionnaires completed by patients diagnosed with melanoma. Results: We found that our patients are health-conscious regarding cardiovascular diseases and attend cancer screenings on recall. However, their knowledge about melanoma is insufficient. Most of them perform skin self-examination, but they do not know what to check. Melanoma is detected mostly by the patients themselves, but it takes more than one year to consult a doctor. Our study confirmed that patients’ attitude toward melanoma is an important factor influencing early detection. We found that physical examination and communication about skin cancer prevention is not part of the routine medical care. Conclusions: It is important to improve knowledge about melanoma among the general population and health care providers and to emphasize that early detection can save lives. Orv. Hetil., 2016, 157(51), 2028–2033.

Leukaemia cutis is a relatively rare manifestation in chronic lymphocytic leukaemia, characterized by a diverse morphology of skin lesions. We report two patients who developed zosteriform skin symptoms; however, the histological analysis revealed leukaemia infiltration as the cause of their symptoms. Contrary to previous reports, varicella zoster virus DNA was detectable in the lesions. These findings suggest that varicella zoster virus plays an active role in the development of zosteriform leukaemia cutis.

Ulcus vulvae acutum Lipschütz or acute genital ulcer is a distinct clinical entity characterized by sudden painful genital ulceration occurring mostly in young and virgin girls with malaise, fever and other systemic symptoms. This distressing syndrome is rare and may be presented to dermatologists, gynecologists or pediatricians. Its diagnosis and therapy can be challenging. We present two young female patients with ulcus vulvae acutum. The cause of the disease could not be confirmed in our patients, but, interestingly, both patients had partial IgA deficiency. In the last 100 years, after its first description by Lipschütz, many case reports and series have aimed to identify a specific cause of the disease, without success. These studies mainly focused on infectious agents as causative factors, however, in most cases connection with infection could not be confirmed. Our opinion is that the decreased level of IgA could be a possible explanation for the cause of this syndrome. With our cases we would like to emphasize the possible role of local immunological mechanisms rather than several infectious agents in the development of this little-known disease.

Background The similar genetic background of a pair of twins, and the similar environmental impacts to which they are exposed allow an exact and objective investigation of various constitutional and environmental factors in naevus development. As far as we are aware, this is the first published survey that simultaneously examines cutaneous and ocular pigmented lesions in an appreciable sample of identical and non-identical twins. Methods 172 pairs of twins of Caucasian origin were included in this study. A whole-body skin examination and a detailed ophthalmological examination were performed to determine the density of melanocytic lesions. A standardized questionnaire was used to assess the data relating to constitutional, sun exposure and other variables. Results A notably high proportion of the subjects (36.78%) manifested one or more clinically atypical melanocytic naevi (CAMNs), and approximately one-third (31.4%) of them at least one benign uveal pigmented lesion (BUPL). The incidence of iris freckles (IFs), iris naevi (INs) and choroidal naevi (CHNs) proved to be 25.35%, 5.98% and 3.52%, respectively. The interclass correlation coefficients for common melanocytic naevi (CMNs), CAMNs, and INs were 0.77, 0.76 and 0.86 in monozygotic twins, as compared with 0.5, 0.27 and 0.25 in dizygotic twin pairs, respectively. A statistically significant correlation was found between the prevalence of CAMNs and that of INs. Conclusions This significant correlation suggests the existence of a subgroup of Caucasian people with an increased susceptibility to both cutaneous and ocular naevus formation. There is accumulating evidence that, besides the presence of cutaneous atypical naevi, INs can serve as a marker of a predisposed phenotype at risk of uveal melanoma. The correlation between cutaneous and ocular pigmented lesions underlines the need for the adequate ophthalmological screening of subjects with CAMNs and INs.

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring.

Background Euromelanoma is a skin cancer education and prevention campaign that started in 1999 in Belgium as 'Melanoma day'. Since 2000, it is active in a large and growing number of European countries under the name Euromelanoma. Objective To evaluate results of Euromelanoma in 2009 and 2010 in 20 countries, describing characteristics of screenees, rates of clinically suspicious lesions for skin cancer and detection rates of melanomas. Methods Euromelanoma questionnaires were used by 20 countries providing their data in a standardized database (Belgium, Croatia, Cyprus, Czech Republic, FYRO Macedonia, Germany, Greece, Hungary, Italy, Lithuania, Luxembourg, Malta, Moldavia, Portugal, Serbia, Slovenia, Spain, Sweden, Switzerland and Ukraine). Results In total, 59 858 subjects were screened in 20 countries. Most screenees were female (64%), median ages were 43 (female) and 46 (male) and 33% had phototype I or II. The suspicion rates ranged from 1.1% to 19.4% for melanoma (average 2.8%), from 0.0% to 10.7% for basal cell carcinoma (average 3.1%) and from 0.0% to 1.8% for squamous cell carcinoma (average 0.4%). The overall positive predictive value of countries where (estimation of) positive predictive value could be determined was 13.0%, melanoma detection rates varied from 0.1% to 1.9%. Dermoscopy was used in 78% of examinations with clinically suspected melanoma; full body skin examination was performed in 72% of the screenees. Conclusion Although the population screened during Euromelanoma was relatively young, high rates of clinically suspected melanoma were found. The efficacy of Euromelanoma could be improved by targeting high-risk populations and by better use of dermoscopy and full body skin examination. © 2011 European Academy of Dermatology and Venereology.

Electrochemotherapy (ECT) is a novel therapeutic option for the treatment of cutaneous and subcutaneous metastases of malignant melanoma. During the treatment, electric pulses are applied to tumor nodules to deliver nonpermeant or poorly permeant chemotherapeutic agents into the cells, increasing local cytotoxicity of anticancer drugs. We compared the clinical effectiveness of ECT as an alternative palliative treatment option for unresectable metastatic lesions of malignant melanoma with a systematic review of reported outcomes.One hundred fifty-eight cutaneous and subcutaneous metastases of nine patients were treated with ECT. All treatments were performed under general anesthesia using intravenous bleomycin injection. Median follow-up was 195 days.In our case series, complete response rate was 23%, and partial response rate was 39%. We observed no change in 30% and progressive disease in 8% of cases.ECT is a simple and effective treatment of single or multiple cutaneous and subcutaneous metastases of melanoma with minimal side effects. Our results provide further data for the growing body of evidence in recently published studies that ECT used for palliation has clinical benefit. The authors have indicated no significant interest with commercial supporters.

OBJECTIVES Electrochemotherapy (ECT) is a novel therapeutic option for the treatment of cutaneous and subcutaneous metastases of malignant melanoma. During the treatment, electric pulses are applied to tumor nodules to deliver nonpermeant or poorly permeant chemotherapeutic agents into the cells, increasing local cytotoxicity of anticancer drugs. We compared the clinical effectiveness of ECT as an alternative palliative treatment option for unresectable metastatic lesions of malignant melanoma with a systematic review of reported outcomes. METHODS One hundred fifty-eight cutaneous and subcutaneous metastases of nine patients were treated with ECT. All treatments were performed under general anesthesia using intravenous bleomycin injection. Median follow-up was 195 days. RESULTS In our case series, complete response rate was 23%, and partial response rate was 39%. We observed no change in 30% and progressive disease in 8% of cases. CONCLUSIONS ECT is a simple and effective treatment of single or multiple cutaneous and subcutaneous metastases of melanoma with minimal side effects. Our results provide further data for the growing body of evidence in recently published studies that ECT used for palliation has clinical benefit. The authors have indicated no significant interest with commercial supporters.

Background Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, is an indispensable step in all primary prevention efforts. Objectives This paper aims to assess the prevalence of different pigmented lesions among schoolchildren and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors. Patients/methods A cross-sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole-body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables. Results One to 10 common melanocytic naevi were found in 27% of the participants, and the naevus numbers were in the range of 10–100 in 67%; 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Statistically significant associations were found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, a history of severe painful sunburns and a family history of a large number of melanocytic naevi. Conclusion Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of a large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.

A hám eredetű tumorok a leggyakrabban előforduló bőrdaganatok. Az arcon és a kézen való gyakori elhelyezkedésük miatt ellátásuk során az onkológiai szempontok mellett esztétikai szempontokat is figyelembe kell venni. Kezelésük során általában elsőként választandó a sebészi kimetszés, de számos más alternatíva is létezik, különösen a felületes, nem mélyre terjedő tumorok esetében. A fotodinámiás terápia bizonyos nem melanoma típusú rosszindulatú bőrdaganatok kezelésében napjainkra széles körben elfogadott eljárássá vált. A fotodinámiás terápia során fényérzékenyítő anyag alkalmazását követően a kezelt bőrfelületet az adott fényérzékenyítő abszorpciós maximumának megfelelő hullámhosszúságú fénnyel sugarazzuk be. A fényérzékenyítő anyagok akkumulációja a gyorsan osztódó sejtekben és újonnan képződött erekben sokkal nagyobb mértékű, mint a környező, egészséges szövetekben – ez biztosítja a kezelés daganatszelektivitását. A terápia során a fény hatására gerjesztett állapotba kerülő fényérzékenyítő anyagból reaktív oxigéngyökök szabadulnak fel, melyek végső soron megváltozott sejtfolyamatokhoz, illetve a sejtek apoptózisához vezetnek. A fotodinámiás terápia hatékonysága solaris keratosis, superficialis basalioma és morbus Bowen esetén bizonyított, kozmetikai eredményessége pedig felülmúlja a többi elfogadott kezelését. A mellékhatások – fájdalom, erythema, pörkképződés, nedvedzés, ödéma – általában enyhék, és gyorsan megszűnnek. A szerzők a Szegedi Tudományegyetem Bőrgyógyászati és Allergológiai Klinikán 2003. december és 2006. január között 212 betegnél végzett fotodinámiás kezelések során szerzett tapasztalataikat ismertetik, és áttekintik a fotodinámiás kezelés dermatoonkológiai irodalmát.

The P48T germ line mutation of p16 was detected in a Hungarian multiple primary melanoma patient (deceased at the age of 39) with no affected family members. Genetic analysis of the patient and his family revealed that the patient was homozygous for the mutation, whereas his parents (father currently aged 69 and mother 63), who are free from any malignancies and atypical moles, are both heterozygous for the mutation. Our data suggest that the P48T mutation of p16 is a strong melanoma-predisposing factor, but the fact that the heterozygous mutant parents have not yet exhibited melanoma or atypical moles indicates that the penetrance of this allele might depend on modifying factors. The rare P48T germ line mutation of p16 has been reported previously in only four independent studies, all in patients with Italian ancestry. Here, we first report the inheritance of the rare P48T mutation of CDKN2A in a Hungarian family with a homozygous multiple primary melanoma member and unaffected heterozygous family members. The question of whether the mutation detected in Hungary is the result of an independent event, or migration of the founder mutation occurred at some time in the past, necessitates further investigations.

There is a growing body of evidence supporting the theory that cutaneous dysplastic naevus syndrome patients are at increased risk of developing not only skin but also uveal melanoma. The relationship between dysplastic naevus syndrome and ocular naevi needs to be clarified. In this study we investigated the ocular pigmented findings in patients with dysplastic naevus syndrome and compared the results with a control group (subjects without atypical moles) in order to investigate the frequency of ocular naevi among dysplastic naevi-bearing patients. A total of 152 dysplastic naevus syndrome patients were enrolled in our investigation. The control group consisted of 142 sex-, age- and skin type-matched healthy volunteers without cutaneous dysplastic naevi or skin melanoma. Conjunctival and uveal pigmented findings and iris colour were recorded during a detailed ophthalmic examination. A greater number of conjunctival naevi (3.2% versus 0%), iris naevi (5.2% versus 1.4%), iris freckles (17% versus 5.6%) and choroidal naevi (5.2% versus 0.7%) were detected in the dysplastic naevus syndrome group compared with the controls. The difference reached statistical significance in the case of conjunctival naevi, choroidal naevi and iris freckles. Our results confirm the hypothesis that dysplastic naevus syndrome patients might have overstimulation of their melanocytic system not only in the skin but also in the uvea, leading to increased benign (as well as rarely malignant) melanocytic proliferation. Dysplastic naevus syndrome patients should be screened by ophthalmologists because of the increased frequency of different ocular pigmented alterations.

The genetic predisposition to melanoma is quite heterogeneous. The major locus for melanoma predisposition is the cell cycle regulatory CDKN2A gene on chromosome 9p21 though alterations in it have been detected in only 20 40% of melanoma prone families. However, with regard to the frequency of melanoma-prone families linked to 9p21, the frequency of germline coding mutations of the CDKN2A gene is lower than expected. We set out to investigate whether the rare IVS1+37 G/C intronic mutation of the CDKN2A gene recently identified in a Hungarian melanoma prone family, influences mRNA splicing regulation. To this end, CDKN2A minigenes containing the wild type and the mutant intronic sequence were created and transfected into HeLa cells with the aim of study of the mRNA transcripts. The results revealed the emergence of a differential splicing pattern from the wild type and the mutant minigene, suggesting that this mutation may alter the splicing of CDKN2A primary mRNA and therefore might have a pathogenetic role in familial melanoma. We believe that these results confirm the importance of the identification and characterization of CDKN2A intronic mutations with a view to improvement of our understanding of the pathogenesis and the explanation of why the frequency of germline coding mutations of the CDKN2A gene is lower than expected in melanoma-prone families linked to chromosome 9p21.

Summary Background Even though progress has been made, the detection of melanoma still poses a challenge. In light of this situation, the Nevisense electrical impedance spectroscopy (EIS) system (SciBase AB, Stockholm, Sweden) was designed and shown to have the potential to be used as an adjunct diagnostic tool for melanoma detection. Objectives To assess the effectiveness and safety of the Nevisense system in the distinction of benign lesions of the skin from melanoma with electrical impedance spectroscopy. Methods This multicentre, prospective, and blinded clinical study was conducted at five American and 17 European investigational sites. All eligible skin lesions in the study were examined with the EIS-based Nevisense system, photographed, removed by excisional biopsy and subjected to histopathological evaluation. A postprocedure clinical follow-up was conducted at 7 ± 3 days from the initial measurement. A total of 1951 patients with 2416 lesions were enrolled into the study; 1943 lesions were eligible and evaluable for the primary efficacy end point, including 265 melanomas – 112 in situ and 153 invasive melanomas with a median Breslow thickness of 0·57 mm [48 basal cell carcinomas (BCCs) and seven squamous cell carcinomas (SCCs)]. Results The observed sensitivity of Nevisense was 96·6% (256 of 265 melanomas) with an exact one-sided 95% lower confidence bound estimated at 94·2% and an observed specificity of 34·4%, and an exact two-sided 95% confidence bound estimated at 32·0–36·9%. The positive and negative predictive values of Nevisense were 21·1% and 98·2%, respectively. The observed sensitivity for nonmelanoma skin cancer was 100% (55 of 48 BCCs and seven SCCs) with an exact two-sided 95% confidence bound estimated at 93·5–100·0%. Conclusions Nevisense is an accurate and safe device to support clinicians in the detection of cutaneous melanoma. What's already known about this topic? Although progress has been made in the detection of melanoma it still poses a challenge. Electrical impedance spectroscopy (EIS) may potentially be used as a diagnostic aid for the detection of melanoma. What does this study add? In the largest international prospective study of its kind in melanoma detection, the EIS system Nevisense was shown to be both accurate and safe in the lesion cohort studied. In the absence of a perfect gold standard, the accuracy of a device should be compared with the consensus diagnosis from multiple experts.

Background Langerhans cell histiocytosis (LCH) is characterized by the proliferation of pathologic Langerhans cells. The disease can develop in any age and can affect almost any organ. Cutaneous involvement is frequent in LCH. The recent demonstration of the activating, oncogenic BRAFV600E gene mutation in LCH samples strongly supports the neoplastic origin of the disease. Objectives Our aim was to analyse the clinical data of the patients and whether BRAFV600E mutation is present in skin lesions of patients with adult onset LCH, and to investigate whether the BRAFV600E mutation status has any effect on the clinical presentation and the outcome of the disease. Methods We diagnosed and treated 15 adult LCH patients in the period of 1987–2012 and collected their clinical data. Three of our patients suffered from skin involvement and 12 patients had multiorgan disease (five patients out of the multisystem group died). Eleven formalin-fixed paraffin-embedded skin samples from 10 patients were available for BRAFV600E mutation analysis. Results Among the 11 examined samples, 6 contained the BRAFV600E mutation (54.5%). Our results indicate that in the adult group of LCH patients the presence of BRAFV600E mutation is similar to what was previously suggested in case of the childhood forms, at least as far as skin lesions are concerned. The BRAF mutation status of our patients does not seem to correlate with the extent and/or the outcome of the disease. Conclusion Our results support the neoplastic origin of LCH and suggest that skin lesions of LCH are sufficient for the diagnosis of the disease and for assessing its BRAF status. In addition, analysis of BRAF status of patients with LCH can lead to the administration of new targeted therapies which may provide better disease control and prognosis.

We have previously reported that the presence of cutaneous dysplastic naevi is a risk factor for uveal melanoma. In the present study our goal was to determine the incidence of different histopathological features of uveal melanoma among 91 patients with or without cutaneous dysplastic naevi. Statistical analysis revealed that the presence of cutaneous dysplastic naevi in uveal melanoma patients is associated with an increased incidence of the prognostically worst forms of uveal melanoma (epithelioid or mixed cell type melanomas). The relative risk was 5.97 (95% confidence interval 1.61-22.14). Our results suggest that the presence of cutaneous dysplastic naevi is not only a risk factor but also a prognostic factor for uveal melanoma.

A 7-year-old girl with generalized erythematous, scaling plaques and vesiculobullous lesions on the extremities was diagnosed as having pemphigus foliaceus. Lesional direct immunofluorescence revealed intercellular IgG. IgA and C 3 deposition. The patient's serum gave positive reactions against one epitope of desmoglein 3 and the epitope of desmoglein 1 in enzyme-linked immunosorbent assays, but the blood sample for indirect immunofluorescence did not display any circulating antibodies. The patient was successfully treated systemically with prednisolone and dapsone. Currently, she is taking dapsone, 12.5 mg daily. She has been free of lesions for the last 3 years.

BACKGROUND: Neonatal blue light phototherapy (NBLP) has been widely and successfully used for the treatment of neonatal jaundice to reduce the plasma concentration of bilirubin and, hence, to prevent kernicterus. Only a few and controversial data are available in the literature as to how NBLP influences melanocytic nevus development. OBJECTIVE: Our goal was to conduct a twin study with the aim of better understanding the role of NBLP in melanocytic nevus development. We also investigated the roles of other environmental and constitutional factors in nevus formation. METHODS: Fifty-nine monozygotic and dizygotic twins were included in this cross-sectional study. One of the twin members received NBLP, and the other did not. A whole-body skin examination was performed to determine the density of melanocytic skin lesions. The prevalence of benign pigmented uveal lesions was evaluated during a detailed ophthalmologic examination. A standardized questionnaire was used to assess data relating to constitutional, sun-exposure, and other variables. To search for possible gene-environmental interactions involved in the appearance of pigmented lesions, the melanocortin 1 receptor variants and the I439V polymorphism of histidine ammonia-lyase genes were also determined in the enrolled twins. RESULTS: NBLP was associated with a significantly higher prevalence of both cutaneous and uveal melanocytic lesions. No association was found between the examined gene polymorphisms and the number of pigmented alterations in the examined study group. CONCLUSIONS: Our data suggest that NBLP could well be a risk factor for melanocytic nevus development. Phototherapy with blue-light lamps is a standard and essential therapeutic modality in neonatal care; therefore, additional in vivo and in vitro studies are necessary to establish its potential long-term adverse effects.

Background: In response to the demands of style and fashion, the number of decorative tattoos has been increasing worldwide. This has been paralleled by a rising incidence of melanocytic proliferations, including melanoma. The coincidence of various dermatological diseases and skin tumors with tattoos has been documented with some frequency, but reports of melanoma associated with tattoos are exceedingly rare. To date, only 13 cases have been documented in the English language literature. The possibility of an association between melanocytic proliferations and tattoos remains an area for further study. Observations: This report presents two cases of melanocytic nevi and one of melanoma occurring in association with a decorative tattoos. Conclusions: At present, the pathogenesis of melanoma developing in a tattoo is unknown. Mere coincidence cannot be ruled out. However, trauma, ultraviolet light exposure, a photoallergic effect, or an inflammatory reaction may promote malignant transformation. Clinicians and histopathologists should be aware of the clinical and pathological features if they are to make a correct diagnosis. Varga E, Korom I, Varga J, Kohan J, Kemeny L, Olah J. Melanoma and melanocytic nevi in decorative tattoos: three case reports.

Although tumors on the surface of the skin are considered to be easily recognizable, neglected advanced skin neoplasms are encountered even in the 21st century. There can be numerous causes of the delay in the diagnosis: fear of the diagnosis and the treatment, becoming accustomed to a slowly growing tumor, old age, a low social milieu, and an inadequate hygienic culture are among the factors leading some people not to seek medical advice. The treatment of such advanced neoplasms is usually challenging. The therapy of neglected cases demands an individual multidisciplinary approach and teamwork. Basal cell carcinoma (BCC), the most common cutaneous tumor, usually develops in the elderly, grows slowly, and has an extremely low metastatic potential; these factors are suggesting that BCCs might well be the “ideal candidates” for neglected tumors. Five neglected advanced cases of BCC were diagnosed in our dermatological institute between 2000 and 2009. The clinical characteristics and treatment modalities of these neoplasms are discussed, together with the possible causes of the neglect.

A melanoma malignumban szenvedő betegek száma évről évre emelkedik a világ számos országában, köztük hazánkban is. A betegség kialakulásában szerepet játszó konstitucionális és környezeti tényezők felismerése, ezáltal a fokozott rizikónak kitett személyek azonosítása a primer prevenció elengedhetetlen eszközei. Célkitűzés: Jelen vizsgálatunkban felmértük a különböző festéksejtes bőrelváltozások előfordulásának gyakoriságát serdülő és fiatal felnőtt korosztály körében. Módszerek: Felmérésünkben 1320, 14 és 18 év közötti középiskolai tanuló vett részt. A bőrgyógyászati szűrővizsgálat során a közönséges festéksejtes anyajegy, az atípusos anyajegy, a veleszületett anyajegy, a lentigo és a szeplő prevalenciáját határoztuk meg. A diákok körében szétosztott kérdőív segítségével arra kerestük a választ, hogy a pigmentált bőrelváltozások, illetve az egyes fenotípusos jellegek, napozási szokások, valamint a rosszindulatú festéksejtes daganatok, a nagyszámú anyajegy családban történő esetleges előfordulása között milyen összefüggés áll fenn. Eredmények: A diákok túlnyomó többsége rendelkezett közönséges festéksejtes anyajeggyel: 1–10 számú anyajegy 27%-nál, 10–100 számú anyajegy 67%-nál, míg nagyszámú, 100 feletti anyajegy 5,4%-nál fordult elő. A vizsgálatban részt vett egyének 24,3%-ánál fordult elő klinikailag atípusos anyajegy, a veleszületett anyajegyek gyakorisága 6,2% volt. A vizsgált faktorok közül a nem, a hajszín, a szemszín, a bőrtípus, a gyermekkori hólyagos napégés előfordulása, valamint a családban előforduló nagyszámú festéksejtes anyajegy statisztikailag szignifikáns kapcsolatot mutatott az egyes pigmentált bőrelváltozások előfordulásának gyakoriságával. Következtetések: A világirodalmi adatokhoz képest igen magas volt az atípusos anyajeggyel, illetve a nagyszámú közönséges anyajeggyel rendelkező fiatalok száma, ami már önmagában is egyértelműen jelzi a bőr rosszindulatú festéksejtes daganatának kialakulására való fokozott hajlamot az adott populáción belül. Eredményeink igazolják, hogy a melanoma megelőzését szolgáló felvilágosító programokkal már a fiatal korosztályokat érdemes megcélozni. Rendszeres egészségnevelő tevékenységgel és megfelelő szűrővizsgálatokkal, a magas kockázatú személyek kiemelésén és gondozásán keresztül a melanoma mortalitási arányának jelentős csökkenését érhetjük el.

To the Editor .— The number of individuals with large numbers of common and atypical melanocytic nevi has been continuously increasing in several white populations. Subjects with dysplastic nevi are at a substantially increased risk for the development of both uveal and cutaneous malignant melanoma.1,2 Numerous epidemiologic data have demonstrated that sunlight exposure is the major environmental factor involved in the development of melanoma, and it also exerts a considerable influence on the nevus count of an individual.3 Blue-light phototherapy …

Twenty adult individuals with chronic leg ulcers caused by venous insufficiency, and 5 patients with full-thickness burns were treated. Twenty of the patients (15 with leg ulcers and 5 with burns) were grafted with separated autologous keratinocytes. In these cases the cells were fixed to the wound bed by a fibrin net. Five other patients (with leg ulcers) were treated with fibrin without keratinocytes. In 16 of the 20 patients grafted with keratinocytes in a fibrin net, the defect healed completely in 14 to 21 days. On the other hand, the fibrin net without keratinocytes failed to significantly accelerate the process of reepithelialization. Our experience suggests that a rapid healing of full-thickness skin defects can be achieved through keratinocyte grafting.