A review of nevus-associated melanoma: What is the evidence?

Cutaneous melanoma may have an adjacent nevus remnant on histological examination in 30% of cases (nevus-associated melanoma, NAM), while it may appear de novo, without a precursor lesion, in the remaining 70% of cases. Nevus-associated melanoma and the concept of acquired melanocytic nevi serving as precursors of melanoma has long been considered as a controversial topic. This controversy is, in part, due to their overall low rate of transformation to melanoma and scarce data on the natural history of progression. Another matter of debate regarded the possibility that the reported differences in NAM vs. de novo melanoma were due to an underestimation of NAM in thicker lesions due to obliteration of the nevus component by the tumour. During the last few years, several evidence has accumulated in order to address these controversies. In this review, we present a comprehensive synthesis of the epidemiological, clinical, dermoscopic and genetic findings in NAM, including thin NAM, compared to de novo melanoma. Answering the questions on nevus-associated melanoma may provide further insight into the classification of these tumours and disentangle their biology and route of development from that of de novo melanoma.

Not all melanomas are created equal: a review and call for more research into nodular melanoma.

Among the histogenic subtypes of melanoma, nodular melanoma (NM) is the major contributor for thicker and fatal melanomas and it has been associated with melanoma-specific death in thin tumours, highlighting an important subgroup of 'aggressive thin' melanomas. This review provides a synthesis of the distinct characteristics of NM, with respect to epidemiology and risk factors, clinical presentation, histopathology, molecular and dermoscopic aspects, and screening practices. The real challenges are to find better biomarkers of aggressiveness and to know whether the control of such aggressive melanomas can be influenced by targeted interventions such as early detection, drug interventions and preventive strategies.

A multicentre study of naevus-associated melanoma vs. de novo melanoma, tumour thickness and body site differences.

BACKGROUND: Whether melanoma in histological contiguity with a naevus [naevus-associated melanoma (NAM)] is distinctly different from melanoma arising de novo remains unclear. OBJECTIVES: To determine whether the characteristics of de novo melanoma differ from NAM and are not due to naevus obliteration in thicker tumours. METHODS: We conducted a multicentre retrospective study of de novo melanoma and NAM in seven referral centres in Europe, Australia and the USA between 2006 and 2015. RESULTS: In a total of 9474 localized melanomas, de novo melanoma was associated with thicker tumours and body site differences compared with NAM. In the subset of T1 melanomas (n = 5307), similar body site differences were found in multivariate analysis by body site. When compared with NAM, de novo melanoma was more likely to affect older individuals (≥ 70 years) when located on the head/neck [odds ratio (OR) 4·65, 95% confidence interval (CI) 2·55-8·46], the trunk (OR 1·82, 95% CI 1·40-2·36) or the upper extremity (OR 1·69, 95% CI 1·14-2·50), was more likely to affect female patients when located on the lower extremities (OR 1·36, 95% CI 1·03-1·80), and was more likely to be of the nodular melanoma subtype (OR 2·23, 95% CI 1·14-4·35) when located on the trunk. De novo melanoma was less likely to have regression present compared with NAM. CONCLUSIONS: Clinicopathological and body site differences between de novo melanoma and NAM support the divergent pathway model of development. These differences were also found in thin melanomas, suggesting that de novo melanomas are different from NAM and their differences are not due to the obliteration of naevus remnants in thicker tumours.

Interval cancers after skin cancer screening: incidence, tumour characteristics and risk factors for cutaneous melanoma.

BACKGROUND: The rate of interval cancers is an established indicator for the performance of a cancer-screening programme. METHODS: We examined the incidence, tumour characteristics and risk factors of melanoma interval cancers that occurred in participants of the SCREEN project, which was carried out 2003/2004 in Schleswig-Holstein, Germany. Data from 350 306 SCREEN participants, who had been screened negative for melanoma, were linked to data of the state cancer registry. Melanoma interval cancers were defined as melanomas diagnosed within 4-24 months after SCREEN examination. Results were compared with melanomas of the pre-SCREEN era (1999-2002), extracted from the cancer registry. RESULTS: The overall relative incidence of melanoma interval cancers in terms of observed/expected ratio was 0.93 (95% CI: 0.82-1.05; in situ: 1.61 (1.32-1.95), invasive: 0.71 (0.60-0.84)). Compared with melanomas of the pre-SCREEN era, the interval melanomas were thinner and had a slightly greater proportion of lentigo maligna melanomas whereas nodular melanomas were less frequent. INTERPRETATION: The results indicate a moderate performance of the SCREEN intervention with an excess of in situ melanomas. In part, the findings might be due to specifics of the SCREEN project, in particular a short-term follow-up of patients at high risk for melanoma.

The impact of dermoscopy on melanoma detection in the practice of dermatologists in Europe: results of a pan-European survey.

BACKGROUND: Dermoscopy is a widely used technique that can increase the sensitivity and specificity of melanoma detection. Information is lacking on the impact of dermoscopy use on the detection of melanoma in the real-life practice of European dermatologists. OBJECTIVE: To identify factors that influence the benefit of using dermoscopy for increasing melanoma detection and lowering the number of unnecessary biopsies in the practice of European dermatologists. METHODS: We conducted a survey of dermatologists registered in 32 European countries regarding the following: the demographic and practice characteristics, dermoscopy training and use, opinions on dermoscopy and the self-estimated impact of dermoscopy use on the number of melanomas detected and the number of unnecessary biopsies performed in practice. RESULTS: Valid answers were collected for 7480 respondents, of which 6602 reported using dermoscopy. Eighty-six per cent of dermoscopy users reported that dermoscopy increased the numbers of melanomas they detected, and 70% reported that dermoscopy decreased the number of unnecessary biopsies of benign lesions they performed. The dermatologists reporting these benefits were more likely to have received dermoscopy training during residency, to use dermoscopy frequently and intensively, and to use digital dermoscopy systems and pattern analysis compared to dermatologists who did not perceive any benefit of dermoscopy for the melanoma recognition in their practice. CONCLUSIONS: Improving dermoscopy training, especially during residency and increasing access to digital dermoscopy equipment are important paths to enhance the benefit of dermoscopy for melanoma detection in the practice of European dermatologists.

Factors driving the use of dermoscopy in Europe: a pan-European survey.

BACKGROUND: When used correctly, dermoscopy is an essential tool for helping clinicians in the diagnosis of skin diseases and the early detection of skin cancers. Despite its proven benefits, there is a lack of data about how European dermatologists use dermoscopy in everyday practice. OBJECTIVES: To identify the motivations, obstacles and modifiable factors influencing the use of dermoscopy in daily dermatology practice across Europe. METHODS: All registered dermatologists in 32 European countries were invited to complete an online survey of 20 questions regarding demographic and practice characteristics, dermoscopy training and self-confidence in dermoscopic skills, patterns of dermoscopy use, reasons for not using dermoscopy and attitudes relating to dermoscopy utility. RESULTS: We collected 7480 valid answers, of which 89% reported use of dermoscopy. The main reasons for not using dermoscopy were lack of equipment (58% of nonusers) and lack of training (42%). Dermoscopy training during residency was reported by 41% of dermoscopy users and by 12% of nonusers (P < 0·001). Dermatologists working in public hospitals were the least likely to use dermoscopy. High use of dermoscopy across the spectrum of skin diseases was reported by 62% of dermoscopy users and was associated with dermoscopy training during residency, the use of polarized light and digital dermoscopy devices, longer dermoscopy practice, younger age and female gender. CONCLUSIONS: Expanding access to dermoscopy equipment, especially in public healthcare facilities and establishing dermoscopy training during dermatology residency would further enhance the substantially high dermoscopy use across European countries.

Cross-sectional analysis of the dermoscopic patterns and structures of melanocytic naevi on the back and legs of adolescents.

BACKGROUND: Junctional (flat) naevi predominate on the extremities, whereas dermal (raised) naevi are found primarily on the head, neck and trunk. Few studies have investigated the anatomical site prevalence of melanocytic naevi categorized using dermoscopy. OBJECTIVES: To identify the prevalence of dermoscopic patterns and structures of naevi from the back and legs of adolescents. METHODS: Dermoscopic images of acquired melanocytic naevi were obtained from the back and legs of students from a population-based cohort in Framingham, Massachusetts. Naevi were classified into reticular, globular, homogeneous or complex dermoscopic patterns. Multinomial logistic regression modelling assessed the associations between dermoscopic pattern and anatomical location. RESULTS: In total 509 participants (mean age 14 years) contributed 2320 back naevi and 637 leg naevi. Compared with homogeneous naevi, globular and complex naevi were more commonly observed on the back than the legs [odds ratio (OR) 29·39, 95% confidence interval (CI) 9·53-90·65, P < 0·001 and OR 6·8, 95% CI 2·7-17·14, P < 0·001, respectively], whereas reticular lesions were less likely to be observed on the back than on the legs (OR 0·67, 95% CI 0·54-0·84, P = 0·001). Naevi containing any globules were more prevalent on the back than on the legs (25% vs. 3·6%, P < 0·001). Naevi containing any network were more prevalent on the legs than on the back (56% vs. 40·6%, P < 0·001). CONCLUSIONS: These findings add to a robust body of literature suggesting that dermoscopically defined globular and reticular naevi represent biologically distinct naevus subsets that differ in histopathological growth pattern, age- and anatomical-site-related prevalence, molecular phenotype and aetiological pathways.

Melanoma prognosis in Europe: far from equal.

BACKGROUND: Comprehensive, population-based analysis of melanoma survival throughout Europe is hindered by the uneven coverage and quality of European cancer registries, and by logistical and financial shortcomings. Mortality-to-incidence ratios (MIRs) have been used as a proxy for estimating survival for multiple cancers and to model melanoma prognosis, higher MIR values reflecting poorer prognosis. Updated and improved pan-European estimates of mortality and incidence rates for melanoma have become available through the International Agency for Research of Cancer project Globocan 2008, showing marked differences among European countries. OBJECTIVES: To analyse MIRs for melanoma across Europe and their relationship with national health expenditures, aiming to identify countries and regions with disproportionately poor prognosis. METHODS: Estimated age-standardized rates of melanoma incidence and mortality provided by Globocan 2008 were used to calculate the MIR for each European country and region. Total health expenditures per capita in European countries for 2008 were provided by the World Health Organization/Global Health Observatory. The potential correlation between MIR and total health expenditure per capita was analysed through Pearson's correlation. RESULTS: Mortality-to-incidence ratios for melanoma ranged between 0·09 in Switzerland and 0·44 in Latvia. The regional average MIR was the highest in Central and Eastern Europe at 0·35; the lowest was in Western Europe, at 0·13. We found a strong inverse correlation between the individual nation's total health expenditure per capita and the calculated melanoma MIR (r = -0·76, P < 0·05). CONCLUSIONS: While further improvement of melanoma registration is necessary, our findings reveal sharp disparities in the prognosis of melanoma across the Continent, correlated with significant differences in health care expenditures.

Demographic, behavioural and physician-related determinants of early melanoma detection in a low-incidence population.

BACKGROUND: Knowledge of the factors that influence early detection of melanoma is important in developing strategies to reduce associated mortality. OBJECTIVES: To identify sociodemographic, behavioural and medical care-related factors associated with melanoma thickness in a low-incidence population but with a high case fatality. PATIENTS AND METHODS: In a multicentre, retrospective, survey-based study of 202 patients with a recent diagnosis of invasive melanoma (< 1 year), we collected data on demographic and behavioural factors, attitudes towards prevention, access to medical care, frequency of skin self-examination (SSE) and physician skin examination (PSE) in relation to melanoma thickness. RESULTS: Thinner tumours (≤ 1 mm, 80 melanomas) were associated with female sex (P ≤ 0.049), nonnodular (superficial spreading melanoma, lentigo maligna melanoma, acral lentiginous melanoma) histological subtypes (P < 0.001), absence of ulceration (P ≤ 0.001), and location other than lower extremity or trunk location (P ≤ 0.004). Patients married at the time of diagnosis or who performed SSE during the year prior to diagnosis were more likely to have thinner tumours than those who did not [odds ratio (OR) 3.45, 95% confidence interval (CI) 1.48-8.04 and OR 2.43, 95% CI 1.10-5.34, respectively]. Full-body skin examination by a physician was not significantly associated with thinner melanoma (OR 1.99, 95% CI 0.66-6.07). CONCLUSIONS: SSE was shown to be an important factor in the detection of thin melanoma, in contrast to partial or full-body PSE, which did not show any statistically significant effect on tumour thickness.

Skin cancer screening participation and impact on melanoma incidence in Germany--an observational study on incidence trends in regions with and without population-based screening.

BACKGROUND: The SCREEN (Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany) project involved population-wide skin cancer screening with whole-body examination by general physicians and dermatologists. It was conducted in the German state of Schleswig-Holstein (July 2003-June 2004), but not in the German state of Saarland. METHODS: The population-based registries of Schleswig-Holstein and Saarland provided data on melanoma incidence before, during, and after SCREEN to assess the association of skin cancer screening with incidence. RESULTS: Approximately 19% of the Schleswig-Holstein population participated in SCREEN (women: 27%, men: 10%). A total of 52% of all melanomas diagnosed during SCREEN in Schleswig-Holstein were detected as part of the project. Melanoma incidence increased during SCREEN (invasive melanoma in women: +8.9 per 100,000 (95% confidence intervals (CI): 6.1; 11.7); men: +4.0 per 100,000 (95% CI: 1.6; 6.4)) and decreased afterwards (women: -10.6 per 100,000 (95% CI: -13.3; -7.9); men: -4.1 per 100,000 (95% CI: -6.5; -1.7)). Similar changes were not observed in Saarland that had no such project. The differences between the two states were greatest among women, the group with the greater SCREEN participation. CONCLUSION: The SCREEN project had a substantial impact on melanoma incidence. This is consistent with the impact of effective screening for other cancers.

Melanoma incidence and mortality in Europe: new estimates, persistent disparities.

BACKGROUND: Melanoma incidence and mortality in Europe are high but there are significant gaps in the epidemiological information available across the continent. OBJECTIVES: With the aim of enhancing the planning of educational programmes for reducing the melanoma burden in Europe, we analysed the most recent incidence and mortality data for Europe with a new focus on the regional disparities of melanoma reporting. METHODS: GLOBOCAN 2008, the standard set of worldwide estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer for 2008, was used to provide the estimated age-standardized rates (world standard population) of melanoma incidence and mortality in European countries and regions. RESULTS: The estimated age-standardized incidence of melanoma (measured per 100 000 person-years) varies widely from 19·2 in Switzerland to 2·2 in Greece. The incidence rate of 4·3 of Central and Eastern Europe (CEE) is less than half of that of Western Europe. Melanoma mortality rates of 1·5 are similar in CEE and Western Europe, although rates vary with a high of 3·2 in Norway and a low of 0·9 in Greece. Over 20 000 deaths from melanoma were estimated in Europe in 2008, with CEE having the largest share (35·5%) among the four geographical European regions. Population-based data are lacking for significant parts of CEE, which must rely on estimates. CONCLUSIONS: The most recent estimates of melanoma incidence and mortality in Europe reveal sharp differences between European countries, possibly related to missed opportunities for early diagnosis and incomplete reporting of melanoma in Eastern Europe.

Do pediatricians counsel families about sun protection?: a Massachusetts survey.

BACKGROUND: Pediatric visits during summer months may be especially opportune times for sun protection counseling for children and their parents. Few data exist on the extent of such counseling. OBJECTIVE: To begin to assess this, we surveyed practicing Massachusetts pediatricians to examine current attitudes and practices of sun protection counseling. DESIGN AND SETTING: Surveys mailed to Massachusetts pediatricians. RESULTS: We received surveys from 756 (60%) of 1263 eligible Massachusetts pediatricians. Almost 70% indicated that they recommended safe sun practices to more than 50% of their patients and their parents during the summer months. Counseling regarding seat belt use, bicycle helmet use, and smoking prevention were ranked higher in priority than sun protection counseling by pediatricians; nutritional guidelines were noted by pediatricians to be a parent's most frequent concern. Four variables were independently associated with a practitioner's providing safe sun recommendations to more than 50% of parents and children: (1) private setting and health maintenance organization practitioners as opposed to academic physicians, (2) high ranking of patients' safe sun knowledge, (3) high priorities of both parents and physicians for sun protection counseling and parental knowledge of safe sun practices relative to other recommendations, and (4) pediatrician interest in receiving instructional materials. CONCLUSIONS: For the most part, summer sun protection counseling among Massachusetts pediatricians seems well integrated into standard practice. Most pediatricians rated their confidence level as high for discussing sun protection and only a few cited inadequate training or poor reimbursement as barriers toward improved counseling. Small steps, such as providing more instructional materials to patients and using office-based reminder systems, may improve the quality of sun protection counseling practices. Incorporating sunburn prevention into the list of routinely recommended injury prevention guidelines for pediatricians should be considered.

Public health interventions for melanoma. Prevention, early detection, and education.

Worldwide melanoma control programs that include some combination of primary prevention, education, and screening activities have only recently begun to undergo an evaluation process. More studies with rigorous design and evaluation are needed. Until then, the proper public health policy guidelines for melanoma control, especially screening, are open to debate. Future studies must determine how screening, early detection, case finding, and education can best be used to reduce mortality and achieve optimal melanoma control.

Use of health services before diagnosis of head and neck cancer among Boston residents.

One hundred thirty incident cases of head and neck cancer in Boston between September 1, 1985, and March 31, 1988, provided interview or medical record review data on the use of health services in the 24 months preceding the diagnosis of cancer. One hundred twenty-four subjects were able to recall whether and how often they visited health care sites in this period, reporting a median number of 10.5 visits; 94% recalled at least one visit. Eighty-nine medical record reviews indicated a median of seven visits. For the most part, these visits were to providers whom subjects considered their regular source of care--sources that provided care in a broad range of locations. These data support a strategy of integrating screening for head and neck cancers into existing health care services.

Factors associated with smoking among children and adolescents in Connecticut.

INTRODUCTION: The age of smoking initiation has dropped over the past four decades. Since behaviors and attitudes adopted in late childhood or early adolescence predict future smoking, it is important to understand the smoking and other risk-taking behaviors and attitudes of children aged 12 and younger. The goal of the analyses presented here was to describe behavioral and attitudinal factors associated with smoking among elementary school (grades 4-6), middle school (grade 7-8), and high school (grades 9-12) students in Connecticut. METHODS: We have used data from 8 years (1988-1996) of an anonymous, self-administered health risk appraisal survey given to children and adolescents in self-selected public and private schools. We compared the proportion of smokers and nonsmokers who reported various behaviors and attitudes and compared them with the chi-square test. RESULTS: Fifteen percent (n = 4,884) of the total population (n = 31, 861) were current smokers. At all grade levels, current smokers were more likely than nonsmokers to engage in risk-taking behaviors, and to report more stress and depression. Indicators of risk-taking and stress were also associated with the intent to smoke among children in grades 4-6. CONCLUSIONS: Smoking occurs within the context of other risk-taking behavior and psychological distress, among both children and older adolescents. Our data provide support for the idea of early identification and targeting of children at high risk of smoking in elementary school, possibly as early as grade four.

Melanoma control in the United States: current status.

Screening and education for melanoma/skin cancer are receiving increasing worldwide attention. In an attempt to improve melanoma control in the United States, where incidence and mortality rates continue to increase, the American Academy of Dermatology (AAD) has provided free skin cancer screenings to more than 600,000 Americans and prevention messages to millions more. This chapter reviews and summarizes ongoing melanoma control activities in the United States, including prevention, education, and early detection/screening. We also address outcome measures in melanoma control and suggest that the unique external and visible nature of skin cancer blurs the distinction between screening and education. Measuring and evaluating the benefits of international melanoma control activities presents many challenging tasks. Future collaborative work must include complementary strategies in melanoma/skin cancer prevention, education, and screening to combat the worldwide increase in melanoma incidence and mortality.