Clinical and Dermoscopic Features of Lichenoid Keratosis: A Retrospective Case Study.

BACKGROUND: Lichenoid keratosis is a benign cutaneous lesion exhibiting many clinical faces and different dermoscopic features. OBJECTIVE: This study aims to determine the pattern of different clinical subtypes of lichenoid keratosis and to establish whether there is any correlation between the clinical variants of lichenoid keratosis and their dermoscopic appearance. METHODS: We retrospectively analyzed the medical records and clinical database of patients who had received a histological diagnosis of lichenoid keratosis. Based on the literature review and the clinical-dermoscopic features of lichenoid keratosis, we divided the lesions into 6 clinical subtypes to evaluate potential correlations between clinical and dermoscopic features in all subtypes. RESULTS: Fifty-one lesions were included in this clinical study. Preoperatively, only 1.9% of cases were clinically diagnosed as lichenoid keratosis, and the most common misdiagnosis was basal cell carcinoma (52.9%). We identified 6 subtypes of lichenoid keratosis and their corresponding dermoscopic features and clues. CONCLUSION: Since lichenoid keratosis has no pathognomonic dermoscopic clues and it is commonly misdiagnosed as malignant skin neoplasms, such as basal cell carcinoma and melanoma, improving the knowledge of both clinical and dermoscopic variability of lichenoid keratosis may help dermatologists to reduce unnecessary surgery and to reduce health care spending.

The Burden of Thin Melanomas in Tuscany, Italy, 1985-2017: Age- and Sex-Specific Temporal Trends in Incidence and Mortality.

A steady increase in the incidence and mortality burden correlated to thin melanomas (≤1 mm) has been reported in recent years in some international studies, but there is currently a paucity of data from the Mediterranean area. We aimed to describe the epidemiological characteristics of thin melanoma in Tuscany, Central Italy. A total of 6002 first cutaneous invasive melanomas occurring from 1985 to 2017 were selected for analysis; data were retrieved from the local population-based cancer registry. The standardized incidence rate was 15.0 per 100,000 in the population, higher among men than women (16.5 vs. 14.1). Incidence rates tended to increase over time across all age group-specific population strata, with annual percent changes moderately higher among men (+8.0%) than women (+6.9%), especially among the elderly. Among both sexes and in each age group, the trend toward increasing incidence rates was particularly strong for thin melanomas. Survival was better among women than men across all categories of thickness. Approximately 15% of deaths occurred among patients with thin lesions, with no major temporal changes in recent years. This study contributes to an improved understanding of melanoma epidemiology in Tuscany and underscores the need for primary prevention strategies tackling the growing burden of thin melanomas.

[Solar ultraviolet radiation risk in outdoor workers: a specific project of Tuscany Region (Italy)]. / Rischio da radiazione solare ultravioletta nei lavoratori outdoor: piano mirato della Regione Toscana.

OBJECTIVE: The aims of Tuscany Regional project were: to study the sun protection attitude of outdoor workers; to measure solar ultraviolet (UV) exposure in work environment; to describe the frequency of photoaging, precancerous lesions, and skin cancers in outdoor workers; to collect information on solar ultraviolet radiation exposure from incident cases of Non-Melanoma Skin Cancer (NMSC) recruited from Tuscany Cancer Registry. DESIGN: Outdoor workers completed a questionnaire devoted to collect information on sun protection attitudes during a typical summer working week. Environmental and personal measurements were carried out. Expert dermatologists examined outdoor workers to assess the frequency of photoaging, precancerous lesions, and skin cancer. A structured questionnaire was mailed to incident cases of NMSC. Information were collected on personal habits and working history, focusing on solar ultraviolet radiation exposure. SETTING AND PARTICIPANTS: Agriculture, construction, quarrying and fishing activities were considered: 292 employees responded to questions about the type of clothing used in the morning and in the afternoon,while working outdoors; 637 outdoor workers underwent skin examination. We contacted 743 cases of NMSC occurred in 2004; 498 subjects accepted to participate in this study. RESULTS: The clothing worn by surveyed subjects was often inadequate compared to the high level of exposure to UV. The skin examination of 637 outdoor workers highlighted 2 melanomas, 7 epitheliomas and 35 actinic keratoses. Among the 498 cases of NMSC, 135 (27%) were diagnosed in outdoor workers. Most represented economic activity sectors were: agriculture, construction, transport, sports. CONCLUSION: The characterization of outside workers revealed unsatisfactory sun protection behaviours. Moreover, previously undetected skin cancers were diagnosed. The study on MNSC confirms the complexity of studying the exposure to UV radiation. The Tuscany Regional project provided useful information on the risk of solar ultraviolet radiation in outdoor workers. Prevention programs are needed.

Protective Measures From Solar Ultraviolet Radiation for Beach Lifeguards in Tuscany (Italy): Shade and Clothing Strategies.

Background: The exposure to solar ultraviolet radiation is a significant risk factor generally underestimated by outdoor workers and employers. Several studies have pointed out that occupational solar exposure increased eye and skin diseases with a considerable impact on the lives and productivity of affected workers.The main purpose of this study was to evaluate the effectiveness against ultraviolet radiation of some measures recently undertaken for the protection of lifeguards in a coastal area of Tuscany. Methods: Different shading structures (gazebos and beach umbrella) were tested during a sunny summer's day on a sandy beach by means of two radiometers; the UV protection offered by some T-shirts used by lifeguards was also tested in the laboratory with a spectrophotometer. Results: The analysed shading structures strongly reduced the ultraviolet radiation by up to 90%, however a not always negligible diffuse radiation is also present in the shade, requiring further protective measures (T-shirt, sunglasses, sunscreen, etc.); the tested T-shirts showed a very good-excellent protection according to the Australian/New Zealand standard. Conclusion: Results obtained in this study suggest how the adoption and dissemination of good practices, including those tested, could be particularly effective as a primary prevention for lifeguards who are subjected to very high levels of radiation for long periods.

Correction to: Thick melanoma in Tuscany.

This corrects the article DOI: 10.23736/S0392-0488.17.05584-5.

Factors Affecting Sentinel Node Metastasis in Thin (T1) Cutaneous Melanomas: Development and External Validation of a Predictive Nomogram.

PURPOSE: Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB. PATIENTS AND METHODS: The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram. RESULTS: Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines. CONCLUSION: We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB.

Thick melanoma in Tuscany.

BACKGROUND: The epidemiologic trends of cutaneous melanoma are similar in several countries with a Western-type lifestyle, where there is a progressively increasing incidence and a low but not decreasing mortality - even increasing in selected cases, especially in the older age groups. Also in Tuscany there is a steady rise in the incidence with prevalence of in situ and invasive thin melanomas, with also an increase of thick melanomas. It is necessary to reduce the frequency of thick melanomas to reduce specific mortality. The objective of the current survey has been to compare, in the Tuscany population, by a case-case study, thin and thick melanoma cases, trying to find out those personal and tumor characteristics which may help to customize preventive interventions. METHODS: The study included nine centers involved in the melanoma diagnosis. A consecutive series of incident invasive melanomas diagnosed in a period of about 18 months (July 2010 to December 2011) was collected and matched according in a ratio of one thick melanoma (cutoff thickness: 1 mm) every two thin melanomas. The investigators filled in a questionnaire on patients' self-reported sun exposure, way of melanoma detection, awareness and performance of self-skin examination, as well as propensity to prevention in general. RESULTS: The results of this survey confirm that older age and the lower education level are associated with a later detection. The habit of performing skin self-examination is crucial in the early diagnosis of thick melanoma. The results of this survey seem to suggest that population aged over 50 years, with few total and few atypical nevi, and limited sun exposure and burning are at higher risk of late diagnosis. It can be assumed that part of the population is not effectively reached by prevention campaigns because they do not recognize themselves as being at risk for skin cancers. CONCLUSIONS: In order to achieve a higher rate of early diagnosis of skin melanoma, a new strategy must be implemented. It could be useful to rethink educational campaigns - which seem to unintentionally leave out subjects more at risk for melanoma - and to renew the active involvement of the general practitioners.

The use of commercially available personal UV-meters does cause less safe tanning habits: a randomized-controlled trial.

UV Index information is currently recommended as a vehicle to raise public awareness about the risk of sun-exposure. It remains unknown to what extent this information can change personal sun-protective behavior. The aim of the study was to analyze the effects of UV-Index (UV-I) information provided by low cost, commercially available UV-I sensors on major indicators of sun-tanning behavior. A randomized-controlled trial was carried out on 94 healthy volunteers aged 21-23 years. After the exclusion of subjects with photosensitive disorders (n=3), 91 subjects were randomized in two arms after stratification based on phototype and sex. Both arms received a diary to be filled every day with a log of intentional sun-exposure during summer. Subjects in the intervention group also received a commercially available UV-I sensor. The UV-I sensors were switched on and the UV-value was recorded in 77% of days with sun-exposure. During days of sun-exposure, subjects randomized to the intervention group had longer average time of sun-exposure (227.7 vs 208.7 min per day, P=0.003), also between noon and 4 pm (P<0.001), and less frequently adopted sun protective measures than controls (hat [6.4%vs 10.2%, P=0.007], sunglasses [23.9%vs 30.8%, P=0.003], sunscreen [41.4%vs 47.2%, P=0.02]) and they experienced more frequent sunburns (27.8%vs 21.5%, P=0.004). The odd ratio of sunburns was 1.60 for subjects in the intervention group compared with controls (after adjustment for sex, sunscreen use and skin type). The mean UV-I value recorded by volunteers was lower (5.6 [SD+/-0.9]) than that (7.3 [SD+/-0.46]) recorded by a professional instrument in the same period at the same latitude. Poststudy laboratory tests showed that the sensor was able to detect only about 60% of the solar diffuse radiation. The use of UV-I sensors changed the sun protective behavior of sunbathers in the direction of less use of sun protective measures. One possible explanation is that the low cost UV-meters may have functioned incorrectly and under-reported UV exposure. This may have led to an underestimation of UV-I values, erroneously reassuring subjects and causing a less protective sunbathing behavior. Another hypothesis relies on a cognitive pitfall in the subjects' dealing with intermediate UV-I values, as they may have been discouraged in the use of sunscreen as they did not feel that they had yet been exposed to very harmful UV radiation.

The p.G23S CDKN2A founder mutation in high-risk melanoma families from Central Italy.

We have investigated the frequency and spectrum of CDKN2A/CDK4 mutations in 23 cutaneous melanoma families from Central Italy (Tuscany). Three distinct mutations were identified in five families. One mutation, p.G23S, was present in three families. Several lines of evidence indicate that p.G23S is a pathogenic mutation: it is located in the functionally important first ankyrinic domain of p16, it was not detected in a sample of 100 control individuals, and it was present in all tested affected individuals from the three families. Haplotype analysis showed a common ancestral origin of the p.G23S mutation. Our data show that the p.G23S mutation is an important cause of hereditary melanoma in Tuscany.

Targeting subjects at high-risk of melanoma.

The current strategies for early diagnosis result at the moment insufficient to make further progresses in the fight against the melanoma. Reaching people not reached by screening activity yet is necessary for reducing mortality from this tumor. The well-known risk factors are still effective, but they have to be implemented by other variables at risk, like sex and age. People aged over 50 years old should be considered at risk, independently from other features. Renewed messages should be addressed to population and general practitioners. In this paper the old and new evidences on main risk factors will be analyzed and supported by the evidences of the literature.

Baseline factors influencing decisions on digital follow-up of melanocytic lesions in daily practice: an Italian multicenter survey.

BACKGROUND: Guidelines for optimized use of digital follow-up of melanocytic lesions are not yet available, and little is known about inclusion criteria adopted in clinical practice. OBJECTIVE: Our purpose was to describe the frequency of digital follow-up adoption in melanoma screening, the characteristics of patients and lesions selected, and the predictors of duration of the intervals of digital follow-up. METHODS: Baseline characteristics of patients and lesions selected for digital follow-up in 12 Italian pigmented lesion clinics were examined. Predictors of a short follow-up interval (4.75) was associated only with a marginal effect on the scheduled duration of follow-up interval (OR 1.34, 95% CI 0.97-1.86). These findings were confirmed by a multivariate analysis. LIMITATIONS: The adoption of different digital dermoscopy systems in the participating centers may have limited the reliability of the TDS assigned by a central group to dermoscopy images. CONCLUSIONS: Practicing dermatologists who use digital epiluminescence microscopy in screening for melanoma decided to submit at least one melanocytic lesion to digital follow-up for approximately 1 patient for every 5 examined. This implies costs and time spent that need to be evaluated together with the benefits of this procedure from a large-scale perspective. The lack of well-defined guidelines for inclusion and exclusion criteria may hamper optimized use of digital follow-up in daily practice.

Melanoma survival: sex does matter, but we do not know how.

The objective of this study was to provide further insights into the prognostic role of female sex in skin melanoma. The prognostic effect of sex in a population-based case series of 3900 skin melanomas in central Italy has been evaluated considering the possible confounding role of many demographic and clinical variables (age, period of diagnosis, Breslow's thickness, Clark level, ulceration, lymph node status, metastasis, histological type, skin site, and pathological T and N). Multiple imputations, according to chained equations, have been used for imputing incomplete values. A Cox proportional hazards model on the risk of death caused by melanoma was fitted. Univariate and multivariate effects of sex and of other variables were computed. The 5-year cause-specific survival was 87% (95% confidence interval: 86-89%) for women and 80% (78-82%) for men. Women had higher rates at any time since diagnosis. After adjustment for other confounders, women had a 34% reduced risk compared with men of dying from skin melanoma (hazard ratio=0.66, 95% confidence interval: 0.56-0.79). The present study confirmed a strong protective effect of female sex on skin melanoma mortality. The protective factor is still unknown.

Spatial analysis of incidence of cutaneous melanoma in the Friuli Venezia Giulia region in the period 1995-2005.

Incidence distribution of cutaneous melanoma depends on phenotypic characteristics of population and geographic location. In Italy, in the period 1999-2003 Friuli Venezia Giulia (FVG) region had the second highest incidence rates for males and the third for females. We analysed melanoma and lip cancer incidence data of the FVG cancer registry for the period 1995-2005. We used Bayesian hierarchical spatial models to describe the spatial pattern by gender. We decomposed the geographical distribution of the risk in two parts: a component linked to chronic exposure and a component related to intermittent exposure. In order to model the chronic component we considered the geographical distribution of incidence cases of lip cancer, for which chronic occupational solar radiation exposure is a documented risk factor. We also analysed the distribution by site and we calculated standardised rates for body surface area. This study documents a significant gradient in the incidence of cutaneous melanoma in FVG. High-standardized incidence rates are present in the area of Trieste and in the coastal area. The descriptive analysis by age group and by site, showed risks associated with intermittent exposures in both genders. For the coastal area the risk is especially high for sites traditionally linked to high cumulative exposures (face and neck), especially among men. The results suggest diagnostic preventive interventions in the populations living in the area of Trieste, given the high rates observed in the young age groups.

Melanoma density and relationship with the distribution of melanocytic naevi in an Italian population: a GIPMe study--the Italian multidisciplinary group on melanoma.

The most frequent site for melanoma is the back in men and the lower limbs in women, where intermittent sun exposure has been reported to be an environmental agent, although studies on age-specific incidence have suggested that melanoma in chronically sun-exposed areas, such as the face, increases with age. To identify the preferential development of melanoma in chronically or intermittently sun-exposed areas and the relationship between body site distribution and parameters such as sex, age, distribution of melanocytic naevi, atypical naevi and actinic keratoses, a prospective epidemiological multicentre study was carried out on all the consecutive melanoma cases diagnosed in a 2-year period from 27 Italian GIPMe centres (GIPMe: the Italian Multidisciplinary Group on Melanoma). Both the relative density of melanoma (RDM), defined as the ratio between observed and expected melanoma for a specific body site, and the average nevi density were identified. The most common melanoma site was the back, a factor that was not affected by either age or sex, even if men had higher density values. Statistically significant higher RDM values were observed in women aged more than 50 years for leg lesions and in the anterior thighs for young women (<50 years), whereas the lowest values were observed in the posterior thighs in women of any age. Facial RDM was statistically significantly higher than expected in both male and female patients more than 50 years of age. Melanoma was associated with a significantly higher atypical naevi density only for the back, chest and thighs. Indeed, facial melanoma was related to the presence of more than four actinic keratoses and not naevi density. To the best of our knowledge, the RDM method was applied for the first time together with naevus density calculation to obtain these data, which strongly substantiate the 'divergent pathway' hypothesis for the development of melanoma, but not find a direct correlation between melanoma and nevi for each anatomical site.

The problem of false-positive diagnosis in melanoma screening: the impact of dermoscopy.

The predictive value of melanoma diagnosis made by visual examination during pigmented lesion screening is low. This creates the problem of false-positive diagnoses, which lead to unnecessary treatment and scarring. The purpose of this study was to evaluate the impact of dermoscopy (epiluminescence microscopy, dermatoscopy) on the false-positive rate in the routine melanoma screening activity of a pigmented lesion clinic (PLC). In a series of 133 subjects consecutively referred to the PLC, lesions defined as suspicious or equivocal on visual examination were examined by dermoscopy. Only lesions also defined as suspicious on dermoscopy were excised; other lesions were observed at follow-up examinations. Among the 2542 pigmented lesions observed, clinical examination led to identification of 43 suspicious lesions, 13 of which were also suspicious on dermoscopy and were subsequently excised. Histopathological examination revealed three malignant melanomas. Compared with visual examination alone, the addition of dermoscopy to the subgroup of clinically equivocal lesions resulted in an increase in specificity from 98.4% to 99.6% and in positive predictive value from 6.9% to 23%. The specificity of the visit outcome 'subject to be referred for surgical excision' increased from 69.2% to 92.3%. No false-negative melanoma diagnoses on dermoscopy were observed during a follow-up period of 4 years. The addition of dermoscopy to routine PLC activity as a second-level examination led to a reduction in the number of false-positive diagnoses, thus producing an overall increase in the specificity and positive predictive value of melanoma diagnosis.

Results of surveillance programme aimed at early diagnosis of cutaneous melanoma in high risk Mediterranean subjects.

OBJECTIVE: To investigate the impact of a surveillance program aimed at early diagnosis of melanoma in a cohort of subjects classified at risk on the basis of their number of nevi. To compare the number of observed cases of melanoma in the cohort to that expected number in the general population of the same area. METHODS: Two hundred and eighteen subjects with no personal or family history of melanoma residing in the Florence district who showed more than 30 common acquired nevi and 3 or more atypical nevi (high-risk) have been followed for an average period of 3.4 years (range 1-6.5); an additional intermediate-risk group with 237 subjects was also enrolled. RESULTS: Four incident melanomas were detected in 218 high-risk subjects followed for a total of 741.7 person-years; no melanoma was detected in the lower risk group. All the 4 detected melanomas were in situ (Clark level I), with an average interval since enrollment of 4.6 years (range 1.4-6.5). In accordance with age-and sex-specific incidence rates of melanoma (including in situ forms) in the general population of the area, the standardized incidence ratio (SIR) in the cohort was 44.1 (95% CI 16.5-117.5). CONCLUSIONS: Subjects with more than 30 common nevi and 3 or more atypical nevi show about a 40-fold increased risk of developing melanoma. Even allowing for some degree of diagnostic anticipation due to periodic controls the risk appears higher than in the intermediate risk population. As a consequence of active follow up of individuals, all the detected tumors were at favourable prognosis. Periodic examination of these subjects should therefore be recommended as part of a prevention program for cutaneous melanoma in southern European populations.

Relationship between Latitude and Melanoma in Italy.

Objective. Evaluate the ecological relationship between skin melanoma epidemiology and latitude in Italy. Methods. We used data from the Italian network of cancer registries (Airtum). In a Poisson model, we evaluated the effect on incidence, mortality, and survival of latitude, adjusting for some demographic, social, phenotypic, and behavioural variables. Results. Incidence increased in Italy by 17% for each degree of increase in latitude. The effect of latitude was statistically significantly present also adjusting for other variables (incidence rate ratio = 1.08). The effect of latitude on increasing mortality (mortality rate ratio = 1.27) and improving survival (relative excess risk of death = 0.93) was no longer present in the multivariate model. Conclusion. Melanoma incidence, mortality, and survival vary in Italy according to latitude. After adjustment for several confounders, incidence still grows with growing latitude. Presumably, latitude expresses other variables that might be related to individual susceptibility and/or local care.