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.

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.

Correction to: Thick melanoma in Tuscany.

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

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.

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.

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.

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.

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.

The thickness of melanomas has decreased in central Italy, but only for thin melanomas, while thick melanomas are as thick as in the past.

The objective of this study was to evaluate the time trend of melanoma thickness in a population-based case series. All invasive (n=2862) and in-situ (n=605) cutaneous melanoma incident cases diagnosed in 1985-2004 were retrieved from the Tuscany Cancer Registry, central Italy. Standardized (European population) incidence rates were computed for four periods: 1985-1989, 1990-1994, 1995-1999, 2000-2004, and for Breslow thickness classes (< or =1, 1.01-2.00, >2 mm). The annual percent change (APC) of the standardized rates was computed. Thickness was evaluated on the basis of sex, age, morphology type, site and period of time. Median thickness was evaluated by means of a nonparametric K-sample test. The incidence rate of melanoma rose significantly for both invasive (APC=+5.1%) and in-situ lesions (APC=+11.1). The sex distribution of patients with invasive melanoma did not change over time (mean male/female ratio 0.95). The mean age at diagnosis did not change (57.2 years; SD=17.2 years). From 1985-1989 to 2000-2004 the median value of thickness decreased from 1.68 to 0.8 mm (P<0.001). Within the Breslow categories the median value of thickness decreased significantly for thin melanomas (< or =1 mm) but not for intermediate (1.01-2.00) or for thick melanomas (>2 mm). Among the most common melanoma types, the median thickness decreased for superficial spreading melanomas but not for nodular melanomas. Over time, the incidence of melanoma has increased notably and the median thickness has decreased. However, median thickness has decreased only among thin melanomas, whereas it has not changed for thick melanomas, most of which are of the nodular type.

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.

Frequency and characteristics of melanomas missed at a pigmented lesion clinic: a registry-based study.

To ensure the removal of all melanomas at an early phase, a number of benign lesions are currently excised for diagnostic evaluation. Nevertheless, little is known about the frequency of melanomas missed (neither recognized nor excised for diagnostic verification) by early detection practices. This study aimed to investigate the diagnostic performance of a specialized pigmented lesion clinic (PLC) through linkage with a local cancer registry. In 1997, 1741 individuals resident in the area of Florence and Prato, Italy, the catchment area of the Tuscany Cancer Registry (RTT), were consecutively examined at a specialized PLC that has been running since 1992 at the Department of Dermatology of Florence. The outcomes of dermatological consultations retrieved from PLC case notes were compared with all the diagnoses of both in situ and invasive melanoma recorded by the RTT until 31 December 1999. The performance of the PLC in detecting cutaneous melanoma was evaluated in terms of sensitivity, specificity and predictive values, with the RTT data as the gold standard. In the population examined at the PLC, 15 newly incident melanomas, all histologically demonstrated, were recorded by the RTT. In 13 of the 15 cases, excision of the lesion had been recommended by PLC staff, while two melanomas, one in situ and one level II 0.60 mm thick invasive, were missed and were subsequently excised 586 and 824 days, respectively, after the first PLC examination. The clinical and dermoscopic features of the invasive lesion were in agreement with a 'featureless' melanoma, and lacked the well-established parameters of malignancy. A total of 67 benign pigmented skin lesions were excised for diagnostic evaluation. Thus the PLC showed a sensitivity in detecting cutaneous melanoma of 86.7% (95% confidence interval [CI] 85.1-88.3%), a specificity of 95.4% (95% CI 94.3-96.3%), a positive predictive value of 13.7% (95% CI 12.1-15.3%) and a negative predictive value of 99.9% (95% CI 99.7-100.0%). The ratio of melanomas to benign skin lesions excised was 1:5.1. In conclusion, specialized examination of pigmented skin lesions at the PLC offered good level of diagnostic performance, with an acceptable cost in terms of benign lesions removed and overall a low risk of missing melanomas.

Addition of dermoscopy to conventional naked-eye examination in melanoma screening: a randomized study.

OBJECTIVE: We sought to assess the difference in lesion management between combined examination (naked-eye and dermoscopy) and conventional naked-eye examination in evaluations for melanoma; and to assess the impact on patient treatment of facilities for digital follow-up of diagnostically equivocal lesions. METHODS: We conducted a randomized, controlled trial at a pigmented lesion clinic in a university hospital. A total of 938 consecutive subjects presenting between November 1, 2001, and March 31, 2002, were eligible and 25 were excluded because they were younger than 12 years of age; hence 913 subjects were enrolled. Participants were randomized to combined examination with mandatory excision of equivocal lesion (arm B) and with possibility of digital follow-up according to the clinician's decision (arm C), or to conventional naked-eye examination (mandatory excision of equivocal lesion) (arm A). The same pigmented lesion clinic staff examined all subjects. RESULTS: Combined examination determined a significant reduction in the percentage of patients referred for operation (9.0% vs 15.6%) (P =.013). When facilities for digital follow-up of equivocal lesions were available, the percentage of patients classified as harboring lesions difficult to diagnose increased (group C, 35.8%; group B, 17.8%; P <.01). About half of them were immediately referred for operation whereas the remainder submitted to second examination (digital follow-up). Two melanomas (1 in situ and 1 invasive, 0.40-mm thick) were diagnosed after second examination performed 6 months later. The number of melanomas eventually excised within the study were similar among the 3 allocation groups (3, 2, and 3, respectively). CONCLUSIONS: the addition of dermoscopy to conventional naked-eye examination is associated with a significant reduction of number of pigmented skin lesions excised for diagnostic verification. The possibility of digital follow-up of equivocal lesions is associated with a not negligible occurrence of initial melanomas left unexcised until the second consultation.

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.

Effect of lesion size on the diagnostic performance of dermoscopy in melanoma detection.

BACKGROUND: Dermoscopy is able to correctly classify a higher number of melanomas than naked-eye examination. Little is known however about factors which may influence the diagnostic performance during practice. The aim of the study was to analyze the effect of size of the lesion on diagnostic performance of dermoscopy in melanoma detection. METHODS: Eight dermatologists examined clinical and, separately, clinical and dermoscopic (combined examination) images of 200 melanocytic lesions previously excised [64 melanomas, 24 in situ and 40 invasive (median thickness 0.30 mm) and 136 melanocytic nevi]. After examination, diagnostic performance was analyzed in accordance with the major diameter of the lesions divided into 3 groups, i.e. small (less than 6 mm), intermediate (between 6 and 9 mm) and large (10 mm or more) lesions. These groups were shown to be highly comparable concerning the microstaging of melanomas (median thickness value 0.30, 0.22 and 0.32 mm, respectively). RESULTS: Dermoscopy increased the diagnostic performance of naked-eye examination of both intermediate and large lesions [sensitivity value: +19.3 (p = 0.002) and +10.3 (p = 0.007); diagnostic accuracy value: +7.4 (p = 0.004) and +6.1 (p = 0.07)]. On the contrary, no statistically significant increase was found dealing with small lesions (sensitivity +3.7, p = 0.66; diagnostic accuracy -1.7, p = 0.55). CONCLUSIONS: The diagnostic improvement associated with the addition of dermoscopy to naked-eye examination is influenced by the size of the lesion, i.e. it is lacking with lesions up to 6 mm in diameter. The optimized use of dermoscopy in melanoma detection is obtained dealing with melanocytic lesions 6 mm in diameter or larger.

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.