Tuscan consensus on the use of UVBnb phototherapy in the treatment of psoriasis.

Psoriasis (PSO) is traditionally defined as an immune-mediated, inflammatory dermatological disease characterized by a chronic-relapsing course and associated with multifactorial inheritance (genetic predisposition and influence of various environmental factors). Considered until recently a dermatological disease only, today PSO is correctly known as a systemic one because of the involvement of multiple organs with important impact on social life and relationships. PSO is found in the 0.3-4.6% of the world's population, while its prevalence in the Italian population is estimated at 2.8%. Therefore, if we consider that in Tuscany more than 100,000 people out of 3,672,202 suffer of psoriasis, it is of paramount importance to focus on a shared clinical and therapeutic protocol to manage the disease. With the aim of ensuring diagnostic-therapeutic suitability, high levels of care and standardization of treatment, a unique clinical-therapeutic management model has been developed and validated in Tuscany, involving all accredited regional dermatological centers. Among the possible alternatives to be implemented in the treatment of patients with mild, moderate-severe psoriasis, UVBnb phototherapy is widely used alone or in association with other systemic and non-systemic devices. Despite this, there is still no universally shared therapeutic protocol. In this context the CO.FO.TO working group (Consensus Fototerapia Toscana) is born with the aim of defining and validating the main guidelines in the use of phototherapy with UVBnb in psoriasis; the guidelines are based both on the real-life experience of the different centers of reference in the region and on the revision of the recent literature.

Sun-Protection Behavior, Pubertal Development and Menarche: Factors Influencing the Melanocytic Nevi Development-The Results of an Observational Study of 1,512 Children.

Observational studies consistently show that melanocytic nevus prevalence increases with age and that phenotypic traits are significantly associated with nevus count in children. An observational study of 1,512 children and adolescents from 2010 to 2013 was conducted. Study dermatologists counted the full body, arm, and facial nevi of each participant. Children and their parents were asked to complete a survey to gather data on personal characteristics, pubertal development, and early-life sun exposure. The main aim of the study was to establish pediatric nevus prevalence and its relationship with age, phenotype, sex, menarche, early-life sun exposure, and sun-protection behaviors. Females had a significantly lower nevus count compared with males, but this sex-related difference was significantly modified by menarche. Sun exposure and sun-protection habits were all significantly associated with nevus count; in particular, children who used sunscreen with a sun-protection factor > 30 had a lower nevus count compared with sun-protection factor ≤ 30 sunscreen users. This study shows that sex, menarche status, and sun-protection practices significantly influence nevus count in this pediatric population.

Discrepant alterations in main candidate genes among multiple primary melanomas.

BACKGROUND: Alterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM). METHODS: One hundred twelve MPM patients (96 cases with two primary melanomas, 15 with three, and 1 with four) were included into the study. Paired synchronous/asynchronous MPM tissues (N=229) were analyzed for BRAF mutations and cKIT/CyclynD1 gene amplifications. RESULTS: BRAF mutations were identified in 109/229 (48%) primary melanomas, whereas cKIT and CyclinD1 amplifications were observed in 10/216 (5%) and 29/214 (14%) tumor tissues, respectively. While frequency rates of BRAF mutations were quite identical across the different MPM lesions, a significant increase of cKIT (p<0.001) and CyclinD1 (p=0.002) amplification rates was observed between first and subsequent primary melanomas. Among the 107 patients with paired melanoma samples, 53 (49.5%) presented consistent alteration patterns between first and subsequent primary tumors. About one third (40/122; 32.8%) of subsequent melanomas presented a discrepant pattern of BRAF mutations as compared to incident primary tumors. CONCLUSIONS: The low consistency in somatic mutation patterns among MPM lesions from same patients provides further evidence that melanomagenesis is heterogeneous and different cell types may be involved. This may have implications in clinical practice due to the difficulties in molecularly classifying patients with discrepant primary melanomas.

Combined fluorescence-Raman spectroscopic setup for the diagnosis of melanocytic lesions.

Two optical fibre-based probes for spectroscopic measurements on human tissues were designed and developed. The two probes combine fluorescence and Raman spectroscopy in a multimodal approach. The fluorescence excitation was provided by two laser diodes emitting in the UV (378 nm) and in the visible (445 nm) range, while a third source in the NIR (785 nm) was used for Raman. The device was tested on freshly excised human skin biopsies clinically diagnosed as malignant melanoma, melanocytic nevus, or healthy skin. Discrimination of lesions based on their fluorescence and Raman spectra showed good correlation with the subsequent histological examination.

Excess body weight and increased Breslow thickness in melanoma patients: a retrospective study.

Excess body weight has been shown to increase the risk for development of several common cancers, such as postmenopausal breast, colon, endometrium, kidney, and esophagus cancers. The main aim of the present study was to investigate the potential relationship between excess body weight, assessed in terms of BMI, and Breslow thickness in 605 patients affected by primary cutaneous melanoma. Particularly, we evaluated the occurrence of thick melanoma (>1 mm) in overweight compared with nonoverweight patients. The effect of BMI (≥25 vs. <25 kg/m2) on the risk of having a diagnosis of thick melanoma was estimated in terms of odds ratio (OR) by logistic regression analysis, adjusted for age, sex, and histological type. Significant differences in overweight versus nonoverweight patients were found with respect to sex distribution. In fact, the occurrence of thick melanoma was greater in overweight women than in nonoverweight women (OR=1.64). When the analysis was restricted to postmenopausal women, the corresponding OR increased further to 2.50. In conclusion, a positive association between excess body weight and the risk of thick melanoma was found only in female patients. On stratifying patients into subgroups, the relationship between the risk of being diagnosed with a thick melanoma (>1.0 mm) and overweight status (BMI≥25 kg/m2) was significantly affected by both sex and menopausal status. Despite limitations because of both the study design and the relatively small numbers of patients in certain subgroups, overweight status may be associated with an increased Breslow thickness in postmenopausal women.

Epidemiology of melanoma: is it still epidemic? What is the role of the sun, sunbeds, Vit D, betablocks, and others?

The incidence of cutaneous malignant melanoma is continuously increasing worldwide, but only minimal changes in mortality have been observed. This phenomenon has brought into question whether this increased incidence reflects a true or apparent melanoma epidemic. The most recent data suggest that this epidemiological trend may be explained by the existence of a certain degree of melanoma overdiagnosis, especially of thin lesions, which probably would never progress to advanced disease if left untreated. However, acute sun exposure and widespread use of sunbeds may also justify the increase in melanoma incidence. Recently, both vitamin D and beta-blocker use seem to play a beneficial role in melanoma progression.

Dermoscopy, confocal laser microscopy, and hi-tech evaluation of vascular skin lesions: diagnostic and therapeutic perspectives.

Vascular skin lesions comprise a wide and heterogeneous group of malformations and tumors that can be correctly diagnosed based on natural history and physical examination. However, considering the high incidence of such lesions, a great number of them can be misdiagnosed. In addition, it is not so rare that an aggressive amelanotic melanoma can be misdiagnosed as a vascular lesion. In this regard, dermoscopy and confocal laser microscopy examination can play a central role in increasing the specificity of the diagnosis of such lesions. In fact, the superiority of these tools over clinical examination has encouraged dermatologists to adopt these devices for routine clinical practice, with a progressive spread of their use. In this review, we will go through the dermoscopic and the confocal laser microscopy of diagnosis of most frequent vascular lesions (i.e., hemangiomas angiokeratoma, pyogenic granuloma, angiosarcoma) taking into particular consideration the differential diagnosis with amelanotic melanoma.

The prognostic impact of the anatomical sites in the 'head and neck melanoma': scalp versus face and neck.

Cutaneous melanoma is a malignant neoplasia with several demographic and histopathological prognostic factors. Many studies stress that the head and neck region has a worse prognosis compared with other localizations, but the reasons for this worse prognosis are unclear. Therefore, the aim of our study is to analyse the poor prognosis of head and neck melanoma (HNM) with respect to the other anatomical sites, considering the face and neck (F&N) and the scalp separately. We carried out a retrospective analysis of 757 melanoma patients. In particular, we studied the prognostic impact of different melanoma skin localizations (head and neck, trunk, upper extremities and lower extremities). Afterwards, we divided HNM into two subgroups, F&N and scalp, to evaluate their impact in the HNM prognosis. Data showed a significantly lower 5-year overall survival probability for HNM (78.9 versus 93.1% for other body sites; P=0.05). Moreover, on analysing the two anatomical areas considered among HNM, we observed a 5-year overall survival of 81.8% for F&N and 66.7% for scalp. HNM has different and worse prognostic features with respect to other sites, but this trend is not only because of scalp melanoma but is also determined by F&N melanoma, which we believe to be underestimated until now.

Is skin self-examination for cutaneous melanoma detection still adequate? A retrospective study.

OBJECTIVE: The aim of this retrospective study was to analyze the relationship between detection pattern, tumor thickness, patient demographics, and personal and family history of melanoma in the era of noninvasive diagnosis. METHODS: All patients with primary cutaneous melanoma who presented to the Department of Dermatology at the University of Florence between January 2000 and November 2010 were interviewed at the time of their final histopathological diagnoses of melanoma as part of their clinical record. The treating physician specifically questioned all patients about who had first detected or suspected the lesion that resulted in the histological diagnosis of melanoma. RESULTS: A total of 802 melanoma patients were analyzed. The spouse found approximately 16% of the melanomas, and a similar percentage was discovered by the general practitioner. The largest group of melanomas (36%) was discovered during regular annual skin examinations by dermatologists, while another large group (33%) were discovered by the patients themselves. The data that emerged from our study is that self-detection was associated with a greater probability of having a thick melanoma and, therefore, a poor prognosis (odds ratio 1.56). CONCLUSIONS: Because the current mortality of melanoma is still stable, we are convinced that a new message should be introduced to encourage high-risk patients to have an annual skin examination as a rule.

Features of small melanocytic lesions: does small mean benign? A clinical-dermoscopic study.

The use of dermoscopy is known to increase the sensitivity and specificity in the clinical diagnosis of cutaneous pigmented melanocytic lesions compared with naked-eye examinations. However, small pigmented melanocytic lesions with maximum clinical diameters of 6 mm remain the most significant diagnostic challenge to the clinician, particularly in the diagnosis of small melanoma, both in naked-eye and in dermatoscopic examinations. The aim of the present study was to analyze the clinical and dermatoscopic features of small pigmented melanocytic lesions, focusing on more frequently occurring features in small melanoma to identify them earlier. A total of 103 pigmented melanocytic lesions with diameters less than 6 mm were analyzed. On histopathological examination, 34 of these lesions were diagnosed as melanomas and the remaining lesions (n = 69) were diagnosed as benign, melanocytic lesions. Images of cases were independently and blindly administered to three dermatologist experts in dermoscopy, who were asked to examine the clinical and dermatoscopic images of melanocytic skin lesions separately and to fill out a printed questionnaire to rate the images according to the ABCD clinical criteria and according to typical dermoscopic pattern analyses. The results of the questionnaires were then analyzed and crossed in order to rate the clinical and dermoscopic features of small pigmented lesions. Our study proved that the clinical criteria for diagnosing melanoma are not as reliable in the diagnosis of pigmented lesions of less than 6 mm diameter. However, the use of dermoscopy, even if not nullifying, allows a better classification of small, melanocytic lesions through pattern analysis.

Polymorphisms of estrogen receptors: risk factors for invasive melanoma - a prospective study.

Cross-sectional studies have reported associations between a number of polymorphisms in the estrogen receptor alpha (ERα) gene and the body mass index, hypertension, coronary flow reserve, coronary atherosclerosis, and osteoporosis. There are currently no data examining the genetic polymorphisms of the ERα and estrogen receptor beta (ERß) genes in melanoma patients. The aims of this study were to investigate the associations of genetic polymorphisms of the ERα and ERß genes with melanoma risk. The study group consisted of consecutive patients who visited the Department of Dermatology of the University of Florence between March 2005 and July 2007 for surgical excision of melanoma. In our study, homozygosity for the wild-type alleles showed different results at the PvuII, XbaI, and AluI restriction sites. Only the AluI site showed a lower proportion of the A allele in the melanoma group compared to the control group; the P and X alleles were lower in the control group than in the melanoma group. The distribution of wild-type alleles is important because these alleles have a protective role in the expression of altered proteins, which involves the ERs in our case. Because of the phenotypic prevalence of the wild-type allele, the heterozygotes did not express the polymorphism. The homozygosity of the polymorphic-type alleles shows that a alleles are more frequent in the case group than in the control group, with proportions of 43.8 and 39.5%, respectively. These results suggest that a polymorphism at the AluIrestriction site correlates with a higher proportion of melanoma. Thus, the polymorphism of ERß could ascribe to a higher susceptibility to melanoma.

Estrogens, estrogen receptors and melanoma.

The skin is the largest nonreproductive target tissue on which estrogen plays many beneficial and protective roles. Although neither exogenous hormones nor pregnancy represent significant risk factors for melanoma, epidemiological data suggest a higher survival rate in women with metastatic disease versus men and in premenopausal versus postmenopausal patients. Despite the fact that hyperestrogenic signaling has long been implicated in the initiation and progression of several tumors, the role of estrogens in malignant melanoma is still unclear. The cellular effects of estrogens are mediated by two subtypes of estrogen receptors (ERs). Estrogen receptor ß (ERß), the predominant ER in the skin, antagonizes the proliferative action mediated by estrogen receptor α. According to recent immunohistochemical studies, ERß protein expression decreases progressively with increased Breslow thickness and results in more invasive melanomas; thus, ERß immunophenotype may distinguish melanomas linked to poor prognosis from those with a favorable course and lead to melanoma unresponsiveness to both estrogen and anti-estrogen treatment. Therefore, if future large-scale immunohistochemical and molecular studies point towards ERß as an important factor in malignant melanoma progression, they will open up novel and targeted prognostic and therapeutic perspectives.

Specific challenges in the management of subungual melanoma.

Subungual melanoma (SUM) is infrequent in the general population, accounting for 0.7-3.5% of all cutaneous melanomas. SUM absolute incidence is similar among different racial groups; however, the relative proportion among overall cutaneous melanoma cases within each population varies in relation to the frequency of sun-induced melanoma. Subungual melanoma most commonly presents as a discoloration of the nail, followed by a recalcitrant wound, a tumor, nail splitting and nail bed bleeding. In most cases, the clinical presentation will already exhibit features typical of late-stage lesions because many patients wait for several months or even years before consulting a physician for evaluation of nail changes. Misdiagnosis of SUM as subungual hematoma, chronic trauma or onychomycosis is still a frequent occurrence, significantly reducing the chances for early treatment. An appropriate diagnostic approach is crucial to allow early-stage diagnosis. The correct management of SUM hinges on early diagnosis and selection of the most appropriate surgical technique. Curative treatment of SUM currently entails surgical excision when the extent of invasion is limited.