Thermal Therapy Modulation of the Psoriasis-Associated Skin and Gut Microbiome.

INTRODUCTION: Psoriasis is a systemic immune-mediated disease primarily manifesting as skin redness and inflammation. Balneotherapy proved to be a successful non-pharmacological option to reduce the skin areas affected by the disease, but the specific mechanisms underlying this effect have not been elucidated yet. Here we test the hypothesis that the effect of thermal treatments on psoriatic lesions could be partially mediated by changes in the resident microbial population, i.e., the microbiome. METHODS: In this study, we enrolled patients with psoriasis and monitored changes in their skin and gut microbiome after a 12-bath balneotherapy course with a combination of 16S rRNA amplicon sequencing and metagenomics. Changes in the resident microbiome were then correlated with thermal therapy outcomes evaluated as changes in Psoriasis Area and Severity Index (PASI) and Body Surface Area index (BSA). RESULTS: The amplicon sequencing analysis of the skin microbiome showed that after thermal treatment the microbiome composition of affected areas improved to approach that typical of unaffected skin. We moreover identified some low-abundance bacterial biomarkers indicative of disease status and treatment efficacy, and we showed via metagenomic sequencing that thermal treatments and thermal water drinking affect the fecal microbiome to host more species associated with favorable metabolic health. CONCLUSIONS: Changes in lower-abundance microbial taxa presence and abundance could be the basis for the positive effect of thermal water treatment and drinking on the cutaneous and systemic symptomatology of psoriasis.

Psoriasis is an immune-mediated disease primarily manifesting as skin redness and inflammation that affects 2­3% of the world's population. No cure is currently available for this condition, and patients are offered pharmacological and non-pharmacological options to alleviate the discomfort. Previous studies and clinical practice have shown that thermal water treatment can be a non-pharmacological option to reduce the areas affected by the disease. However, the specific mechanisms causing this reduction have not been clarified yet. Given that neither the chemical nor the physical composition of thermal water can explain this beneficial effect, recent studies have suggested that it might be due to the effect of thermal water on the microbial communities living on the skin (i.e., the skin microbiome). In this work carried out at Terme di Comano, Northern Italy, we describe the effect of thermal water treatment on the skin microbiome of patients with psoriasis and we highlight the potentially beneficial effect of thermal water drinking on the microbial communities living in the gut, namely the gut microbiome. Specifically, we show that after balneotherapy the areas affected by psoriasis have a higher diversity of microbes usually present on healthy skin, potentially explaining the reduction in disease severity after treatment, and we describe how the gut microbiome of patients who drank thermal water changes to host more species linked with favorable metabolic health. These findings highlight that thermal water treatment and drinking could reduce both the skin and systemic symptomatology of psoriasis by affecting the skin and gut microbiome.

Microbiome characterization of alpine water springs for human consumption reveals site- and usage-specific microbial signatures.

The microbiome of water springs is gaining increasing interest, especially in water intended for human consumption. However, the knowledge about large-scale patterns in water springs microbiome is still incomplete. The presence of bacteria in water sources used for human consumption is a major concern for health authorities; nonetheless, the standard microbiological quality checks are focused only on pathogenic species and total microbial load. Using 16S rRNA high throughput sequencing, we characterized the microbiome from 38 water springs in Trentino (Northern Italy) for 2 consecutive years in order to gain precious insights on the microbiome composition of these unexplored yet hardly exploited environments. The microbiological studies were integrated with standard measurements of physico-chemical parameters performed by the Provincial Office for Environmental Monitoring in order to highlight some of the dynamics influencing the microbial communities of these waters. We found that alpha diversity showed consistent patterns of variation overtime, and showed a strong positive correlation with the water nitrate concentration and negatively with fixed residue, electrical conductivity, and calcium concentration. Surprisingly, alpha diversity did not show any significant correlation with neither pH nor temperature. We found that despite their remarkable stability, different water springs display different coefficients of variation in alpha diversity, and that springs used for similar purposes showed similar microbiomes. Furthermore, the springs could be grouped according to the number of shared species into three major groups: low, mid, and high number of shared taxa, and those three groups of springs were consistent with the spring usage. Species belonging to the phyla Planctomycetes and Verrucomicrobia were prevalent and at relatively high abundance in springs classified as low number of shared species, whereas the phylum Lentisphaerae and the Candidate Phyla radiation were prevalent at higher abundance in the mineral and potable springs. The present study constitutes an example for standard water spring monitoring integrated with microbial community composition on a regional scale, and provides information which could be useful in the design and application of future water management policies in Trentino.

Mesorhizobium comanense sp. nov., isolated from groundwater.

Strain 3P27G6T was isolated from an artesian well connected to the thermal water basin of Comano Terme, Province of Trento, Italy. In phylogenetic analyses based on multilocus sequence analysis, strain 3P27G6T clustered together with Mesorhizobium australicum WSM2073T. Genome sequencing produced a 99.51 % complete genome, with a length of 7 363 057 bp and G+C content of 63.53 mol%, containing 6897 coding sequences, 55 tRNA and three rRNA. Average nucleotide identity analysis revealed that all distances calculated between strain 3P27G6T and the other Mesorhizobium genomes were below 0.9, indicating that strain 3P27G6T represents a new species. Therefore, we propose the name Mesorhizobium comanense sp. nov. with the type strain 3P27G6T (=DSM 110654T=CECT 30067T). Strain 3P27G6T is a Gram-negative, rod-shaped, aerobic bacterium. Growth condition, antibiotic susceptibility, metabolic and fatty acid-methyl esters profiles of the strain were determined. Only few nodulation and nitrogen fixation genes were found in the genome, suggesting that this strain may not be specialized in nodulation or in nitrogen fixation.

Factors associated with sunbed use among 3692 outpatients in 18 centers of the Italian Cancer League (LILT).

Indoor tanning is associated with an increased risk of skin cancer. Nonetheless, its use is still widespread. We aimed to investigate the socio-demographic and clinical characteristics of sunbed users in a group of participants in the skin cancer prevention campaign organized by the Italian Cancer League (LILT). During almost 2 years, 4409 individuals were screened in 18 centers. Participants reported having used sunbeds before the age of 15 years in 2.2% of cases, while after age 15 the prevalence of use was 22.2%. Participants with complete information were 3692. Sunbed users aged > 15 years were significantly more frequently females, young, living in Northern Italy, highly educated, and current or former smokers. They had darker phototype, more common nevi, had used sunbeds more frequently before the age of 15, reported a history of sunburns, and use of sunscreens. Indoor tanning is an important public health issue and a relevant target for primary prevention. However, not all countries have adopted the recommendations issued by the World Health Organization (WHO) on health risks associated with artificial tanning. A deeper insight into the topic may contribute to identify the best prevention strategies.

Netherton Syndrome in Children: Management and Future Perspectives.

Netherton syndrome (NS) is a genetic, multisystemic disease classically distinguished by a triad of clinical manifestations: congenital ichthyosiform erythroderma, hair shaft abnormalities, and immune dysregulation. Due to the complex pathogenesis of the disease, there are no specific therapies currently accessible for patients with NS. An early diagnosis is crucial to start the correct management of these patients. A multidisciplinary approach, including specialists in immunology, allergology, and dermatology, is necessary to set up the best therapeutic pathway. We conducted a review with the aim to summarize the different therapeutic strategies currently accessible and potentially available in the future for children with NS. However, given the limited data in the literature, the best-tailored management should be decided upon the basis of the specific clinical characteristics of the patients with this rare clinical condition. Further comprehension of the pathophysiology of the disease could lead to more efficacious specific therapeutic options, which could allow a change in the natural history of NS.

Assessing patients' characteristics and treatment patterns among children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is the most common immune-mediated skin disease in childhood. Several treatment options for pediatric AD, both topical and systemic, are currently available. We carried out a single-center observational study with the aim of describing characteristics and treatment patterns in pediatric AD patients. METHODS: The study included 867 patients aged ≤16 years (females 50.5%, mean patient's age 5.9 years, standard deviation ±3.6 years) with a previous doctor-confirmed diagnosis of AD who underwent balneotherapy at the Comano Thermal Spring Water Center (Comano, Trentino, Italy) from April to October 2014. RESULTS: Among the patients included in the study, 41.2% had mild (SCORing Atopic Dermatitis, SCORAD 0-15), 43.6% moderate (SCORAD 16-40) and 15.2% severe AD (SCORAD > 40). A higher occurrence of reported food allergy was observed among children with more severe AD (p < 0.0001), while no association was found between AD severity and reported inhalant allergy or passive smoking (p = 0.15 and 0.92, respectively). Emollients (55.1%) and topical corticosteroids (TCS; 45.7%) were the main treatment options used in the previous month. The use of oral steroids and topical calcineurin inhibitors (TCI) was considerably less common (6.3 and 4.5%, respectively), while no patients were on systemic agents other than steroids. Among patients with severe AD, 9.8% had not used TCS, TCI or any systemic treatments. Moreover, 20.0% of the patients in the study population had followed elimination diets, although only 27.2% of them had a reported food allergy. CONCLUSIONS: A significant difference in the prevalence of reported food allergy emerged across the different AD severity categories. Furthermore, although further data are necessary to confirm our findings, undertreatment in children with AD appeared to be very common, at least among those attending the Comano Thermal Spring Water Center. Moreover, many patients followed elimination diets in the absence of reported food allergy.

Characteristics associated with clinical response to Comano thermal spring water balneotherapy in pediatric patients with atopic dermatitis.

BACKGROUND: Several studies have investigated the efficacy of balneotherapy in atopic dermatitis (AD), including a pediatric open randomized clinical trial conducted at the Comano thermal spring water center, which showed a significant reduction in AD severity and an improvement of the quality of life. However, so far many studies on balneotherapy in pediatric AD have included relatively small populations without identifying patients' characteristics associated with their response. The aim of the present study was to identify any features associated with the clinical response to the Comano thermal spring water balneotherapy in a large cohort of pediatric AD patients. METHODS: An observational study was conducted on 867 children aged ≤16 years (females 50.5%, mean patient's age 5.9 years, standard deviation ±3.6 years) with mild to severe AD who underwent balneotherapy at the Comano thermal spring water center (Comano, Trentino, Italy) from April to October 2014. Patients were stratified according to their disease severity, which was evaluated using five SCORing Atopic Dermatitis (SCORAD) categories before and immediately after a thermal spring water balneotherapy course. Potential characteristics associated with the patients' clinical response to Comano thermal spring water balneotherapy were investigated. RESULTS: A statistically significant improvement in AD severity was observed after Comano thermal spring water balneotherapy (p < 0.0001). A significantly higher percentage of patients achieving improvement in AD severity was reported among children ≤4 years old (p < 0.0001) with early-onset AD (p < 0.0001), severe AD (p < 0.0001) or coexistent reported food allergies (p < 0.01). The therapy was well tolerated, and no relevant adverse effects were reported during the treatment course. CONCLUSIONS: Comano thermal spring water balneotherapy is a safe complementary treatment for pediatric patients with AD, as it was able to reduce the disease severity, especially in children ≤4 years old, with early onset AD, severe AD or concomitant food allergies.

A caregiver-reported global severity assessment in pediatric atopic eczema: the Comano score.

Atopic eczema (AE) is the most common inflammatory skin disease in infancy and its prevalence is rising worldwide. It has a wide social impact on the affected children and their families' lives. AE can have a chronic and heterogeneous course, with periods of remission and relapse of the clinical manifestations. For this reason, its severity assessment through standardized outcome measures becomes a fundamental guide for health professionals, who can manage AE following evidence-based medicine principles in their everyday clinical practice or in clinical trials.Several scoring systems have been recognized to assess the clinical manifestations of AE, both from the physician's and the patient's point of view. Despite the scoring systems standardized for adults, there are very few published options about the expression of a patient/caregiver-centered global severity assessment specifically for pediatric AE. For this reason, the aim of our study was to evaluate a new, quick, user-friendly and feasible caregiver-reported global severity assessment for pediatric AE. Based on a 0-10 numerical rating scale in pediatric AE, we named this scoring system the Comano score.We carried out a cross-sectional observational study enrolling a total of 867 patients aged from 1 to 16 years (males 49.5%, mean patient's age 5.9 years, standard deviation ±3.6 years) with a previous doctor-confirmed diagnosis of AE, who underwent balneotherapy at Comano Thermal Center (Comano, Trentino, Italy). A strong correlation between Comano score and SCORing Atopic Dermatitis (SCORAD) was observed (r = 0.74, p < 0.0001).According to our results, the Comano score may be a promising new tool for the expression of a caregiver-reported global severity assessment in pediatric AE. However, further data are needed to confirm our preliminary findings before health professionals can use this scoring system in their everyday clinical practice to manage pediatric AE. Still, as a patient-focused measure, the Comano score may facilitate delivering person-centered care so as to define a measure for a clinical impact that can be meaningful to the subject, which is gaining importance in modern medicine.

Genomic and metagenomic insights into the microbial community of a thermal spring.

BACKGROUND: Water springs provide important ecosystem services including drinking water supply, recreation, and balneotherapy, but their microbial communities remain largely unknown. In this study, we characterized the spring water microbiome of Comano Terme (Italy) at four sampling points of the thermal spa, including natural (spring and well) and human-built (storage tank, bathtubs) environments. We integrated large-scale culturing and metagenomic approaches, with the aim of comprehensively determining the spring water taxonomic composition and functional potential. RESULTS: The groundwater feeding the spring hosted the most atypical microbiome, including many taxa known to be recalcitrant to cultivation. The core microbiome included the orders Sphingomonadales, Rhizobiales, and Caulobacterales, and the families Bradyrhizobiaceae and Moraxellaceae. A comparative genomic analysis of 72 isolates and 30 metagenome-assembled genomes (MAGs) revealed that most isolates and MAGs belonged to new species or higher taxonomic ranks widely distributed in the microbial tree of life. Average nucleotide identity (ANI) values calculated for each isolated or assembled genome showed that 10 genomes belonged to known bacterial species (> 95% ANI), 36 genomes (including 1 MAG) had ANI values ranging 85-92.5% and could be assigned as undescribed species belonging to known genera, while the remaining 55 genomes had lower ANI values (< 85%). A number of functional features were significantly over- or underrepresented in genomes derived from the four sampling sites. Functional specialization was found between sites, with for example methanogenesis being unique to groundwater whereas methanotrophy was found in all samples. CONCLUSIONS: Current knowledge on aquatic microbiomes is essentially based on surface or human-associated environments. We started uncovering the spring water microbiome, highlighting an unexpected diversity that should be further investigated. This study confirms that groundwater environments host highly adapted, stable microbial communities composed of many unknown taxa, even among the culturable fraction.

Unexplored diversity and strain-level structure of the skin microbiome associated with psoriasis.

Psoriasis is an immune-mediated inflammatory skin disease that has been associated with cutaneous microbial dysbiosis by culture-dependent investigations and rRNA community profiling. We applied, for the first time, high-resolution shotgun metagenomics to characterise the microbiome of psoriatic and unaffected skin from 28 individuals. We demonstrate psoriatic ear sites have a decreased diversity and psoriasis is associated with an increase in Staphylococcus, but overall the microbiomes of psoriatic and unaffected sites display few discriminative features at the species level. Finer strain-level analysis reveals strain heterogeneity colonisation and functional variability providing the intriguing hypothesis of psoriatic niche-specific strain adaptation or selection. Furthermore, we accessed the poorly characterised, but abundant, clades with limited sequence information in public databases, including uncharacterised Malassezia spp. These results highlight the skins hidden diversity and suggests strain-level variations could be key determinants of the psoriatic microbiome. This illustrates the need for high-resolution analyses, particularly when identifying therapeutic targets. This work provides a baseline for microbiome studies in relation to the pathogenesis of psoriasis.

Experimental metagenomics and ribosomal profiling of the human skin microbiome.

The skin is the largest organ in the human body, and it is populated by a large diversity of microbes, most of which are co-evolved with the host and live in symbiotic harmony. There is increasing evidence that the skin microbiome plays a crucial role in the defense against pathogens, immune system training and homoeostasis, and microbiome perturbations have been associated with pathological skin conditions. Studying the skin resident microbial community is thus essential to better understand the microbiome-host crosstalk and to associate its specific configurations with cutaneous diseases. Several community profiling approaches have proved successful in unravelling the composition of the skin microbiome and overcome the limitations of cultivation-based assays, but these tools remain largely inaccessible to the clinical and medical dermatology communities. The study of the skin microbiome is also characterized by specific technical challenges, such as the low amount of microbial biomass and the extensive human DNA contamination. Here, we review the available community profiling approaches to study the skin microbiome, specifically focusing on the practical experimental and analytical tools necessary to generate and analyse skin microbiome data. We describe all the steps from the initial samples collection to the final data interpretation, with the goal of enabling clinicians and researchers who are not familiar with the microbiome field to perform skin profiling experiments.

A 10-Year Follow-Up Study of Subjects Recruited in a Health Campaign for the Early Diagnosis of Cutaneous Melanoma: Suggestions for the Screening Timetable.

BACKGROUND: Cutaneous melanoma affects people at a relatively young age. The possibility of making a screening at the population level is strongly limited because of the high costs and the shortage of well-trained operators. OBJECTIVE: To evaluate the possibility of a sustainable timetable of screening examinations for cutaneous melanoma. METHODS: Subjects who contacted the Lega Italiana per la Lotta contro i Tumori (Italian League against Cancer) between January 2001 and December 2004 were followed up to December 2013 through linkage with the Trento Skin Cancer Registry. The cumulative incidence of cutaneous melanoma was calculated and compared with that observed in the general population. RESULTS: Fifteen newly diagnosed cutaneous melanomas were observed in 3,635 subjects during the screening phase, while 14 new cases were diagnosed within December 2013, in the period of follow-up after the screening. The 95% confidence interval for the cumulative incidence of screened subjects included the cumulative incidence of the general population. No new cutaneous melanomas were detected in a 2-year period, after the first examination, 2 cases within 3 years. CONCLUSIONS: Based on our study, we think that in a selected population a screening programme can be performed every 2-3 years. This could help make a screening possible/sustainable for the early diagnosis of cutaneous melanoma in a public health context.

Increased frequency of minimal homozygous deletions is associated with poor prognosis in primary malignant melanoma patients.

Identification of prognostic melanoma-associated copy number alterations (CNAs) is still an area of active research. Here, we investigated by high-resolution array comparative genomic hybridization (aCGH) a cohort of 31 paraffin-preserved primary malignant melanomas (MMs), whose prognosis was not predictable on the basis of conventional histopathological parameters. Although we identified a variety of highly recurrent sites of genomic lesions, the total number of CNAs per patient was not a discriminator of MM outcome. Furthermore, validation of aCGH by quantitative PCR on an extended population of 65 MM samples confirmed the absence of predictive value for the most recurrent CNA loci. Instead, our analysis revealed specific prognostic potential of the frequency of homozygous deletions (representing less than 3% of the total CNAs on average per sample), which was strongly associated with sentinel lymph node (SLN) invasion (P = 0.003), and distant metastasis (P = 0.003). Increased number of homozygous deletions was also indicative of poor patient survival (P = 0.01), both in our samples and in an independent validation of public dataset of primary and metastatic MMs. Moreover, we identified 77 hotspots of minimal common homozygous deletions, enriched in genes involved in cell adhesion processes and cell-communication functions, which preferentially accumulated in primary MMs showing the most severe outcome. Therefore, specific loss of gene loci in regions of minimal homozygous deletion may represent a pivotal type of genomic alteration accumulating during MM progression with potential prognostic implication.

Improving triage and management of patients with skin cancer: challenges and considerations for the future.

Skin cancer is the most common malignancy in humans, thus representing a major health concern. Because of the increasing attention to skin cancer prevention, there has been a growing workload for dermatology clinics, with patients referred from primary care requiring assessment of suspicious skin tumors. This places a strain on limited specialist resources and can create a paradoxical situation wherein an early diagnosis becomes increasingly difficult for those patients who actually do suffer from skin cancer. The aim of these recommendations is to propose an updated, rational system of triage, involving improved accuracy of diagnosis and more timely management of skin cancer by both general practitioners and dermatologists.

Clinical relevance of sentinel lymph node status examined with conventional histology and molecular biology.

AIMS AND BACKGROUND: The presence of nodal metastases in patients with primary cutaneous melanoma adversely affects the biological behavior and is related to a poor prognosis. The role of sentinel lymph node biopsy is still debated. The aim of this study was to evaluate the prognostic role of sentinel lymph node biopsy with respect to disease-free period and overall survival. PATIENTS AND METHODS: Patients with invasive cutaneous melanoma who underwent sentinel lymph node biopsy in the Santa Chiara Hospital of Trento between October 1997 and December 2002 were evaluated. The lymph nodes were examined with conventional histology, S100 and tyrosinase in immunohistochemistry, and tyrosinase in molecular biology. RESULTS: There were 144 patients with 198 sentinel lymph nodes. A significant association was found in conventional histology with Clark level and Breslow thickness. The prognostic role of sentinel lymph node status was independent of the other considered variables. However, no significant association was found with the molecular biology test. A significant excess of positive results at molecular biology was found. CONCLUSIONS: Sentinel lymph node biopsy is an important independent prognostic factor for invasive cutaneous melanoma, but only when evaluated with conventional histology. As a result of this study, we stopped performing the tyrosinase test in molecular biology.

Incidence and mortality data from cutaneous melanoma in Trentino: registry-based study.

BACKGROUND: The province of Trento has been the target of health campaigns for early diagnosis of cutaneous melanoma for 30 years. OBJECTIVE: To evaluate incidence and mortality data of skin melanoma in the province from January 1992 to December 2001. METHODS: The study is based on the provincial skin cancer registry and the regional mortality registry. Standardized incidence and mortality rates were computed, and time trends were evaluated. Incidence rates were modeled using Poisson regression. RESULTS: Five hundred fifty-four melanomas were diagnosed (226 in males and 328 in females). No period effect was revealed. Incidence rates in females were about 1.24 times those in males. No significant trend in mortality rates was observed. CONCLUSION: We examined incidence and mortality data of cutaneous melanoma during a 10-year period and failed to find any significant trend. It seems we have reached a plateau after many years of continuous, intensive health campaigns.

Clinical validation of an automated system for supporting the early diagnosis of melanoma.

BACKGROUND: Early diagnosis and surgical excision is the most effective treatment of melanoma. Well-trained dermatologists reach a high level of diagnostic accuracy with good sensitivity and specificity. Their performances increase using some technical aids as digital epiluminescence microscopy. Several studies describe the development of computerized systems whose aim is supporting dermatologists in the early diagnosis of melanoma. In many cases, the performances of those systems were comparable to those of dermatologists. However, this cannot tell us whether a system is able to support dermatologists. Actually, the computerized system might correctly recognize the same lesions that the dermatologist does, without providing them any useful advice and therefore being useless in recognizing early malignant lesions. PURPOSE: We present a novel approach to enhance dermatologists' performances in the diagnosis of early melanoma. We provide results of our evaluation of a computerized system combined with dermatologists. METHODS: A Multiple-Classifier system was developed on a set of 152 cases and combined to a group of eight dermatologists to support them by improving their sensitivity. RESULTS: The eight dermatologists have average sensitivity and specificity values of 0.83 and 0.66, respectively. The Multiple-Classifier system performs as well as the eight dermatologists (sensitivity range: 0.75-0.86; specificity range: 0.64-0.89). The combination with the dermatologists shows an average improvement of 11% (P=0.022) of dermatologists' sensitivity. CONCLUSION: Our results suggest that an automated system can be effective in supporting dermatologists because it recognizes different malignant melanomas with respect to the dermatologists.

Epidemiology of skin tumors: data from the cutaneous cancer registry in Trentino, Italy.

BACKGROUND: A Skin Cancer Registry was established in the province of Trento in northeast Italy in 1992 with the aim of collecting data on all cutaneous tumors affecting residents. These neoplasms are responsible for considerable morbidity and utilization of the Health Service because of their high frequency and, therefore, knowledge of the exact incidence is very important in planning health policies. Registry data are also very helpful in performing studies of analytical and descriptive epidemiology. METHODS: For each patient, we collected personal data, phenotypical characteristics, professional history, concurrent diseases, previous therapy or trauma, and all data regarding the tumors. Patients were interviewed in person or, less frequently, by phone. All data were verified and put in a computerized file, in a protected room. The Statistics Institute of Trento University analyzed the data. Comparison among means was performed using the analysis of variance and differences among proportions were tested by chi-squared analysis. Poisson regression and the likelihood ratio test were used to compare incidence rates. We analyze here the data regarding epiteliomas and melanoma. RESULTS: During the study period we registered 3435 primary skin tumors in 2868 individuals. Crude incidence rates, calculated using the number of subjects (not the number of tumors), were 87.9 for basal cell carcinoma (BCC), 28.9 for squamous cell carcinoma (SCC), and 14.2 for cutaneous melanoma (CM), per 100,000 per annum. We also calculated the same figures in females and males and specific incidence rates in both sexes and evaluated the distribution of skin cancer according to sex and anatomical site. CONCLUSION: We report the analysis of the data collected by the Skin Cancer registry in a 6 year period and compare the data with published data in literature and with data of a previously registered melanoma file. Our results confirm the high incidence of nonmelanoma skin cancers and the variation in the histological patterns of CM.