Redefining the number needed to excise.

The number needed to excise (NNE) is a metric used to convey the efficiency of dermatological practice by serving as a gauge for the diagnostic accuracy of melanoma. Rather than an NNE for melanoma alone, we assert that the NNE should measure all skin cancer types and we present data on NNE from two clinical sites demonstrating the utility and trends in NNE over time.

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.

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.

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.

[ß-blockers: a new and emerging treatment for melanoma]. / ß-bloccanti: nuova prospettiva terapeutica per il melanoma.

Recent studies have underlined the innovative theories concerning the role of neuroendocrine system on the tumor and metastasis microenvironment. These observations have suggested the possibility that drugs originally intended for the treatment of cardiovascular disease, the ß-adrenergic receptor blockers (ß-blockers), may provide new therapeutic opportunities for the control of tumor progression. A large number of observational studies showed the protective effect of ß-blockers in breast cancer, but more recently, similar findings were also reported in other cancers such as prostate cancer and melanoma. The results of these studies have shown that the use of ß-blockers, but not other antihypertensive drugs, was associated with a significant increase of the disease free survival and of the overall survival. With regard to melanoma, a recent study by De Giorgi et al. showed a 36% reduction in risk of disease progression for each year of treatment with ß-blockers. These data, originating from prospective studies, cannot be considered conclusive and require validation by means of clinical trials that are underway.

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.

Contrast-enhanced ultrasound: a filter role in AJCC stage I/II melanoma patients.

One of the most significant advances in melanoma staging is sentinel lymph node biopsy (SLNB). It is a surgical technique to detect occult nonpalpable micrometastases in regional lymph nodes. Recently, contrast-enhanced ultrasound (CEUS) was introduced as a noninvasive procedure, in spite of SLNB, for the detection of SLNs in patients with cutaneous melanoma. The main purpose of this study was to evaluate the diagnostic accuracy of CEUS in the diagnostic workup of patients with melanoma in comparison with the final histology of SLNs detected through preoperative lymphoscintigraphy. Fifteen patients with cutaneous melanoma underwent prompt excisional biopsy with narrow margins in order to avoid impairment of the melanoma lymphatic basin and were referred for SLNB according to routine indications between January and February 2009. In our study CEUS showed, albeit based on a small patient sample, a negative predictive value of 100%, that means that all negative results were confirmed by negative SLN histopathological examination; all ultrasonographically negative lymph nodes corresponded to nonmetastatic sentinel nodes.

Treatment of disseminated granuloma annulare with allopurinol: case report.

Granuloma annulare (GA) is a rare disease characterized by granulomatous inflammation of the dermis. A variant form of the disease, disseminated granuloma annulare (DGA), can be observed in about 15% of affected patients. Localized GA is likely to resolve spontaneously within months or a few years, whereas DGA can persist for decades. Various therapies have been suggested in these cases, but none of them has been demonstrated to be consistently efficacious. Allopurinol has been successfully used in granulomatous diseases such as sarcoidosis or reactions to polymethylmethacrylate spheres; therefore, we decided to evaluate the possible efficacy of this drug in three patients with long-lasting, therapy-resistant DGA.

Paraneoplastic vasculitis and paraneoplastic vascular syndromes.

Paraneoplastic syndromes are localized or diffuse pathologic manifestations that may occur in subjects affected by neoplastic diseases, even occult ones. Among the many clinical manifestations of paraneoplastic syndromes, cutaneous ones are quite common. It is estimated that skin manifestations may represent the very first diagnostic sign of a neoplastic disease in about 1% of patients. Many paraneoplastic syndromes with skin manifestations are caused by vascular alterations. In case of solid tumors, migrant thrombophlebitis and blood hypercoagulability can be seen, whereas in case of hematological neoplasms, vasculitis, and erythromelalgia can occur. Paraneoplastic vasculitis and paraneoplastic vascular syndromes are challenging issues in dermatology and general medicine. The present article will review the actual knowledge in the argument, together with providing hints for its diagnosis and management.

Cutaneous manifestations of breast carcinoma.

The incidence of breast carcinoma cutaneous manifestation in patients with breast carcinoma is 23.9%. The most common sites of breast carcinoma cutaneous manifestation are the chest wall and abdomen, but they can occur at the extremities and in the head/neck region. Due the high incidence of breast carcinoma, these cutaneous manifestations are the most common metastases seen by dermatologists. In clinical practice, cutaneous metastases show a wide range of clinical manifestations. Nodules are the most common presentation, but several other patterns are described below.

Synchronous angiosarcoma, melanoma and morphea of the breast skin 14 years after radiotherapy for mammary carcinoma.

With the improvement in survival after breast cancer there has been increasing interest in the long-term effects of radiotherapy, including the development of tumours. Compared with the general population, breast cancer survivors have a 10-50% higher risk of developing a second cancer. Radiotherapy may play a role in the onset of such lesions. We describe here the case of a 68-year-old woman who developed synchronous cutaneous angiosarcoma, melanoma and morphea of the breast skin and the local area, 14 years after radiotherapy for breast carcinoma. Given the risk of post-radiation secondary primaries in breast cancer patients, long-term surveillance is necessary, with particular attention being paid to skin changes in the irradiation field. Radiation-induced morphea is a rare complication in which immunological abnormalities may stimulate malignant transformation. Long-term studies are required to clarify the pathogenesis of these rare associations.

Tuscan Consensus on the diagnosis, treatment and follow up of adult atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory disease with a chronic-relapsing course that is intensely itchy. A correct diagnosis of AD in adults and consequently appropriate clinical therapeutic management is a critical issue for extreme clinical expression heterogeneity and various grades of disease severity. In order to ensure high levels of care and standardization of clinical therapeutic management of Adult AD, the decision was taken to create an AD Tuscan Consensus Group (the Group), to work on and validate a consensus based regional clinical-therapeutic management model. The aims of the Group were to find agreement on the criteria for diagnosis, scoring of severity, multidisciplinary approach and treatment of adult atopic dermatitis and to create an easier way for patients to access specialized dermatology outpatient services and importantly to reduce waiting lists and costs related to the management of AD. The Tuscan Consensus Group adopted a simplified Delphi method, in three principal steps: 1) literature metanalysis and critical review of patient's clinical experience to identify the main areas considered questionable or uncertain; 2) discussion of those areas requiring consensus and statement definition through four different sub-committees (diagnosis, severity evaluation, scoring and comorbidities); 3) a consensus based simplified process with final approval of each statement by plenary vote with approval >80% of the participants. The Group here presents and discusses the consensus based recommendation statements on adult atopic dermatitis.

Focused UV-B narrowband microphototherapy (Biopsorin). A new treatment for plaque psoriasis.

Skin irradiation with ultraviolet light B (UV-B) and in particular the emission peak at 311 nm represents an effective therapeutic regimen for psoriasis. Excessive tanning, photoaging, and skin cancerization do occur mainly in subjects with skin phototype I to III. The possibility of developing skin cancer is parallel to the skin surface area under treatment and to the overall irradiation dose. We report here on a new focused phototherapy method releasing UV-B with a peak at 311 nm, which consists in the selective irradiation of single psoriatic patches with a new device equipped with a special optic fiber. The treatment is effective, safe and well tolerated. Psoriasis Area and Severity Index 75 is achieved in 64% of patients after 12 sessions of treatment. The Physician Global Assessment evaluation significantly improves in all treated patients.

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.

Propranolol for Off-label Treatment of Patients With Melanoma: Results From a Cohort Study.

IMPORTANCE: Preclinical and retrospective studies showed that ß-blockers inhibit angiogenesis and disrupt migration of melanoma cells via inhibition of noradrenaline-dependent responses. OBJECTIVE: To study the clinical effectiveness of ß-blocker therapy in patients with melanoma and to determine whether propranolol improves progression-free survival in patients with melanoma. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective study in patients treated for melanoma in our center with propranolol for off-label use. Patients with histologically confirmed stage IB to IIIA cutaneous melanoma and no evidence of metastasis were eligible for the study. At the time of diagnosis, they were asked to take propranolol (80 mg daily) as an off-label adjuvant treatment. If they accepted the treatment, they were considered part of the propranolol cohort (PROP). If they refused treatment but agreed to participate in the study control group, they were considered part of the nonpropranolol cohort (No-PROP). MAIN OUTCOMES AND MEASURES: The primary outcome was progression-free survival. Disease progression was assessed by evaluating the presence of lymphatic, in-transit, or visceral metastases, and the cause of death was recorded. RESULTS: Among the 53 patients (median [interquartile range] age 63 [48-75] years; 33 men) included in the study, 19 were eligible for the PROP cohort. Thirty-four patients otherwise eligible but unwilling to take propranolol were enrolled in the No-PROP cohort. The 2 cohorts were comparable in terms of demographic characteristics and primary prognostic factors at baseline. After adjusting for known prognostic factors, Cox models confirmed that use of propranolol at the time of diagnosis was significantly inversely associated with recurrence of melanoma with approximately an 80% risk reduction for propranolol users (hazard ratio, 0.18; 95% CI, 0.04-0.89; P = .03). CONCLUSIONS AND RELEVANCE: In the absence of randomized, double-blind, placebo-controlled clinical trials, this study is the first off-label study of which we are aware of propranolol for melanoma treatment. These results confirm recent observation that ß-blockers protect patients with thick cutaneous melanoma from disease recurrence. This study is in accordance with the present policy of "drug repurposing" in oncology. Repurposing the vast arsenal of approved drugs with a nononcology primary purpose may prove an attractive and inexpensive strategy for offering more effective treatment options to patients with cancer.

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.

ß-Blocker use and reduced disease progression in patients with thick melanoma: 8 years of follow-up.

Previous observational studies have reported the protective effect of ß-blockers on the progression of different types of cancers. In 2011, we published a prospective study, including patients with histologically confirmed malignant melanoma in stage II-IIIA. In total, 25% of them reported previous use of ß-blockers that were administered at any time for any other diseases. After a median follow-up of 2.5 years, 34% of the patients in the untreated group showed disease progression. In contrast, only 3% of the patients in the treated group showed progression. We report the findings obtained in the same cohort after a longer period of ß-blocker therapy and follow-up (8 years). We prospectively reviewed data of the patients enrolled in the original prospective study. Disease progression was assessed by evaluating the presence of lymphatic, in-transit or visceral metastases. Deaths by any cause and deaths because of melanoma were recorded. A multivariate Cox proportional hazards model was used to evaluate the effect of ß-blocker use on disease-free survival and overall survival, adjusting for significant confounders. After a median follow-up of 8 years and a median duration of ß-blocker use of 7.6 years, 45% of the patients in the untreated group and 30% of the patients in the treated group showed disease progression. Notably, in the untreated group 35% patients died from melanoma and only 17% patients died from melanoma in the treated group. Results of this hospital-based prospective cohort study with a median follow-up of 8 years confirmed our previous results that the use of ß-blockers significantly reduced the risk of recurrence and mortality in melanoma patients.