Genital and extragenital oncological risk in women with vulvar lichen sclerosus: A multi-center Italian study.

Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus. METHODS: A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio. RESULTS: Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4-22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32-9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1-5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer. CONCLUSIONS: Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus.

SIIV position paper: clinical approach to vulval diseases. Need for quality standards.

This paper summarizes the position of the Italian Society of Vulvology on the clinical approach to vulval disease. A thorough history (general medical, gynaecological, and vulval history) is essential for a successful and fruitful vulvological examination. Characteristics of pruritus (itch) and pain, that are the two main vulval symptoms, should be collected and reported with precision, according to duration, temporal course, location, provocation, and intensity. Physical examination must consider both the general condition of the patient and the specific vulval region, that must be examined following a standardized methodology. The physical examination of the vulva is carried out with naked eye and adequate natural or halogen lighting. The subsequent use of instrumental magnification can be considered on particular parts of skin/mucosa, already highlighted with the first inspection. Also, palpation is essential, allowing to appreciate physical features of vulval lesions: consistency, surface, soreness, adherence to underlying plans. Finally, the five-step approach of the International Society for the Study of Vulvo-vaginal Disease about Terminology and Classification of Vulvar Dermatological Disorders (2012) is summarized. A vulval biopsy may be useful in the following situations: when clinical diagnosis is uncertain, lesion not responding to treatment; histologic confirmation for a clinical diagnosis and exclusion or confirmation of a suspected neoplastic intraepithelial or invasive pathology.

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.

Melanoma and pregnancy.

The last decades were characterized by a worldwide increasing incidence in melanoma. Almost 35% of diagnosed with melanoma women are in childbearing age. Malignant melanoma is the most common malignancy during pregnancy. Considering this background it is clear how melanoma and pregnancy has becoming one of the main topic of discussion. Current knowledge about pregnancy and melanoma is characterized by many controversies and divergences. The real incidence of melanoma in childbearing and the impact of pregnancy on the prognosis of melanoma is still unclear. There are many uncertainties regarding other aspects of women with melanoma during childbearing, such as the changing in moles, the prognosis and the management. Every changing nevus that would raise concern for malignancy in a pregnant patient should be investigated and surgery should be performed safely using local anesthetic. Pregnancy can affect the staging and treatment of melanoma especially in advanced stage, the decision about introduction or continuation of treatment in the event of pregnancy should be preceded by an analysis of the potential benefits and risks. The role of hormonal changes during pregnancy on melanoma is continually debated. At present, there is a lack of a European guideline on this topic and this review aims to address the most controversial issues such as the roles of hormones, staging and therapeutic difficulties of melanoma during pregnancy. The authors' aim is to help the clinician in the difficult decision-making process concerning the woman suffering from melanoma and her child.

Tolerability and safety of biological therapies for psoriasis in daily clinical practice: a study of 103 Italian patients.

Studies comparing the safety and tolerability of biological therapies for psoriasis in the long-term and in daily clinical practice are lacking. Most published studies are of selected patients with short-term (3-6 months) follow-up. We performed a retrospective cohort study of 103 patients in order to describe the frequency and the clinical features of adverse events, and to evaluate and compare the tolerability and safety of efalizumab, etanercept, infliximab, and adalimumab in clinical practice. A total of 136 courses of biological therapies were administered, with a mean duration of 16 months/patient; 55 patients received efalizumab, 45 etanercept, 33 infliximab, and 3 adalimumab. Infliximab had an incidence rate ratio of suspension due to severe adverse events 5.9 times (95% confidence interval (95% CI) 1.9-18, p < 0.001) higher than etanercept and 9.8 times (95% CI 3.2-30.1, p < 0.001) higher than efalizumab. Safety profiles for efalizumab and etanercept were more favourable than for infliximab. Concerning tolerability, we found that more patients responded to infliximab, but long-term tolerability was higher for both efalizumab and etanercept due to the better safety profile and a higher compliance to therapy.

In vivo characterization of the inflammatory infiltrate and apoptotic status in imiquimod-treated basal cell carcinoma.

BACKGROUND: Imiquimod use in the treatment of basal cell carcinoma (BCC) has proven to be successful in a large percentage of cases, inducing tumor regression; however, the exact cellular mechanism has not been fully clarified. AIM: To measure the morphological changes in the tumor microenvironment and the markers of apoptosis in skin biopsies from patients with BCC before and after imiquimod treatment. METHODS: In this open label study, skin biopsies obtained from 11 patients with BCC were evaluated before and after imiquimod treatment for: (i) morphological changes in the tumor microenvironment, with specific emphasis on the immunophenotype of inflammatory cells around the tumor; and (ii) markers of apoptosis, including expression of death receptors. RESULTS: Imiquimod treatment induced a significant increase in the mononuclear inflammatory response. In the majority of cases, the cellular infiltrate was predominantly composed of CD3(+)/CD4(+) T cells, suggesting that the effector response is mediated by CD3(+)/CD4(+) lymphocytes, with a minor cytotoxic and natural killer (NK) component. An increase in the cytotoxic CD3(+)/CD8(+) T-cell population was also observed. Imiquimod treatment was associated with a marked increased in CD20(+) B cells, and a less pronounced enhancement in cells of monocyte-macrophage origin (CD68(+)) surrounding, or within, the tumor. This finding indicates either that macrophages play a minor role in the imiquimod-induced response, or the recruitment of these cells is related to time and dose. Imiquimod treatment decreased CD1A(+) Langerhans cells in the epidermis and increased the number of CD1A(+) dendritic cells within the tumor aggregates. Imiquimod reduced Bcl-2 expression, but no difference was found in Bax, Fas/FasL, and p53 expression in BCC cells. CONCLUSIONS: Our results support the hypothesis that imiquimod activity in the treatment of BCC is partly a result of a pro-inflammatory action mediated by CD3(+)/CD4(+) lymphoid cells and of a pro-apoptotic activity associated with decreased Bcl-2 expression.

Application of optical coherence tomography in non-invasive characterization of skin vascular lesions.

BACKGROUND: Optical coherence tomography (OCT) is a new non-invasive approach for real-time in vivo tissue characterization. A promising use of OCT can be the assessment of the architecture of lesions with some degree of inhomogeneities, such as vascular lesions. Knowledge of the size and depth of the vascular structures can be useful for the diagnosis and for choosing the best treatment. OBJECTIVE: The purpose of this study was to investigate a series of vascular lesions by means of OCT in order to obtain new insights into the non-invasive, pre-operative analysis of these lesions. METHODS: Seven vascular lesions were included in the study. Histopathological diagnosis showed two haemangiomas and one haemolymphangioma; the remaining four cases were classified as haemangiomas on the basis of their clinical appearance. RESULTS: In all lesions, OCT analysis was able to visualize different areas of the lesion from the horny layer to the dermis showing a clear image of the vascular proliferation. Specifically, oval to roundish signal-poor areas sharply demarcated by a surrounding signal-rich layer were observed in good correlation with histopathology. CONCLUSION: The analysis of vascular lesions by OCT provides a new insight into non-invasive diagnosis and can be helpful in the selection of the most appropriate treatment.

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

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

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

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

Features of regression in dermoscopic diagnosis: a confounding factor? Two clinical, dermoscopic-pathologic case studies.

BACKGROUND: In dermoscopy, the presence of regression areas is generally associated with melanocytic lesions and is often considered a clue of malignancy. However, some lesions included in the differential diagnosis of melanoma may show dermoscopic regression parameters. Regression may indeed be one of the most confounding dermoscopic parameters because it tends to cover, or rather to destroy, other parameters, thus often hindering a correct diagnosis. OBJECTIVE: We propose to raise the issue of the actual diagnostic role of this parameter. METHODS: We discuss two clinical cases (melanoma and basal cell carcinoma) with major dermoscopic regression features. CONCLUSION: Dermoscopic regression parameters should not be regarded as almost pathognomonic signs of melanocytic lesions. Rather, they should be taken into account only after having considered other dermoscopic parameters of greater diagnostic significance and just as signs that may better typify the lesion.

Ungual basal cell carcinoma on the fifth toe mimicking chronic dermatitis: case study.

BACKGROUND: The finger, toe, and nail unit are rare sites of basal cell carcinoma (BCC). Only a few patients with BCC of the foot have been described in the world literature, and ungual BCC is even less frequent. OBJECTIVE: To discuss through a case report the clinical features and diagnosis of BCC of the foot. METHODS: We report an unusual case of BCC of the nail unit of the fifth toe of an elderly woman that mimicked chronic dermatitis. CONCLUSION: Our case clearly highlights the need for biopsy and histopathologic examination whenever we see inflammatory lesions with a loss of substance that are refractory to systemic or topical treatments.