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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.

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

Hidradenoma papilliferum (HP) is a rare, slow-growing, benign adnexal tumour with apocrine differentiation. It usually affects the anogenital region in adult women and is clinically polymorphous, mimicking other benign or malignant neoformations. The dermoscopic features of vulval HP have not been reported yet. We report the clinical and dermoscopic features in a case series of histopathologically proven vulval HPs. Dermoscopy may be a useful tool for the diagnosis of vulval HP. To our knowledge, our paper represents the first report of dermoscopic findings in a series of vulval HPs in a multiracial population.

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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.

T he 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.

Background: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. Objective: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. Methods: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. Results: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. Conclusions: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

BACKGROUND In dermoscopy, the presence of regression areas is generally associated with melanocytic lesions and is often considered as 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, as 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 2 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, which may better typify the lesion.

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.We propose to raise the issue of the actual diagnostic role of this parameter.We discuss two clinical cases (melanoma and basal cell carcinoma) with major dermoscopic regression features.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.

In order to investigate the possible role of dermoscopy in the non-invasive classification of combined nevi, we analyzed dermoscopic features of a series of combined nevi consecutively excised. Two dermatologists expert in dermoscopy retrospectively evaluated all images based on the presence of dermoscopic findings to analyze which epiluminescence microscopy features were more frequently associated with each type of combined nevus. Dermoscopy may provide useful information in the non-invasive diagnosis of combined nevi, allowing a conservative management, but this may be limited to combined nevi including a blue nevus component. Conversely, combined nevi including a Spitz nevus component may be difficult to classify even by dermoscopy, thus requiring careful monitoring or surgical excision.

Multiple blue nevi have rarely been reported, and the majority of the lesions are located on the trunk and lower extremities. The blue nevus is a rare lesion on genital mucosa and may cause confusion in differential diagnosis with other pigmented lesions such as genital melanocytic macules, lentigo simplex, and malignant melanoma. Here, we describe an unusual patient who presented with a sudden onset in adulthood of multiple blue nevi on the glans penis. The epiluminescence examination revealed a substantially homogenous bluish pigmentation, which led us to favor a diagnosis of blue nevus, whereas not entirely excluding the possibility of a regressing melanoma or a metastatic melanoma. Because of the well-known diagnostic value of the blue hue in the diagnosis of malignancy by dermoscopy, a careful examination of these lesions should be made in order to minimize any risk of misclassification with melanoma.

Background: It is mandatory that a new diagnostic method be validated by comparison with a well-established reference procedure before being introduced for use in clinical practice. In the field of pigmented skin lesions (PSL), clinical examination should be considered the reference procedure for new diagnostic methods, such as dermoscopy. However, it has not yet been established which is the best photographic procedure for obtaining the most informative clinical images to be used in a formal diagnostic setting. Methods: In this study we investigated the diagnostic information provided by the two most popular methods currently used for clinical photographing of PSL: ‘contact’ images obtained with a Dermaphot (Heine Ltd) at original × 10 magnification without oil application and ‘distant’ images obtained with a macro objective from a distance of 10 cm. Results: Two experienced dermatologists observed clinical images of a series of 57 PSL (11 melanomas, 31 melanocytic nevi, 10 pigmented basal cell carcinomas, and four other diagnoses). The degree of concordance between the diagnoses based on ‘contact’ and ‘distant’ images (melanoma/non-melanoma) was very good (k = 0.819). Regarding histology, the degree of concordance was better when the diagnosis was based on ‘contact’ images (k = 0.54) than ‘distant’ images (k = 0.47). In particular, ‘contact’ images were superior to ‘distant’ images for diagnosis of non-melanoma lesions (specificity of melanoma diagnosis 87.7% vs. 83.6%), but we found no difference in melanoma detection (73% of sensitivity for both methods). Conclusions: Although the two photographic procedures appear to provide similar levels of diagnostic information, the ‘contact’ method seems to provide a higher specificity for melanoma diagnosis.

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.

In dermoscopy, the correct recognition of the single parameters is fundamental to achieve great diagnostic accuracy, but the scarce morphologic expression of a parameter may lead to diagnostic errors. We report the case of a 27-year-old white man presenting a pigmented lesion of the back, which was present since puberty. Clinical examination revealed on the back the presence of a flat, gray-blue lesion and at the periphery a small dark-brown papule. An assessment of the lesion by means of dermoscopy was performed. The purpose of this report was to analyze the Blue Hue in dermoscopy with its histopathologic correlates, starting with the discussion of a clinical case.

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.

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.

Background Palmo-plantar psoriasis (PPP) is a disabling condition that significantly impairs quality of life. PPP tends to be resistant to conventional therapies and may last for several years. Topical treatments are usually ineffective. Systemic therapy with oral retinoids and psoralen plus ultraviolet A is frequently required, although it rarely leads to remission. Study design We conducted an open-label, pilot study to evaluate treatment of PPP with efalizumab, an anti-CD11a monoclonal antibody approved for the treatment of chronic, refractory moderate to severe plaque psoriasis in adults. Methods Five patients with severe PPP received efalizumab treatment for 24 weeks. Results All five patients responded favourably by week 12 and showed further improvement at week 24 of uninterrupted therapy. Mean physician-assessed severity scores and patient-reported outcome scores improved almost 75% after 12 weeks and 90% after 24 weeks. At week 32, three patients maintained the response seen at week 24, while two patients suspended efalizumab. Conclusions Efalizumab therapy was well tolerated and effective in five patients with severe PPP, allowing a significant improvement in quality of life. Conflicts of interest None declared

A 24-year-old woman was referred to our dermatology clinic for assessment of vulvar papules. They had been present for at least 2 years, during which time she had tried a course of imiquimod 5% cream, a wart treatment. The lesions, aside from causing significant embarrassment, had not changed in

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.

Background Skin self-examination (SSE) is associated with thinner melanomas in both North American and Italian patients. The knowledge of conditions associated with SSE may help in refining educational strategies for the prevention of melanoma. Objective The aim of the study was to investigate the frequency of SSE and the factors associated with SSE in subjects followed at a specialized pigmented lesion clinic (PLC) in Italy. Patients/methods A series of 299 consecutive subjects who visited the Florence PLC was investigated by means of a self-administered questionnaire regarding SSE habits. The statistical association between SSE and selected variables was examined by univariate and multivariate analyses. Results In the univariate analysis, variables significantly associated with SSE were: green/blue eyes, phototype I/II, the presence of large numbers of common acquired and atypical melanocytic naevi, sunscreen use, having had a previous PLC examination, and having received a leaflet explaining SSE. SSE was less frequent in women using sunbeds and more frequent in those performing breast self-examination. Using the multivariate model, which included all the variables associated with SSE in the previous analysis, we found that, among males, the only variable significantly associated with SSE was the report of having received a leaflet explaining SSE [odds ratio (OR) 3.02, 95% confidence interval (CI) 1.24–7.38]. Among females, having had a previous consultation at a PLC was significantly associated with SSE (OR 4.84, 95%CI 1.57–14.93); this might be because of the explanation and advice about skin cancer prevention customarily provided as a part of the PLC consultation at our department. Conclusion Educational tools, including a leaflet explaining SSE and counselling given within previous PLC visits, seem to play a crucial role in promoting SSE habits in subjects followed at a specialized PLC consultation.

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.

The diagnosis of seborrheic keratosis is, in general, a clinical one, but in some cases, the differential diagnosis between pigmented seborrheic keratosis and malignant melanoma is difficult. Dermoscopy may improve the early diagnosis of vulvar melanoma and thus play a role in the preoperative classification of pigmented lesions at this particular site. We report the first case of a pigmented seborrheic keratosis of the vulva clinically mimicking a malignant melanoma, whose dermoscopic features have been investigated together with their pathologic correlates. Dermoscopically our case shows the absence of comedo-like openings and the presence of the pseudo-network. Dermoscopy is therefore a useful method for the differential diagnosis of pigmented lesions even in the vulva.

Objectives Basal Cell Carcinoma (BCC) is the most common human malignant neoplasm. It does not occur only in anatomical areas commonly exposed to sunlight, but also in relatively protected body sites such as the axillae, the groin and buttocks, and in regions which are entirely protected from the sun, like the vulva. The aim of this study is to assess the impact and clinical features of BCCs in the vulva versus other anatomical sites. Methods For this purpose, we retrospectively reviewed all the histological diagnoses of BCCs made between 1995 and 2003 in the Department of Human Pathology and Oncology of the University of Florence, Italy. Results Out of 3604 cases of BCC, 63 were in the vulva. The average age of patients suffering from the latter was 70.35 years. The average size of the vulvar BCCs was 2.1 cm and 18 (28%) were ulcerated at presentation. Conclusions Our study shows that vulvar BCC is not a particularly rare occurrence; in fact it should be suspected whenever lesions that we believe to be inflammatory do not respond to usual treatment. In our experience, mucocutaneous examination of this anatomical area should be performed especially in patients with a history of skin cancer. In case of suspicion, a biopsy is recommended to obtain a preoperative confirmatory diagnosis.

Multiple blue nevi have rarely been reported, and the majority of the lesions are located on the trunk and lower extremities. The blue nevus is a rare lesion on genital mucosa and may cause confusion in differential diagnosis with other pigmented lesions such as genital melanocytic macules, lentigo simplex, and malignant melanoma. Here, we describe an unusual patient who presented with a sudden onset in adulthood of multiple blue nevi on the glans penis. The epiluminescence examination revealed a substantially homogenous bluish pigmentation, which led us to favor a diagnosis of blue nevus, whereas not entirely excluding the possibility of a regressing melanoma or a metastatic melanoma. Because of the well-known diagnostic value of the blue hue in the diagnosis of malignancy by dermoscopy, a careful examination of these lesions should be made in order to minimize any risk of misclassification with melanoma.

Background Multiple basal cell carcinomas (BCCs) are infrequently seen in patients under 30 years of age. Their occurrence at a young age is often linked to some genodermatosis, including Nevoid Basal Cell Carcinoma Syndrome (NBCCS). The exposure to ionizing radiation is also considered to be a predisposing factor in the development of BCCs. Methods We report the case of a 35-year-old patient who presented with seven synchronous, nodular, brownish-pigmented BCCs, confined within the radiation-treated cutaneous areas, 15 years after receiving Cobalt-60 (60Co) irradiation for Hodgkin’s disease. Results On the basis of clinical, radiological, and anamnestic data we excluded a NBCCS, thus proposing irradiation as the cause of the multiple synchronous pigmented BCCs. Conclusions Previous therapeutic ionizing radiation leads to an increased risk of BCCs confined to the region of the body to which radiotherapy was delivered. We consider our patient’s BCCs represents a late adverse effect of the treatment with Cobalt-60.