Search

The increase life expectancy led to an expected increase in skin cancer incidence in older patients. Their treatment can require a complex decision-making process. Limited data are available on characteristics, management and outcome of skin tumours in nonagenarian and centenarian patients. The aim of our study was to describe epidemiology, clinical-pathological features and treatment strategies of skin cancers in a cohort of patients aged ≧95 years. A total of 116 patients ≧95 years of age presented for the evaluation of 225 skin lesions (mean of 1.94 lesions per patient). The mean age was 97.4 years, 57.8% were women. Most patients had an ECOG score of 3 (49.3%) or 4 (32%). Lesions were mainly located on the head and neck area (74.2%), upper (7.1%) and lower (6,2%) limbs. The majority of patients presented with non-melanoma skin cancers (183/225; 81.3%), 25/225 (11.1%) had actinic keratosis, 5 (2.2%) melanoma and 2 (0.9%) atypical fibroxanthoma. Forty-eight lesions (21.3%) were treated with surgery, 58 (25.8%) with radiotherapy. The management of 73 lesion (32.4%) was discussed at the multidisciplinary tumour board meeting. One patient died for the progression of a squamous cell carcinoma; 74 patients died for causes unrelated to skin tumours, 36 are still alive after a mean follow-up of 27.27 months. This cohort study confirms that age is not per se a contraindication for treatment of skin cancers in elderly patients. Our results support the importance of a patient-centred care approach that should take into consideration patient's preferences, comorbidities, compliance and possible adverse events.

Background: Scalp melanomas are usually thicker and show worse prognosis than other sites and other head and neck melanomas. One hypothesis to explain this aggressive behavior could be diagnosis delay attributed to hair concealment of lesions. Methods: Primary melanomas of the scalp diagnosed over two decades at four reference centers in Australia and Italy were included. Hair coverage and visibility of the lesions were assessed on preoperative photographic documentation by two investigators and correlated with some prognostic factors (Breslow thickness, mitotic rate, and ulceration). Patients records and pathology reports provided clinical and histological data. Results: The majority of 113 melanomas included were located on easily visible areas of the scalp – hairless scalp (49%) or hairline (15%). The remaining ones (36%), considered to be hair-covered, showed more frequently thinning of hair (63%) than a dense hair coverage (37%). Melanomas of “hairy scalps” were more frequently invasive (81%) and had higher median Breslow (0.8±1.3mm) than those arising on bald scalps or areas with thinning of hair (43%; 0±0.6mm), P=0.004. However, when considering only the invasive cases (n=55), Breslow thickness and mitotic rate were not statistically different between concealed and easily visible areas. Melanomas detected by a doctor were thinner than those first noticed by the patient, relatives, or a hairdresser (P&nbsp

Recently, 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) topical solution has been included in the National Italian portfolio for lesion-directed treatment of grade I/II actinic keratosis (AKs) located on the face or scalp. To describe the utility of dermoscopy and RCM in treatment response monitoring of a series of AKs treated with 5-FU/SA as lesion-directed therapy. Consecutive patients were prospectively treated for a maximum of 12 weeks with 5-FU/SA for AKs located on the face or scalp. Clinical, dermoscopic, and confocal images of one index AK were acquired at each visit and pre-specified criteria were evaluated. Clinical, dermoscopic, and confocal responses were evaluated at last follow-up visit. Fourteen patients were enrolled, of which five were treated for 12 weeks, seven for 8, and two for 4 weeks. At a median follow up of 30 weeks, 64.3% (9/14) index AKs achieved complete clinical, 50% (7/14) complete dermoscopic and 42.9% (6/14) complete confocal clearance. Local skin reaction was mild and significantly decreased during therapy administration. Although the small number of cases, our study underlines the utility of both dermoscopy and in-vivo RCM in 5-FU/SA treatment response monitoring for AKs located on the face or scalp.

Background Ingenol mebutate (IngMeb) 0.015% gel is an approved field treatment option for non-hyperkeratotic non-hypertrophic actinic keratosis (AK) of face and scalp. Efficacy of IngMeb has been assessed only on a clinical ground, in the majority of studies. Dermoscopy is a pivotal tool for the diagnosis of AK, while its role in evaluating the response to non-surgical therapies for AK has not been fully defined. Objectives Our study aims to determine whether some dermoscopic features of AK of the face and scalp areas may independently predict the response to IngMeb therapy. Methods Clinical and dermoscopic responses, 1 month after 0.015% IngMeb therapy, were retrospectively evaluated using a per-patient and per-lesion approach. Safety was evaluated through local skin reaction composite score calculation. Demographic, clinical and dermoscopic factors were then evaluated via univariate and multivariate logistic regression analysis to assess independent predictors of response. Results Fifty-five patients with 245 AKs were enrolled. Clinically, per-patient response evaluation identified 25 (45.4%) poor/partial and 30 (54.5%) complete responders, corresponding on a per-lesion approach to 66 (26.9%) and 179 (73.1%) AKs, respectively. Dermoscopy reclassified 14 patients in the per-patient and 48 AKs in the per-lesion analysis from complete to poor/partial responders. Multivariate logistic regression analysis showed that AKs dermoscopically characterized by red pseudonetwork and located on the face were independently associated with a complete dermoscopic response to 0.015% IngMeb therapy, while microerosions were negative predictors. Conclusion Specific dermoscopic features of AK may predict the response to 0.015% IngMeb therapy, together with the location on the face.

Background Nevus-associated melanoma (NAM) has been regarded as a distinct biological entity from de-novo melanoma (DNM); however, static dermoscopy often fails in differentiating these entities. Digital dermoscopic monitoring allows to identify dynamic changes occurring during follow-up; this may improve diagnostic accuracy and potentially our knowledge on NAM biology. We aimed to define main independent factors associated with NAM diagnosis and those influencing follow-up time in a population of melanomas excised at follow-up. Methods A cohort of melanomas excised at follow-up was retrospectively and consecutively selected. NAMs and DNMs were compared according to baseline features and main dermoscopic changes occurring during follow-up. Univariate and multivariable logistic and Cox's regression analysis were performed to respectively define factors associated with NAM diagnosis and those influencing the risk for excision. Results Eighty-six melanomas were enrolled, of which 21 (24.4%) were nevus-associated. During follow-up NAMs mainly underwent atypical network modifications (47.6%), followed by inverse network (28.6%) and dermoscopic island (23.8%) worsening or appearance. DNMs were also mainly characterized by atypical network modifications (47.7%), however, a significant proportion of cases underwent irregular pigmentation/dots/globules or regression changes (29.2%), which were rarely seen among NAMs. Furthermore, both multivariable logistic and Cox's regression analysis demonstrated a significant association between NAM and a longer follow-up. Conclusions We demonstrated that among melanomas excised at follow-up, different patterns of dermoscopic changes may be found between NAMs and DNMs. This finding, together with the association of NAM with a longer follow-up time, supports the hypothesis of different biological behavior of these two entities.

Background Imiquimod 3.75% cream (Zyclara® Meda, Stockholm, Sweden) is a new field-directed therapy for actinic keratosis (AK). Objectives The aim is to evaluate efficacy and the morphologic dynamic changes induced by this treatment by means of dermatoscopy and reflectance confocal microscopy (RCM) of imiquimod 3.75% cream for the treatment of AKs of the face or scalp and to evaluate. Methods Thirty-two patients were treated with Imiquimod 3.75% cream. Demographic parameters, AK-FAS and AKASI scores and side-effects were collected. RCM and dermatoscopy on one target AKs were performed at each visit. We collected images at baseline (T0), after 1 week from the end of the first 2-week cycle (T1), after 1 week from the end of the entire treatment (T2) and 2 months after the end of treatment (T3). Results One target representative AK in the selected area of treatment of each patient was analysed. All dermoscopic and confocal parameters were reduced 2 months after the end of the therapy (T3) with a substantial reduction of AKASI and AK-FAS scores, and 17 cases (54.8%) were completely solved. Confocal microscopic analysis showed a reduction of keratinocytes disarray in 77.4% of cases; none showed crusts and parakeratosis. Inflammation was considerably decreased and was observed only in 12.9% of patients at the last visit. This improvement was not assessed on dermatoscopy because of inflammation and background erythema, which adversely influenced the assessments. LSRs were observed in almost all the patients during treatment being more severe after the first cycle of treatment (T1). Conclusions Imiquimod 3.75% cream is effective in treating clinical and subclinical AKs with an easy management of side-effects. Dermatoscopy and mostly RCM allow non-invasive monitoring of treatment response in vivo.

Background In vivo reflectance confocal microscopy significantly improves melanoma diagnosis as compared to clinical/dermoscopic examination alone. Several confocal criteria have been described allowing to differentiate melanoma from nevi; by combining different criteria, three pure confocal scores (Pellacani 2005, Segura 2009 and Pellacani 2012) and one mixed dermoscopic/confocal score (Borsari 2018) were constructed. Objective Our aim was to externally validate and compare the performance of these confocal scores. Methods We retrospectively enrolled excised melanocytic lesions which underwent confocal examination in a 2-year period. Lesions located on the face and acral sites were excluded. Both dermoscopic and confocal criteria considered in the four scores were evaluated by experts. Subsequently, specificity and sensitivity levels for each score were calculated, together with the positive and negative predictive values and likelihood ratios; also, receiver operating characteristic curves were constructed. Results A total of 389 patients with 422 lesions were retrospectively enrolled, of which 162 (38.4%) were melanomas and 260 (61.6%) were nevi (189 common and 71 Spitz/Reed nevi). The highest sensitivity levels were recorded for Segura 2009 with cut-off ≥-1 (92.0%), while Pellacani 2005 with cut-off ≥5 achieved the highest specificity (69.6%). The score by Borsari et al. showed the highest levels of positive and negative predictive values (59.8% and 91.5%) and likelihood ratios (2.4 and 0.1) as well as the highest area under the curve values (0.76; 95% CI 0.72-0.81; P Conclusions High levels of accuracy were found for each of the four considered scores. No differences were found among scores in confirming melanoma diagnosis when positive; however, the score by Borsari 2018 was the best in excluding melanoma diagnosis when negative.

Melanomas and nevi displaying regression features can be difficult to differentiate. To describe reflectance confocal microscopy features in benign and malignant pigmented skin lesions characterized by regression features in dermoscopy. Methods: Observational retrospective study. Inclusion criteria were presence of dermoscopic features of regression; availability of clinical, dermoscopic and RCM imaging; definite histopathologic diagnosis. The study sample comprised 217 lesions; 108 (49.8%) melanomas and 109 were benign lesions, of which 102 (47.0%) nevi and 7 (3.2%) lichen planus like keratosis (lplk). Patients with melanoma were significantly older than those with benign lesions (61.9±15.4 vs. 46.1±14.8; p

Introduction A relatively novel application for dermoscopy and reflectance confocal microscopy (RCM) is their use in the monitoring of topical treatment response for non-melanoma skin cancer. Actinic keratosis (AK) is the early phase of a multistep biologic continuum leading to invasive squamous cell carcinoma. A number of topical therapies are now available for the treatment of AK but their disadvantages include long treatment duration and prolonged local reactions. Ingenol mebutate is a newer therapy for AK which is only applied for 2 or 3 days. Case Report Dermoscopy and RCM findings in two patients with AK treated with ingenol mebutate confirm that it induces rapid lesion necrosis and specific neutrophil-mediated, antibody-dependent cellular cytotoxicity. Necrosis occurs via mitochondrial membrane disruption, with subsequent eradication of residual tumor cells via transient inflammation. Local skin reactions to ingenol mebutate should be considered part of the drug’s mechanism of action rather than an adverse effect. Conclusion Ingenol mebutate is a valuable therapy for the treatment of AK. This case report adds further evidence to the usefulness of dermoscopy and RCM in the assessment and monitoring of treatment outcome. Electronic supplementary material The online version of this article (doi:10.1007/s13555-016-0094-9) contains supplementary material, which is available to authorized users.

We present an unusual onset of cutaneous lichen planus (LP) in a middle-aged patient. The initial presentation as solitary, indolent pink lesion, required further investigations to rule out malignancy and especially amelanotic melanoma. Dermoscopy and reflectance confocal microscopy findings revealed to be helpful in our case, addressing the correct diagnosis.

Nearly 20% of melanomas occur on the head and neck area(1) but only 2-5% arise on the scalp.(2) Several studies reported a worse prognosis of scalp melanoma compared to other body sites, being unclear the reason for this phenomenon.(3) Melanoma and non-melanoma skin cancer of the scalp are most frequent in bald men older than 65 years. This article is protected by copyright. All rights reserved.

Background Although several dermoscopic features of in situ melanoma have been identified, data on confocal features of in situ melanoma are still lacking. Objectives To identify reflectance confocal microscopy (RCM) features of in situ melanoma and to develop a diagnostic score combining dermoscopy and RCM. Methods In total, 120 in situ melanoma and 213 nevi (test set) were retrospectively analysed to assess the presence of dermoscopic and RCM criteria. Facial and acral lesions were excluded. Spearman's correlation, univariate and multivariate regression models were used to identify features significantly correlated with in situ melanoma diagnosis. Multivariate results on the test set allowed the development of a multistep algorithm, that was tested on a validation set of 100 lesions. Results The dermoscopic findings of an atypical network and regression were independent predicting factors for in situ melanoma diagnosis [odds ratio (OR) 3·44, 95% CI (confidence interval) 1·70-6·97 and OR 4·17, 95% CI 1·93-9·00, respectively]. Significant confocal predictors for malignancy were epidermal pagetoid spread (OR 2·83, 95% CI 1·32-6·04) and junctional cytological atypia (OR 3·39, 95% CI 1·38-8·30 if focal, OR 8·44, 95% CI 3·21-22·16 if widespread). A multistep diagnostic algorithm able to predict in situ melanoma with a sensitivity of 92·5% and a specificity of 61% was developed. The validation set confirmed the high diagnostic value (sensitivity 92%, specificity 58%). Conclusions An easy and reproducible multistep algorithm for in situ melanoma detection is suggested, that can be routinely used in tertiary centres.

Background: Lower limbs represent an uncommon location for basal cell carcinoma (BCC) and only few reports have described dermoscopic features of BCC in this body site. Since BCCs of the lower limbs frequently display nonclassic BCC dermoscopic criteria, they can simulate other benign or malignant lesions. Objective: Our aim was to describe the dermoscopic features of BCC located on lower limbs and to define which criteria were more associated with their benign- or malignant-looking appearance. Methods: We conducted a retrospective study enrolling consecutive patients with histologically confirmed BCCs of the lower limbs. Lesions were classified in 7 categories according to the clinical and dermoscopic global appearance. Clear BCC, squamous cell carcinoma (SCC) or Bowen disease-like, Kaposi disease-like, melanoma-like, and aspecific pattern were considered malignant-looking lesions; however, seborrheic keratosis-like and dermatofibroma-like were considered benign-looking. To define which dermoscopic criteria were independently associated with benign- or malignant-looking appearance, we conducted a multivariate logistic regression analysis. Results: A total of 81 BCCs were enrolled: 18 (22%) were benign-looking lesions (of which 11 were seborrheic keratosis-like and 7 dermatofibroma-like) and 63 (78%) were malignant-looking BCCs (of which 24 were clear-cut BCCs, 23 SCC-like, 2 Kaposi disease-like, 9 melanoma-like, and 5 had aspecific pattern). Multivariate regression analysis showed that erosions/ulceration and vessels were independently associated with malignant-looking appearance. The most represented vessels were glomerular and polymorphic, which are more frequently encountered in SCC, together with ulceration. Conclusion: BCC of the lower legs frequently simulates other benign or malignant lesions, with SCC being the main differential diagnosis.

The accuracy of melanoma-specific dermoscopic criteria has been tested mainly in studies including invasive tumors. Scarce evidence exists on the usefulness of these criteria for the diagnosis of melanoma in situ (MIS). IMPORTANCE The accuracy of melanoma-specific dermoscopic criteria has been tested mainly in studies including invasive tumors. Scarce evidence exists on the usefulness of these criteria for the diagnosis of melanoma in situ (MIS). OBJECTIVE To investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of MIS. DESIGN, SETTING, AND PARTICIPANTS A diagnostic accuracy study with retrospective patient enrollment was conducted in 3 centers specializing in skin cancer diagnosis and management. A total of 1285 individuals with histopathologically diagnosed MIS or other flat, pigmented skin tumors that were histopathologically diagnosed or monitored for at least 1 year were included. Dermoscopic images of MIS and other flat, pigmented skin tumors were evaluated by 3 independent investigators for the presence of predefined criteria. Evaluators were blinded to the clinic dermoscopic and histopathologic diagnosis. MAIN OUTCOMES AND MEASURES Frequencies of dermoscopic criteria per diagnosis were calculated. Crude odds ratios, adjusted odds ratios, and corresponding 95% CIs were calculated by univariate and multivariate logistic regression, respectively. RESULTS A total of 1285 patients were included in the study (642 [50%] male); mean age was 45.9 years (range, 9-91 years). Of a total of 1285 lesions obtained from these patients, 325 (25.3%) were MIS; 574 (44.7%) were nevi (312 [24.3%] excised and 262 [20.4%] not excised); 67 (5.2%) were seborrheic keratoses, solar lentigines, or lichen planus-like keratoses; 91 (7.1%) were pigmented superficial basal cell carcinomas; 26 (2.0%) were pigmented intraepithelial carcinomas; 100 (7.8%) were Reed nevi; and 102 (7.9%) were invasive melanomas with a Breslow thickness less than 0.75 mm. The most frequent dermoscopic criteria for MIS were regression (302 [92.9%]), atypical network (278 [85.5%]), and irregular dots and/or globules (163 [50.2%]). The multivariate analysis revealed 5 main positive dermoscopic indicators of MIS: atypical network (3.7-fold; 95% CI, 2.5-5.4), regression (4.7-fold; 95% CI, 2.8-8.1), irregular hyperpigmented areas (5.4-fold; 95% CI, 3.7-8.0), prominent skin markings (3.4-fold; 95% CI, 1.9-6.1), and angulated lines (2.2-fold; 95% CI, 1.2-4.1). When compared only with excised nevi, 2 of these criteria remained potent MIS indicators, namely, irregular hyperpigmented areas (4.3-fold; 95% CI, 2.7-6.8) and prominent skin markings (2.7-fold; 95% CI, 1.3-5.7). CONCLUSIONS AND RELEVANCE Clinicians should take into consideration the aforementioned dermoscopic indicators for the diagnosis of MIS.

Background Nevi of special sites encompass a class of benign lesions characterized by the presence of atypical clinical and histopathologic features that can be difficult to distinguish from melanoma. Dermoscopy and reflectance confocal microscopy may improve the clinical assessment of melanocytic lesions in order to avoid unnecessary excisions. Objectives The aim of this study was to assess the value of specific dermoscopic and confocal criteria in distinguishing melanomas from nevi of the breast area. Methods Dermoscopic and confocal images from consecutive patients with at least 1 clinically and/or dermoscopically equivocal melanocytic skin lesion of the breast area were retrospectively evaluated. In this case-control study, only histopathologically-proven melanomas (cases) and nevi (controls) were included. Spearman's coefficients were first calculated to flag significant correlation; then univariate and multivariate logistic regression analysis were performed to assess which factors were independently associated with the histopathological diagnosis. Finally, a mixed dermoscopic/confocal score was created to distinguish nevi from melanomas on the breast area. Results The study population included 55 skin lesions of the breast area, 34 (61.8%) nevi and 21 (38.2%) melanomas. Among dermoscopic criteria, atypical network and irregular pigmentation resulted independently associated with melanoma diagnosis (OR: 11.1; 95%CI 1.0-119.9; P:.048 and OR: 6.5; 95%CI 1.1-37.5; P:.037, respectively). Furthermore, on RCM examination the presence of pagetoid cells was an independent positive predictor for melanoma (OR: 38.5; 95%CI 3.9-379.6; P:.002). The mixed score showed high levels of sensitivity and specificity, 95.2% and 82.4%, respectively, which were higher than dermoscopic and confocal evaluations alone. Conclusion The combined use of dermoscopy and confocal microscopy in the triage of pigmented lesions of the breast area may help in increasing the diagnostic accuracy and avoiding unnecessary excisions. This article is protected by copyright. All rights reserved.

The use of confocal microscopy is possible using two different modalities: first, at patient's bedside for a rapid in vivo diagnosis of basal cell carcinoma and second, in the operating room directly on freshly excised specimen for a fast ex vivo margin-controlled surgery. In the current review, we report the main application of confocal microscopy for basal cell carcinoma diagnosis and management in both modalities.

Background Diagnosis of bullous pemphigoid (BP) and pemphigus is based on clinical features, histology, immunofluorescence and laboratory data. Objectives To evaluate features of BP and pemphigus at reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in order to provide a rapid non-invasive bed-side diagnosis. Secondary objective was to evaluate the detectability of clinically non-visible lesions. Methods This was an observational, retrospective, multicentre study in which patients with suspicious lesions for BP or pemphigus underwent clinical assessment, RCM, OCT, blood tests and skin biopsy for histological and direct immunofluorescence examinations from January 2014 to December 2015. A total of 72 lesions in 24 selected patients were evaluated. Additionally, apparently unaffected skin at two different distances [near (1-2 cm) and far (2-3 cm)] from each lesion was examined to test subclinical lesion detectability. Results RCM was able to detect subepidermal and intra-epidermal blisters, respectively, in 75% and 50% of the patients affected by BP and pemphigus. At OCT, the exact blister level was identified in all patients. Acantholytic cells were observed only at RCM in pemphigus (62.5%). Fibrin deposition inside the blisters was only found in BP, evidenced both at RCM and OCT. Among patients with BP, subclinical blisters were detected in nine (9.4%) clinically healthy skin, while among patients with pemphigus were observed in 10 (20.8%) apparently unaffected skin. Conclusion RCM and/or OCT provide useful information for a rapid diagnosis of BP and pemphigus and for the identification of biopsy site. Combined use of RCM and OCT is optimal because associates the higher resolution of RCM with the greater penetration depth of OCT. OCT could be an optimal tool for treatment monitoring, especially in the cases of subclinical lesions. However, histopathologic and immunologic examinations remain the gold standard for establishing the final diagnosis.

Background Squamous cell carcinoma (SCC) of the skin is a highly prevalent neoplasm. The management and the prognosis of this tumor is dependent on its invasiveness and its grade of differentiation. Objectives To evaluate whether specific dermoscopic and reflectance confocal microscopy (RCM) criteria can predict the diagnosis of invasive SCC vs in situ SCC and poorly differentiated compared with well- and moderately differentiated SCC. Methods Dermoscopic and RCM images of SCCs were retrospectively evaluated for the presence of predefined criteria. Results Among 143 SCC, 121 cases had a complete set of images and thus were included in the study set. The head and neck area was the most frequently involved body site (74/121; 61.1%) followed by extremities (36/121, 29.7%) and trunk (11/121, 9.1%). Seventy tumors were in situ (57.8%), while 51 were invasive (42.1%), of these 11 were poorly differentiated (21.5%), 16 were moderately differentiated (31.3%), and 24 were well differentiated (47.0%). Chi-squared analysis demonstrated that invasive SCC were characterized by polymorphic vessels, erosion/ulceration, architectural disarrangement, speckled nucleated cells in the dermis, irregularly dilated vessels and absence of hyperkeratosis. Botton-hole vessels, white structureless areas and dotted or glomerular vessels were significantly associated with in situ lesions. Poorly differentiated SCC were typified by red areas, erosion/ulceration and architectural disarrangement. Well or moderately differentiated SCC were associated with white areas and speckled nucleated cells in the epidermis. Conclusion Clinical, dermscopic and RCM images provide useful information that should be integrated in order to achieve the optimal therapeutic management for the patient. This article is protected by copyright. All rights reserved.

Background: Actinic keratosis (AK) is a common keratinocyte intraepidermal neoplasia. Objective: To assess AK prevalence and potential risk factors in patients attending Italian general dermatology clinics. Materials & methods: This retrospective study was conducted on clinical data from consecutive white outpatients aged ≥30 years, attending 24 general dermatology clinics between December 2014 and February 2015. AK prevalence (entire population) and multivariate risk factor analysis (patients with current/previous AK and complete data) are presented. Results: AK prevalence in 7,284 patients was 27.4% (95% CI: 26.4-28.4%); 34.3% in men and 20.0% in women (p70 years), history of other non-melanoma skin cancers (OR: 2.7 [2.2-3.3]), residence in southern Italy/Sardinia (OR: 2.6 [2.1-3.0]), working outdoors >6 hours/day (OR: 1.9 [1.4-2.4]), male gender (OR: 1.7 [1.4-2.0]), facial solar lentigos (OR: 1.6 [1.4-1.9]), light hair colour (OR: 1.5 [1.2-1.8]), prolonged outdoor recreational activities (OR: 1.4 [1.2-1.7]), light eye colour (OR: 1.3 [1.1-1.6]), skin type I/II (OR: 1.3 [1.1-1.6]), and alcohol consumption (OR: 1.2 [1.0-3.3]). BMI ≥25.0 (OR: 0.6 [0.5-0.7]), regular sunscreen use (OR: 0.7 [0.6-0.8]), and a lower level of education (OR: 0.8 [0.7-1.0]) were independent protective factors. Conclusions: AK prevalence was high in Italian dermatology outpatients. We confirm several well-known AK risk factors and reveal possible novel risk and protective factors. Our results may inform on the design and implementation of AK screening and educational programmes.

Background The latest AJCC classification has included the number of mitoses as a factor for upstaging thin melanomas. Meanwhile, while dermoscopy has often been used to predict melanoma thickness, its value in predicting number of mitoses remains unknown. Objective Our aim is to evaluate the correlation between dermoscopic features and the presence of mitoses in a consecutive cohort of thin melanomas. Methods A case control study has been performed to identify specific dermoscopic parameters that could differentiate thin melanomas with 1 or more mitoses per mm2 from those without mitoses. Results Of 177 melanomas equal to or thinner than 1 mm, 131 (74%) lesions had no mitoses and 46 (36%) lesions had at least 1 mitosis × mm2. Dermoscopic features associated with the presence of 1 or more mitoses were the following: peripheral streaks (OR 4.11; 95% CI 1.94–8.71) and black colour (OR 4.70; 95% CI; 2.28–9.68). In contrast, atypical pigment network (OR (0.30; 95% CI 0.15–0.61)) and brown colour (OR 0.36; 95% CI 0.18–0.75) were associated to melanomas without mitoses. The same variables were also associated to the increasing number of mitoses at linear regression. Conclusion Black colour and peripheral streaks can predict the presence of mitoses in thin melanoma, while atypical pigment network and brown colour are associated to thin melanoma without mitoses.

Background Reflectance confocal microscopy (RCM) is an imaging device that permits non-invasive visualization of cellular morphology and has been shown to improve diagnostic accuracy of dermoscopically equivocal cutaneous lesions. The application of double reader concordance evaluation of dermoscopy-RCM image sets in retrospective settings and its potential application to telemedicine evaluation has not been tested in a large study population. Objective To improve diagnostic sensitivity of RCM image diagnosis using a double reader concordance evaluation approach; to reduce mismanagement of equivocal cutaneous lesions in retrospective consultation and telemedicine settings. Methods 1000 combined dermoscopy-RCM image sets were evaluated in blind by 10 readers with advanced training and internship in dermoscopy and RCM evaluation. We compared sensitivity and specificity of single reader evaluation versus double reader concordance evaluation as well as the effect of diagnostic confidence on lesion management in a retrospective setting. Results Single reader evaluation resulted in an overall sensitivity of 95.2% and specificity of 76.3%, with misdiagnosis of 8 melanomas, 4 basal cell carcinomas and 2 squamous cell carcinomas. Combined double reader evaluation resulted in an overall sensitivity of 98.3% and specificity of 65.5%, with misdiagnosis of 1 in-situ melanoma and 2 basal cell carcinomas. Conclusion Evaluation of dermoscopy-RCM image sets of cutaneous lesions by single reader evaluation in retrospective settings is limited by sensitivity levels that may result in potential mismanagement of malignant lesions. Double reader blind concordance evaluation may improve the sensitivity of diagnosis and management safety. The use of a second check can be implemented in telemedicine settings where expert consultation and second opinions may be required.

Importance Reflectance confocal microscopy (RCM) improves diagnostic accuracy in skin cancer detection when combined with dermoscopy; however, little evidence has been gathered regarding its real impact on routine clinical workflow, and, to our knowledge, no studies have defined the terms for its optimal application. Objective To identify lesions on which RCM performs better in terms of diagnostic accuracy and consequently to outline the best indications for use of RCM. Design, Setting, and Participants Prospectively acquired and evaluated RCM images from consecutive patients with at least 1 clinically and/or dermoscopically equivocal skin lesion referred to RCM imaging, from January 2012 to October 2014, carried out in a tertiary referral academic center. Main Outcomes and Measures A total of 1279 equivocal skin lesions were sent for RCM imaging. Spearman correlation, univariate, and multivariate regression models were performed to find features significantly correlated with RCM outcome. Results In a total of 1279 lesions in 1147 patients, RCM sensitivity and specificity were 95.3% and 83.9%, respectively. The number of lesions needed to excise to rule out a melanoma was 2.4. After univariate and multivariate regression analysis, head and neck resulted as the most appropriate body location for confocal examination; RCM showed a high diagnostic accuracy for lesions located on sun-damaged skin (adjusted odds ratio [aOR], 2.13; 95% CI, 1.37-3.30; P=.001) and typified by dermoscopic regression (aOR, 2.13; 95% CI, 1.31-3.47; P=.002) or basal-cell carcinoma specific criteria (aOR, 9.35; 95% CI, 1.28-68.58; P=.03). Conclusions and Relevance Lesions located on the head and neck, damaged by chronic sun-exposure, and dermoscopically typified by regression represent best indications for the use of RCM.

Background Longitudinal melanonychia might be difficult to differentiate and the use of dermoscopy can be useful for the preoperative evaluation and management decision. Objectives The aim of our study was to investigate clinical and dermoscopic criteria of acquired longitudinal melanonychia in adults to identify the best predictors of melanoma using a multivariate analysis and to explore eventual new dermoscopic criteria for nail melanoma diagnosis. Methods In this retrospective observational study, 82 histopathologically diagnosed, acquired nail pigmented bands were collected and examined. All variables were included in the analysis and examined as possible predictors of nail melanoma. Both univariate and multivariable analyses have been performed. Results Among 82 cases, 25 were diagnosed as nail melanoma and 57 as benign lesions (including 32 melanocytic nevi and 25 benign melanocytic hyperplasia). Melanoma cases were significantly associated with a width of the pigmented band higher than 2/3 of the nail plate, grey and black colours, irregularly pigmented lines, Hutchinson and micro-Hutchinson signs, and nail dystrophy. Granular pigmentation, a newly defined dermoscopic criterion, was found in 40% of melanomas and only in 3.51% of benign lesions. Conclusions Dermoscopic examination of longitudinal melanonychia provides useful information that could help clinicians to improve melanoma recognition.

Background/purpose: Multiphoton microscopy (MPM) enables the assessment of unstained living biological tissue with submicron resolution, whereas fluorescence lifetime imaging microscopy (FLIM) generates image contrast between different states of tissue characterized by various fluorescence decay rates. The aim of this study was to compare the healthy skin of young individuals with that of older subjects, as well as to assess the skin at different body sites, by means of MPM and FLIM. Methods: Nineteen elderly patients were examined on the outer side of the forearm, whereas 30 young individuals were assessed on the dorsal and volar sides of the forearm and on the thigh. Results: Cell and nucleus diameters, cell density and FLIM vary according to the epidermal cell depth and the skin site. In elderly subjects, epidermal cells show morphologic alterations in shape and size, with smaller cell and nucleus diameters; the number of basal cells is decreased, whereas the mean fluorescence lifetimes at both the upper and the lower layers increase. Conclusion: This study provides quantitative and qualitative data on normal epidermis at different skin sites at different ages and represents a reference for the clinician attempting to understand the effectiveness of MPM and FLIM in discriminating diseased states of the skin from normal ones.

Introduction La pemphigoide bulleuse (PB) et le pemphigus vulgaire (PV) sont des maladies auto-immunes caracterisees par la presence de bulles cutanees et ou muqueuses. Le diagnostic de ces maladies bulleuses repose sur une combinaison de criteres cliniques, histologiques, d’immunofluorescence et biologique. L’utilite de la microscopie confocale de reflectance de (MRC) et tomographie par coherence optique (OCT) pour le diagnostic de BP et de PV a ete rapporte dans un petit nombre de cas. Nous rapportons l’examen en MRC et l’examen OCT des caracteristiques de BP et PV. Materiel et methodes Il s’agissait d’une etude observationnelle multicentrique dans laquelle les patients presentant des lesions suspectes pour BP ou PV ont eu un examen clinique, en MRC (Vivascope 3000® Caliber) et OCT (Vivosight®, Mickelson) ; de plus etaient realises un examen histologique et une immunofluorescence directe et indirecte. Vingt-quatre patients (16 avec PB et 8 avec PV) etaient evalues. Trois zones etaient examinees pour chaque patient : 2 lesions et une zone de peau saine. Resultats La RCM et l’OCT ont tous deux permis de visualiser un decollement sous-epidermique et bulles intra-epidermiques chez tous les patients atteints de BP et PV. L’OCT etait la methode la plus appropriee pour l’identification du niveau exact de la bulle, alors que la MRC permettait d’observer l’acantholyse de keratinocytes des bulles de PV. Des depots de fibrine et des septa a l’interieur des bulles ne se trouvaient que dans les PB et non dans les PV aussi bien en OCT que MCIV. Discussion Il est maintenant possible au clinicien de determiner le type et le niveau de clivage d’une bulle et de differencier PB ou PV de maniere non-invasive. Par ailleurs, il est possible d’examiner les bulles sans fixation ce qui permet de visualiser le cloisonnement par des septa de fibrine lors de la PB. Conclusion La MCIV et l’OCT peuvent aider le clinicien dans le diagnostic de BP et PV au cours d’un examen rapide est simple a realiser de maniere non-invasive. De plus, ces techniques peuvent etre utiles pour la selection du site de biopsie.

Summary Background By dermoscopy, regression structures are substantially defined by the presence of white and blue areas in the lesion image. As fibrosis and melanosis are often seen in malignant melanoma (MM), the presence of dermoscopic signs of regression may represent a clue for the diagnosis of malignancy. Objectives To assess the frequency and extent of dermoscopic signs of regression in melanoma in situ (MIS) and to describe its dermoscopic features. Methods Dermoscopic images of 85 MIS, 85 invasive MMs and 85 dermoscopically equivocal lesions with a histological diagnosis of naevus were evaluated by three dermatologists, who assessed the presence of 11 parameters of regression. Results The number of regression parameters per lesion increased according to melanoma thickness. White areas, the grey-blue veil and widespread blue areas were more frequent in invasive MMs than in the other two lesion groups, whereas light brown areas and regression of dermoscopic structures were more frequent in MIS. Peppering was observable in the same percentage of MIS and invasive MMs. Blue areas were more frequently structureless in equivocal lesions and invasive MMs, whereas the reticular pattern prevailed in MIS. Conclusions Frequency, morphology, extent and distribution of regression vary according to melanoma thickness and diameter. Lesions with reticular blue regression and light brown areas should undergo surgical excision for the suspicion of MIS. Moreover, the identification of the reticular pattern of blue regression can be considered a significant discriminator and a reliable predictor of MIS.

Cleft formation is thought to be a retraction artefact observed in histopathology due to formalin fixation dehydration. However, cleft-like retraction spaces between intraepidermal nests of melanocytes and adjacent epidermis are observed on histopathology more frequently in Spitz/Reed naevi and melanomas than in other melanocytic proliferations.

SummaryBackground Dermoscopically, one of the most common findings in melanocytic lesions is a globular pattern. A regular globular pattern is a common finding in naevi. Melanoma can also show a globular pattern, with globules typically irregular in size, colour and distribution. Objectives To investigate the likelihood of diagnosing melanoma according to distinct dermoscopic and confocal aspects. Methods Dermoscopic and confocal aspects of 83 excised melanocytic lesions dermoscopically showing globules were analysed. Results Our study population included 39 acquired melanocytic naevi, 16 Spitz naevi and 28 melanomas. Univariate analysis showed that regular distribution of globules on dermoscopy is associated with a ninefold lower risk for melanoma, whereas an irregular distribution is associated with an almost 10-fold increased risk for melanoma. Concerning confocal features, dense nests are associated with a fivefold lower risk for melanoma, whereas loosely arranged nests are associated with an almost sixfold risk for melanoma; moreover, the presence of round cells is associated with a 17-fold lower risk for melanoma, whereas pleomorphic cells are associated with an almost 16-fold risk for melanoma. Conclusions So that melanoma is not missed, clinicians should carefully analyse globular lesions in adults, focusing, in particular, on the distribution of globules and on the presence of confocal cytological atypia.

Background: Actinic Keratosis (AK) is the clinical manifestation of cutaneous dysplasia of epidermal keratinocytes, withprogressive trend towards squamous cell carcinoma. Objective: To evaluate the strength of the correlation between keratinocyte atypia, as detected by Reflectance Confocal Microscopy (RCM) and histopathology, and to develop a more objective atypia grading scale for RCM quantification,through a discrete ranking. Methods: A total of 48 AKs and two control areas (photodamaged and non-photodamaged skin) were selected for this study. All these areas were documented by RCM and biopsied for histopathology. One representative image of the epidermis was selected for RCM and for histopathology and used for side-by-side comparison with purpose written soft-ware. The assessor chose which of two images displayed more keratinocyte atypia, and an ordered list from the imageshowing the least to the most keratinocyte atypia was generated. Three evaluations were obtained for RCM and two for histopathology. Results: Good interobserver correlation was obtained for RCM and histopathology grading, with high concordance between RCM and histopathology grading Conclusions: Expert rater scan consistently distinguish different grades of cytological atypia. Non-invasive RCM data from in vivo imaging can be graded for keratinocyte atypia, comparable to histopathological grading. Refereed/Peer-reviewed

Summary Background The presence of pigmentation might influence the management of basal cell carcinoma (BCC), with pigmented BCC responding poorly to certain treatments. Clinical studies report on a generally lower frequency of pigmentation compared with dermoscopic and histopathological studies, but the true frequency at which pigmentation occurs in clinically nonpigmented BCC has not been studied in detail. Objectives To compare the clinical and dermoscopic frequency of pigmentation in a series of histopathologically diagnosed BCCs and to correlate it with patient demographics, tumour location and histopathological subtype. Methods Clinical and dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of pigmentation. Dichotomous outcome variables were clinically pigmented and dermoscopically pigmented BCC. All separate dermoscopic variables were included in the analysis. Differences in proportions were evaluated using Pearson's chi-square test. Results Five hundred and seven BCCs from 507 patients with a mean age of 67 years and a male-to-female ratio of 1·35 : 1 were included in the study. Clinically, 295 tumours were judged as nonpigmented. Of those, dermoscopy disclosed pigmentation in 88 cases (29·8%). Overall, blue-grey ovoid nests were the most frequent dermoscopic pattern (n = 184, 36·3%), followed by multiple blue-grey dots/globules (n = 147, 29%) and maple-leaf-like areas (n = 70, 13·8%). Superficial tumours exhibited mainly maple-leaf-like areas, spoke-wheel areas and brown dots, whereas pigmented nodular BCC was most frequently typified by the presence of blue-grey ovoid nests. Conclusions Dermoscopy allows detection of pigmentation in about 30% of clinically nonpigmented BCCs, providing additional information that may aid the clinical choice of adequate treatment modalities.

Summary Background Amelanotic melanoma represents a diagnostic challenge both clinically and dermoscopically. Few studies based on case series have explored the possibility of using reflectance confocal microscopy (RCM) to diagnose amelanotic melanoma. Objectives To validate a new confocal feature, named hyporeflective pagetoid cells (HPCs), for the diagnosis of amelanotic melanoma. Methods A group of 20 amelanotic melanomas and a control population of nonpigmented melanocytic naevi (10), hypo/nonpigmented nonmelanocytic lesions (20) and pigmented melanomas (20), imaged by RCM, were retrospectively evaluated. The presence of HPCs and other diagnosis-specific confocal features was assessed and correlated with histopathology. Results HPCs were present, and usually abundant, in the majority of amelanotic melanomas (85%). As expected, they were also observed in Spitz naevi. On histopathology, they were correlated with pagetoid infiltration of hypomelanotic melanocytes in all melanocytic lesions. Few nonmelanocytic lesions (three squamous cell carcinomas, two seborrhoeic keratoses and one basal cell carcinoma) showed the presence of HPCs. In these cases, they corresponded to enlarged or dyskeratotic keratinocytes by histopathology. Conclusions The identification of HPCs in the epidermis is a new parameter that is frequently found in amelanotic melanoma. Possible confounders are represented by atypical keratinocytes that can be present in nonmelanocytic lesions. However, the whole architecture and the presence of additional diagnostic criteria should be considered in order to obtain a correct diagnosis.