Diagnostic accuracy of ex vivo fluorescence confocal microscopy in Mohs surgery of basal cell carcinomas: a prospective study on 753 margins.

BACKGROUND: Frozen histological sections are used for intraoperative margin assessment during Mohs surgery. Fluorescence confocal microscopy (FCM) is a new tool that offers a promising and faster alternative to frozen histology. OBJECTIVES: To evaluate prospectively in a clinical setting the accuracy of FCM vs. frozen sections in margin assessment of basal cell carcinoma (BCC). METHODS: Patients with BCC scheduled for Mohs surgery were prospectively enrolled. Freshly excised surgical specimens were examined by FCM and then frozen sections were evaluated. Permanent sections were obtained, in order to validate the sample technique. A blind re-evaluation was also performed for discordant cases. Sensitivity and specificity levels, as well as positive and negative predictive values (PPV and NPV, respectively), were calculated and receiver-operating characteristic curves generated. RESULTS: We enrolled 127 BCCs in as many patients (40·2% females). Seven hundred and fifty-three sections were examined. All BCCs were located in the head and neck area. In evaluating the performance of FCM vs. frozen sections, sensitivity was 79·8%, specificity was 95·8%, PPV was 80·5% and NPV was 95·7% [area under the curve 0·88, 95% confidence interval 0·84-0·92 (P < 0·001)]. Forty-nine discordant cases were re-evaluated; 24 were false positive and 25 false negative. The performance of FCM and frozen sections was also evaluated according to the final histopathological assessment. CONCLUSIONS: We found high levels of accuracy for FCM vs. frozen section evaluation in intraoperative BCC margin assessment during Mohs surgery. Some technical issues prevent the wide use of this technique, but new devices promise to overcome these limitations.

Sclerosing nevus with pseudomelanomatous features: dermoscopic and confocal aspects.

BACKGROUND: Sclerosing nevus with pseudomelanomatous features (SNPFs) is a clinical and pathologic entity that mimics melanoma both clinically and histologically. The lesion is a melanocytic nevus, histologically characterized by fibrosis and a pseudomelanomatous proliferation. It is typically seen in young to middle-aged individuals, mainly on the back, where microtrauma or inflammatory changes are more frequent. Dermoscopic description of SNPF has been reported so far in one case series. OBJECTIVE: The aim of our study was to describe the dermoscopic and confocal features of SNPF. METHODS: Histopathologically confirmed cases of SNPF were retrospectively collected from three referral centres in Italy. Only lesions with available clinical, dermoscopic and histopathological data were included; confocal images were also retrieved, when available. Lesions were evaluated for the presence of 12 dermoscopic and five confocal criteria previously described. RESULTS: The study population included 93 lesions in as many patients (71 men and 22 women; median age: 38 years). Dermoscopically, we found a predominance of dark colours, in particular brown and blue, which were found in all lesions and the vast majority of the lesions (86/93; 92.5%) displayed at least one structureless area. By the combination of colours and structures, we observed that the majority of the lesions (67/92; 72%) were characterized by more than one structure and more than one colour. Confocal evaluation was performed on a subset of 24/93 lesions showing a regular architecture pattern (19/24 cases, 79%), with a predominance of the ringed pattern. The presence of focal cytologic atypia at the dermal-epidermal junction was present in 12/24 cases (50%) with a prevalent dendritic-shaped cell proliferation. CONCLUSIONS: The current study demonstrated that SNPF was frequently characterized, on dermoscopic examination, by more than one structure and more than one colour and on confocal microscopy by a regular ringed pattern with focal dendritic atypical cells.

In vivo dermoscopic and confocal microscopy multistep algorithm to detect in situ melanomas.

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.

Dermoscopy and reflectance confocal microscopy for monitoring the treatment of actinic cheilitis with ingenol mebutate gel: Report of three cases.

Actinic cheilitis (AC) can precede the development of squamous cell carcinoma (SCC) of the lip, a location with higher risk of invasiveness and metastasis. Herein, we reported the use of ingenol mebutate (IngMeb) 0.015% gel on three consecutive days to treat three patients suffering from AC. All the three patients achieved complete clearance of AC with rapid clinical effect, favorable safety profile, good patient's compliance related to short time of applications, and few local skin reactions. So IngMeb is an attractive new therapy for AC. Moreover, the present case report adds further evidence to the usefulness of dermoscopy and Reflectance confocal microscopy (RCM) in the assessment and monitoring of treatment outcome.

Integration of dermoscopy and reflectance confocal microscopy for distinguishing melanomas from nevi of the breast area.

BACKGROUND: Nevi of special sites encompass a class of benign lesions characterized by the presence of atypical clinical and histopathological features that can be difficult to distinguish from melanoma. Dermoscopy and reflectance confocal microscopy may improve the clinical assessment of melanocytic lesions 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 one 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 analyses 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:0.048 and OR: 6.5; 95% CI 1.1-37.5; P:0.037, 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:0.002). 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.

Basal cell carcinoma: the utility of in vivo and ex vivo confocal microscopy.

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.

Tracking actinic keratosis of face and scalp treated with 0.015% ingenol mebutate to identify clinical and dermoscopic predictors of treatment response.

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.

Association between dermoscopic and reflectance confocal microscopy features of cutaneous melanoma with BRAF mutational status.

BACKGROUND: Melanomas harbouring common genetic mutations might share certain morphological features detectable with dermoscopy and reflectance confocal microscopy. BRAF mutational status is crucial for the management of metastatic melanoma. OBJECTIVES: To correlate the dermoscopic characteristics of primary cutaneous melanomas with BRAF mutational status. Furthermore, a subset of tumours has also been analysed for the presence of possible confocal features that might be linked with BRAF status. METHODS: Retrospectively acquired dermoscopic and confocal images of patients with melanoma in tertiary referral academic centres: Skin Cancer Unit in Reggio Emilia and at the Melanoma Unit in Barcelona. Kruskal-Wallis test, logistic regressions, univariate and multivariate analyses have been performed to find dermoscopic and confocal features significantly correlated with BRAF mutational status. RESULTS: Dermoscopically, the presence of irregular peripheral streaks and ulceration were positive predictors of BRAF-mutated melanomas with a statistically significance value, while dotted vessels were more represented in wild-type melanomas. None of the evaluated reflectance confocal microscopy features were correlated with genetic profiling. CONCLUSIONS: Ulceration and irregular peripheral streaks represent dermoscopic feature indicative for BRAF-mutated melanoma, while dotted vessels are suggestive for wild-type melanoma.

Trichoblastoma: is a clinical or dermoscopic diagnosis possible?

BACKGROUND: Trichoblastoma is a rare benign skin tumour that must be differentiated from basal cell carcinoma for its benign course and favourable outcome. OBJECTIVES: To describe clinical and dermoscopic features of solitary primitive trichoblastoma and to compare them with trichoblastic basal cell carcinoma (tBCC). METHODS: Digital dermoscopic images of 19 trichoblastoma and 19 tBCC were compared and reviewed by a dermatologist experienced in dermoscopy. RESULTS: The most striking dermoscopic difference between trichoblastoma and tBCC was the presence of blue-grey globules and blue-grey ovoid nests that were found to be more frequent but not exclusive of tBCC. Arborizing vessels were found both in trichoblastoma and tBCC, with a lower frequency in the latter. CONCLUSION: Histology remains the gold standard to differentiate trichoblastoma from tBCC.

Unusual sites for poromas are not very unusual: a survey of 101 cases.

BACKGROUND: Poromas are benign adnexal tumours generally believed to be of eccrine origin, which usually develop on palmoplantar sites. However, it is thought that a percentage of poromas develop on non-palmoplantar or 'unusual' sites. AIM: To review cases of poromas with reference to their clinicoepidemiological characteristics, paying particular attention to the those located on sites other than the palms and soles. METHODS: All histologically confirmed poromas seen at our department between 1994 to 2012 were reviewed. The clinicoepidemiological data recorded included age at diagnosis, gender, location, size, colour, and preoperative and pathological diagnoses. RESULTS: In total, 101 poromas were reviewed, corresponding to 0.0058% of all the epithelial skin tumours biopsied in our department. The mean age was 65.05 years (range 30-100 years), and the male to female ratio was 1.52. All the lesions were solitary and asymptomatic, with no sign of bleeding. The most common presentation was a red or reddish lesion, particularly at palmoplantar sites, where 33 (32.7%) of the 101 poromas were located, Poromas found at other affected sites were more usually skin-coloured, and these lesions included 7 neoplasms located in the armpits and 18 on the head and neck. The correct preoperative diagnosis was made in 12 cases of 33 detected poromas (36%), all of which were localized to the palmoplantar surfaces. CONCLUSIONS: Based on our experience, we consider that there are no 'unusual' sites for poromas, and palmoplantar poromas were in fact in the minority. Furthermore, some localizations suggest derivation of these palmoplantar poromas from the folliculosebaceous apocrine unit.

Clinically and/or histologically pigmented poromas in Caucasian patients.

AIM: Pigmented poromas are rarely reported and considered to be more common in non-white people and on non-acral sites. Objective of the present study was to report our cases of pigmented poromas with particular attention to the presence of clinical and/or microscopic evidence of pigmentation, their characteristics and the diagnostic pitfall with other pathologies. METHODS: All the histologically confirmed poromas observed from January 1994 to July 2012 were considered. Clinic-epidemiological data were collected. The presence of clinical pigmentation was recorded as well as the presence of melanin pigmentation or melanocytes in the histologic specimens. RESULTS: One hundred and one patients with poromas were collected. All the patients were Caucasians. All the lesions were solitary. Only three patients had a clinically visible pigmented poromas. In eight cases the presence of melanin and melanocytes did not produce a clinically visible pigmentation. All the poromas with pigmentation did not occur on palmo-plantar surfaces. CONCLUSION: Pigmented poromas may be observed even in Caucasian patients and their clinical aspect mimic basal cell carcinoma and/or melanoma. The presence of pigment visible at the histology may not be observed in the clinical expression. The absence of pigmentation on palmo-plantar location is confirmed in all the reported cases.

Tinea capitis in the paediatric population in Milan, Italy: the emergence of Trichophyton violaceum.

Tinea capitis (TC) is the most common type of dermatophytosis in children. The epidemiology of TC depends on the geographical areas, and it changes over time. The aim of the study is to determine the incidence of TC and to identify the causative species in children observed at Dermatology Outpatient Department of the University of Milan, Italy, between January 2004 and December 2011. Four hundred and eighty-six children with suspected dermatomycosis were observed; TC was the most prevalent dermatomycoses with 86 cases. The most common isolated dermatophyte in scalp lesions was Trichophyton violaceum with 33 cases. The most recent epidemiological Italian studies still show zoophilic fungi as primary cause of TC. We are the first medical team in Italy to demonstrate a dominance of anthropophilic fungi, in particular T. violaceum.