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Importance: Previous systematic reviews and meta-analyses have concluded that given data paucity, a comparison of reflectance confocal microscopy (RCM) with dermoscopy is complex. They recommend comparative prospective studies in a real-world setting of suspect lesions., Objective: To test the hypothesis that RCM reduces unnecessary lesion excision by more than 30% and identifies all melanoma lesions thicker than 0.5 mm at baseline., Design, Setting, and Participants: This randomized clinical trial included 3165 patients enrolled from 3 dermatology referral centers in Italy between January 2017 and December 2019, with a mean (SD) follow-up of 9.6 (6.9) months (range, 1.9-37.0 months). The consecutive sample of 3165 suspect lesions determined through dermoscopy were eligible for inclusion (10 patients refused). Diagnostic analysis included 3078 patients (48 lost, 39 refused excision). Data were analyzed between April and September 2021., Interventions: Patients were randomly assigned 1:1 to standard therapeutic care (clinical and dermoscopy evaluation) with or without adjunctive RCM. Information available guided prospective clinical decision-making (excision or follow-up)., Main Outcomes and Measures: Hypotheses were defined prior to study initiation. All lesions excised (baseline and follow-up) were registered, including histopathological diagnoses/no change at dermoscopy follow-up (with or without adjunctive RCM). Number needed to excise (total number of excised lesions/number of melanomas) and Breslow thickness of delayed diagnosed melanomas were calculated based on real-life, prospective, clinical decision-making., Results: Among the 3165 participants, 1608 (50.8%) were male, and mean (SD) age was 49.3 (14.9) years. When compared with standard therapeutic care only, adjunctive RCM was associated with a higher positive predictive value (18.9 vs 33.3), lower benign to malignant ratio (3.7:1.0 vs 1.8:1.0), and a number needed to excise reduction of 43.4% (5.3 vs 3.0). All lesions (n = 15) with delayed melanoma diagnoses were thinner than 0.5 mm., Conclusions and Relevance: This randomized clinical trial shows that adjunctive use of RCM for suspect lesions reduces unnecessary excisions and assures the removal of aggressive melanomas at baseline in a real-life, clinical decision-making application for referral centers with RCM., Trial Registration: ClinicalTrials.gov Identifier: NCT04789421.

Background: There is lack of studies on the diagnostic accuracy of dermoscopy and reflectance confocal microscopy (RCM) for dark pigmented lesions., Objective: To assess the diagnostic accuracy of dermoscopy plus confocal microscopy for melanoma diagnosis of dark pigmented lesions in real life., Methods: Prospective analysis of difficult dark lesions with clinical/dermoscopic suspicion of melanoma referred for RCM for further analysis. The outcome could be excision or dermoscopic digital follow-up., Results: We included 370 clinically dark lesions from 350 patients (median age, 45 y). Because of the clinical/dermoscopic/RCM approach, we saved 129 of 213 unnecessary biopsies (specificity of 60.6%), with a sensitivity of 98.1% (154/157). The number needed to excise with the addition of RCM was 1.5 for melanoma diagnosis., Limitations: Single institution based; Italian population only., Conclusions: This study showed that RCM coupled with dermoscopy increases the specificity for diagnosing melanoma, and it helps correctly identify benign lesions. Our findings provide the basis for subsequent prospective studies on melanocytic neoplasms belonging to patients in different countries., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 the International Society of Dermatology.)

Importance: The clinical and dermoscopic features of the vast majority of uncommon variants of cutaneous melanoma have been rarely reported, leading to difficulty in making accurate diagnoses., Objective: To define the main clinical and dermoscopic features of the most frequently reported but uncommon histologic variants of cutaneous melanoma., Evidence Review: A 2-step systematic review of the literature was performed (from inception to November 2018) using PubMed, Embase, and Cochrane Central Register of Controlled Trials databases. The first step identified those uncommon variants of melanoma for which at least 1 case reporting dermoscopy was described in the literature. The keywords searched were melanoma, uncommon, rare, dermoscopy, and dermatoscopy. In the second step, each previously identified uncommon variant was searched for in the same databases by combining the following terms with melanoma, dermoscopy, and dermatoscopy: amelanotic, hypopigmented, animal, melanocytoma, balloon, desmoplastic, follicular, nested, nevoid, dermal, spitz*, spindle, and verrucous. The institution's database was also searched from January 2012 to September 2019 for histopathologically confirmed cases of the same melanoma variants. Each reviewer also assessed the quality of reporting in the included articles based on previously described guidelines., Findings: In total, 62 articles met the inclusion criteria, reporting 433 melanoma cases. An additional 56 cases of uncommon melanoma variants were retrieved from the institution's database for a total of 489 cases: 283 cases of amelanotic superficial spreading melanoma, 18 cases of animal-type and pigmented epithelioid melanocytoma, 7 cases of balloon cell melanoma, 71 cases of desmoplastic melanoma, 3 cases of follicular melanoma, 10 cases of nested melanoma, 33 cases of nevoid melanoma, 2 cases of primary dermal melanoma, 57 cases of spitzoid melanoma, and 5 cases of verrucous melanoma. These variants of melanoma occurred more frequently in women than men (147 cases vs 132 cases). Clinically, these tumors were mainly palpable (162 of 217 [74.7%]) or amelanotic (283 of 489 [57.9%]) lesions that could resemble other benign or malignant skin conditions; dermoscopy typically revealed a homogeneous pinkish background, white structures, and polymorphic vessels. The mean age of all included was 58 years (range, 1-89 years)., Conclusions and Relevance: Uncommon melanoma variants may resemble both inflammatory disorders and other cutaneous neoplasms, representing a diagnostic pitfall even for the most experienced dermatologist. The purpose of this systematic review was to provide an extensive and detailed overview of specific clinical and dermoscopic features of each uncommon melanoma variant, highlighting the main criteria for differentiating these variants from other benign or malignant skin lesions.

Basal cell carcinoma (BCC) is usually diagnosed by clinical and dermatoscopy examination, but diagnostic accuracy may be suboptimal. Reflectance confocal microscopy (RCM) imaging increases skin cancer diagnostic accuracy. To evaluate additional benefit in diagnostic accuracy of handheld RCM in a prospective controlled clinical setting. A prospective, multicenter study in 3 skin cancer reference centers in Italy enrolling consecutive lesions with clinical-dermatoscopic suspicion of BCC (ClinicalTrials.gov: NCT04789421). A total of 1005 lesions were included, of which 474 histopathologically confirmed versus 531 diagnosed by clinical-dermatoscopic-RCM correlation, confirmed with 2 years of follow-up. Specifically, 740 were confirmed BCCs. Sensitivity and specificity for dermatoscopy alone was 93.2% (95% CI, 91.2-94.9) and 51.7% (95% CI, 45.5-57.9); positive predictive value was 84.4 (95% CI, 81.7-86.8) and negative predictive value 73.3 (95% CI, 66.3-79.5). Adjunctive RCM reported higher rates: 97.8 (95% CI, 96.5-98.8) sensitivity and 86.8 (95% CI, 82.1-90.6) specificity, with positive predictive value of 95.4 (95% CI, 93.6-96.8) and negative predictive value 93.5 (95% CI, 89.7-96.2). Study conducted in a single country. Adjunctive handheld RCM assessment of lesions clinically suspicious for BCC permits higher diagnostic accuracy with minimal false negative lesions. [ABSTRACT FROM AUTHOR]

It is well known that adnexal skin tumors can simulate other cutaneous neoplasia and that various types of benign and malignant skin tumors can develop or modify during pregnancy. Here, we report a case of trichoblastoma mimicking a keratoacanthoma arising in a nevus sebaceous during pregnancy. Given its unique clinical and dermoscopic features, this case highlights the pivotal role of clinicopathological correlation in the diagnosis of adnexal tumors with an atypical clinical presentation. [ABSTRACT FROM AUTHOR]

Clinically and dermoscopically, trichoepithelioma (TE) often mimics basal cell carcinoma (BCC).[[1], [3]] In this multicentre case-control study, we sought to determine the clinical and dermoscopic features associated with TE as compared to BCC. Dermoscopic features of trichoepithelioma: A multicentre observational case-control study conducted by the International Dermoscopy Society These criteria were significant predictors of TE over BCC on univariate logistic regression and multivariate analysis (Figure 1). 1 TABLE Frequencies of dermoscopic features among trichoepithelioma (TE) and basal cell carcinoma (BCC). [Extracted from the article]

Background: Basal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort. Objective: To identify dermoscopic "trump" characteristics for differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings. Methods: Retrospective, multicentric comparative study of atypical, non‐facial basal cell carcinoma (≥1 seven‐point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results. Results: A total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001). Conclusions: These findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence. [ABSTRACT FROM AUTHOR]

Background: Advanced squamous cell carcinoma (SCC) can be discriminated easily from actinic keratosis (AK) based on clinical and dermatoscopic features. However, at the initial stage of dermal invasion, SCC might still be clinically flat and discrimination from AK remains challenging, even with the addition of dermatoscopy.Objective: The aim of this study was to investigate the clinical and dermatoscopic criteria that could suggest early invasion and serve as potent predictors to discriminate early SCC from AK.Methods: Clinical and dermatoscopic images of histopathologically diagnosed AKs and early SCCs were evaluated for the presence of predefined criteria by 3 independent investigators.Results: A total of 50 early SCCs and 45 AKs were included. The main positive dermatoscopic predictors of early SCC were dotted/glomerular vessels (odds ratio [OR] 3.83), hairpin vessels (OR 12.12), and white structureless areas (OR 3.58), whereas background erythema represented a negative SCC predictor (OR 0.22).Limitations: The retrospective evaluation of images. Moreover, the differential diagnosis included in the study is restricted between AK and early SCC.Conclusions: We identified potent predictors for the discrimination of AK and early SCC that may better guide management decisions in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Background: Infiltrative basal cell carcinoma (BCC) has a higher risk for post-surgical recurrence as compared to the most common low-aggressive superficial and nodular BCC. Independent diagnostic criteria for infiltrative BCC diagnosis have not been still defined. Improving the pre-surgical recognition of infiltrative BCC might significantly reduce the risk of incomplete excision and recurrence. Objective: The aim of this study is to define clinical and dermoscopic criteria that can differentiate infiltrative BCC from the most common low-aggressive superficial and nodular BCC. Methods: Clinical and dermoscopic images of infiltrative, superficial, and nodular BCC were retrospectively retrieved from our database and jointly evaluated by two experienced dermoscopists, blinded for the histologic subtype. Pairwise comparisons between the three histologic subtypes were performed and multivariable logistic regression models were constructed in order to define clinical and dermoscopic factors independently associated with each subtype. To validate our findings, two experienced dermoscopists not previously involved in the study were asked to evaluate clinical and dermoscopic images from an external dataset, guessing the proper BCC subtype between infiltrative, nodular and superficial, before and after being provided with the study results. Result: A total of 481 histopathologically proven BCCs (51.4% nodular, 33.9% superficial, and 14.8% infiltrative) were included. We found that infiltrative BCC mostly appeared on the head and neck as an amelanotic hypopigmented plaque or papule, displaying ulceration on dermoscopic examination, along with arborizing and fine superficial telangiectasia. Shiny white structures were also frequently observed. Multivariate regression analysis allowed us to define a clinical-dermoscopic profile of infiltrative BCC. Conclusions: We defined the clinical-dermoscopic profile of infiltrative BCC, allowing to differentiate this variant from superficial and nodular BCC. This will improve pre-surgical recognition of infiltrative forms, reducing the risk for post-surgical recurrence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dermoscopic patterns of melanoma metastases: interobserver consistency and accuracy for metastasis recognition. The skin, with subcutaneous tissue and lymph nodes, is the most common site of distant melanoma metastasis which occurred in 42%-59% of patients.[1] The clinical appearance of cutaneous melanoma metastasis typically includes single or grouped variably pigmented papules and nodules.[[2]] Several articles reported different classifications of dermoscopic characteristics of cutaneous melanoma metastases. [Extracted from the article]