Dermatoscopy and reflectance confocal microscopy for basal cell carcinoma diagnosis and diagnosis prediction score: A prospective and multicenter study on 1005 lesions.

BACKGROUND: 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. OBJECTIVE: To evaluate additional benefit in diagnostic accuracy of handheld RCM in a prospective controlled clinical setting. METHODS: A prospective, multicenter study in 3 skin cancer reference centers in Italy enrolling consecutive lesions with clinical-dermatoscopic suspicion of BCC (ClinicalTrials.gov: NCT04789421). RESULTS: 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). LIMITATIONS: Study conducted in a single country. CONCLUSIONS: Adjunctive handheld RCM assessment of lesions clinically suspicious for BCC permits higher diagnostic accuracy with minimal false negative lesions.

A risk-scoring model for the differential diagnosis of lentigo maligna and other atypical pigmented facial lesions of the face: The facial iDScore.

BACKGROUND: Due to progressive ageing of the population, the incidence of facial lentigo maligna (LM) of the face is increasing. Many benign simulators of LM and LMM, known as atypical pigmented facial lesions (aPFLs-pigmented actinic keratosis, solar lentigo, seborrheic keratosis, seborrheic-lichenoid keratosis, atypical nevus) may be found on photodamaged skin. This generates many diagnostic issues and increases the number of biopsies, with a subsequent impact on aesthetic outcome and health insurance costs. OBJECTIVES: Our aim was to develop a risk-scoring classifier-based algorithm to estimate the probability of an aPFL being malignant. A second aim was to compare its diagnostic accuracy with that of dermoscopists so as to define the advantages of using the model in patient management. MATERIALS AND METHODS: A total of 154 dermatologists analysed 1111 aPFLs and their management in a teledermatology setting: They performed pattern analysis, gave an intuitive clinical diagnosis and proposed lesion management options (follow-up/reflectance confocal microscopy/biopsy). Each case was composed of a dermoscopic and/or clinical picture plus metadata (histology, age, sex, location, diameter). The risk-scoring classifier was developed and tested on this dataset and then validated on 86 additional aPFLs. RESULTS: The facial Integrated Dermoscopic Score (iDScore) model consisted of seven dermoscopic variables and three objective parameters (diameter ≥ 8 mm, age ≥ 70 years, male sex); the score ranged from 0 to 16. In the testing set, the facial iDScore-aided diagnosis was more accurate (AUC = 0.79 [IC 95% 0.757-0.843]) than the intuitive diagnosis proposed by dermatologists (average of 43.5%). In the management study, the score model reduced the number of benign lesions sent for biopsies by 41.5% and increased the number of LM/LMM cases sent for reflectance confocal microscopy or biopsy instead of follow-up by 66%. CONCLUSIONS: The facial iDScore can be proposed as a feasible tool for managing patients with aPFLs.

Amelanotic/hypomelanotic lentigo maligna: Dermoscopic and confocal features predicting diagnosis.

BACKGROUND: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma (AHLM/LMM) may be very difficult to diagnose at an early stage. OBJECTIVES: To quantify the predictive value of dermoscopic and reflectance confocal microscopy (RCM) features for AHLM/LMM. METHODS: Dermoscopic and RCM images of histopathologically diagnosed AHLM/LMM, amelanotic/hypomelanotic benign lesions (AHBL), and amelanotic/hypomelanotic basal and squamous cell carcinomas (AHBCC/AHSCC) of the head and neck from consecutive patients were retrospectively collected and blindly evaluated by three observers to assess presence or absence of dermoscopic and RCM criteria. RESULTS: Overall, 224 lesions in 216 patients including LM/LMM (n = 55, 24.6%), AHBL (n = 107, 47.8%) and AHBCC/AHSCC (n = 62, 27.7%) were analysed. Multivariable analysis showed that milky-red areas (OR = 5.46; 95% CI: 1.51-19.75), peripheral light brown structureless areas (OR = 19.10; 4.45-81.96), linear irregular vessels (OR = 5.44; 1.45-20.40), and asymmetric pigmented follicles (OR = 14.45; 2.77-75.44) at dermoscopy, and ≥3 atypical cells in five fields (OR = 10.12; 3.00-34.12) and focal follicular localization of atypical cells at dermo-epidermal junction (DEJ) (OR = 10.48; 1.10-99.81) at RCM were significantly independent diagnostic factors for AHLM/LMM vs. AHBL. In comparison with AHBCC/AHSCC, peripheral light brown structureless area (OR = 7.11; 1.53-32.96), pseudonetwork around hair follicles (OR = 16.69; 2.73-102.07), and annular granular structures (OR = 42.36; 3.51-511.16) at dermoscopy and large dendritic (OR = 6.86; 3.15-38.28) and round pagetoid cells (OR = 26.78; 3.15-227.98) at RCM led to a significantly increased risk of diagnosing AHLM/LMM. CONCLUSIONS: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma may have the same dermoscopic features of AHM on other body sites, such as milky red areas, peripheral light brown structureless areas and linear irregular vessels. These features, asymmetric pigmented follicles and at RCM ≥ 3 atypical cells in five fields and focal follicular extension of atypical cells at DEJ may help in recognizing AHLM/LMM even when LM conventional features (e.g., obliteration of hair follicles under dermoscopy and large pagetoid cells under RCM) are absent or present only in very small areas of the lesion.

Development and Implementation of a Web-Based International Registry Dedicated to Atypical Pigmented Skin Lesions of the Face: Teledermatologic Investigation on Epidemiology and Risk Factors.

Background: Atypical pigmented facial lesions (aPFLs) often display clinical and dermoscopic equivocal and/or overlapping features, thus causing a challenging and delayed diagnosis and/or inappropriate excisions. No specific registry dedicated to aPFL paired with clinical data is available to date. Methods: The dataset is hosted on a specifically designed web platform. Each complete case was composed of the following data: (1) one dermoscopic picture; (2) one clinical picture; (3) two lesion data, that is, maximum diameter and facial location (e.g., orbital area/forehead/nose/cheek/chin/mouth); (4) patient's demographics: family history of melanoma, history of sunburns in childhood, phototype, pheomelanine, eyes/hair color, multiple nevi/dysplastic nevi on the body; and (5) acquisition device (videodermatoscope/camera-based/smartphone-based system). Results: A total of 11 dermatologic centers contributed to a final teledermoscopy database of 1,197 aPFL with a distribution of 353 lentigo maligna (LM), 146 lentigo maligna melanoma (LMM), 231 pigmented actinic keratoses, 266 solar lentigo, 125 atypical nevi, 48 seborrheic keratosis, and 28 seborrheic-lichenoid keratoses. The cheek site was involved in half of aPFL cases (50%). Compared with those with the other aPFL cases, patients with LM/LMM were predominantly men, older (69.32 ± 12.9 years on average vs. 62.69 ± 14.51), exhibited larger lesions (11.88 ± 7.74 mm average maximum diameter vs. 9.33 ± 6.46 mm), and reported a positive history of sunburn in childhood. Conclusions: The iDScore facial dataset currently represents a precious source of data suitable for the design of diagnostic support tools based on risk scoring classifiers to help dermatologists in recognizing LM/LMM among challenging aPFL in clinical practice.

Dynamic dermoscopic and reflectance confocal microscopic changes of melanocytic lesions excised during follow up.

BACKGROUND: Digital dermoscopy follow up (DDF) is useful in improving the recognition of melanoma, catching early changes over time, although benign nevi can also show changes. Reflectance confocal microscopy (RCM) improves accuracy in diagnosing melanoma and decreases the number of unnecessary resections. OBJECTIVE: To evaluate dynamic dermoscopic and RCM changes during follow up of equivocal melanocytic lesions and assess the impact of adjunctive RCM to DDF for melanoma diagnosis. METHODS: A retrospective, multicenter study of extrafacial atypical melanocytic lesions excised during follow up was performed. Morphologic changes were evaluated, comparing dermoscopy and RCM baseline and follow-up images. RESULTS: One hundred thirty-seven atypical melanocytic lesions were studied, including 14 melanomas and 123 benign nevi. Significantly greater changes in DDF of atypical network, regression, atypical streaks, and asymmetrical growth as well as in dynamic RCM of atypical cells and dermal-epidermal junction disarray were noted in melanomas. With adjunctive dynamic RCM and major changes at DDF, sensitivity reached 100%, with 40.6% specificity. LIMITATIONS: Selected series of difficult to recognize lesions, with both DDF and dynamic RCM images. CONCLUSION: Adjunctive dynamic RCM improves early melanoma recognition sensitivity.

Correction to: Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases.

In the original version of this article [1], published on 7 November 2017, affiliation 18 has been incorrectly assigned to the authors Serena Magi and Laura Mazzoni. They are only affiliated to the Skin Cancer Unit, Istituto Tumori Romagna (IRST), Meldola, Italy (affiliation 5).

Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases.

BACKGROUND: Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence. METHODS: All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005-2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence. RESULTS: Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01-2 mm (OR 7.22; 95% CI 2.73-19.05), BT 2.01-4 mm (OR 7.04; 95% CI 2.54-19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65-474.86) (p < 0.0001)]. Furthermore, mitotic rate (MR) was significantly correlated with NM histotype: [(MR 3-5 mitoses/mm2 (OR 2.62; 95% CI 1.01-6.83) and MR > 5 mitoses/mm2 (OR 4.87; 95% CI 1.77-13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01-2.00 mm (HR 1.55; 95% CI 0.51-4.71), BT 2.01-4.00 mm (HR 2.42; 95% CI 0.89-6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95-10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm2 (HR 2.34; 95% CI, 1.11-4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19-5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis. CONCLUSIONS: We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence.

Discrepant alterations in main candidate genes among multiple primary melanomas.

BACKGROUND: Alterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM). METHODS: One hundred twelve MPM patients (96 cases with two primary melanomas, 15 with three, and 1 with four) were included into the study. Paired synchronous/asynchronous MPM tissues (N=229) were analyzed for BRAF mutations and cKIT/CyclynD1 gene amplifications. RESULTS: BRAF mutations were identified in 109/229 (48%) primary melanomas, whereas cKIT and CyclinD1 amplifications were observed in 10/216 (5%) and 29/214 (14%) tumor tissues, respectively. While frequency rates of BRAF mutations were quite identical across the different MPM lesions, a significant increase of cKIT (p<0.001) and CyclinD1 (p=0.002) amplification rates was observed between first and subsequent primary melanomas. Among the 107 patients with paired melanoma samples, 53 (49.5%) presented consistent alteration patterns between first and subsequent primary tumors. About one third (40/122; 32.8%) of subsequent melanomas presented a discrepant pattern of BRAF mutations as compared to incident primary tumors. CONCLUSIONS: The low consistency in somatic mutation patterns among MPM lesions from same patients provides further evidence that melanomagenesis is heterogeneous and different cell types may be involved. This may have implications in clinical practice due to the difficulties in molecularly classifying patients with discrepant primary melanomas.

Preliminary analysis of the melanoma multimedia educational program for general practitioners on behalf of the Italian Melanoma Intergroup.

According to the National Oncological Plan 2023-2027 on the importance of multidisciplinary and interactive e-learning training, the Italian Melanoma Intergroup (IMI) has developed MelaMEd (Melanoma Multimedia Education), a national project for general practitioners (GPs) on the prevention and detection of cutaneous melanoma through an online platform and an online course. MelaMEd enables participants to i) recognize skin lesions that require specialist dermatological assessment, ii) select patients at high risk of melanoma and iii) be informed of the diagnosis and treatment pathway of patients with melanoma. A free online platform and online course were developed and launched in June 2022. Before starting the course, enrolled participants fill out a pre-training questionnaire concerning the basic knowledge of the disease and the recognition and management of suspicious lesions. After the course, participants will fill out the same questionnaire again. The online course will end in December 2023. Here we present a preliminary analysis of the pre-training results (January 2023-July 2023). The data have been analyzed descriptively. So far, five healthcare centers have participated in the project for a total of 1320 participants. Of these, 298 compiled the pre-training questionnaire. Forty-seven percent of them were aged <40 years. Respondents were almost divided between GPs (47%) and resident GPs (48%). Among the theoretical questions, the ABCDE rule and ugly duckling sign are well known (96% and 91% of correct answers, respectively), but a lower percentage (68%) of respondents knows the EFG rule for the recognition of nodular melanomas and the statement of Breslow thickness (29%). Regarding the series of clinical images of pigmented skin lesions and their management, the percentages rate of accuracy varied from 33% to 87%: melanoma (5 cases) ranges from 36% to 71%, melanocytic nevi (3 cases) from 33% to 84%, whereas the percentages rate of referral for dermatological evaluation varied from 44% to 99%. Melanoma cases referred to dermatologist ranges from 67% to 99%. This preliminary analysis on pre-train-ing questionnaire mainly showed a lack of knowledge of the two major points of melanoma diagnosis (EFG) and management (Breslow thickness), as well as a low rate of participants. We will compare the proportions of correct answers to the questionnaires before and after the course once available.

The combination of dermoscopy and reflectance confocal microscopy increases the diagnostic confidence of amelanotic/hypomelanotic lentigo maligna.

The dermoscopic diagnosis of amelanotic/hypomelanotic lentigo maligna/lentigo maligna melanoma (AHLM/LMM) may be very difficult in its early stages because of lack of pigment. Reflectance confocal microscopy (RCM) is an imaging technique that is especially helpful for the diagnosis of lentigo maligna. To determine the diagnostic performances of dermoscopy and RCM in the diagnosis of AHLM/LMMs we evaluated dermoscopic and RCM images of consecutive cases of histopathologically confirmed AHLM/LMMs, amelanotic/hypomelanotic basal cell carcinoma and squamous cell carcinoma (AHBCCs/AHSCCs), amelanotic/hypomelanotic benign lesions (AHBLs), and actinic keratoses (AKs) from five participating centers. Sensitivity, specificity, accuracy, predictive values, and level of diagnosis confidence were calculated for both diagnostic procedures. Both dermoscopy and RCM showed diagnostic performance >97% in the diagnosis of AHLM/LMMs versus AHBCC/AHSCCs and their combination slightly improved diagnostic performance, with accuracy increasing from 98.0% to 99.1%. Similarly, RCM in combination with dermoscopy showed a tiny increase in the diagnostic performance in the diagnosis of AHLM/LMMs versus AHBLs (accuracy increased from 87.2% to 88.8%) and versus AKs (accuracy increased from 91.4% to 93.4%). Although the increase in diagnostic performance due to RCM was modest, the combination of dermoscopy and RCM greatly increased the level of confidence; high confidence in the diagnosis of AHLM/LMMs versus AHBLs increased from 36.2% with dermoscopy alone to 76.6% with dermoscopy plus RMC. Based on our results, dermoscopy and RCM should be complementary to improve not only diagnostic accuracy but also the level of diagnostic certainty in the diagnosis of AHLM/LMMs.

Evaluation of a training course for general practitioners within the melanoma multimedia education programme of the Italian Melanoma Intergroup: a study protocol.

The text discusses the role of general practitioners (GPs) in the prevention and early diagnosis of melanoma, a type of skin cancer. It highlights the need for GPs to be able to recognize suspicious skin lesions and refer patients to specialist dermatology centers. However, many GPs lack comprehensive training in diagnosing melanoma. The text mentions that various training courses have been conducted for GPs, but their impact on clinical practice has been limited. The MelaMEd Programme is an e-learning course developed by the Italian Melanoma Intergroup (IMI). The programme aims to provide GPs with comprehensive knowledge of melanoma prevention, diagnosis, and treatment. It includes an e-learning section, and a dedicated platform called MelaMEd platform, which offers a multimedia atlas of melanoma. The objective of the study is to evaluate the impact of the MelaMEd programme on GPs' diagnostic accuracy, knowledge of melanoma, and management of suspicious lesions. The methodology involves administering pre-training and post-training questionnaires to participants, assessing their diagnostic skills and evaluating the training course's effectiveness. The study aims to demonstrate the effectiveness of the MelaMEd programme in improving GPs' ability to recognize and manage melanoma. It also seeks to identify areas for improvement and recommend interventions to enhance diagnostic accuracy. The results will be analyzed statistically using descriptive, univariate, and multivariate analysed methods.

Pattern Analysis of Benign and Malignant Atypical Melanocytic Skin Lesions of Palms and Soles: Variations of Dermoscopic Features According to Anatomic Site and Personal Experience.

Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. Aims: To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. Methods: A dataset of 471 aMPPLs-excised in the suspect of malignancy-was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. Results: A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the "fingers area" (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most "difficult" to diagnose, the parallel ridge pattern was poorly recognized and irregular/regular fibrillar patterns often misinterpreted. Regarding the aMPPL of the "heel area", the parallel furrow pattern (p = 0.014) and lattice-like pattern (p = 0.001) significantly discriminated benign cases, while asymmetry of colors (p = 0.002) and regression structures (p = 0.025) malignant ones. In aMPPLs of the "plantar arch", the lattice-like pattern (p = 0.012) was significant for benignity and asymmetry of structures, asymmetry of colors, regression structures, or blue-white veil for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. Conclusions: This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas.

Is Pediatric Melanoma Really That Different from Adult Melanoma? A Multicenter Epidemiological, Clinical and Dermoscopic Study.

PURPOSE: To improve the diagnostic accuracy and optimal management of pediatric melanomas. METHODS: We conducted a retrospective descriptive, multicenter study of the epidemiological, clinical, and dermoscopic characteristics of histopathologically proven melanomas diagnosed in patients less than 18 years old. Data on sociodemographic variables, clinical and dermoscopic characteristics, histopathology, local extension, therapy and follow-up, lymph node staging, and outcome were collected from the databases of three Italian dermatology units. We performed a clinical evaluation of the morphological characteristics of each assessed melanoma, using both classic ABCDE criteria and the modified ABCDE algorithm for pediatric melanoma to evaluate which of the two algorithms best suited our series. RESULTS: The study population consisted of 39 patients with a histologically confirmed diagnosis of pediatric melanoma. Comparing classic ABCDE criteria with the modified ABCDE algorithm for pediatric melanomas, the modified pediatric ABCDE algorithm was less sensitive than the conventional criteria. Dermoscopically, the most frequent finding was the presence of irregular streaks/pseudopods (74.4%). When evaluating the total number of different suspicious dermoscopy criteria per lesion, 64.1% of the lesion assessments recognized two dermoscopic characteristics, 20.5% identified three, and 15.4% documented four or more assessments. CONCLUSIONS: Contrary to what has always been described in the literature, from a clinical point of view, about 95% of our cases presented in a pigmented and non-amelanotic form, and these data must be underlined in the various prevention campaigns where pediatric melanoma is currently associated with a more frequently amelanotic form. All the pediatric melanomas analyzed presented at least two dermoscopic criteria of melanoma, suggesting that this could be a key for the dermoscopic diagnosis of suspected pediatric melanoma, making it possible to reach an early diagnosis even in this age group.

Long-term vemurafenib therapy in advanced melanoma patients: cutaneous toxicity and prognostic implications.

BACKGROUND: The introduction of targeted therapies for the treatment of BRAF-mutated metastatic melanoma was associated with different cutaneous adverse events (AEs). OBJECTIVES: To describe the type, frequency and severity of cutaneous AEs related to vemurafenib; to understand the association between AEs and vemurafenib efficacy in terms of median overall survival (OS) and median progression-free survival (PFS); to identify molecular characteristics of long-term responders. METHODS: This observational, retrospective, monocentric study included all consecutive patients with unresectable stage III or stage IV melanoma and BRAF V600E mutation that started treatment with vemurafenib between May 2012 and May 2014. RESULTS: 62 patients with a median age of 56 years (range 26-82) were enrolled and received vemurafenib for a median period of 7.9 months (range 0.8-63.7). Among them, 45 patients presented at least one skin AE, 12 reduced the dosage due to cutaneous toxicity, and only one firstly reduced and after stopped the therapy. No specific molecular biomarkers were detected in long-term survivors. CONCLUSIONS: Among long-term survivors, skin AEs seem to be less frequent and less severe. Results on multivariable analysis revealed that the presence of at least one G2 toxicity is a protective factor considering PFS, but not in terms of OS.

Effect of Reflectance Confocal Microscopy for Suspect Lesions on Diagnostic Accuracy in Melanoma: A Randomized Clinical Trial.

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.

Proportion of Thick versus Thin Melanomas as a Benchmarking Tool.

BACKGROUND: The ratio of benign moles excised for each malignant melanoma diagnosed (number-needed-to-excise (NNE)) is a metric used to express the efficiency of diagnostic accuracy of melanoma. The literature suggests a progressive effort to reduce the NNE, thus raising concerns about missing early melanoma because the NNE does not capture the most significant outcome for melanoma prognosis, which is linked to the Breslow thickness. A lower NNE could reduce health costs related to melanoma diagnosis only if doing so does not increase the proportion of thicker melanomas. OBJECTIVES: The diagnostic performance by two tertiary referral centres using the NNE and proportion of thick (Breslow thickness > 1 mm) versus thin (Breslow thickness ≤ 1 mm) excised melanoma (thick/thin ratio: TTR) was compared to determine if a lower NNE is associated with a greater proportion of thicker melanoma. Combining TTR with NNE allows a better estimate of the effectiveness in melanoma diagnosis, assessing both the overall cost for a given pool of excised melanomas and costs due to unnecessary nevi excision at a particular dermatology centre. METHODS: Demographic data and Breslow thickness of excised melanoma were extracted from patient histologic records at two referral centres for melanoma (Parma Dermatology Unit and Ravenna and Meldola Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori. IRCCS (IRST)) on all skin tumours excised between 2002 and 2011 and diagnosed as melanoma or melanocytic nevus. NNE and TTR were calculated and compared among the considered variables. Logistic regression was used to assess the contribution of each variable in predicting a higher TTR. RESULTS: Data from 16,738 excised lesions were analysed. The IRST Unit reported a mean NNE of 4.6, whereas the Parma Unit excised 10.6 nevi for each melanoma. No statistically significant differences existed in the mean (IRST Unit, 0.56 ± 0.89 mm; Parma Unit, 1.07 ± 2.2 mm) and median (range) Breslow thickness (IRST Unit, 0.4 (9) mm; Parma Unit 0.4 (30) mm). The TTR between centres was significantly different (Parma Unit, 24%; IRST Unit, 12%; p < 0.001). Based on logistic regression, the diagnosing centre was the most powerful factor in determining a thickness of >1 mm among diagnosed melanomas (OR = 1.8; 95% CI, 1.2-2.7; p < 0.01), with all other factors being equal. The NNE decreased at both centres from younger-to-older patients, whereas the TTR increased simultaneously; however, the increase in TTR was non-significantly related to NNE reduction after adjusting for confounders (age, gender, and localization). CONCLUSIONS: A better diagnostic performance is capable of reducing the NNE and TTR, i.e., unnecessary excisions of melanocytic nevi can be reduced without increasing the risk of overlooking melanomas. The TTR, in addition to the NNE, allows stakeholders to better estimate the effectiveness in melanoma diagnosis because both overall costs for a given pool of excised melanomas and costs due for unnecessary nevi excision at a particular dermatology centre can be compared.

Sunburn-related variables, secular trends of improved sun protection and short-term impact on sun attitude behavior in Italian primary schoolchildren: Analysis of the educational campaign "Il Sole Amico" ("The sun as a friend").

Sun protection early in life is an essential issue for primary prevention of skin cancers. The Il Sole per Amico was an educational campaign among 66 Italian primary schools. A total of 12,188 questionnaires were completed at baseline. Overall, 9.4% children reported >1 sunburn during the last year and 44.7% parents a use of sunlamps. Independent factors associated with sunburns were: age, lower level of parents' education, light eye and skin color, freckles, nevi on arms, intense sun exposure during the last year, sporadic use of sunscreens, and parental use of sunlamps. A total of 7280 (59.7%) questionnaires were completed at the end of the educational intervention. No significant difference was documented about behavior between the pre- and post-intervention periods. A significant reduction was instead found in both prevalence of recent sunburns and total number of sunburn episodes after comparison with the data obtained by identical questionnaire in the same geographic areas in the "Sole Si Sole No" project in 2001.

Dermoscopy and confocal microscopy for metachronous multiple melanomas: morphological, clinical, and molecular correlations.

Cutaneous melanoma is one of the most frequent malignancies of the skin in Caucasian populations. Patients who develop cutaneous melanoma are at increased risk of developing a second primary melanoma. The estimated incidence of multiple primary melanoma (MPM) ranges from 1.2% to 8.2% of cases, with a high preponderance of melanomas occurring metachronously. The aim of this study was to describe dermoscopic, microscopic, clinical, and molecular correlations between first and subsequent melanomas in patients with metachronous MPMs. Twenty-four paired melanomas from 12 MPM patients were evaluated for architectural characteristics based on dermoscopy and confocal microscopy, as well as for mutations in BRAF and NRAS genes by Sanger-based sequencing analysis. Specific scores used for classifying features of dermoscopy (global pattern; 7-point check list; ABCD Stolz score) and confocal microscopy (Segura and Pellacani) were compared with genetic and histological data. Consistency in dermoscopic patterns between the primary and subsequent cutaneous melanomas were observed in about two thirds of cases, whereas concordant features based on confocal microscopy were found in only about two fifths of cases. The majority of patients (7/12; 58%) presented consistent BRAF/NRAS mutation patterns between first and subsequent primary melanomas. A significant association between BRAF mutations and Pellacani score was evident. Similarities between the index melanoma and subsequent cutaneous melanomas were observed with regards to dermoscopic features and, to a much less extent, confocal microscopy findings. Our data further indicate that the Pellacani score may be used to predict BRAF mutations.

Parental Use and Educational Campaigns on Sunbed Use Among Teenagers and Adolescents.

This study aimed to evaluate the prevalence of sunbed use among teenagers and the association between familial behavior and the adoption of UV-protective practices in this age group. We also assessed the impact of an educational program on students' knowledge about the potential risks of sunbed use. The educational intervention focused on: (i) skin effects of UV radiation, (ii) photoaging and photocarcinogenesis, (iii) risk factors for skin cancer, (iv) indoor sun tanning and misleading concepts such as possible protective effect of sunbed use on skin cancer risk, (v) sun protection and relation with skin phototype, and (vi) early diagnosis of melanoma using the ABCDE check list and the ugly duckling sign. We carried out a survey of 3098 students and found a strong association between parental sunbed use and students' use of the same (P < 0.0001). Students who attended the educational intervention were more aware that sunbed use cannot prevent sunburns (P = 0.03) than those who did not attend, making adjustments for confounding variables. However, sunbed use by parents influenced the desire to use a sunbed more than participation in the educational intervention (P < 0.0001). In conclusion, although our results indicate that educational interventions can improve knowledge of the risk of sunbed use. They also reveal a strong correlation between sunbed use by teenagers and parental behavior that highlights the importance of educational interventions involving families.