Dermoscopic Features of Melanocytic Nevi in Cardiofaciocutaneous and Costello Syndromes.

Importance: Somatic variants in the RAS/MAPK pathway genes are commonly associated with melanocytic nevi and melanoma, whereas germline variants in these genes are associated with RASopathies, syndromes involving multiple organs, including the skin. Nevi counts may be higher in some RASopathies, but studies on features observed through dermoscopy are limited. Objective: To determine the distinguishing dermoscopic features of melanocytic nevi and how the RAS pathway influences them by comparing nevi in patients with cardiofaciocutaneous syndrome (CFC) and Costello syndrome (CS). Design, Setting, and Participants: In this prospective cohort study, patients with CFC and CS, 2 RASopathies caused by variants in the downstream and upstream components of the RAS/MAPK pathway, were recruited from the international CFC and CS family conferences. Some patients with CFC also elected to participate in a longitudinal follow-up study. Main Outcomes and Measures: The main outcomes were dermoscopic features and, in the longitudinal follow-up study, nevi counts, which were recorded over time. Results: A total of 39 patients, 16 with CFC and 23 with CS, were enrolled (overall cohort: 26 [66.7%] female; median [IQR] age, 13.0 [7.6-22.0] years). The 112 nevi overall frequently displayed an organized dermoscopic pattern (CFC, 61 [84.7%]; CS, 34 [85.0%]) rather than a disorganized pattern (CFC, 6 [8.3%]; CS, 1 [2.5%]). Of the organized nevi, homogenous brown was the most common pattern (CFC, 41 [67.2%]; CS, 22 [64.7%]), followed by reticular (CFC, 11 [18.0%]; CS, 7 [20.6%]) and globular (CFC, 9 [14.8%]; CS, 5 [14.7%]). Pigmented networks occurred in 12 nevi in CFC (16.7%) and 6 nevi in CS (15%; P > .99). Of these, 6 CFC-associated nevi (50%) and no CS-associated nevi had atypical networks (P = .05). Six patients with CFC in the follow-up study developed significantly more nevi within 5 years (median [IQR] increase, 24.5 [10-120] nevi; P = .04). Conclusions and Relevance: In this cohort study, the findings suggest that nevi in patients with CFC and CS commonly display organized homogenous brown dermoscopic patterns, and the number of nevi may significantly increase over time in those with CFC. A disorganized pattern and atypical networks may be more frequent in patients with CFC. Future studies are needed to determine the risk of melanoma in individuals with CFC or CS.

Importance of Both Clinical and Dermoscopic Findings in Predicting High-Risk Histopathological Subtype in Facial Basal Cell Carcinomas.

INTRODUCTION: Being able to recognize high-risk facial basal cell carcinoma (BCC) may lead to fewer incomplete excisions and inappropriate treatments. OBJECTIVES: We sought to investigate clinical and dermoscopic criteria for predicting facial BCC subtypes, analyze the interobserver agreement between readers, and develop a diagnostic algorithm to predict high-risk histopathological subtype. METHODS: In this single-center, retrospective investigation, 6 independent readers evaluated predefined clinical and dermoscopic criteria in images of histopathologically verified primary facial BCCs including: topography, border demarcation, vessels, ulceration, white porcelain areas, shiny white blotches and strands, and pigmented structures and vessels within ulceration. RESULTS: Overall, 297 clinical and dermoscopic image pairs were analyzed. The strongest associations with high-risk subtype were: "bumpy" topography (OR 3.8, 95% CI, 3.1-4.7), ill-defined borders (OR 3.4, 95% CI 3.1-4.7), white porcelain area (OR 3.5, 95% CI 2.8-4.5), and vessels within ulceration (OR 3.1, 95% CI 2.4-4.1). Predominantly focused vessels were a positive diagnostic criterium for either nodular (OR 1.7, 95% CI 1.3-2.2) or high-risk (OR 2.0, 95% CI 1.6-2.5) subtypes and a strong negative diagnostic criterium for superficial BCC (OR 14.0, 95% CI 9.6-20.8). Interobserver agreement ranged from fair to substantial (κ=0.36 to 0.72). A diagnostic algorithm based on these findings demonstrated a sensitivity of 81.4% (95% CI, 78.9-83.7%) and a specificity of 53.3% (95% CI, 49.7-56.9%) for predicting high-risk BCC subtype. CONCLUSIONS: Integration of both clinical and dermoscopic features (including novel features such as topography and vessels within ulceration) are essential to improve subtype prediction of facial BCCs and management decisions.

Challenging Diagnosis of Basal Cell Carcinoma: A Case Report Emphasizing the Clinical Utility of Dermoscopy.

Dermatological conditions often present diagnostic challenges due to their diverse manifestations and overlapping clinical features. In such cases, dermoscopy, a non-invasive imaging technique, has emerged as a valuable tool to enhance diagnostic accuracy and guide clinicians in reaching an appropriate differential diagnosis. By visualizing subsurface skin structures and microvascular patterns, dermoscopy provides additional information that complements clinical examination, aiding in the recognition of specific dermatoses and the differentiation between benign and malignant skin lesions. Herein, we present a case that demonstrates the utility of dermoscopy in distinguishing between an initial broad list of differential diagnoses, namely, basal cell carcinoma, squamous cell carcinoma in situ, and other inflammatory dermatitides, such as psoriasis and atopic dermatitis, and narrowing down the differential diagnosis to just one likely diagnosis, which was basal cell carcinoma in our case.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society.

BACKGROUND: The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. OBJECTIVES: Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. METHODS: Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs. RESULTS: We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. CONCLUSIONS: The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.

Applications of Ultraviolet and Sub-ultraviolet Dermatoscopy in Neoplastic and Non-neoplastic Dermatoses: A Systematic Review.

Dermatoscopy is a non-invasive and cost-efficient imaging technique augmenting clinical examination in neoplastic and non-neoplastic dermatoses. Recently, novel dermatoscopic techniques based on principles of reflectance/absorption and excited fluorescence have been developed. However, comprehensive data on their applications are sparse, and terminology is inconsistent. In this systematic review, we addressed the principles of ultraviolet (UV) imaging and proposed categorization based on spectral characteristics and signal acquisition, as well as discussed documented and potential clinical applications, safety measures during examination, and limitations associated with reflectance and fluorescence dermatoscopy. A literature search was conducted in the PubMed medical database until 2 December 2023 according to PRISMA guidelines, and 28 papers fit the scope of this review, whereas additional relevant articles were included to provide broader context regarding the chosen terminology, chromophores described, safety of sub-UV/UV, and regulations for light-emitting devices. UV and sub-UV dermatoscopy, categorized into different methods on the basis of the emitted wavelength and signal acquisition process (reflectance versus fluorescence), augment conventional dermatoscopy by optimizing safety margins in melanoma, facilitating early detection of tumor recurrence, and enhancing visualization in non-neoplastic conditions, including pigmentation disorders, intertrigo, papulo-desquamative dermatoses, and beyond. The review highlights the limitations of these techniques, including difficulty in differentiating melanin from hemoglobin, challenges in evaluating uneven surfaces, and artifacts. Although UV dermatoscopy complements conventional dermatoscopy, clinicians should be aware of their peculiarities, artifacts, limitations, and safety concerns to optimize their diagnostic accuracy and ensure patient's safety.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments.

Full-body skin examination in screening for cutaneous malignancy: a focus on concealed sites and the practices of Australian dermatologists.

BACKGROUND: Full-body skin examination (FSE) is a vital practice in the diagnosis of cutaneous malignancy. Precisely how FSE should be conducted with respect to concealed site inclusion remains poorly elucidated. OBJECTIVE: To establish the approach of Australian dermatologists to concealed site examination (CSE). METHODS: A cross-sectional study was performed consisting of an online self-administered 11-question survey delivered to fellows of the Australasian College of Dermatologists. RESULTS: There were 237 respondents. Anogenitalia was the least often examined concealed site (4.6%), and 59.9, 32.9, and 14.3% reported always examining the scalp, breasts, and oral mucosa, respectively. Patient concern was the most frequently cited factor prompting examination, while many cited low incidence of pathology and limited chaperone availability as the main barriers to routine examination of these sites. CONCLUSION: Most Australian dermatologists do not routinely examine breasts, oral mucosal, or anogenital sites as part of an FSE. Emphasis should be made on identifying individual patient risk factors and education regarding self-examination of sensitive sites. A consensus approach to the conduct of the FSE, including concealed sites, is needed to better delineate clinician responsibilities and address medicolegal implications.

Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

Perifollicular linear projections: A dermatoscopic criterion for the diagnosis of lentigo maligna on the face.

BACKGROUND: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. OBJECTIVE: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face. METHODS: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. RESULTS: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). LIMITATIONS: Retrospective study. CONCLUSION: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model.

Acquired Melanocytic Nevi Mimicking Acral Lentiginous Melanoma in a Patient Taking a BRAF Inhibitor.

This case report describes a patient in their 60s with metastatic colon cancer who developed multiple new dark nevi within 2 months of initiating encorafenib and panitumumab therapy.

Delphi Consensus Among International Experts on the Diagnosis, Management, and Surveillance for Lentigo Maligna.

INTRODUCTION: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. OBJECTIVES: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. METHODS: A modified Delphi method was used. The invited participants were either members of the International Dermoscopy Society, academic experts, or authors of published articles relating to skin cancer and melanoma. Participants were required to respond across three rounds using a 4-point Likert scale). Consensus was defined as >75% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing. RESULTS: Of the 31 experts invited to participate in this Delphi study, 29 participants completed Round 1 (89.9% response rate), 25/31 completed Round 2 (77.5% response rate), and 25/31 completed Round 3 (77.5% response rate). Experts agreed that LM diagnosis should be based on a clinical and dermatoscopic approach (92%) followed by a biopsy. The most appropriate primary treatment of LM was deemed to be margin-controlled surgery (83.3%), although non-surgical modalities, especially imiquimod, were commonly used either as alternative off-label primary treatment in selected patients or as adjuvant therapy following surgery; 62% participants responded life-long clinical follow-up was needed for LM. CONCLUSIONS: Clinical and histological diagnosis of LM is challenging and should be based on macroscopic, dermatoscopic, and RCM examination followed by a biopsy. Different treatment modalities and follow-up should be carefully discussed with the patient.

Prospective validation of dermoscopy-based open-source artificial intelligence for melanoma diagnosis (PROVE-AI study).

The use of artificial intelligence (AI) has the potential to improve the assessment of lesions suspicious of melanoma, but few clinical studies have been conducted. We validated the accuracy of an open-source, non-commercial AI algorithm for melanoma diagnosis and assessed its potential impact on dermatologist decision-making. We conducted a prospective, observational clinical study to assess the diagnostic accuracy of the AI algorithm (ADAE) in predicting melanoma from dermoscopy skin lesion images. The primary aim was to assess the reliability of ADAE's sensitivity at a predefined threshold of 95%. Patients who had consented for a skin biopsy to exclude melanoma were eligible. Dermatologists also estimated the probability of melanoma and indicated management choices before and after real-time exposure to ADAE scores. All lesions underwent biopsy. Four hundred thirty-five participants were enrolled and contributed 603 lesions (95 melanomas). Participants had a mean age of 59 years, 54% were female, and 96% were White individuals. At the predetermined 95% sensitivity threshold, ADAE had a sensitivity of 96.8% (95% CI: 91.1-98.9%) and specificity of 37.4% (95% CI: 33.3-41.7%). The dermatologists' ability to assess melanoma risk significantly improved after ADAE exposure (AUC 0.7798 vs. 0.8161, p = 0.042). Post-ADAE dermatologist decisions also had equivalent or higher net benefit compared to biopsying all lesions. We validated the accuracy of an open-source melanoma AI algorithm and showed its theoretical potential for improving dermatology experts' ability to evaluate lesions suspicious of melanoma. Larger randomized trials are needed to fully evaluate the potential of adopting this AI algorithm into clinical workflows.

Paradoxical effect of epinephrine on lesion redness and vascularity.

INTRODUCTION: Epinephrine is commonly used in combination with local anesthetic (lidocaine/epinephrine) due to its beneficial vasoconstrictive properties. Typically, pallor is appreciated after injection as a sign of effect; however, we observed that some cutaneous malignancies paradoxically revealed increased redness and vascularity after injection of lidocaine/epinephrine. In this study, we investigate this phenomenon among a series of biopsied lesions to identify characteristics of lesions associated with increased redness and/or vascularity. OBJECTIVES: To determine characteristics of lesions which become redder or more vascular after injection with lidocaine/epinephrine prior to biopsy. METHODS: This cross-sectional study consisted of a convenience sample of lesions scheduled for biopsy. Lesions were photographed prior to and 7 min after injection of lidocaine/epinephrine as a part of standard care. Two readers blinded to study objectives and histopathological diagnosis assessed lesions for changes in redness and vascular features. RESULTS: Fifty-four lesions from 47 patients-61.7% male, mean age 64.8 years, age-range 24-91 were included. Thirty-six lesions were biopsy confirmed malignant, with 5 in situ and 31 invasive malignancies; the remaining 18 lesions were benign. In comparison with non-malignant lesions, malignant lesions were associated with an increase in clinically appreciable vascular features after injection of lidocaine/epinephrine, X2 (1) = 21.600, p < 0.001. Further stratification into benign, in situ, and invasive lesions strengthened the association, X2 (1) = 23.272, p < 0.001. CONCLUSIONS: Combination lidocaine/epinephrine has been shown to paradoxically increase the visibility of vessels seen in cutaneous malignancies. This is consistent with prior literature suggesting aberrant adrenergic signaling in neoangiogenic vessels.