GI.1 Norovirus Neutralizing Antibody Levels Are Correlated with GI.1 Histo-blood Group Antigen-Blocking Antibody Levels.

BACKGROUND: The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histoblood group antigen (HBGA)-blocking assays. METHODS: Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/GI.1 (P1) virus strain. Results were compared to those previously determined using HBGA-blocking assays. RESULTS: Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r=0.81, P<0.001) with those measured by HBGA-blocking. CONCLUSIONS: GI.1-specific HBGA-blocking antibodies are a surrogate for neutralization of GI.1 norovirus.

Position statement of the EADV Artificial Intelligence (AI) Task Force on AI-assisted smartphone apps and web-based services for skin disease.

BACKGROUND: As the use of smartphones continues to surge globally, mobile applications (apps) have become a powerful tool for healthcare engagement. Prominent among these are dermatology apps powered by Artificial Intelligence (AI), which provide immediate diagnostic guidance and educational resources for skin diseases, including skin cancer. OBJECTIVE: This article, authored by the EADV AI Task Force, seeks to offer insights and recommendations for the present and future deployment of AI-assisted smartphone applications (apps) and web-based services for skin diseases with emphasis on skin cancer detection. METHODS: An initial position statement was drafted on a comprehensive literature review, which was subsequently refined through two rounds of digital discussions and meticulous feedback by the EADV AI Task Force, ensuring its accuracy, clarity and relevance. RESULTS: Eight key considerations were identified, including risks associated with inaccuracy and improper user education, a decline in professional skills, the influence of non-medical commercial interests, data security, direct and indirect costs, regulatory approval and the necessity of multidisciplinary implementation. Following these considerations, three main recommendations were formulated: (1) to ensure user trust, app developers should prioritize transparency in data quality, accuracy, intended use, privacy and costs; (2) Apps and web-based services should ensure a uniform user experience for diverse groups of patients; (3) European authorities should adopt a rigorous and consistent regulatory framework for dermatology apps to ensure their safety and accuracy for users. CONCLUSIONS: The utilisation of AI-assisted smartphone apps and web-based services in diagnosing and treating skin diseases has the potential to greatly benefit patients in their dermatology journeys. By prioritising innovation, fostering collaboration and implementing effective regulations, we can ensure the successful integration of these apps into clinical practice.

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.

A Bivalent Human Norovirus Vaccine Induces Homotypic and Heterotypic Neutralizing Antibodies.

A GII.2 outbreak in an efficacy study of a bivalent virus-like particle (VLP) norovirus vaccine, TAK-214, in healthy US adults provided an opportunity to examine GII.4 homotypic vs. GII.2 heterotypic responses to vaccination and infection. Three serological assays (VLP-binding, histoblood group antigen-blocking, and neutralizing) were performed for each genotype. Results were highly correlated within a genotype but not between genotypes. Although the vaccine provided protection from GII.2-associated disease, little GII.2-specific neutralization occurred after vaccination. Choice of antibody assay can affect assessments of human norovirus vaccine immunogenicity.

Antibodies Produced in Response to a Live-Attenuated Dengue Vaccine Are Functional in Activating the Complement System.

BACKGROUND: Antibody-driven complement system (CS) activation has been associated with protection against symptomatic dengue virus (DENV) infection. Aggregation, opsonization, lysis, and phagocytosis are mechanisms triggered by antibody-antigen immunocomplexes following fixation of the component 1q (C1q) and activation of the classical pathway. As a result, DENV neutralization and clearance are facilitated, whereas antibody-dependent enhancement of infection is inhibited. We investigated the ability of antibodies produced in response to Takeda's dengue vaccine candidate, TAK-003, to fix C1q and activate CS. METHODS: Serum samples were collected from seronegative and seropositive participants in a phase 2 clinical trial (DEN-203), pre- and postvaccination. Samples were evaluated for the presence of complement-fixing antibodies (CFAs) against DENV using a Luminex multiplex-based immunoassay. RESULTS: TAK-003 elicited production of CFAs against all 4 DENV serotypes, which persisted for 1 year postvaccination, irrespective of baseline serostatus. CFA levels were correlated with neutralizing antibody titers and virus-binding total IgG and IgG1 concentrations. Furthermore, efficiency of CFA fixation was greater in samples with higher polyclonal IgG avidity. CONCLUSIONS: These results indicate that antibodies produced after TAK-003 vaccination are functional in both activating CS and neutralizing virus infection by all DENV serotypes, which may contribute to efficacy of TAK-003. CLINICAL TRIALS REGISTRATION: NCT01511250.

Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus.

Antibodies capable of activating the complement system (CS) when bound with antigen are referred to as "complement-fixing antibodies" and are involved in protection against Flaviviruses. A complement-fixing antibody test has been used in the past to measure the ability of dengue virus (DENV)-specific serum antibodies to activate the CS. As originally developed, the test is time-consuming, cumbersome, and has limited sensitivity for DENV diagnosis. Here, we developed and characterized a novel multiplex anti-DENV complement-fixing assay based on the Luminex platform to quantitate serum antibodies against all four serotypes (DENV1-4) that activate the CS based on their ability to fix the complement component 1q (C1q). The assay demonstrated good reproducibility and showed equivalent performance to a DENV microneutralization assay that has been used to determine DENV serostatus. In non-human primates, antibodies produced in response to primary DENV1-4 infection induced C1q fixation on homologous and heterologous serotypes. Inter-serotype cross-reactivity was associated with homology of the envelope protein. Interestingly, the antibodies produced following vaccination against Zika virus fixed C1q on DENV. The anti-DENV complement fixing antibody assay represents an alternative approach to determine the quality of functional antibodies produced following DENV natural infection or vaccination and a biomarker for dengue serostatus, while providing insights about immunological cross-reactivity among different Flaviviruses.

Comparison of Microneutralization and Histo-Blood Group Antigen-Blocking Assays for Functional Norovirus Antibody Detection.

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels. METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays. RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking. CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses. CLINICAL TRIALS REGISTRATION: NCT02475278.

Comparison of the accuracy of human readers versus machine-learning algorithms for pigmented skin lesion classification: an open, web-based, international, diagnostic study.

BACKGROUND: Whether machine-learning algorithms can diagnose all pigmented skin lesions as accurately as human experts is unclear. The aim of this study was to compare the diagnostic accuracy of state-of-the-art machine-learning algorithms with human readers for all clinically relevant types of benign and malignant pigmented skin lesions. METHODS: For this open, web-based, international, diagnostic study, human readers were asked to diagnose dermatoscopic images selected randomly in 30-image batches from a test set of 1511 images. The diagnoses from human readers were compared with those of 139 algorithms created by 77 machine-learning labs, who participated in the International Skin Imaging Collaboration 2018 challenge and received a training set of 10 015 images in advance. The ground truth of each lesion fell into one of seven predefined disease categories: intraepithelial carcinoma including actinic keratoses and Bowen's disease; basal cell carcinoma; benign keratinocytic lesions including solar lentigo, seborrheic keratosis and lichen planus-like keratosis; dermatofibroma; melanoma; melanocytic nevus; and vascular lesions. The two main outcomes were the differences in the number of correct specific diagnoses per batch between all human readers and the top three algorithms, and between human experts and the top three algorithms. FINDINGS: Between Aug 4, 2018, and Sept 30, 2018, 511 human readers from 63 countries had at least one attempt in the reader study. 283 (55·4%) of 511 human readers were board-certified dermatologists, 118 (23·1%) were dermatology residents, and 83 (16·2%) were general practitioners. When comparing all human readers with all machine-learning algorithms, the algorithms achieved a mean of 2·01 (95% CI 1·97 to 2·04; p<0·0001) more correct diagnoses (17·91 [SD 3·42] vs 19·92 [4·27]). 27 human experts with more than 10 years of experience achieved a mean of 18·78 (SD 3·15) correct answers, compared with 25·43 (1·95) correct answers for the top three machine algorithms (mean difference 6·65, 95% CI 6·06-7·25; p<0·0001). The difference between human experts and the top three algorithms was significantly lower for images in the test set that were collected from sources not included in the training set (human underperformance of 11·4%, 95% CI 9·9-12·9 vs 3·6%, 0·8-6·3; p<0·0001). INTERPRETATION: State-of-the-art machine-learning classifiers outperformed human experts in the diagnosis of pigmented skin lesions and should have a more important role in clinical practice. However, a possible limitation of these algorithms is their decreased performance for out-of-distribution images, which should be addressed in future research. FUNDING: None.

Dermoscopy and dermatopathology correlates of cutaneous neoplasms.

Dermoscopy is increasingly used by clinicians (dermatologists, family physicians, podiatrists, doctors of osteopathic medicine, etc) to inform clinical management decisions. Dermoscopic findings or images provided to pathologists offer important insight into the clinician's diagnostic and management thought process. However, with limited dermoscopic training in dermatopathology, dermoscopic descriptions and images provided in the requisition form provide little value to pathologists. Most dermoscopic structures have direct histopathologic correlates, and therefore dermoscopy can act as an excellent communication bridge between the clinician and the pathologist. In the first article in this continuing medical education series, we review dermoscopic features and their histopathologic correlates.

Usefulness of dermoscopy to improve the clinical and histopathologic diagnosis of skin cancers.

Multiple studies have shown that dermoscopy increases the sensitivity and specificity for the detection of skin cancers compared with examination by the naked eye. Dermoscopy can also lead to the detection of thinner and smaller cancers. In addition, dermoscopy leads to the more precise selection of lesions requiring excision. In essence, dermoscopy helps clinicians differentiate benign from malignant lesions through the presence or absence of specific dermoscopic structures. Therefore, because most dermoscopic structures have direct histopathologic correlates, dermoscopy can allow the prediction of certain histologic findings present in skin cancers, thus helping select management and treatment options for select types of skin cancers. Visualizing dermoscopic structures in the ex vivo specimens can also be beneficial. It can improve the histologic diagnostic accuracy by targeted step-sectioning in areas of concern, which can be marked by the clinician before sending the specimen to the pathologist, or by the pathologist on the excised specimen in the laboratory. In addition, ex vivo dermoscopy can also be used to select tumor areas with genetic importance because some dermoscopic structures have been related to mutations with theragnostic relevance. In the second article in this continuing medical education series, we review the impact of dermoscopy on the diagnostic accuracy of skin cancer, how dermoscopy can affect the histopathologic examination, and which dermoscopic features may be more relevant in terms of histologic and genetic prediction.

Current concepts in advanced sinonasal mucosal melanoma: a single institution experience.

PURPOSE: To present outcome measures of sinonasal mucosal melanoma (SMM) patients with particular focus on current radiological and therapeutic options, especially in the non-curative setting (immunotherapy). METHODS: Retrospective study on SMM patients treated at our institution between January 1992 and December 2018. RESULTS: FDG-PET/MRI has emerged as the new hybrid imaging modality, addressing the need for high local tissue contrast in the paranasal sinuses and the skull base, while allowing for whole-body staging in search for distant metastases, including the brain. Primary treatment protocols consisted of tumor resection in 30/34 patients (88%), palliative radiation therapy (RT) in 3/34 patients (9%) and best supportive care therapy in 1/34 patient (3%). Of all the initially operated patients, 25/30 patients (83%) received adjuvant RT. A total of 9/34 patients (26%) was treated with immunotherapy after the previous combined therapy. For patients treated in curative intention, we observed a 1-year overall survival (OS) of 60% (18/30 patients) and a 3-year OS of 40% (12/30 patients). For patients treated with immunotherapy, median progression-free survival (PFS) was 5 months (IQR 0-13.75), with a maximum PFS of 16 months (combination of nivolumab and ipilimumab). However, there was no difference in OS in patients treated with immunotherapy vs. no immunotherapy (log rank 0.99). CONCLUSIONS: Sinonasal mucosal melanoma is a highly aggressive tumor, requiring multimodal therapy and developing a substantial incidence of distant metastases. The introduction of FDG-PET/MRI offers new possibilities in the radiological assessment of the tumor and immunotherapy has altered the management in the non-curative setting, resulting in a substantial progression-free survival in selected cases.

Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists.

Background: Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, but data comparing a CNN's diagnostic performance to larger groups of dermatologists are lacking. Methods: Google's Inception v4 CNN architecture was trained and validated using dermoscopic images and corresponding diagnoses. In a comparative cross-sectional reader study a 100-image test-set was used (level-I: dermoscopy only; level-II: dermoscopy plus clinical information and images). Main outcome measures were sensitivity, specificity and area under the curve (AUC) of receiver operating characteristics (ROC) for diagnostic classification (dichotomous) of lesions by the CNN versus an international group of 58 dermatologists during level-I or -II of the reader study. Secondary end points included the dermatologists' diagnostic performance in their management decisions and differences in the diagnostic performance of dermatologists during level-I and -II of the reader study. Additionally, the CNN's performance was compared with the top-five algorithms of the 2016 International Symposium on Biomedical Imaging (ISBI) challenge. Results: In level-I dermatologists achieved a mean (±standard deviation) sensitivity and specificity for lesion classification of 86.6% (±9.3%) and 71.3% (±11.2%), respectively. More clinical information (level-II) improved the sensitivity to 88.9% (±9.6%, P = 0.19) and specificity to 75.7% (±11.7%, P < 0.05). The CNN ROC curve revealed a higher specificity of 82.5% when compared with dermatologists in level-I (71.3%, P < 0.01) and level-II (75.7%, P < 0.01) at their sensitivities of 86.6% and 88.9%, respectively. The CNN ROC AUC was greater than the mean ROC area of dermatologists (0.86 versus 0.79, P < 0.01). The CNN scored results close to the top three algorithms of the ISBI 2016 challenge. Conclusions: For the first time we compared a CNN's diagnostic performance with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN. Irrespective of any physicians' experience, they may benefit from assistance by a CNN's image classification. Clinical trial number: This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).

Update on adjuvant melanoma therapy.

PURPOSE OF REVIEW: We review the results from relevant clinical trials and discuss current strategies in the melanoma adjuvant setting. RECENT FINDINGS: The favorable therapeutic efficacy and the significant less toxicity of nivolumab compared with ipilimumab, fully substitutes today's approval of ipilimumab, regardless mutation status, whereas in BRAF-mutated patients, dabrafenib and trametinib seem to confirm their high efficacy also in adjuvant setting. The use of interferon is restricted to patients with ulcerated melanoma and countries with no access to the new drugs. SUMMARY: Systemic adjuvant treatment after complete disease resection in high-risk melanoma patients aims to increase relapse-free survival (RFS) and overall survival (OS). According to the eighth edition of melanoma classification of American Joint Committee on Cancer (AJCC), the prognosis in stage III patients is heterogeneous and depends not only on N (nodal) but also on T (tumor thickness) category criteria. Recent data from randomized, phase-3 clinical trials analyzing the use of adjuvant anti-programmed death-1 and targeted therapies ultimately affect the standard of care and change the landscape of the adjuvant treatment.

Critical aspects to achieve a high-quality melanoma clinic.

PURPOSE OF REVIEW: With incidence of melanoma growing worldwide and new therapies prolonging the survival of patients with advanced disease, complex medical care is needed. RECENT FINDINGS: Best care of complicated melanoma cases is achieved in specialized referral centers. Aims to provide optimized melanoma therapy, best patient-reported treatment outcome, and successful clinical and translational research, necessitate a dedicated interdisciplinary team. SUMMARY: We report on critical aspects of the interaction between patients, medical care givers, clinical trial and biobanking teams, and emphasize the importance of interdisciplinary tumor boards. Specialized skin cancer nurses and local patient advocacy groups should be involved in patient care and could be the binding link between the patients and the treatment team.

25-Hydroxyvitamin-D3 serum modulation after use of sunbeds compliant with European Union standards: A randomized open observational controlled trial.

BACKGROUND: Regular use of sunbed exposure has been reported to increase 25-hydroxyvitamin-D3 [25(OH)D] serum levels. However, the influence of sunbeds compliant with the recent European Union standard EN-60335-2-27 on 25(OH)D serum levels is unknown. OBJECTIVE: We investigated the impact of standard sunbed use compliant with the European Union standard on 25(OH)D serum modulation and well-being. METHODS: In a randomized controlled study, 25(OH)D serum levels were measured at enrollment, after 1 week, and after completion of the 12-week period of sunbed use with twice weekly exposure and compared with the control group without any sunbed exposure. RESULTS: In the sunbed intervention group (N = 31), a 27% increase of mean 25(OH)D levels was noted 1 week after starting sunbed use (P < .01). However, after 12 weeks, mean 25(OH)D levels had declined and were no longer different from baseline (P = .06). After 12 weeks, 25(OH)D levels did not differ between the intervention and control group (P = .36). Also the 5-item World Health Organization Well-Being Index score did not differ between the sunbed and control groups (P = .19). LIMITATIONS: For ethical reasons recruitment was limited to persons actively seeking sunbed exposure. CONCLUSIONS: Standard use of sunbeds compliant with the European Union standard induced a transient increase of 25(OH)D levels, whereas no change in well-being was observed.

Accuracy of dermatoscopy for the diagnosis of nonpigmented cancers of the skin.

BACKGROUND: Nonpigmented skin cancer is common, and diagnosis with the unaided eye is error prone. OBJECTIVE: To investigate whether dermatoscopy improves the diagnostic accuracy for nonpigmented (amelanotic) cutaneous neoplasms. METHODS: We collected a sample of 2072 benign and malignant neoplastic lesions and inflammatory conditions and presented close-up images taken with and without dermatoscopy to 95 examiners with different levels of experience. RESULTS: The area under the curve was significantly higher with than without dermatoscopy (0.68 vs 0.64, P < .001). Among 51 possible diagnoses, the correct diagnosis was selected in 33.1% of cases with and 26.4% of cases without dermatoscopy (P < .001). For experts, the frequencies of correct specific diagnoses of a malignant lesion improved from 40.2% without to 51.3% with dermatoscopy. For all malignant neoplasms combined, the frequencies of appropriate management strategies increased from 78.1% without to 82.5% with dermatoscopy. LIMITATIONS: The study deviated from a real-life clinical setting and was potentially affected by verification and selection bias. CONCLUSIONS: Dermatoscopy improves the diagnosis and management of nonpigmented skin cancer and should be used as an adjunct to examination with the unaided eye.

Evaluation of the National Swiss Skin Cancer Screening Campaign 2013: Do We Do the Right Thing.

BACKGROUND: Skin cancer prevention and screening programs are performed in many countries. Their benefit is discussed controversially. OBJECTIVE: Our aim is to evaluate the Skin Cancer Screening Program 2013 in Switzerland by following up screenees upon interventions. METHODS: Quality was assessed by personal follow-up via phone/e-mail of every patient that had been screened during this campaign and histological follow-up of all participants with suspicious skin lesions. RESULTS: Of the 1,087 screenees requiring interventions, 263 agreed to participate in the follow-up. We were able to obtain 66 histology reports. During this campaign 33 malignant lesions (8 melanomas) were removed. CONCLUSION: The overall melanoma detection rate in our free Skin Cancer Screening Program is comparable to those in European public activities. The costs of free screening programs compare favorably with the prevented potential therapeutic costs of late-stage melanoma. The low response rate of screenees agreeing to be followed up limits conclusions of this study.

Differential Diagnosis of Seborrheic Keratosis: Clinical and Dermoscopic Features.

Seborrheic keratosis (SK) is a benign epidermal keratinocytic tumor that is extremely common, particularly in individuals over the age of 50. Most individuals with SK will have more than one lesion and the presence of over 10 lesions in the same person is not uncommon. Although the clinical morphology of most SK with their stuck-on, symmetric, keratotic, and waxy appearance makes them easy to identify, many manifest a morphology resembling melanoma or squamous cell carcinoma. One can argue that such cases will ultimately not prove to be problematic since a simple biopsy will easily reveal their benign nature and eliminate any concerns. However, the cost and morbidity associated with the biopsy of benign lesions should not be underestimated. Methods to improve our in vivo ability to correctly identify SK will prove beneficial not only to the health care system in general but to the individual patient specifically. The issue of greater concern resides with skin cancers that mimic SK or when skin cancers arise in association with SK. Needless to say, in vivo methods to help identify malignancy and differentiate them from benign lesions would be welcomed by all. Fortunately, we do now have in vivo imaging methods such as dermoscopy that can improve the clinician's diagnostic accuracy. In this article, we summarize the current knowledge regarding the clinical and dermoscopic features of SK, and provide clues to aid in their diagnosis.

J Drugs Dermatol. 2017;16(9):835-842.

Clinical and dermoscopic characteristics of melanomas on nonfacial chronically sun-damaged skin.

BACKGROUND: Melanomas on chronically sun-damaged skin (CSDS) can be difficult to identify and often manifest morphologic features that overlap with benign lesions. OBJECTIVE: We describe and analyze the clinical and dermoscopic characteristics of melanomas on nonfacial CSDS. METHODS: Melanoma cases on nonfacial CSDS were retrospectively identified from the biopsy specimen logs of 6 melanoma clinics. Clinical and dermoscopic images were combined into 1 database. Demographics, clinical, dermoscopic, and histopathologic information were analyzed. Descriptive frequencies were calculated. RESULTS: One hundred eighty-six cases met the inclusion criteria: 142 melanomas in situ (76%) and 39 invasive (21%; mean thickness, 0.49 mm). Lentigo maligna was the most common histopathologic subtype (n = 76; 40.9%). The most frequent dermoscopic structures were granularity (n = 126; 67.7%) and angulated lines (n = 82; 44%). Vascular structures were more frequent in invasive melanomas (56% vs 12% of in situ melanomas). Most manifested 1 of 3 dermoscopic patterns: patchy peripheral pigmented islands, angulated lines, and tan structureless with granularity pattern. LIMITATIONS: This was a retrospective study, and evaluators were not blinded to the diagnosis. In addition, interobserver concordance and sensitivity and specificity for dermoscopic structures were not evaluated. CONCLUSION: Outlier lesions manifesting dermoscopic structures, such as granularity, angulated lines, or vessels and any of the 3 described dermoscopic patterns should raise suspicion for melanoma.