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Melanoma: HELP
Articles by Horacio Cabo
Based on 8 articles published since 2008
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Between 2008 and 2019, H. Cabo wrote the following 8 articles about Melanoma.
 
+ Citations + Abstracts
1 Review A clinico-dermoscopic approach for skin cancer screening: recommendations involving a survey of the International Dermoscopy Society. 2013

Argenziano, Giuseppe / Giacomel, Jason / Zalaudek, Iris / Blum, Andreas / Braun, Ralph P / Cabo, Horacio / Halpern, Allan / Hofmann-Wellenhof, Rainer / Malvehy, Josep / Marghoob, Ashfaq A / Menzies, Scott / Moscarella, Elvira / Pellacani, Giovanni / Puig, Susana / Rabinovitz, Harold / Saida, Toshiaki / Seidenari, Stefania / Soyer, H Peter / Stolz, Wilhelm / Thomas, Luc / Kittler, Harald. ·Dermatology and Skin Cancer Unit, Arcispedale Santa Maria Nuova IRCCS, Viale Risorgimento 80, Reggio Emilia 42100, Italy. Electronic address: g.argenziano@gmail.com. ·Dermatol Clin · Pubmed #24075542.

ABSTRACT: Dermoscopy is useful for skin cancer screening, but a detailed approach is required that integrates this tool into a rational clinical work flow. To investigate clinician perceptions and behavior in approaching patients with skin tumors, a survey was launched by electronic mail through the International Dermoscopy Society. After 4 months, the responses were analyzed and significant findings calculated. Considering the current approach of study participants in examining patients for skin cancer, an up-to-date system of triage is presented in this review, which aims to promote an improved diagnostic accuracy and more timely management of skin malignancy.

2 Article Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma. 2016

Puig, Susana / Potrony, Miriam / Cuellar, Francisco / Puig-Butille, Joan Anton / Carrera, Cristina / Aguilera, Paula / Nagore, Eduardo / Garcia-Casado, Zaida / Requena, Celia / Kumar, Rajiv / Landman, Gilles / Costa Soares de Sá, Bianca / Gargantini Rezze, Gisele / Facure, Luciana / de Avila, Alexandre Leon Ribeiro / Achatz, Maria Isabel / Carraro, Dirce Maria / Duprat Neto, João Pedreira / Grazziotin, Thais C / Bonamigo, Renan R / Rey, Maria Carolina W / Balestrini, Claudia / Morales, Enrique / Molgo, Montserrat / Bakos, Renato Marchiori / Ashton-Prolla, Patricia / Giugliani, Roberto / Larre Borges, Alejandra / Barquet, Virginia / Pérez, Javiera / Martínez, Miguel / Cabo, Horacio / Cohen Sabban, Emilia / Latorre, Clara / Carlos-Ortega, Blanca / Salas-Alanis, Julio C / Gonzalez, Roger / Olazaran, Zulema / Malvehy, Josep / Badenas, Celia. ·Melanoma Unit, Dermatology Department, Hospital Clínic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain. · Centro Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. · Departament de Medicina, Universitat de Barcelona, Barcelona, Spain. · Consejo Nacional de Ciencia y Tecnología (CONACYT), Ciudad de México, México. · Melanoma Unit, Biochemistry and Molecular Genetics Department, Hospital Clínic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain. · Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain. · Universidad Católica de Valencia, Valencia, Spain. · Molecular Biology Unit, Instituto Valenciano de Oncologia, Valencia, Spain. · Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. · Escola Paulista de Medicina - UNIFESP, São Paulo, Brazil. · International Research Center, AC Camargo Cancer Center, São Paulo, Brazil. · Dermatology Department and Post-Graduation Program of Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil. · Servicio de Dermatología, Hospital Dr. Sótero del Río, Santiago de Chile, Chile. · Servicio de Dermatología, Hospital San Juan de Dios, Santiago, Chile. · Pontificia Universidad Católica de Chile, Santiago de Chile, Chile. · Department of Dermatology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. · Unidad de Lesiones Pigmentadas, Cátedra de Dermatología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay. · Instituto de Investigaciones Medicas "A Lanari," Universidad de Buenos Aires, Buenos Aires, Argentina. · Consultorio Dermatológico Drs. Cohen Sabban y Cabo, Buenos Aires, Argentina. · Hospital Especialidades Centro Medico Nacional La Raza, Mexico, DF, Mexico. · Departamento de Ciencias Básicas, Escuela de Medicina Universidad de Monterrey, Monterrey, Mexico. · Departamento de Introducción a la Clínica, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico. · Servicio de Dermatología, Hospital Universitario "Dr. José Eleuterio González," Monterrey, Mexico. ·Genet Med · Pubmed #26681309.

ABSTRACT: PURPOSE: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. METHODS: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. RESULTS: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. CONCLUSION: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736.

3 Article Recurrent melanocytic nevi and melanomas in dermoscopy: results of a multicenter study of the International Dermoscopy Society. 2014

Blum, Andreas / Hofmann-Wellenhof, Rainer / Marghoob, Ashfaq A / Argenziano, Giuseppe / Cabo, Horacio / Carrera, Cristina / Costa Soares de Sá, Bianca / Ehrsam, Eric / González, Roger / Malvehy, Josep / Manganoni, Ausilia Maria / Puig, Susana / Simionescu, Olga / Tanaka, Masaru / Thomas, Luc / Tromme, Isabelle / Zalaudek, Iris / Kittler, Harald. ·Public, Private, and Teaching Practice of Dermatology, Konstanz, Germany. · Medical University of Graz, Graz, Austria. · Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York. · Skin Cancer Unit, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy. · Medical Research Institute "A. Lanari," University of Buenos Aires, Buenos Aires, Argentina. · Melanoma Unit, Department of Dermatology, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en red de enfermedades raras (CIBERER) Enfermedades rara, Barcelona, Spain. · Skin Cancer and Dermatology Center, Hospital AC Camargo São Paulo, Brazil. · Public and Private Practice of Dermatology, Lille, France. · Departamento de Introducción a la Clínica, Facultad de Medicina, UANL, Monterrey, México. · Department of Dermatology, University of Brescia, Brescia, Italy. · First Dermatological Clinic, Carol Davila University of Medicine and Pharmacy, Colentina Hospital, Bucharest, Romania. · Department of Dermatology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan. · Department of Dermatology, Lyon 1 University Centre Hospitalier Lyon Sud, Pierre Bénite, France. · Department of Dermatology, Centre du Cancer, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium. · Department of Dermatology, Medical University of Vienna, Vienna, Austria. ·JAMA Dermatol · Pubmed #24226788.

ABSTRACT: IMPORTANCE Differentiating recurrent nevi from recurrent melanoma is challenging. OBJECTIVE To determine dermoscopic features to differentiate recurrent nevi from melanomas. DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study of 15 pigmented lesion clinics from 12 countries; 98 recurrent nevi (61.3%) and 62 recurrent melanomas (38.8%) were collected from January to December 2011. MAIN OUTCOMES AND MEASURES Scoring the dermoscopic features, patterns, and colors in correlation with the histopathologic findings. RESULTS In univariate analysis, radial lines, symmetry, and centrifugal growth pattern were significantly more common dermoscopically in recurrent nevi; in contrast, circles, especially if on the head and neck area, eccentric hyperpigmentation at the periphery, a chaotic and noncontinuous growth pattern, and pigmentation beyond the scar's edge were significantly more common in recurrent melanomas. Patients with recurrent melanomas were significantly older than patients with recurrent nevi (mean [SD] age, 63.1 [17.5] years vs 30.2 [12.4] years) (P<.001), and there was a significantly longer time interval between the first procedure and the second treatment (median time interval, 25 vs 8 months) (P<.001). In a multivariate analysis, pigmentation beyond the scar's edge (P=.002), age (P<.001), and anatomic site (P=.002) were significantly and independently associated with the diagnosis of recurrent melanoma in dermoscopy. CONCLUSIONS AND RELEVANCE Dermoscopically, pigmentation beyond the scar's edge is the strongest clue for melanoma. Dermoscopy is helpful in evaluating recurrent lesions, but final interpretation requires taking into account the patient age, anatomic site, time to recurrence, growth pattern, and, if available, the histopathologic findings of the first excision.

4 Article Dermoscopy of acral melanoma: a multicenter study on behalf of the international dermoscopy society. 2013

Braun, Ralph P / Thomas, L / Dusza, S W / Gaide, O / Menzies, S / Dalle, S / Blum, A / Argenziano, G / Zalaudek, I / Kopf, A / Rabinovitz, H / Oliviero, M / Perrinaud, A / Cabo, H / Pizzichetta, M / Pozo, L / Langford, D / Tanaka, M / Saida, T / Perusquia Ortiz, A M / Kreusch, J / De Giorgi, V / Piccolo, D / Grichnik, J M / Kittler, H / Puig, S / Malvehy, J / Seidenari, S / Stanganelli, I / French, L / Marghoob, A A. ·Department of Dermatology, University Hospital Zürich, Zürich, Switzerland. ·Dermatology · Pubmed #24296632.

ABSTRACT: BACKGROUND: Most studies on dermoscopy of acral lesions were conducted in Asian populations. In this study, we analyzed these features in a predominantly Caucasian population. OBJECTIVE: Estimate the prevalence of dermoscopic features in acral lesions, and assess their level of agreement between observers. METHODS: In this retrospective multicenter study, 167 acral lesions (66 melanomas) were evaluated for 13 dermoscopic patterns by 26 physicians, via a secured Internet platform. RESULTS: Parallel furrow pattern, bizarre pattern, and diffuse pigmentation with variable shades of brown had the highest prevalence. The agreement for lesion patterns between physicians was variable. Agreement was dependent on the level of diagnostic difficulty. CONCLUSION: Lesions with a diameter >1 cm were more likely to be melanoma. We found as well that a benign pattern can be seen in parts of melanomas. For this reason one should evaluate an acral lesion for the presence of malignant patterns first.

5 Article Dermoscopic evaluation of nodular melanoma. 2013

Menzies, Scott W / Moloney, Fergal J / Byth, Karen / Avramidis, Michelle / Argenziano, Giuseppe / Zalaudek, Iris / Braun, Ralph P / Malvehy, Josep / Puig, Susana / Rabinovitz, Harold S / Oliviero, Margaret / Cabo, Horacio / Bono, Riccardo / Pizzichetta, Maria A / Claeson, Magdalena / Gaffney, Daniel C / Soyer, H Peter / Stanganelli, Ignazio / Scolyer, Richard A / Guitera, Pascale / Kelly, John / McCurdy, Olivia / Llambrich, Alex / Marghoob, Ashfaq A / Zaballos, Pedro / Kirchesch, Herbert M / Piccolo, Domenico / Bowling, Jonathan / Thomas, Luc / Terstappen, Karin / Tanaka, Masaru / Pellacani, Giovanni / Pagnanelli, Gianluca / Ghigliotti, Giovanni / Ortega, Blanca Carlos / Crafter, Greg / Ortiz, Ana María Perusquía / Tromme, Isabelle / Karaarslan, Isil Kilinc / Ozdemir, Fezal / Tam, Anthony / Landi, Christian / Norton, Peter / Kaçar, Nida / Rudnicka, Lidia / Slowinska, Monika / Simionescu, Olga / Di Stefani, Alessandro / Coates, Elliot / Kreusch, Juergen. ·Sydney Melanoma Diagnostic Centre, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia. scott.menzies@sswahs.nsw.gov.au ·JAMA Dermatol · Pubmed #23553375.

ABSTRACT: IMPORTANCE: Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. OBJECTIVE: To determine the dermoscopy features of NM. DESIGN: Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. SETTING: Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES: Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. RESULTS: Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. CONCLUSIONS AND RELEVANCE: When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.

6 Article Accuracy in melanoma detection: a 10-year multicenter survey. 2012

Argenziano, Giuseppe / Cerroni, Lorenzo / Zalaudek, Iris / Staibano, Stefania / Hofmann-Wellenhof, Rainer / Arpaia, Nicola / Bakos, Renato Marchiori / Balme, Brigitte / Bandic, Jadran / Bandelloni, Roberto / Brunasso, Alexandra M G / Cabo, Horacio / Calcara, David A / Carlos-Ortega, Blanca / Carvalho, Ana Carolina / Casas, Gabriel / Dong, Huiting / Ferrara, Gerardo / Filotico, Raffaele / Gómez, Guillermo / Halpern, Allan / Ilardi, Gennaro / Ishiko, Akira / Kandiloglu, Gulsen / Kawasaki, Hiroshi / Kobayashi, Ken / Koga, Hiroshi / Kovalyshyn, Ivanka / Langford, David / Liu, Xin / Marghoob, Ashfaq A / Mascolo, Massimo / Massone, Cesare / Mazzoni, Laura / Menzies, Scott / Minagawa, Akane / Nugnes, Loredana / Ozdemir, Fezal / Pellacani, Giovanni / Seidenari, Stefania / Siamas, Katherine / Stanganelli, Ignazio / Stoecker, William V / Tanaka, Masaru / Thomas, Luc / Tschandl, Philipp / Kittler, Harald. ·Dermatology Unit, Medical Department, Arcispedale Santa Maria Nuova, Viale Risorgimento 80 - 42100 Reggio Emilia, Italy. g.argenziano@gmail.com ·J Am Acad Dermatol · Pubmed #21982636.

ABSTRACT: BACKGROUND: Early excision is the only strategy to reduce melanoma mortality, but unnecessary excision of benign lesions increases morbidity and healthcare costs. OBJECTIVE: To assess accuracy in melanoma detection based on number-needed-to-excise (NNE) values over a 10-year period. METHODS: Information was retrieved on all histopathologically confirmed cutaneous melanomas or melanocytic nevi that were excised between 1998 and 2007 at participating clinics. NNE values were calculated by dividing the total number of excised lesions by the number of melanomas. Analyses included changes in NNE over time, differences in NNE between specialized clinical settings (SCS) versus non-specialized clinical settings (NSCS), and patient factors influencing NNE. RESULTS: The participating clinics contributed a total of 300,215 cases, including 17,172 melanomas and 283,043 melanocytic nevi. The overall NNE values achieved in SCS and NSCS in the 10-year period were 8.7 and 29.4, respectively. The NNE improved over time in SCS (from 12.8 to 6.8), but appeared unchanged in NSCS. Most of the effect on NNE in SCS was due to a greater number of excised melanomas. Higher NNE values were observed in patients younger than 40 years and for lesions located on the trunk. LIMITATIONS: No data concerning the use of dermatoscopy and digital monitoring procedures were collected from the participating centers. CONCLUSION: Over the 10-year study period, accuracy in melanoma detection improved only in specialized clinics maybe because of a larger use of new diagnostic techniques such as dermatoscopy.

7 Article Dermoscopy of pigmented lesions of the mucosa and the mucocutaneous junction: results of a multicenter study by the International Dermoscopy Society (IDS). 2011

Blum, Andreas / Simionescu, Olga / Argenziano, Giuseppe / Braun, Ralph / Cabo, Horacio / Eichhorn, Astrid / Kirchesch, Herbert / Malvehy, Josep / Marghoob, Ashfaq A / Puig, Susana / Ozdemir, Fezal / Stolz, Wilhelm / Tromme, Isabelle / Weigert, Ulrike / Wolf, Ingrid H / Zalaudek, Iris / Kittler, Harald. ·Private and Teaching Practice of Dermatology, Seestrasse 3a, 78464 Konstanz, Germany. a.blum@derma.de ·Arch Dermatol · Pubmed #21680757.

ABSTRACT: OBJECTIVE: To better characterize the dermoscopic patterns of mucosal lesions in relation to the histopathologic characteristics. DESIGN: Retrospective and observational study. SETTING: Fourteen referral pigmented lesion clinics in 10 countries. PATIENTS: A total of 140 pigmented mucosal lesions (126 benign lesions, 11 melanomas, 2 Bowen disease lesions, and 1 metastasis) from 92 females (66%) and 48 males (34%) were collected from October 2007 through November 2008. MAIN OUTCOME MEASURES: Scoring the dermoscopic patterns (dots, globules, or clods, circles, lines, or structureless) and colors (brown, black, blue, gray, red, purple, and white) and correlation with the histopathologic characteristics. RESULTS: Based on univariate analysis and 2 diagnostic models, the presence of structureless zones inside the lesions with blue, gray, or white color (the first model) had a 100% sensitivity for melanoma and 92.9% sensitivity for any malignant lesion, and 82.2% and 83.3% specificity for benign lesions in the group with melanoma lesions and the group with malignant lesions, respectively. Based on the colors (blue, gray, or white) only (the second model), the sensitivity for the group with melanoma was 100% and for the group with any malignant lesion was 92.9%, and the specificity was 64.3% and 65.1%, respectively. Patients with malignant lesions were significantly older than patients with benign lesions (mean [SD] ages, 60.1 [22.8] years vs 43.2 [17.3] years, respectively). CONCLUSION: The combination of blue, gray, or white color with structureless zones are the strongest indicators when differentiating between benign and malignant mucosal lesions in dermoscopy.

8 Article Dermoscopic evaluation of amelanotic and hypomelanotic melanoma. 2008

Menzies, Scott W / Kreusch, Juergen / Byth, Karen / Pizzichetta, Maria A / Marghoob, Ashfaq / Braun, Ralph / Malvehy, Josep / Puig, Susana / Argenziano, Giuseppe / Zalaudek, Iris / Rabinovitz, Harold S / Oliviero, Margaret / Cabo, Horacio / Ahlgrimm-Siess, Verena / Avramidis, Michelle / Guitera, Pascale / Soyer, H Peter / Ghigliotti, Giovanni / Tanaka, Masaru / Perusquia, Ana M / Pagnanelli, Gianluca / Bono, Riccardo / Thomas, Luc / Pellacani, Giovanni / Langford, David / Piccolo, Domenico / Terstappen, Karin / Stanganelli, Ignazio / Llambrich, Alex / Johr, Robert. ·Faculty of Medicine, University of Sydney, Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia. scott.menzies@email.cs.nsw.gov.au ·Arch Dermatol · Pubmed #18794455.

ABSTRACT: OBJECTIVE: To determine the predictive dermoscopic features of amelanotic and hypomelanotic melanoma. DESIGN: A total of 105 melanomas (median Breslow thickness, 0.76 mm), 170 benign melanocytic lesions, and 222 nonmelanocytic lesions lacking significant pigment (amelanotic, partially pigmented, and light colored) were imaged using glass-plate dermoscopy devices and scored for 99 dermoscopic features. Diagnostic models were derived from and tested on independent randomly selected lesions. SETTING: Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES: Sensitivity, specificity, and odds ratios for individual features and models for the diagnosis of melanoma and malignancy. RESULTS: The most significant negative predictors of melanoma were having multiple (>3) milialike cysts (odds ratio, 0.09; 95% confidence interval, 0.01-0.64), comma vessels with a regular distribution (0.10; 0.01-0.70), comma vessels as the predominant vessel type (0.16; 0.05-0.52), symmetrical pigmentation pattern (0.18; 0.09-0.39), irregular blue-gray globules (0.20; 0.05-0.87), and multiple blue-gray globules (0.28; 0.10-0.81). The most significant positive predictors were having a blue-white veil (odds ratio,13; 95% confidence interval, 3.9-40.0), scarlike depigmentation (4.4; 2.4-8.0), multiple blue-gray dots (3.5; 1.9-6.4), irregularly shaped depigmentation (3.3; 2.0-5.3), irregular brown dots/globules (3.2; 1.8-5.6), 5 to 6 colors (3.2; 1.6-6.3), and predominant central vessels (3.1; 1.6-6.0). A simple model distinguishing melanomas from all nonmelanomas had a sensitivity of 70% and a specificity of 56% in the test set. A model distinguishing all malignant lesions from benign lesions had a sensitivity of 96% and a specificity of 37%. Conclusion Although the diagnostic accuracy of dermoscopy for melanoma lacking significant pigment is inferior to that of more pigmented lesions, features distinguishing the former from benign lesions can be visualized on dermoscopic evaluation.