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.

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.

Stardust Pattern as Evolution of Pigmented Spitz Nevi During Childhood.

INTRODUCTION: Spitz nevi (SN) are benign melanocytic proliferations frequently occurring in children. Some pigmented SN with a starburst pattern evolve into the "stardust" one, which is characterized by a central, black to gray, hyperpigmented area and remnants of a brown network at the periphery. These dermoscopy changes are often the first alert to induce excision. OBJECTIVES: The aim of this study is to enlarge the case series of stardust SN in children, in order to increase confidence with this new dermoscopic pattern and reduce unnecessary excisions. METHODS: This retrospective observational study was conducted with SN cases received from IDS members. The inclusion criteria were: clinical and/or histopathologic diagnosis of Spitz naevus with starburst appearance in children <12 years old, availability of a dermoscopic image at baseline and after follow-up of at least 1 year, availability of patient data. The dermoscopic images and their changes over time were assessed by three evaluators in consensus. RESULTS: 38 SN were enrolled, with a median age of 7 years and a median FUP duration of 15,5 months. Comparing the evolution with time of FUP, no significant differences were found between growing and involuting lesions in terms of patient age and sex, location and palpability of lesions. CONCLUSIONS: The long follow-up reported in our study could really support the concept of benignity of changing SN. A conservative approach is acceptable for nevi showing the stardust pattern, because it may be considered a physiological evolution of pigmented Spitz nevus, and urgent surgeries could be avoided.

Indications for Digital Monitoring of Patients With Multiple Nevi: Recommendations from the International Dermoscopy Society.

Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring. Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice.

Extrafacial Lentigo Maligna: A Clinical And Dermoscopic Analysis According to Localization.

INTRODUCTION: Whether extrafacial lentigo maligna (EFLM) differs clinically and/or dermoscopically according to location has not been analyzed in depth. OBJECTIVES: To evaluate clinical and dermoscopic characteristics regarding different localization in a series of EFLM. METHODS: We conducted a retrospective analysis of clinical and dermoscopic characteristics of 69 histologically proven EFLM retrieved from the database of two private institutions. RESULTS: Of the 69 EFLM included in the study, 25 (36.2%) were located in posterior trunk (PT), 16 (23.2%) in anterior trunk (AT), 15 (21%) in upper extremities (UE), and 13 (18.8%) in lower extremities (LE). Mean diameter among localization were as follows: 14.3 mm in PT, 11.8 mm in AT, 14 mm in UE, and 10 mm in LE (p 0.44). The most frequent dermoscopic criteria were angulated lines and tan structureless areas (70%), followed by atypical pigment network (60%), both with similar distribution among groups. Angulated lines pattern was the most frequent global pattern, observed in 55% of cases. Tan structureless/granularity pattern and patchy peripheral pigmented islands pattern were seen in 15.6% and 11.6% cases, respectively. No statistically significant differences were observed in the distribution of global dermoscopic pattern in the different localizations. CONCLUSIONS: From the clinical point of view, EFLM did not differ in terms of patient's age and diameter regarding localization. Upon dermoscopy, we found no significant differences in the overall dermoscopic pattern in the different localizations.

Clinical and Dermoscopic Approaches to Diagnosis of Frontal Fibrosing Alopecia: Results From a Multicenter Study of the International Dermoscopy Society.

INTRODUCTION: Frontal fibrosing alopecia (FFA) is a form of primary lymphocytic scarring alopecia characterized by a progressive recession of the fronto-temporal hairline. Although the clinical presentation of FFA is very typical, biopsy for histopathological examination is still recommended to confirm the diagnosis. Currently, a growing number of skin and mucosal inflammatory diseases are diagnosed with modern noninvasive techniques such as dermoscopy without the necessity of a biopsy. OBJECTIVES: The International Dermoscopy Society (IDS) aimed to test the ability of its members to diagnose classic FFA through clinical and dermoscopic parameters and to compare acquired data to the largest cohort studies published since 1994. METHODS: This is an observational, cross-sectional study describing patient demographics, clinical presentation and diagnostic tools used in a sample of FFA patients collected by IDS members. A literature search was then performed using Pubmed to review studies reporting more than 100 cases. RESULTS: IDS members submitted 188 cases demonstrating a predominant female population (98.4%). In 71.8% of the cases, the clinical presentation and the trichoscopic findings allowed for the diagnosis. Out of 24 revised studies, 13 showed that clinical and trichoscopic features were decisive for the diagnosis in almost all cases. CONCLUSIONS: Demographic and clinical data of our cohort were mostly comparable to previous reported data on FFA. The relevant role of the clinical and trichoscopic features in diagnosing FFA was confirmed by our study and the reviewed literature. Trichoscopy could be considered a worldwide-acknowledged non-invasive technique for the diagnosis of FFA.

International Dermoscopy Society criteria for non-neoplastic dermatoses (general dermatology): validation for skin of color through a Delphi expert consensus.

BACKGROUND: The International Dermoscopy Society (IDS) recently released a set of five basic dermoscopic parameters (vessels, scales, follicular findings, "other structures," and specific clues) encompassing a total of 31 subitems to standardize the use of dermoscopy in non-neoplastic dermatoses, yet they have been developed taking into account Caucasian/Asian skin, with consequent possible limitations if used in dark skin. OBJECTIVES: To validate the abovementioned criteria for the use in dark-skinned patients (phototypes IV-VI) through an expert consensus. METHODS: The two-round Delphi method was adopted, with an iterative process consisting of two rounds of email questionnaires. Potential panelists were recruited via e-mail from all over the world based on their expertise on dermoscopy of non-neoplastic dermatoses in skin of color. RESULTS: Twenty-two panelists took part in the validation process. All of the five originally proposed parameters and subitems reached agreement during the first round, aside from "follicular red dots." Additionally, during round 1, five new subitems were proposed (perifollicular scales distribution, follicular openings obliteration, broken hairs, eccrine pigmentation, and eccrine ostia obliteration), along with the possibility to change the denomination of parameter 3 (from "follicular findings" to "follicular/eccrine findings") and split it into two subparameters ("follicular findings" and "eccrine findings"). All such proposals reached agreement during the second round and therefore were included in the final list, for a total of 37 items. CONCLUSIONS: Although nearly all the dermoscopic criteria originally proposed by the IDS are applicable even to darker phototypes, several additional variables need to be assessed.

International registry of dermatological manifestations secondary to COVID-19 infection in 347 Hispanic patients from 25 countries.

BACKGROUND: The infection by coronavirus disease 2019 (COVID-19) has been associated with multiple cutaneous manifestations, although characterization of them in Hispanic patients with darker skin phototypes is lacking. The objective of this study is to characterize the clinical dermatological manifestations associated with COVID-19 infection in cases with few or without general symptoms in patients from Latin America. METHODS: Cross-sectional study using a questionnaire that was made for health professionals (physicians with a specialty in dermatology) to investigate dermatological lesions associated with COVID-19 infection in patients from 25 countries of Latin America. The survey was active from June 9 to July 30, 2020. RESULTS: In this study, information was collected from a total of 347 patients. We found a female gender predominance: 179/347 (51.6%). The mean age at presentation was 40.87 years. The most frequent dermatological manifestations were maculopapular rash and urticarial lesions, followed by papulovesicular lesions, vesicular lesions, chilblain-like lesions, papular lesions, ecchymosis, petechial purpura, pityriasis rosea-like lesions, pruritus, palmoplantar dysesthesias, transient livedo, acral necrosis, palpable purpura, livedo racemosa, and retiform purpura. As far as we know, there are no previous reports of pruritus and palmoplantar dysesthesias. CONCLUSIONS: This registry emphasizes skin manifestations as an important criterion for establishing the diagnosis of COVID-19 infection in Latin American countries. This information will be useful for the early identification of suspected cases by health professionals (dermatologists and nondermatologists) and will allow contact tracing to mitigate the impact on health systems at different levels.

Dermoscopy in general dermatology (non-neoplastic dermatoses) of skin of colour: a comparative retrospective study by the International Dermoscopy Society.

BACKGROUND: Dermoscopy has been shown to be a useful supportive tool to assist the diagnosis of several non-neoplastic dermatoses (i.e. inflammatory, infiltrative and infectious skin diseases), yet data on skin of colour is still limited. OBJECTIVES: To characterize dermoscopic features of non-neoplastic dermatoses in dark-skinned patients in order to identify possible clues that may facilitate the differential diagnosis of clinically similar conditions. MATERIALS & METHODS: Members of the International Dermoscopy Society were invited to submit cases of any non-neoplastic dermatosis developing in patients with Fitzpatrick Phototypes V-VI whose diagnosis had been confirmed by the corresponding gold standard diagnostic test. A standardized assessment of the dermoscopic images and a comparative analysis according to clinical presentation were performed. Seven clinical categories were identified: (I) papulosquamous dermatoses; (II) facial hyperpigmented dermatoses; (III) extra-facial hyperpigmented dermatoses; (IV) hypopigmented dermatoses; (V) granulomatous dermatoses; (VI) sclerotic dermatoses; and (VII) facial inflammatory dermatoses. RESULTS: A total of 653 patients (541 and 112 with Phototype V and VI, respectively) were recruited for the analysis. Thirty-six statistically significant dermoscopic features were identified for papulosquamous dermatoses, 24 for facial hyperpigmented disorders, 12 for extra-facial hyperpigmented disorders, 17 for hypopigmented disorders, eight for granulomatous dermatoses, four for sclerotic dermatoses and 17 for facial inflammatory diseases. CONCLUSION: Our findings suggest that dermoscopy might be a useful tool in assisting the diagnosis of clinically similar non-neoplastic dermatoses in dark phototypes by revealing characteristic clues. Study limitations include the retrospective design, the lack of a direct dermoscopic-histological correlation analysis and the small sample size for less common diseases.

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.

Expert-Level Diagnosis of Nonpigmented Skin Cancer by Combined Convolutional Neural Networks.

Importance: Convolutional neural networks (CNNs) achieve expert-level accuracy in the diagnosis of pigmented melanocytic lesions. However, the most common types of skin cancer are nonpigmented and nonmelanocytic, and are more difficult to diagnose. Objective: To compare the accuracy of a CNN-based classifier with that of physicians with different levels of experience. Design, Setting, and Participants: A CNN-based classification model was trained on 7895 dermoscopic and 5829 close-up images of lesions excised at a primary skin cancer clinic between January 1, 2008, and July 13, 2017, for a combined evaluation of both imaging methods. The combined CNN (cCNN) was tested on a set of 2072 unknown cases and compared with results from 95 human raters who were medical personnel, including 62 board-certified dermatologists, with different experience in dermoscopy. Main Outcomes and Measures: The proportions of correct specific diagnoses and the accuracy to differentiate between benign and malignant lesions measured as an area under the receiver operating characteristic curve served as main outcome measures. Results: Among 95 human raters (51.6% female; mean age, 43.4 years; 95% CI, 41.0-45.7 years), the participants were divided into 3 groups (according to years of experience with dermoscopy): beginner raters (<3 years), intermediate raters (3-10 years), or expert raters (>10 years). The area under the receiver operating characteristic curve of the trained cCNN was higher than human ratings (0.742; 95% CI, 0.729-0.755 vs 0.695; 95% CI, 0.676-0.713; P < .001). The specificity was fixed at the mean level of human raters (51.3%), and therefore the sensitivity of the cCNN (80.5%; 95% CI, 79.0%-82.1%) was higher than that of human raters (77.6%; 95% CI, 74.7%-80.5%). The cCNN achieved a higher percentage of correct specific diagnoses compared with human raters (37.6%; 95% CI, 36.6%-38.4% vs 33.5%; 95% CI, 31.5%-35.6%; P = .001) but not compared with experts (37.3%; 95% CI, 35.7%-38.8% vs 40.0%; 95% CI, 37.0%-43.0%; P = .18). Conclusions and Relevance: Neural networks are able to classify dermoscopic and close-up images of nonpigmented lesions as accurately as human experts in an experimental setting.

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/).

Collision skin lesions-results of a multicenter study of the International Dermoscopy Society (IDS).

BACKGROUND: Collision lesions as two independent and unrelated skin tumors often manifest an atypical morphology. OBJECTIVE: To determine the combinations of collision skin lesions (CSLs). METHODS: Twenty-one pigmented lesion clinics in nine countries included 77 histopathologically proven CSLs in this retrospective observational study. RESULTS: Seventy-seven CSLs from 75 patients (median age 59.8 years) were analyzed; 24.7% of CSLs were located on the head and neck area, 5.2% on the upper extremities, 48.1% on the trunk, and 11.7% on the lower extremities; 40.3% revealed a melanocytic component (median age 54.7 years), followed by 45.5% with a basal cell carcinoma (BCC) (median age 62.4 years) and 11.7% with a seborrheic keratosis (median age 64.7 years). CSLs with a BCC component were more often found on the head and neck area compared to tumors with a melanocytic component (34.3% versus 16.1%). Lesions with a melanocytic component were more often detected on the trunk compared to lesions with a BCC (64.5% versus 37.1%). Patients with CSLs with epidermal-epidermal cell combination were older than patients with epidermal-dermal cell combination (63 versus 55.2 years), were more often male than female (63% versus 43.3%), more often had the lesion on the head and neck area (32.6% versus 13.3%), and less often on the upper (2.2 % versus 10%) or lower extremities (8.7% versus 16.6%). CONCLUSIONS: CSLs consist of a heterogeneous group of lesions of varying cell types. They are associated with advancing age and cumulative UV-exposure. CSLs manifest a complex morphology making it challenging to diagnose correctly.

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.

Usefulness of dermoscopy in the diagnosis and monitoring treatment of demodicidosis.

Demodicidosis is a common infestation and should be considered in the differential diagnosis of recurrent or recalcitrant perioral dermatitis or rosacea-like eruptions of the face. We report on a 34-year-old male, who presented with facial erythema and desquamation accompanied by a pruritic sensation. Dermoscopic examination revealed Demodex tails and Demodex follicular openings, both specific features of this entity. Microscopically, standardized skin surface biopsy test was pathogenic and the patient had positive response to anti-demodectic drugs. To our knowledge, a few reports of the dermatoscopic features of demodicidosis have been published in the literature. Dermoscopy offers a potential new option for a real-time validation of Demodex infestation and a useful tool for monitoring treatment.

Proposal for management and dermoscopy follow-up of nevi in patients affected by oculocutaneous albinism type Ia.

Albino patients are at great risk for developing cutaneous neoplasms, including melanomas. In this paper we describe the dermatoscopic findings of nevi in two patients with oculocutaneous albinism type Ia (OCA-Ia) highlighting that they manifest a vascular pattern similar to that described for amelanotic melanoma. We propose managing these patients with dermoscopy, using the comparative approach, digital follow up (DFU), and reflectance confocal microscopy as a complementary tool for difficult cases.

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

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.