Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

BACKGROUND: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. METHODS: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. RESULTS: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. CONCLUSIONS: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT.

BACKGROUND: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved. METHODS: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics. RESULTS: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance. CONCLUSION: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling.

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.

Dermoscopy in Selected Latin American Countries: A Preliminary Look into Current Trends and Future Opportunities Among Dermatology Residency Programs.

INTRODUCTION: Skin cancer remains a global public health burden. Dermoscopy is a useful technique that aids in early detection and increases diagnostic accuracy with adequate training. However, dermoscopy is not uniformly taught to residents worldwide. Dermoscopy training in Latin American dermatology residency programs has not been explored. OBJECTIVES: To assess current dermoscopy training among dermatology residency programs in Latin America (eg training modalities, preferred/most effective modalities per residents, diseases/pathologies taught). METHODS: Cross-sectional survey distributed via e-mail between March and May 2021. Chief residents from Argentina, Brazil, Colombia, Costa Rica, Chile, Ecuador, Guatemala, Mexico, Panama, and Uruguay were invited to participate. RESULTS: 81 chief residents completed the questionnaire (81/126, 64.2%). Seventy-two percent of programs had an established dermoscopy curriculum, with dedicated hours of training varying greatly by program. Institutions commonly utilized sessions with "unknown" dermoscopy images and direct teaching by experts in the clinical setting as supplements to lectures, also described by residents as most effective. The most commonly taught methods included pattern analysis (74.1%), the two-step algorithm (61.7%), and the ABCD rule (59.3%). Almost all respondents reported desiring additional training during residency and believe that dermoscopy training should be a requirement to graduate from residency. CONCLUSIONS: This study highlights a preliminary look into current landscape in dermoscopy training among selected Latin American dermatology residency programs, demonstrating room for improvement and standardization in dermoscopic education and training. Our results serve as a baseline reference and provide valuable information to guide future educational initiatives incorporating successful teaching strategies (eg. spaced education/repetition, flipped classroom model) used in dermatology and other fields.

Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families.

Germline mutations in CDKN2A are frequently identified among melanoma kindreds and are associated with increased atypical nevus counts. However, a clear relationship between pathogenic CDKN2A mutation carriage and other nevus phenotypes including counts of common acquired nevi has not yet been established. Using data from GenoMEL, we investigated the relationships between CDKN2A mutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families. Compared with individuals without a pathogenic mutation, those who carried one had an overall higher prevalence of atypical (odds ratio = 1.64; 95% confidence interval = 1.18-2.28) nevi but not 2-mm nevi (odds ratio = 1.06; 95% confidence interval = 0.92-1.21) or 5-mm nevi (odds ratio = 1.26; 95% confidence interval = 0.94-1.70). Stratification by case status showed more pronounced positive associations among non-case family members, who were nearly three times (odds ratio = 2.91; 95% confidence interval = 1.75-4.82) as likely to exhibit nevus counts at or above the median in all three nevus categories simultaneously when harboring a pathogenic mutation (vs. not harboring one). Our results support the hypothesis that unidentified nevogenic genes are co-inherited with CDKN2A and may influence carcinogenesis.

Tratamiento con vemurafenib: indicación de mapeo corporal y seguimiento digital dermatoscópico / Vemurafenib treatment: indication of body mapping and dermoscopic digital follow-up

El Vemurafenib es un inhibidor de la enzima serina/treonina quinasa BRAF utilizado en el tratamiento de pacientes con melanoma con diseminación loco-rregional y enfermedad metastásica, portadores de la mutación V600E del gen BRAF. Se ha asociado a múltiples efectos adversos cutáneos de los cuales se destaca la posibilidad de generar cambios en los nevos melanocíticos, aparición de nuevos nevos e incluso de segundos melanomas. El seguimiento digital dermatoscópico con mapeo corporal, ha demostrado utilidad en el diagnóstico precoz de melanoma.Presentamos dos casos clínicos de pacientes con ante-cedentes de melanoma en tratamiento con inhibido-res de BRAF (BRAFi) e inhibidores de BRAF y MEK (MEKi) en quienes se realizó seguimiento digital der-matoscópico con mapeo corporal. Se detectaron cambios en nevos melanocíticos preexistentes, aparición segundos melanomas y metástasis cutáneas.El grupo de pacientes con antecedentes de melanoma y en tratamiento con BRAFi o combinación de BRA-Fi y MEKi se beneficia especialmente del control der-matológico con seguimiento digital dermatoscópico y mapeo corporal.

Vemurafenib is an inhibitor of the serine / threonine kinase BRAF enzyme currently used in the treatment of patients with locoregional spread and metastatic melanoma carriers of the mutationV600E of the BRAF gene. It has been associated with multiple cu-taneous adverse effects including changes in melanocytic nevi, appearance of new nevi and even second melanomas. Dermoscopic digital follow-up with total body mapping has proven useful in the early diagnosis of melanoma.We present two cases of patients with a history of me-lanoma in treatment with BRAF inhibitors (BRAFi) and inhibitors of BRAF and MEK (MEKi) in whom a digital dermoscopic follow-up was performed with body mapping. Changes in preexisting melanocytic nevi, second melanomas and cutaneous metastases were detected.The group of patients with a history of melanoma and in treatment with BRAFi or a combination of BRAFi and MEKi especially benefits from dermato-logical surveillance with digital dermoscopic follow-up and total body mapping.

Sweet´s syndrome and pancreatic neoplasm: an atypical association

El síndrome de Sweet es una dermatosis inflamatoria poco común, que se ha asociado a tumores malignos, principalmente de tipo hematológico. Presentamos un caso clínico de síndrome de Sweet asociado con una rara neoplasia pancreática, siendo uno de los pocos casos reportados en la literatura médica acerca de esta asociación.

Sweet's syndrome is an uncommon inflammatory dermatosis, which has been associated with malignant tumors, mainly of hematological type. We report a clinical case of Sweet syndrome associated with a rare pancreatic neoplasm, which is one of the few cases reported in the medical literature about this association.

Nevo de Spitz en la infancia: el gran simulador de melanoma / Spitz nevus in childhood: the great melanoma simulator

El melanoma infantil ha aumentado su incidencia en los últimos años. Clínicamente suele presentarse como como una lesión amelanótica o con escaso pigmento, sobreelevada, en ocasiones sangrante. El principal diagnóstico diferencial se plantea con lesiones banales, y en ocasiones con lesiones melanocíticas como el nevo de Spitz/Reed. El nevo de Spitz se caracteriza por ser una pápula redondeada, solitaria, color piel topografiada en cara o extremidades. El nevo de Reed se presenta como un tumor plano o sobreelevado, oscuro, más frecuentemente en miembros inferiores. El tratamiento del mismo depende de la edad del paciente. En menores de doce años con lesiones típicas, suele tomarse una conducta expectante, mientras que si estas lesiones aparecen luego de esta edad se recomienda la exéresis, ya que podría tratarse de un melanoma.

The incidence of pediatric melanoma has been increasing. The most frequent clinical presentation is amelanotic lesions, lacking pigmentation and usually elevated, sometimes bleeding. Differential diagnosis includes benign lesions and may also include melanocytic lesions such as Spitz/Reed nevi. Spitz nevus usually presents as a solitary, rounded or oval papule, skin coloured, mainly affecting the face or limbs. Reed nevus is characterized by a dark tumor plane or elevated, often affecting the lower limbs. The treatment of these nevi depends on the patient´s age. Children under 12 years old with a typical lesion may undergo clinical and dermoscopic follow-up. In older patients, excision is recommended due to the probability of melanoma.

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT

BACKGROUND:Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved.METHODS:In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics.RESULTS:MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance.CONCLUSION:The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling(AU)

Nevo de Spitz en la infancia: el gran simulador de melanoma / Spitz nevus in childhood: the great melanoma simulator

El melanoma infantil ha aumentado su incidencia en los últimos años. Clínicamente suele presentarse como como una lesión amelanótica o con escaso pigmento, sobreelevada, en ocasiones sangrante. El principal diagnóstico diferencial se plantea con lesiones banales, y en ocasiones con lesiones melanocíticas como el nevo de Spitz/Reed. El nevo de Spitz se caracteriza por ser una pápula redondeada, solitaria, color piel topografiada en cara o extremidades. El nevo de Reed se presenta como un tumor plano o sobreelevado, oscuro, más frecuentemente en miembros inferiores. El tratamiento del mismo depende de la edad del paciente. En menores de doce años con lesiones típicas, suele tomarse una conducta expectante, mientras que si estas lesiones aparecen luego de esta edad se recomienda la exéresis, ya que podría tratarse de un melanoma(AU)

Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families

Germline mutations in CDKN2A are frequently identified among melanoma kindreds and are associated with increased atypical nevus counts. However, a clear relationship between pathogenic CDKN2A mutation carriage and other nevus phenotypes including counts of common acquired nevi has not yet been established. Using data from GenoMEL, we investigated the relationships between CDKN2A mutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families. Compared with individuals without a pathogenic mutation, those who carried one had an overall higher prevalence of atypical (odds ratio = 1.64; 95% confidence interval = 1.18-2.28) nevi but not 2-mm nevi (odds ratio = 1.06; 95% confidence interval = 0.92-1.21) or 5-mm nevi (odds ratio = 1.26; 95% confidence interval = 0.94-1.70). Stratification by case status showed more pronounced positive associations among non-case family members, who were nearly three times (odds ratio = 2.91; 95% confidence interval = 1.75-4.82) as likely to exhibit nevus counts at or above the median in all three nevus categories simultaneously when harboring a pathogenic mutation (vs. not harboring one). Our results support the hypothesis that unidentified nevogenic genes are co-inherited with CDKN2A and may influence carcinogenesis(AU)

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(AU)

Clinical, dermoscopic and histopathologic features of genital and extragenital lichen sclerosus

Background  Little is currently known about the dermoscopic patterns of genital and extragenital lichen sclerosus (LS). In order to evaluate and compare the dermoscopic and histopathologic patterns of genital and extragenital lichen sclerosus, a retrospective analysis of clinical, dermoscopic and histopathologic features of genital and extragenital LS, collected between March 2010 and December 2011 at four dermatology clinics in Greece, Italy, Serbia and Uruguay was performed.Observations  A total of 29 lesions from 14 (mean age 62.8 years) and 12 (mean age 53.5 years) patients with genital and extragenital LS, respectively were analyzed. Mean duration of disease was 3.5 years for genital and 1.8 years for extragenital LS. White-yellowish structureless areas were seen in all cases of genital and extragenital LS; however linear vessels occurred at higher frequency in genital than in extragenital lesions (85.7% vs. 33.3%, respectively). Extragenital LS revealed two different time-related patterns: keratotic plugs were more prevalent in lesions with short duration (<2 years), whereas longer persisting lesions appeared atrophic and revealed fine chrysalis structures.Conclusions  Our morphologic study provides novel insights into the morphologic diversity of LS at different body sites and different stages of progression(AU)

Dermatoscopía en lesiones melanocíticas : propuesta de puntos críticos de corte de score dermatoscópico total para el diagnóstico oportuno de melanoma

La dermatoscopía ha demostrado elevar la capacidad diagnóstica en etapas tempranas de melanoma. Entre sus sistemas de cuantificación de riesgo, el score dermatoscópico total (TDS) es uno de los más utilizados. Su estrategia de validación consistió en aplicarlo en un vasto grupo de lesiones melanocíticas que incluyeron melanomas de fácil diagnóstico clínico con altos valores de TDS, por lo que el "punto de corte" resultó de alta exigencia, lo que explica la disminución del valor predictivio de la prueba negativa (VPPN) en lesiones clínicamente dudosas (LCD) entre melanoma "fino" y nevo con intensa actividad funcional. El objetivo del presente estudio fue estudiar "puntos de corte" de TDS aplicables a LCD que logren disminuir la proporción de falsos negativos. Material y método: De un total de 2.396 lesiones melanocíticas, 187 fueron resecadas y estudiadas. Algo más de la mitad se integró por nevos melanocíticos adquiridos o congénitos, lentigos actínicos y melanomas clínicamente evidentes, mientras que 92 correspondieron a LCD de melanoma, las que constituyeron nuestro grupo de estudio. En cada una se calculó el TDS según los criterios clásicos. La anatomía patológica permitió establecer diagnóstico en todos los casos y conformar dos grupos, que fueron testados en cuanto a sexo, edad, fototipo, presencia de síndromes familiares de múltiples nevos y de nevos atípicos, o ambos (SNM y SNA). Resultados: La anatomía patológica mostró 63 nevos melanocíticos (grupo A) y 29 melanomas (grupo B). No existieron diferencias significativas en cuanto a sexo, edad, fototipo o presencia de SNM o SNA. Con los valores de TDS se calcularon los parámetros de exactitud y se elaboró una curva ROC a fin de determinar el "punto de corte" mas apropiado, que para este grupo de lesiones resultó algo más bajo que el de Stolz, con 93.1 porciento de sensibilidad, 85.7 porciento de especificidad y 96.4 porciento de VPPN. Conclusión: Nuestros resultados muestran que para el caso de LCD el "punto de corte" propuesto logra un excelente VPPN sin afectación de los niveles de sensibilidad y especificidad. Pensamos que serán necesarias series mas numerosas y estudios prospectivos para validar esta propuesta