Current management of patients with cutaneous melanoma with a positive sentinel lymph node / Tratamiento actual de pacientes con melanoma cutáneo y ganglio centinela positivo

Abstract Introduction : Immediate completion lymph node dissection (CLND) performed in patients with a positive sentinel lymph node biopsy (SLNB) cutaneous melanoma is not associated with improved melanoma specific survival versus active surveillance (AS) using nodal ul trasound. Clinical practice experience and outcomes of AS and adjuvant therapy is now starting to be published in literature. Methods : Retrospective analysis of patients with a positive-SLNB between June/2017-February/2022. Impact of management on any-site recurrence free survival (RFS), isolated nodal recurrence (INR), distant metasta sis-free survival (DMFS) and melanoma-specific survival (MSS) was evaluated. Results : From 126 SLNB, 31 (24.6%) were positive: 24 received AS and 7 CLND. Twenty-one (68%) received ad juvant therapy (AS, 67% and CLND, 71%). With a median follow-up of 18 months, 10 patients developed recur rent disease with an estimated 2-yr RFS of 73% (CI95%, 0.55-0.86) (30% in AS group vs. 43% in dissection group; P = 0.65). Four died of melanoma with an estimated 2-yr MSS of 82% (CI 95%, 0.63-0.92) and no differences between AS and CLND groups (P = 0.21). Estimated 2-yr DMFS of the whole cohort was 76% (CI 95%, 0.57-0.88) with no differences between groups (P = 0.33). Conclusion : Active surveillance strategy has been adopted for most positive-SLNB cutaneous melanoma patients. Adjuvant therapy without immediate CLND was delivered in nearly 70% of patients. Our results align with outcomes of randomized control trials and previous real-world data.

Resumen Introducción : La linfadenectomía inmediata (LI) re alizada en pacientes con biopsia de ganglio centinela (BGC) positivo por melanoma cutáneo no está asociada a mejoría en la supervivencia libre de enfermedad vs. vigilancia activa (VA). Resultados oncológicos y experi encia en la práctica clínica con dicha conducta asociados a tratamiento adyuvante comienzan a ser publicados en la literatura. Métodos : Análisis retrospectivo incluyendo paci entes con BGC-positiva por melanoma cutáneo entre junio/2017-febrero/2022. Se evaluó impacto del manejo en: supervivencia libre de recurrencia (SLR), recurren cia ganglionar aislada (RGA), supervivencia libre de metástasis a distancia (SLMD) y supervivencia libre de enfermedad (SLE). Resultados : De 126 pacientes, 31 (24.6%) fueron positi vos: en 24 se realizó VA y en 7 LI. Veintiún pacientes (68%) recibieron tratamiento adyuvante (VA, 67% y LI, 71%). Con una media de seguimiento de 18 meses, 10 pacientes presentaron recurrencia de la enfermedad con una SLR estimada a 2 años del 73% (CI95%, 0.55-0.86) (30% en VA vs. 43% en LI; P = 0.65). Cuatro murieron de melanoma con una SLE a 2 años del 82% (CI 95%, 0.63-0.92); sin diferencia entre ambos grupos (P = 0.21). La SLMD a 2 años de toda la cohorte fue de 76% (CI 95%, 0.57-0.88; P = 0.33). Conclusión : La vigilancia activa se ha adoptado como conducta para la mayoría de los pacientes con BGC-positivo. El tratamiento adyuvante sin linfadenectomía inmediata se realizó en cerca del 70% de nuestra serie. Los resultados de nuestra serie son similares a los re portados en la literatura.

Ganglio centinela en el melanoma cutáneo / Sentinel node in cutaneous melanoma

La biopsia selectiva del ganglio centinela (BSGC) se ha desarrollado de tal manera que reemplazó a la linfadenectomía electiva en el tratamiento del melanoma cutáneo (MC). Numerosos estudios demostraron que el estado del ganglio centinela es un factor pronóstico independiente en relación con la supervivencia global y la supervivencia libre de enfermedad de los pacientes con melanoma. El objetivo del presente trabajo fue realizar una revisión bibliográfica para comprender la utilidad y las indicaciones de la BSGC en pacientes con MC a partir de la evidencia actual publicada.

Sentinel lymph biopsy (SLNB) has been developed in such a way that is has replaced elective lymphadenectomy in the treatment of cutaneous melanoma (CM). Numerous studies have shwn that sentinel node status is an independent prognostic factor in relation to overall survival and disease-free survival of patients with CM. The purpose of this article is to carry out a literature review to understand the usefulness and indications of SLNB in patients with CM based on the current evidence.

Efeito do treinamento resistido na sobrevida de camundongos c57bl/6 com caquexia associada ao melanoma cutâneo / Effect of resisted training on survival of c57bl / 6 mice with cachexia associated with cutaneous melanoma

OBJETIVO: O objetivo desse estudo foi verificar o efeito do treinamento resistido na sobrevida de camundongos C57BL/6 com caquexia associada ao melanoma cutâneo. MATERIAL E MÉTODOS: A amostra foi constituída por 64 (camundongos C57BL/6 fêmeas, com idade entre 10 e 12 semanas, com cerca de 50 ± 5 gramas de peso corporal. Os camundongos foram distribuídos aleatoriamente em quatros grupos: i. camundongos controle, com indução de tumor, inativos fisicamente (Controle, n = 16); ii. camundongos submetidos ao treinamento resistido diário somente antes da indução tumoral (Treino 1, n = 16); iii. camundongos submetidos ao treinamento resistido diário antes e após da indução tumoral (Treino 2, n = 16); iv. camundongos submetidos ao treinamento resistido diário após a indução tumoral e apresentado quadro caquético (Treino 3, n = 16). No procedimento para treinamento resistido (TR) com choque, foi utilizada uma escada com 110 cm de altura, 18 cm de largura, 2 cm entre os degraus e 80 graus de inclinação. No procedimento para TR com choque, foi utilizada uma escada 110 cm de altura, 18 cm de largura, 2 cm entre os degraus e 80 graus de inclinação. O exercício resistido baseia-se na subida dos camundongos. Na plataforma de saída, aplicava-se um choque elétrico como estímulo para subir as escadas, nesta etapa era aplicada o choque nas quatro patas do animal com uma tensão elétrica de 20 volts a uma frequência de 45 Hertz durante seis séries de oito repetições, cada uma com noventa segundos de intervalo entre as séries. Os grupos de camundongos foram submetidos a acompanhamento por no máximo 15 dias após o diagnóstico da caquexia a fim de comparar a sobrevida geral relacionada ao câncer entre os grupos de estudo. As curvas de sobrevivência de KaplanMeier foram estimadas para cada evento e as curvas dos diferentes grupos foram comparadas usando o teste de Log-rank. O tempo de sobrevida proposta foi de 25 dias após inoculação. RESULTADOS: Os resultados apresentados nesse estudo mostraram que não houve diferença significativa (p <0,05) entre as propostas de treino. CONCLUSÃO: Não houve diferença na sobrevida de animais com caquexia associada ao modelo tumoral singênico de melanoma cutâneo com intervenção de exercício resistido ou sedentários.

OBJECTIVE: The objective of this study was to verify the effect of resistance training on the survival of C57BL / 6 mice with cachexia associated with cutaneous melanoma. MATERIAL AND METHODS: The sample consisted of 64 (female C57BL/6 mice, aged between 10 and 12 weeks, with approximately 50 ± 5 grams of body weight. The mice were randomly distributed into four groups: i. control mice, with tumor induction, physically inactive (Control, n = 16); ii. mice submitted to daily resistance training only before tumor induction (Training 1, n = 16); iii. Mice submitted to daily resistance training before and after tumor induction (Training 2, n = 16); iv. Mice submitted to daily resistance training after tumor induction and presented a cachectic condition (Training 3, n = 16). In the resistance training procedure (RT) with shock, a 110 cm high, 18 cm wide, 2 cm between the steps, and 80 degrees inclination ladder was used. In the procedure for shock resistance training (TR), a ladder 110 cm high, 18 cm wide, 2 cm between the rungs, and 80 degrees of inclination was used. The resisted exercise is based on the climbing of the mice. On the exit platform, an electric shock was applied as a stimulus to climb the stairs. In this step, the shock was applied to the four legs of the animal with an electric voltage of 20 volts at a frequency of 45 Hertz during six series of eight repetitions, each with ninety-seconds intervals between the series. The mice groups underwent follow-up for no more than 15 days after diagnosis of cachexia to compare overall cancer-related survival between the study groups. Kaplan-Meier survival curves were estimated for each event, and the curves of the different groups were compared using the Log-rank test. The proposed survival time was 25 days after inoculation. RESULTS: The results presented in this study showed no significant difference (p <0.05) between the training proposals. CONCLUSION: There was no difference in animals' survival with cachexia associated with the syngeneic melanoma skin tumor model with either resistance exercise or sedentary intervention.

Cutaneous metastatic melanoma in a Siberian tiger (Panthera tigris altaica) - case report / Melanoma cutâneo metastático em um tigre-siberiano (Panthera tigris altaica) - relato de caso

A male 15-year-old captive Siberian tiger (Panthera tigris altaica) developed pelvic limb hypermetry over the past 10 years. Recently, an ulcerated black nodule located caudally to the right ear was observed. The animal was submitted to surgery for removing the tumor, but died during anesthetic recovery. At necropsy, another infiltrative nodule was observed caudally to the right ear. Histologically, both nodules corresponded to melanocytic neoplasia, varying from heavily pigmented to amelanotic, with metastasis to mediastinal lymph nodes, spleen and lung. Lipofuscinosis and corpora amylacea were histologically observed in the central nervous system. Macroscopic and histologic findings confirmed the diagnosis of skin metastatic melanoma in a captive adult Siberian tiger.(AU)

Um tigre-siberiano (Panthera tigris altaica) de cativeiro, macho, de 15 anos de idade, apresentou hipermetria dos membros pélvicos nos últimos 10 anos, e recentemente, foi observado um nódulo preto e ulcerado caudalmente à orelha direita. O animal foi submetido à cirurgia para remoção do nódulo e morreu durante a recuperação anestésica. À necropsia, outro nódulo infiltrativo, foi detectado caudalmente a orelha direita. Histologicamente, ambos os nódulos correspondiam à neoplasia melanocítica, com células variando de fortemente pigmentadas a amelanóticas, com metástase para linfonodos mediastinais, baço e pulmão. Havia lipofucsinose e corpora amilácea no sistema nervoso central. Os achados macroscópicos e histológicos confirmam o diagnóstico de melanoma cutâneo metastático em um tigre-siberiano adulto de cativeiro.(AU)

Comparación entre los melanomas de cabeza y cuello con los de tronco y extremidades / Comparison between head and neck melanomas with trunk and extremity melanomas

Antecedentes: los melanomas en cabeza y cuello (MCC) han sido asociados con factores pronósticos diferentes de aquellos en otras localizaciones. Objetivo: comparar características demográficas, clínicas y resultados del tratamiento quirúrgico de pacientes con MCC y pacientes con melanomas en tronco y extremidades (MTE). Material y métodos: se llevó a cabo una revisión retrospectiva de las historias clínicas de pacientes operados por melanoma entre enero de 2012 y diciembre de 2017. Quince pacientes (22,3%) tuvieron MCC y 52 (77,7%) MTE. Resultados: ambos grupos tuvieron edad similar (63,8 ± 21,1 versus 58,5 ± 16), pero los MCC mostraron una tendencia con predominio masculino (80% versus 61,3%). Los MCC tuvieron menor espesor tumoral que los MTE (2,07 versus 5,5 mm) y mayor porcentaje de melanoma in situ, 5 (33,3%) versus 8 (15,3%), pero requirieron vaciamientos ganglionares más a menudo (33% versus 25%) así como reconstrucción del defecto primario con colgajos locales y miocutáneos. Durante el seguimiento, en el grupo de MCC, dos pacientes desarrollaron recidivas locales que fueron extirpadas, y otros tres desarrollaron metástasis a distancia en pulmón, intestino delgado y abdomen y fallecieron por la enfermedad; en el grupo de MTE un paciente tuvo recidiva local y cinco fallecieron de metástasis sistémicas. El tamaño de la muestra no permitió aplicar pruebas de significación entre las diferencias encontradas. Conclusión: los MCC se presentan en un amplio rango de edad y estadios, y tuvieron algunas diferencias clínicas con el MTE. Los defectos producidos por la extirpación de la lesión primaria requieren procedimientos reconstructivos más complejos la mayoría de las veces y se aconseja un abordaje multidisciplinario.

Background: Head and neck melanomas (HNMs) have been associated with prognostic factors different from those on other locations. Objective: The goal of the present study was to compare the demographic and clinical characteristics and the outcomes of surgical treatment between patients with HNM and those with trunk and extremity melanoma (TEM). Material and methods: The clinical records of patients undergoing surgery for melanoma between October 2014 and April 2018 were retrospectively reviewed. Fifteen patients (22.3%) had HNM and 52 (77.7) presented TEM. Results: There were no differences in age between both groups (63.8 ± 21.1 versus 58.5 ± 16), but there was a trend toward higher percentage of men in the HNM group (80% versus 61.3%). Patients with HNM had lower tumor thickness than those with TEM (2.07 versus 5.5 mm), higher incidence of melanoma in situ [5 (33.3%) versus 8 (15.3%)]; lymph node resection was more common (33% versus 25%) as well as reconstruction of the primary defect with local and musculocutaneous flaps. During follow-up, two patients in the HNM group developed local recurrences that were excised and three presented distant metastases in the lung, small bowel and abdomen and finally died due to the disease. In the TEM group, one patient had local recurrence and five died due to systemic metastases. The sample size was not sufficient to assess statistically significant differences. Conclusion: Head and neck melanomas occur in a wide age range and stages and has some clinical differences with TEM. The defects produced after the excision of the primary lesion often require more complex procedures and should be managed with a multidisciplinary approach.

Melanoma cutáneo: algunas consideraciones actuales / Cutaneous melanoma: some current considerations

El melanoma cutáneo es una enfermedad grave y potencialmente mortal que afecta a la población de todo el orbe y que se encuentra condicionada por muchos factores de riesgo relacionados con algunos estilos de vida, que pueden ser modificables. El hallazgo oportuno y precoz de esta entidad clínica eleva la sobrevida de las personas afectadas y favorece el resultado terapéutico; sin embargo, en ocasiones no se diagnostica a tiempo. Actualmente ya se presenta en individuos más jóvenes de 25-29 años de edad y con gran probabilidad de generar metástasis, lo cual constituye una preocupación en el ámbito de la salud. Al respecto, se decidió efectuar esta revisión bibliográfica, con el fin de actualizar algunos elementos sobre el tema y darlos a conocer a la comunidad médica nacional y extranjera.

The cutaneous melanoma is a severe and potentially mortal disease that affects the population of the whole world and that is conditioned by many risk factors related to some lifestyles that can be modified. The opportune and early finding of this clinical entity elevates the survival of affected people and it favors the therapeutic result; however, it is not diagnosed on time occasionally. At present it is already presented in younger individuals with 25-29 years old and with great probability of generating metastasis, which constitutes a concern in the health field. In this respect, it was decided to make this literature review, with the purpose of to update some elements on the topic and to make them known in the national and foreign medical community.

Câncer de pele: conhecendo e prevenindo a população / Meta skin cancer: knowing and preventing population

O câncer de pele é a neoplasia de maior incidência no Brasil. Essa doença apresenta diferentes linhagens: câncer de pele não melanoma (CPNM) e o tipo melanoma (MC) sendo esses os tipos mais comuns. O CPNM é o mais frequente e trata-se de um tumor de crescimento lento, localmente invasivo e de bom prognóstico se tratado de forma adequada e oportuna, todavia a demora no diagnóstico pode levar a ulcerações e deformidades físicas graves. Esse estudo constitui uma revisão integrativa da literatura, com foco sobre o tema a ser estudado; avaliação dos dados aplicando critérios de inclusão e exclusão; análise dos dados extraindo das fontes primárias as características da amostra e método. A exposição aos raios ultravioletas pode causar alterações no DNA dos melancólicos resultando no risco de carcinogênese em nevos melanócitos na infância. O período da infância e a adolescência são considerados períodos críticos de vulnerabilidade aos efeitos da exposição solar. Esse comportamento pode levar ao desenvolvimento do câncer não melanoma ou do melanoma maligno na vida adulta. Foi constatado que o índice de câncer de pele é maior em pacientes com idade superior a 60 anos do que em jovens, pois apresentam um número maior de lesões. Porém é importante abordar o assunto sobre o desenvolvimento da neoplasia ainda na infância, e as medidas adequadas de fotoproteção

Relación entre ganglio centinela positivo y el espesor de Breslow en pacientes con melanoma cutáneo primario / Relationship between positive sentinel lymph node and Breslow's depth in patients with primary cutaneous melanoma

Introducción: es sabido que el pronóstico del melanoma cutáneo depende, entre otros factores, de la existencia de diseminación linfática a ganglios. La biopsia del ganglio centinela busca identificar metástasis ganglionares subclínicas. Objetivo: el presente estudio tuvo por objetivo analizar la asociación entre la presencia de ganglio centinela positivo, identificado mediante rastreo con radioisótopo 99mTc-coloide de Renio, y el espesor de Breslow hallado en la lesión primaria a nivel cutáneo. Metodología: se analizaron 52 pacientes. Se realizó la búsqueda del ganglio centinela por el método de rastreo con radioisótopo 99mTc-coloide de Renio y posterior biopsia del mismo, en pacientes tratados en el Instituto Nacional de Cancerología de México, entre enero de 2015 a agosto de 2016, con diagnóstico de melanoma cutáneo y espesor de Breslow mayor o igual a 1mm o con menor a 1mm y otros criterios de riesgo como la ulceración. Aquellos con biopsia positiva fueron sometidos a linfadenectomía. Además, se recogieron las siguientes variables: sexo, edad, localización, tipo de melanoma, espesor de Breslow y ulceración. Resultados: la edad media de la muestra fue 57 ± 15 años. El 63,5% de los pacientes fue del sexo masculino. El tipo histológico más frecuente fue el melanoma de extensión superficial (69,2%). Se detectó positividad del ganglio centinela en 46,2% y 28,8% presentó Breslow >4,0 mm. Se encontró relación entre la presencia de ganglio centinela positivo y espesor de Breslow (p=0,007). Conclusiones: a medida que aumenta el espesor de Breslow, lo hace también el encuentro de metástasis en ganglio centinela. Se recomienda realizar estudios de casos y controles para evaluar el factor predictivo que puede llegar a tener el encontrar ganglio centinela positivo.

Introduction: It is known that the prognosis of cutaneous melanoma depends, among other factors, on the existence of lymphatic spread to lymph nodes. Sentinel node biopsy seeks to identify subclinical lymph node metastases. Objective: The present study aimed to analyze the association between the presence of positive sentinel lymph node, identified by Rhenium 99mTc-colloid radioisotope tracing, and the Breslow´s depth found in the primary lesion at the cutaneous level. Methodology: 52 patients were analyzed. The sentinel lymph node was searched by the rhenium 99mTc-colloid radioisotope and subsequent biopsy of it in patients treated at the Instituto Nacional de Cancerología of Mexico, between January 2015 and August 2016, with a diagnosis of cutaneous melanoma and Breslow's depth greater-than or equal to 1mm or less-than 1mm and other risk criteria such as ulceration. Those patients with positive biopsy underwent lymphadenectomy. In addition, the following variables were collected: sex, age, location of the lesion, type of melanoma, Breslow's depth, and ulceration. Results: Mean age of the sample was 57±15 years. 63.5% of the patients were male. The most frequent histological type was superficial spreading melanoma (69.2%). 46.2% had positive sentinel lymph node. 28.8% presented Breslow >4.0 mm. A relationship was found between the presence of positive sentinel lymph node and Breslow's depth (p=0.007). Conclusions: As Breslow's depths increases, so does the metastasis encounter in sentinel lymphs nodes. It is recommended to carry out case-control studies to evaluate the predictive factor that may result in finding a positive sentinel lymph node.

Predictores de metástasis de ganglio centinela en melanoma cutáneo / Predictors for sentinel lymph node metastasis of cutaneous melanoma

Antecedentes: se han descripto múltiples factores de riesgo para el compromiso del ganglio centinela en melanoma cutáneo, pero existe discrepancia en cuanto a la importancia de cada uno de ellos. El objetivo de este estudio fue identificar factores predictores de metástasis del ganglio centinela en pacientes con melanoma cutáneo. Material y métodos: se incluyeron los mapeos linfáticos realizados en pacientes con melanoma cutáneo entre 2001 y 2013. Se evaluaron variables demográficas y características del tumor primario. Se realizaron análisis univariado y multivariado en busca de factores predictivos del compromiso del ganglio centinela. Resultados: en el período citado se efectuaron 117 mapeos linfáticos; 25 pacientes (21,3%) presentaron ganglio centinela positivo. La edad y la localización de la lesión primaria no se asociaron con riesgo de metástasis linfática. Los melanomas con espesor de 1 a 4 mm se asociaron con mayor compromiso ganglionar que aquellos con espesor menor de 1 mm, y aquellos con espesor mayor de 4 mm tuvieron aún mayor tasa de ganglio centinela positivo. La presencia de ulceración y el tipo histológico nodular tuvieron mayor compromiso del ganglio centinela. La regresión tumoral y el número de mitosis no se relacionaron con la positividad del ganglio centinela. En el análisis multivariado solo el índice de Bres-low mayor de 4 mm y el tipo histológico nodular presentaron significación estadística. Conclusiones: la ulceración, el índice de Breslow y el tipo histológico nodular se asocian a mayor compromiso del ganglio centinela. El índice de Breslow y el tipo histológico nodular serían predictores independientes de compromiso ganglionar en melanoma cutáneo.

Background: multiple risk factors have been described in order to predict sentinel lymph node (SLN) compromise in patents with cutaneous melanoma. However, there is no agreement as to the impor-tance of each of those factors. The aim of this study was to identify risk factors of SLN metastasis. Methods: consecutive SLN biopsies in patents with cutaneous melanoma in the period 2001-2013 were included. Demographic factors and primary tumor characteristics were evaluated and univariate and multivariate analyses were performed. Results: of 117 SLN biopsies, 25 patents (21.3%) had a positive SLN. Age and tumor locaton were not associated with risk of lymphatic metastasis. Patents with Breslow thickness 1-4 mm were associated with more nodal involvement than those with thickness < 1mm and those with > 4mm had even higher rate of positive SLN. Ulceraton and nodular histology showed higher SLN compromise. Tumor regres-sion and number of mitoses were not associated with positive SLN. In the multivariate analysis Breslow thickness > 4mm and nodular histologic type showed statstical significance. Conclusions: ulceraton, Breslow thickness and nodular histologic type are associated with the SLN status. Furthermore, Breslow thickness and nodular histologic type could be independent predictor factors of SLN involvement.

Bap1 y neoplasias melanocíticas / Bap1 and melanocytic neoplasms

El melanoma maligno cutáneo (MMC) es un cáncer genéticamente heterogéneo, en cuya patogénesis participarían varios genes. Algunos de estos activan la vía MAP kinasa (BRAF, NRAS, KIT, NF1), mientras que otros confieren una mayor susceptibilidad a melanoma familiar, como CDKN2A, CDK4, MITF y BAP1. BAP1 (BRCA1-associated-protein 1) ha sido descrito como una proteína que se une a BRCA1 para inhibir el crecimiento celular. Actualmente se sabe que es producto de un gen supresor de tumores (denominado BAP1) y que actúa como una enzima con actividad deubiquitinasa, la cual se asocia a varios complejos de proteínas, regulando diversas vías celulares relacionadas con el ciclo celular, diferenciación y muerte celular, así como también gluconeogénesis y respuesta a daño del ADN. Tanto su actividad deubiquitinasa como su localización nuclear son relevantes para su función en la supresión de tumores.

Malignant cutaneous melanoma (MMC) is a genetically heterogeneous cancer and various genes participate in its pathogenesis. Some of these genes activate the MAP kinase pathway (BRAF, NRAS, KIT, NF1) and others are related to a higher susceptibility to familial melanoma like CDKN2A, CDK4, MITF y BAP1. BAP1 (BRCA1-associated –protein 1) has been described as a BRCA1-binding protein inhibiting cell growth. This protein is a product of a gene with tumor suppressor activity, the protein being a deubiquitinase associated to multiple protein complexes regulating various cellular pathways, including the cell cycle, differentiation and cell death, as well as gluconeogenesis and DNA damage response. Both deubiquitinase activity and location to the nucleus are relevant to its tumor suppressor function.

Características del melanoma cutáneo primario en el Instituto Nacional de Cancerología 2006-2010 / Characteristics of primary cutaneous melanoma in the Colombian National Cancerology Institute 2006-2010

Objetivos: Describir las principales características del melanoma cutáneo en el Instituto Nacional de Cancerología, centro de referencia del cáncer, en Bogotá, Colombia. Materiales y métodos: Estudio descriptivo, retrospectivo, de las características demográficas, clínicas e histológicas de los pacientes con diagnóstico de melanoma cutáneo primario, en el Instituto Nacional de Cancerología entre 2006 y 2010. Resultados: Se incluyeron un total de 599 pacientes, de los cuales el 57,4% eran mujeres (n = 344) y el 42,6% hombres (n = 255). La edad media de diagnóstico fue de 60,8 años. La mayoría de los casos fueron procedentes de Bogotá, con el 56,3% (n = 329). Fue más frecuente el área urbana como sitio de residencia habitual (n = 500). La media de frecuencia anual fue de 115 casos nuevos por año. La localización más frecuente fue acral, con el 42,2% (n = 253), seguido de cabeza y cuello (n = 186). Concordando con la localización, el subtipo más frecuente fue el melanoma lentiginoso acral, con el 43,7% (n = 262), seguido por el lentigo maligno, con el 24% (n = 144). En cuanto a la profundidad, se observó una frecuencia igual de melanomas in situ y melanomas con Breslow > 4 mm, ambos con el 19% de los casos. Se encontró que la mayoría de los lentigos malignos, el 75% (n = 108), fueron in situ o con un Breslow ≤ 1 mm; por el contrario, los lentiginosos acrales y los nodulares tuvieron un Breslow > 4 mm con mayor frecuencia (con el 26,3%, n = 69, y el 45,4%, n = 10, respectivamente). El estadio más frecuente fue el III, con el 26,2% de los casos (n = 157). Conclusiones: Se evidenció un mayor porcentaje de melanomas en mujeres y mayor frecuencia de melanomas acrales. Un número importante de pacientes se ubicaron en estado avanzado, por lo que se requieren mayores acciones para la detección temprana del melanoma.

Objectives: To describe the main characteristics of cutaneous melanoma in the National Cancerology Institute, a cancer reference center in Bogota, Colombia. Materials and methods: A descriptive, retrospective study was conducted on the demographic, clinical and histological characteristics of patients diagnosed with primary cutaneous melanoma in the National Cancerology Institute between 2006 and 2010. Results: A total of 599 patients were included, of whom 57.4% were females (n= 344) and 42.6% males (n=255). The mean age at diagnosis was 60.8 years. The majority of cases, 56.3% (n=329), were from Bogota. It was also the most common urban area where the patients had their usual residence (n=500). The mean annual frequency was 115 new cases per year. The most frequent location was acral, with 42.2% (n=253), followed by head and neck (n=186). In accordance with the location, the most common sub-type was acral lentiginous melanoma, with con 43.7% (n=262), followed by lentigo maligna, with 24% (n=144). As regards the depth, a similar frequency was observed for melanomas in situ and melanomas with Breslow >4 mm, both with 19% of the cases. It was found that the large majority of the lentigo maligna, 75% (n=108) were in situ or with a Breslow ≤1 mm. On the other hand, acral lentiginous and nodular melanomas had a higher frequency of Breslow >4 mm (with 26.3% n=69 and 45.4% n=10, respectively). Stage III was the most common stage, with 26.2% (n=157) of the cases. Conclusions: A higher percentage of melanomas were observed in women, as well as a higher frequency of acral melanomas. A signifi cant number of patients were in an advanced stage, thus greater action is required for the early detection of melanoma.

Melanoma dérmico hiperpigmentado de bajo grado de malignidad (melanoma de tipo animal): reporte de cuatro casos / Hyperpigmented dermal melanoma of low-grade of malignancy (animal-type melanoma): report of four cases

El melanoma animal o hiperpigmentado es un subtipo infrecuente de melanoma con células melanocíticas epitelioideas y fusadas muy pigmentadas. Esta entidad sería similar al llamado “melanoma de tipo equino”, una forma de melanoma de bajo grado de malignidad que afecta a los caballos grises. Se reportan cuatro casos, tres hombres y una mujer, cuyas edades variaron de 22 a 84 años; el estudio histopatológico confirmó melanoma dérmico hiperpigmentado; dos casos mostraron ganglio centinela positivo y un caso evolucionó con metástasis múltiples. Tres casos están en control o tratamiento sin evidencias de recidiva o metástasis. El melanoma animal es considerado un subtipo de melanoma de conducta poco agresiva y de mejor pronóstico, pese a su tendencia a las metástasis ganglionares. Los casos presentados mostraron una conducta menos agresiva que la esperada para el espesor de Breslow y estadio clínico en estos casos. Se requieren más estudios para poder identificar variables que permitan predecir el comportamiento biológico y así protocolizar el tratamiento de esta entidad, considerada por algunos como diferente del melanoma.

Animal type or hyperpigmented melanoma is an infrequent subtype of melanoma with heavily pigmented epithelioid and spindle melanocytes. This entity is similar to the so-called “equine-type melanoma”, an indolent variant of melanoma affecting gray horses. We report four cases, three males and one female, whose ages varied from 22 to 84 years; the histopathological study confirmed the diagnosis of hyperpigmented dermal melanoma; two cases showed positive sentinel lymph nodes and one case evolved with multiple metastases. Three cases are in control or under therapy without evidence of recurrences and/or metastases. Animal-type melanoma is considered a subtype of melanoma with indolent behavior and better prognosis, despite its tendence to develop lymph node metastases. The present cases showed a less aggressive behavior than expected for the Breslow’s thickness and clinical stage. More studies are needed to identify variables to predict its behavior and propose therapy protocols for this tumor, considered by some authors a different type of melanoma.

Melanoma cutáneo: mortalidad y características de los tumores incidentes en los dos extremos de la vida en la Argentina / Cutaneous melanoma in argentina: mortality and primary tumor

Objetivos. Conocer y comparar en la Argentina, en los jóvenes y adultos, la mortalidad por melanoma cutáneo (MC) y las características de casos incidentes para aportar información útil en el diseño y evaluación de acciones de prevención. Diseño. descriptivo y retrospectivo. Métodos. Se consideraron para el estudio: los jóvenes < 30 años (J) y adultos > 74 años (AM). Los datos de las defunciones para el cálculo de tasas de mortalidad en los períodos 1981-89, 90-98 y 99-07 fueron proporcionados por la Dirección de Estadísticas e Información de Salud del Ministerio de Salud. La información sobre los casos incidentes se obtuvieron del Registro Argentino de Melanoma Cutáneo (RAMC) para el período enero 2002- diciembre 2009. De ellos se estudió la localización, el espesor de Breslow y el tipo histológico.Resultados. En los sucesivos períodos las muertes por MC en J de ambos sexos fue 97, 93 y 123, y en AM 416, 654 y 1.307, respectivamente. En los AM las tasas de mortalidad aumentaron en el tiempo, y fueron siempre menores para las mujeres que para losvarones (varones: 6,3 muertes por MC promedio por cada 100.000 individuos por año en 81-89 a 13,4/100.000 99-07; mujeres: 4,4/100.000 81-89 a 7,5/100.000 en 99-07). El RAMC registró 4.100 casos, 258 fueron en J y 665 en AM. Fueron mujeres el 63% en J y el 47% en AM (p< 0,05). En las mujeres, el 56% de los MC en J y el 36% en AM tuvieron Breslow ≤ 1,00 mm (p< 0,004). En las mujeres predominaron las lesiones en piernas (el 43,4% en J y el 42,2% en AM), mientras que en los hombres fueron el 19,8% y el 12,4% respectivamente (p< 0,005). Conclusión. En las mujeres jóvenes, el menor espesor de Breslow al momento del diagnóstico y las menores tasas de mortalidad por MC con menor incremento temporal de las mismas podrían ser reflejo de una mayor influencia de las acciones de prevención y una mayor atención del propio cuerpo y de la salud por parte del género femenino. Cabe esperar que la continuidad de las actividades del ...

Objectives. To compare mortality rates and main features of cutaneous malignant melanoma(CMM) between two age groups in Argentina (young and elderly patients), in order to increaseknowledge as well as improve planning and preventive actions for this disease.Study design. descriptive and retrospective.Methods. Group J was defined as patients younger than 30 years of age and Group AM patientsover 74 years old. Death reports for periods 1981-89 / 90-98 / 99-07 were provided by theDepartment of Statistics of the Health Ministry and incident cases between 2002 and December2009 by the Argentine Registry of Cutaneous Malignant Melanoma (RAMC). Tumor location,Breslow thickness index and histopathology characteristics were analyzed for all cases.Results. For successive periods, the total number of CMM-associated deaths for both gendersin Group J was 97, 93 and 123 respectively; while these figures were for Group AM 416, 654 and1,307 respectively. On older patients an increase in mortality rates was observed over elapsedtime, being always lower for women than for men (mortality rates for men were 6.3 /100,000population per year during the period of 1981-1989 and 13.4/100,000 between the years1999-2007. Mortality rates for women were: 4.4/100,000 during 1981-1989 and 7.5/100,000and in 1999-2007). RAMC registered 4,100 new cases, of which 258 belonged to Group J and665 to Group AM. Women comprised 63% on group J and 47% on group AM (p<0, 05). Womencomprised 56% of CMM in Group J and 36% on Group AM, having a Breslow tumor thickness≤ 1.00mm (p<0,004). Primary tumors located on lower limbs were more frequently observedamong women (43.4% and 42.2% for Group J and AM respectively), whereas on men this was19.8% and 12.4%, respectively (p<0,005)...

Immunohistochemical assessment of E-cadherin, beta-catenin, CEACAM-1 and PTEN: tumor progression markers in melanoma / Análise imuno-histoquímica dos marcadores de progressão tumoral, E-caderina, beta-catenina, CEACAM-1 e PTEN em melanomas

INTRODUCTION AND OBJECTIVE: The aim of the present study is the immunohistochemical assessment of tumor progression markers (E-cadherin, β-catenin, CEACAM-1 and PTEN) in primary cutaneous melanomas and their correlation with prognostic factors. METHOD: Primary lesions in patients with cutaneous melanoma were recorded as to clinical data (age, gender, location and metastases) and anatomopathologic data (Breslow, Clark level, margins, histological type, mitosis, ulceration, regression, satellitosis and TIL type). It was made a comparison between immunohistochemical expression of the markers and prognostic and anatomopathologic factors. RESULTS: Breslow thickness was > 1 mm (thick) in 21 patients (48.83 percent) and < 1 mm (thin) in 22 (51.16 percent). There was a higher CEACAM-1 positive expression in thick melanomas than in thin ones (p = 0.002). There was a more frequent E-cadherin (p = 0.008), b-catenin (p = 0.001) and PTEN (p = 0.005) positive expression in thin melanomas than in thick ones. There was a more frequent CEACAM-1 positive expression in superficial (p = 0.003) and deep (p = 0.002) samples of thick melanomas than in thin ones. No statistically significant differences between clinical and histopathological data were found when comparing patients with (n = 6) and without metastasis (n = 15). DISCUSSION AND CONCLUSION: There was a higher positivity for E-cadherin, b-catenin and PTEN in thin melanomas, whereas there was a higher positivity for CEACAM-1 in thick melanomas.

INTRODUÇÃO E OBJETIVO: O objetivo do presente estudo está na avaliação imuno-histoquímica de marcadores de progressão tumoral (E-caderina, β-catenina, CEACAM-1 e PTEN) em melanomas cutâneos primários e sua correlação com fatores prognósticos. MÉTODO: Lesões primárias de pacientes portadores de melanoma cutâneo foram tabuladas quanto a dados clínicos (idade, sexo, localização e metástases) e anatomopatológicos (Breslow, nível de Clark, margens, tipo histológico, mitoses, ulceração, regressão, satelitose e tipo de TIL). Foi realizada comparação da expressão imuno-histoquímica dos marcadores em estudo com fatores prognósticos clínicos e anatomopatológicos. RESULTADOS: Breslow foi > 1 mm (espesso) em 21 pacientes (48,83 por cento) e ≤ 1 mm (fino) em 22 (51,16 por cento). CEACAM-1 foi mais positivo em melanomas grossos que em finos (p = 0,002). E-caderina (p = 0,008), β-catenina (p = 0,001) e PTEN (p = 0,005) foram mais frequentemente positivos em melanomas finos que em grossos. CEACAM-1 foi mais frequentemente positivo nas porções superficiais (p = 0,003) e profundas (p = 0,002) dos melanomas grossos que nas dos finos. Não houve diferenças estatisticamente significativas entre dados clínicos e histopatológicos quando comparamos os pacientes com (n = 6) e sem (n = 15) metástases. DISCUSSÃO E CONCLUSÃO: Observou-se maior tendência de positividade para E-caderina, b-catenina e PTEN em melanomas finos. Por sua vez, CEACAM-1 demonstrou maior frequência de positividade nos melanomas grossos.

Melanoma cutáneo / Cutaneous melanoma

El melanoma cutáneo es el tumor más maligno de la piel y tiene una gran capacidad para producir metástasis. Desde hace 50 años su incidencia ha aumentando considerablemente en el mundo, incluyendo México. Aun cuando se conocen algunos factores de riesgo, el diagnóstico y tratamiento temprano son las únicas estrategias que han demostrado mejorar el pronóstico de quienes lo padecen, siendo su manejo todo un reto. En este artículo se presenta una revisión y actualización del melanoma cutáneo, su epidemiología, etiología, los factores de riesgo asociados, la clasificación, los criterios diagnósticos, importancia del ganglio centinela, manejo, tratamiento y prevención.

Cutaneous melanoma is the most malignant skin tumor with great potential to develop metastases. For 50 years, its incidence has greatly increased worldwide, including Mexico. Although some risk factors are known, early diagnosis and treatment are still the only strategies that have shown to improve prognosis. Management of cutaneous melanoma is still a challenge. In this article we present a review and update of cutaneous melanoma, its epidemiology, etiology, risk factors, classification, diagnosis criteria, relevance of the sentinel node, management, treatment, and prevention.

A proteína p16 e o melanoma cutâneo / P16 protein and cutaneous malignant melanoma

Nas últimas décadas, é intensa a procura de uma explicação genética sobre a origem, o crescimento e a progressão do melanoma cutâneo. A tentativa de encontrar uma ligação direta entre as mutações gênicas e a origem da doença tem sido o objetivo dos pesquisadores dedicados ao estudo dessa neoplasia. Diversos métodos são utilizados na busca de uma avaliação prognóstica para a progressão do melanoma, citando-se, entre eles, a pesquisa do linfonodo sentinela, a imuno-histoquímica, as técnicas moleculares e a técnica de microarray. A necessidade de estabelecer um método, com excelente sensibilidade e especificidade, tem levado os pesquisadores a buscarem melhores evidências. É importante para esses estudos a obtenção de dados confiáveis sobre as técnicas, progressão e sobrevida livre de doença. Por meio da imuno-histoquímica, técnica relativamente simples e de baixo custo, a expressão da proteína p16 pode ser analisada e correlacionada com o prognóstico da doença. No melanoma cutâneo, a expressão da proteína diminui, à medida que aumenta sua agressividade, ou seja, é forte nos nevos e melanomas in situ e fraca ou ausente nos melanomas metastáticos. Em alguns estudos, a comparação com outros marcadores é analisada. A finalidade deste estudo é fazer uma revisão da literatura internacional sobre o uso da proteína p16 como fator prognóstico para o melanoma, bem como avaliar a importância das alterações do gene p16INK4a, corresponsáveis pela gênese e evolução do melanoma

In the last decades there has been an intense search for a genetic explanation of the origin, growth and progression of cutaneous melanoma. The attempt to find a direct link between gene mutations and the root of the disorder has been the aim of researchers devoted to the study of this neoplasia. Many are the methods used in the search of a prognostic evaluation for the progression of melanoma, e.g. research on the sentinel lymph node, immunohistochemistry, molecular techniques and the microarray technique. The need for a method with optimal sensitivity and specificity has led researchers to search for better evidence. For these studies it is important to obtain reliable data on the techniques, progression and survival free of disease. By means of immunohistochemistry, which is a relatively simple, low cost technique, the p16 protein expression can be assessed and correlated with disease prognosis. In cutaneous melanoma, p16 expression decreases as its aggressiveness increases, i.e. it is strong in the nevi and melanomas in situ and weak or absent in the metastatic melanomas. Other studies have analyzed how it compares with other markers. The purpose of this study is to make a review of the international literature on the use of p16 protein as a prognostic factor for melanoma, as well as to evaluate the importance of alterations in the p16INK4a gene, co-responsible for the genesis and progress of melanoma

Melanoma cutáneo asociado a nevo previo / Cutaneous melanoma associated with previous nevus

El melanoma maligno es una neoplasia originada en los melanocitos de la piel y otras localizaciones. No existe información en nuestro país acerca de su incidencia y prevalecencia, sí se sabe cuáles son los factores de riesgo más importantes. El melanoma puede originarse de novo o a partir de lesiones melanocíticas previas. La noción de que un nevo melanocítico pueda servir como lesión precursora es sustentada por evidencias clínicas e histológicas. Realizamos en el Hospital Privado de Córdoba un estudio observacional, retrospectivo y analítico. El objetivo de este trabajo fue conocer cuál es la frecuencia de asociación de melanomas malignos que se desarrollan sobre nevos previos. Fueron analizados un total de 134 melanomas. En 32 pacientes (24%), los melanomas estuvieron histológicamente asociados con nevos, con espesores de Breslow mayores de 1 mm el porcentaje de asociación fue de 16.3%, y con Breslow menores de 1 mm, 38.1%. Al evaluar los melanomas en relación a la clasificación de Breslow y Clark, se objetivó que el grupo de melanomas asociados a nevos presentó un espesor de Breslow y niveles de Clark bajos y en el análisis estadístico fueron predictores significativos en la probabilidad de hallar esta asociación (p < 0.027). Este estudio demuestra que sólo el espesor del tumor es un factor predictivo independiente en la asociación melanoma-nevo, el resto de las variables estudiadas no arrojaron resultados significativos desde el punto de vista estadístico. Los pacientes deben ser educados para el control de nuevas lesiones pigmentadas así como para la modificación de nevos preexistentes.

The malignant melanoma is a neoplasia originated from the melanocytes located in the skin and other locations. Even though there is not information regarding its incidence and prevalence in our country, its most important risk factors are known. The melanoma can originate de novo or from previous melanocytic lesions. The concept that a melanocytic nevus can serve as a precursor lesion is supported by clinical and histological evidence. An observational, retrospective and analytical study was carried out in the Hospital Privado de Córdoba. The objective was to determine which is the frequency of association of malignant melanomas that develop on previous nevus. A total of 134 melanomas were analyzed. In 32 cases (24%), the melanomas were histologically associated with nevus, in individuals with Breslow's depth bigger than 1 mm the percentage of association was 16.3% while in those exhibiting Breslow smaller than 1 mm the percentage of association was 38.1%. Having evaluated the melanomas in relation to the Breslow and Clark classification, we observed that the nevus associated melanoma group showed less Breslow thickness and low Clark levels, which, by statistical analysis were shown to be significant predictors of the probabilty of finding this association (p < 0.027). This study demonstrates that the tumor thickness by itself is an independent predictive factor of the association melanoma-nevus. However, the rest of the variables studied did not throw significant results from the statistical point of view. In conclusion, patients must be educated for the control of new pigmented injuries as well as for the modification of preexisting nevi.

Melanoma cutâneo com longo tempo de história clínica. Impacto na conduta e no prognóstico. Relato de caso / Skin melanoma with long time of clinical history. Impact on Conduct and prognosis. Case report

Há evidências que a frequência do melanoma esteja aumentando de forma universal.Embora mais frequente na pele, pode acometer as leptomeninges, conjuntiva e úvea, trato gastrointestinal e mucosas.Sinais de alerta para o diagnóstico do melanoma cutâneo são as mudanças de características de nevo pigmentado preexistente ou lesão névica aparecendo de novo.Os sinais de alerta são reunidos no acrônimo ABCDE, que deve ser de domínio da classe médica, independentemente da especialidade.Como evidenciado no presente relato, o atraso no diagnóstico do melanoma resulta em piora significativa do prognóstico.Indivíduos de pele negra e orientais são particularmente propensos a desenvolver melanoma lentiginoso acral, o mais comum das regiões palmoplantares e subungueais.

Melanoma cutâneo: doença curável? Revisão de literatura e apresentação de um organograma de investigação e tratamento / Cutaneous melanoma: curable disease? Literature review and presentation of an organogram of investigation and treatment

O melanoma cutâneo é hoje o tumor que mais cresce em incidência no mundo. Representa cerca de 4% dos tumores cutâneos. Apresenta prognóstico bem mais reservado em relação ao carcinoma basocelular e epidermóides. Tem fatores de risco bem estudados, como, por exemplo, a história familiar e a exposição solar demasiada. Apresenta como fator prognóstico principal a presença de linfonodos comprometidos nas respectivas cadeias de drenagem. A primeira linha de tratamento é a cirúrgica, destacando-se na área de tratamento medicamentoso o uso de drogas biológicas, como interferon e a interleucina. Seu prognóstico geral de sobrevida em 10 anos varia entre 85% em países desenvolvidos, até 56% em países em desenvolvimento. Os autores realizam uma revisão bibliográfica criteriosa, além de proporem um organograma de investigação e tratamento baseado em dados de literatura internacional (AU)

At the present time the incidence of cutaneous melanoma is growing very fast and it has the highest rising rates in the world. It is responsible for approximately 4% of the cutaneous tumors, and has a worse prognosis when compared to basocelular or epidermoidis. Some risk factors are well studied, like the family history and excess of sun exposure. The most important prognostic factor is the lymph nodes involvement. The gold standard treatment, when possible, is surgery. The pharmacologic treatment is based on the use of biologic drugs like interferon and interleukins. The general prognosis varies from a survival of 56% in 10 years in underdeveloped countries to 85% in developed ones. The authors perform a careful review of the literature and propose a diagnosis and treatment protocol for these patients (AU)

Epidemiología del melanoma cutáneo / Epidemiology of cutaneous melanoma

Durante las últimas décadas hubo un aumento de la incidencia del melanoma cutáneo en la población caucásica del mundo, aunque este tumor puede afectar a cualquier grupo étnico. En la actualidad se considera a la exposición solar intermitente como un factor de riesgo cierto, en el desarrollo del melanoma cutáneo. La incidencia del melanoma cutáneo en Auckland, Nueva Zelanda, es la mayor del mundo. En Europa, la incidencia y la mortalidad fue creciente hasta que en la década de los 80 se estabilizó. En EEUU también se observó una estabilización de la incidencia. Con respecto a la edad, según la bibliografía consultada la incidencia aumenta a partir de los 20 años; en algunos pacientes con más de 200 nevos y sin pautas de protección solar antes de los 5 años de vida. También se observa aumento de la incidencia en los adultos mayores de 60 años de edad. Con respecto al sexo, en los EEUU y la Argentina es más frecuente en los hombres y en Europa en el sexo femenino.

During the last decades there was an increase of incidence of cutaneous melanoma in Caucasian population worldwide, but this tumor can affect any ethnic group. Nowadays, the intermittent solar exposition is a well known predisposing factor. The incidence in Auckland, New Zealand, is the highest in the world. In Europe and in the USA, the incidence and mortality rates decreased until the 80's when it stabilized. Regarding the age of appearance, the incidence increases starting at 20 years of age in patients with more than 200 nevi and without history of sun protection in childhood. There was also an increase in the incidence in adults (>60 y-o). The distribution by sex in USA and Argentina is more frequent in males and in Europe in females.