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.

Metastasis of melanoma in non-sentinel nodes in patients with metastatic sentinel node. Can we avoid complementary lymphadenectomy?

BACKGROUND: Lymph mapping with sentinel node biopsy is the standard procedure for lymph node staging in patients with cutaneous melanoma with a tumor thickness of 1 mm or greater. Patients who have metastases in sentinel node must undergo complementary lymphadenectomy; however, it has not been shown to improve survival. OBJECTIVE: To know the prevalence in our setting of metastases in the product of complementary lymphadenectomy in patients with metastatic sentinel node. METHOD: Evaluation of a descriptive, retrospective, observational and analytical cohort of patients with metastatic sentinel node submitted to lymphadenectomy. Multivariate analysis of tumor thickness, neural invasion, location, sentinel node number, serum DHL level, lymph nodes dissected and extracapsular spread. RESULTS: 67 patients, 35 women and 32 men with a mean of 66 years, 22% had metastases in lymph nodes from complementary lymphadenectomy, 19% of them with extracapsular spread; no relationship with the Breslow level. Extracapsular spread in the sentinel node, lymphadenectomy time, and perineural invasion in the primary tumor were prognostic factors for non-sentinel node metastasis. CONCLUSIONS: In this series, 22% of the patients with a sentinel node-positive have metastases in the non-sentinel nodes, 19% of them with extracapsular spread, which justifies complementary lymphadenectomy.

ANTECEDENTES: El mapeo linfático con biopsia del ganglio centinela es el procedimiento estándar de estadificación ganglionar en pacientes con melanoma cutáneo con grosor tumoral de 1 mm o mayor. Los pacientes que tienen metástasis en él deben ser sometidos a linfadenectomía complementaria; sin embargo, esta no ha mostrado mejorar la superviviencia. OBJETIVO: Conocer la prevalencia en nuestro medio de metástasis en el producto de linfadenectomía complementaria en pacientes con ganglio centinela metastásico. MÉTODO: Evaluación de una cohorte descriptiva, retrospectiva, observacional y analítica de pacientes con ganglio centinela metastásico sometidos a linfadenectomía, con análisis multivariado de grosor tumoral, invasión neural, localización, número de ganglios centinela, concentración sérica de deshidrogenasa láctica, ganglios disecados en linfadenectomía y ruptura capsular. RESULTADOS: Hubo 67 pacientes (35 mujeres y 32 hombres), con una media de 66 años de edad, en el 22% hubo metástasis en ganglios de linfadenectomía complementaria y en el 19% ruptura capsular; sin relación con el nivel de Breslow. La ruptura capsular en el ganglio centinela, el tiempo de linfadenectomía y la invasión perineural fueron factores pronóstico de metástasis en ganglios no centinela. CONCLUSIONES: En esta serie, el 22% de los pacientes tuvieron metástasis en ganglios no centinela, el 19% de ellos con ruptura capsular, lo cual justifica la linfadenectomía complementaria.

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.

[Melanoma cutáneo. Etapificación ganglionar con base en la evidencia actual].

Most patients with cutaneous melanoma present with clinical stage 1 at diagnosis, i.e., with no evidence of lymph node or systemic metastases. However, since this is a type of neoplasm with high affinity to lymphatic tissue, between 30 and 60% of patients are estimated to have occult metastases on the lymph nodes of the area that drains the primary tumor site at the moment of diagnosis. This possibility depends on several histologic factors, especially thickness of the neoplasm. Historically, in order to reduce the rate of regional recurrence, lymphadenectomy was an essential part of cutaneous melanoma treatment, which has associated morbidity. In the decade of 1990, Morton et al. reported that lymph is initially received by a single lymph node in the lymphatic basin and that its histological status predicts the status of the others and that, therefore, in patients with sentinel lymph node free of metastases lymphadenectomy is not necessary, which reduces morbidity. In the present manuscript, indications, contraindications and requirements for sentinel lymph node identification are described, as well as its current value in cutaneous melanoma diagnostic and therapeutic process.

La mayoría de los pacientes con melanoma cutáneo se presenta en etapa clínica 1, es decir, sin evidencia de metástasis ganglionares ni sistémicas, sin embargo, al ser una neoplasia con alta linfofilia, se estima que al momento del diagnóstico entre 30 y 60 % de los pacientes tiene metástasis ocultas en los ganglios linfáticos de la zona que drena el sitio del tumor primario. Esta posibilidad depende de varios factores histológicos, principalmente el grosor de la neoplasia. Históricamente y con objeto de lograr disminuir la tasa de recurrencias regionales, la linfadenectomía, con la morbilidad asociada, era parte esencial del tratamiento. En la década de 1990, Morton et al. reportaron que un solo ganglio de la zona linfoportadora recibe la linfa inicialmente y que su estado histológico predice el estado de los demás, de tal manera que la linfadenectomía no es necesaria en pacientes con ganglio centinela sin metástasis, lo que disminuye la morbilidad. En el presente manuscrito se describen las indicaciones, contraindicaciones y requisitos para efectuar la identificación del ganglio centinela, así como su valor actual en el proceso diagnóstico terapéutico del melanoma cutáneo.

Melanoma Arising in a Melanocytic Nevus. / Melanoma asociado a nevo melanocítico.

The association of melanoma with a preexisting melanocytic nevus varies considerably between series, depending on whether the association is based on histological signs (4%-72%) or a clinically evident lesion (42%-85%). Histological association with a nevus correlates with favorable prognostic factors, whereas a clinical association correlates with unfavorable factors. In this review, we discuss the characteristics of nevus-associated melanoma from different perspectives: Whiteman's divergent pathway hypothesis for the development of cutaneous melanoma; and the factors involved in nevogenicity, including both the genetic and molecular factors involved in the development of the melanoma and its precursor lesions. Finally, a cumulative analysis of the 16 162 cases reported in the literature revealed that 29.8% of melanomas are histologically associated with a melanocytic nevus.

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

Cost of Cutaneous Melanoma by Tumor Stage: A Descriptive Analysis. / Estudio descriptivo de costes en melanoma cutáneo de diferentes estadios.

BACKGROUND AND OBJECTIVE: The basis for optimal resource allocation is an understanding of requirements during the diagnostic and treatment phases. Costs associated with the rising incidence of cutaneous melanoma are considerable. We undertook an up-to-date analysis of the cost of diagnosis, treatment, and follow-up according to tumor stage. METHODS: We constructed descriptive tables following a theoretical model of direct costs based on amounts published in directives for the Spanish national health system and in international guidelines for managing cutaneous melanoma according to stage at diagnosis and clinical course. The tables allowed us to calculate the cost of treating individual patients as well as the expected cost for all patients with tumors in the same stage. RESULTS: Individual patients would generate costs ranging from €1689 (for a stage I tumor) to €88, 268 (stage IV). The largest differences were between stages IA and IB-IIA and between stages III and IV. Costs differed greatly between patients with early-stage tumors and favorable outcomes and those with recurring tumors, which cost 50-fold more in the first year and 20-fold more after 10 years of follow-up. CONCLUSIONS: The high cost of diagnosing advanced-stage cutaneous melanoma calls attention to the need to promote primary prevention and early detection. Our findings provide the knowledge base for cost-effectiveness studies in this disease.

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.

[Update on surgical treatment of primary and metastatic cutaneous melanoma]. / Actualización en el tratamiento quirúrgico del melanoma cutáneo primario y metastásico.

Melanoma is a common cutaneous tumour. It is of great importance due to its increasing incidence and aggressive behaviour, with metastasis to lymph nodes and internal organs. When suspecting melanoma, excisional biopsy should be performed to obtain complete histological information in order to determine the adverse factors such as ulceration, mitosis rate, and Breslow depth, which influence preoperative staging and provide data for sentinel lymph biopsy decision making. The indicated management for melanoma is wide local excision, observing recommended and well-established excision margins, depending on Breslow depth and anatomical location of the tumour. Therapeutic lymphadenectomy is recommended for patients with clinically or radiologically positive lymph nodes. This article reviews surgical treatment of melanoma, adverse histological factors, sentinel lymph node biopsy, and radical lymphadenectomy. Details are presented on special situations in which management of melanoma is different due to the anatomical location (plantar, subungual, lentigo maligna), or pregnancy.

Yield of Computed Tomography at Baseline Staging of Melanoma.

BACKGROUND: Current guidelines call for baseline imaging only for very high-risk (T4b) primary cutaneous melanomas. OBJECTIVES: To estimate the frequency of computed tomography (CT) at baseline staging of primary cutaneous melanoma and the diagnostic yield of CT; and to describe the types and frequencies of incidentaloma findings. MATERIAL AND METHODS: Cross-sectional study of cutaneous melanoma cases (tumor classifications Tis to T4bN0M0) attended between 2008 and 2014 in a specialized melanoma unit. Reports of CT scans performed during baseline staging were reviewed to determine the frequency of positive scan results, incidentaloma findings, unit cost for detection of metastasis, and factors associated with the decision to order CT. RESULTS: CT results were available for 310 of the 419 patients included (73.99%). The tumor classifications were as follows: Tis, 17; T1, 137; T2, 71; T3, 48; and T4, 37. The CT results were negative in 81.61%, and incidentalomas were found in 18.06%. Additional primary tumors were found in 2 patients (0.64%), and metastasis was identified in one patient (0.32%). The cost of finding the case of metastasis was €71,234.90. A T2 tumor classification (odds ratio [OR], 8.73) and age under 70 years (OR, 3.53) were associated with greater likelihood of CT being ordered. Excision of the primary tumor in the melanoma unit (OR, 0.08) was associated with less likelihood of ordering CT. CONCLUSIONS: The results for this patient series support current recommendations restricting CT at baseline to cases where there is high risk of metastasis (stagesiiC-iii).

[Sentinel lymph node biopsy in melanoma: our experience over 8 years in a universitary hospital]. / Biopsia selectiva del ganglio centinela en melanoma: experiencia durante 8 años en un hospital universitario.

BACKGROUND: Since the introduction of sentinel lymph node biopsy, its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. Our experience of sentinel lymph node biopsy for melanoma is presented and evaluated. MATERIAL AND METHODS: A cohort study was conducted on 69 patients with a primary cutaneous melanoma and with no clinical evidence of metastasis, who had sentinel lymph node biopsy from October-2005 to December-2013. Sentinel lymph node biopsy was identified using preoperative lymphoscintigraphy and subsequent intraoperative detection with gamma probe. RESULTS: The sentinel lymph node biopsy identification rate was 98.5%. The sentinel lymph node biopsy was positive for metastases in 23 patients (33.8%). Postoperative complications after sentinel lymph node biopsy were observed in 4.4% compared to 38% of complications in patients who had complete lymphadenectomy. CONCLUSION: The sentinel lymph node biopsy in melanoma offers useful information about the lymphatic dissemination of melanoma and allows an approximation to the regional staging, sparing the secondary effects of lymphadenectomy. More studies with larger number of patients and long term follow-up will be necessary to confirm the validity of sentinel lymph node biopsy in melanoma patients, and especially of lymphadenectomy in patients with positive sentinel lymph node biopsy.

[Dermoscopy in cutaneous melanoma]. / Dermatoscopia en melanoma cutáneo.

BACKGROUND: The mortality of cutaneous melanoma has not declined over the past 50 years. The only interventions that can reduce mortality are primary prevention and early diagnosis, and the dermoscopic evaluation is essential to achieve this. Dermoscopy identifies characteristics of melanoma that would go unnoticed to the naked eye. The aim of this paper is to report the most frequent dermoscopic findings in patients diagnosed with in situ and invasive melanoma. MATERIAL AND METHODS: An observational and retrospective study of contact dermoscopy was performed using LED DermliteTM and camera DermliteTM dermoscope. The findings evaluated were: asymmetry in two axes, association of colours, lack of pigment, irregular points, atypical network, pseudopods, blue veil, ulceration, and peri-lesional pink ring. These dermoscopic findings were compared with the histological diagnosis. RESULTS: The study included 65 patients with cutaneous melanoma; 10 in situ, and 55 invasive. The mean Breslow in invasive melanoma was 3 mm. Most patients (35) had localization in extremities. In all patients, the most frequent dermoscopic finding was asymmetry in two axes, followed by association of two or more colours; in melanoma in situ, asymmetry was the most frequent, followed by atypical-irregular points. In invasive melanoma asymmetry in two axes, the association of two or more colours, and pseudopods, were the most frequent findings. CONCLUSION: Asymmetry in two axes is the most common dermoscopic finding in in situ and invasive melanoma. The presence of two or more colours in a pigmented lesion should be suspected in an invasive melanoma.

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.

Diagnostic imaging in dermatology: utility of PET-CT in cutaneous melanoma.

Malignant melanoma accounts for 5% of all malignant skin tumors and its incidence is increasing. In the natural course of melanoma, tumors grow locally and can spread via the lymph system or the blood. Because survival is directly related to the stage of the disease at diagnosis, early detection (secondary prevention) has an impact on prognosis. Positron emission tomography (PET) is a nuclear medicine technique that generates images using molecules labeled with positron-emitting isotopes. The most widely used molecule is fluorodeoxyglucose (FDG). Because of the elevated glycolytic rate in tumor cells, which results in increased FDG uptake, greater quantities of FDG become trapped in tumor cells, enabling external detection. Today, most PET scanners are multimodal PET-computed tomography (CT) scanners, which provide more detailed information by combining morphological information with functional PET findings. The possible utility of PET-CT in patients with malignant melanoma is a subject of debate. Various questions have been raised: when the scan should be performed, whether PET-CT has advantages over conventional diagnostic methods, and whether PET-CT provides a real benefit to patients. In this review of the literature, we will analyze each of these questions.

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.